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Article No : a02_001

Amines, Aliphatic
KARSTEN ELLER, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic
of Germany
ERHARD HENKES, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic
of Germany
ROLAND ROSSBACHER, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic
of Germany
HARTMUT HÖKE, Weinheim, Federal Republic of Germany

1. Introduction. . . . . . . . . . . . . . . . . . . . . . . 647 4.6. Economic Aspects . . . . . . . . . . . . . . . . . . 659

2. General Chemical Properties. . . . . . . . . . 648 5. Cycloalkylamines . . . . . . . . . . . . . . . . . . . 660
2.1. Salt Formation. . . . . . . . . . . . . . . . . . . . . 648 6. Cyclic Amines . . . . . . . . . . . . . . . . . . . . . 664
2.2. Conversion to Carboxamides . . . . . . . . . . 648 7. Fatty Amines . . . . . . . . . . . . . . . . . . . . . . 670
2.3. Conversion to Sulfonamides. . . . . . . . . . . 648 7.1. Properties . . . . . . . . . . . . . . . . . . . . . . . . 670
2.4. Reaction with Carbonyl Compounds . . . . 648 7.2. Production . . . . . . . . . . . . . . . . . . . . . . . . 672
2.5. Reaction with Carbon Dioxide and Carbon 7.3. Analysis and Quality Control . . . . . . . . . 674
Disulfide. . . . . . . . . . . . . . . . . . . . . . . . . . 650 7.4. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675
2.6. Reaction with Epoxides . . . . . . . . . . . . . . 650 7.5. Economic Aspects . . . . . . . . . . . . . . . . . . 676
2.7. Alkylation . . . . . . . . . . . . . . . . . . . . . . . . 650 8. Diamines and Polyamines . . . . . . . . . . . . 677
2.8. Formation of Isocyanates and Ureas . . . . 650 8.1. Diamines . . . . . . . . . . . . . . . . . . . . . . . . . 677
2.9. Reaction with Acrylonitrile . . . . . . . . . . . 651 8.1.1. 1,2-Diaminoethane (Ethylenediamine) . . . . 677
2.10. Formation of Isonitriles . . . . . . . . . . . . . . 651 8.1.2. Diaminopropanes. . . . . . . . . . . . . . . . . . . . 679
2.11. Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . 651 8.1.3. Higher Diamines . . . . . . . . . . . . . . . . . . . . 681
2.12. Dealkylation. . . . . . . . . . . . . . . . . . . . . . . 651 8.2. Oligoamines and Polyamines . . . . . . . . . . 682
3. General Production Methods . . . . . . . . . . 651 8.2.1. Physical Properties . . . . . . . . . . . . . . . . . . 682
3.1. Production from Alcohols . . . . . . . . . . . . 651 8.2.2. Chemical Properties. . . . . . . . . . . . . . . . . . 684
3.2. Production from Carbonyl Compounds. . 652 8.2.3. Production, Analysis, and Uses . . . . . . . . . 684
3.3. Production from Nitriles . . . . . . . . . . . . . 653 9. Chiral Amines . . . . . . . . . . . . . . . . . . . . . 685
3.4. Production from Alkyl Halides . . . . . . . . 654 10. Toxicology and Occupational Health . . . . 685
3.5. Production from Nitro Compounds . . . . . 654 10.1. General Aspects . . . . . . . . . . . . . . . . . . . . 685
3.6. Production from Olefins . . . . . . . . . . . . . 654 10.2. Toxicology of Specific Amines . . . . . . . . . 688
3.7. Other Processes . . . . . . . . . . . . . . . . . . . . 655 10.2.1. Alkylamines, Cyclic Amines, and
4. Lower Alkylamines . . . . . . . . . . . . . . . . . 655 Polyamines . . . . . . . . . . . . . . . . . . . . . . . . 688
4.1. Physical Properties . . . . . . . . . . . . . . . . . 655 10.2.2. Fatty Amines. . . . . . . . . . . . . . . . . . . . . . . 691
4.2. Storage and Transportation. . . . . . . . . . . 655 11. Acknowledgment . . . . . . . . . . . . . . . . . . . 692
4.3. Quality Specifications and Analysis . . . . . 656 References . . . . . . . . . . . . . . . . . . . . . . . . 692
4.4. Production . . . . . . . . . . . . . . . . . . . . . . . . 656
4.5. Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657

1. Introduction more than eight atoms per carbon chain, are

generally known as fatty amines and are dis-
Primary, secondary, and tertiary amines are cussed in Chapter 7.
distinguished on the basis of the number of In 1849, WURTZ prepared methylamines and
hydrogen atoms in ammonia that have been ethylamines by hydrolysis of the corresponding
replaced by organic groups. Substitution at the alkyl isocyanates, trialkyl cyanurates, and alky-
nitrogen atom by a fourth substituent gives lureas [1]. However, HOFMANN was the first to use
quaternary ammonium compounds. The lower the terms ‘‘primary’’, ‘‘secondary’’, and ‘‘tertia-
aliphatic amines are those with up to six carbon ry’’ and to carry out fundamental work on the
atoms per alkyl chain. Long-chain amines, with synthesis, properties, and structure of amines [2].

 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

DOI: 10.1002/14356007.a02_001
648 Amines, Aliphatic Vol. 2

In general, naturally occurring amines are Very good yields are obtained, particularly with
relatively complex compounds (e.g., alkaloids, carboxylic acid chlorides, for which the reaction is
vitamins, and amino acids); however, some low- highly exothermic. With carboxylic acids, the
er alkylamines and diamines, such as tetramethy- reaction often stops at the initially formed ammo-
lenediamine (putrescine) and pentamethylene- nium salt. This type of reaction is utilized indus-
diamine (cadaverine), are known as degradation trially, for example, in the synthesis of various
or decomposition products of proteins. herbicides with an acid amide structure.
With a worldwide production (2000) of sev-
eral 100 000 t/a, the aliphatic amines are among
the most important organic intermediates in the 2.3. Conversion to Sulfonamides
chemical industry. The range of uses of these
compounds is correspondingly wide. Major uses The reaction with benzenesulfonyl chloride is
include those in the production of agrochemicals utilized for distinguishing among primary, sec-
(in particular, herbicides), dyes, drugs, surfac- ondary, and tertiary amines (Hinsberg test), as
tants, and plastics, as auxiliaries for the rubber, well as for their preparative separation. Whereas
textile, and paper industries, and as anticorrosion primary amines form alkali-soluble N-alkyl ben-
agents and process chemicals for gas scrubbing. zenesulfonamides, secondary amines give alkali-
insoluble N,N-dialkyl benzenesulfonamides, and
tertiary amines do not react under these condi-
2. General Chemical Properties tions. Limitations can arise with long-chain pri-
mary amines, which are alkali-insoluble despite
The chemistry of the aliphatic amines is deter- their acidic hydrogen, and with tertiary amines,
mined by the electron lone pair on the nitrogen which may undergo quaternization with the sul-
atom and by the tendency of the hydrogen atoms fonyl chloride.
bonded to nitrogen to be replaced by other

2.1. Salt Formation

Because they carry alkyl substituents, the ali-

phatic amines are stronger bases than ammonia
(see Table 1); with acids, they form salts that are
very soluble in water but insoluble in organic
solvents. This property, combined with the dif-
ference in solubility between amine and salt,
makes amines good acid acceptors and solvents
for gas scrubbing and for certain extraction pro-
cesses (e.g., in the synthesis of semisynthetic

2.2. Conversion to Carboxamides

Amines react with carboxylic acids and their

esters, chlorides, and anhydrides to give the
corresponding substituted carboxamides: 2.4. Reaction with Carbonyl

Depending on the reaction conditions and the

compound employed, carbonyl compounds react
with amines to form imines (Schiff bases) (2) or
Vol. 2 Amines, Aliphatic 649

Table 1. Physical properties of commercial alkylamines

CAS Flash
registry point, pKb
Compound number Formula Mr mp,  C bp,  C d420 n20

C (25  C)

Ethylamine [75-04-7] C2H5NH2 45.09 80.6 16.6 0.6829 1.3663 52 3.25
Diethylamine [109-89-7] (C2H5)2NH 73.14 50 56.3 0.7056 1.3864 23 2.88
Triethylamine [121-44-8] (C2H5)3N 101.19 115 89.3 0.7275 1.4010 11 3.24
Propylamine [107-10-8] C3H7NH2 59.11 83 47.8 0.7173 1.3870 30 3.41
Dipropylamine [142-84-7] (C3H7)2NH 101.19 63 109.2 0.7400 1.4050 7 3.09
Tripropylamine [102-69-2] (C3H7)3N 143.26 93.5 156 0.7558 1.4171 36 3.35
Isopropylamine [75-31-0] (CH3)2CHNH2 59.11 95.2 32.4 0.6886 1.3742 37 3.37
Diisopropylamine [108-18-9] [(CH3)2CH]2NH 101.19 61 84 0.7169 1.3924 17 3.43
(20  C)
Butylamine [109-73-9] C4H9NH2 73.14 49.1 77.8 0.7414 1.4031 8 3.39
Dibutylamine [111-92-2] (C4H9)2NH 129.25 62 159 0.7670 1.4177 39 3.04
Tributylamine [102-82-9] (C4H9)3N 185.36 70 213 0.7771 1.4291 70 3.11
Isobutylamine [78-81-9] (CH3)2CHCH2NH2 73.14 85.5 68 0.7360 1.3988 16 3.59
Diisobutylamine [110-96-3] [(CH3)2CHCH2]2NH 129.25 77 139 0.7450 1.4090 25.5 3.18
Triisobutylamine [1116-40-1] [(CH3)2CHCH2]3N 185.36 21.8 191.5 0.7684 1.4252 3.68
1-Methylpropylamine [13952-84-6] C2H5CH(CH3)NH2 73.14 10.4 63.5 0.7246 1.3932 20 3.43
(D , L )
Bis(1-methyl)propylamine [626-23-3] [C2H5CH(CH3)]2NH 129.25 70 135 0.7534 1.4111 21
(D , L )
1,1-Dimethylethylamine [75-64-9] (CH3)3CNH2 73.14 67.5 44.4 0.6958 1.3784 9 3.39
Pentylamine [110-58-7] C5H11NH2 87.16 55 104.4 0.7547 1.4118 7 3.36
Dipentylamine [2050-92-2] (C5H11)2NH 157.30 32 202 0.7771 1.4272 71 2.82
Tripentylamine [621-77-2] (C5H11)3N 227.44 240 – 5 0.7907 1.4366 88
2-Pentylamine [625-30-9] C3H7CH(CH3)NH2 87.16 91.5 0.7384 1.4027
3-Pentylamine [616-24-0] (C2H5)2CHNH2 87.16 91 0.7479 1.4063
2-Methylbutylamine [96-15-1] C2H5CH(CH3)CH2NH2 87.16 95.4 0.7490 1.4114 3
3-Methylbutylamine [107-85-7] (CH3)2CH(CH2)2NH2 87.16 60 95 0.7505 1.4083 4 3.98
Bis(3-methylbutyl) [544-00-3] [(CH3)2CH(CH2)2]2NH 157.30 44 188 0.7669 1.4235
Tris(3-methylbutyl) [645-41-0] [(CH3)2CH(CH2)2]3N 227.44 235 0.7848 1.4331 82
Hexylamine [111-26-2] C6H13NH2 101.19 19 130 0.7660 1.4180 34 3.44
Octylamine [111-86-4] C8H17NH2 129.25 0 179.6 0.7826 1.4294 58 3.35
2-Ethylhexylamine [104-75-6] C4H9CH(C2H5)CH2NH2 129.25 <70 169.2 0.7894 1.4313 53
Decylamine [2016-57-1] C10H21NH2 157.30 17 220.5 0.7936 1.4369 3.36
N-Methylbutylamine [110-68-9] C4H9NHCH3 87.16 75 91 0.7341 1.4010 0 6
N-Ethylbutylamine [13360-63-9] C4H9NHC2H5 101.19 70 108 – 9 0.7398 1.4040 9
N,N-Dimethyle- [598-56-1] C2H5N(CH3)2 73.14 <70 36 0.6754 1.3720 45
N,N-Dimethyliso- [996-35-0] (CH3)2CHN(CH3)2 87.16 136 66 0.7151 1.3905 27
N-Ethyldiiso- [7087-68-5] [(CH3)2CH]2NC2H5 129.25 <50 127 0.751 1.4140 10
Allylamine [107-11-9] CH2¼CH-CH2-NH2 57.09 88 53.2 0.7621 1.4205 20 4.28
Diallylamine [124-02-7] (CH2¼CH-CH2)2NH 97.16 88 111 0.7874 1.4387 21 4.87
N,N-Dimethyl-2- [107-99-3] ClCH2CH2N(CH3)2 107.58 110 1.4286
N,N-Diethyl-2- [100-35-6] ClCH2CH2N(C2H5)2 135.64 146 – 7 0.9166 1.4358
3-Methoxypropylamine [5332-73-0] CH3O(CH2)3NH2 89.14 116 – 9 0.8727 1.4191 48

enamines (3); these products can be hydrogenat- are usually not isolable. Aldehydes generally
ed to give more highly alkylated amines. This react faster than ketones. Secondary amines can
reaction is an important method for synthesizing only form enamines, and tertiary amines neither
higher amines. The intermediate hemiaminals (1) of the two products.
650 Amines, Aliphatic Vol. 2

This oxyalkylation reaction is one of the most

important industrial reactions of aliphatic amines
and is utilized for the preparation of flocculants,
surface coating resins, drug intermediates, and
products for gas scrubbing (! Ethanolamines
and Propanolamines).

2.7. Alkylation
An amine, an aldehyde, and a compound with
an activated hydrogen atom, such as a ketone, can The reaction of amines with alkyl halides and
react to form a Mannich base. dialkyl sulfates to give, ultimately, quaternary
ammonium compounds is utilized in preparative
pharmaceutical chemistry and for the preparation
of anticorrosion agents and biocides.

The reaction of alkyl halides with ammonia is

In this case, the condensation product between not very useful for the preparation of primary or
the aldehyde and the amine is attacked by the secondary amines since these are stronger bases
C – H acidic compound, in this case the ketone. and preferentially attack the halides. Tertiary
amines can be prepared, though. On a laboratory
scale, primary amines can be obtained by using
2.5. Reaction with Carbon Dioxide and tetramethylenehexamine, and secondary amines
Carbon Disulfide with cyanamide.
The carbamic acid or dithiocarbamic acid formed
in this reaction is unstable but can be isolated as a 2.8. Formation of Isocyanates and
salt or an ester. Ureas

The reaction of phosgene with primary amines

leads first to the corresponding carbonyl chlo-
ride; subsequent cleavage of hydrogen chloride
Dithiocarbamates obtained from various gives the alkyl isocyanate. Excess amine reacts
amines play a key role as vulcanization accel- with the isocyanate with formation of ureas:
erators in the rubber industry.

2.6. Reaction with Epoxides

Primary amines react with epoxides to give a

mixture of mono- and dioxyalkylated deriva-
tives, whereas secondary amines give only
monooxyalkylated compounds, and tertiary
amines form quaternary ammonium compounds.
This reaction is important in the preparation of
various herbicides with urea, carbamate, or thio-
carbamate structures and, particularly in the
case of polyfunctional amines, in polyurethane
Vol. 2 Amines, Aliphatic 651

chemistry. The reaction of secondary amines Oxidation with nitrous acid can be used to
with phosgene proceeds via an analogous inder- distinguish among primary, secondary, and ter-
mediate chloride to form N,N0 -tetraalkylureas. tiary amines. Primary amines undergo diazotiza-
tion followed by loss of gaseous nitrogen and
afford alcohols by reaction of the intermediate
2.9. Reaction with Acrylonitrile carbenium ion with water. Secondary amines
react to give yellow N-nitrosoamines. Normally,
The addition of a primary or secondary amine to tertiary amines do not react.
acrylonitrile to form an aminopropionitrile is
utilized industrially on a large scale for the RCH2 NH2 þHNO2 !RCH2 OHþH2 OþN2
preparation of higher diamines and polyamines,
because the nitrile can be readily hydrogenated to ðRCH2 Þ2 NHþHNO2 !ðRCH2 Þ2 NN ¼ OþH2 O
the amine.
The formation of nitrosamines can be a seri-
½!RNHðCH2 Þ3 NH2 
ous problem, particulary with secondary amines,
since they are highly mutagenic. During normal
use they are not formed, but upon contact with
nitrites or nitrous oxides traces can be produced
2.10. Formation of Isonitriles that give rise to problems during handling. Air
contamination with secondary amines is thus
Primary amines react with trichloromethane un- considered quite problematic.
der basic conditions to form isonitriles:
RNH2 þCHCl3 þ3KOH!RNCþ3KClþ3H2 O
2.12. Dealkylation
Because of the strong unpleasant odor of the
isonitriles, the reaction can be used as a test for Tertiary amines can be dealkylated by converting
primary amines. For the lower amines, the reac- them to basic quaternary ammonium salts, which
tion can be used synthetically as well. An alter- decompose upon heating. If only methyl groups
native route uses the N-alkylformamides to syn- are present, they are eliminated as methanol or
thesize isonitriles. dimethyl ether; all higher alkyl groups furnish
alkenes, e.g.,

2.11. Oxidation

In contrast to their salts, the free amines are

sensitive to oxidation, giving various products,
depending on the oxidizing agent and the type of
amine. Tertiary amines are oxidized by hydrogen This reaction, known as the Hofmann degra-
peroxide to amine oxides, whereas the corre- dation, is seldom utilized synthetically, but used
sponding compounds formed from primary and to be important for elucidating the structure of
secondary amines undergo further reaction to give unknown amines.
the corresponding hydroxylamines or aldoximes:

3. General Production Methods

3.1. Production from Alcohols

The reaction of the appropriate alcohol with am-

monia over a suitable catalyst is now the most
common process for the preparation of lower
alkylamines. In this reaction, the product is always
a mixture of primary, secondary, and tertiary
652 Amines, Aliphatic Vol. 2

amines because the primary amine formed initially intermediate aldehydes, formation of Schiff base
can react further with one or two molecules of from these aldehydes and the amine product, and
alcohol. While the initial conversion of the alcohol nitrile formation, which occurs at high tempera-
to the primary amine is close to thermoneutral, the tures and low hydrogen pressures.
formation of secondary and tertiary amines is
exothermic and thus thermodynamically favored.
Also, the primary amine is more nucleophilic than
ammonia and hence has a higher reactivity. The
product distribution can be controlled to a certain
extent by means of the reaction conditions (tem-
perature, excess of ammonia, residence time).
Because the mixture of products usually obtained
does not correspond to market requirements,
amines that are not marketable can be recycled.
Thus, the yield of the desired amine can be in-
creased to above 90 %.
Previously, this reaction was carried out with
pure dehydration catalysts (e.g., alumina, silica,
titania, thorium oxide, tungsten oxide, chromium A two- to eightfold excess of ammonia is used
oxides, phosphates or various mixed oxides such as to shift the equilibrium towards the primary
silica – alumina, clays, or zeolites [3]) and tem- amines. Although hydrogen is not required as
peratures up to 500  C; however, use of these a direct reactant, in its absence imines, enamines,
catalysts is now restricted to the production of and even nitriles are formed. Hydrogen also
methylamines. For the conversion of an alcohol maintains the activity of the catalyst by removing
containing two or more carbon atoms, catalysts carbonaceous deposits and metal carbides or
possessing hydrogenating and dehydrogenating nitrides and prevents disproportionation of the
properties have become important. The catalysts amine products [6]. The various versions of the
used are mainly based on nickel, cobalt, copper or process have been reviewed in detail [7]. Several
iron, and to a lesser extent platinum or palladium. surface-bound intermediates were identified by
Noble metal catalysts have a tendency to cause Fourier transform IR spectroscopy [8]. While the
C – C or C – N bond cleavage and can hence give amination of diols and polyols in principle fol-
lower selectivities. Promoters such as Ag, Zn, In, lows the same rules as for the monools, the
Mn, Mo, and alkali metals are added to improve occurrence of numerous side reactions, for in-
catalyst performance. Mostly, the active compo- stance, cyclizations, is a complicating factor [9].
nents are supported on a carrier such as Al2O3, The same method is also useful for alkylating
SiO2, or ZrO2. Zeolites have been suggested as primary or secondary amines instead of ammonia.
carriers to improve the selectivity towards primary When an amine and an alcohol having different
amines [4]. In this process, the alcohol, ammonia, aliphatic substituents react, the product is a mixed
and hydrogen are passed continuously over the aliphatic amine. For example, N,N-dimethylethy-
catalyst in a fixed-bed reactor. The reaction takes lamine can be obtained from dimethylamine and
place at about 0.5 – 25 MPa and about 100 – ethanol. To avoid transalkylation at the nitrogen
250  C, depending on the catalyst and on whether atom in reactions of this type, copper catalysts are
the liquid-phase or the gas-phase process is used. recommended [10]. Copper chromite is a partic-
Mechanistic details of the process have been ularly effective catalyst for long-chain tertiary
reviewed [5]. The first and rate-determining step amines such as dimethyldodecylamine [11].
is the dehydrogenation of the alcohol to the
carbonyl compound. Addition of ammonia is
followed by loss of water to yield an imine or 3.2. Production from Carbonyl
an enamine, which is hydrogenated to the final Compounds
amine. Side reactions are amine disproportion-
ation, especially at higher reaction temperatures, Aldehydes and ketones are used in preference to
and to a lesser degree aldol condensation of the alcohols for amine synthesis if this is more
Vol. 2 Amines, Aliphatic 653

economical. Generally, this is the case only for 3.3. Production from Nitriles
the lower aldehydes (obtained from oxo synthe-
sis) and acetone obtained as a byproduct in the Frequently, nitriles can be obtained more eco-
production of phenol (Hock synthesis). nomically than the corresponding alcohols or
The reaction between a carbonyl compound carbonyl compounds. They are synthesized by
and ammonia or an amine occurs in two steps: ammoxidation, the addition of an amine or an
the imine or Schiff base formed initially is alcohol to acrylonitrile, or from the correspond-
hydrogenated with hydrogen in a second step ing carboxylic acid. Nitriles are converted into
to give the amine. The usual procedure is similar the corresponding amines, preferably by catalyt-
to that for the conversion of alcohols; the reac- ic hydrogenation:
tion mixture, comprising the carbonyl com-
pound, ammonia and hydrogen, is passed over
a fixed-bed catalyst. In some cases, it can be
advantageous to carry out the reaction in two
stages. The carbonyl compound and ammonia or
the amine react first, the water of reaction is
removed, and only then is the hydrogenation
carried out [12].
The essential difference between the amina-
tion of an aldehyde or ketone and that of an
alcohol is that in the former hydrogen is a reactant
and is consumed in a stoichiometric amount. The
substantially higher heat of reaction of this pro-
cess (e.g., 60.4 kJ/mol for acetone [13] versus Noble metal (palladium, platinum, rhodium),
7.1 kJ/mol for isopropyl alcohol) necessitates a nickel, or cobalt catalysts are generally em-
fundamentally different reactor design. In gener- ployed, but iron catalysts have been used to an
al, the process is carried out in the vapor phase at increasing extent [15], largely for economic rea-
100 – 160  C and atmospheric or slightly above sons. Whereas the supported noble metals permit
atmospheric pressure. High-pressure processes the use of relatively mild reaction conditions
can also be employed if the heat of reaction can (20 – 100  C, 0.1 – 0.5 MPa), pressures as high
be removed by appropriate measures, such as a as 25 MPa and temperatures of up to 180  C are
high recycle rate or with a multitubular reactor. required with nickel or cobalt catalysts. When di-
Since the reaction temperatures are lower than or polynitriles are hydrogenated to di- or poly-
for the reaction of alcohols, in principle, higher amines, a base such as NaOH is often added to the
selectivities can be achieved. catalyst [16]. There are various versions of the
Generally, the same catalysts as for the hydro- process, but those most often used are the batch
genative amination of alcohols can be used; process with a suspended catalyst and the con-
control of product distribution by adjusting the tinuous process with a fixed-bed catalyst.
amount of excess ammonia and workup by dis- Side reactions resulting in the formation of
tillation are also much the same. Comprehensive secondary amines always occur, but these can be
reviews of industrial and preparative possibilities suppressed by the addition of ammonia, sodium
for synthesis of amines from carbonyl com- hydroxide solution, or an acid [7]. Alternatively,
pounds are available [7], [14]. process conditions can be adjusted to make the
It is also possible to use other reducing agents formation of secondary or tertiary amines the
instead of hydrogen, but these are of little indus- principal reaction. This alternative is of interest,
trial importance. This is often due to the difficulty for example, in the synthesis of di- and triethy-
of handling and the cost of the reagents (e.g., lamines from acetonitrile [17] or dibutylamine
selenophenol or NaBH4). The Leuckart – Wal- from butyronitrile [18].
lach reaction, in which ammonium formate is The hydrogenation of acrylonitrile is a special
used to aminate the carbonyl compound with case. Whereas saturated amines are normally the
formation of CO2 as byproduct, has found some only products of this reaction, the use of copper
use. chromite as a catalyst instead of noble metals,
654 Amines, Aliphatic Vol. 2

nickel, or cobalt leads to allylamine and dially- the process. Nitroparaffins are more difficult to
lamine [19]. hydrogenate than their aromatic counterparts
Many important nitrile hydrogenations to [21].
form the corresponding amines are based on Functionalization of alkenes with NO or NO2
previous addition reactions of acrylonitrile. Al- has been described; the reaction follows a radical
cohols add to acrylonitrile only in the presence of path and affords a mixture of products, among
a basic catalyst such as NaOH, KOH, or quater- them nitroalkenes. Reduction of the latter also
nary ammonium hydroxides. Since amines are leads to amines, but has found no industrial
themselves sufficiently basic, addition occurs application so far. Likewise, primary amines
readily. Sometimes higher temperatures are were obtained from paraffins by nitration with
needed for cyanoethylation, and stabilizers have HNO3 or liquid NO2 and hydrogenation of the
been described to avoid polymerization of acry- resulting nitroparaffin/ketone mixture in the
lonitrile [20]. presence of ammonia [22]. The preparation of
1,2-diamines from nitroolefins and O-alkylhy-
droxylamines has been described [23].
3.4. Production from Alkyl Halides

The reaction of an alkyl halide with ammonia or 3.6. Production from Olefins
an amine gives an alkylammonium halide, from
which the amine can be liberated with a caustic Amines having a tertiary alkyl group adjacent to
alkali solution. Although a standard method of the nitrogen atom (e.g., tert-butylamine) are
preparative chemistry, this route is industrially difficult to obtain by conventional synthetic
important only for the preparation of ethylene- methods. These compounds can be prepared
diamine, the homologous polyamines, and a few readily by addition of hydrogen cyanide to an
special amines such as allylamine and some alkene, e.g., 2-methylpropene, in an acidic me-
small-volume pharmaceuticals. The reasons for dium:
this restricted use are the lack of cheap starting
materials, corrosion and product-quality pro-
blems that arise in the processing of halides, and
the need to dispose of the salt that is formed.

3.5. Production from Nitro


Whereas the reduction of nitro compounds is one This process, known as the Ritter reaction
of the most important methods for the synthesis [24], is carried out at 30 – 60  C, and the result-
of aromatic amines, this route has not become ing formamide intermediate is hydrolyzed when
important for the production of aliphatic amines. the reaction mixture is heated to ca. 100  C. To
Because the availability of appropriate nitroalk- liberate the amine, the acidic mixture is neutral-
anes is restricted, this method is used only in a ized to give sodium formate and the salt of the
few special cases, e.g., the production of 2-ami- original acid, i.e., sodium sulfate. Because hy-
no-1-butanol, the precursor for the antitubercu- drocyanic acid is difficult to handle and causes
lotic ethambutol. corrosion problems, one carbon atom is lost as
The reduction proceeds via the nitroso or formate, and significant amounts of salts (ca.
hydroxylamine intermediate, in some cases even 3.3 kg/kg tert-butylamine) must be disposed of
at room temperature, and gives the amine in in deep wells, this process is restricted to amines
yields of 90 % or more. Platinum, palladium, that cannot be obtained by one of the methods
rhodium, nickel, or copper is used as the hydro- described in Sections 3.1, 3.2, 3.3, 3.4, and 3.5.
genation catalyst [7]. The reaction is highly Besides tert-butylamine and tert-octylamine,
exothermic (ca. 500 kJ/mol per nitro group), and these are only a few amines of pharmaceutical
therefore heat must be removed rapidly to control interest.
Vol. 2 Amines, Aliphatic 655

Although advantageous thermodynamical- 4. Lower Alkylamines

ly, the direct addition of ammonia or an amine
to an olefinic double bond is restricted to a few 4.1. Physical Properties
cases in which either an activated amine or a
compound with an activated double bond is Ethylamine is gaseous at room temperature;
employed, for example, the addition of an diethylamine, triethylamine, and higher amines
amine to acrylonitrile. It is however possible up to about twelve carbon atoms per alkyl chain
to achieve the addition of ammonia to unac- are liquid, and long-chain amines containing still
tivated alkenes under pressure and by using higher alkyl groups are solid.
catalysts. The most effective catalysts are The short-chain amines are readily soluble in
acidic zeolites. The first successful demonstra- water, alcohol, ether, and conventional organic
tion was the formation of ethylamines from solvents. Amines containing more than five car-
ethylene and ammonia with H-mordenite [25]. bon atoms are only partially or very sparingly
Although the conversion for the direct amina- soluble in water. The solubility in water generally
tion of alkenes is low, being limited by kinetic decreases with increasing temperature, and in
factors and the thermodynamic equilibrium, some cases the miscibility gap vanishes at lower
the selectivity for monoalkylamines can be temperatures. For example, triethylamine is
excellent given the proper choice of zeolite completely miscible with water below about
and alkene. Small-pore zeolites are most suit- 18  C but is only partially miscible with water
able for ethylamines [26], while medium-pore above this temperature. Therefore, industrial
zeolites can be used to prepare tert-butylamine phase separations (amine/water) are often carried
[27]. Certain large-pore zeolites have been out at elevated temperatures.
found to offer improvements over medium- All alkylamines, but particularly the lower
pore zeolites [28–30]. members, which have high vapor pressures, have
Homogeneously catalyzed amination of al- a characteristic ammonia odor. The odor de-
kenes is restricted to some special cases [31], creases with increasing substitution.
[32]. Although not very selective, hydrofor- Physical properties of importance for charac-
mylation of alkenes in the presence of ammo- terizing and handling the alkylamines are sum-
nia or amines [33] might find applications in marized in Table 1. For further data, reference
future. So far it is hampered by the fact that in may be made to the relevant tables and the
addition to the amines arising from the n- producers’ data sheets.
aldehyde and isoaldehyde, significant amounts
of alcohols are formed besides dimerization
products [34]. 4.2. Storage and Transportation

The aliphatic amines are usually stored in car-

3.7. Other Processes bon steel or stainless steel containers; relatively
small amounts can be kept in glass or ceramic
The hydrogenation of aromatic amines to cy- vessels. Nonferrous metals such as copper, alu-
cloalkylamines is industrially restricted to the minum, zinc, lead, and their alloys (e.g., brass)
production of cyclohexylamines (see Chap. 5). A are not resistant to amines. Aqueous amine
process for synthesizing amines from carbon solutions are basic and slowly etch glass. Ethy-
monoxide, hydrogen, and ammonia or amines lamine must be stored under pressure because it
over an activated iron catalyst by a method of the boils below room temperature. Isopropylamine
Fischer – Tropsch-type was described [35], but (bp 32.4  C) is usually stored in cooled and
this is not used on an industrial scale. All other isolated tanks or in pressurized containers. To
synthetic routes described in the literature, for facilitate storage and transport, these amines are
instance reduction of amides [36], are so far also produced and distributed in the form of
essentially laboratory methods that are suitable aqueous solutions (e.g., 40 % or 70 %). The
for the preparation of small quantities and are aliphatic amines have a virtually unlimited shelf
carried out on an industrial scale only in isolated life, but they should be stored under nitrogen to
cases. For details see [3]. avoid contact with carbon dioxide (resulting in
656 Amines, Aliphatic Vol. 2

formation of carbamates) and atmospheric water content by the Karl Fischer method, titra-
moisture. tion of the imine content by oximation, and the
All of the amines discussed here are inflam- determination of physical properties.
mable. Some of them have very low flash points
(see Table 1), and they form explosive mixtures
with air. Hence, when these compounds are 4.4. Production
stored and transported, the relevant statutory
regulations for inflammable liquids or pressur- With few exceptions, aliphatic amines of indus-
ized gases must be observed. Because these vary trial importance are produced by any one of the
greatly from country to country, they cannot be methods described in Chapter 3. The main routes
discussed in detail here. start from the corresponding hydroxyl or carbon-
To prevent odor nuisance (odor thresholds are yl compounds. The choice of process depends
below 0.1 ppm in some cases) and impermissible mainly on the following criteria:
emissions, special precautions must be taken
during storage and, in particular, during transfer 1. Price of the starting materials
from one container to another. Where the process 2. Availability of the starting materials
cannot be carried out in a closed system and 3. Conversion of any existing plants to allow for
relatively large amounts are handled, absorption different pressures in the two processes
plants for washing off-gas must be provided. 4. Availability of hydrogen (hydrogen con-
Scrubbing with water is frequently adequate, but sumption and pressure differ in the two
better treatment of off-gas is achieved by scrub- processes)
bing with an acid. For smaller plants, adsorption 5. Fiscal reasons (taxes or subsidies on particular
on active carbon filters is advisable under certain materials, e.g., ethanol)
circumstances. This method has the additional
advantage that the adsorbed amines can be Because these factors vary greatly from coun-
recovered. try to country, and in some cases even from
The toxicity (Chap. 10) of these amines also region to region, and are changing continually,
makes it necessary to take certain precautions the reasons for the choice of a particular process
with regard to occupational safety. These in- depend strongly on individual circumstances.
clude, in particular, avoiding inhalation of amine Currently (2000) the commercial use of the
vapors by using respiratory equipment and reli- alcohol route is prevalent.
able prevention of skin and eye contact with fluid The aliphatic amines of large-scale industrial
amines by wearing protective clothing. importance (mainly C2 – C4) can be produced in
a multipurpose plant that can be used for the
production of various amines under similar reac-
4.3. Quality Specifications and tion conditions, with only small differences in
Analysis workup.
The reaction of an alkyl halide with ammonia
In the case of individual amines, the quality or an amine typically results in formation of
specifications are very high. Particularly for sodium halide as an undesired byproduct. This
amines with a wide range of uses (e.g., ethyla- synthetic route is used for ethylenediamine and
mine), specifications require a purity of above special amines such as allylamines (Chap-
99.7 %, although usually 98.0 – 99.5 % purity is ter 3.4). Ethylenediamine can also be produced
considered adequate. Some end uses impose from ethanolamine and ammonia or directly from
additional maximum values on the content of ethylene oxide.
water, ammonia, and unsaturated amines or, in Other production processes have become im-
the case of tertiary amines, on the content of portant only for a few amines. Examples are the
primary and secondary amines. production of tert-butylamine from isobutene
The amine content is determined by acid and hydrogen cyanide or, since 1987, by direct
titration of the basic nitrogen, and the purity is amination [37] (Section 3.6).
determined preferably by gas chromatography. Another industrial route to alkylamines is the
Also of importance is the determination of the addition of amines to acrylonitrile followed by
Vol. 2 Amines, Aliphatic 657

hydrogenation. Examples are 1,3-diaminopro- this case all three ethylamines are separated in a
pane and dipropylenetriamine, produced by com- specially designed distillation unit and marketed.
bination of ammonia and acrylonitrile and sub- To construct a multipurpose plant, it must first
sequent hydrogenation, and the hydrogenation of be decided whether the synthesis is to be run at
3-alkoxypropionitriles, which are produced by low to medium (0.1 – 3 MPa) or high pressure
addition of alcohols to acrylonitrile to give 3- (5 – 30 MPa). The design of the distillation unit
alkoxypropylamines (Section 3.3). depends on the range of amines to be produced.
When the conversion of alcohol to amine is For the whole range of lower alkylamines (start-
performed in the liquid phase under high pressure ing with ethylamines) a complicated system of
(typically 20 MPa) the plant can consist of a five to six distillation towers is needed. With three
synthesis unit with a cylindrical reactor, heat distillation towers, a plant for a restricted portfolio
exchangers, high- and medium-pressure (3 MPa) of alkylamines can be run. The first pressure tower
separators and a distillation unit. The distillation (typically 1.5 – 1.8 MPa) separates ammonia/
towers separate ammonia/low-boiling alkyla- low-boiling amine, the second water, and the
mine, water, and high-boiling residues and re- third the desired alkylamine. The excess amines
move the monoalkylamine from di- and trialk- are reycled to the synthesis unit. For instance, a
ylamine. Ammonia/low-boiling alkylamine is monoalkylamine can be produced by feeding pure
generally used in excess and recycled to the alcohol and ammonia or by feeding recycled di-
synthesis reactor. Water is typically isolated by and trialkylamines, fresh alcohol, and ammonia.
phase separation and fed to a wastewater treat- Instead of ammonia low-boiling amines such as
ment system. If the reaction mixture does not methylamine or dimethylamine can be used for
meet market requirements, the excess amines can the synthesis of mixed amines. An example is the
be returned to synthesis stage since the mono-, production of N,N-dimethylethylamine from eth-
di-, and trialkylamines are in thermodynamic anol and dimethylamine.
equilibrium (see Section 3.1).
Reactions in the gas phase are typically carried
out in low-pressure reactor systems which require 4.5. Uses
only one gas – liquid separator (3 MPa) and can
be set up with cheaper equipment. Figure 1 Ethylamines. Of the amines discussed here,
shows a simplified flow diagram of the catalytic with a worldwide market volume (2000) of about
gas-phase reaction of ethanol with ammonia. In 80 000 t/a, the ethylamines are the most impor-

Figure 1. Continuous process for the production of ethylamines [38]

a) Vaporizer; b) Heat exchanger; c) Superheater; d) Catalytic converter; e) Product cooler; f) Gas separator; g) Ammonia
column; h) Monoethylamine column; i) Diethylamine column; j) Decanter; k) Triethylamine column
658 Amines, Aliphatic Vol. 2

tant lower aliphatic alkylamines. For tax reasons, operations. Important examples of these uses
in Japan ethylamines are produced from acetal- are in the synthesis of semisynthetic penicillins
dehyde, while in other countries ethanol is mostly and cephalosporins, and as solubilizers for herbi-
used. The general production processes are simi- cides in combination with 2,4-dichlorophenox-
lar; differences lie in the catalyst used, the distil- yacetic acid or 2,4,5-trichlorophenoxyacetic acid.
lation conditions, and the recycle streams (e.g., Triethylammonium is the cationic component of
[39]). Production of di- and triethylamine from the herbicide Garlon 3A (Dow Elanco). Other
acetonitrile is described in [17]. important fields of use include polyurethane cat-
The principal use of monoethylamine is in the alysts (for example, the hardening of core sands in
production of herbicides of the triazine type by cold-box casting), curing catalyst for phenol –
reaction with cyanuric chloride. Important com- formaldehyde resins, anticorrosion agents, paper,
mercial products are atrazine (Novartis), ame- textile and photographic auxiliaries, and anodic
tryne (Novartis), cyanazine (ACC, DuPont), electrocoating.
simazine (Novartis), terbutryn (Novartis), desme-
tryn (Novartis), terbumeton (Novartis), secbume- Propylamines. The commercial demand for
ton (Novartis), simetryn (Novartis) and terbutyla- n-propylamines and isopropylamines is together
zine. Lately, the demand for atrazine has decreased about the same as that for the ethylamines.
due to environmental concerns, and it has been Monoisopropylamine is the most important prod-
banned in certain western European countries. A uct and is used particularly in the production of
triazine derivative has also been suggested as herbicides such as bentazon (BASF), Roundup
stabilizer for chlorine in swimming pools [40]. (Monsanto), imazapyr (ACC) and the triazines
Ethylamine, via N-ethylcyclohexylamine, also ametryne (Novartis), atrazine (Novartis), desme-
ends up in the herbicide cycloate (see below). The tryn (Novartis), prometryn (Novartis), pramitol
fungicide cymoxanil (DuPont) is also made from (Novartis), dipropetryn (Novartis), and propa-
ethylamine. The ethylamine demand for rubber zine (Novartis, Makteshim-Agan and Drexel).
applications, for instance, toluene ethylsulfona- Other applications encompass the nematicide
mide, is declining. fenamiphos (Bayer), the fungicide iprodione
A large percentage of the total diethylamine (Rhône-Poulenc), insecticides, pharmaceuticals,
production is used for N,N-diethylaminoethanol, and surfactants.
which is formed by reaction with ethylene oxide Dipropylamine is required principally as a start-
and finds application as a corrosion inhibitor and in ing material for the synthesis of herbicides, e.g.,
coatings. Diethylamine is also used for the produc- trifluralin (Dow), oryzalin (Dow), EPTC (Zeneca),
tion of vulcanization accelerators. Reaction with and vernolate (Zeneca). The other propylamines
carbon disulfide gives a dithiocarbamate that can are of minor importance compared to monoiso-
be oxidized to a thiuram disulfide. The most propylamine and dipropylamine. Diisopropyla-
important commercial products are sodium and mine is mostly used for agrochemicals such as the
zinc diethyldithiocarbamate and tetraethylthiuram herbicides diallate and triallate (Monsanto), but
disulfide. Diethylamine is used for the production also for rubber accelerators such as DIBS (N,N-
of certain agrochemicals, such as rice herbicides diisopropyl-2-benzothiazylsulfenamide). n-Pro-
[e.g., Napropamide (Zeneca) and Thiobencarb pylamine is used for agrochemicals and pharma-
(Kumiai)] or insecticides [e.g., Phosphamidon ceuticals. Tripropylamine is an intermediate for
(Novartis, DuPont) and Pirimiphos-methyl (Zene- pharmaceuticals and corrosion inhibitors.
ca)], pharmaceuticals, radical scavengers (diethyl-
hydroxylamine), and insect repellents (N,N- Butylamines. Diisobutylamine is the princi-
diethyl-3-methylbenzamide, Autan). pal starting material for the herbicide Butylate
Of the three ethylamines, triethylamine has the (Zeneca). tert-Butylamine is primarily employed
widest range of uses and is also the most expen- for the synthesis of vulcanization accelerators, for
sive product owing to the unfavorable distribution instance, TBBS (N-tert-butyl-2-benzothiazylsul-
of monoethylamine, diethylamine, and triethyla- fenamide) and TBSI (N-tert-butyl-2-benzothia-
mine in production. Much of the triethylamine is zylsulfenimide). tert-Butylamine is also used
used as an organic acid acceptor in synthesis or as for the production of herbicides, i.e., terbacil
a salt former in precipitation and purification (DuPont) and the triazines terbutylazine, terbu-
Vol. 2 Amines, Aliphatic 659

meton (Novartis), and terbutryn (Novartis) and Some 10 000 t/a of tertiary alkyl primary
insecticides (e.g., diafenthiuron from Novartis). A amines are manufactured by Rohm & Haas by
derivative has also been proposed as stabilizer for means of the Ritter reaction. These primene
cosmetics [41]. The synthesis of vulcanization amines range from tert-octylamine to C18 – C22.
accelerators of the sulfenamide type is an impor- Of the unsaturated amines, diallylamine has
tant outlet for dibutylamine (e.g., sodium dibu- the most significant market (ca. 1000 t/a); it is
tylthiocarbamate, zinc dibutyldithiocarbamate or used for the production of N,N-diallyldichlora-
tetrabutylthiuram disulfide); the demand for this cetamide. Copolymers of dimethyldiallylammo-
amine for other purposes (e.g., corrosion protec- nium chloride with acrylates or acrylamides are
tion, flotation agents, cutting oils, plastics, and used for water treatment. N-Ethylmethallylamine
intermediates for insecticides (e.g., carbosulfan) is employed for herbicide production (Dow’s
and pharmaceuticals) is less important. sonalan).
Monobutylamine is an intermediate for the Although chloroalkylamines (mainly chlor-
production of plasticizers (e.g., the rubber accel- oethyl- and chloropropyl-N,N-dialkylamines)
erator dibutylthiourea), agrochemicals (e.g., are not important in terms of the amounts em-
DuPont’s fungicide benomyl), pharmaceuticals ployed, they are important starting materials for
(e.g., the antidiabetic tolbutamide), emulsifying the production of a number of pharmaceuticals
agents, dyes, and UV absorbers. (principally neuroleptics).
Tributylamine is also used commercially (a Although not a lower alkylamine, polyiso-
few 100 t/a) as a polymerization catalyst and as butenamine (PIBA) is produced with the same
an acid acceptor. sec-Butylamine is consumed in technology by amination of the hydroformyla-
small amounts for herbicides such as bromacil tion product of polyisobutene (PIB) with a
(DuPont) or secbumeton (Novartis). molecular mass of about 1000 [42]. About
10 000 t/a PIBA is used as an detergent in
Other Amines. Of the C4þ monoamines, finished additive packages for gasoline to im-
only few are of commercial importance. Octy- prove the mechanical functioning of the engine,
lamine is required, for example, for the produc- lower fuel consumption, and give improved
tion of biocides, as a solvent for pesticides, and as emission characteristics.
precursor for N-octylpyrrolidone – which is used
for the cleaning of printing machines – whereas
2-ethylhexylamine is employed for the produc- 4.6. Economic Aspects
tion of oil additives and for insecticides. Di-2-
ethylhexylamine is used for oil additives, dyes, Worldwide production capacity for aliphatic
and pharmaceutical applications. Tri-2-ethylhex- amines including fatty amines but excluding
ylamine (bp 337.9  C) is also commercially methylamines is estimated to be ca. 500 000 t/a,
available and mainly used in coatings. Tridecy- of which about 40 % is attributable to the United
lamine (mixture of isomers) is used for the States and about 30 % to western Europe. Because
production of the fungicide tridemorph (BASF). of the large number of producers and the varying
A mixture of the pentylamines finds use in dril- capacities of multipurpose plants, exact figures for
ling applications. N,N-Dimethylethylamine is an annual worldwide production are not available.
important epoxy and urethane catalyst, for in- Apart from those who produce mainly for their
stance, in sand-core applications. It is made from own requirements, the most important producers of
ethanol and dimethylamine. N,N-Dimethyliso- lower aliphatic amines are Air Products, Hoechst
propylamine, usually obtained from acetone and Celanese, and Elf Atochem in the United States;
dimethylamine under hydrogenating conditions, BASF, Elf Atochem, Hoechst Celanese, and ICI in
is also used in foundry applications. N-Ethyldii- Western Europe; Daicel in Japan; and Nordeste/
sopropylamine (H€ unig’s base) finds use as a good Oxiteno in Brazil.
acid acceptor. Mono-, di-, and trihexylamine are Manufacturing costs vary significantly de-
also commercially available, but represent very pending on the availability of the starting mate-
minor products. Isoamylamine (3-methyl-1-bu- rials and the type of process, e.g., continuous
taneamine) is an intermediate for pharmaceuti- dedicated plant vs. batch process in a multipur-
cals and agrochemicals. pose plant.
660 Amines, Aliphatic Vol. 2

5. Cycloalkylamines Chemical Properties. Chemically cyclohex-

ylamine has much in common with the acyclic
Cyclopentylamine [1003-03-8], aminocy- aliphatic amines [3], [43]. Cyclohexylamine re-
clopentane, C5H11N, Mr 85.15, is a colorless acts with chlorine to form N,N-dichlorocyclo-
liquid, mp  85  C, bp 106 – 108  C (at hexylamine [44]. For conversion to azomethines
101.3 kPa), d420 0:8689, n20
D 1:4482, flash point and their chemistry, see [45]. N-Cyclohexylide-
17  C, with an ammoniacal odor. necyclohexylamine reacts with chloramine
to give 1-cyclohexyl-3,3-pentamethylenediazir-
idine, which can be hydrolyzed to give cyclohex-
ylhydrazine [46]. Cyclohexylamine and formal-
dehyde together react with peracetic acid to give
2-cyclohexyloxaziridine [47]. In addition to
Production. Cyclopentylamine is produced
using alkyl halides, alkyl sulfates, or alkyl phos-
from cyclopentanone and ammonia over nickel
phates, cyclohexylamine can be alkylated with
catalysts at 20 MPa and 150 – 200  C in the
an alcohol in the presence of a catalyst, such as
presence of circulating hydrogen over a fixed-
aluminum oxide, copper, nickel, cobalt, or plati-
bed catalyst.
num (reviewed in [48], [49]), or by the Leuck-
art – Wallach method [50].
Uses. Cyclopentylamine is used in small
amounts as an intermediate for the potato and
Production. Cyclohexylamine can be pro-
rice fungizide pencycuron (Bayer, Nihon To-
duced by catalytic hydrogenation of aniline
kushu, Noyaku Seizo).
under pressure. High yields are obtained with
nickel or cobalt catalysts treated with basic
Cyclohexylamine [108-91-8], aminocyclo-
oxides [51]. Raney cobalt treated with calcium
hexane, cyclohexanamine, hexahydroaniline,
oxide and sodium carbonate gives a cyclohex-
hexahydrobenzenamine, aminohexahydroben-
ylamine yield of more than 96 % at 6 MPa and
zene, C6H13N, Mr 99.18, is a colorless liquid,
230  C [52]. Noble metals also are employed as
mp  17.8  C, bp 134.5  C (at 101.3 kPa),
catalysts [53].
d425 0:8647, n20
D 1:4592. The alternative synthesis from cyclohexanol
and ammonia over supported cobalt catalysts
[54] is also an important method; calcium silicoa-
luminates are also suitable catalysts [55]. In this
process, cyclohexanol reacts at 20 MPa and
220  C with at least 3 mol of ammonia in the
Viscosity presence of circulating hydrogen over a fixed-bed
t,  C 0 20 50 75 catalyst. Using the same continuous procedure,
h, Pa  s 3.73 2.10 1.14 0.77 cyclohexanone can be hydrogenated with ammo-
nia under amination conditions [56]; nickel or
Vapor pressure
cobalt catalysts are used for this process, which is
t,  C 20 60 100 120
carried out at 0.1 – 20 MPa. Cyclohexylamine can
p, kPa 1.43 8.66 35.99 65.31
also be obtained by reacting phenol with hydrogen
Specific heat capacity
and ammonia over a rhodium catalyst [57].
t,  C 20 70 145
c, J g1K1 2.366 2.583 2.910
Heat of vaporization 399.86 J/g
Quality. The purity of the commercial prod-
Flash point (closed cups) 26.5  C uct is above 99.5 % and is determined by gas
Ignition temperature (class T3) 265  C chromatography; contaminants are ammonia and
Ignition range in air 1.6 – 9.4 vol % water.

Cyclohexylamine is infinitely miscible with Storage and Transportation. Cyclohexyl-

water and conventional organic solvents. With amine can be stored and shipped in iron tanks.
water it forms an azeotrope that contains 44.2 % Nonferrous metals, particularly copper-contain-
cyclohexylamine and boils at 96.4  C. ing materials, are attacked and are therefore
Vol. 2 Amines, Aliphatic 661

unsuitable. The amine discolors on contact with Specific heat capacity 2.14 J g1 K1 (at 20  C)
2.47 J g1 K1 (at 140  C)
air and therefore must be kept under nitrogen.

Uses. Cyclohexylamine is used primarily as N-Methylcyclohexylamine is infinitely misci-

corrosion inhibitor and vulcanization accelerator. ble with water, methanol, acetone, toluene, and
Alone or mixed with other compounds, it has an cyclohexane.
anticorrosive action [58], for example, when used
as an additive in heating oil or in the operation of Production. N-Methylcyclohexylamine can
steam boilers. It is also employed as a salt-form- be prepared by a procedure similar to that used
ing and amide-forming component in many ap- for cyclohexylamine, i.e., by hydrogenation of
plications, for example, in the above mentioned methylaniline over a supported nickel catalyst
vulcanization accelerators (CBS, N-cyclohexyl- [63] or from cyclohexanone and methylamine
2-benzothiazylsulfenamide [59]), plasticizers under hydrogenation conditions [64]. Cyclohex-
[salts with dodecanethiol and mercaptobenzothia- ylamine reacts with methanol over copper, zinc,
zole (CMBT)] [60]], emulsifiers (emulsification or copper – calcium catalysts [65].
of active ingredients in water with cyclohexylam-
monium alkylbenzenesulfonate [61]) and coagu- Uses. N-Methylcyclohexylamine is used as
lators (salt with acetic acid). Salts of C10 – C14 a component of vulcanization accelerators [66],
fatty acids prevent foam formation in mineral oils but the market size is relatively small.
[62]. Cyclohexylamine functions as a hardener
for epoxy resins and as a catalyst for polyur- N,N-Dimethylcyclohexylamine [98-94-2],
ethanes. Sodium cyclohexylsulfamate and calci- cyclohexyldimethylamine, C8H17N, Mr 127.23,
um cyclohexylsulfamate (cyclamates) are impor- is a colorless liquid, mp <–50  C, bp 159  C (at
tant artificial sweeteners. In polyamide polymer- 101.3 kPa), d425 0:8467, n20
D 1:4519, h 3 mPa  s
izations, cyclohexylamine is employed as chain (at 25  C).
terminator to control the molecular mass. Other
applications of cyclohexylamine are for instance
in herbicide production. An example is DuPont’s
Hexazinone [3-cyclohexyl-6-(dimethylamino)-
1-methyl-1,3,5-triazine-2,4-(1H,3H)-dione]. The
total market for cyclohexylamine is around
20 000 t/a. Manufacturers include Air Products,
BASF, Bayer, and Hoechst Celanese. Vapor pressure
t,  C 20 40 60 80 100 120 140
N-Methylcyclohexylamine [100-60-7], p, kPa 0.29 1.05 3.21 8.29 18.13 35.99 63.72
C7H15N, Mr 113.2, is a colorless liquid, mp  9  C, Flash point 
38.1 C
bp 150  C (at 101.3 kPa), d425 0:8533, n20
D 1:4551, Ignition temperature (class T4) 200  C
h 5 mPa  s (at 25  C). Explosion limits in air 0.79 and 7.0 vol %
(corresponding to 41.8
and 370 g/m3)
Heat of vaporization 285.6 J/g
Specific heat capacity 1.88 J g1K1 (at 20  C)
2.51 J g1K1 (at 140  C)

Vapor pressure The compound is sparingly soluble (1 %) in

t, C 20 40 60 80 100 120 140
water, but the solubility of water in dimethylcy-
p, kPa 0.48 1.72 4.68 11.48 24.13 46.26 81.31
clohexylamine is ca. 20 %. N,N-Dimethylcyclo-
hexylamine is miscible with conventional organ-
Flash point 36.1  C ic solvents.
Ignition temperature (class T3) 255  C
Explosion limits in air 2.2 and 10.5 vol %
(corresponding to 103 Production. N,N-Dimethylcyclohexylamine
and 494 g/m3) is produced by hydrogenation of dimethylaniline
662 Amines, Aliphatic Vol. 2

at 180  C and 6 MPa [67] or by amination of cide cycloate (Zeneca’s Ro-Neet), which is ob-
cyclohexanone under hydrogenation conditions tained by converting N-ethylcyclohexylamine
in the presence of dimethylamine [68]. In princi- into S-ethyl-N-ethyl-N-cyclohexylthiocarbamate.
ple, it could also be obtained from phenol by A minor use of N-ethylcyclohexylamine is for
reaction with dimethylamine, but this route is vulcanization accelerators.
commercially less attractive.
Dicyclohexylamine [101-83-7], dodecahy-
Uses. N,N-Dimethylcyclohexylamine is a drodiphenylamine, N,N-dicyclohexylamine, N-
catalyst for the production of polyurethane, par- cyclohexylcyclohexanamine, perhydrodipheny-
ticularly for making foams, and for this purpose it lamine, C12H23N, Mr 181.32, is a colorless liquid,
is used as the free base [69] or as the salt of an mp  0.1  C, bp 256  C (at 101.3 kPa), bp
organic acid [70]. The curing temperature of 133  C (at 2.6 kPa), d425 0:9104, n20
D 1:4852.
baking finishes comprising polyurethane-form-
ing substances can be reduced by 50 – 80  C by
adding weakly acidic derivatives of the amine
[71]. Like pyridine, dimethylcyclohexylamine
catalyzes certain reactions and is slightly more
efficient than pyridine in the preparation of acid
chlorides with thionyl chloride [72]. It can be Flash point 105  C
used as corrosion inhibitor and as an antioxidant Ignition temperature (class T3) 240  C
Explosion limits in air 0.83 and 4.6 vol %
in fuel oils. (corresponding to 62 and
350 g/m3)
N-Ethylcyclohexylamine [5459-93-8], Specific heat capacity 1.88 J g1 K1 (at 20  C)
C8H17N, Mr 127.2, is a colorless liquid, mp  43 2.47 J g1 K1 (at 140  C)
C, bp 165  C (at 101.3 kPa), d420 0:846,
D 1:4525, h 1.39 mPa  s (at 20 C).
 Dicyclohexylamine is sparingly soluble in
water (ca. 0.16 % at 28  C) but is readily soluble
in the conventional solvents.

Production. Dicyclohexylamine can be

formed as a byproduct in the production of
cyclohexylamine from aniline or cyclohexa-
Vapor pressure nol/cyclohexanone [73]. When desired as the
t,  C 20 40 80 120 end product, dicyclohexylamine is obtained by
p, kPa 0.24 0.84 6.13 27.59 amination of cyclohexanone under hydrogena-
Flash point 46  C tion conditions [74] or, in higher yield, from
Ignition temperature 245  C
cyclohexanone and cyclohexylamine over Pd/C
(class T3)
Explosion limit in air 1.2 and at a hydrogen pressure of 0.4 MPa [75]. Dicy-
7.6 vol % clohexylamine can also be obtained by amina-
tion of phenol under hydrogenation conditions,
or by the reaction of phenol with aniline over Pd/
N-Ethylcyclohexylamine is only slightly C at 0.5 MPa under hydrogenation conditions
soluble (2.3 %) in water, but the solubility of [76].
water in ethylcyclohexylamine is 25 %. The
amine is miscible with conventional organic Uses. Dicyclohexylamine and its salts have
solvents. good anticorrosion properties in the vapor
Ethylcyclohexylamine is produced by hydro- phase [77]. Paper treated with the nitrite is
genation of ethylaniline at 180  C and 6 MPa used as anticorrosion paper. The nitrite also
[67] or by amination of cyclohexanone under imparts these properties when incorporated into
hydrogenation conditions in the presence of ethy- alkyd resins [78]. Like the other cyclohexyla-
lamine [68]. The amine is a starting material for mines, dicyclohexylamine is useful as a com-
the preplant sugar beet, grass, and spinach herbi- ponent of vulcanization accelerators (for in-
Vol. 2 Amines, Aliphatic 663

stance DCBS, N,N-dicyclohexyl-2-benzothia- clude fibers, pigments, films, and epoxy curing
zylsulfenamide, or DCMBT, the salt with 2- agents.
mercaptobenzothiazole) and of pesticides. It is
also consumed as a processing chemical for 2,2-Bis(4-aminocyclohexyl)propane [3377-
antibiotics and as fuel oil additive. 24-0], isopropylidenedi(cyclohexylamine),
C15H30N2, Mr 238.42, mp 51 – 53  C, bp 155 –
N-Methyldicyclohexylamine [7560-83-0], 160  C (at 0.65 kPa), d420 0:99.
N,N-dicyclohexylmethylamine, N-cyclohexyl-
N-methyl-cyclohexanamine, C13H25N, Mr
195.35, is a liquid, bp 275  C (at 101.3 kPa),
d425 0:9207, n25D 1:4881, h 10.2 mPa  s (at
25  C), flash point 66  C.

2,2-Bis(4-aminocyclohexyl)propane can be
obtained by amination of the corresponding
bishydroxy compound in the liquid phase under
pressure. Product yields of ca. 90 % are obtained
over hydrogenation catalysts containing palladi-
um [57], ruthenium [80] or cobalt, manganese,
and phosphoric acid [81]. Alternatively, hydro-
Vapor pressure
genation of the condensation product of aniline
t,  C 63 90 150 190 248
and acetone, bisaniline A, furnishes the same
p, kPa 0.133 0.599 2.66 13.33 66.65 compound. The industrial product is a mixture
of three stereoisomers. Concentration of the
trans,trans isomer by treating the isomer mixture
N-Methyldicyclohexylamine is sparingly sol- with phosphoric acid under reduced pressure at
uble in water and THF but readily soluble in 230  C or by recrystallization from branched
acetone, methanol, toluene, cyclohexane, and octanes [82] is important because polymerization
chloroform. It is prepared by methylating dicy- of the pure isomer gives polyamides of better
clohexylamine with dimethyl sulfate or by the quality.
Leuckart – Wallach reaction [79] and has uses
similar to those of the other cyclohexylamines, e. Cyclooctylamine [5452-37-9], C8H17N, Mr
g., as a urethane foam catalyst. 127.23, is a liquid, mp  48  C, bp 80  C (at
1.3 kPa), mp of hydrochloride 244 – 245  C, mp
4,40 -Diaminodicyclohexylmethane [1761- of picrate 193 – 194  C, d420 0:9280, n20
D 1:4804,
71-3], methylene bis(4,40 -cyclohexylamine), bis flash point 62  C.
(4-aminocyclohexyl)methane, 4,40 -methylene-
biscyclohexanamine, C13H26N2, Mr 210.36, mp
60 – 62  C (cis,cis), 64 – 65  C (trans,trans), bp
330 – 331  C (at 101.3 kPa), d420 0:96, flash
point 153.5  C, is a water insoluble solid.
The amine can be produced by the Ritter
reaction of cyclooctanol with hydrocyanic acid
[83], by reduction of cyclooctanone oxime
with sodium and an alcohol [84], by Ritter
The large-volume product 4,40 -diaminodi- reaction of cyclooctene with hydrocyanic acid
cyclohexylmethane is manufactured by several [85], or by catalytic hydrogenation of cyclooc-
companies by the catalytic hydrogenation of tanone under amination conditions [86]. Cy-
methylene dianiline. The isomer distribution in clooctylamine is used as a component of urea
the yield is controlled, since the main product herbicides, e.g., cycluron (BASF). Its chemical
from the amine is the isocyanate, which is used behavior is analogous to that of other primary
in urethane coatings. Other applications in- amines.
664 Amines, Aliphatic Vol. 2

Cyclododecylamine [1502-03-0], C12H25N, Chemically, pyrrolidine behaves like a sec-

Mr 183.34, mp 31 – 32  C, bp 95 – 96  C (at ondary amine in every respect. For example, it
0.25 kPa), n32:5
D 1:4849; mp of hydrochloride undergoes Leuckart – Wallach and Mannich re-
268 – 270  C, mp of picrate 232 – 234  C, flash actions and is readily converted into an enamine.
point 121  C. In the presence of a catalyst, such as platinum
at 360  C or rhodium at 650  C [91], pyrrole
is formed. In the presence of a copper catalyst,
N-methylpyrrolidone is converted into N-

Production. Pyrrolidine can be produced

Cyclododecylamine is produced by reduc- from butanediol and ammonia, e.g., over an
tion of cyclododecanone oxime with sodium aluminum thorium oxide catalyst at 300  C
and an alcohol [87], by catalytic reduction of [92] or over a nickel catalyst at 200  C and
nitrocyclododecane with hydrogen [88], by Rit- 20 MPa under hydrogenation conditions. It can
ter reaction of cyclododecene with hydrocyanic also be produced from THF and ammonia over
acid [89], or by hydrogenation of cyclododeca- aluminum oxide at 275 – 375  C [93].
none under amination conditions [90]. The re-
action of cyclododecylamine with propylene Uses. Pyrrolidine is used virtually exclu-
oxide leads to a product that can undergo cycli- sively for the synthesis of pharmaceuticals, in-
zation to give the fungicide Dodemorph cluding antibiotics. In addition, it is used for
(BASF). The compound behaves chemically as producing vulcanization accelerators.
a primary amine.
N-Methylpyrrolidine [120-94-5], 1-methyl-
pyrrolidine, C5H11N, Mr 85.15, colorless liquid;
mp  90  C, bp 80 – 81  C (at 101.3 kPa),
6. Cyclic Amines d420 0:7992, n20 
D 1:4236, flash point  21 C.

Pyrrolidine [123-75-1], tetrahydropyrrole,

C4H9N, Mr 71.12, is a colorless liquid, mp  60
C, bp 87 – 88  C (at 101.3 kPa), d420 0:8576,
D 1:4428, h 1.1 mPa  s (at 20 C).
Piperidine [110-89-4], hexahydropyridine,
pentamethyleneimine, azacyclohexane, cyclo-
pentimine, cypentil, hexazane, C5H11N, Mr
85.15, derives its name from the alkaloid piper-
ine, the pepper flavoring, in which piperidine is
present as piperic acid piperidide.
Flash point 3 C
Ignition temperature (class T2) 345  C
Explosion limits in air 1.6 and 10.6 vol %
(corresponding to 47
and 314 g/m3)
Specific heat capacity 2.20 J g1 K1 (at 21  C) Piperidine, a colorless liquid, mp  10.5  C,
2.25 J g1 K1 (at 65  C) bp 106.4  C (at 101.3 kPa), with a sharp ammo-
2.27 J g1 K1 (at 77  C) nia odor, is hygroscopic and fumes in air;
Heat of vaporization 529 J/g (at 0.1 MPa)
d420 0:8613 (the temperature dependence of the
density is given in [94]), n20
D 1:4532.

Pyrrolidine is infinitely miscible with water Vapor pressure

and conventional organic solvents such as meth- t,  C 13.0 25.0 40.0 51.0 67.8 78.8 87.2
anol, acetone, ether, and chloroform. It acts as a p, kPa 2.0 4.0 8.0 13.3 26.7 40.0 53.3
Vol. 2 Amines, Aliphatic 665

The vapor pressure curve is given in [95]; is the preferred catalyst. The use of piperidine is
flash point 3  C, dissociation constant particularly advisable where the reactants or
1.6  103 (at 25  C). Piperidine is infinitely products are unstable in the presence of stronger
soluble in water, lower alcohols and ketones, bases.
ethers, aliphatic and aromatic hydrocarbons, eth-
yl acetate, and DMF. It forms an azeotrope with N-Methylpiperidine [626-67-5], C6H13N,
water: Mr 99.18, colorless liquid; mp  18  C, bp
106 – 107  C (at 101.3 kPa), d420 0:8157,
p, kPa 100.8 53.3 26.7 n20 
D 1:4378, flash point 3 C.
bp,  C 93.7 76.9 61.4
Piperidine, mass fraction in % 63.7 68.1 76.0

The preparation of enamines from piperidine

takes place particularly smoothly [96], [97], [98].
Uses. N-Methylpiperidine is used for the
Unlike open-chain amines, cyclic amines react
production of a growth regulator for cotton
with aldehydes to give aminals as intermediates
[99]. Only pyrrolidine is comparably versatile.
N-Ethylpiperidine [766-09-6], C7H15N, Mr
Production. Pyridine obtained from tar dis-
113.20, colorless liquid; bp 131  C (at
tillation is contaminated by sulfur-containing
101.3 kPa), d420 0:8237, n20
D 1:4440, flash point
compounds and therefore can be hydrogenated
19  C.
economically only in a two-stage process. The
crude pyridine is first hydroraffined over a sulfi-
dic metal catalyst at 280 – 310  C and then
hydrogenated quantitatively to piperidine at
120 – 160  C over a Ni – Al2O3 catalyst
[100]. Sulfur-free pyridine can be hydrogenated Uses. N-Ethylpiperidine has found use as a
over a ruthenium [101] or cobalt catalyst. catalyst in polycarbonate manufacture.
The preparation of piperidine by aminolysis
of 1,5-pentanediol under hydrogenation condi- Hexamethyleneimine [111-49-9], HMI,
tions at 225 – 260  C and 20 MPa over a cobalt azacycloheptane, hexahydroazepine, homopi-
catalyst has been described [102], but can also be peridine, perhydroazepine, C6H13N, Mr 99.18,
affected with nickel catalysts. A similar prepara- is a liquid, mp  37  C, bp 139  C (at
tion from tetrahydrofurfuryl alcohol also has 101.3 kPa), d420 0:8799, n20
D 1:4658, flash point
been described [103]. When piperidine is pre- 30  C, ignition temperature 255  C.
pared by hydrogenating glutarates [104], glutaric
acid [105], or glutaraldehyde [106], the reaction
is carried out in the presence of a large excess of

Uses. The secondary amine piperidine is Hexamethyleneimine and water form a 1/1
highly reactive and is therefore frequently em- azeotrope that boils at 95 – 95.5  C. The hex-
ployed as an intermediate for pharmaceuticals amethyleneimine – water solubility curve is giv-
[107] and for plant protection agents. It is also en in [112]. The chemical behavior of hexam-
used as a vulcanization accelerator in rubber ethyleneimine is determined entirely by the
manufacture and as an oil or fuel additive [108]. secondary amino group.
Piperidine and, in many cases, piperidine
acetate are useful catalysts for condensation Production. Hexamethyleneimine is pro-
reactions, e.g., the Knoevenagel reaction [109], duced in 84 % yield by heating hexamethyle-
aldol condensation [110], and the condensation nediamine at 350  C in a stream of hydrogen.
of a nitroparaffin with an aldehyde [111]. How- The catalyst, ammonium vanadate on activated
ever, for the last of these reactions, diethylamine alumina, is prereduced with hydrogen at
666 Amines, Aliphatic Vol. 2

500  C [113]. Residues from the industrial Chemically, morpholine behaves as a second-
distillation of hexamethylenediamine can be ary amine in every respect. It forms complexes
converted into hexamethyleneimine over alu- with many cations. In addition to the Leuckart –
minum silicate or aluminum oxide in a stream Wallach and Mannich reactions, the conversion
of nitrogen [114]. For the preparation from to enamines has become important [96], [97].
caprolactam, see [115]. Hexamethyleneimine Morpholine, pyrrolidine, and piperidine are pre-
can be prepared by dimerizing acrolein, reduc- ferred to the open-chain amines for these reac-
ing the product to 2-hydroxymethyltetrahydro- tions because they react faster with the carbonyl
pyran, expanding the ring to give oxepane, component.
followed by treatment with ammonia over alu-
minum oxide at 350  C [116]. Production. Morpholine can be obtained
from diethanolamine by cyclization with sul-
Uses. The most important use is the conver- furic acid or via diethanolamine hydrochloride
sion of hexamethyleneimine into S-ethylhexahy- [117] or from di(2-chloroethyl) ether and am-
dro-1H-azepine-1-carbothioate, the selective monia [118]. Industrially more important is the
rice herbicide Molinate (C2H5S–CO–NC6H12, amination of diglycol under hydrogen pressure
Zeneca). Minor amounts of hexamethyleneimine and over a cobalt or nickel catalyst [42], [119].
are used for the production of rubber vulcaniza- Other catalysts are described in [120]. An
tion accelerators, resins, pharmaceuticals, and important byproduct frequently obtained is
textile auxiliaries; numerous patents describe the 2-(2-aminoethoxy)ethanol, which is the result
anticorrosive action of hexamethyleneimine and of simple amination without subsequent cycli-
its derivatives. zation; after separation of morpholine, this
compound can be recycled to the synthesis
Morpholine [110-91-8], tetrahydro-2H- reactor.
1,4-oxazine, diethylene oximide, diethylenimide
oxide, 1-oxa-4-azacyclohexane, C4H9NO, Mr Quality and Storage. When produced from
87.12, is a colorless hygroscopic liquid; mp  diglycol, commercial morpholine is more than
5  C, bp 128.2  C (at 101.3 kPa), d420 1:007, 99 % pure; the main impurities are N-ethylmor-
D 1:4542, h 2.3 mPa  s (at 20 C). pholine and ethylenediamine. Morpholine can be
stored for an unlimited time in iron containers if it
is protected from atmospheric moisture and car-
bon dioxide. Copper, zinc, and their alloys are
unstable towards morpholine.
Vapor pressure
Uses. Morpholine is an intermediate for a
t,  C 10 20 40 60 80 100 120 large number of pharmaceuticals, crop protec-
p, kPa 0.57 1.1 3.2 8.3 20.5 40.9 81.8 tion agents, dyes, and optical brighteners. An
Critical pressure 5.302 MPa
important use is the conversion to vulcaniza-
Critical temperature 344  C
Flash point 43  C tion accelerators or sulfur donors, which are
Ignition temperature 275  C based on 2-mercaptobenzothiazole, dithiocar-
Explosion limits in air 1.8 vol % and 15.2 vol % bamic acid, thiuram polysulfides, or sulfena-
Specific heat capacity 1.2 J g1K1 (at 25  C)
mides, e.g., MBS [2-(4-morpholinylmercapto)
2.15 J g1K1 (at 100  C)
Heat of vaporization 505 J/g (at 25  C) benzothiazole], DTDM (4,40 -dithiodimorpho-
425 J/g (at 128  C) line), and MBSS (4-morpholinyl-2-benzothia-
zyl disulfide). Salts of morpholine with long-
chain fatty acids, such as oleic or stearic acid,
Morpholine is infinitely miscible with water have waxlike properties and are used as
and conventional solvents such as methanol, emulsifiers.
acetone, benzene, and glycol. The mixture con- Because water and morpholine have similar
sisting of 88 % morpholine and 12 % water has a volatilities and the latter is an anticorrosion
freezing point below  50  C and a viscosity of agent, it is useful in steam cycles [121], aqueous
7.45 mPa  s at 20  C. hydraulic liquids [122], and similar systems. Up
Vol. 2 Amines, Aliphatic 667

to 550  C, no substantial loss occurs as a result of N-Formylmorpholine [4394-85-8], 4-mor-

decomposition. pholinecarbaldehyde, C5H9NO2, Mr 115.13, mp
An aqueous solution of morpholine (2 M) can 20 – 21  C (anhydrous), 9  C (5 % water), –
be used for removing CO2, H2S, or HCN from 3  C (10 % water), bp 244  C (anhydrous),
gases [123]. In the extraction of aromatic com- 172  C (2 % water), 151  C (5 % water), 132  C
pounds from hydrocarbon mixtures, morpholine (8 % water) (all at 101.3 kPa), d420 1:1268,
is highly selective [124]. n20 
D 1:4835, flash point 124 C, is hygroscopic.

Morpholine Derivatives. N-Methylmor-

pholine and N-ethylmorpholine are used as
catalysts for the production of polyurethane
foams. N-Formylmorpholine is used as a selec-
tive solvent for the extraction of high-purity N-(2-Hydroxyethyl)morpholine [622-40-2],
aromatic compounds in the Formex process 4-(2-hydroxyethyl)morpholine, 4-morpholi-
(Snamprogetti). noethanol, C6H13NO2, Mr 131.17, mp  1  C,
bp 227  C (at 100.9 kPa), d420 1:0733,
D 1:4760, flash point 99 C, is used as an
N-Methylmorpholine [109-02-4], 4-methyl- intermediate for pharmaceuticals.
1-oxa-4-azacyclohexane, C5H11NO, Mr 101.15,
mp  65  C, bp 114  C (at 101.3 kPa),
d420 0:919, n20 
D 1:4347, h 0.90 mPa  s (at 20 C),

flash point 13 C.

N-(2-Aminoethyl)morpholine [2038-03-1],
2-morpholinoethylamine, 4-(2-aminoethyl)mor-
pholine, C6H14N2O, Mr 130.19, mp 24  C, bp
205  C (at 101.3 kPa), d420 1:001, n20
D 1:4755,
Methylmorpholine can be obtained from flash point 175  C, is used as an intermediate
diethylene glycol and methylamine or by react- for pharmaceuticals.
ing morpholine with formaldehyde to give N-
hydroxymethylmorpholine and reducing the
product with excess formaldehyde [125], formic
acid [126], or hydrogen over cobalt or manga-
nese catalysts under pressure [127]. Another
important reaction is the alkylation of morpho- Piperazine [110-85-0], 1,4-diethylenedia-
line with methanol at a total pressure above mine, hexahydropyrazine, dispermine, hexahy-
3.5 MPa and a hydrogen partial pressure above dro-1,4-diazine, C4H10N2, Mr 86.14, forms
1 MPa [128]. strongly hygroscopic, colorless lamellar crystals
Alkylmorpholines are also obtained by cycli- with a typical amine odor, mp 109.6  C, bp
zation of bis(2-chloroethyl) ether with an amine 148  C (at 101.3 kPa), mp of the hexahydrate
[129] or of diethylene glycol with an amine in the 42.0  C.
presence of hydrogen and a hydrogenation cata-
lyst [130].

N-Ethylmorpholine [100-74-3], C6H13NO,

Mr 115.18, mp  63  C, bp 134 – 137.5  C (at
Vapor pressure
101.3 kPa), d420 0:913, n20
D 1:4415, h 1.05 mPa  t,  C
s (at 20  C), flash point 27  C, is miscible with
110.8 121.7 125 140.6
p, kPa 30.3 44.6 49.6 79.7
water. Flash point 98  C
Ignition temperature 340  C
Explosion limits in air 3.93 kPa and 12.0 kPa
(corresponding to 139 g/m3
and 430 g/m3)
668 Amines, Aliphatic Vol. 2
These are the saturated vapor pressures above piperazine at
64.0  C and 90.5  C.
been known [132], but has remained unimpor-
Specific heat capacity 2.94 J g1 K1 (at 130  C) tant. The polymers so formed have a heat resis-
2.99 J g1 K1 (at 140  C) tance superior to that of conventional polyamides
Heat of vaporization 47.3 J/g but require the use of stabilizers [133].
The use of 1,4-bis(1-aziridinylcarbonyl)pi-
perazine or 1,4-bis(chloroacetyl)piperazine for
Piperazine is readily soluble in water, metha- curing gelatine for photographic purposes was
nol, and ethanol but only slightly soluble in proposed [134].
diethyl ether, benzene, and heptane. Piperazine
has the chemical properties of a secondary amine. N-Methylpiperazine [109-01-3], 1-methyl-
Vapor-phase dehydrogenation over copper chro- piperazine, C5H12N2, Mr 100.16, colorless hygro-
mite or palladium gives pyrazine. scopic liquid, mp  6  C, bp 138  C (at
101.3 kPa), d420 0:9021, n20
D 1:4658, flash point
Production. Piperazine is obtained as a by- 42  C.
product in the production of ethylenediamine, in
particular when ethanolamine is used as starting
material [131]. If ethanolamine reacts with am-
monia at 150 – 220  C and 10 – 25 MPa, piper-
azine can be distilled from the reaction mixture,
which also contains unreacted ethanolamine, N-Ethylpiperazine [5308-25-8], 1-ethylpi-
ethylenediamine, diethylenetriamine, aminoethy- perazine, C6H14N2, Mr 114.19, colorless liquid,
lethanolamine, and polyamines. mp  60  C, bp 157  C (at 101.3 kPa),
Piperazine is obtained with a purity of 99 %, d420 0:8989, n20 
D 1:4690, flash point 47 C.
and can be converted to flakes, even after con-
version to the hexahydrate. Frequently, it is
transported as an approximately 65 % aqueous
solution, which has a low melting point of about
45  C and hence corresponds roughly to an
eutectic mixture. The purity is determined in N, N0 -Dimethylpiperazine [106-58-1], 1,4-
most cases by gas chromatography. If it can be dimethylpiperazine, C6H14N2, Mr 114.19, color-
assumed that organic impurities are absent, the less liquid, mp  1  C, bp 131 – 132  C (at
purity can be determined titrimetrically (HCl or 101 kPa), d420 0:8509, n20 D 1:4463, flash point
HClO4) in aqueous solution. 18  C, can be used as catalyst for polyurethane
foams and as an intermediate for cationic surfac-
Storage. Since piperazine is corrosive, the tants. It is obtained from piperazine and methanol
flakes are stored in barrels lined with a polyeth- or formaldehyde under aminating conditions.
ylene sack. To avoid yellowing, the barrels
should be air tight and not exposed to direct
sunlight. The aqueous solution is stored at
50 – 60  C in insulated iron tanks that can be

Uses. Piperazine, in the form of the hexahy- N-(2-Aminoethyl)piperazine [140-31-8],

drate or as salts, is used as an anthelmintic in AEP, 1-(2-aminoethyl)piperazine, 2-piperazin-
human and veterinary medicine. Furthermore, 1-ylethylamine, C6H15N3, Mr 129.21, colorless
the piperazine ring is a constituent of a large liquid, mp  19  C, bp 218 – 222  C (at
number of other pharmaceuticals. It is also an 101.3 kPa), d420 0:9842, n20 D 1:5000, flash point
intermediate for dyes, corrosion inhibitors, rub- 93  C, h 15 mPa  s (at 20  C) is corrosive,
ber vulcanization accelerators, insecticides, and toxic, and hygroscopic. AEP is a byproduct of
surfactants. ethylenediamine production and is used as a
The production of polyamides from pipera- hardener for epoxy resins, as an urethane cata-
zine and aliphatic dicarboxylic acids has long lyst, and also acts as a corrosion inhibitor [135]. It
Vol. 2 Amines, Aliphatic 669

is also an intermediate for dyes, surfactants and washing with petroleum ether give 95 % pure
various pharmaceuticals. triethylenediamine; sublimation gives a 98 %
pure product. Processes starting from piperazine
derivatives (N-hydroxyethylpiperazine, N,N0 -
bishydroxyethylpiperazine or N-aminoethylpi-
perazine) are described in [137], [139]. Dealumi-
nated or untreated ZSM-5 zeolites are claimed to
N-(2-Hydroxyethyl)piperazine [103-76- produce TEDA from various precursors, includ-
4], HEP, 1-(2-hydroxyethyl)piperazine, 1-piper- ing ethanolamine and piperazine [140]. Com-
azineethanol, C6H14N2O, Mr 130.19, mp  10 pared to the amorphous catalysts, the zeolite
C, bp 246  C (at 101.3 kPa), d420 1:0595, catalysts have the advantage of shape selectivity.
D 1:5058, flash point 135 C. HEP is obtained
during ethyleneamine production and used for Uses. The only important industrial use of
corrosion inhibitors, pharmaceuticals, surfac- triethylenediamine is as a hardener for polyure-
tants, and synthetic fibers. thane foams [141]. However, more effective aza-
and diazabicyclooctane derivatives intended for
the same purpose have been the subject of patent
applications [142].

Hexamethylenetetramine [100-97-0],
HMTA, hexamine, methenamine, 1,3,5,7-tetra-
Triethylenediamine [280-57-9], TEDA, azaadamantane, 1,3,5,7-tetraazatricyclo[
1,4-diazabicyclo[2.2.2]octane, Dabco, C6H12N2, (3,7)]decane, C6H12N4, Mr 140.19, is a highly
Mr 112.17, is a highly symmetrical molecule with symmetrical molecule with an adamantane struc-
a cage structure. The colorless extremely hygro- ture. Trade names: Urotropin, Formin, Amino-
scopic crystals melt at 159.8  C; bp 174  C, pKa1 form. It crystallizes from ethanol as colorless,
2.95, pKa2 8.60, flash point 50  C. hygroscopic rhombododecahedra.

Triethylenediamine reacts virtually quantita- At reduced pressure (2 kPa), hexamethylene-

tively with bromine to give a 1/1 adduct. With tetramine sublimes at 230 – 270  C, virtually
alkyl halides it forms quaternary salts, even in without decomposition, mp > 270  C (de-
nonpolar solvents. Apart from its highly nucleo- comp.), r 1.3394 g/cm3 (at 22  C), enthalpy of
philic nature, triethylenediamine exhibits cata- formation 124.1  0.75 kJ/mol. For further
lytic activity in base-catalyzed reactions. thermodynamic data, see [143]. For the IR spec-
trum, see [144]. The vapor pressure between 20
Production. Triethylenediamine can be pro- and 280  C can be calculated from the formula
duced from ethylenediamine or ethanolamine log(p/kPa) ¼ – 524.8/(T/K) þ 1.334 [145].
[136], diethanolamine [137], or diethylenetria- Flash point 250  C.
mine [138] with a variety of different catalysts. At 12  C, 81.3 g of hexamethylenetetramine
All processes give only moderate yields. For dissolves in 100 g of water; the solubility de-
example, in the presence of a catalyst consisting creases slightly with increasing temperature. The
of 86 % silicon dioxide and 12 % aluminum dissociation constant is 1.4  109 (temperature
oxide at 360  C and atmospheric pressure, not given). The solubility of hexamethylenetet-
diethylenetriamine gives about equal amounts ramine in 100 g of various solvents at 20  C is as
of piperazine, alkylpiperazines, pyrazines, and follows: 13.4 g in chloroform, 7.25 g in metha-
ethylenediamine and homologues in addition to nol, 2.89 g in absolute ethanol, 0.65 g in acetone,
the bicyclic compound. Fractional distillation, 0.23 g in benzene, 0.14 g in xylene, 0.06 g in
subsequent recrystallization from acetone, and ether, and near zero in petroleum ether.
670 Amines, Aliphatic Vol. 2

Hexamethylenetetramine gives a monobasic Quality. As a rule, the industrial product is

reaction, but with strong acids it is dibasic. The 99 % pure. The compound is purified by stepwise
equilibrium C6H12N4 þ 6 H2O
6 CH2O þ crystallization (see [152]). The addition of par-
4 NH3 in aqueous solution permits the use of affin, benzoic acid, acid amides, or diatomaceous
hexamethylenetetramine as a formaldehyde or earth gives free-flowing products [153].
ammonia donor. Thermolysis leads to hydro-
cyanic acid in a yield of 73 % at 800  C, and Uses. Hexamethylenetetramine can be used
92 % at 1200  C [146]. Nitration gives 1,2,3- as an ammonia or formaldehyde donor, for ex-
trinitro-1,2,3-triazine, which is an important ample, in the production of phenol resins, urea –
explosive (hexogen, cyclonite, RDX). The in- formaldehyde resins and in fuel tablets. Further
tact tricyclic structure can be alkylated and uses are the production of the high explosives
arylated at the nitrogen atom and halogenated hexogen and octogen, vulcanization accelera-
at the carbon atom. It undergoes a large number tors, and anticorrosion agents. Proposed uses
of addition reactions: adduct formation with relate to the activation of chlorites as bleaches
phosgene, disulfur dichloride, and many inor- [154] and the preservation of foodstuffs [155],
ganic salts. paints, finishes, and latexes [156], and as anti-
bacterial agent for the urinary tract.
Production. Formaldehyde and ammonia
can be converted into hexamethylenetetramine
in the gas phase, in aqueous solution, or in a 7. Fatty Amines
suspension in an inert solvent, although the most
important of these procedures is that carried out Straight-chain primary, secondary, and tertiary
in water. The usual process gives a pure product amines with chain lengths between 8 and 24 carbon
in yields near 90 % and includes an economical atoms are commonly known as fatty amines. This
drying step. group of compounds also includes derivatives such
If aqueous solutions of ammonia (27 %) and as the N-alkyl-1,3-propanediamines. Of commer-
formaldehyde (30 %) react continuously at up to cial importance are fatty amine mixtures, such as
95  C in a V4A stainless steel tubular reactor, it is coco amine, tallow amine, hydrogenated tallow
necessary to dewater a 14 % solution of amine, oleylamine, and soya amine, which are
hexamethylenetetramine [147]. If formaldehyde derived from naturally occurring fatty acids. More
and ammonia are reacted in the vapor phase, the recently, alkylamines of similar structure were
product is precipitated with cold water [148] or produced from synthetic feedstocks such as olefins
is discharged with an aqueous solution of or paraffins, and these also are called fatty amines
hexamethylenetetramine [149]. (b-amines, branched chain amines, aminoalka-
The heat of reaction in aqueous solution is nols). Only partly covered are fatty amine ethox-
230 kJ/mol, and in the vapor phase 745 kJ/mol. ylates, fatty alkyl quaternary ammonium salts,
Therefore, the presence of a minimum amount of alkyl betaines and fatty amine oxides, although
water is desirable. In this method [150], ammonia all of these are fatty amine derivatives.
gas and formaldehyde gas are passed continu-
ously into the boiling reaction solution. The
boiling point is brought to 50 – 70  C. The heat 7.1. Properties
of hydration and heat of reaction vaporize the
water of condensation. The hexamethylenetetra- Physical Properties. Table 2 lists typical
mine is removed in crystalline form or as a compositions of fatty amine mixtures. The prop-
concentrated solution. erties of these can be varied to some extent by
In another method, ammonia gas and formal- blending chain lengths with the desired physical
dehyde solution react at pH 7.5 – 8 and 50 – characteristics. Fatty acids are also available in
90  C, and the product is granulated by spray fractionated form and thus narrower ranges of
drying in a hot inert gas stream (220 – 250  C), fatty amines may be produced.
or by spraying it onto hexamethylenetetramine
particles in a fluidized bed in an air stream at Solubilities of selected fatty amines in polar
80 – 115  C [151]. and nonpolar organic solvents are given in
Vol. 2 Amines, Aliphatic 671

Table 2. Mixture composition of primary fatty amines (mass fraction in %) [157]

Number of carbon atoms in alkyl chain

Saturated alkyl Unsaturated alkyl*

6 8 10 12 14 15 16 17 18 140 160 180 180 Other

Coco 0.5 8 7 50 18 8 1.5 6 1
Hydrogenated-tallow 1 4 0.5 30 1.5 60 0.5 0.5 2
Tallow 1 3 0.5 29 1 23 1 3 37 1.5
Oleyl 0.5 3.5 0.5 4 1 5 1.5 5 76 3
Soya 0.5 1 16 15 1 49.5 13 4
A single prime indicates one double bond; a double prime, two double bonds.

Table 3. Solubility (g per 100 mL at 30 C) of fatty amines in organic

solvents [158] 26.5 Pa for dodecylamine to 2.7  102 Pa
(0.27  103 mbar) for eicosylamine. Some
2-Propanol Hexane physical properties of pure compounds and
Primary amines commercial mixtures are given in Table 4.
Dodecylamine ¥ ¥ The oscillation of melting points between the
Tetradecylamine 458 216 series of odd-chain and even-chain homologues
Hexadecylamine 169 64.8
Octadecylamine 86 27.9
is shown in Figure 2. This effect disappears in
Secondary amines derivatives of primary fatty amines.
Dioctylamine ¥ ¥ Almost all amines derived from natural
Didodecylamine 55 27.5 sources have an even number of carbon atoms.
Dioctadecylamine 1.2 (50  C) 2.1 (40  C)
Tertiary amines
Diamines and 2-(alkylimino)diethanols [N,N-
Trioctylamine ¥ ¥ bis(2-hydroxyethyl)alkylamines] are low-melt-
Tridodecylamine 23.9 ¥ ing pasty solids. Unsaturation decreases the
Trioctadecylamine 36.4 melting points of the amines relative to the fully
saturated compounds. Fatty amines and their
Table 3. Only the short-chain fatty amines with derivatives are cationic surfactants (! Surfac-
8 – 10 C atoms per alkyl chain are of limited tants) and show strong substantivity to the neg-
solubility in water. atively charged surface of most solids, e.g.,
cotton, minerals, and metals, and thus change
Vapor Pressures at ambient temperature the physical properties of the substrates [163],
are generally very low and decrease from [164].

Table 4. Physical properties of fatty amines [159–162]

Formula Mr mp,  C bp*,  C Hydrochloride decomp. Acetate mp,  C

temp.,  C

Pure primary amines

Octylamine C8H17NH2 129.25 0.1 180.0 198
Decylamine C10H21NH2 157.30 15.9 221.8 194
Dodecylamine C12H25NH2 185.35 28.2 259.1 179 – 181 56.0 – 56.3
Tetradecylamine C14H29NH2 213.41 38.0 292.3 150 – 167 66.0 – 66.8
Hexadecylamine C16H33NH2 241.46 46.0 321.9 148 – 166 74.0 – 74.2
Octadecylamine C18H37NH2 269.52 53.1 348.5 158 – 161 79.8 – 80.0
Eicosylamine C20H41NH2 297.57 59.5 372.5 151 – 154 85.0 – 85.2
Docosylamine C22H45NH2 325.63 65.3 394.6 150 – 153 88.8 – 89.0
Commercial mixtures of primary amines
Coco amine 12 – 17 130 – 227 ca. 50
Oleylamine 200 – 210
Tallow amine 32 – 40 200 – 230 ca. 55
Hydrogenated-tallow amine 48 – 56 ca. 60
Soya amine 27 – 30
At 101.3 kPa for pure compounds, at 3.6 kPa for mixtures
672 Amines, Aliphatic Vol. 2

5. Oxyalkylation with ethylene oxide, a more

selective reaction than alkylation. The un-
catalyzed reaction with primary amines at
150 – 200  C yields almost exclusively 2-
(alkylimino)diethanols (N,N-bis(2-hydro-
xyethyl) fatty amines). Base catalysis even
at temperatures as low as 100  C leads to bis
(polyoxyethyl) amines [168]. Under mild
conditions (80  C, 350 Pa) and in the pres-
ence of water or acids, secondary and tertiary
Figure 2. Melting points of primary amines amines react readily with ethylene oxide to
form the corresponding bis- or mono(2-hy-
droxyethyl) quaternary ammonium salts
Chemical Properties. Fatty amines, like [169–171]. Long-chain epoxides undergo a
short-chain amines, are stronger bases than am- similar reaction [172], but products from
monia. Their ionization constants [165] do not ethylene and propylene oxide are the only
change significantly with chain length (see important commercial products.
Table 5), and their reactions are similar to those 6. Reaction of fatty amines with halogenated
known from the lower homologues. carboxylic acids or with lactones to give
The following are industrially important amphoteric compounds (betaines).
reactions: 7. Michael addition to activated double bonds.
For example, the important 1,3-propanedia-
1. Salt formation with inorganic and organic mines are synthesized by the reaction of a
acids. The hydrochlorides are slightly more primary fatty amine with acrylonitrile fol-
soluble and the acetates considerably more lowed by hydrogenation of the intermediate
soluble in water than the free amines. Acet- 2-(alkylimino)ethanenitrile [173].
ates and salts of higher fatty acids are readily 8. Mannich reactions with formaldehyde and
soluble in organic solvents [158]. The melt- nucleophiles, such as aldehydes, nitroparaf-
ing points of the salts are higher than those of fins, or phenols, to form polyfunctional de-
the free amines. rivatives [174–176].
2. Conversion into N-alkyl carboxamides with 9. Reaction with phosgene to form isocyanates
carboxylic acids or their derivatives. and ureas.
3. Reaction with carbon dioxide to give carba- 10. Oxidation by hydrogen peroxide, peroxoa-
mates, which are formed as contaminants in cids, or ozone to give amine oxides. Indus-
amines exposed to air. trially, oxidation of tertiary amines to amine
4. Alkylation with excess of strong nucleo- oxides by hydrogen peroxide is very impo-
philes, such as methyl chloride, benzyl chlo- tant since the products find use as
ride, or dimethyl sulfate, leading eventually surfactants.
to quaternary ammonium compounds. This
reaction is normally carried out in aqueous
alcohol as the solvent and in the presence of 7.2. Production
alkali as the proton acceptor [166], [167].
Fatty amines can be produced from natural fats
and oils or from synthetic raw materials [177].
Table 5. pKb Values of amines in water at 25 C*
Production from Fatty Nitriles. The most
R RNH2 R2NH R3N important source of fatty amines is still fatty
Methyl 3.38 3.29 4.24
nitriles, which are themselves formed from
Ethyl 3.37 3.02 fatty carboxylic acids and ammonia over op-
Octyl 3.35 3.00 tional dehydrating catalysts (Al2O3, SiO2,
Octadecyl 3.40 3.00 ZnO, bauxite, or salts of Ti, Fe, Mn, or Co)
The pKb of NH3 in water at 25  C is 4.79. in batch liquid-phase reactors or continuous
Vol. 2 Amines, Aliphatic 673

liquid- and vapor-phase reactors at 160 – N,N-dimethylalkylamines can also be pro-

430  C and 0.03 – 0.7 MPa. The principal raw duced from fatty nitriles and dimethylamine
materials are coconut oil, palm kernel oil, and [186]. Both types of methyl-substituted tertiary
tallow. amines are accessible also from primary alcohols
Depending on the process, the nitriles are [187], [188], and this route is used almost
purified by distillation or used as such. The fatty exclusively.
acid feedstocks may be fractionated beforehand Efforts to use methanol or hexamethylenetet-
as well. Hydrogenation of nitriles can lead to all ramine to methylate the nitriles with different
three types of amine, depending on reaction catalysts to obtain N,N-dimethylalkylamines or
conditions. Hydrogenation may be batch or con- N-methyldialkylamines are descibed in [189].
tinuous and is sensitive to catalyst poisons from
the natural feedstock. Production from Alcohols or Carbonyl
Compounds. Fatty amines are produced by re-
Primary Amines are formed by hydrogena- ductive alkylation of ammonia or substituted
tion of fatty nitriles, typically at 80 – 140  C and amines with primary linear alcohols (C8 – C18)
1 – 4 MPa, over nickel or cobalt catalysts. Ra- at 90 – 190  C under low pressure (atmospheric
ney cobalt or copper chromite catalysts are used up to 0.7 MPa) in the presence of a Raney nickel
to obtain unsaturated amines [178–180]. To catalyst. If water is continuously removed from
avoid formation of secondary amines, ammonia the reactor, only secondary and tertiary amines
is commonly used as a suppressant; a solvent may are obtained [190–192]. Similarly, aldehydes can
also be used. be converted into primary amines by reductive
amination at 110 – 120  C and 1.5 MPa with rare
Secondary Amines. If ammonia is continu- earth-promoted cobalt catalysts [193]. Oxo alde-
ously or periodically vented from the reactor and hydes react with methylamine to form imines,
temperatures of 150 – 210  C and pressures of which are then hydrogenated to give N-methy-
5 – 20 MPa are maintained, saturated and unsat- lalkylamines at 115  C and 3 MPa with a Raney
urated secondary amines can be obtained in nickel catalyst [194]. Similarly, both alcohols and
yields of > 90 % [181], [182]. Catalysts mainly aldehydes can be converted into N,N-dimethyl
used are nickel, cobalt, and copper chromite. tertiary amines with dimethylamine. Alcohols are
converted into amines at 230  C at atmospheric
Tertiary Amines. Symmetrical trialkyla- pressure with copper chromite catalysts, whereas
mines are obtained similarly to the secondary fatty aldehydes require noble metal, copper che-
amines, but usually mixtures of primary, second- late, or copper carboxylate catalysts [195–198].
ary, and tertiary amines result. Tertiary amines The widely used fatty alkyl dimethylamines
may also be produced from nitriles via the imine are nowadays almost exclusively produced from
RCH¼NH and Schiff base RCH¼N–CH2R by long-chain natural, oxo, or Ziegler fatty alcohols
using supported nickel catalysts at 230  C and (C12 – C18). Conversion is achieved by reacting
0.7 MPa hydrogen partial pressure [183]. dimethylamine with the fatty alcohol at elevated
More important are the N-alkyl-N-methylalk- temperatures and pressures with copper, copper
ylamines and the N,N-dimethylalkylamines, chromite, or nickel catalysts. Alternatively, the
which can be synthesized by the Leuckart reac- fatty alcohol can initially be converted to the
tion of primary or secondary amines [184], [185]: primary fatty amine by using ammonia and a
nickel catalyst and subsequently treated with
formaldehyde as described above. Some other
two-stage processes starting from fatty alcohols
RNH2 þ2CH2 Oþ2HCOOH!RNðCH3 Þ2 þ2CO2 þ2H2 O
and with sodium alkyl sulfates or chlorides as
intermediates have been described, but direct
Industrially, the reduction of the formalde- conversion with dimethylamine is the most
hyde may be achieved with hydrogen and a attractive.
nickel catalyst, e.g.:
RNH2 þ2CH2 Oþ2H2 !RNðCH3 Þ2 þ2H2 O
Production from Olefins. a-Olefins can be
converted to 1-bromoalkanes by radical addition
674 Amines, Aliphatic Vol. 2

(anti-Markovnikov) of hydrogen bromide [199]. These fatty amines have an uneven number of
Reaction with ammonia furnishes primary fatty carbon atoms and are hence distinct from the
amines, and using dimethylamine results in ter- more common primary amines from the nitrile
tiary fatty amines. A higher amount of branched route.
chain isomers is likely for the a-olefin route as
compared with the alcohol route. N-Alkyl-1,3-propanediamines. These so
Under hydrocarbonylation conditions, a-ole- called fatty diamines are obtained by acryloni-
fins and dimethylamine form N,N-dimethylalk- trile addition to fatty amines followed by hydro-
ylamines directly if highly selective noble metal genation in the presence of ammonia:
catalysts are used [200]. Use of the less specific
tributylphosphinecobalt catalysts leads to mix-
tures of amines and alcohols [201].
In a Ritter reaction, a-olefins react with hy-
drogen cyanide or acetonitrile in concentrated
sulfuric acid or aqueous hydrogen fluoride, via Acrylonitrile addition may be catalyzed by the
the intermediate 2-acylaminoalkane, to give presence of methanol and is conducted at tem-
branched alkyl primary amines (b-amines). The peratures between 30 and 90  C. Hydrogenation
reaction is not specific, and positional isomers are is performed under the same conditions as for the
also formed [202], [203]. fatty nitrile hydrogenations above. Polyamines
Aluminum alkoxides, as formed in the Ziegler may also be obtained similarly.
process, can be used to convert secondary amines
into tertiary amines [204].
7.3. Analysis and Quality Control
Production from Alkane Derivatives. Ni-
troalkanes with a statistical distribution of nitro Because of their relatively high basicity, fatty
groups can be hydrogenated over Pd/C at 190  C amines can be titrated easily with acids. Most of
and 3.9 MPa to form secondary alkyl primary the amines are insoluble in water; therefore,
amines in yields of up to 93 % [205]. Nickel organic solvents, such as isopropyl alcohol, are
catalysts can also be used. Selectively chlorinat- commonly used. End points are determined col-
ed alkanes react with dimethylamine to yield up orimetrically (bromophenol blue) or potentiome-
to 65 % terminal tertiary amine [206]. trically. In the second case, perchloric acid and
glacial acetic acid are preferred as titrant and
Production from Other Starting Materi- solvent, respectively.
als. Glycerides and methyl esters of fatty acids Industrial mixtures of amines normally con-
can be converted into fatty nitriles at 220 – 300  C tain up to 90 % of the main compound. These
provided ammonia is vented rapidly. Yields of mixtures are analyzed by stepwise titrations with
nitrile and glycerine in excess of 80 % were re- acid. The total basicity is determined first. Pri-
ported with zinc carboxylate or aryl sulfate cata- mary amines then are removed with salicylalde-
lysts [207]. Under hydrogenation conditions over hyde, and primary and secondary amines can be
Zn – Al catalysts at high pressures (10 – 30 MPa) removed with phenylisothiocyanate or acetic
and temperatures (200 – 350  C), coconut glycer- acid, so that the remaining free amine can be
ides can be converted into primary coco amine. titrated with acid. Unsaturated amines are deter-
Glycerine, however, decomposes completely un- mined by means of the iodine number. Because
der these conditions [208]. amine groups also consume iodine, the original
Primary fatty amides can be converted in high Wijs method must be slightly modified by using
yields into odd-chain primary amines by Hof- acetic acid as the solvent. The resulting amine
mann degradation of the chloroamide intermedi- salt absorbs the halide at a much slower rate than
ate [209]: the double bonds.
Quaternary ammonium compounds usually
are determined by solvent partition titration with
anionic surfactants or sodium tetraphenylboron
[210]. Iodine numbers of quaternary ammonium
Vol. 2 Amines, Aliphatic 675

compounds are obtained in sodium lauryl sulfate this application. A third area of application are
containing chloroform to prevent the free iodine wash cycle softeners, in which quaternaries are
from being retained by the nonaqueous phase. A combined with other detergents to achieve both
summary of approved wet chemical test methods cleaning and softening.
(AOCS, ASTM) is given in [211]. The fatty quaternary ammonium compounds
Chain-length distribution and hydrocarbon used were formerly mainly dimethyl dihydroge-
content of fatty amines are determined by gas nated tallow ammonium chloride, but this com-
chromatography [212–216]; nitrile and amide pound was replaced in many countries by other
impurities are determined by IR spectroscopy surfactants because of its lack of biodegradability
[217], [218]. and potential aquatic toxicity. Nowadays the
More recently, NMR spectroscopy has been most widely used quaternaries are ester quats,
used for determination of quaternary ammonium which are not derived from fatty amines but from
compounds in the presence of free amines [219] fatty acids, alcoholamines (e.g., triethanola-
and also for establishing the relative amounts of mine), and methylating agents.
primary, secondary, and tertiary amines in mix- Amine ethoxylates, mainly derived from pri-
tures [220]. mary tallow, hydrogenated tallow and coconut
Fatty amines can be stored in carbon steel amines, are also used in large amounts for
containers; aluminum, copper or their alloys are textiles.
to be avoided. Quaternary amines are more cor-
rosive and thus require lined drums or stainless Flotation. One of the first commercial uses
steel. With water hydrates are formed by primary of primary fatty amines was in the beneficiation
and secondary amines and carbamates with CO2. of potash [221]. In this process, fatty amine salts
adhere to the surface of potassium chloride,
allowing it to be removed by froth flotation and
7.4. Uses leaving the sodium chloride in the tailings. The
technique spread to other mineral beneficiation
Fabric Softeners. By far the largest use of processes [222], the most important of which are
fatty amines and in particular their quaternary phosphate rock, precious metals, lead, zinc, cop-
derivatives used to be in fabric softening. Prior to per, molybdenum, tin, fluorspar, feldspar, mag-
the early 1950s, fabric softeners were not needed nesite, limestone, mica, manganese, silica, and
because most detergents were based on tallow- coal. In general, any negatively charged surface
derived soap formulations and some of the active can be removed from a system with an amine salt.
detergent remained on the textile and resulted in a Ore flotation accounts for the largest direct use of
softer dried fabric. However, the advent of syn- primary fatty amines. Other fatty amines used for
thetic detergents created the market for fabric mining are quaternary componds and some dia-
softeners in home care and institutional mines, but these are less important.
Most of these softeners are used in rinse cycles Corrosion Inhibition. Large quantities of
where a 3 – 8 % formulated aqueous dispersion amines are used in corrosion inhibition. The
is added leaving 0.1 – 0.2 % active quaternary cationic amino group adheres to the surface of
ammonium compound on the surface of the metals and prevents attack by corrosive liquids
clothes. Since the 1980s, concentrates have been and gases. Primary amines and N-alkyl-1,3-pro-
developed, which contain up to 50 % active panediamines are used most frequently for this
ingredients. In another usage, a quaternary fabric purpose. The amines may be neutralized with
softener is applied to a substrate, such as paper, to oleic, naphthenic, and acetic acids to adjust their
woven or nonwoven cloth, or to a foam and then solubility. A typical oil-soluble inhibitor formu-
added to the drying cycle. The formulation con- lation contains N-tallow-1,3-propanediamine
tains a quaternary ammonium compound and a dioleate.
transfer agent that allows the active ingredient to
be transferred to the cloth during the drying Asphalt Emulsification. The cationic
cycle. The prevention of static build-up is actu- nature of fatty amines makes them useful as
ally more important than the softening action in emulsifiers for asphalt. Primary amines, diamines,
676 Amines, Aliphatic Vol. 2

polyamines, alkoxylated amines, and fatty quater- Fatty amines, diamines, and ethoxylated
nary ammonium compounds can be used in this amines also can be used as pigment-grinding
application. The formulation used depends on the aids and as dispersants for pigments in paints,
properties of the emulsion desired. The cationic coatings, and magnetic tape. The most widely
emulsion can be rapid, medium, or slow set. In all used compound is N-tallow-1,3-propanediam-
cases a cationic emulsifier is used at a low concen- monium dioleate. The amine compound coats
tration (0.2 – 2.0 wt % of the emulsion). When the the pigment particle, making it more readily and
cationic emulsion is mixed with the negatively evenly dispersible in the formulation.
charged aggregate, for instance limestone, the The organo-clay market also is a very large
emulsion breaks, thereby setting the road-covering user of quaternary fatty amines. Most of this
formulation. Fatty amines, because of their posi- market is satisfied with methyl or benzyl quater-
tive charge, also increase the adherence of the nary ammonium chlorides produced from mono-
asphalt to the aggregate. For di- and polyamines, or dihydrogenated tallow amine. In either case,
asphalt emulsification is by far the largest applica- the cations of the quaternary ammonium chloride
tion and they are also the most important surfac- are exchanged with those of the clay, mostly
tants for this purpose. bentonite, to produce clay platelets separated
with a hydrophobic compound. These organo-
Other Applications. Significant amounts of clay products are used as thickening agents,
primary amines are used as fertilizer anticaking mainly in drilling muds and oil-based coatings,
agents. Frequently, fatty amine salts are also but also in the paint industry.
added to other mineral products to prevent caking Some primary amines, amine salts, di- and
of the powdered mineral. polyamines, e.g., lauryl and tallow amines, po-
There are many other applications for fatty sess biocidal properties; monoalkyl quaternary
amines in agriculture as emulsifiers, adjuvants, amines with a C10 – C18 chain act as germicides
and intermediates in pesticide production. Much and antiseptics and therefore have a wide range
of their usefulness relies on the controllable lipid of biocidal applications, for example, in house-
solubility, which aids penetration or absorption holds, swimming pools, and oil fields.
of many active pesticides. Among the emulsifiers Primary amines are also important lubricants
used are ethoxylated amines and quaternary am- since their polar nitrogen end attaches to metals
monium compounds. Some of the surfactants while the nonpolar chains form an oily film above
also can act as foaming agents or foam stabilizers the surface. They are also used as petroleum
[223]. additives. Secondary amines have few direct uses
Neutralization of various herbicidal acids and are mainly used as intermediates for ethox-
with fatty amines enhances their activity be- ylation or quaternization. Tertiary amines with
cause the corresponding salts are more soluble three long chains are of minor commercial sig-
in oil and less volatile than the free amines nificance, but can be used, for instance, as deicers
[224–227]. In some cases, the N,N-dimethy- for motor fuels. The fatty alkyldimethylamines
lalkylamines were found to control the growth are used almost exclusively as intermediates for
of suckers or unwanted leaves, thereby produc- alkyl betaines, amine oxides, and quaternary
ing a better grade of product, for example, in ammonium salts.
tobacco [228]. The reaction of dodecylamine
and cyanamide leads to dodecylguanidine (Do-
dine from ACC, Agrimont, Chemolimpex, and 7.5. Economic Aspects
Drexel), which is an excellent fungicide for
fruit trees. The economics of fatty amines production gen-
Many fatty alkylamine derivatives are used as erally depend on the worldwide fat and oil market
additives in plastic formulations. For example, process. Most of the fatty amine products are
bis(2-hydroxyethyl)alkylamines are added to made from tallow and coconut oils; others are
polypropylene or polyethylene as internal anti- made from oils such as soybean, palm, and
static agents, either as 100 % amines or as a 75 % cottonseed. Minor amounts of tall oil acids are
solid masterbatch to prevent static charge build- used. When pure chain lengths are required, these
up at low humidities. can be obtained by fractionating the acid mixture
Vol. 2 Amines, Aliphatic 677

found in the initial triglyceride. Pure fractions are

much more expensive than mixtures. Primary
and secondary amines have a much larger market
than tertiary amines.
The nitrile route, which is mainly used for the Viscosity
production of primary and secondary amines, t,  C 25 60 100
accounted for 300 000 t/a world capacity in h, mPa  s 1.35 0.7 0.4

1996 for all alkylamines and their derivatives

and has decreased since the early 1990s from
about 370 000 t/a due to declining demand for
the poorly biodegradable dihydrogenated tallow Vapor pressure

dimethyl ammonium salts for fabric softeners. t,  C 20 40 60 80 100

p, kPa 1.21 3.87 11.13 26.53 55.99
The fatty alcohol and a-olefin route, which is
mainly used for the production of alkyldimethy-
lamines and their derivatives, is less important
but is expected to surpass the nitrile route in the
Flash point 39.4  C
long run. In Europe, the largest producers em- Ignition temperature (class T2) 390  C
ploying the nitrile route are Akzo Nobel, Clar- Explosion limits in air 2.7 and 16.6 vol %b
iant, Ceca, and Olefina, in North America Witco (corresponding to
and Akzo Nobel, in South America Akzo Nobel, 67.4 and 415 g/m3)
Specific heat capacity 3.41 J g1 K1 (at 100  C)
Clariant, and Quimi Kao, in Asia Kao and Lion- 3.45 J g1 K1 (at 110  C)
Akzo. 3.50 J g1 K1 (at 120  C)
The most important producers of N,N-dimeth- Heat of vaporization 636.4 J/g (at 0.1 MPa)
yl fatty amines are Procter & Gamble, Albe- 660 J/g (at 40 kPa)

marle, and Lonza in the United States, Clariant,

Albright & Wilson, and Kao in Europe, and Kao Vapor pressures, thermodynamic data, densi-
and Lion-Akzo in Asia. Worldwide demand was ties, and viscosities have been shown in graphical
estimated at about 100 000 t/a in 1998. In 1988 it form [230]. Diaminoethane is infinitely miscible
was only ca. 75 000 t/a. North America accounts with water, methanol, diethyl ether, acetone, and
for 59 % of the installed capacity, Europe for benzene but is only slightly soluble in lower
28 %, and Asia for 8 %. hydrocarbons. It reacts, however, with carbon
Because most fatty amines offered commer- tetrachloride or methylene chloride. It forms
cially contain mixed alkyl chain lengths, trade binary azeotropes with water, several alcohols,
names are common; a comprehensive list can be or toluene [231].
found in [229]. In Europe, about 20 000 t were
sold in 1996 as the underivatized primary, sec- Chemical Properties. As a primary diamine,
ondary or tertiary amines. diaminoethane forms stable mono- and diacid
salts. The free base can be liberated from these
salts by inorganic alkali solutions. The mononi-
8. Diamines and Polyamines trate and dinitrate are highly explosive in the dry
state. The reaction of diaminoethane with chlor-
8.1. Diamines oacetic acid or with formaldehyde and hydrogen
cyanide or an alkali-metal cyanide to give ethy-
8.1.1. 1,2-Diaminoethane lenediaminetetraacetic acid or its salts is partic-
(Ethylenediamine) ularly important (! Ethylenediaminetetraacetic
Acid and Related Chelating Agents). Diami-
(For triethylenediamine, see ‘‘Triethylenediamine’’) noethane forms complex salts with salts of cop-
per, manganese, cobalt, and other transition
Physical Properties. 1,2-diaminoethane [107- elements.
15-3], EDA, C2H8N2, Mr 60.10, is a colorless If diaminoethane is heated with a fatty acid
liquid, mp 10.9  C, bp 117  C (at 101.3 kPa), under conditions favoring dehydration, the pro-
d420 0:8978, n20
D 1:4571. duct is a mono- or diamide, which can be
678 Amines, Aliphatic Vol. 2

converted into an imidazoline by cyclization. At hydroxyethylpiperazine (HEP). The monoetha-

high temperatures and pressures and in the pres- nolamine process has cost advantages over the
ence of a catalyst, ammonia is eliminated from ethylene dichloride process, circumvents chlo-
diaminoethane, and the resulting product under- ride disposal, and prevents the formation of
goes cyclization to give piperazine. Diami- chlorinated hydrocarbons. Lower amines can be
noethane reacts with aldehydes and ketones to recycled to increase the amount of higher etha-
give Schiff bases, which in turn can be hydroge- nolamines; cyclic products are much more abun-
nated to give secondary amines. The Schiff base dant than in the EDC process. Product distribu-
can also cyclize to afford imidazolidines. Con- tion is dependent on reactant ratio, temperature,
densation with 1,2-diketones results in the elimi- pressure, and conversion. Nickel – rhenium cat-
nation of water to give the corresponding 2,3- alysts have often been employed [239], but many
dihydropyrazines, which can be readily dehydro- other nickel catalysts with different promoters
genated to pyrazines [232]. Phosgene reacts with have also been suggested, for instance, Ni –
diaminoethane to give the hydrochloride of N,N0 - Re – B supported on alumina [240] or Ni –
ethyleneurea (2-imidazolidone) [233]. One mole Co – Cu – Re – B on silica [241].
of diaminoethane reacts with two moles of car- A third important and very cost effective
bon disulfide in the presence of a basic catalyst to production process is the reaction of ethylene
give ethylene bisdithiocarbamate [234]. With oxide with ammonia [242], as developed by
only one mole of carbon disulfide, ethyle- Berol (now Akzo) in Sweden. Among the by-
nethiourea is formed. Similarly, ethyleneurea is products of this process are DETA, piperazine
obtained from carbon dioxide. With two moles of and di- and triethanolamine. Union Carbide has
acrylonitrile, diaminoethane undergoes a smooth recently brought a similar process into operation.
cyanoethylation reaction [235]. The production of diaminoethane by the reaction
of formaldehyde with hydrocyanic acid, ammo-
Production. 1,2-Diaminoethane is mainly nia, and hydrogen [243], of chloroacetyl chloride
produced by treating ethylene dichloride (EDC) with ammonia [244], and by hydrogenation of
with aqueous or liquid ammonia at about 100  C aminoacetonitrile [245] are of lesser importance.
in the liquid phase [236]. This so-called EDC
process has been modified frequently [237]; the Quality, Analysis, and Storage. The purity of
reactant ratio, product recycle, pH, reactor ge- diaminoethane, determined by titration and gas
ometry, temperature, and pressure control the chromatography, is usually above 99 %. For stor-
product mix. Byproducts include the higher oli- age, containers made of stainless steel and alumi-
gomers diethylenetriamine (DETA), triethylene- num are preferred to avoid deterioration of the
tetramine (TETA), and tetraethylenenpentamine color number when the product is stored for long
(TEPA). An unavoidable coproduct of the EDC periods. Because it is corrosive, EDA should not
process is the amine hydrochloride, which must be stored in containers made of copper, copper
be neutralized with caustic soda, lime, or other alloys, or uncoated iron. Frequently containers
bases to form, e.g., sodium or calcium chloride. made of iron coated with plastics, such as Lupolen
Ethylenediamine is either extracted or distilled (BASF) or phenolic resins, are used for shipping
from the aqueous stream after neutralization. If and storing diaminoethane. Tin-lined drums can
deemed necessary, the higher amines can be also be employed. Because the amine is hygro-
recycled to optimize EDA production and vice scopic and reacts with carbon dioxide in the air,
versa. About two-thirds of the installed ethyle- tanks must be flushed with nitrogen before use.
nediamine capacity still relies on the EDC This also avoids discoloration during storage.
A second process is the reaction of mono- Uses. Diaminoethane is mainly used in de-
ethanolamine with ammonia and hydrogen over a tergents, resins, crop protection agents, paper
nickel or cobalt catalyst at 20 MPa and 150 – chemicals, lubricants, and pharmaceuticals. The
230  C [238]. The yield of 1,2-diaminoethane is chelating agent ethylenediaminetetraacetic acid
74 %, based on an ethanolamine conversion of (EDTA) and its salts are important products, in
93 %. Byproducts are mainly DETA and pipera- particular in the United States. They are made
zine, but also aminoethylpiperazine (AEP) and by reaction of EDA with formaldehyde and
Vol. 2 Amines, Aliphatic 679

hydrogen cyanide or sodium cyanide together was estimated at 250 000 t [253]; capacities are
with an excess of sodium hydroxide. Tetraace- around 340 000 t/a. The European market is ca.
tylethylenediamine (TAED), which is obtained 100 000 t/a with an annual growth rate of 3 – 4 %
from EDA, is used in the detergent industry as a [254]; the U.S. market has a similar size, and the
cold-bleach activator. It has become the fasted- Japanese is ca. 15 000 t/a. Major producers are
growing EDA product in the last years. Hydro- Union Carbide, Dow, Akzo Nobel, Tosoh, BASF,
xyethylethylenediamine is also converted into and Bayer. In the United States and Japan, the
chelating agents. Several nitrogen-containing ethylenediamine market is smaller than that of the
surfactants are produced from fatty acids and higher ethyleneamines, and vice versa in Europe.
EDA or aminoethylethanolamine, available from
EDA and ethylene oxide. Nonreactive polyamide
resins produced from EDA and diacids also 8.1.2. Diaminopropanes
consume large amounts of EDA. They find use
as adhesives and for printing inks. In the past few years, the demand for diamino-
The zinc and manganese salts of ethylene- propanes and in particular for N-substituted 1,3-
bisdithiocarbamic acid, obtained from EDA, are diaminopropanes has increased sharply in a large
used as fungicides (maneb, mancozeb, zineb or variety of fields.
metiram) and have a significant market. Other
fungicides based on EDA are known, e.g., those 1,2-Diaminopropane [78-90-0], propyl-
of the imidazoline type. ene-1,2-diamine, C3H10N2, Mr 74.13, mp 
The EDA-derivative N,N-ethylene bis(steara- 36.6  C, bp 120.9  C (at 101.3 kPa), d420 0:872,
mide) (EBS) has lubricating properties and is used n20 
D 1:446, h 1.6 mPa  s (at 20 C), flash point

as a mold-release agent, for the processing of 33 C, is a colorless liquid that is very hygro-
thermoplastic resins, in paper coating, wire pro- scopic and miscible with water and most organic
duction, etc. EDA is also used for gasoline and solvents. It forms azeotropes with butanol, 2-
lubricant additives and for surfactant production. methylpropanol, and toluene and has a strong
Diaminoethane – polyester condensates that ammoniacal odor.
are hydroxymethylated with formaldehyde can
be used as plasticizers for phenol – formalde-
hyde resins [246]. The use of condensates of
diaminoethane, epoxides, and urea as nitrogen-
containing polyol components for the production
of polyurethane foams is proposed in [247]. The Because 1,2-dichloropropane does not react
addition of EDA to viscose fiber spinning baths is smoothly with ammonia, 1,2-diaminopropane is
said to improve the tensile strength of the fiber usually prepared by aminating a mixture of 2-
[248]. In the wet spinning of polyurethane fibers, amino-1-propanol and 1-amino-2-propanol, which
diaminoethane is a rapid-action curing agent is obtained from propylene oxide and ammonia
[249]. The incorporation of diaminoethane into [255]. The process differs from corresponding
diisocyanate – polyester prepolymers results in processes for the production of diaminoethane in
useful polymers for the production of elastic that the temperature in the catalytic amination is
polyurethane fibers [250]. Ethyleneurea deriva- higher (190 – 230  C). Producers of 1,2-diamino-
tives prepared from diaminoethane are used for propane include Bayer and BASF.
textile finishing. Diaminoethane is employed as a 1,2-Diaminopropane is used as an intermedi-
stabilizer for rubber latex. In the mineral oil ate for crop-protection agents, e.g., Basfungin
industry, diaminoethane can act as a stabilizer (BASF). Analogous to the ethylenediamine de-
for halogen-containing high-pressure lubricating rivatives, the zinc dithiocarbamate propineb
oils [251] and, in the form of Schiff bases with (Bayer) acts as a fungicide. Especially in the
ketones, is also used as a metal deactivator [252]. United States, derivatives of the amine are used
as fuel and lubricant additives.
Economic Aspects. Ethylenediamine and its
homologues are large-scale chemical products. 1,3-Diaminopropane [109-76-2], propyl-
The global demand for ethyleneamines in 1998 ene-1,3-diamine, trimethylenediamine, propane-
680 Amines, Aliphatic Vol. 2

diamine, C3H10N2, Mr 74.13, mp  11.8  C, bp 1-Amino-3-methylaminopropane [6291-84-

136  C (at 101.3 kPa), d420 0:8834, n20
D 1:459, h 5], N-methyl-1,3-propanediamine, methylami-
2.0 mPa  s (at 20  C), flash point 48  C. 1,3- nopropylamine, C4H12N2, Mr 88.15, bp 140 –
Diaminopropane is a colorless liquid that is 141  C (at 101.3 kPa), d420 0:852, n20 D 1:4479,
miscible with water and most organic solvents. flash point 35  C, is a byproduct of the produc-
tion of N-methyldipropylenetriamine and results
from addition of methylamine to acrylonitrile
followed by hydrogenation.
1,3-Diaminopropane is produced in a two-
stage continuous process, under a pressure of
10 – 20 MPa. In a first reactor, acrylonitrile
reacts with excess ammonia at 70 – 100  C to 1-Amino-3-dimethylaminopropane [109-55-
give 2-aminopropionitrile and bis(cyanoethyl) 7], 3-dimethylamino-1-propylamine, DMAPA,
amine. The mixture of aminonitriles is then N,N-dimethyl-1,3-diaminopropane, C5H14N2, Mr
hydrogenated in a downstream reactor over a 102.18, mp < – 60  C, bp 133  C (at 101.3 kPa),
fixed-bed catalyst (cobalt or nickel) at 60 – d420 0:8112, n20 
D 1:4350, h 1.6 mPa  s (at 20 C),
120  C to give 1,3-diaminopropane and bis(ami- flash point 32  C, ignition temperature 305  C
nopropyl)amine [256]. The yield of 1,3-diami- (class T2), is a colorless liquid and a lachrymator.
nopropane can be increased by adding a polar
solvent and water or by using a large excess of
ammonia. Most of the 1,3-diaminopropane pro-
duced is converted into the textile-finishing agent
1,3-Diaminopropane is also utilized for the pro- It is produced by addition of dimethylamine to
duction of a chelating agent used in the photo acrylonitrile and subsequent hydrogenation in
industry and for anticorrosion agents. the presence of ammonia. DMAPA is used pri-
marily for the synthesis of betaines which are
N-Substituted Diaminopropanes. N-Sub- employed as personal care products and for dish
stituted 1,3-diaminopropanes can be prepared washing. Of minor importance is the consump-
from acrylonitrile and an amine, also with such tion for the production of flocculants and ion
a two-stage procedure. It is usually more efficient exchangers.
to produce the substituted aminopropionitrile
batchwise and then hydrogenate it continuously 1-Amino-3-diethylaminopropane [104-78-9],
in the presence of ammonia [257]. In some cases, N,N-diethyl-1,3-propanediamine, N,N-diethyl-1,3-
hydrogenation also can be carried out batchwise diaminopropane, N,N-diethylaminopropylamine,
over Raney nickel or Raney cobalt. A primary C6H18N2, Mr 130.2, mp  60  C, bp 169  C (at
amine or ammonia reacts with acrylonitrile in a 101.3 kPa), d420 0:829, n20 D 1:4424, h 1.4 mPa  s
molar ratio of about 1/2 to give (after subsequent (at 20  C), flash point 53  C is made by addition of
hydrogenation) alkylbis(aminopropyl)amine, RN diethylamine to acrylonitrile and subsequent hy-
[(CH2)3NH2]2, as the principal product, whereas drogenation. The market for this product is rela-
until the molar ratio exceeds 1/1, the principal tively small.
product is a 1-amino-3-alkylaminopropane, RNH
(CH2)3NH2. Dialkylamines give 1-amino-3-
Major producers of diamines, oligoamines,
and polyamines of acrylonitrile include Hunts-
man and BASF. 1-Amino-3-cyclohexylaminopropane [3312-
The following liquid, water-miscible N- 60-5], N-cyclohexylpropylene-1,3-diamine, N-
substituted diaminopropanes are industrially im- cyclohexyl-1,3-propanediamine, C9H20N2, Mr
portant. Their chief use is as components of 156.27, mp  16  C, bp 113  C (at 1.3 kPa),
epoxy resins: d420 0:9154, n20 
D 1:4810, h 9.4 mPa  s (at 20 C),
Vol. 2 Amines, Aliphatic 681

flash point 103  C, ignition temperature 205  C

(class T3) is made by addition of cyclohexyl-
amine to acrylonitrile and subsequent hydrogena-
tion. 1,4-Diaminobutane can be produced from
1,4-dichloro-2-butene or 1,4-dihalobutane
(obtainable from the reaction of butadiene or
tetrahydrofuran with a halogen), preferably via
the phthalimido compounds. Alternatively, 1,4-
diaminobutane can be prepared by hydrogenat-
ing succinodinitrile [259].
[110-95-2], C7H18N2, Mr 130.23, mp < –70  C, 1,5-Diaminopentane [462-94-2], penta-
bp 145 – 146  C (at 1.3 kPa), d419 0:7837, methylenediamine, cadaverine, C5H14N2, Mr
D 1:4234, flash point 31 C can be made by 102.18, mp 9  C, bp 178 – 180  C (at
methylation of 1,3-diaminopropane with form- 101.3 kPa), d425 0:867, n20D 1:4582, flash point
aldehyde or from dimethylaminopropionitrile 62  C, can be prepared by methods similar to
and dimethylamine and is an intermediate for those described for 1,4-diaminobutane. The start-
corrosion inhibitors, textile auxiliaries, flotation ing materials are 1,5-dichloropentane (obtain-
agents, and emulgators. It is also employed as a able from tetrahydropyran), glutarodinitrile, or
catalyst for polyurethanes and as a hardener for glutaraldehyde (e.g., Relugan, BASF). The com-
epoxy resins. pound is hygroscopic and has a very bad odor.

1,8-Diaminooctane [373-44-4], octamethy-

lenediamine, C8H20N2, Mr 144.26, mp 52 – 53  C,
8.1.3. Higher Diamines bp 225 – 226  C (at 101.3 kPa), flash point
165  C is hygroscopic. It is used for the production
1,3-Diaminobutane [590-88-5], C4H12N2, of fungicides and is obtained by hydrogenation of
Mr 88.15, bp 138 – 141  C (at 101.3 kPa), suberonitrile (1,6-dicyanohexane).
d420 0:8536, n20
D 1:4449, can be produced from
crotonaldehyde by amination under hydrogena-
tion conditions [258].

1,10-Diaminodecane [646-25-3], deca-

methylenediamine, H2N(CH2)10NH2, C10H24N2,
Mr 172.31, mp 61 – 62  C, bp 140  C (at
1.6 kPa).
Diamines with four to five carbon atoms are
important intermediates for pharmaceuticals. 1,12-Diaminododecane [2783-17-7], H2N
However, the production of these diamines is (CH2)12NH2, C12H28N2, Mr 200.37, mp 66 –
restricted by the fact that the starting materials 67  C, bp 304  C (at 101.3 kPa), flash point
are difficult to obtain and that there is a strong 155  C can be used as a spacer in affinity
tendency for cyclization during preparation. chromatography.
Diamines containing more than six carbon
1,4-Diaminobutane [110-60-1], tetra- atoms can be obtained readily by hydrogenating
methylenediamine, putrescine, C4H12N2, Mr the corresponding dinitriles over a Raney nickel
88.15, mp 27 – 28  C, bp 158 – 159  C (at catalyst in a batch procedure under pressure at up
101.3 kPa), d425 0:8704, n20
D 1:4569, flash point to 125  C. A five- to tenfold excess of liquid
63  C, occurs as colorless crystals that are solu- ammonia is used, with or without methanol
ble in water and conventional organic solvents. solvent [260].
682 Amines, Aliphatic Vol. 2

Higher diamines can be prepared continu- trimethylcyclohexane, C10H22N2, Mr 170.30, mp

ously, as described for the production of hexam- 10  C, bp 247  C (at 101.3 kPa), d420 0:922,
ethylenediamine. For methods of preparing spe- n20 
D 1:4880, flash point 112 C.
cific higher diamines, see [3].

2-(Diethylamino)ethylamine [100-36-7],
N,N-diethylethylenediamine, 1-amino-2-(N,N-
diethylamino)ethane, N,N-diethyl-1,2-ethane-
diamine, diethylaminoethylamine, C6H16N2, Mr
116.21, mp < – 70  C, bp 146  C (at
101.3 kPa), d420 0:8222, n20
D 1:4360, flash point
This specialty diamine is produced by Degus-
30  C. sa-H€uls and BASF. It is made from isophorone
nitrile, ammonia, and hydrogen, which leads to
simultaneous imination and hydrogenation of the
resulting imine and nitrile groups [263]. Catalysts
employed are mainly cobalt or ruthenium. Iso-
phorone diamine is employed as a hardener for
epoxy resins and as an intermediate for isophor-
one diisocyanate; its market is considerable. Very
1-Diethylamino-4-aminopentane [140-80- important for the applications is the cis/trans
7], N,N-diethyl-1,4-pentanediamine, novoldia- isomer ratio, which should be as high as possible,
mine, C9H22N2, Mr 158.29, bp 191  C (at since the trans isomer reacts more sluggishly.
101.3 kPa), d420 0:821, n20 D 1:4442, flash point
68  C, is a colorless liquid that is soluble in water N, N, N0 , N0 -Tetramethyl-1,6-hexanedia-
and the usual organic solvents. mine [111-18-2], N,N,N0 ,N0 -tetramethylhexa-
methylenediamine, C10H24N2, Mr 172.31, bp
209 – 210  C (at 101.3 kPa), d420 0:7981,
D 1:4363, flash point 73 C, can be made from
adipodinitrile and dimethylamine or from 1,6-
hexanediamine and formaldehyde and is used
The diamine is produced by a conventional for instance as a catalyst for polyurethanes and
method, for example, by aminating 1-diethyla- hardener for epoxy resins.
minopentan-4-one under hydrogenation condi-
tions, by hydrogenating the oxime, or by aminat-
ing 1-diethylaminopentan-4-ol. The ketone is
obtained from 2-chloroethyldiethylamine by
synthesis of the acetoacetate, and 1-diethylami-
nopentan-4-ol is obtained by Mannich conden-
sation of diethylamine, formaldehyde, and 1-
butyn-3-ol followed by hydrogenation of the 8.2. Oligoamines and Polyamines
product, or is prepared from 1-methyltetrahydro-
furan [261], [262]. Producers of 1-diethylamino- 8.2.1. Physical Properties
4-aminopentane are BASF and some Chinese
producers. Derivatives of 1-diethylamino-4-ami- Diethylenetriamine [111-40-0], DETA, bis
nopentane are particularly important as antima- (2-aminoethyl)amine, 2,20 -diaminodiethyla-
larial agents [262] (e.g., chloroquine from mine, 3-azapentane-1,5-diamine, C4H13N3, Mr
Bayer). 103.17, is a colorless liquid, mp  39  C, bp
207  C (at 101.3 kPa), d420 0:9542, n20
D 1:4859, h
3-Aminomethyl-3,5,5-trimethylcyclohexy- 7 mPa  s (at 20  C).
lamine [2855-13-2], isophorone diamine,
IPDA, (5-amino-1,3,3-trimethyl-1-cyclohexyl-
methyl)amine, 1-amino-3-aminomethyl-3,5,5-
Vol. 2 Amines, Aliphatic 683

3.32, 6.67, 9.20, and 9.92. Technical-grade

Vapor pressure
TETA is sometimes available as a distillation
t,  C 20 89 174 cut that also contains branched isomers and
p, kPa 0.049 1.333 40.0 cyclic compounds.

Tetraethylenepentamine [112-57-2],
TEPA, 1,4,7,10,13-pentaazatridecane, C8H23N5,
Flash point 102  C
Ignition temperature 330  C (class T2)
Mr 189.30, is a slightly yellowish viscous liquid,
Specific heat capacity 3.44 J g1 K1 (at 190  C) mp  40  C, bp 340  C (at 101.3 kPa),
3.48 J g1 K1 (at 200  C) d420 0:9994, n20 
D 1:505, h 96.2 mPa  s (at 20 C).
3.53 J g1 K1 (at 210  C) Technical-grade TEPA may be available as a
Heat of vaporization 456.4 J/g (at 0.1 MPa)
485.7 J/g (at 40 kPa)
distillation cut that also contains branched iso-
Dissociation constant 7.07105 mers and cyclic compounds.
Surface tension 43.8 mN/m (at 25  C)
40.8 mN/m (at 50  C)
Coefficient of expansion 9.1104 (at 55  C).

The amine is infinitely miscible with water,

methanol, acetone, ether, and benzene, but insol-
Vapor pressure
uble in heptane. Because of its reactivity, CCl4
cannot be used as solvent. DETA is hygroscopic t C 20 195 300

and has a strong ammoniacal odor. p, kPa 0.0013 13.5 40

Dissociation constant 6.5105
Flash point 163  C
Triethylenetetramine [112-24-3], TETA,
N,N0 -bis(2-aminoethyl)ethylenediamine, 1,8-dia-
Tetraethylenepentamine is infinitely miscible
mino-3,6-diazaoctane, 1,4,7,10-tetraazadecane,
with water, methanol, acetone, benzene, and
C6H18N4, Mr 146.24, is a colorless to yellowish
diethyl ether but is insoluble in heptane and
oily viscous liquid, mp  35  C, bp 277  C (at
reacts violently with CCl4.
101.3 kPa), d420 0:9818, n20
D 1:4986, h 26.7 mPa
s (at 20  C).
Pentaethylenehexamine [4067-16-7],
PEHA, C10H28N6, Mr 232.37, mp  26  C, bp
136 – 144  C (at 0.02 kPa), d420 1:0020, flash
point 186  C, commercially is of minor impor-
tance. Technical-grade PEHA may be available
as a distillation cut that also contains branched
Vapor pressure isomers and cyclic compounds.
t,  C 20 144 240
p, kPa 0.001 1.33 40.0

Flash point 135  C Dipropylenetriamine [56-18-8], 1-amino-

Heat of vaporization 374.7 J/g (at 0.1 MPa) 3-(3-aminopropyl)aminopropane, bis(aminopro-
Dissocation constant
397.8 J/g (at 40 kPa)
pyl)amine, C6H17N3, Mr 131.22, mp  15.1  C,
bp 238  C (at 101.3 kPa), d420 0:9386, n20
D 1:4846,
flash point 118  C, vapor pressure < 0.001 kPa
TETA is hygroscopic, corrosive, and has a at 20  C, dissociation constant 3.96  104, h
strong ammoniacal odor. With water a crystalline 9.6 mPa  s (at 20  C), is miscible with water,
hydrate is formed. Like DETA, it is completely methanol, and conventional organic solvents.
miscible with water and many polar organic
solvents, but less so with lipids; with CCl4 a
violent reaction occurs. Its four pKa values are
684 Amines, Aliphatic Vol. 2

N-Methyldipropylenetriamine [105-83-9], piperazine; if the temperature is about 400  C,

1-amino-3-N-methyl-N-(3-aminopropyl)-amino- the cyclization reaction gives pyrazine directly
propane, C7H19N3, Mr 145.25, mp  32  C, bp [268].
234  C (at 101.3 kPa), d420 0:9040, n20D 1:4732, h
7.4 mPa  s (at 20  C), flash point 107  C, ignition
temperature 250  C (class T3), is miscible with 8.2.3. Production, Analysis, and Uses
water and conventional organic solvents.
Diethylenetriamine is obtained as a byproduct in
the synthesis of 1,2-diaminoethane from dichlo-
roethane (ethylene dichloride, EDC), ethylene
oxide, or ethanolamine and ammonia. Triethy-
lenetetramine, tetraethylenepentamine, and pen-
3-(2-Aminoethyl)-aminopropylamine taethylenehexamine are other byproducts from
[13531-52-7], N-(2-aminoethyl)-1,3-diaminopro- the EDC process for 1,2-diaminoethane. More
pane, C5H15N3, Mr 117.19, mp  10  C, bp 80  C selective production methods have been de-
(at 0.3 kPa), d20 0.9401, n20
D 1:4805, flash point scribed as well, in particular for DETA, mostly

98 C. starting with EDA [269].
A number of polyamines are obtained by
cyanoethylation of diaminoethane or a diamino-
propane with acrylonitrile, followed by hydro-
genation of the product [133]. For instance,
N,N0 -Bis(3-aminopropyl)-1,2-diami- dipropylenetriamine is produced as byproduct
noethane [79554-59-9], N,N0 -bis(3-aminopro- by hydrogenation of the addition product of
pyl)ethylenediamine, C8H22N4, Mr 174.3, mp ammonia and acrylonitrile [256]; it is used as
1.5  C, bp 170  C (at 0.3 kPa). curing agent for epoxy resins. N-Methyldipropy-
lenetriamine is obtained from methylamine and
The regulations governing storage and trans-
portation of the oligoamines and polyamines are
8.2.2. Chemical Properties the same as those for 1,2-diaminoethane. For
storage of DETA, TETA, and TEPA, plastic-
Because they possess terminal primary amino lined, stainless steel or aluminum containers are
groups, condensates of 1,2-diaminoethane react best suited. Carbon steel leads to iron contami-
very much like 1,2-diaminoethane itself. The nation. A nitrogen atmosphere without carbon
higher condensates of 1,3-diaminopropane have dioxide is necessary for DETA. TETA and TEPA
similar properties. Dibasic acids react with oli- are sometimes stored under air, but nitrogen is
goamines and polyamines to give polyamides superior. Purity is determined preferably by ti-
[264]. A number of urea compounds can be tration, and analysis is performed by fractional
obtained from oligoamines, e.g., diethylenetria- distillation. The oligoamines, e.g., diethylene-
mine, or from polyamines [265]. These amines triamine, can be also analyzed by gas chroma-
react with aliphatic dihalides to give water-solu- tography, but this method is unsuccessful for the
ble cationic products [266] and with epichloro- higher polyamines, owing to their low vapor
hydrin to give anionic polymers [267]. pressures.
In a manner similar to diaminoethane, diethy- Many uses of the higher acyclic ethyleneamines
lenetriamine reacts with formaldehyde and sodi- are similar to those of EDA itself, the most impor-
um cyanide to give diethylenetriaminepentaace- tant being lubricant oil additives, polyamide resins,
tic acid, which also has complex-forming prop- epoxy curing agents, surfactants, and oil field
erties. Diethylenetriamine undergoes also a chemicals [231]. Polyisobutenylsuccinimides de-
smooth cyanoethylation reaction [235]. The oli- rived from TETA, TEPA, or PEHA are important
goamines react directly with formaldehyde to motor oil additives. Polyamide resins produced
give permethylated products. At elevated tem- from DETA or TETA with adipic acid are treated
peratures, diethylenetriamine can be cyclized to with epichlorohydrin and used as wet-strength
Vol. 2 Amines, Aliphatic 685

additives in paper manufacture. Polyamine-modi- quent fractional crystallization can also be used
fied urea – formaldehyde resins are also used as for optical resolution [273].
wet-strength additives for cellulose fibers. DETA The chiral amines can be directly incorporated
and TETA or their ethoxylation products are used in pharmaceuticals or used as chiral auxilaries in
as curing agents for epoxy resins. Polyamine synthesis. For instance, (S)-1-phenylethylamine
amides possessing terminal primary amino groups, has been used for the optical resolution of the
which are prepared from fatty acids and polya- analgesic Naproxen [274].
mines, serve the same purpose.
Amidoamines obtained from the reaction of a
fatty acid and a polyamine, in particular DMA- 10. Toxicology and Occupational
PA and DETA, have similar uses to the more Health
expensive fatty amines, e.g., as asphalt emulsi-
fiers, flotation agents, and corrosion inhibitors. 10.1. General Aspects
If the solid amidoamines are further heated to
200 – 240  C, cyclization to imidazoline deri- The aliphatic amines are highly irritating or
vatives is induced. Since these are liquids they corrosive. In their nonprotonated form they are
posses handling advantages over the amidoa- lipid soluble and therefore penetrate rapidly into
mines; the uses are similar, and the polyamines the lower layers of the exposed tissue. Even in
mostly used for production are DETA and low concentration the vapors cause swelling and
TETA. Polyamine derivatives are also used for damage in the mucous membranes of the eye and
textile finishing. The most important DETA the respiratory tract.
applications are chelating agents (diethylenetri-
nitrilopentaacetic acid) and wet-strength paper Acute Toxicity and Local Effects. Gener-
additives. The latter application is increasing ally, the LD50 (rat, oral or dermal) is on the order
since the paper industry is replacing mela- of 100 – 1.000 mg/kg [275]. The symptoms are
mine – formaldehyde resins with polyamide – caused mainly by high penetrability, corrosion,
epichlorohydrin resins which operate under alkalosis, and, in some cases, by functional in-
neutral pH conditions. terference with nerve-impulse conduction. The
LD50 values of the hydrochlorides are usually
higher because they do not cause corrosion and
9. Chiral Amines alkalosis: 1600 – 3200 mg/kg (rat, oral) [275].
Acute toxic values, local effects on exposed skin
With the trend in modern pharmaceutical and and eyes, and occupational exposure limits in
agricultural chemistry towards enantiomerically Germany [276] and the United States [277] are
pure compounds, amines, being important inter- compiled in Table 6.
mediates in both areas, came into demand in their Irritation and corrosion of the skin and mu-
chiral forms. Some can be taken from the chiral cous membranes were observed frequently in
pool and others made from it, but a growing humans [275], [316], also on exposure to the
proportion of the market for these specialities is vapor [317]. Accidental inhalation of large
being synthesized. Although enantiomeric syn- amounts can cause headache, nausea, excitation,
theses or resolutions are sometimes available and short convulsions [275]. Some aliphatic
[270], they tend to use very expensive reagents, amines, especially di- and polyamines, can cause
so that enzyme-catalyzed processes offer a sig- sensitization of the skin and the respiratory tract
nificant economic advantage. Enzymatic resolu- (allergies) [275], [318].
tion of a racemic mixture affords a pure enantio- b-Chloroalkylamines have an alkylating po-
mer, albeit with loss of the other enantiomer. tential in addition to their corrosiveness. There-
Both enantiomers are obtained in pure form by fore, they are suspected carcinogens.
enantioselective acylation, after which the (R)-
amide and the unchanged (S)-amine are separat- Systemic Toxicity. In neutral media the
ed by simple distillation [271], [272]. Formation amines are almost completely protonated to the
of diastereomeric salts by neutralizing a racemic ammonium compounds. Therefore, interaction
amine with an optically active acid and subse- with the cation channels of the nerve-cell
Table 6. Survey of acute toxicological data and occupational exposure limits of aliphatic amines

Acute toxicological data Occup. exposure limitsd [276],


Substance CAS no. LD50a mg/kg Source LC50 (inhal.)b g/m3 Source Local Source MAK (1998), TLV (1997),
irritationc mL/m3 mL/m3

Ethylamine [75-04-7] 400 – 800 (o, rt) [278], [279], 12.6 (4 h, 20 – 22  C, rt) [281] c [282] 10 10
Amines, Aliphatic

Diethylamine [109-89-7] 450 – 650 (o, rt, ms) [282], [283] 12.1 (4 h, 20 – 22  C, rt) [283], [284] c [283], [285], 5 5
580 – 820 (d, rbt) [287], [288]
Triethylamine [204-44-8] 460 – 590 (o, rt, ms) [283], [288], 10.9 (4 h) [291] c [292], [293] 1 1
[282], [290]
Dipropylamine [142-84-7] 200 – 690 (o, rt) [294], [282] ca. 4.2 (4 h) [294] c [295] n.e. n.e.
925 (d, rbt)
Isopropylamine [75-31-0] 120 – 820 (o, rt) [283], [296], > 9.8 to < 19.6 (4 h) [283], [296] c [283], [297] 5 5
Cyclohexylamine [108-91-8] 710 (o, rt) [298] > 16 (4 h) [299] c [275] 10 10
320 (d, rbt)
4,4’-Diaminodi- [1761-71-3] 300 – 1000 [281], [300], - c [281], [300], n.e. n.e.
cyclohexylmethane (o, rt, ms, rbt) [301] [302]
Piperazine [110-85-0] ca. 2200 (o, rt) [281] no mortality (8 h, satur.) [281] c [281] n.e. 5 mg/m3
(as HCl)
1-(2-Aminoethyl) [140-31-8] 1500 – 2100 (o, rt) [281], [294] no mortality (8 h, satur.) [281] c [281], [294] n.e. n.e.
piperazine ca. 870 (d, rbt)
Pyrrolidine [123-75-1] 300 – 450 (o, rt) [303] > 4.5 – 11.7 (4 h, rt) [281] c [304], [305] n.e. n.e.
5.9 (o, rt); 1.3 [306]
(2 h, ms)
Ethylenediamine [107-15-3] ca. 700 – 1400 (o, rt) [275], [281] > 5 (6 h) [281] c [275], [281] 10 10
3-Aminopropyl [109-55-7] 930 – 1800 (o, rt) [307] > 4.3 (4 h) (irritating) [281] c [281] n.e. n.e.
Diethylenetriamine [111-40-0]  1080 (o, rt) [275], [308], no mortality (8 h, satur.) [281], [309] c [281] n.e. 1
ca. 700 – 1000 [309]
(d, rbt)
Triethylenetetramine [112-24-3] ca. 2800 – 4940 (o, rt) [298], [310] no mortality (8 h, satur.) [310] c [310] n.e. n.e.
550 – 820 (d, rbt)
Hexamethylene [111-49-9] ca. 350 (o, rt) [281] - - c [281] n.e. n.e.
Vol. 2
Vol. 2 Amines, Aliphatic 687

membranes is possible. This may result in a

change of permeability for physiologically im-

portant cations and thus in inhibition of impulse


conduction along the nerve fibers. The essential

structural element of most local anesthetics is a
tertiary amino group. If significant amounts of
these substances are present in the blood, effects


adverse to the impulse conduction of the heart

and especially to the inhibitory neurons of the
[313], [314]

CNS result. The clinical symptoms range from

excitation to clonic convulsions. Consequently,

excitation of the CNS with increased blood pres-

sure and short spasms were observed along with
irritation and injury to the respiratory tract on
no, weak

accidental inhalation of large amounts of aliphat-

ic amines.

Long-chain mono- and dialkylamines are po-

tential histamine liberators and may produce
reddening and edema of the skin and mucous
membranes, itching, decreased blood pressure,
tachycardia, and bronchioconstriction [275],

[319]; the maximum effect occurs with C10

monoamines and C14 diamines. Certain aliphatic
di- and polyamines, such as putrescine [110-60-
1] (H2N(CH2)4NH2), spermidine [124-20-9]
(H2N(CH2)4NH(CH2)3NH2), and spermine [71-
44-3] (H2N(CH2)3NH(CH2)4NH(CH2)3NH2),
are found characteristically in proliferating cells

and are formed under the influence of hormones,

natural growth stimuli, specific tumor promoters,
[313], [314]

and other factors. Their physiological action is

apparently involved in cell division and tissue

proliferation [320].

Metabolism. In many cases, little is known

1050 – 1600 (o, rt)

about the metabolism of alkylamines. Generally,

ca. 500 – 900

once absorbed, alkylamines do not accumulate

1850 (o, ms)

rt ¼ rat, ms ¼ mouse, rbt ¼ rabbit, o ¼ oral, d ¼ dermal.

9200 (o, rt)

and are rapidly released from the organism,

satur. ¼ saturated atmosphere, rt ¼ room temperature.
(o, ms)

mostly into the urine, either unchanged (e.g.,

diethylamine, cyclohexylamine) or metabolical-
ly converted. Reactions catalyzed by the cyto-
chrome P450 system include the oxidative de-
amination of primary alkylamines and N-deal-


kylation of secondary and tertiary amines [321].

This enzyme system competes with an unspecific
flavin-containing monooxygenase that produces
n.e. ¼ not established

N-oxides from tertiary amines and hydroxyla-

mines from secondary amines. Furthermore, N-
c ¼ corrosive.

methyltransferases may alkylate mono-, di-, and


trialkylamines [321]. In addition, by monoamine


oxidase, primary, secondary, and tertiary amines

can be oxidatively dealkylated stepwise to

688 Amines, Aliphatic Vol. 2

aldehydes (or carboxylic acids), ammonia, and 0.05 mg/m3, but with morphological, apparently
hydrogen peroxide [321]. The oxidation rate reversible changes in the lung and cerebral neu-
increases with increasing chain length; methyl- rons at the highest concentration [326]. On the
amine is not transformed by monoamine oxidase other hand, 50 mL/m3 (150 mg/m3) was the
[322], [323]. Short-chain mono- and diamines lowest concentration to show mild, but signifi-
are also oxidized by diamine oxidase (histami- cant effects in the lung and liver of rabbits on
nase); those most readily oxidized are 1,4-buta- prolonged inhalation [285]. There were no visi-
nediamine and the C5 – C6 monoamines. ble signs of toxicity following exposure of rats to
Secondary amines (including those with cy- 25 mL/m3 (75 mg/m3) for 120 d, but a moderate,
clic structures), and to some extent tertiary bronchiolar hyperplasia of lymphoid cells [286].
amines, can be chemically transformed into car- It was assumed that diethylamine may exert a
cinogenic N-nitrosodialkylamines in the pres- certain neurotoxic effect, which, however, was
ence of nitrites or nitrates under reducing not confirmed by others [286].
conditions. Under experimental conditions, no sensitizing
potential was observed [331]. Diethylamine it-
self showed no mutagenic potential. Although
10.2. Toxicology of Specific Amines the carcinogenic N-nitrosodiethylamine is
formed in the presence of nitrite, combined ad-
10.2.1. Alkylamines, Cyclic Amines, and ministration in the feed and drinking water gave
Polyamines no evidence of increased tumor incidence in a
lifelong study with rats [332].
Ethylamine [75-04-7], alkaline liquid, in
neat form gaseous at room temperature, is readily Triethylamine [204-44-8], oily, alkaline
absorbed through the skin and respiratory tract liquid, once absorbed, is rapidly excreted un-
[282], but easily excreted in the urine after partial changed or as its N-oxide in the urine [333],
metabolism [324]. Exposure to the vapor may [334]. Exposure to the vapor may transiently
transiently impair vision in humans (‘‘blue impair vision in humans (‘‘blue haze’’): concen-
haze’’) [325]. The odor threshold in air is ca. trations without visual effect are in the range of
0.027 – 0.27 mL/m3 ( 0.5 mg/m3) [326], 1.4 – 2.7 mL/m3 [293], [335]. Its exciting effect
[327]. In rabbits, inhalation of 50 mL/m3 on the CNS is more pronounced than that exerted
(94 mg/m3) for 6 weeks resulted in local and by the other lower ethyl homologues; effects on
systemic organ lesions (corneal erosions and parasympathetically controlled musculature and
edemas, pneumonia, peribronchitis, focal mus- inhibition of nerve pulse transmission in sypm-
cular degeneration of the heart) [285]. Transient pathetic ganglia can be explained by inhibition of
physiological effects were seen after prolonged cerebral monoamine oxidase [292], [335]; how-
exposure of rats to vapors (0.06 – 3.69 mg/m3, ever, triethylamine does not inhibit neuromuscu-
90 d) with no effects at 0.015 mg/m3. At the lar impulse transmission [292]. Under experi-
highest concentration, morphological changes in mental conditions and in humans, no sensitizing
the lung and cerebral neurons apparently were potential was observed [335]. The odor threshold
reversible [326]. in air is reported from < 0.09 to 1.4 mL/m3
( 0.33 mg/m3) [326], [335].
Diethylamine [109-89-7], alkaline liquid,
once absorbed, is rapidly excreted unchanged in Dipropylamine [142-84-7], alkaline liquid,
the urine [328]. Exposure to low vapor concen- may cause headache, nausea, faintness, and lung
trations are reported to transiently impair vision edema on inhalation. The odor threshold in air is
in humans (reduction of sensitivity to light): no- 0.02 – 0.1 mL/m3 ( 0.4 mg/m3) [295].
effect threshold 0.022 – 0.028 mL/m3 ( 0.08
mg/m3) [326], [329]. The odor threshold in air is Isopropylamine [75-31-0], alkaline liquid:
ca. 0.02 – 0.3 mL/m3 ( 0.9 mg/m3) [329], Signs of respiratory irritation may occur at about
[330]. Transient physiological effects in rats after 24 mg/m3 and above ( 10 mL/m3) in humans
90-d exposure to vapors were reported to already [297]. In rats, a NOAEL was defined as 100 mg/
be visible at 0.37 – 4.19 mg/m3 with no effects at m3 for prolonged inhalation (1 month) [336]. The
Vol. 2 Amines, Aliphatic 689

substance was void of any teratogenic effects months [281], [301]. Several in vitro [281], [349]
after exposure of pregnant rats to up to 1000 mg/ and in vivo mutagenicity studies [281], [301]
m3 [337]. An odor threshold in air is reported to gave no evidence of a mutagenic or clastogenic
be between 5 – 10 mL/m3 ( 24 mg/m3) [297]. potential.

Cyclohexylamine [108-91-8], alkaline liq- Piperazine [110-85-0], alkaline solid, is

uid, is readily absorbed by the oral and respira- almost completely absorbed from the intestinal
tory route, but only slowly through the skin, and tract on oral ingestion. Acute intoxications occa-
is rapidly excreted in the urine almost unchanged sionally follow therapeutic treatment of animals
[338]. It has a strong fishlike odor (odor threshold with piperazine salts (as anthelmintics), and
ca. 2.5 mL/m3 ¼ 10.4 mg/m3) [299], [338]. symptoms include adverse neurologic events
First signs of a sympathomimetic effect in hu- such as ataxia, muscle tremor, muscular weak-
mans (elevation of the arterial blood pressure) are ness, and vomiting [350]. In humans, headache,
reported at a daily dose of 5 mg/kg [338]. nausea, coordination disorders, and exanthems
Cyclohexylamine has been studied intensively have been observed occasionally during repeated
because it is a metabolite of the sweetener saccha- intake of piperazine salts in daily doses of 30 –
rin. Intake of either up to 300 mg/kg of the HCl salt 75 mg/kg [351]. Apparently, sensitizations of
daily in the feed of rats for two years and lifelong the skin and also the respiratory tract can occur;
[339–341] or of up to about 750 mg/kg daily in the these are also caused by the dihydrochloride
feed of mice (0.3 and 0.5 % HCl salt) for  80 [352–354]. Based on several observations, espe-
weeks [342], [343] did not lead to higher incidence cially in workers in Germany, piperazine was
of tumors. Accelerated basal metabolic rate and included in the list of allergens which are also
reduced spermatogenesis were observed in rats suspected of inducing respiratory sensitization,
after 90 d [344] at daily doses of 2000 and but no MAK value was established [355], [356].
6000 ppm (HCl salt), but no such symptoms were Although experimental data suggest that
evident at 600 ppm (ca. 20 mg amine per kilo- piperazine itself is unlikely to be mutagenic and
gram) daily intake. In other long-term feeding carcinogenic, there is strong evidence that the
studies, no convincing evidence of toxicity was combination with nitrite produces malignant
apparent at doses of 5 to ca. 20 mg kg1 d1 [299]. tumors in animals: for reviews, see [357], [358].
In a multigeneration study (two years,
150 mg/kg daily of cyclohexylammonium chlo- 1-(2-Aminoethyl)piperazine [140-31-8],
ride), the fertility of rats was not affected ad- alkaline liquid: Sensitization was observed in
versely in spite of slight atrophy of the testicles animal experiments [359].
[341]. Based on these and other results [345],
[346], it is concluded that no mutagenicity, Pyrrolidine [123-75-1], alkaline liquid: As
carcinogenicity, or teratogenicity is suspected with other amines, sympathomimetic action is
for cyclohexylamine [347], [338]. observed and results in increased blood pressure
and a tendency to convulsions [304]. In an inha-
4,40 -Diaminodicyclohexylmethane [1761- lation study on male rats [360], exposure to
71-3], alkaline solid, was shown to have skin- 2.6 mg/m3 for 6 months caused increasing exci-
sensitizing potential [302], [348]. On resorption, tation of the nervous system, inhibition of diure-
predominant clinical signs of intoxication were sis and spermatogenesis without impairment of
hyperexcitability, excessive salivation, and con- spermatozoon mobility and fertility; however,
vulsions in animals; repeated oral dosing (50 – morphological alterations were evident from an
100 mg kg1 d1 in rats and mice for 10 and increase in the number of tubuli seminiferi with
16 d, respectively, 50 mg/kg in dogs for up to 82 desquamation of the seminiferous epithelium.
weeks) resulted in gastrointestinal hemorrhagic Experimental data suggest that pyrrolidine itself
inflammations, nephritis, and fatty changes to the is unlikely to be mutagenic [303] and carcino-
liver [281], [300], [348]. No changes in methe- genic: in limited long-term studies in rats and
moglobin or in other hematological parameters mice in the presence of nitrite in drinking water to
were induced in cats on repeated doses of 50 and favor nitrosation, there was no evidence of a
100 mg kg1 d1, given twice per week over 2 carcinogenic effect [361], [362].
690 Amines, Aliphatic Vol. 2

Ethylenediamine [107-15-3], alkaline liq- pregnant and nonpregnant guinea pigs, signifi-
uid: Dermatitis related to primary irritation and cant amounts were absorbed by the strongly
also to sensitization occurs frequently [275]. irritated skin, leading to toxic effects in the
Sensitization of the mucous membranes of the kidneys, liver, brain, and placenta and causing
respiratory tract with asthmatic symptoms has abortion [310], [374], [375]. Triethylenetetra-
also been described [363], [364]. After oral ad- mine proved to be a mutagen in vitro [376] but
ministration in rats and mice at up to 1000 mg not in vivo [310].
kg1 d1 of the dihydrochloride salt, no terato-
genic effects were produced [365–367], and there Hexamethyleneimine, hexahydro-1H-aze-
was no evidence for an impairment of reproduc- pine [111-49-9], for acute toxicity data: see
tion in a two-generation study [365]: 250 mg Table 6.
kg1 d1 dihydrochloride salt (ca. 112 mg kg1
d1 base) can be considered the NOAEL [368]. Hexamethylenetetramine [100-97-0],
Several in vitro tests gave no evidence for a HMTA, urotropin, is rapidly absorbed from the
mutagenic potential [369–371]. gastrointestinal tract, and the majority is excreted
unchanged in the urine [311].
3-Dimethylamino-1-propylamine [109-
55-7], alkaline liquid: There are indications of Irritation and Sensitization. In animals,
contact and possibly respiratory allergy in rela- HMTA exhibited a skin-sensitizing potential
tion to occupational exposure [307]. Less than [377]. Several reports in industry [378–380]
0.9 ppm of 3-dimethylaminopropylamine in the suggest an association between HMTA exposure
workplace air may adversely affect respiratory and the increased occurrence of irritative, aller-
function [372]. The skin-sensitizing potential gic events among workers: this was often en-
was verified in an animal study. In an oral 28- countered with hot processing in the rubber and
d study with rats (gavage, 7 times per week.), foundry industries. Sensitized persons frequently
clinical symptoms including pulmonary and car- showed positive responses on patch testing,
diac failure were noted at 250 mg kg1 d1, but although the causative agent remained obscure
no treatment-related effects at a level of 50 mg [379], [381]. They can suffer from asthmatic or
kg1 d1 [307]. asthmalike attacks on inhaling HMTA [382].

Diethylenetriamine [111-40-0], alkaline Systemic Toxicity. Experience from thera-

liquid: sensitization of the skin and possibly peutic use in the past, especially for the preven-
respiratory tract occurs frequently [275], [309]. tion of recurrent urinary tract infections in human
Experience from occupational medicine suggests patients, support the low toxicity on prolonged
that the latter has to be considered the main oral ingestion of up to 4 g/d per individual. Some
adverse effect that may occur in humans [309]. 1 – 7 % of the patients experienced untoward
Following oral administration, diethylenetria- events such as gastrointestinal intolerance (nau-
mine is readily absorbed and rapidly excreted, sea, vomiting, abdominal cramps) and unspecific
mainly via the urine and feces [309]. In rats, no skin reactions (pruritus, urticaria, erythematous
histopathological changes were observed after eruptions) [383]. Chronic animal studies with
90-d feeding up to the highest dietary level of HMTA administered in the diet or drinking water
15 g/kg (ca. 1200 mg kg1 d1), [373] while in did not reveal any evidence of a carcinogenic
cats and rabbits, repeated oral doses of ca. potential and account for a high chronic NOAEL
200 mg kg1 d1 and above as base or HCl salt of more than 1000 mg kg1 d1 [384–386].
resulted in severe gastritis, lung edema or pneu-
monia, and kidney lesions [281], [309]. Mutagenicity. The majority of studies failed
to reveal any in vitro or in vivo genotoxic activi-
Triethylenetetramine [112-24-3], alkaline ty. At cytotoxic or sublethal doses ( 10 g/kg)
liquid: may induce lung edema on inhalation of [311], a weak mutagenic effect was found in male
its vapors. The compound is also an effective skin mice [387], but there was no positive response at
sensitizer [275]. Following repeated dosing (ca. up to 1500 mg/kg [388], while a cytogenetic
50 mg each, 17 – 55 times) onto the skin of assay after single oral and repeated doses of
Vol. 2 Amines, Aliphatic 691

one-third of the LD50 in mice was clearly nega- In isolated cases, morpholine showed a weak
tive [389]. Furthermore, the compound is de- mutagenic acticity; however, most of the experi-
scribed as mutagenic for larvae of Drosophila mental in vitro and in vivo data confirmed that
(dose not specified) [382]. purified morpholine did not give any evidence of
a mutagenic potential [281], [313], [314], [395].
Teratogenicity and Reproduction. In several Furthermore, longterm studies (in rats and ham-
multigeneration studies on rats, no treatment- sters with feed containing 0.1 % base [396], in
related abnormalities or developmental defects mice with drinking water containing up to 0.24 %
in the offspring or reproductive defects in the base [397], and inhalation of up to 530 mg/m3 in
parental generation were seen following high rats [398]) failed to reveal an inherent cancero-
oral doses of up to more than 1500 mg kg1 d1 genic potential of morpholine [313], [314]. How-
[311], [386]. In a study with female beagles (600 ever, there is a possibility of nitrosation in the
and 1250 ppm of HMTA in the feed (15 – 31 mg presence of traces of nitrous acid or nitrogen
kg1 d1), from the 4th to 56th day after mating), oxides [303], [399]: N-nitrosomorpholine is a
slight embryotoxic effects were found at higher potent carcinogen [313], [395].
doses but no malformations [390].

Morpholine [110-91-8], alkaline liquid, is 10.2.2. Fatty Amines

well absorbed by the oral, dermal, and inhalation
route, but rapidly excreted, mainly unchanged, in Skin and Eye Irritation. Fatty amines are
the urine. Experimental evidence suggests that local irritants of eyes, skin, and mucous mem-
morpholine is unlikely to induce skin sensitiza- branes. Both the primary amines and the propa-
tion [314], [391]. nediamines are generally regarded as severely
Common signs of toxicity following repeated irritating and possibly corrosive. Even dilute
dosing are local irritation and inflammations of solutions (5 %) of fatty amines may cause irre-
the stomach, respiratory tract, and eyes, as well as versible damage to the eye; cornea inflammation
systemic effects primarily on the liver and kid- caused by 1 % solutions heals without permanent
neys. In rats, exposure to 250 mL/m3 (890 mg effects. Concentrated solutions of salts of fatty
kg1 d1, 6 h/d, 5 d/week, 90 d) [392] and to up amines and quaternary ammonium compounds
to 150 mL/m3 (543 mg/m3, 6 h/d, 5 d/week, 104 are almost neutral but they have an irritating
weeks) [393], [313] produced focal erosions and potential similar to the free bases. Ethoxylation
squamous-cell metaplasia of the nasal cavities of fatty amines reduces the irritating effects.
and turbinates and ocular irritation, but no he- A small number of workers became sensitized
matological or organ effects; at 90 mg/m3 to selected fatty amines. Symptoms included skin
(25 mL/m3, subchronic) and 36 mg/m3 rash, dermatitis, eye swelling, and a sensation of
(10 mL/m3, chronic), no treatment-related ef- the skin, described as ‘‘crawling’’. Appropriate
fects at all were identified. These data may be skin and eye protection must be worn when
taken as NOAELs, although one earlier Russian handling fatty amines.
publication [394] claimed that some adverse
effects were conspicuous on the spleen and in Inhalation. At ambient temperatures only
the red and white blood counts in rats and guinea the short-chain amines, especially if branched,
pigs after four-month inhalation of 70 mg/m3 have sufficient vapor pressure to present any
and less (see also [313]). hazard by inhalation. The LC100 of 2-ethylhex-
After oral application, no toxic signs were ylamine is 1.3 mg/L (rat, 4 h) [400], whereas
found in mice receiving 70 – 140 mg kg1 d1 exposure to air saturated with N,N-di-(tridecyl)
base in drinking water as morpholine oleate for tridecanamine for eight hours resulted in no
90 days [396]. deaths [401].
In a subacute feeding test (four weeks, rats), a
daily dose of 323 mg/kg led to increased weight Acute and Chronic Oral Toxicity. None of
of the suprarenal gland accompanied by retarded the fatty amines are highly toxic by ingestion.
development of body weight; daily doses of 27 The more corrosive ones, such as coco-1,3-dia-
and 93 mg/kg were without effect [303], [313]. minopropane, have oral LD50 values as low as
692 Amines, Aliphatic Vol. 2

147 mg/kg, whereas compounds of higher 19 C. Barnett, Ind. Eng. Chem. Prod. Res. Dev. 8 (1969)
molecular weight, such as di(hydrogenated- 145.
tallow) dimethylammonium chloride, are relatively 20 LCE Partnership, US 5 196 589, 1993 (A. J. O’Lenick,
J. M. Clumpner).
nontoxic, with oral LD50 values of 7000 mg/kg and
21 Engelhard Industries, GB 925 458, 1960.
higher [402]. 22 Gulf Research & Development Co., US 3 366 686, 1964
Chronic feeding studies have shown that rats (R. W. Rosenthal, R. Seekircher); Texaco, US
fed with 500 ppm of 1-octadecylamine in the diet 3 739 027, 1971 (W. C. Gates Jr.,
for two years showed no observable adverse 23 Mitsui Petrochemical Ind., JP 10 095 753, 1996.
health effects, whereas dogs fed the same level 24 J. J. Ritter, J. Kalish, J. Am. Chem. Soc. 70 (1948) 4084.
for twelve months showed mainly nonpathologic 25 Air Products, US 4 307 250, 1981 (J. Peterson, H.
irritant effects on the mucosa of the gastrointes- Fales), US 4 375 002, 1981 (J. Peterson, H. Fales).
26 Air Products, EP 77 016, 1982 (M. Deeba, W. J. Ambs).
tinal tract [403].
27 BASF, DE 3 326 579 1983 (V. Taglieber, W. H€olderich,
R. Kummer, W. D. Mross, G. Saladin). BASF, DE
11. Acknowledgment 3 327 000 1983 (V. Taglieber, W. H€olderich, R. Kum-
mer, W. D. Mross, G. Saladin).
28 BASF, DE 19 524 241, 1995 (U. Dingerdissen, R.
Based on the corresponding article from the fifth Kummer, P. Stops, J. Herrmann, H.-J. L€utzel, K. Eller).
edition, written by GERD HEILEN, HANS JOCHEN 29 BASF, DE 19 530 177, 1995 (U. Dingerdissen, R.
MERCKER, DIETER FRANK, RICHARD A. RECK, and Kummer, P. Stops, U. M€uller, J. Herrmann, K. Eller).
RUDOLF J€aCKH 30 BASF, DE 19 545 875, 1995 (K. Eller, R. Kummer, P.
Stops). BASF, DE 19 545 876, 1995 (K. Eller, R.
Kummer, P. Stops).
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694 Amines, Aliphatic Vol. 2

121 M. F. Obrecht, Effluent Water Treat. J. 4 (1964) 279. 152 Phillips Petroleum, US 3 547 597, 1967 (G. E. Hayes).
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139 Air Products and Chemicals, EP 69 322, 1981 (J. E. Wells). 167 Akzona Inc., US 4 237 064, 1980 (R. A. Reck).
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BE 743 974, 1969 (S. Weiss). Sawyer).
Vol. 2 Amines, Aliphatic 695

184 Armour, GB 860 922, 1961 (S. H. Shapiro, F. Pilch). 219 A. E. Merbach, Mitt. Geb. Lebensmittelunters. Hyg. 66
185 Lion Fat and Oil, US 4 248 801, 1981 (S. Tomidokoro, (1975) 176.
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186 Hoechst, US 3 444 205, 1969 (W. Froehlich, H. Ober- 221 DuPont, US 2 088 325, 1937 (J. E. Kirby).
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187 Kao Soap Co., JP Kokai 81 152 441, 1981. 223 L. L. Johnsen, Weeds 13 (1965) 123 – 130.
188 BASF, DE 2 639 648, 1978 (H. Hoffmann, H. Mueller, 224 Armour, US 3 246 015, 1966 (H. L. Lindaberry, W. W.
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189 L. Barrault, Y. Pouilloux, Catal. Today 37 (1997) 137. 225 Akzona, US 3 506 433, 1970 (W. W. Abramitis, R. A.
190 Archer-Daniels-Midland Co., US 3 223 734, 1965 (H. Reck).
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191 Gulf Research & Development Co., US 2 953 601, 1960 S. H. Nurse, B. J. Watt).
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192 BASF, DE 2 645 712, 1978 (H. Hoffmann, H. Mueller, Reck).
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196 UOP, DE 3 014 455, 1981. (1937) 300.
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