Europaisches Patentamt

European Patent Office @ Publication number: 0 011 0 4 8

A1
Office europeen des brevets

EUROPEAN PATENT APPLICATION

y) Application number: 79810087.1 @ int. cia C 07 C 102/00, C 07 C 1 0 3 / 4 4 ,

C 0 7 C 103/82, C 07 C 1 4 3 / 7 8 ,
g) Date of filing: 05.09.79 C 0 7 C 85/11
11 C07C41/01, C 0 7 C 7 6 / 0 2 ,
C07C79/35, C 0 7 C 9 3 / 1 4

% Priority: 11.09.78 US 941533 @ Applicant: Toms River Chemical Corporation,

Route 37, P.O. Box 71, Toms River, New
Jersey 08753 (US)

Date of publication of application: 14.05.80

Bulletin 80/10 @ inventor: Lang, Philip Charles, Dr., 151 Edgemere
Drive, R.D. 2, Toms River, New Jersey 08753 (US)

@ Representative: Schirner, Rolf et al, Patentabteilung

Designated Contracting States: CH DE FR GB der CIBA-GEIGY AG Postfach, CH-4002 Basel (CH)

A process for the manufacture of substantially pure 3-amino-4-alkoxy-acy!aniiides from 2,4-dinitrochlorobenzene.

A
(7) A process for the manufacture of a substantially iso- OR
merically pure acylanilide of the structure NH,
OR
[ I
.NH, \ /
l < \
NH2
Y
with an acylating agent, to give an alcohol solution of the
NHXR, acylanilide, wherein substantially equivalent amounts of the
acylating agent and the diamino compound are used and
where R is hydrogen, lower alkyl, hydroxy-lower alkyl or therein the treatment is carried out by the slow, drop-wise
00 lower alkoxy-lower alkyl; RR,1 is lower alkyl, phenyl, lower addition of the acylating agent at a temperature in the range
alkylphenyl, lower alkoxy, lower alkoxyphenyl, of about 0 to 5 C. The process is particularly advantageous
o chlorophenyl, nitrophenyl, dichlorophenyl, chloro-lower when the alcohol solution of the diamino compound is
alkyl, cyano-lower alkyl, lower alkyl, amino, sulfamoyl- produced by reduction of a suspension of the correspon-
phenyl, carbamoylphenyl or lower alkoxy-lower alkyl; and X ding dinitro compound in the alcohol.
is -CO-or-S02-; comprising the step of treating an alcohol
is-CO-or-S02-;
O solution of a diamino compound of the structure
O

Q.
HI

ACTORUM AG
 In the m a n u f a c t u r e of many commercial or p o t e n t i a l l y commer-
cial azo dyes, a key intermediate is an a n i l i d e coupler intermediate
of the structure set out as formula I

where R is hydrogen, lower alkyl, hydroxy-lower alkyl or lower

alkoxy-lower alkyl, R is lower alkyl, phenyl, lower alkylphenyl,
lower alkoxy, lower alkoxyphenyl, chlorophenyl, nitrophenyl, dichloro-

phenyl, chloro-lower alkyl, cyano-lower alkyl, lower alkylamino,

sulfamoylphenyl, carbamoylphenyl or lower alkoxy-lower alkyl; and
X is -CO- or -S02-. (Throughout this specification, R, R' and X h a v e
the meanings here designated, unless it is specifically stated other-
wise.)

Such commercial azo dyes are found, for example, in U.S. patents
916,323; 3,232,693; 3,268,507; 3,325,471; 3,520,871; 3,522,235;
3,533,722 and 3 , 7 4 0 , 1 8 9 .

In commercial practice, anilides of the structure of formula I

have commonly been made a c c o r d i n g to the following reaction sequence:
 This rather expensive manufacturing procedure results in the
desired product I without contamination with the isomeric compound
XIII or the diacyl compound XIV.

According to Example 6 of U.S. patent 3,919,314, which issued

November 11, 1975 on a p p l i c a t i o n of Richard John M e r r i o t t , the direct
acylation of 2,4-diaminoanisole with acetic anhydride in aqueous so-
lution in the presence of h y d r o c h l o r i c acid gives a mixture of com-
pounds I and XIII where R is methyl and -XR is -COCH3. U.S. 4,079,079,
which issued March 14, 1978 on a p p l i c a t i o n of Richard James Gait also
teaches the production of a m i x t u r e of isomers I and XIII by a c e t y l a -
tion of 2 , 4 - d i a m i n o a n i s o l e dihydrochloride in aqueous solution at a
maintained pH of 1.5 - 3.5.

Other aqueous processes of a c y l a t i o n have been taught to y i e l d

the single desired isomer compound I where R is -CH3 an -XRl is

-COCH3, but at lower yield. German 1 , 5 4 3 , 6 2 5 , Example 1, teaches the

acylation of f r e s h l y - d i s t i l l e d 2,4-diaminoanisole with acetic an-
hydride in water solution, without the addition of h y d r o c h l o r i c acid,
to give 3-amino-4-methoxyacetanilide in 75 % y i e l d before re-
crystallization. Publication, Board of F e d e r a l Intelligence Agency,
P.B. 74 051, p. 33 t e a c h e s a similar conversion of 2,4-diaminoanisole
to 2 - a m i n o - 4 - a c e t a m i d o a n i s o l e , in aqueous solution, with acetic an-
hydride, in the presence of magnesia at 65% yield.

It is thus quite surprising that substitution of an a l c o h o l

for the water of the P.B. 74 051 p r o c e d u r e gives a markedly improved
yield of 90-92% while still maintaining the selectivity needed to
give compound I exclusively. The p r o c e s s here taught and c l a i m e d
further differs from the P.B. 74 051 p r o c e d u r e in not using an e x c e s s
of a c y l a t i n g agent and in adding the acylating agent to the 2,4-
diaminoanisole (or equivalent 2,4-diaminophenol or other ether there-
of) at a lower temperature.

British patent 1,324,303 teaches the acetylation of 2,4-di-

amino-l-(beta-phenoxyethoxy)benzene in a l c o h o l i c solution, in the

presence of magnesia. However, British 1,324,303 uses an excess of

acylating agent, added at room t e m p e r a t u r e , rather than at 0 to 5C,
and w i t h o u t the slow or dropwise addition of the acylating agent.
Analysis of the acetylated product is not given in the British agent.
The B r i t i s h patent does not teach the acetylation of any simple lower
alkyl ethers of 2,4-diaminophenol. Acetylation of 2 , 4 - d i a m i n o a n i s o l e
according to the procedure of the British patent, has been found to
give a 77-80% yield of compound I, contaminated with 20-22% of
compound XIV and 0.4% of compound X I I I .

It is further to be noted that all of the above-described

acylation procedures, except that of B r i t i s h 1,324,303, require
freshly-distilled 2,4-diaminoanisole or i t s equivalent as starting
material. Inasmuch as 2 , 4 - d i a m i n o a n i s o l e is carcinogenic, it is ad-

vantageous to m a n u f a c t u r e the desired coupler intermediate, 3-amino-

4-methoxyacetanilide, or its equivalent, without isolation of t h e

diamino starting material.

By the process of this invention, the desired coupling inter-

mediate compound I is obtained, substantially pure, in high yield
from 2 , 4 - d i n i t r o c h l o r o b e n z e n e , according to the following reaction
scheme:

The y i e l d of I by t h i s procedure is 80-85% of t h e o r y , based

on s t a r t i n g material XV. T y p i c a l l y the acylation product containing

isomerically pure product I, obtained by t h i s procedure, analyzes as
follows: 90% I, 3.5% XIV, 0.5% XVII, 0.75% ash, and 4.7% w a t e r , with

no d e t e c t a b l e amount of the isomeric product XIII. The y i e l d and

analysis here reported is obtained on the final product I, produced
by the three-step synthesis set out above, without isolation of the
intermediates XVI and XVII. As can be a p p r e c i a t e d , an o v e r a l l yield
of 80-85% in a t h r e e - s t e p synthesis, requires an average yield of
about 95% for each of the three steps. As to p u r i t y of the organics
in the product, subtracting out ash and w a t e r , one finds the product
to be 95.7% 1, 3.7% XIV and 0.5% XVII. For the m a n u f a c t u r e of a z o -

dyes, this product is substantially pure and can be used with no

practical distinction over the product obtained by the art process,
x @ X I @ X I I @ I .

It is critical to the success of this process that the R1X-

acylating agent, used in the last step of this process can be u s e d
in an amount (by weight) that is substantially equivaltne to the
diamino compound XVII. It is further critical that the R X-acylating

agent be added slowly at a substantially constant rate, for instance,

dropwise over a period of about 1 to 3 h o u r s , preferably about 1.5

to about 2 hours, at a temperature in the range of about -5 to a b o u t

15C, preferably about 0 to about 5C, such that the acylation is

substantially complete before the temperature is raised above the

selected reaction temperature. The lower limit of the time range for
the addition of the acylating agent is critical, to allow the

acylation to proceed without any temporary and l o c a l build-up of

excess acylating agent in the reaction solution. The upper limit
is not critical and can be extended at w i l l . The lower temperature
range is selected so as to give a reasonable reaction rate. The

upper temperature range is governed by the discovery that the amount

of d i - a c y l a t i o n , versus the desired mono-acylation, increases with
the reaction temperature. Below about 5C t h e r e is very little or no
do-acylation. Above about 15C the product will be c o n t a m i n a t e d with
substantial amounts of d i - a c y l a t e d product and, in view of the strict
stoichiometric addition of a c y l a t i n g agent, corresponding amounts of

non-acylated diamine.

Any of the commonly used acylating agents of the art are

eligible for use h e r e i n . The chosen acylating agents are those that
will attach an R'X-group to an amine, namely the R ' X - a c y l a t i n g

agents, such as a c e t y l - a c y l a t i n g agents or m e t h a n e s u l f o n y l - a c y l a t i n g

agents. By R l x - a c y l a t i n g agent is thus meant an a c y l a t i n g agent that

converts an amine, such as a n i l i n e , to an amide, such as a n i l i d e ,

thus: C6H5NH2 C6H5NHXR1. Exemplary of e l i g i b l e Rlx-acylating agents
are acid halides, particularly acid chlorides and acid bromides such

as a c e t y l chloride, benzoyl chloride, benzenesulfonyl chloride and

the like, lower alkyl isocyanates such as e t h y l isocyanate and t h e
like and acid anhydrides, such as acetic anhydride, propionic anhydri-
de and the like.

It is particularly advantageous to carry out the described

inventive process without isolation of the intermediates XVI and
XVII. Both intermediates XVI and XVII are formed and o b t a i n e d in
alcohol solution by t h i s procedure, and are advantageously used w i t h -

out isolation therefrom.

As a s p e c i a l non-preferred example of this process, where R

is H, 2,4-dinitrophenyl (XVI) is reduced to 2,4-diaminophenyl (XVII)
and a c y l a t e d to give I where R is H. The l a t t e r compound, if desired,

may be e t h e r i f i e d , particularly with a di-(lower alkyl) sulfate, to

give I where R is lower alkyl.

As can be a p p r e c i a t e d from the above descriptions, the reac-

tions of t h i s process are advantageously carried out in an a l c o h o l i c
medium. When R of compounds XVI, XVII and I is other than h y d r o g e n ,
the alcohol used in c o n v e r t i n g 2,4-dinitrochlorobenzene to compound
XVI is, of n e c e s s i t y , of s t r u c t u r e ROH. For the conversion of XVI t o
XVII to I, where R is other than H, the alcohol ROH may be used as
the medium, or any lower alcohol, particularly methanol or e t h a n o l .
When R of compounds XVI, XVII and I is hydrogen, the synthesis is
started with 2,4-dinitrophenol (XVI where R is H) and the chosen al-
cohol for the reaction medium may be any a l c o h o l of s t r u c t u r e ROH,
where R is not hydrogen, particularly methanol of e t h a n o l .

The p r o c e s s of this invention is further illustrated by t h e

following specific examples.
Example 1:
Conversion of 2 , 4 - d i n i t r o c h l o r o b e n z e n e to 3 - a m i n o - 4 - m e t h o x y a c e t a n i l i d e
(Step 1) Into a 2 liter flask equipped with stirrer, reflux
condenser and thermometer was charged 632 g methanol and 213 g m e l t e d
2,4-dinitrochlorobenzene (mp. 47C). The mass was s t i r r e d to give a
solution. To t h i s stirred solution was added 86 g of 50% a q u e o u s
sodium h y d r o x i d e solution (or 42 g of sodium h y d r o x i d e flake) at a
rate to heat the reaction solution to gentle reflux. After all the
sodium h y d r o x i d e had been added, the reaction solution was h e a t e d
at reflux for one hour. The heat was removed and the reaction mass was
allowed to cool.

(Step 2) The e n t i r e reaction mass now c o n t a i n i n g 2,4-dinitro-

anisole was charged into a 2 liter Parr autoclave bomb, model 4522,
purged with nitrogen, and t r e a t e d by a d d i t i o n of 4.0 g of 5% p a l l a -
dium on carbon. The bomb was purged with hydrogen and p r e s s u r i z e d to
about 60 psig with rapig agitation. The t e m p e r a t u r e rose adiabatically
to 60C, after which cooling was r e q u i r e d to m a i n t a i n 60C u n t i l

hydrogen uptake ceased and the reduction was complete. The bomb was
then cooled, vented and purged with nitrogen, and the catalyst
filtered off. The washed catalyst may be used 5-6 times. The r e s u l t i n g
2.4-diaminoanisole/methanol solution is assayed for 2,4-diaminoanisole
by p e r c h l o r a t e titration. The y i e l d of 2 , 4 - d i a m i n o a n i s o l e , based on
the 2,4-dinitroanisole, was e s s e n t i a l l y quantitative. The p e r c h l o r a t e

assay was run on an a c c u r a t e l y weighed 2 to 3 g a l i q u o t of the

reaction solution, diluted with 70 to 80 ml of a c e t o n i t r i l e . The

sample was titrated potentiometrically with a glass/calomel electrode,

using 0.2 N perchloric acid.

(Step 3) The above 2,4-diaminoanisole/methanol solution was

charched into a 2-liter flask equipped with stirrer, dropping funnel,
thermometer and gas inlet/exit tubes. The r e a c t i o n flask was p u r g e d
with nitrogen and cooled to 0 to 5C. To the reaction flask was a d d e d
22 g magnesium oxide, followed by e x a c t l y one e q u i v a l e n t weight of
acetic anhydride, based on the analyses of the 2,4-diaminoanisole,
added dropwise over 1-3/4 to 2 hours at a uniform rate. For each mole
of 2 , 4 - d i a m i n o a n i s o l e , 102 g a c e t i c anhydride was used. The r e a c t i o n

mass was m a i n t a i n e d at 0 to 5C d u r i n g the addition of the acetic

anhydride. Teh r e a c t i o n mass was then h e a t e d to d i s t i l l off approxi-

mately 700 ml m e t h a n o l . 300 ml water was added and d i s t i l l a t i o n was
continued until the pot temperature reached 98C. The r e a c t i o n mass
was cooled to room t e m p e r a t u r e and a d j u s t e d in volume to 550 ml by
addition of w a t e r . After further cooling to 0 to 5C, the reaction

product was o b t a i n e d by f i l t r a t i o n . The p r o d u c t on the filter was

washed twice with two 50 ml p o r t i o n s of ice water and a i r dried to
give 167 g of s u b s t a n t i a l l y pure procudt, which analyzed as 151 g o f
3-amino-4-methoxyacetanilide, 5.9 g of 3 - a c e t a m i d o - 4 - m e t h o x y a c e t a n i -
lide, 0.8 g of 2 , 4 - d i a m i n o a n i s o l e , 0.8 g of ash, and 7.9 g of w a t e r ,
with no d e t e c t a b l e 5-amino-2-methoxyacetanilide. Teh 151 g y i e l d of
3-amino-4-methoxyacetanilide represents 80% of theory, based on t h e
2,4-dinitrochlorobenzene starting material. In r e p e a t e d runs, the
yield of 3 - a m i n o - 4 - m e t h o x y a c e t a n i l i d e (excluding any ash, water,
2,4-diaminoanisole and 3 - a c e t a m i d o - 4 - m e t h o x y a c e t a n i l i d e , as a b o v e )
was 80-85/ of t h e o r y based on 2 , 4 - d i n i t r o c h l o r o b e n z e n e , and 90-92% o f

theory based on 2 , 4 - d i a m i n o a n i s o l e .

The p e r c e n t s of mono- and d i - a c e t y l a t e d material were deter-

mined by l i q u i d chromatography, using a Waters Associates Model
ALC 202 c h r o m a t o g r a p h i c apparatus with a Microbondapak C-18 column
of 0.25 inch o.d. x 1 foot, with 3:1 distilled water-methanol as
eluant and an i n t e r n a l standard of pure m a t e r i a l . Product distri-
bution data of mono- and d i a c e t y l a t e d products:
Example 2:
Alternate reduction of 2 , 4 - d i n i t r o a n i s o l e
The r e a c t i o n mass from the first step of Example 1, containing
2,4-dinitroanisole was treated by the addition of 800 g of ice. The
resulting solid 2,4-dinitroanisole was isolated by f i l t r a t i o n and
washed with 1 to 2 liters of cold w a t e r . The wet p r e s s c a k e was added

slowly (exothermic), over a period of 1 hour, to a m i x t u r e of 1200 g

water, 400 g iron powder and 60 g a c e t i c acid, at 85-90C, under a

nitrogen atmosphere. The r e a c t i o n mass was held for about 1 hour at
90-95C, cooled to about 5C, and treated with 80 g of 50% a q u e o u s
sodium h y d r o x i d e and an exact equivalent of a c e t i c anhydride (about
90 g). The r e a c t i o n mass was analyzed for 2,4-diaminoanisole, by
perchlorate titration (as described in Example 1) p r i o r to the alkali
addition. The a c e t i c anhydride was added dropwise, over a period of
about 2 hours, while the temperature of the reaction mass was m a i n -
tained at about 0 to 5C. Following the addition of the acetic
anhydride, the pH was a d j u s t e d to 6 . 8 - 7 . 0 . The r e a c t i o n product was
treated with 20 g of activated charcoal and 10 g of d i a t o m a c e o u s
earth at 95C and f i l t e r e d to c l a r i f y . The f i l t e r residue was washed
three times with 100 ml of hot w a t e r . The combined filtrate and
washings was treated with salt (to 10%), cooled to 0 to 5C, and
filtered to give substantially pure crystalline product, which

assayed at 129 g of 3 - a m i n o - 4 - m e t h o x y a c e t a n i l i d e , 68% of t h e o r y

based on the 2,4-dinitrochlorobenzene starting material.

Example 3: 3-amino-4-ethoxyacetanilide
According to the procedure of Example 1, substituting 632 g
of e t h a n o l for the methanol used therein, 2,4-dinitrochlorobenzene
was c o n v e r t e d to 3 - a m i n o - 4 - e t h o x y a c e t a n i l i d e , in 80% y i e l d .

Example 4: 3-amino-4-methoxypropionanilide
According to the procedure of Example 1, substituting 130 g
of p r o p i o n i c anhydride for the acetic anhydride used therein, 2,4-
dinitrochlorobenzene was converted to 3 - a m i n o - 4 - m e t h o x y p r o p i o n a n i l i d e ,
in 80% y i e l d .

Example 5: 3-amino-4-methoxybenzanilide
According to the procedure of Example 1, substituting 135.5 g
of benzoyl chloride for the acetic anhydride used therein, 2,4-di-
nitrochlorobenzene was c o n v e r t e d to 3 - a m i n o - 4 - m e t h o x y b e n z a n i l i d e , in
79% y i e l d .

Example 6: 3-amino-4-methoxybenzenesulfonanilide
According to the procedure of Example 1, substituting 176.5 g
of benzene sulfonyl chloride for the acetic anhydride used therein,
2,4-dinitrochlorobenzene was converted to 3 - a m i n o - 4 - m e t h o x y b e n z e n e -
sulfonanilide, in 77% y i e l d .

Example 7: 3-amino-4-propoxyacetanilide
According to the procedure of Example 1, substituting 632 g
n-propanol for the 632 g methanol used therein 2,4-dinitrochloroben-
zene was converted to 3-amino-4-propoxyacetanilide, in 77% y i e l d .

Example 8: 3-amino-4-hydroxyacetanilide
According to the procedure of Example 2 and Step 3 of Example
1, substituting 184 g of 2 , 4 - d i n i t r o p h e n o l for the 2,4-dinitroanisole
used therein, a methanol solution of i s o m e r i c a l l y pure 3-amino-4-
hydroxyacetanilide was produced in good y i e l d . For use as a coupler
intermediate, the 3-amino-4-hydroxyacetanilide of this Example may
be e t h e r i f i e d by t r e a t m e n t of the methanol solution thereof with
sodium h y d r o x i d e to make the sodium salt of the phenol, followed by
dimethylsulfate at 30 to 35C.

Example 9: 3-amino-4-ethoxyacetanilide by Solvent Bchamp R e d u c t i o n

Into a 2-liter resin kettle, equipped with stirrer, reflux
condenser and thermometer, was charched 632 g e t h a n o l . To the ethanol

was added carefully, below 50C, in 15-20 m i n u t e s , 42.0 g sodium

hydroxide. To t h i s was added, in 15 to 20 m i n u t e s , 213 g 2 , 4 - d i n i t r o -
chlorobenzene, with the temperature maintained below 50C. The

resulting mixture was heated to r e f l u x and held at reflux for 3 hours

to give an e t h a n o l solution of 2 , 4 - d i n i t r o p h e n e t o l e . After cooling

to room t e m p e r a t u r e , the ethanolix reaction solution was treated
with 340 g iron powder and 200 ml w a t e r , exhigiting a mild exotherm.
A solution of 12 ml h y d r o c h l o r i c acid, 12 ml g l a c i a l acetic acid and
100 ml water was added dropwise over 1 hour at a rate to m a i n t a i n
62-75C. This reaction mass was r e f l u x e d under a nitrogen atmosphere
for 3 hours, then cooled to 0 to 5C, and assayed for 2,4-diamino-
phenetole by p e r c h l o r a t e titration. To the cooled rejection mass was
added 80 g sodium h y d r o x i d e (50% aqueous solution), and then an e x a c t
equivalent amount of a c e t i c anhydride, about 90-94 g acetic anhydride,
depending on the perchlorate assay. The t e m p e r a t u r e was m a i n t a i n e d at
0 to 5C during this addition. The a c e t i c anhydride was added dropwise
over a period of about 2.5 hours. Following the addition of the acetic

anhydride, the pH was adjusted to 6 . 8 - 7 . 0 . The r e a c t i o n product was

treated with 20 g of a c t i v a t e d charcoal and 10 g of d i a t o m a c e o u s
earth at 80C and f i l t e r e d to clarify. The f i l t e r residue was washed
three times with 50 ml of not 1:1 ethanolwater. The combined filtrate

and washings was h e a t e d to d i s t i l l off ethanol, until the pot

temperature reached 98C. The aqueous pot residue was cooled to 10-
15C and f i l t e r e d to give substantially pure crystalline product,
assayed at 126 g of 3 - a m i n o - 4 - e t h o x y a c e t a n i l i d e , 65-70% of t h e o r y ,

based on the 2.4-dinitrochlorobenzene starting material.

As in the above Examples, the following compounds were or

could be made:
 The a c y l a n i l i d e s produced by the process of this invention

are useful as coupler intermediates in the synthesis of u s e f u l azo-

syes. For instance the navy blue dye of structure XXI may b e
synthesized from compound I, as taught in U.S. patent 3,533,722,
according to the following reaction sequence:

The above reaction sequence can also be c a r r i e d out on I ,

where X and R1 are as above, and R is HOCH2HC2-, to give the analog
of d y e s t u f f XXI, where the 3-ethoxy group is replaced by the hydroxy-
ethoxy group. The r e q u i r e d coupler intermediate I for this preparation
is obtained by the process of Example 1, substituting ethylene glycol
for the methanol used therein.

Other couplers which are readily made from an a c y l a n i l i d e of

this invention include

Particularly useful navy dyes are obtained by c o u p l i n g XXII

and XXIII with diazotized 2,4-dinitro-6-bromoaniline. Coupler XXII i s
obtained by s e q u e n t i a l alkylation of 3 - a m i n o - 4 - m e t h o x y a c e t a n i l i d e ;
first with one e q u i v a l e n t of a c r y l o n i t r i l e and then one e q u i v a l e n t
of d i e t h y l s u l f a t e . Coupler XXIII is obtained by a l k y l a t i o n of 3 - a m i n o -
4-methoxyacetanilide with two e q u i v a l e n t s of e t h y l e n e oxide, followed

by e s t e r i f i c a t i o n with two e q u i v a l e n t s of a c e t i c anhydride.

 1. A process for the m a n u f a c t u r e of an a c y l a n i l i d e compound of

the structure

where R is hydrogen, lower alkyl, hydroxy-lower alkyl or lower alkoxy-

lower alkyl; R1 is lower alkyl, phenyl, lower alkylphenyl, lower
alkoxy, lower alkoxyphenyl, chlorophenyl, nitrophenyl, dichlorophenyl,
chloro-lower alkyl, cyano-lower alkyl, lower alkyl, amino, sulfamoyl-
phenyl, carbamoylphenyl or lower alkoxy-lower alkyl; and X is -CO-

or -S02-; comprising the step of treating an a l c o h o l solution of a

diamino compound of the structure

with a substantially equivalent weight of an R 1 X - a c y l a t i n g agent,

added over a period of at least about 1 hour at a temperature in t h e

range of about 0 to about 5C, to give an alcohol solution of t h e

acylanilide compound.

2. The p r o c e s s of claim 1, wherein R and R are independently

methyl, ethyl, n-propyl, or n - b u t y l , X is -CO-, and the alcohol is
ROH.
3. The p r o c e s s of claim 2, wherein R and R are each independently
methyl or e t h y l .

4. The p r o c e s s of claim 1, further comprising a first step of

subjecting an a l c o h o l sLspension of a d i n i t r o compound of the
structure

to r e d u c i n g conditions to give an a l c o h o l solution of the diamino

compound for the subsequent treatment with the Rlx-acylating agent,
without isolation of the diamino compound from the alcohol solution.

5. The p r o c e s s of claim 4, wherein R is lower alkyl, hydroxy-

lower alkyl or lower alkoxy-lower alkyl.

6. The p r o c e s s of claim 5, wherein the reducing conditions include

hydrogen gas under super-atmospheric pressure, in the presence of a

noble metal catalyst, and s t i r r i n g .

7. The p r o c e s s of claim 6, wherein R and Ra r e each independently

methyl or e t h y l , X is -CO-, and the alcohol is ROH.

8. The p r o c e s s of claim 4, w h e r e i n the reducing conditions include

iron in aqueous or a l c o h o l i c suspension at a pH in the range of 3 - 6 . 5 .

9. A process for the m a n u f a c t u r e of an a c y l a n i l i d e of t h e

structure
where R and R1 are each independently methyl or ethyl, comprising
the steps of

1) providing a suspension of 2,4-dinitro-chlorobenzene in a n

alcohol of structure ROH, and

2) sequentially treating the alcoholic suspension with alkali,

hydrogen gas in the presence of a noble metal catalyst, and a s u b -
stantially equivalent weight of an R l - C O - a c y l a t i n g agent added over
a period of at least about 1 hour at a temperature in the range of
about 0 to about 5C,

whereby the 2 , 4 - d i n i t r o c h l o r o b e n z e n e is c o n v e r t e d to the acylanilide,

without i s o l a t i o n or p u r i f i c a t i o n of the i n t e r m e d i a t e s .

10. The p r o c e s s of claim 9, wherein the hydrogen gas is at a

pressure of about 40-80 psig and the noble metal catalyst is a

palladium on carbon catalyst.