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Chemistry 52, Organic 2

Prerequisite: Chemistry 51
Grading Scheme
Recitation Grade:

100 pts average 75

Laboratory Grade

100 pts average 75

Lecture Exams

100 pts

Final

100 pts

Total

400 pts

Old exams and quizzes:


academic.brooklyn.cuny.edu/chem/howell/jhowell.htm
Safety: goggles, pregnancy
Cheating: F
jhowell@brooklyn.cuny.edu

Goals of the course:


1. Structure of organic molecules, relation
of structure to reactivity
2. Organic reaction patterns
3. Mechanism of reactions
4. Synthesis of organic compounds
5. Techniques of the trade

Scaling of Raw Grades for Recitation and Lab


1. Omit the student,
B, that dropped the
course.
2. Get the average
to 75
Multiply these sums by
4.9342

or

Note that student D


was absent from two
labs and will be low
for that reason. We
will deal with D later.

Multiply these sums


by 0.49342
In both cases get
the same
result.

Now we have to spread the grades out so that there is a reasonable


distribution about the desired average of 75. This is done by expanding
or contracting the set of grades around the average so that the
maximum turns out to be 95.

Now for the student D who is outside of the desirable limits (50
95). We move his raw grade up to 70 so that D does not skew the
scaling process. D receives a scaled grade of about 51.

Trends for Relative Acid


Totally unionized
Strengths
in aqueous
solution

Aqueous Solution

Totally ionized in
aqueous solution.

Example
Recall

OH

CH3CH2OH

pKa = 9.95
Stronger
acid
H2O + PhOH

phenol, PhOH

H3O+ + PhO-

Ka = [H3O+][PhO-]/[PhOH] = 10-

ethanol, EtOH

H2O + EtOH

pKa = 15.9
Weaker acid
H3O+ + EtO-

Ka = [H3O+][EtO-]/[EtOH] = 10-15.9

9.95

Ethanol, EtOH, is a weaker acid than phenol, PhOH.


It follows that ethoxide, EtO-, is a stronger base than phenolate, PhO-.
For reaction PhOH + EtOPhO- + EtOH where does
equilibrium lie?
Weaker base.
Stronger
K = 10-9.95 / 10-15.9 = 106.0
base
Query: What makes for strong (or weak) acids?

What affects acidity?


1. Electronegativity of the atom holding the negative charge.
Increasing
acidity.

CH3O - + H+

CH3OH
CH3NH2

CH3NH - + H+

CH3CH3

CH3CH2- + H+

Increasing
Increasing basicity
electronegativity
of
of anion.
atom bearing negative
charge. Increasing
stability of anion.

2. Size of the atom bearing the negative charge in the anion.


Increasing
acidity.

CH3OH

CH3O - + H+; pKa = 16

CH3SH

CH3S - + H+; pKa = 7.0

Increasing
Increasingsize
basicity
of
atom
of anion.
holding
negative charge.
Increasing stability of
anion.

What affects acidity? - 2


3. Resonance stabilization, usually of the anion.

Acidity

OH

Increasing
resonance
basicity
of
stabilization
the
anion.
. Increased
anion
stability.

phenol, PhOH

CH3CH2OH
ethanol, EtOH

CH3CH2O - + H+

No resonance structures!!
Note that phenol itself enjoys resonance but
charges are generated, costing energy, making
the resonance less important. The more
important resonance in the anion shifts the
equilibrium to the right making phenol more
acidic.

OH

OH

etc.

An example: competitive Bases


& Resonance
Two different bases or two sites in the same molecule
may compete to be protonated (be the base).
Acetic acid can be protonated at two sites.
Pi bonding
electrons
converted
to nonbonding.

H+

H
H

acetic acid

Nonbonding
electrons
converted
to pi O H
bonding.
O

Which conjugate
acid is favored?

The more stable


one! Which is that?
Recall resonance
provides additional
stability by moving
pi or non-bonding
electrons.

No valid
resonance
structures for this
cation.

An example: competitive Bases &


Resonance
Comments on the importance of the resonance structures.
All atoms obey
octet rule!
H

H+
H

acetic acid

The carbon is electron


deficient 6 electrons, not
8. Lesser importance
H

All atoms obey


octet rule!

What affects acidity? - 3


4. Inductive and Electrostatic Stabilization.

Acidity.

H3CCH2OH

F3CCH2OH

H3CCH2O - + H+

Increasing anion
Increasing anion
stability.
basicity.

F3CCH2O - + H+

Due to electronegativity
of F small positive
charges build up on C
resulting in stabilization
of the anion.
Effect drops off with distance. EtOH pKa = 15.9

What affects acidity? - 4

Increasing Acidity of HA

Increasing Basicity of A-

Note. The NH25. Hybridization of the atom bearing the charge. H-A H+ + A:-.
is more basic
than the RCCsp3
sp2
sp
ion.
More s character, more stability, more electronegative,
H-A more acidic, A:- less basic.

Know this order.

Example of hybridization
Effect.
terminal alkyne
RCCH + LiCH2CH2CH2CH3
base
acid
RCCH + AgNO3

HCH2CH2CH2CH3 + RCCLi

AgCCR (ppt)

non-terminal alkyne
RCCR + LiCH2CH2CH2CH3
RCCR + AgNO3

NR

No Reaction

What affects acidity? - 5


O
H

6. Stabilization of ions by solvents (solvation).

O
H

H
O

Solvation
provides
stabilization.

Comparison of alcohol acidities.


OH

OH

OH

H
O

pKa = 15.9
ethanol

17
propan-2-ol

18

2-methylpropan-2-ol

Crowding inhibiting solvation

Solvation, stability of anion, acidity

(CH3)3CO -,
crowded

Example
para nitrophenol is more acidic than phenol. Offer an explanation

OH

+ H

Why? Could be due to


destabilization of the unionized
form, A, or stabilization of the
ionized form, B.

OH

+ H

N
O

The lower lies further to the right.

Examine the equilibrium for p-nitrophenol. How does


the nitro group increase the acidity?
O

OH

+ H

N
O

OH

N
O

First the unionized


acid.

Note carefully that in these


resonance structures charge is
created: + on the O and in the ring
or on an oxygen. This decreases the
importance of the resonance.

OH

OH

OH

N
O

Examine both sides


of equilibrium.
What does the nitro
group do?

Structure D occurs only due to


the nitro group. The stability it
provides will slightly decrease
acidity.

Resonance structures A, B and C are comparable to those in the phenol itself


and thus would not be expected to affect acidity. But note the + to

Now look at the anion. What does the nitro group do?
Remember we are interested to compare with the phenol
phenolate equilibrium.
O
OH

+ H

N
O

In these resonance structures


charge is not created. Thus these
structures are important and
increase acidity. They account for
the acidity of all phenols.

Structure D occurs only due to


the nitro group. It increases
acidity. The greater amount of
N
N
N
N
significant resonance in the anion
O
O
O
O
O
O
O
O
accounts for the nitro increasing
D
B
C
A
the acidity.
Resonance structures A, B and C are comparable to those in the phenolate
anion itself and thus would not be expected to affect acidity. But note the +
to attraction here

Carboxylic Acid Structure


The functional group of a carboxylic
acid is a carboxyl group.
O
C
O H

O
O H

COOH

CO2H

Alternative representations for a carboxyl group

The general formula for an aliphatic


carboxylic acid is RCOOH; that for an
aromatic carboxylic acid is ArCOOH.

Nomenclature - IUPAC
names: drop the -e from the
parent alkane and add the suffix -oic
acid.
acid

IUPAC

O
HCOOH

CH3COOH

Methanoic acid
(Formic acid)

Ethanoic acid
(Acetic acid)

OH
3-Methylbutanoic acid
(Isovaleric acid)

If the compound contains a carbon-carbon


double bond, change the infix -anan to -en-.
en
O

O
OH

OH

Propenoic acid trans-2-Butenoic acid


(Acrylic acid)
(Crotonic acid)

OH
trans-3-Phenylpropenoic acid
(Cinnamic acid)

Nomenclature - IUPAC
The carboxyl group takes precedence
over most other functional groups.
OH

OH
(R)-5-Hydroxyhexanoic
acid

OH
5-Oxohexanoic acid

O
H2 N

OH
4-Aminobutanoic acid

Nomenclature - IUPAC
Dicarboxylic acids: add the suffix -dioic
acid to the name of the parent alkane
containing both carboxyl groups.
O

HO

O
OH

O
Ethanedioic acid
(Oxalic acid)
O
HO

O
OH HO

O
Butanedioic acid
(Succinic acid)

HO

O
OH

Propanedioic acid
(Malonic acid)
O

O
OH

HO

OH
O

Pentanedioic acid
(Glutaric acid)

Hexanedioic acid
(Adipic acid)

Nomenclature - IUPAC

If the carboxyl group is bonded to a ring, name


the ring compound and add the suffix -carboxylic
acid.
acid
2
3

COOH

2-Cyclohexenecarboxylic
acid

HOOC

COOH

trans-1,3-Cyclopentanedicarboxylic
acid

Benzoic acid is the simplest aromatic carboxylic


acid.
COOH

to show
the location of substituents.
COOHUse numbers
COOH
COOH
OH

COOH

COOH
Benzoic 2-Hydroxybenzoic 1,2-Benzenedicarboxylic 1,4-Benzenedicarboxylic
acid
acid
acid
acid
(Salicylic acid)
(Phthalic acid)
(Terephthalic acid)

Nomenclature-Common
When common names are used, the
letters etc. are often used to
locate substituents.
O

5
1 OH
4 3 2

O
H2 N

OH

4-Aminobutanoic acid
(-Aminobutyric acid, GABA)

OH
NH2
(S)-2-Aminopropanoic acid
[(S)--Aminopropionic acid;
L-alanine]

Physical Properties
In the liquid and solid states, carboxylic acids are
associated by hydrogen bonding into dimeric
structures.

Physical Properties
Carboxylic acids have significantly higher
boiling points than other types of organic
compounds of comparable molecular
weight.
They are polar compounds and form very strong
intermolecular hydrogen bonds.

Carboxylic acids are more soluble in water


than alcohols, ethers, aldehydes, and
ketones of comparable molecular weight.
They form hydrogen bonds with water molecules
through both their C=O and OH groups.

Physical Properties
Table 17.2

Molecular Boiling
Weight
Point
(C)
(g/mol)

Solubility
(g/100 g H2 O)

Structure

Name

CH3 COOH

Acetic acid

60.1

118

Infinite

CH3 CH2CH2OH

1-Propanol

60.1

97

Infinite

CH3CH2CHO

Propanal

58.1

48

16

88.1

163

Infinite

88.1
86.1

137
103

2.3
Slight

CH3(CH2)4 COOH Hexanoic acid 116.2


CH3 (CH2) 5CH2OH 1-Heptanol
116.2
CH3(CH2)5CHO Heptanal
114.1

205

1.0

176
153

0.2
0.1

CH3(CH2)2 COOH Butanoic acid


CH3 (CH2) 3CH2OH 1-Pentanol
CH3(CH2)3CHO Pentanal

Physical Properties
Water solubility decreases as the
relative size of the hydrophobic portion
of the molecule increases.

Acidity

Carboxylic acids are weak acids.


Values of pKa for most aliphatic and aromatic
carboxylic acids fall within the range 4 to 5.
The greater acidity of carboxylic acids relative to
alcohols (both compounds that contain an OH
group) is due to resonance stabilization of the
carboxylate anion.

CH3

CH3

These contributing structures are equivalent;


the carboxylate anion is stabilized
by delocalization of the negative charge

Acidity
Electron-withdrawing substituents near the
carboxyl group increase acidity through their
inductive effect.

Formula: CH3COOH ClCH2COOH


Name:
pKa :

Acetic
acid
4.76

Cl2CHCOOH

Chloroacetic Dichloroacetic
acid
acid
2.86
1.48
Increasing acid strength

Cl3CCOOH

Trichloroacetic
acid
0.70

Acidity
The form of a carboxylic acid present in
aqueous solution depends on the pH of
the solution.
O
O
O
O
OH
OH
R-C-OH
R-C-OH + R-C-OR-C-O
H+
H+
predominant
present in equal
predominant
species when the
concentrations when
species when
pH of the
the pH of the
the pH of the
solution is
solution is equal to
solution is 7.0
2.0 or less
the pKa of the acid
or greater

Reaction with Bases

Carboxylic acids, whether soluble or


insoluble in water, react with NaOH,
KOH, and other strong bases to give
water-soluble salts.
COOH + NaOH
Benzoic acid
(slightly soluble
in water)

H2 O

COO Na

+ H2 O

Sodium benzoate
(60 g/100 mL water)

They also form water-soluble salts with


ammonia and amines.
COOH + NH3
Benzoic acid
(slightly soluble
in water)

H2 O

COO NH4

Ammonium benzoate
(20 g/100 mL water)

Reaction with Bases


Carboxylic acids react with sodium
bicarbonate and sodium carbonate to
form water-soluble salts and carbonic
acid.
Carbonic acid, in turn, breaks down to
carbon dioxide and water.
CH3COOH + NaHCO3
H2 CO3
CH3COOH + NaHCO3

CH3COO Na + H2 CO3
CO2 + H2O
- +
CH3COO Na + CO2 + H2O

Reaction with
bases
The acid-base
properties of
carboxylic acids
allow an easy
separation of
carboxylic acids
from waterinsoluble
nonacidic
compounds.

Preparation
Carbonation of Grignard reagents
Treatment of a Grignard reagent with
carbon dioxide followed by acidification
gives a carboxylic acid.
O
MgCl + C
O
Carbon dioxide
O
C-O

[ MgCl] +

A magnesium carboxylate

HCl
H2 O

O
C-OH + Mg 2+
Cyclopentanecarboxylic acid

Oxidation
Primary alcohol
Na Cr O
RCH2OH 2 2 7

Na2Cr2O7
RCH=O

RCO 2H

Na2Cr2O7 (orange) Cr3+


(green) Actual reagent is
H2CrO4, chromic acid.
Secondary
Na2Cr2O7
R2CHOH

R2C=O KMnO4 (basic) can also


be used. MnO2 is
produced.

Tertiary
R3COH

NR

The failure of an attempted


oxidation (no color change) is
evidence for a tertiary
alcohol.

Oxidation: Aldehyde
Carboxylic
Recall from the discussion of alcohols.

Milder oxidizing reagents can also be used

RCHO

Ag(NH3)2+

RCO2- + Ag

Tollens Reagent test for


aldehydes

Haloform Reaction, overall


O
O

CH3

CX3
CO2-

X2
NaOH

O
CH3

methyl

NaOH
+ HCX3

The last step which produces the


haloform, HCX3 only occurs if there is
an methyl group, a methyl directly
attached to the carbonyl.
If done with iodine then the formation of
iodoform, HCI3, a bright yellow
precipitate, is a test for an methyl
group (iodoform test).

Example

OH

OH

Na2Cr2O7
acid

HO

CH2OH

CO2H

Oxidation using PCC


Primary
alcohol
PCC
RCH2OH

Secondary
PCC
R2CHOH
R2C=O

Stops here, is not


oxidized to carboxylic
RCH=O
acid

Periodic Acid Oxidation


OH

O
OH

HIO4

glycol

HIO3

two aldehydes
OH

HIO4

HO

+ HIO3
aldehydes
O

carboxylic acid

O
O

HO

HIO4

+ HIO3

OH

carboxylic acid

carboxylic acid

OH
O

2 HIO4

O
HO

+ 2 HIO3

OH
OH

Hydrolysis of Nitriles, RCN

Work on mechanism of hydrolysis

Methanol to Acetic Acid


Acetic acid is synthesized by
carbonylation of methanol.
The carbonylation is exothermic.
CH3 OH + CO

O
CH3 COH H = -138 kJ(33 kcal)/mol

The Monsanto process uses a soluble


rhodium(III) salt and HI to catalyze the
reaction.

Mechanism for Monsanto Process: methanol to acetic acid.

Product

Complicated process. Lets look in some detail.

Reactant

Mechanism for Monsanto Process: methanol to acetic acid


First. Look at the Rh
complexes
Hexa coordinate
complex
Iodide negative, CO
neutral, CH3CO
negative. Thus Rh(III).

Tetra coordinate
complex
Iodide negative, CO
neutral. Thus Rh(I)

Hexa coordinate
complex
Iodide negative, CO
neutral, CH3
negative. Thus Rh(III).
oxidized.
PentaRh
coordinate
complex
Iodide negative, CO
neutral, CH3CO

Some Inorganic Chemistry:


Oxidative addition-reductive elimination

Mn+ + X-Y

M(n+2)+
X-

YH

Ph3P
Cl

Ir

CO
PPh3

Vaskas compound

Ox. Addn
+ H2
Reduc. Elim.

Ph3P
Cl

Ir III
CO

Very important in activation of hydrogen

H
PPh3

Insertion-deinsertion

M-X + L

M-L-X

O
(CO)5Mn-C-CH3

(CO)5Mn-CH3 + CO

Very important in catalytic C-C bond forming reactions


(polymerization, hydroformylation)
Also known as migratory insertion for mechanistic reasons
CH3
OC
OC

Mn
CO

H3 C

H3 C
CO
CO

CO

O
Mn
OC
CO
CO

CO

CO

C
CO
O
Mn
OC
CO
CO

echanism for Monsanto Process: methanol to acetic acid.


Second: Look at the
reactions
Reductive
Elimination.

Tetra coordinate
complex
Rh(I)
Oxidative
Addition.

Hexa coordinate
complex
Rh(III).

Hexa coordinate
complex
Rh(III).

Rh(III)
.
Insertion Reaction, Migratory
Insertion

Reduction of Carboxylic Acids


The carboxyl group is very resistant to reduction.
It is not affected by catalytic hydrogenation
under conditions that easily reduce aldehydes
and ketones to alcohols, and reduce alkenes
and alkynes to alkanes. Nor is it reduced by
NaBH4.
Lithium aluminum hydride reduces a carboxyl
group to a 1 alcohol.
reduction is carried out in diethyl ether, THF, or
otherOnonreactive, aprotic solvent.
COH

1. LiAlH4
2. H2O

CH2 OH + LiOH + Al(OH) 3


4-Hydroxymethylcyclopentene

Selective Reduction
Carboxyl groups are not affected by catalytic
reduction under conditions that reduce
O
Oand ketones.
OH
O
aldehydes
OH + H2
5-Oxohexanoic acid

Pt
25C, 2 atm

OH
5-Hydroxyhexanoic acid
(racemic)

O
OHby NaBH
O
NorOare carboxyl
groups reduced
4.

1. NaBH4
C6 H5
OH
C6 H5
OH
2. H2 O
5-Oxo-5-phenylpentanoic acid
5-Hydroxy-5-phenylpentanoic acid
(racemic)

Fischer Esterification
Esters can be prepared by treating a
carboxylic acid with an alcohol in the
presence of an acid catalyst,
commonly H2SO4, ArSO3H, or gaseous
O
O
H
SO
2
4
HCl.
OH
Ethanoic acid
(Acetic acid)

HO
Ethanol
(Ethyl alcohol)

+ H2 O
O
Ethyl ethanoate
(Ethyl acetate)

Fischer Esterification
Fischer esterification is an equilibrium
reaction.
By careful control of experimental
conditions, it is possible to prepare esters
in high yield.
If the alcohol is inexpensive relative to the
carboxylic acid, it can be used in excess to
drive the equilibrium to the right.
Alternatively, water can be removed by
azeotropic distillation .

Mechanism of Fischer Esterification.


Consists of two parts
Acid catalyzed addition
of alcohol to the
carbonyl group.

Acid catalyzed elimination


of water to re-establish the
carbonyl group.

Compare with the mechanism


for formation of a hemiacetal
(next)

hemiacetal formation in Acid


Protonation of
carbonyl (making the
oxygen more
electronegative)
Attack of the (poor)
nucleophile on (good)
electrophile.

Deprotonation

Overall, we have added


the alcohol to the
carbonyl.

Can use diazomethane to form methyl


esters.
Diazomethane, CH2N2
A potentially explosive, toxic, yellow gas
is a hybrid of two contributing
structures.
H C N N:

H C N N:

Treating a carboxylic acid with


diazomethane gives a methyl ester.
O
RCOH + CH2 N2

ether

Diazomethane

O
RCOCH3 + N2
A methyl ester

Diazomethane Mechanism
Esterification occurs in two steps.
Step 1: Proton transfer to diazomethane.
O
R C O H +

CH2 N N

R C O:

A carboxylate
anion

CH3 N N

Methyldiazonium
cation

Step 2: Nucleophilic displacement of N2.


O

R C O: + CH3 N N

SN2

O
R C O CH3 + N N

Acid Chlorides
The functional group of an acid
halide is a carbonyl group bonded to
a halogen atom.
Among the acid halides, acid chlorides
O
O
O
are by far the most common and
the
C-Cl
-C-X
CH3 CCl
most widely used.
Functional group
of an acid halide

Acetyl
chloride

Benzoyl
chloride

Acid Chlorides
Acid chlorides are most often prepared
by treating a carboxylic acid with thionyl
chloride.
O

+ SOCl2
OH
Cl + SO2 + HCl
Butanoic acid Thionyl chloride Butanoyl chloride

Acid Chlorides Mechanism


Two steps.
Step 1: Reaction with SOCl2 transforms
OH, a poor leaving group, into a
chlorosulfite group, a good leaving
group.
O

R-C-O-H + Cl-S-Cl

R C O S Cl + H-Cl
A chlorosulfite
group

Acid Halides
Step 2: Attack of chloride ion gives a
tetrahedral carbonyl addition
intermediate, which collapses to give
O theO acid chloride.
R

Cl

Cl -

O R

O
O

O
Cl

Cl

A tetrahedral carbonyl
addition intermediate

R-C-Cl

SO2

Cl

Decarboxylation
Decarboxylation: The loss of CO2
from a carboxyl group.
Most carboxylic acids require a very
high temperature for thermal
decarboxylation.
O
decarboxylation
R-C-OH
R-H + CO2
heat

Decarboxylation
Exceptions are carboxylic acids that
have a carbonyl group beta to the
carboxyl group
This type of carboxylic acid undergoes
decarboxylation on mild heating.
O

warm

OH
3-Oxobutanoic acid
(Acetoacetic acid)

Acetone

+ CO
2

Mechanism: Thermal decarboxylation of a


-ketoacid
Thermal decarboxylation of a -ketoacid
involves rearrangement of six electrons
in a cyclic six-membered transition
H
H
state.
O
O
O
O

(1)

CO2

(A cyclic six-membered
transition state)

only this carboxyl


has a C=O beta to it.

(2)

HO
O

Enol of
a ketone

A ketone

O
OH

HO
O
Oxalosuccinic acid

OH + CO2

HO
O
-Ketoglutaric acid

Decarboxylation of Malonic
Acid
Decarboxylation occurs if there is any
carbonyl group beta to the carboxyl.
Malonic acid and substituted malonic
acids.
O
O
140-150C
HOCCH2 COH
Propanedioic acid
(Malonic acid)

O
CH3COH + CO2

Mechanism of Malonic Acid


Decarboxylation
Thermal decarboxylation of malonic
acids also involves rearrangement of six
electrons in a cyclic six-membered
transition state.
O
HO

(1)
O

HO

O
+ C
O

(2)

A cyclic six-membered
Enol of a
transition state
carboxylic acid

Same as earlier mechanism, except that have OH here

O
HO
A carboxylic
acid

+ CO2