Transcript Acides carboxyliques

Carboxylic acids and their
derivatives
© E.V. Blackburn, 2011
Structure
O
R
O
O
H
Ar
O
H
O
H
O
carboxy group
© E.V. Blackburn, 2011
Structure of derivatives
O
R
X
O
R
O
R
O
acyl halide
acid halide
O
R
NH 2
amide
anhydride
O
R
OR'
ester
© E.V. Blackburn, 2011
The acyl group
O
O
O
R
R
O
X
R
R
NH 2
R
O
OR'
O
R
O
© E.V. Blackburn, 2011
Nomenclature
HCO2H
formic acid (from Latin formica, ant)
CH3CO2H
acetic acid (from Latin acetum, vinegar)
CH3CH2CO2H
propionic acid (from Greek protos, first
and piôn, fat)
CH3(CH2)2CO2H
butyric acid (from Latin butyrum, butter)
CH3(CH2)3CO2H
valeric acid (valerian root)
CH3(CH2)4CO2H
caproic acid (from Latin caper, goat)
CH3(CH2)6CO2H
caprylic acid
CH3(CH2)8CO2H
capric acid
© E.V. Blackburn, 2011
Nomenclature
   
C C C C
O
O
H
CH3CH2CHCO 2H
NH 2
-aminobutyric acid
© E.V. Blackburn, 2011
Nomenclature
CH3CHCO 2H
OH
-hydroxypropionic
acid or lactic acid
H3C
CHCH 2CH2CO2H
isocaproic acid
H3C
© E.V. Blackburn, 2011
Aromatic acids
Br
CO2H
p-bromobenzoic acid
CH3
CO2H
m-toluic acid
© E.V. Blackburn, 2011
Aldehydes - non-systematic
names
H
O
KMnO 4
H
form(ic acid)aldehyde
CH3CH2CHCH 2CHO
CH3
H
O
HO
formic acid
-methylvaleraldehyde
© E.V. Blackburn, 2011
IUPAC
CH3CH2CO2H
(CH3)2CHCH2CH2CO2H
(CH3)2CHCH=CHCH(OH)CO2H
propanoic acid
4-methylpentanoic acid
2-hydroxy-5-methyl3-hexenoic acid
C-1
© E.V. Blackburn, 2011
Cyclic acids
Saturated cyclic acids are named as cycloalkanecarboxylic
acids:
O
OH
CH3
cis-2-methylcyclohexanecarboxylic acid
© E.V. Blackburn, 2011
Salts of carboxylic acids
Na + O
C
O
benzo(ic acid)ate
sodium benzoate
(CH3CO2)2Ca
calcium acetate or calcium ethanoate
© E.V. Blackburn, 2011
Nomenclature of derivatives
CH3CO2H
HO
O
acetic acid
ethanoic acid
benzoic acid
© E.V. Blackburn, 2011
Nomenclature of acyl halides
CH3CO2H
HO
O
acetic acid
ethanoic acid
O
benzoic acid
Cl
O
H 3C
Cl
ethanoic acidyl chloride
ethanoyl chloride
acetyl chloride
benzoyl chloride
Change -ic acid to -yl halide
© E.V. Blackburn, 2011
Nomenclature of anhydrides
CH3CO2H
HO
O
acetic acid
ethanoic acid
O
H 3C
O
H 3C
benzoic acid
O
O
O
O
acetic acidanhydride
acetic anhydride
benzoic anhydride
ethanoic anhydride
change acid to anhydride
© E.V. Blackburn, 2011
Nomenclature of amides
CH3CO2H
HO
O
acetic acid
ethanoic acid
benzoic acid
O
O
NH 2
NH 2
H3C
acetamide
ethanamide
benzoic acidamide
benzamide
change -ic or -oic acid to -amide
© E.V. Blackburn, 2011
Nomenclature of esters
CH3CO2H
HO
O
acetic acid
ethanoic acid
benzoic acid
O
O
OC2H5
O
H3C
ethyl acetic acidate
ethyl acetate
ethyl ethanoate
phenyl benzoate
change -ic acid to name of alcohol group or phenol + -ate
© E.V. Blackburn, 2011
Order of precedence of functional
groups
O
R
O
O > R
>
R
OH
carboxylic
acid
O
R
O
anhydride
ester
O
> RCN
nitrile
> R
H
aldehyde
OR'
O
O
> R
X
alcanoyl
halide
> R
NH 2
amide
O
> R
R'
ketone
> ROH
alcohol
> RNH 2
amine
© E.V. Blackburn, 2011
Physical properties
Intermolecular hydrogen bonding is very important.
H O +
+O
C R
R C
O
O H
-
In the solid and liquid states, carboxylic acids
exist as dimers. Mp and bp values are far higher
than the corresponding alcohols.
© E.V. Blackburn, 2011
Physical properties of acid
derivatives
Polar compounds: the acyl halides, anhydrides, and esters
have boiling points which are very similar to those of
aldehydes and ketones of equivalent molecular weight.
However, the amides.......
O
R
N
H
O
H
R
R
O
H
N
H
H
O
N
H
R
© E.V. Blackburn, 2011
Dissociation of carboxylic
acids
H2O + RCO 2H
RCO 2- + H3O+
[RCO2-][H3O+]
Ka =
[RCO2H]
H2O + RCO2-
~ 10-5
RCO2H + OH-
© E.V. Blackburn, 2011
Relative acidities
RCO2H > H2O > ROH > HC CH > NH 3 > RH
Relative basicities
RCO2- < OH- < RO- < HC C- < NH2- < R-
© E.V. Blackburn, 2011
Acidity of carboxylic acids
H+ + RO -
ROH
O
R+
R
O H
O
O
R
O H
+
O H
O
R
O
O
-
R
-
O
R
O
O
© E.V. Blackburn, 2011
Structure of carboxylate ions
O
R
O
O
-
R
-
O
R
O
O
1.20 Å
O
H C
OH
1.27 Å
1.34 Å
O
H C O
© E.V. Blackburn, 2011
Substituent effects
O
G < C O
O
G > C O
Ka
CH3CO2H ClCH2CO2H Cl2CHCO2H Cl3CCO2H
1.76x10-5
136x10-5
5530x10-5 23200x10-5
Ka
HCO2H
17.7x10-5
CH3CO2H
1.76x10-5
CH3CH2CH2CO2H
1.52x10-5
© E.V. Blackburn, 2011
Salts of carboxylic acids
OHRCO2H
H+
RCO2-
• crystalline, non-volatile, decompose on heating to
300 - 400C.
• sodium, potassium and ammonium salts are all
water soluble and insoluble in non-polar solvents.
© E.V. Blackburn, 2011
Salts of carboxylic acids
RCO2H + NaOH
water insoluble
RCO2H
NaHCO 3
RCO2- Na + + H2O
water soluble
RCO2- Na + + H2O + CO2
NB: Phenols do not react with bicarbonate.
© E.V. Blackburn, 2011
Preparation of carboxylic
acids
© E.V. Blackburn, 2011
Oxidation of primary alcohols
© E.V. Blackburn, 2011
Oxidation of arenes
© E.V. Blackburn, 2011
Oxidation of arenes
CH3
CO2H
hot
KMnO 4
CH3
p-xylene
CO2H
terephthalic acid
© E.V. Blackburn, 2011
The haloform reaction
(CH3)3C C CH3 + Cl2 + OHO
(CH3)3C C CCl 3
O
OHCHCl 3 + (CH3)3CCO2-
© E.V. Blackburn, 2011
Carboxylation of Grignard
reagents
R
-
MgX
+
O C +
O -
O
R C
OMgX
H+
RCO2H
+ Mg 2+
+ X-
© E.V. Blackburn, 2011
Carboxylation of Grignard
reagents
H3C
Mg
H3C C Cl
H3C
H3C
H3C C MgCl
H3C
i) CO2
ii) H+
H3C
H3C C CO2H
H3C
2,2-dimethylpropanoic
acid
© E.V. Blackburn, 2011
Hydrolysis of nitriles
R C N
or
Ar C N
acid
+ H2O
or
base
RCO2H
+ NH3
ArCO 2H
© E.V. Blackburn, 2011
Preparation of nitriles - an SN2
reaction
CH3CH2CH2CH2Br + CN- 
CH3CH2CH2CH2CN
primary halide
(CH3)3CBr + CN-  (CH3)2C=CH2 + HCN
© E.V. Blackburn, 2011
Nomenclature of nitriles
CH3CH2CN - 3 carbon chain
propane + nitrile = propanenitrile
propionic acid - ic acid + onitrile = propiononitrile
CN
benzonitrile
CH3CN
ethanenitrile
acetonitrile
CH3(CH2)3CN
pentanenitrile
valeronitrile
© E.V. Blackburn, 2011
The acyl group


R
o
120

C
G
sp2

O

© E.V. Blackburn, 2011
Reactivity of aldehydes and
ketones
:Nu
R
O
'R

Nu 
'R C O
R
Nu H2O
'R C OR
Nu
'R C OR
Nu
'R C OH
R
© E.V. Blackburn, 2011
Reactivity of carboxylic acid
derivatives – nucleophilic addition elimination
OR C Nu
G
O
R
G
:Nu
O
G:
+
R
Nu
G = -OH, -X, -OOCR, -NH2, or -OR
Why?
© E.V. Blackburn, 2011
Reactivity of carboxylic acid
derivatives
The ease of loss of the leaving group, G, depends on its
basicity:
G = HO-, X-, RCO2-, NH2- , or ROG = H-, R- ?
© E.V. Blackburn, 2011
Reactivity of carboxylic acid
derivatives
H+
OH+
O:
R
R
G
+
OH
+
OH
R
G
R
Nu:
OH
Nu
G
G
R
R
Nu
G
OH
Nu
G
+
OH
R
+ G:
Nu
© E.V. Blackburn, 2011
Base hydrolysis
-
O
R
R
G
R
HO:
OOH
G
O
R
O
R
+ G:
OH
OHR
OH
O
OH
G
O
- + H 2O
O
© E.V. Blackburn, 2011
Acid hydrolysis
H+
OH+
O:
R
R
G
G
+
OH
H2O:
OH
R
OH2
G+
OH
R
OH
G
OH
R
OH
+ GH
R
R
G
-H+
+H+
OH
OH2
G+
OH
R
OH
G
OH
R
OH
+ GH
+
OH
R
+ HG
R
OH
+
OH
-H+
O
R
OH
OH
© E.V. Blackburn, 2011
SN2 v acyl substitution
SN2
Nu:
Nu
G
G
:Nu
R
+ G:
Nu
O
O
R
G
ONu
G
R
Nu
G
O
G:
+
R
Nu
© E.V. Blackburn, 2011
Nucleophilic displacement reactivity
more reactive
O
R
less reactive
RCl
Cl
O
R
RNH 2
NH 2
O
R
R-O-R'
OR'
© E.V. Blackburn, 2011
Haloform reaction
(CH3)3C C CH3 + Cl2 + OHO
(CH3)3C C CCl 3
O
OHCHCl 3 + (CH3)3CCO2-
© E.V. Blackburn, 2011
Haloform reaction
-
OH
(CH3)3C C CCl 3
O
OH
(H3C)3C
CCl 3
O-
OH
(H3C)3C
CCl 3
O-
(CH3)3C C OH
O
(H3C)3C C OH
O
-
CCl 3
HO -
H 2O
+ -CCl 3
(H3C)3C C OO
HCCl 3
© E.V. Blackburn, 2011
acid chlorides
O
O
R
O
H
R
Cl
Use thionyl chloride (SOCl2), phosphorus trichloride
(PCl3) or phosphorus pentachloride (PCl5).
© E.V. Blackburn, 2011
acid chlorides
O
O
O
H
SOCl 2
Cl

benzoyl
chloride
O
O2N
O
H
PCl5
O2N
O
Cl

NO 2
NO 2
3,5-dinitrobenzoyl
chloride
© E.V. Blackburn, 2011
Reactions of acyl halides conversion into acids
O
O
+ H 2O
Cl
benzoyl
chloride
+ HCl
OH
benzoic acid
© E.V. Blackburn, 2011
Reactions of acyl halides conversion into amides
© E.V. Blackburn, 2011
Reactions of acyl halides conversion into esters
O
+ R'OH
R
Cl
O
R
+ HCl
OR'
Cl
H3CO
O CH OH
3
O
© E.V. Blackburn, 2011
Reactions of acyl halides Friedel - Crafts’ acylation
O
+ ArH
R
AlCl 3
Cl
O
R
+ HCl
Ar
O
CH3CH2COCl
AlCl 3
© E.V. Blackburn, 2011
Reactions of acyl halides with
diorganocopper reagents
O
R C Cl + (CH 3)2Cu Li
A Gilman reagent
(CH3CH2)2Cu Li
O
H3C C Cl
O
R C CH 3
O
H3C C CH2CH3
© E.V. Blackburn, 2011
Reactions of acyl halides - the
Rosemund reduction
RCOCl or ArCOCl
H2, Pd-BaSO4
quinoline
RCHO or ArCHO
A special catalyst is used: palladium on barium sulfate
which has been deactivated (poisoned) with an amine
such as quinoline.
© E.V. Blackburn, 2011
Lithium tri-tertbutoxyaluminium hydride
O 1. LiAlH(O-t-Bu) , Et O, -78C
3
2
O
Cl 2. H2O
H
© E.V. Blackburn, 2011
Reaction with carboxylate ions
© E.V. Blackburn, 2011
Anhydrides - preparation of
acetic anhydride
CH3CO2H
AlPO 4
700C
H2C=C=O + H 2O
ketene
O
H2C=C=O + CH 3CO2H
H3C
O
H 3C
O
acetic anhydride
© E.V. Blackburn, 2011
Preparation of other
anhydrides
Nucleophilic substitution of an acyl halide with a
carboxylate anion.
© E.V. Blackburn, 2011
Hydrolysis of anhydrides
© E.V. Blackburn, 2011
Aminolysis of anhydrides
© E.V. Blackburn, 2011
Alcoholysis of anhydrides
(CH3CO)2O + CH3OH
CH3CO2CH3 + CH3CO2H
methyl
acetate
© E.V. Blackburn, 2011
Acylation
(CH3CO) 2O +
AlCl 3
O
+ CH3CO2H
© E.V. Blackburn, 2011
Preparation of esters
O
R
O
O
H + R'OH
R
O
R' + H2O
SOCl 2
R'OH
O
R
Cl
© E.V. Blackburn, 2011
Preparation of esters
Br
Br
COCl
pyridine
+ C2H5OH
CO2C2H5
+ HCl
© E.V. Blackburn, 2011
Preparation of esters
CH3CO2H +
H+
CH2OH

RCHCH 2CH2CO2- Na +
OH
CH2OCCH 3
O
O
H+
OH
-
O
R H
-lactone
© E.V. Blackburn, 2011
Reactions - base hydrolysis
-
O
R
OR'
HO:
R
O
OH
OR'
R
O
- + R'OH
O
rate = k[OH-][ester]
How can we prove that OH- attacks the acyl carbon
and not the alkyl carbon?
© E.V. Blackburn, 2011
Reactions - base hydrolysis
C 2H 5
O
Cl
+ H O
H
CH3
C 2H 5
O
C O
H
CH3
(+)-2-butanol
[] = +13.8o
© E.V. Blackburn, 2011
Predicted result for alkyl oxygen bond breaking
C 2H 5
C2H5
O
C O
H
CH3
-
OH
H
OH
CH3
(-)-2-butanol
or racemate
© E.V. Blackburn, 2011
Predicted result for acyl oxygen bond breaking
C2H5
O
C O
HO
-
H
CH3
C2H5
HO
H
CH3
(+)-2-butanol
So what happens when we perform the reaction?
(+)-2-butanol is obtained - [] = +13.8o
acyl - oxygen bond breaking occurs
© E.V. Blackburn, 2011
Acyl - oxygen bond breaking further proof using isotopic
labels
O
H3CH2C
+ OH
OC2H5
18
-
O
H3CH2C
18
+ C2H5OH
OH
© E.V. Blackburn, 2011
However......?
-
O
HO + R
OR'
- O HO C OR'
R
O
HO
+ R'O -
R
-
O
O
+ R'OH
R
© E.V. Blackburn, 2011
O
+ OH
R
18
18O-
18
-
R
OC2H5
O
OC2H5
OH
+ C2H5O-
R
OH
H2O
18
18
OH
R
OC2H5
OH
O
18
+ OH
R
OC2H5
-
R
O
O
18
18OH
R
O-
OC2H5
+ C2H5OH
OH
R
+ C2H5O-
O
© E.V. Blackburn, 2011
Reactions - acid hydrolysis
H+
O
R
OR'
OH
+ H2O
+
R OR'
OH
R C OR'
OH2
+
OH
R C O
OH R'
-H+
H+
OH
+
R O
R' OH
R C OR'
OH2
+
OH
R C O
OH R'
OH H
R C O +
OH R'
© E.V. Blackburn, 2011
Reactions - acid hydrolysis
OH
R C O
OH R'
OH H
R C O +
OH R'
OH
+
R OH
H+
OH H
R C O +
OH R'
OH
+
R OH
O
R
OH
+ R'OH
+ H+
© E.V. Blackburn, 2011
Aminolysis of esters
O
H3C
+ NH 3
OC2H5
O
H 3C
+ C2H5OH
NH 2
© E.V. Blackburn, 2011
Transesterification
O
R
+ R"OH
OR'
O
R
+ R'OH
OR"
© E.V. Blackburn, 2011
Transesterification - acid
catalysed
O
R
+ H
OR'
+
R
OH
+
OR'
O
R
R
OR"
R"OH
OH
R
OR'
+ OR"
H
OH H
OH
+
R
OR'
+
OR" -R'OH
OR"
© E.V. Blackburn, 2011
Transesterification - basic
conditions
O-
O
R
+ R"O-
R
OR'
-
O
R
OR"
OR'
OR"
OR'
O
-
R
OR"
+ R'O
© E.V. Blackburn, 2011
Transesterification - a preparation of
polyvinyl alcohol
HgSO 4
HC CH + CH3CO2H
O
CH3COCH=CH 2
polymerisation
CH3OH - bp 65
H2SO4/
o
-CH2-CH-CH 2-CH-CH 2O
O
C O polyvinyl
C O
H 3C
H3C
acetate
-CH2-CH-CH 2-CH-CH 2OH
OH
+ CH3CO2CH3 - bp 57 o
© E.V. Blackburn, 2011
Reactions of ester with
Grignard reagents
R
O
R"MgX
O
OR'
R
R"MgX
R"
R"
R
+ R'OMgX
R"
OMgX
H 2O
R"
R
R"
OH
tertiary alcohol
© E.V. Blackburn, 2011
Preparation of amides
O
R
O
H
O
O
H
O
SOCl 2
R
SOCl 2
O
NH 3
R
Cl
O
NH 3
Cl
NH 2
O
NH 2
© E.V. Blackburn, 2011
Preparation of amides from
acyl chlorides
Br
Br
+ 2NH 3
Cl
O
p-bromobenzoyl
chloride
+ NH 4Cl
H 2N
O
p-bromobenzamide
© E.V. Blackburn, 2011
Preparation of amides from
acyl chlorides
O
Cl
+
NH 2
O
N
H
N-phenylbutanamide
© E.V. Blackburn, 2011
Reactions - acid catalysed
hydrolysis
O
R
H
+
R
NH 2
R
OH
R
OH
NH 3
+
OH
+
N
H2
+
OH
OH
+
N
H2
OH
R
R
NH 2
+
NH 2
H2O
R
OH +
OH2
NH 2
NH 3 + RCO2H
© E.V. Blackburn, 2011
Reactions - base hydrolysis
O-
O
R
NH 2
HO OR
NH 2
O
H
R
NH 2
O
H
OR
O-
NH 2
HO -
OR
-
O
H OH
NH 2
O
-
NH 3 + OH +
R
O-
© E.V. Blackburn, 2011
Hofmann degradation
O
R
NH 2
or
O
Ar
OBrRNH 2 or ArNH 2
1o amine
NH 2
O
NH 2
NH 2
Cl2/OH-
© E.V. Blackburn, 2011
Hofmann degradation
O
R
N
H
HO -
O
H
R
N
-
H
R
Br-Br
O
R
O
-
N
Br
O
OH
H
R
-
OH
R-N=C=O
N
Br
H + Br-
HO
C O
R N
-
NBr
R-N=C=O
-
O
C O
R N H-O-H
H
© E.V. Blackburn, 2011
Reduction of acids
1. LiAlH4, THF
RCH2OH
RCO2H
+
2. H3O
1o alcohol
© E.V. Blackburn, 2011
Reduction of esters
i. LiAlH 4
O
R
+
OR' ii. H
O
CH3CH2CH=CHCOCH 2CH3
RCH2OH + R'OH
1. LiAlH 4
2. H+
CH3CH2CH=CHCH 2OH + CH3CH2OH
© E.V. Blackburn, 2011
Hell-Volhard-Zelinsky reaction
CH3CH2CO2H
Cl2/P
Cl
CH3CCO2H
H
Cl
CH3CCO 2H
Cl2/P
Cl
CH3CCO 2H
H
Cl
Cl
CH3CCO2H
Cl2/P
Cl
© E.V. Blackburn, 2011
Halocarboxylic acids
RCHCO 2H
Br
RCHCO 2H
Br
+ NH 3
+ NaOH
RCHCO 2H
NH 2
-aminoacid
RCHCO 2H
OH
-hydroxyacid
© E.V. Blackburn, 2011
Halocarboxylic acids
RCHCO 2H
+ NaCN
Br
RCHCO 2H
CN
H2O/H+
RCHCO 2H
dicarboxylic acid
CHCHCO 2H
Br
+ KOH/alcohol
CO2H
RCH=CHCO 2H+
RCH=CHCO 2H
© E.V. Blackburn, 2011
Hell-Volhard-Zelinsky reaction
O
H
OH
O
PBr3
H
OH
R R
R
Br
Br
R
R R
Br2
enol
O
Br
R R
OH
H2O
O
Br
Br
R R
© E.V. Blackburn, 2011
Spectroscopy
IR:
C=O stretching ~ 1710 cm-1 (dimer), ~1760 cm-1 (monomer)
O-H stretching - broad range (3400 - 3600 cm-1)
NMR:
OH proton occurs in the region  = 9-13 ppm.
© E.V. Blackburn, 2011