Download - Carboxylic acids and their derivatives
Carboxylic acids and their derivatives
Synthesis of acidsProperties of acidsNomenclature of acidsReactions of acidsAcid derivatives and their propertiesNomenclature of acid derivativesReactions of acid derivatives
Carboxylic acids
The carboxylic acid functional group consist of a carbonyl group that has a hydroxyl group attached to the carbonyl carbon.
Carboxylic acid groups are generally written as R-COOH or
R-CO2H
Carboxylic acids are generally weak acids that are only partially ionized.
C O
O
R H + H2O RO
O-R
O-
O+ H3O+[ ]
Properties of carboxylic acids
Boiling PointsHigher boiling points than similar alcohols, due to dimer formation.
Acetic acid, b.p. 118C
Melting Points
Aliphatic acids with more than 8 carbons are solids at room temperature. Double bonds (especially cis) lower the melting point. Note these 18-C
acids: Stearic acid (saturated): 72C Oleic acid (one cis double bond): 16C Linoleic acid (two cis double bonds): -5 (cis,cis-9,12-octadecadienoic
acid)
Properties of carboxylic acids
Solubility
Water solubility decreases with the length of the carbon chain.
Up to 4 carbons, acid is miscible in water. More soluble in alcohol. Also soluble in relatively nonpolar solvents like chloroform
because it dissolves as a dimer.
Acidity
Structure of Carboxyl
Carbon is sp2 hybridized. Bond angles are close to 120. O-H eclipsed with C=O, to get overlap of
orbital with orbital of lone pair on oxygen.
Substituent Effects on Acidity
Acid + Base salt + “water”
Naming Carboxylic acids
Historical names are commonly used for many carboxylic acids.
Positions of substituents on the chain are labeled with Greek letters.
CH3COH
O
acetic acid
Common Carboxylic acid Names
CO2H CO2H
CO2H
formic acid acetic acid propionic acid butyric acid
Benzoic acid phthalic acid
HO
OH
CH3
O
OHCH3CH2
O
OH
CH3CH2CH2
O
OH
Common Carboxylic acid Names
OH
OHO
O
CH2
O
HO
O
OHCH2
O
HOCH2
O
OH
oxalic acid malonic acid succinic acid
O
HO
O
OH
adipic acid IUPAC: hexanedioic acid
Naming Carboxylic acids
IUPAC Names
Remove -e from alkane (or alkene) name, add -oic acid. The carboxylic acid group has priority over all over groups.
The carbon of the carboxyl group is #1.
CH3CH2CHC
Cl
OH
O
2-chlorobutanoic acid
PhC
HC
H
COOH
trans-3-phenyl-2-propenoic acid (cinnamic acid)
Naming Cyclic Acids
When the -CO2H is bonded to a cycloalkane ring the compound is named as a cycloalkanecarboxylic acids.
Aromatic acids are named based on benzoic acids.
COOH
CH(CH3)2
2-isopropylcyclopentanecarboxylic acid
COOH
OH
o-hydroxybenzoic acid(salicylic acid)
Dicarboxylic Acids
Aliphatic diacids are usually called by their common names (to be memorized).
For IUPAC name, number the chain from the end closest to a substituent.
Two carboxyl groups on a benzene ring indicate a phthalic acid.
HOOCCH2CHCH2CH2COOH
Br
3-bromohexanedioic acid
-bromoadipic acid
COOH
COOH
1,3-benzenedicarboxylic acid m-phthalic acid
Common Carboxylic acid Names
Long chain carboxylic acids are called fatty acid. Fatty acids are generally found as ester in nature.
Fat - a triglyceride - three fatty acids esterified to glycerol (propane-1,2,3-triol) - that is solid at room temperature. Generally animal source. Fatty acid chains are generally saturated.
Oil - a triglyceride that is liquid at room temperature. Generally plant source. Fatty acid chains are generally unsaturated.
See handout for the composition of different fats and oils.
Common Carboxylic acid Names
For fatty acids containing double bonds, the location of the double bond is sometimes specified relative to the last carbon in the chain - the omega () carbon.
CH3(CH2)4 CH2
HH
(CH2)7-COOH
HH
Linoleic acid (an -6 fatty acid)
OH
O
Alpha-linolenic acid (an -3 fatty acid)
Common Carboxylic acid Names
A deprotonated acid is a carboxylate ion. The -oic acid becomes -oate in the deprotonated form. The name of the metal counterion comes first in the compound name.
CH3CO2H + NaOH CH3CO2Na + H2O
Acetic acid Sodium acetate
+ NaOH + H2O
CO2HCO2Na
benzoic acid Sodium benzoate
Acidity of Carboxylic acids
Ka = [RCOO][H+][RCOOH]
The larger the Ka values the stronger the acid.
Since most carboxylic acids have small Ka values (104 and lower), acid strength is often expressed using pKa values.
C O
O
R H + H2O RO
O-+ H3O+
Acidity of Carboxylic acids
pKa = log Ka
pKa and acid strength are inversely related
Strong acids have small pKas
Most carboxylic acids have pKa vales in the 4.0 to 5.0 range.
HCOOH pKa = 3.75
CH3COOH pKa = 4.74
Benzoic acid pKa = 4.19
Acidity of Carboxylic acids
CO2H CO2H
OCH3
CO2H
NO2
Which to the stronger acid?
pKa 4.19 4.46 3.41
Acidity of Carboxylic acids
The proximity of electron withdrawing groups has an effect.
Cl
COOH
Cl
COOHCH2 CH CH2 CH2CH3 CH2
pKa = 2.86 pKa = 4.52
Acid-Base reaction
spectroscopy of carboxylic acids
C=O of COOH 1710 cm1 (conjugation lowers )
-O-H stretch of carboxylic acid 2500 - 3500 cm1
-O-H stretch of alcohol 3300 cm1
(2800 - 3200 cm1)
Proton NMRO
CH3-CH2-CH2-C-O-H
10-12 ppm2.41.61.0
13C-NMRO
CH3-CH2-CH2-CH2-CH2-C-O-H
181 ppm
34
25
31
2214
Synthesis of acids
Synthesis of acids
Synthesis of acids
Synthesis of acids
Synthesis of acids
R CN R CO2HH+ / H2O
R CN R CO2-
OH - / H2O
Nitriles can undergo either acid or base catalyzed hydrolysis to form carboxylic acids or carboxylates.
RCH2-X + CN - RCH2-CNacetone
Nitriles can easily be prepared from the corresponding halides.
Synthesis of acids
Malonic ester synthesis:
CO2Et
CH2
CO2Et
1) CH3CH2O- Na+
2) R-X
CO2Et
CH
CO2Et
R
Diethyl malonate
CO2Et
CH
CO2Et
R2) H + , heat
1) OH - CO2H
CH2R
This second step is a decarboxylation reaction.
Synthesis of acids
CH2CH3
Br
conc. KMnO4 / heat
1) Mg / ether
2) CO2
3) H+
CHCH3
Br
CO2H
CO2HNa2Cr2O7 / H2SO4
Synthesis of acids Commercial sources
Many carboxylic acids are derived commercially from natural sources. Straight chain acid with 6 to 18 are readily obtained from fats and oil. Fats and oils are composed of triesters of glycerol (triglyceride). The acid is obtained by either acid or base hydrolysis of the ester groups. The base hydrolysis is called saponification (the making of soap) produces the carboxylate salt. Acid hydrolysis gives the free acid.
Synthesis of acids Commercial sources
Acetic acid is produced via both fermentation and catalytic processes.
Other acids such as benzoic acid, phthalic acid and adipic acid are produced via oxidation of an appropriate substrate.
Reactions of acids
The reactivity of these acid derivatives is dependent on the basicity of the leaving group. (List the leaving groups in order of increasing basicity.)
Synthesis of acid chlorides
Synthesis of esters from acids
Ester synthesis
Esterification under acid conditions (Fischer esterification)
R O H
OH
OR
H+
R O+
OH
OR H
HR
O+
OR
H
H2OR
O
OR
Esterification using diazomethane
Yields of the methyl ester are very good. However, diazomethane is a toxic, explosive gas. The reagent is generated just before it is used. Ether solutions of this reagent are relatively safe to work with.
Ester from acid Chlorides
What is the mechanism for this reaction?
Synthesis of amide from acids
The initial formation of the ammonium carboxylate salt is an exothermic reaction. The reaction mixture is then typically heated to 125-150°C to convert the salt to the amide with loss of water.
Synthesis of amide from acid chlorides
The HCl that is generated by this reaction must be neutralized or scavenged from the reaction mixture to prevent the protonating of unreacted amine. This is often done with pyridine, NaOH or Na2CO3. The reaction must be kept dry since acid chloride will react with water to give the acid.
Synthesis of acid anhydrides
RO
Cl+ R'
O
HOR O R'
O O
+ HCl
Acid anhydride
Acid anhydrides react similarly to acid chlorides to form esters and amides.
Reduction of Acids
Note that esters undergo an analogous reaction with LAH.
Reduction of Acid Chlorides
Nomenclature and reactions of acid derivatives
Naming Esters
Esters are named as alkyl carboxylates. Alkyl from the alcohol, carboxylate from
the carboxylic acid precursor.
Cyclic Esters
Reaction of -OH and -COOH on same molecule produces a cyclic ester, lactone.
To name, add word lactone to the IUPAC acid name or replace the -ic acid of common name with -olactone.
O
OH
OH
H+
O
O
+ H2O
4-hydroxybutanoic acid lactone γ -hydroxybutyrolactone
4-hydroxybutanoic acid γ-hydroxybutyric acid
Reactions of Esters
OO
H
O
R-C-O-R' R''-NH2
H3O+
R''-OH , H+
OH-
R-C-N-R'' + R'-OH
R-C-O-R'' + R'-OH
R-COOH + R'-OH
R-COO-+ R'-OH
transesterification
saponificaton
O
R''
OHR-C-O-R'
1) LiAlH4
2) H2O
1) 2 R''MgX, ether
2) H3O+
R-OH + R'-OH
R-C-R"
Amides
Product of the reaction of a carboxylic acid and ammonia or an amine.
Not basic because the lone pair on nitrogen is delocalized by resonance.
Classes of Amides
1 amide has one C-N bond (two N-H). 2 amide or N-substituted amide has two
C-N bonds (one N-H). 3 amide or N,N-disubstituted amide has
three C-N bonds (no N-H).
R
O
N H
H
R
O
N R'
R'
R
O
N H
R'
Classes of Amides
DMF is a common polar and aprotic solvent that is often used in the laboratory. Because of the very strong hydrogen bonding in 1° and 2° amides they have very high melting and boiling points.
Naming Amides
For 1 amide, drop -ic or -oic acid from the carboxylic acid name, add -amide.
For 2 and 3 amides, the alkyl groups bonded to nitrogen are named with N- to indicate their position.
CH3CHC N
O
CH2CH3
CH3
CH3
N-ethyl-N,2-dimethylpropanamideN-ethyl-N-methylisobutyramide
Cyclic Amides
Reaction of -NH2 and -COOH on same molecule produces a cyclic amide, lactam.
To name, add word lactam to the IUPAC acid name or replace the -ic acid of common name with -olactam.
4-aminobutanoic acid lactam-butyrolactamN
O
H
Reactions of Amides
O
O
O
H
H3O+
OH-R-C-O + R'-NH2
R-C-OH + R'-NH3+
-
1) LiAlH4
2) H2O
R-C-N-R' -
R-CH2-NH-R'
POCl3
X2 , OHR-NH2
R-CN(or P2O5)
(only work with 1 amides)
Naming Nitriles
For IUPAC names, add -nitrile to the alkane name.
Common names come from the carboxylic acid. Replace -ic acid with -onitrile.
CH3CHCH2CH2CH2CN
Br
5-bromohexanenitrile-bromocapronitrile
C N
Cyclohexanecarbonitrile
Nitriles synthesis
Unlike other acid derivatives nitriles do not contain a carbonyl.
Nitriles can be prepared by treating an amide with POCl3 or at high temperature over an alumina catalyst.
R C
O
NH2 R CN POCl3
R C
O
NH2 R CN Al2O3 / NH3 / 300 C
+ H2O
Reactions of Nitriles
R-X + NaCN
ketone or aldehyde + NaCN, HCN
Ar-N2+ + CuCN
amide + POCl3
nitrile (or cyanohydrin)
O1) R'MgX , ether
2) H3O+
1) LiAlH4
2) H2O
H2O
H+ or OH -
R-CN
R-C-R'
R-CH2-NH2
R-COOH (or R-COO )-
(Note: shorter periods of hydrolysis can yield an intermediate amide)
Acid Halides
Named by replacing -ic acid with -yl halide.
C
O
Cl CH3CHCH2C
Br O
Br
benzoyl chloride
3-bromobutanoyl bromide-bromobutyryl bromide
Acid Halides
R
O
Cl
OOO
O
O
HO
C
R'-C-OHR-C-O-C-R'
R'-OH
R'-NH2
H2O
R-C-O-R'
R-C-N-R'
R-C-OH
( + HCl )
( + HCl )
( + HCl )
( + HCl )
(Pyridine or NaHCO3(aq) is used to help control acidity since protonating the N stops the reaction.
R
O
ClOC
LiAlH(O-tBu)3
R'2CuLi
R-CHO
R-C-R'
Acid Anhydrides
Two molecules of acid combine with the loss of water to form the anhydride.
A carboxylate ion is the leaving group in nucleophilic acyl substitution reactions.
To name an anhydride drop the word acid and replace with anhydride.
R C
O
O H RC
O
OH R C
O
O C
O
R
CH3 C
O
O C
O
CH3
ethanoic anhydrideacetic anhydride
Acid Anhydrides
1,2-benzenedicarboxylic anhydridephthalic anhydride
O
O
O
Acid Anhydrides
O
OO
O
O
H
O O
O
R-C-OH
R-C-O-C-R
R'-OH , H+
R'-NH2
H2O
R-C-O-R'
R-C-N-R'
R-C-OH
+
R-C-OH+
R-C-OH+
OO O
C-R OR-C-O-C-R , AlCl31)
2) H2O R-C-OH+
(Note: The benzene ring cannot be strongly deactivated.)
Multifunctional Compounds
The functional group with the highest priority determines the parent name.
Acid > ester > amide > nitrile > aldehyde > ketone > alcohol > amine > alkene > alkyne.
C
CN
O
OCH2CH3 ethyl o-cyanobenzoate
Solubility
Acid chlorides and anhydrides are too reactive to be used with water or alcohol.
Esters, 3 amides, and nitriles are good polar aprotic solvents.
Solvents commonly used in organic reactions: Ethyl acetate Dimethylformamide (DMF) Acetonitrile
1H NMR Spectroscopy
13C NMR Spectroscopy
Acid Chloride to Anhydride
Acid or carboxylate ion attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H+ is
abstracted.
+ HClC
O
R OC
O
R'
_
C
O
R Cl
OH C
OR'
C
O
R ClR' C
O
O H+
- H+
Acid Chloride to Ester
Alcohol attacks the C=O. Tetrahedral intermediate forms. Chloride ion leaves, C=O is restored, H+ is
abstracted.
+ HClC
O
R OR'
_
C
O
R Cl
OH R'
C
O
R Cl+
- H+
R' O H
Acid Chloride to Amide
Ammonia yields a 1 amide A 1 amine yields a 2 amide A 2 amine yields a 3 amide
Anhydride to Ester
Alcohol attacks one C=O of anhydride. Tetrahedral intermediate forms. Carboxylate ion leaves, C=O is restored,
H+ is abstracted.
Anhydride to Amide
Ammonia yields a 1 amide A 1 amine yields a 2 amide A 2 amine yields a 3 amide
Ester to Amide
Nucleophile must be NH3 or 1 amine. Prolonged heating required.
Transesterification
One alkoxy group can be replaced by another with acid or base catalyst.
Use large excess of preferred alcohol.