Chap 18. Carboxylic acid s and their derivatives. Nucleophilic substitutio n at the acyl carbon 18.1 Introduction The carboxyl group, -COOH, -CO 2 H, is one of the most widely occurri ng functional groups in chemistry and biochemistry. Not only are ca rboxylic acids themselves importa nt, but the carboxyl group is the parent group of a large family of related compounds.
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Chap 18. Carboxylic acids and their derivatives. Nucleophilic substitution at the acyl carbon 18.1 Introduction The carboxyl group, -COOH, -CO 2 H, is.
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Chap 18. Carboxylic acids and their derivatives. Nucleophilic subst
itution at the acyl carbon
18.1 Introduction
The carboxyl group, -COOH, -CO2H, is one of the most widely occurring functional groups in chemistry and biochemistry. Not only are carboxylic acids themselves important, but the carboxyl group is the parent group of a large family
of related compounds.
All of these carboxylic acid derivatives contain the acyl group, RCO-. As a result, they are often called acyl compounds. They are called carboxylic acid derivat
18.7B Base-promoted hydrolysis of esters: Saponification ( 皂化反应)
R
O
OR' + NaOHH2O
R
O
ONa + R'OH
Ester Sodium carboxylate Alcohol
R
O
OR'Ester
NaOH+ R
O-
OR'
OH
R
O
OH + -OR' R
O
ONa + HOR'
酯的碱性条件下的水解 ----- 称为皂化反应。
Evidence for this mechanism comes from studies done with isotopically labeled este
rs.( 同位素的标记来研究酯的水解机理)
R
O
O
Ester
NaOH+ R
O
ONa + HOR'18 18
R'
a b
a
õ£Ñõ¼üÍéÑõ¼ü
R
O
ONa + HOR'18
b
实验证明;酯的水解一般按照酰氧键断裂方式进行。
18.7C Lactones ( 内酯)
CH3CHCH2CH2C OH
O
OH
- hydroxy pentanoic acid
O
O
CH3
- ÎìÄÚõ¥ - ôÇ»ùÎìËá
CH2CH2CH2CH2C OH
O
- hydroxy pentanoic acid
- ÎìÄÚõ¥- ôÇ»ùÎìËá
OH
O
O
Erythromycin A 红霉素(抗生素的一种)
O
O
OHHO
H
O
OH
O
O
O
O
HO
N(CH3)2
CH3
CH3
OHCH3
OCH3
O
HO H
CH2OH
Vitamin C
H
HO
OH
άÉúËØ C
O
18.8 Amides ( 酰胺)
18.8A Synthesis of amides
Amides can be prepared in a variety of ways starting with acyl chlorides, acid anhydrides, esters, carboxylic acids, and carboxylic salts. All of these methods involve nucleophilic substitution reactions by ammonia or an amine at an acyl carbon. As we might expect, acid chlorides are the most reactive and carboxyla
te ions are the least.
18.8B Amides from acyl chloride
Primary amines, secondary amines, and ammonia all react rapidly with acid chlorides to from amides.
R
O
Cl + HNH2 R
O
NH2 + NH4Cl
An amide
R
O
Cl + HNHR R
O
NHR + RN+H3Cl-
An N-substituted amide
R
O
Cl + HNRR' R
O
NRR' + HN+RR'Cl-
An N,N-disubstituted amide
酰氯是非常活泼的,它很容易与氨,伯胺,仲胺反应生成酰胺
Reaction Mechanism
R
O
Cl + HNH2 R
O
NH2 + NH4Cl
An amide
R
O
Cl + NH3 R
O-
Cl
N H
H
H+
R
O
NH2
+ HCl
NH3
NH4Cl
18.8C Amides from carboxylic anhydrides
Acid anhydrides react with ammonia and with primary and secondary amines and form amides through ractions that are analogous to those
of acyl chlorides.
+ HNH2 R
O
NH2 + RCO2NH4
R
O
O
An amide
O
R
+ HNHR R
O
NHR + RCO2N+H3
An N-substituted amide
R
O
O
O
R
+ HNRR' R
O
NRR' + RCO2RR'H2N+
An N,N-disubstituted amide
R
O
O
O
R
+ HNH2O
O
O
Phthalic anhydride
O
O
NH2
OH
150-160oC
NH
O
OPhthalimide
ÁÚ±½¶þ¼×õ£ÑÇ°·ÁÚ±½¶þ¼×Ëáôû
- H2O
18.8G Nitriles from the dehydration of amides
( 由酰胺制腈)Amides react with P2O5 or with boiling
acetic anhydride to form nitriles.
R
O
NH2P2O5 or (CH3CO)2O
R C N
A nitrile
+ H3PO4 or CH3CO2H
ëæ
heat, - H2O
18.8H Hydrolysis of nitriles (腈的水解)
R C N
A nitrileëæ
H+, H2O
OH- , H2O
heat
heat
RCOOH
RCOO-
CH2Cl CH2COOH
NaCN
CH2CN
H+, H2O, heat
±½ÒÒëæ
18.8I Lactams ( 内酰胺 )Cyclic amides are called lactams.
NH
NH
NHO
R
O
R
O
R
A
- Lactam
A - Lactam - LactamA
N
S
NH
O
R
O
CH3
CH3
COOH
R = C6H5CH2 -
R = C6H5CH -
NH2
R = C6H5OCH2 -
( penicillin G)
(ampicillin)
(penicillin V)
(ÇàùËØ G)
( penicillin)
Polyamides (聚酰胺)NH
O
H2O-OC(CH2)5NH2
O
¾ÛºÏ *
O
(CH2)5NH
O
(CH2)5NH *
nNylon-6
ÄáÁú-6
¼ºÄÚõ£°·
- Caprolactam
¾ÛºÏO
(CH2)5
O
NH
nNylon-6,6
ÄáÁú-6,6
n HOC(CH2)4COH + n H2N (CH2)6NH2
O O
Adipic acid Hexamethylenediamine(CH2)6 NH
¾Û¼º¶þõ£¾Û¶þ°·
1£¬6-¼º¶þ°·¼º¶þËá
Nylon 6 or Nylon 6,6 can also be converted into fibers by melt spinning. ( 熔融纺丝 )
18.9 α- Halo Acids (α- 卤代酸)Aliphatic carboxylic acids react with bromine or chlorine in the presence of phosphorus (or a
phosphorus halide) to give α- halo acids.O
OH1) X2 , P
2) H2ORCH2
RCHCO2H
X
- halo acidO
OH1) Br2 , P
2) H2O
- Bromobutanoic acid
CH3CH2CH2
Butanoic acid
CH3CH2CHCOOH
Br
- ä嶡ËᶡËá
α- Halo acids are important synthetic intermediates because they are capable of reacting with a
variety of nucleophiles;
1 ) Conversion to α- hydroxy acids
(α- 卤代酸可以转换成 α- 羟基酸)
- Bromobutanoic acid
CH3CH2CHCOOH
Br
- ä嶡Ëá
1) K2CO3, H2O
100 oC2) H2O
CH3CH2CHCOOH
OH
2-Hydroxybutanoic acid 2-ôÇ»ù¶¡Ëá (69%)
2 ) Conversion to α- amino acids
(α- 卤代酸可以转换成 α- 氨基酸)
- Bromobutanoic acid
CH3CH2CHCOOH
Br
- ä嶡Ëá
CH3CH2CHCOOH
NH2-Aminobutanoic acid 2-°±»ù¶¡Ëá
NH3
18.10 Derivatives of carbonic acid(碳酸的衍生物)
Carboic acid H2CO3 is an unstable compound that decomposes spontaneously (to produce carbon dioxide and water) and, therefore, can not be isolated. However, many acyl chlorides, esters, and amides that are derived from carbonic acid are stable compounds that have im
portant applications.
Carbonyl dichloride (ClCOCl), a highly toxic compound that is also called phosgene, can be thought of as the diac