Transcript Chapter-16B

Chapter 15:
Functional Derivatives of Carboxylic
Acids
Sections 15.1-15.9
Chemistry 2060, Spring 2060, LSU
15-1
Sections
Chapter 15: Aldehydes and Ketones
1.
2.
3.
4.
5.
6.
7.
8.
9.
Introduction
Structure and nomenclature
Characteristic properties
Reaction with water: hydrolysis
Reaction with alcohols
Reactions with ammonia and amines
Interconversion of functional derivatives
Esters with Grignard reagents
Reduction
Chemistry 2060, Spring 2060, LSU
15-2
Carboxyl Derivatives
In this chapter, we study four classes of organic
compounds
• under the general formula of each is a drawing to help
you see how it is related to the carboxyl group
O
RCCl
An acid chlorid e
-H2 O
O
RC-OH H-Cl
Chemistry 2060, Spring 2060, LSU
O O
RCOCR'
An acid an hydride
-H2 O
O
O
RC-OH H-OCR'
O
RCOR'
An ester
-H2 O
O
RC-OH H-OR'
O
RCNH2
An amid e
-H2 O
O
RC-OH H-NH2
15-3
Acid Chlorides
The functional group of an acid halide is an acyl
group bonded to a halogen
• the most widely used are the acid chlorides
• to name, change the suffix -ic acid to -yl chloride
O
CH3 CCl
Eth anoyl chlorid e
(Acetyl chlorid e)
Chemistry 2060, Spring 2060, LSU
O
CCl
Ben zoyl ch loride
15-4
Acid Anhydrides
The functional group of an acid anhydride is two
acyl groups bonded to an oxygen atom
• the anhydride may be symmetrical (two identical acyl
groups) or mixed (two different acyl groups)
• to name, replace acid of the parent acid by anhydride
O O
CH3 COCCH3
Acetic anhydride
Chemistry 2060, Spring 2060, LSU
O O
O O
COC
CH3 COC
Benzoic anhydride
Acetic benzoic
anhydride
15-5
Acid Anhydrides
A phosphoric acid anhydride contains two
phosphoryl groups bonded to an oxygen atom
• shown here are two phosphoric anhydrides
• each is shown on the right as it would be ionized at pH
7.4, the pH of blood
Chemistry 2060, Spring 2060, LSU
O O
HO-P-O-P-OH
OH OH
D iph os phoric acid
(Pyrop hosph oric acid )
O O
O-P-O-P-O
O O
D iphosp hate ion
(Pyroph os phate ion)
O O O
HO-P-O-P-O-P-OH
OH OH OH
Triph os phoric acid
O O O
O-P-O-P-O-P-O
O- O- OTriphosph ate ion
15-6
Esters
The functional group of an ester is an acyl group
bonded to -OR or -OAr
• name the alkyl or aryl group bonded to oxygen
followed by the name of the acid
• change the suffix -ic acid to -ate
O
O
CH3 COCH2 CH3
Ethyl Ethan oate
(Eth yl acetate)
Chemistry 2060, Spring 2060, LSU
O
O
O
D iethyl bu tanedioate
(D iethyl succinate)
15-7
Lactones
Lactone: a cyclic ester
• IUPAC: name the parent carboxylic acid, drop the suffix
-ic acid, and add -olactone
• the location of the oxygen atom on the carbon chain is
commonly indicated by a Greek letter
O
4-Butanolactone 
(A -lacton e)
Chemistry 2060, Spring 2060, LSU
1
O
2
3 4


15-8
Phosphoric esters
Phosphoric acid forms mono-, di-, and triesters
• name by giving the name of the alkyl or aryl group(s)
bonded to oxygen followed by the word phosphate
• in more complex phosphate esters, it is common to
name the organic molecule followed by phosphate
O
CH3 O-P-OH
OCH3
D imethyl
phosp hate
Chemistry 2060, Spring 2060, LSU
CHO
H OH
HO H
H OH
H OH O
CH2 -O-P-OOD -Glucose
6-ph os phate
CHO
HO
H3 C
O
-
CH2 O-P-O
ON
Pyrid oxal p hosph ate
15-9
Amides
The functional group of an amide is an acyl group
bonded to a trivalent nitrogen
• IUPAC: drop -ic acid from the name of the parent acid
and add -amide
• if the amide nitrogen is bonded to an alkyl or aryl
group, name the group and show its location on
nitrogen by NO
CH3 CNH2
A cetamide
(a 1° amide)
Chemistry 2060, Spring 2060, LSU
O H
CH3 C-N
CH3
O CH3
H-C-N
CH3
N-Methylacetamide N ,N-D imethyl(a 2° amid e)
formamid e (DMF)
(a 3° amide)
15-10
Lactam
Lactam: a cyclic amide
• name the parent carboxylic acid, drop the suffix -ic acid
and add -lactam
• the location of the nitrogen atom in the ring is
commonly indicated by a Greek letter, , , etc.
O

2 1
3
NH
H3 C
3-Bu tanolactam
A-lactam)



3
4

O
2
5
1
6

NH
6-Hexanolactam
An -lactone)
• 6-hexanolactam is an intermediate in the synthesis of
nylon 6 (Section 17.5A)
Chemistry 2060, Spring 2060, LSU
15-11
The Penicillins
The penicillins are a family of -lactam antibiotics
• one of the first discovered was penicillin G
the penicillins differ
in the group bonded
to the acyl carbon
H
CH2 C
O
Penicillin G
Chemistry 2060, Spring 2060, LSU
N
O
H H
S CH3
N
CH3
COOH
15-12
The Penicillins
• amoxicillin, a -lactam antibiotic
HO
O
H
H
S
HN
NH2
N
O
COOH
Chemistry 2060, Spring 2060, LSU
15-13
Cephalosporins
The cephalosporins are also -lactam antibiotics
O
The cep halosporins
differ in th e grou p
bonded to th e carbonyl
carbon...
N
H
NH2
O
H H
N
S
...and th e group b on ded
to th is carbon of the
six-memb ered rin g
CH3
COOH
Keflex
(a -lactam antibiotic)
Chemistry 2060, Spring 2060, LSU
15-14
Characteristic Reactions
Nucleophilic acyl substitution: an additionelimination sequence resulting in substitution of
one nucleophile for another
• the reaction depends on having a suitable leaving
group bonded to the acyl carbon, here indicated Lv
-
O
+
C
R
Lv
-
Nu
R
O
O
C
C
Nu
Lv
Tetrah edral carbonyl
addition in termediate
Chemistry 2060, Spring 2060, LSU
R
+
Lv
-
Nu
Su bstitu tion
product
15-15
Characteristic Reactions
• in the general reaction, we showed the nucleophile as
an anion; this need not be the case
• neutral molecules such as water, alcohols, ammonia,
and amines can also serve as nucleophiles
• in the general reaction, we showed the leaving group
as an anion to illustrate an important point about them:
the weaker the base, the better the leaving group
O
NR2
OR
OCR
X
Increasin g leaving ability
Increasin g b asicity
Chemistry 2060, Spring 2060, LSU
15-16
Characteristic Reactions
• halide ion is the weakest base and the best leaving
group; acid halides are the most reactive toward
nucleophilic acyl substitution
• amide ion is the strongest base and the poorest leaving
group; amides are the least reactive toward
nucleophilic acyl substitution
O
RC-NH2
Amide
O
RC-OR'
Ester
O O
RC-OCR
A nhydride
O
RC-X
A cid h alide
Increasin g reactivity toward n ucleoph ilic acyl su bstitu tion
Chemistry 2060, Spring 2060, LSU
15-17
Hydrolysis - Acid Chlorides
• low-molecular-weight acid chlorides react rapidly with
water
• higher molecular-weight acid chlorides are less soluble
in water and react less readily
O
CH3 CCl + H2 O
Chemistry 2060, Spring 2060, LSU
O
CH3 COH + HCl
15-18
Hydrolysis - Acid Anhydrides
• low-molecular-weight acid anhydrides react readily
with water to give two molecules of carboxylic acid
• higher-molecular-weight acid anhydrides also react
with water, but less readily
O O
CH3 COCCH3 + H2 O
Chemistry 2060, Spring 2060, LSU
O
O
CH3 COH + HOCCH3
15-19
Hydrolysis - Esters
Esters are hydrolyzed only slowly, even in boiling
water
Hydrolysis becomes more rapid if they are heated
with either aqueous acid or aqueous base
Hydrolysis in aqueous acid is the reverse of Fischer
esterification
O
R
C
OH
+
OCH3
+ H2 O
H
R
O
+
H
C
OH
R
C
OH
+ CH3 OH
H3 CO
Tetrah edral carbonyl
addition in termediate
Chemistry 2060, Spring 2060, LSU
15-20
Hydrolysis - Esters
Hydrolysis of an ester in aqueous base is often
called saponification
• each mole of ester hydrolyzed requires 1 mole of base;
for this reason, ester hydrolysis in aqueous base is
said to be base promoted
O
RCOCH3 + NaOH
H2 O
O
-
RCO Na
+
+
CH3 OH
• base-promoted ester hydrolysis involves formation of a
tetrahedral carbonyl addition intermediate followed by
its collapse
Chemistry 2060, Spring 2060, LSU
15-21
Hydrolysis - Esters
• step 1: addition of hydroxide ion to the carbonyl carbon
O
R-C-OCH3
+
O
R-C OCH3
OH
OH
• step 2: collapse of the addition intermediate
O
O
R-C OCH3
R-C OH
+
OCH3
OH
• step 3: proton transfer completes the reaction
O
R-C O H
Chemistry 2060, Spring 2060, LSU
+
OCH3
O
R-C O
+
H-OCH3
15-22
Hydrolysis - Esters
There are two major differences between acidcatalyzed and base-promoted ester hydrolysis
1. for acid-catalyzed hydrolysis, acid is required in only
catalytic amounts; for base-promoted hydrolysis, base
is required in equimolar amounts
2. hydrolysis of an ester in aqueous acid is reversible;
base-promoted hydrolysis is irreversible
Chemistry 2060, Spring 2060, LSU
15-23
Hydrolysis - Amides
Hydrolysis of an amide requires much more
vigorous conditions than hydrolysis of an ester
• hydrolysis in aqueous acid requires 1 mole of acid for
each mole of amide
• the products are a carboxylic acid and an ammonium
or an amine salt
O
O
NH2 +
Ph
2-Phenylbutan amide
Chemistry 2060, Spring 2060, LSU
H2 O + HCl
H2 O
heat
OH
+
+
-
NH4 Cl
Ph
2-Phen ylb utanoic acid
15-24
Hydrolysis - Amides
• hydrolysis of an amide in aqueous base requires 1
mole of base per mole of amide
• the products are a carboxylate salt and an amine
O
CH3 CNH
+
N-Phenylethanamide
(N-Phenylacetamide,
Acetanilide)
Chemistry 2060, Spring 2060, LSU
NaOH
H2 O
heat
O
+
CH3 CO Na + H2 N
Sodiu m acetate
Aniline
15-25
Hydrolysis
A summary
O
R-C-Cl + H2 O
O O
R-C-O-C-R + H2 O
O
R-C-OR' + H2 O
O
R-C-NH2 + H2 O
Chemistry 2060, Spring 2060, LSU
NaOH
H2 SO4
NaOH
HCl
O
R-C-OH + HCl
O
O
R-C-OH + HO-C-R
O
R-C-O-Na+ + R'OH
O
R-C-OH + R'OH
O
R-C-O-Na+ + NH3
O
+ R-C-OH + NH4 Cl
15-26
Reaction with Alcohols
Acid chlorides react with alcohols to give an ester
and HCl
O
Cl + HO
Butanoyl
chloride
Cyclohexanol
O
O
+
HCl
Cyclohexyl butanoate
Chemistry 2060, Spring 2060, LSU
15-27
Reaction with Alcohols
Acid anhydrides react with alcohols to give 1 mole
of ester and 1 mole of carboxylic acid
O O
O
CH3 COCCH3 + HOCH2 CH3
Acetic anhydride
Ethan ol
O
CH3 COCH2 CH3 + CH3 COH
Ethyl acetate
Acetic acid
• aspirin is prepared by the following reaction:
COOH
OH
O O
+ CH3 COCCH3
2-Hydroxyben zoic Acetic
acid
anh yd rid e
(Salicylic acid)
Chemistry 2060, Spring 2060, LSU
COOH
O
O
Acetylsalicylic
acid
(Asp irin )
+ CH3 COOH
Acetic
acid
15-28
Reaction with Alcohols
Esters undergo an exchange reaction called
transesterification
• the exchange is acid catalyzed
• the original -OR group is exchanged for a new -OR
group
O
Ph
HO
OCH3 +
O
H2 SO4
OH
Ph
O
Ph + 2 CH OH
3
O
O
Meth yl
benzoate
Chemistry 2060, Spring 2060, LSU
1,2-Ethan ediol
(Ethylene glycol)
A dies ter of
eth ylen e glycol)
15-29
Reaction with Alcohols
Amides to not react with alcohols under any
conditions
Summary of reactions with alcohols
O
R-C-Cl + HOR"
O
R-C-OR" + HCl
O O
R-C-O-C-R + R"OH
O
O
R-C-OR" + HO-C-R
O
H2 SO4
R-C-OR' + R"OH
O
R-C-OR" + R'OH
O
R-C-NH2 + R"OH
Chemistry 2060, Spring 2060, LSU
N o Reaction
15-30
Reaction with NH3 and Amines
Acid halides react with ammonia, 1° amines, and 2°
amines to form amides
• 2 moles of the amine are required per mole of acid
chloride; one to form the amide and one to neutralize
the HCl formed
O
O
Cl + 2 NH3
Hexan oyl
ch loride
Chemistry 2060, Spring 2060, LSU
Ammonia
+
-
NH2 + NH4 Cl
Hexan amid e
Ammonium
chloride
15-31
Reaction with NH3 and Amines
Acid anhydrides react with ammonia, and with 1°
and 2° amines to form amides
• 2 moles of ammonia or amine are required; one to form
the amide and one to neutralize the carboxylic acid
byproduct
• here the reaction is broken into two steps
O O
CH3 COCCH3 + NH3
O
CH3 COH + NH3
O O
CH3 COCCH3
Chemistry 2060, Spring 2060, LSU
+ 2 NH3
O
O
CH3 CNH2 + CH3 COH
O
CH3 CO- NH4 +
O
O
CH3 CNH2 + CH3 CO- NH4 +
15-32
Reaction with NH3 and Amines
Esters react with ammonia, and with 1° and 2°
amines to form amides
• esters are less reactive than either acid halides or acid
anhydrides
O
Ph
O
O
Ethyl phenylacetate
+
N H3
Ph
N H2 + HO
Phenyl acetamide
Ethanol
Amides do not react with ammonia, or with 1° or 2°
amines
Chemistry 2060, Spring 2060, LSU
15-33
Reaction with NH3 & Amines
Summary
O
R-C-Cl + 2 NH3
O O
R-C-O-C-R + 2 NH3
O
R-C-OR' + NH3
O
R-C-NH2 + NH4 + ClO
O
R-C-NH2 + R-C-O-NH4 +
O
R-C-NH2 + R'OH
O
R-C-NH2 N o reaction w ith ammonia or amines
Chemistry 2060, Spring 2060, LSU
15-34
Interconversion
interconversion of functional groups
Chemistry 2060, Spring 2060, LSU
15-35
Esters with Grignard Reagents
a formic ester with 2 moles of Grignard reagent
followed by hydrolysis gives a 2° alcohol
O
HCOCH3 + 2 RMgX
An es ter of
formic acid
OH
magnes ium H O, HCl
2
alkoxide
salt
HC-R + CH3 OH
R
A 2° alcohol
reaction of an ester other than a formate gives a 3°
alcohol
O
CH3 COCH3 + 2 RMgX
An es ter of any acid
oth er th an formic acid
Chemistry 2060, Spring 2060, LSU
magnes ium H O, HCl
2
alkoxide
salt
OH
CH3 C-R + CH3 OH
R
A 3° alcohol
15-36
Esters with Grignard Reagents
• Steps 1 and 2
1
O
2
CH3 -C-OCH3 + R MgX
1
O [ MgX]
+
O
CH3 -C OCH3
R 2
CH3 -C
+
-
CH3 O [ MgX]
R
A magnes ium s alt
A ketone
• Steps 3 and 4
4
-
+
3
3 O
CH3 -C + R MgX
CH3 -C-R
R
A ketone
R
Magn esium salt
Chemistry 2060, Spring 2060, LSU
O [MgX]
4
H O H, HCl
OH
CH3 -C-R
R
A 3° alcohol
15-37
+
Reduction
• esters are reduced by LiAlH4 to two alcohols
• the alcohol derived from the carbonyl group is primary
O
Ph
OCH3
1 . LiA lH4 , e t he r
2 . H2 O, HCl
Methyl 2-phenylpropanoate
Ph
OH + CH3 OH
2-Phenyl-1propanol
Methanol
• NaBH4 does not normally reduce esters, but it does
reduce aldehydes and ketones
O
O
NaBH4
OEt
Chemistry 2060, Spring 2060, LSU
Et OH
OH O
OEt
15-38
Reduction
• LiAlH4 reduction of an amide gives a 1°, 2°, or 3° amine,
depending on the degree of substitution of the amide
O
NH2
Octanamide
1 . LiAlH4
2 . H2 O
NH2
1-Octanamine
O
NMe2
1 . LiAlH4
2 . H2 O
N,N -D imethylben zamide
Chemistry 2060, Spring 2060, LSU
NMe2
N ,N-D imeth ylb enzylamine
15-39
Some Interconversions
• from Example 15.7
O
Ph
SOCl2
CH3 OH, H2 SO4
OH
Fischer
Phenylacetic esterification
acid
1 . LiAlH4
2 . H2 O
O
O
Ph
NH3
Ph
OCH3
(a)
1 . LiAlH4
2 . H2 O
Ph
OH
(d )
Chemistry 2060, Spring 2060, LSU
NH3 ( 2 eq)
CH3 OH
O
Ph
Cl
NH2
(b )
1 . LiAlH4
2 . H2 O
Ph
NH2
(c)
15-40