Download Problem: How would you prepare the following esters? a) Butyl

Problem: How would you prepare the following esters?
a) Butyl acetate
b) Methyl butanoate
Acid Halides
!
Review: Acylation of benzene (and substituted benzene):
!
Hydrolysis: Acid halides L Acids
!
Acid halides react vigorously with water
R
O
C
OH 2
Cl
acid
chloride
O
C Cl
R
O
H
H
O
C
R
O
H
H
OH
O
C
R
OH + HC l
carboxylic
acid
!
Performed with a base (NaOH or pyridine) to remove HCl.
!
Alcoholysis: Acid halides L Esters
R
O
C
O
+
R'OH
RCOR'
a lcoh ol
e ster
Cl
a cid
ch lorid e
!
Also performed in the presence of NaOH or pyridine.
!
The reaction is affected by steric hindrance, i.e., primary alcohols are more reactive than
secondary which are more reactive than tertiary.
O2N
O
CCl
+ (CH ) CHCH OH
32
2
O2N
3,5-Dinitrobenzoyl
chloride
Isobutyl alcohol
O2N
O
COCH2CH(CH3)2
O2N
Isobutyl 3,5-dinitrobenzoate
!
How might you prepare the following esters using an acid chloride?
a) CH3CH2COOCH3
b) CH3COOCH2CH3
c) Ethyl benzoate
Problem: Which method would you use to prepare cyclohexyl benzoate, Fischer esterfication or a reaction
of an acid chloride with an alcohol?
!
Aminolysis: Acid halides L Amides
!
Acid chlorides react with ammonia and amines to yield amides.
!
Performed with excess ammonia or NaOH to neutralize the HCl produced.
O
RCCl +
acyl
chloride
O
RCNR'2 + R'2NH2+ Clamide
2 R'2NH
ammonia
or amine
O
CCl
O
C
+ HN
Benzoyl
chloride
Piperidine
NaOH
N
N-Benzoylpiperidine
Problem: How would you prepare the following amides from an acid chloride and an amine or ammonia?
a) N-Methylpropanamide
c) N,N-Diethylbenzamide
d) Propanamide
Problem: What amide would be produced from the following?
O
CCl
+
(CH3 CH2 ) 3N
!
Reduction: Acid halides L Primary Alcohols
!
Reaction of an acid halide with LiAlH4 acidic conditions to yield an aldehyde intermediate
(not isolated) and finally further reduction to a primary alcohol.
!
The attack begins as a nucleophilic acyl substitution reaction in which the hydride ion attacks
the carbonyl carbon.
O
R C Cl
H
acid chloride
O
R C H
O
R C Cl
H
aldehyde
H
RCH2OH
1o alcohol
!
H3O+
O
R C H
H
The aldehyde intermediate can be isolated by using a gentler reducing agent such as lithium
tri-tert-butoxyaluminum hydride.
O
CCl
1. LiAlH(OC)CH3) 3, ether
O
CH
2. H3 O+
Benzoyl chloride
Benzaldehyde
!
Reduction of Acid Chlorides with Organometallic Reagents.
!
Grignard reagents react with acid chlorides to yield tertiary alcohols.
O
RCCl
+
R'
1. 2 R'MgX
2 R'MgX
2. H3O +
acid
chloride
O
CCl
R
OH
R'
3 o alcohol
1. CH3MgBr
CH3MgBr
2. H3O+
Not isolated
Note: Omit Gilman reagent subsection.
Problem: Prepare the following alcohol by reacting an acid chloride with a Grignard reagent.
CH3 CH2
(CH3 )2 CHCOH
CH3 CH2
1,1-Diethyl-3-methylpropanol
Reactions of Acid Anhydrides
!
Acid anhydrides undergo the same reactions as the acid chlorides.
!
Only half of the anhydride molecule is used. The other half acts as a leaving group. The bond
is cleaved between oxygen and one of the carbonyl groups.
!
Hydrolysis to yield acids
R
O
C
O
O
R
+ H O
2
O
COH
O
O
O
2
R C OH
+ H2O
O
Phthalic
anhydride
COH
O
Phthalic acid
(1,2-Benzenedicarboxylic
anhydride)
!
R
Alcoholysis to yield esters
O
C
O
O
R
+ R'OH
O
O
R C OR' + R C OH
!
R
O
C
Aminolysis to yield amines
O
O
!
R
+ 2 NH3
Reduction to yield primary alcohols
R
!
O
O
R C NH2 + R C O- +NH4
O
C
O
O
1. LiAlH4
R
2. H3O+
RCH2OH
Remember the synthesis of aspirin?
O
C
O
C
NaOH
O O
OH +
CH3COCCH3
H2O
OH
Acetic
anhydride
Salicylic acid
(o-Hydroxybenzoic acid)
O
O
C
OH
CH3
Aspirin
(an ester)
Problem: What product would you expect from the reaction of 1 equivalent of methanol with phthalic
anhydride?