Download Chapter 1 Structure and Bonding

Ch. 19-20 Lect. 2 Carboxylic Acids and Derivatives
I.
Alkanoyl Halides
A.
Preparation
1) Inorganic esters utilized, just as in conversion of alcohols to alkyl halides
2) PBr3, SOCl2 convert carboxylic acids to alkanoyl halides
O
R
SOCl2
-HCl
OH
O
R
R
H
R
OSOCl
O
H
Cl
OH
R
OSOCl
OSOCl
Cl
H
O
O
O S
Cl
Cl
B.
+
+
O
R
Cl
+
O S O
Nomenclature
1) Pentanoic acid becomes pentanoyl chloride
2)
+
H+Cl-
O
CH3CH2CH2CH2
Cyclohexane carboxylic acid becomes cyclohexanecarbonyl chloride
O
Cl
Cl
C.
Reactivity: most reactive and useful derivative
1.
Modified LiAlH4 reagent LiAl[OC(CH3)3]3H required to prevent over-reduction to alcohols
2.
Organocuprates are less reactive alkyl metal reagents to prevent second addition to ketone
3.
4.
5.
6.
Amines do addition-elimination to give amides
Alcohols do addition-elimination to give esters
Acids do addition-elimination to give anhydrides
Water does addition-elimination to give acids
II.
Anhydrides
A.
Preparation
1) As just seen, the reaction of an acid and an alkanoyl halide form anhydrides
2) The –OH group of the acid is a weak nucleophile for the reactive alkanoyl halide
3) Dehydration of two carboxylic acids can also work if 5-6 membered ring forms
O
O
R
O
OH
R
O
Cl
R
COOH
O
O
R
COOH
-H2O
O
O
B.
Nomenclature
1) Replace “acid” with “anhydride” for the components
2) Acetic anhydride; Butanedioc anhydride
3) Unsymmetric anhydrides or mixed anhydrides are possible
O
O
O
O
Acetic propanoic anhydride
Acetic anhydride
H3C
O
CH2CH3
H3C
O
CH3
C.
Reactivity
1) All the alkanoyl halides reactions work for anhydrides, but are slower
2) Leaving group is a carboxylate anion, removed by aqueous extraction
3) Use anhydride as an activated substitute for reactions with carboxylic acids
III. Esters
A.
Preparation
1) As seen, alcohols do addition-elimination to alkanoyl halides to give esters
2) Acid catalyzed addition-elimination of alcohols to carboxylic acids is also useful
3) Esterification (and Ester Hydrolysis) Mechanism
O
H
R
OH
O
+ H
O
+
R
R
O
H3C +
H
O
+
R
O
O H
CH3
O
CH3O H
OH
H
R
H
O
O
R
OH
+
H
O +
R
H
O H
CH3
H
H
O
H
O
H
O
HOCH3
R
O CH3
O CH3
CH3
4)
Intramolecular esterifications give cyclic esters called lactones
O
HO
H2SO4, H2O
COOH
-H2O
O
Favored for 5-6
membered rings
B.
NH2
O
O
2-methylpropyl propanoate
3-methylbutyl pentanoate
methyl 2-aminobenzoate
Reactivity
1. Ester hydrolysis forms the component alcohol and carboxylic acid
a. Acid catalyzed reaction is the reverse of esterification shown above
b. Base catalyzed ester hydrolysis is also possible
O
R
OMe
O
O
C.
O
Nomenclature: named as alkyl alkanoates
-OH
O
R
O CH3
2.
R
O
-OCH3
O CH3
R
O
-OCH3
O H
OH
R
H+, H2O
O
Transesterification occurs with alcohols
a. Acid or base catalyzed conversion of one ester to another
b. Control the equilibrium by adding a large excess of the new alcohol
O
O
CH3CH2OH
O CH3
+
H
or -OCH2CH3
R
O CH2CH3
3.
Ester + Amine + Heat gives Amides (amines are more nucleophilic than alcohols)
O
R
O
O CH3
+
CH3NH2
R
N CH3
H
4.
Grignard Reagents + Esters give Alcohols
a. The first reaction is an addition-elimination giving a Ketone product
b. The Ketone reacts with another Grignard molecule giving the alcohol
O
O
OH
RMgBr
H3C
O CH3
5.
O
R
H3C
R
RMgBr
H3C
R
R
Esters can be reduced by hydrides to alcohols or aldehydes
a. LiAlH4 fully reduced the ester to an alcohol (similar to Grignard above)
b. DIBAL reduces ester only to an aldehyde
H
O
Al
R
O CH3
DIBAL = diisobutylaluminum hydride
H
D.
Esters in Nature
1. Esters are important aroma and flavor agents in natural foods
O
a. Isopentyl acetate = banana oil
H3C
O
b. Octyl acetate = orange oil
c. Methyl salicylate = oil of wintergreen
O
H3C
O
O
O
OH
2.
Waxes are long chain esters O
a. Beeswax
CH3(CH2)24
b.
O
(CH2)29CH3
Spermaciti: sperm whale wax
CH3(CH2)14
3.
Fats and Oils = triesters of glycerol (1,2,3-propanetriol)
H2C O
CH2OH
CHOH
O
RCOOH
HC O
CH2OH
Glycerol
O
O
C O
H2
O Saturated Fat or Oil
O
(CH2)15CH3
IV. Amides
A.
Preparation
1) Amines react with carboxylic acids as bases and as nucleophiles
O
O
:NH3
Kinetic product
R
O H
R
O NH4+
2)
Heating favors the thermodynamic product: amide
O
R
3)
O H
R
Amino acids cyclize to give lactams
H3N+
B.
O
:NH3
Thermodynamic product
NH2
O
heat, -H2O
NH
COO-
Nomenclature: alkanamides or cycloalkanecarboxamides
Br
O
N
H3C
O
NH2
NHCH3
N-methylacetamide
O
4-bromo-N-ethyl-N-methylpentanamide
cyclohexanecarboxamide
C.
Reactivity: least reactive of the carboxylic acid derivatives
1. Resonance structures prevent rotation around C—N bond
a. Ea = 21 kcal/mol for rotation about this single bond
b. Two peaks seen in the proton NMR
O
H3C
O
..
N
CH3
H3C
CH3
CH3
2.
+ CH
3
N
Hydrolysis requires heat and concentrated acid or base
a. Proteins are held together by strong amide bonds; they don’t break easily
O
H3C
O
+
N
H or -OH
CH3
OH2
H3C
OH
CH3
3.
Al
O
H3C
Reduction to Amine by LiAlH4
N
CH3
CH3
LiAlH4
H
O
R
.. CH3
R
N
H
CH3
H
CH3
N+
CH3
Iminium ion
H
H
R
CH3
N
H
CH3
V.
Alkanenitriles
A.
Preparation: SN1 or SN2 reaction of haloalkanes
2
Br
B.
N
1
3
1
4
2
-CN
3
N
Nomenclature
1) Alkanenitriles or cycloalkanenitriles
N
butanenitrile
C.
Reactivity: synthesis of carboxylic acids
1) Acid catalyzed mechanism
NH
R
H
N
R
H
R
2)
3)
4)
R
N H
+
NH2
NH2+
+
OH
NH
+
+
R
cyclohexanecarbonitrile
OH
R
OH
+
OH2
N H
R
NH2
-H+
R
O
+
H
-H+
OH2+
OH2
amide
hydrolysis
Similar Base catalyzed mechanism
Adds one carbon to the haloalkane, then turns it into carboxylic acid
Make derivatives from there; take advantage of all of their reactions
RCOOH