Carboxylic Acid Derivatives. Nucleophilic Substitution: 1) Addition & 2)
Elimination. GUAR: A General Utilitarian Approach for Reactions of. Acid
Derivatives ...
Systematic Names of Functions
Carboxylic Acid Derivatives Nucleophilic Substitution: 1) Addition & 2) Elimination GUAR: A General Utilitarian Approach for Reactions of Acid Derivatives (Carbon,Sulfur & Phosphorous)
Systematic Names of Acid Functions
Malonic Acid / Condensations and Barbiturates
Barbiturates / Condensations
Malonic Acid
Urea + Malonic Acid & Derivatives
HO
O
O
C
C
H
C
1864
Present
H
Anesthetics / “ Sleeping
OH
H
Malonic ester is hydrolyzed to malonic acid, which reacts with urea to produce barbituric acid.
Pills” Pills” / “Truth Serum” Serum”
>2,500 Compounds
O N
N
O
H
“bluebirds, downers,
O R5 R 5
DEA Schedule II, III & IV:
goofballs, tooties, yellow jackets”” jackets
Nembutal Veronal
Esters Salts of Carboxylic Acids
Question
Cyclic Esters:Lactones Which compound cannot form a lactone? A)
B)
C)
D)
Cyclic Amides: Lactams
Amides O
α
O
α
H N
β
O
H N
δ γ
2-azacyclohexanone δ-valerolactam
β
H N
γ 2-azacyclopentanone γ-butyrolactam
2-azacyclobutanone β-propiolactam
Recognizing Functions
Recognizing Functions
Generic Reaction: Nucleophilic Substitution
In general: ••
Chemical Reactivity of Carboxylic Acid Derivatives
••
O •• R
C
O •• + X
HY HY R
C
+ Y
Reaction is feasible when a less stabilized carbonyl is converted to a more stabilized one (more reactive to less reactive). reactive).
HX HX
most reactive
Generic Steps for Nucleophilic Substitution
O RCCl RCCl
O O
involves formation and dissociation of a tetrahedral intermediate
RCO RCOCR' O A carboxylic acid RCO RCOR' O derivative can be converted by RCN RCNR'2 O nucleophilic acyl substitution to any other RCO RCO– type that lies below it in this table. least reactive
OH
••
O •• R
C
HY
C
X
••
O ••
-HX -HX
R Y
R
C
Y
X
Question When benzoic acid reacts with 18O-enriched methanol (CH318OH) and an acid catalyst, which product will be obtained?
A)
B)
C)
D)
Most reactive
O CH3C O CH3C
Cl
Least stabilized
Reactivity, Electron Delocalization & Relative Acidity-Basicity
The extent of delocalization depends on:
O
1) The electronegativity of X
OCCH3
2) the interaction of X with the π orbital of C=O
O CH3C
OCH2CH3
O Least reactive
CH3C
NH2
•• – •O• • •
••
O •• Most stabilized
RC
••
X
RC +
•• – •O • • • ••
X
RC
+ X
least stabilized C=O
Carboxylate Ions O •• R
C
O
– •• ••O ••
••
•• –
O •• ••
R
C
RCCl RCCl O •• ••
Very efficient electron delocalization and dispersal of negative charge Maximum stabilization
O O RCO RCOCR' O RCO RCOR'
O RCN RCNR'2
O RCO RCO–
most stabilized C=O
Reactivity is Related to Structure Stabilization
Relative rate of hydrolysis
RCCl RCCl O O
very small
1011
RCO RCOCR' O
small
107
RCO RCOR' O
moderate
1.0
RCN RCNR'2
large
< 10-2
O
Relative Acidity-Basicity
Z– will be eliminated if it is a much weaker base than Y– (k–1 >> k2) The more stabilized the carbonyl group, the less reactive it is.
Reaction Coordinate Diagrams for Nucleophilic Acyl Substitution Reactions
(a) the Nu– is a weaker base (b) the Nu– is a stronger base (c) the Nu– and the leaving group have similar basicities
Y– will be eliminated if it is a much weaker base than Z– (k2 >> k–1)