Page 284 - Advanced Organic Chemistry Part B - Reactions & Synthesis

256 Tris-(dimethylamino)aluminum also promotes similar exchange reactions. The
catalysis by titanium and aluminum amides may involve bifunctional catalysis in which
CHAPTER 3
the metal center acts as a Lewis acid while also delivering the nucleophilic amide.
Functional Group
Interconversion
by Substitution,
Including Protection and ′′R O M ′′R O
Deprotection R′′ O M
HNR′
RNH HNR′
RNH HNR′

Interestingly, Sc O SCF is also an active catalyst for these exchange reactions.
3
3 3
The cyano group is at the carboxylic acid oxidation level, so nitriles are potential
precursors of primary amides. Partial hydrolysis is sometimes possible. 146
O
HCl, H O
2
PhCH C N PhCH 2 CNH 2
2
40–50°C
1 h
A milder procedure involves the reaction of a nitrile with an alkaline solution of
hydrogen peroxide. 147 The strongly nucleophilic hydrogen peroxide adds to the nitrile
and the resulting adduct gives the amide. There are several possible mechanisms for
the subsequent decomposition of the peroxycarboximidic adduct. 148

NH NH O
H O
2
RC N + – O H RCOO – RCOOH + H O 2 RCNH 2 + O 2 + H O
2
2
2
In all the mechanisms, the hydrogen peroxide is converted to oxygen and water, leaving
the organic substrate hydrolyzed, but at the same oxidation level.
Scheme 3.6 illustrates some of the means of preparation of amides. Entries 1 and
2 are cases of preparation of simple amides by conversion of the carboxylic acid to an
acyl chloride using SOCl . Entry 3 is the acetylation of glycine by acetic anhydride.
2
The reaction is done in concentrated aqueous solution (∼ 3M) using a twofold excess
of the anhydride. The reaction is exothermic and the product crystallizes from the
reaction mixture when it is cooled. Entries 4 and 5 are ester aminolysis reactions. The
cyano group is an activating group for the ester in Entry 4, and this reaction occurs at
room temperature in concentrated ammonia solution. The reaction in Entry 5 involves
a less nucleophilic and more hindered amine, but involves a relatively reactive aryl
ester. A much higher temperature is required for this reaction. Entries 6 to 8 illustrate
the use of several of the coupling reagents for preparation of amides. Entries 9 and
10 show preparation of primary amides by hydrolysis of nitriles. The first reaction
involves partial hydrolysis, whereas the second is an example of peroxide-accelerated
hydrolysis.

146
W. Wenner, Org. Synth., IV, 760 (1963).
147 C. R. Noller, Org. Synth., II, 586 (1943); J. S. Buck and W. S. Ide, Org. Synth., II, 44 (1943).
148
K. B. Wiberg, J. Am. Chem. Soc., 75, 3961 (1953); J. Am. Chem. Soc., 77, 2519 (1955); J. E. McIsaac,
Jr., R. E. Ball, and E. J. Behrman, J. Org. Chem., 36, 3048 (1971).