Page 254 - Advanced Organic Chemistry Part B - Reactions & Synthesis

226 H 2 O, C H OH
2 5
CH Cl + NaCN CH CN
2
2
CHAPTER 3 reflux 4h
80–90%
Functional Group Ref. 34
Interconversion
by Substitution,
Including Protection and
Deprotection H 2 O, C H OH
2 5
CH CH Br + KCN ClCH CH CH CN
ClCH 2 2 2 2 2 2
reflux 1.5h
40 – 50%
Ref. 35
These reactions proceed more rapidly in polar aprotic solvents. In DMSO, for example,
primary alkyl chlorides are converted to nitriles in1hor less at temperatures of

120 –140 C. 36 Phase transfer catalysis by hexadecyltributylphosphonium bromide
permits conversion of 1-chlorooctane to octyl cyanide in 95% yield in 2 h at 105 C. 37

NaCN
DMSO
CH CH CH CH Cl CH CH CH CH CN
3
2
2
2
2
2
2
3
90–160°C 93%
NaCN
O, decane
H 2
2 6
2
2
2 6
CH 3 (CH ) CH Cl + CH 3 (CH ) CH CN
C H P (C H ) 95%
4 9 3
16 33
105°C, 2h
Catalysis by 18-crown-6 of the reaction of solid potassium cyanide with a variety
38
of chlorides and bromides has been demonstrated. With primary bromides, yields are
high and reaction times are 15–30 h at reflux in acetonitrile 83 C . Interestingly, the

chlorides are more reactive and require reaction times of only about 2 h. Secondary
halides react more slowly and yields drop because of competing elimination. Tertiary
halides do not react satisfactorily because elimination dominates.
3.2.3. Oxygen Nucleophiles
The oxygen nucleophiles that are of primary interest in synthesis are the hydroxide
ion (or water), alkoxide ions, and carboxylate anions, which lead, respectively, to
alcohols, ethers, and esters. Since each of these nucleophiles can also act as a base,
reaction conditions are selected to favor substitution over elimination. Usually, a given
alcohol is more easily obtained than the corresponding halide so the halide-to-alcohol
transformation is not used extensively for synthesis. The hydrolysis of benzyl halides
to the corresponding alcohols proceeds in good yield. This can be a useful synthetic
transformation because benzyl halides are available either by side chain halogenation
or by the chloromethylation reaction (Section 11.1.3).
34 R. Adams and A. F. Thal, Org. Synth., I, 101 (1932).
35
C. F. H. Allen, Org. Synth., I, 150 (1932).
36
L. Friedman and H. Shechter, J. Org. Chem., 25, 877 (1960); R. A. Smiley and C. Arnold, J. Org.
Chem., 25, 257 (1960).
37 C. M. Starks, J. Am. Chem. Soc., 93, 195 (1971); C. M. Starks and R. M. Owens, J. Am. Chem. Soc.,
95, 3613 (1973).
38
F. L. Cook, C. W. Bowers, and C. L. Liotta, J. Org. Chem., 39, 3416 (1974).