Page 260 - Advanced Organic Chemistry Part B - Reactions & Synthesis

232 Phase transfer conditions are used as well for the preparation of azides. 73

CHAPTER 3 CH 3 Br NaN 3 CH 3 N 3
Functional Group CH CH CH CH CH CH
Interconversion 2 CO 2 3 R P + – Br 2 CO 2 3
by Substitution, 4
Including Protection and 4 h, 25°C
Deprotection
Tetramethylguanidinium azide, an azide salt that is readily soluble in halogenated
solvents, is a useful source of azide ions in the preparation of azides from reactive
halides such as -haloketones, -haloamides, and glycosyl halides. 74
There are also useful procedures for preparation of azides directly from alcohols.
Reaction of alcohols with 2-fluoro-1-methylpyridinium iodide followed by reaction
with lithium azide gives good yields of alkyl azides. 75
N 3 –
ROH + + RN 3
+ +
N F N OR N O
CH CH
CH 3 3 3
Diphenylphosphoryl azide reacts with alcohols in the presence of triphenylphosphine
76
and DEAD. Hydrazoic acid, HN , can also serve as the azide ion source under these
3
conditions. 77 These reactions are examples of the Mitsunobu reaction.
+ –
P + C H O CN
ROH + Ph 3 2 5 2 NCO C H ROPPh + C H O CNNHCO C H
2 2 5
2
2 5
3
2 2 5
+
–
ROPPh + N RN + Ph P O
3
3
3
3
Diphenylphosphoryl azide also gives good conversion of primary alkyl and secondary
benzylic alcohols to azides in the presence of the strong organic base diazabicyc-
loundecane (DBU). These reactions proceed by O-phosphorylation followed by S 2
N
displacement. 78
O
OH N 3
(PhO) PN 3
2
CH 3 CH 3
Ar Ar
DBU
This reaction can be extended to secondary alcohols with the more reactive bis-(4-
nitrophenyl)phosphorazidate. 79
73 W. P. Reeves and M. L. Bahr, Synthesis, 823 (1976); B. B. Snider and J. V. Duncia, J. Org. Chem.,
46, 3223 (1981).
74
Y. Pan, R. L. Merriman, L. R. Tanzer, and P. L. Fuchs, Biomed. Chem. Lett., 2, 967 (1992); C. Li,
T.-L. Shih, J. U. Jeong, A. Arasappan, and P. L. Fuchs, Tetrahedron Lett., 35, 2645 (1994); C. Li,
A. Arasappan, and P. L. Fuchs, Tetrahedron Lett., 34, 3535 (1993); D. A. Evans, T. C. Britton,
J. A. Ellman, and R. L. Dorow, J. Am. Chem. Soc., 112, 4011 (1990).
75 K. Hojo, S. Kobayashi, K. Soai, S. Ikeda, and T. Mukaiyama, Chem. Lett., 635 (1977).
76 B. Lal, B. N. Pramanik, M. S. Manhas, and A. K. Bose, Tetrahedron Lett., 1977 (1977).
77
J. Schweng and E. Zbiral, Justus Liebigs Ann. Chem., 1089 (1978); M. S. Hadley, F. D. King,
B. McRitchie, D. H. Turner, and E. A. Watts, J. Med. Chem., 28, 1843 (1985).
78 A. S. Thompson, G. R. Humphrey, A. M. DeMarco, D. J. Mathre, and E. J. J. Grabowski, J. Org.
Chem., 58, 5886 (1993).
79
M. Mizuno and T. Shioiri, J. Chem. Soc., Chem. Commun., 22, 2165 (1997).