1460
V. Kumar, M. P. Kaushik / Tetrahedron Letters 47 (2006) 1457–1460
Grellier, P.; Croft, S. L.; Augustyns, K.; Haemers, A.
Bioorg. Med. Chem. Lett. 2003, 13, 2875–2878.
In summary, we have developed an efficient one-pot syn-
thetic procedure for the preparation of hydroximoyl
chlorides from aldoximes and N-tert-butyl-N-chlorocyan-
amide which can be converted into 2-isoxazolines in one-
pot. The reactions have some merits such as one-pot
reaction, very short reaction time, high yields, mild reac-
tion conditions and the ease of separation. Moreover,
under the reaction conditions, a variety of sensitive
groups remain unaffected.
15. (a) Tabrizi, M. A.; Baraldi, P. G.; Guarneri, M.; Manfre-
dini, S.; Pollini, G. P.; Simoni, D. Tetrahedron Lett. 1991,
32, 683–686; (b) Schwab, W.; Jager, V. Angew. Chem., Int.
Ed. Engl. 1981, 20, 603–605; (c) Anderson, W. K.; Raju,
N. Synth. Commun. 1989, 19, 2237–2242; (d) Wade, P. A.;
Bereznak, J. F.; Palfey, B. A.; Carroll, P. J.; Dailey, W. P.;
Sivasubramanian, S. J. Org. Chem. 1990, 55, 3045–3051;
(e) Curran, D. P.; Scanga, S. A.; Fenk, C. J. J. Org. Chem.
1984, 49, 3474–3478; (f) Heinze, I.; Eberbach, W. Tetra-
hedron Lett. 1988, 29, 2051–2054.
16. Preparation of N-tert-butyl-N-chlorocyanamide:19 A solu-
tion containing 0.28 mol of cyanogen bromide in 350 mL
of anhydrous ether was cooled to 0 ꢁC and tert-butylamine
(1.0 equiv) was added slowly. The reaction mixture was
stirred for another 15 min at the same temperature and the
precipitate of amine hydrobromide formed was removed
by filtration. This filtrate was washed with water (2 ·
100 mL) dried over anhydrous Na2SO4 and the filtrate was
evaporated to half its volume. The resulting solution was
diluted with 75 mL of carbon tetrachloride, cooled to
0 ꢁC, then treated with the theoretical amount of tert-butyl
hypochlorite (1.0 equiv) in 30 mL of carbon tetrachloride
and the mixture allowed to warm to room temperature.
The yellow solution formed was evaporated and the
residue was distilled to afford the desired product, bp
53.5 ꢁC (8 mm Hg), IR (KBr): 2216 cmÀ1 (NCN) and
weak band at 2082 cmÀ1. The positive chlorine of N-tert-
butyl-N-chlorocyanamide was determined by standard
iodometric titration and found to be 26.54% (theoretical
value 26.76%).
17. General procedure for the synthesis of hydroximoyl chlo-
rides. To a stirred solution of aldoxime (5 mmol) in dry
dichloromethane (10 mL) at room temperature was added
slowly N-tert-butyl-N-chlorocyanamide (1.0 equiv) in dry
dichloromethane (5 mL). The reaction took place imme-
diately on mixing with the appearance of a yellow colour
indicating the formation of the hydroximoyl chloride.
Reaction completion was assessed by TLC (in the case of
aromatic aldoximes). tert-Butylcyanamide 5 was formed
as a side product due to dechlorination of reagent 2. The
reaction mixture was washed with water (2 · 20 mL) and
dried over anhydrous Na2SO4. Evaporation of the solvent
gave a mixture of hydroximoyl chloride and tert-butylc-
yanamide. The pure hydroximoyl chloride was obtained
either by recrystallization in DCM/petroleum ether (40–
60 ꢁC) in a 3:7 ratio (in the case of solid products) or
distillation under vacuum (in the case of liquid products).
18. General procedure for the synthesis of 2-isoxazolines. N-
tert-Butyl-N-chlorocyanamide (5 mmol) was added to a
stirred solution of aldoxime (1.0 equiv) and N-phenylma-
leimide (1.0 equiv) in dry DCM (10 mL) at room temper-
ature with subsequent addition of triethylamine
(1.5 equiv). The mixture was stirred for 15–30 min at the
same temperature. After completion of the reaction, the
mixture was washed thoroughly with water (3 · 20 mL)
and dried over anhydrous Na2SO4. Evaporation of the
solvent gave crude 2-isoxazolines, which were purified
either by crystallization in DCM/petroleum ether (40–
60 ꢁC) in a 3:7 ratio (in the case of solid products) or
distillation under vacuum (in the case of liquid products).
19. Neale, R. S.; Marcus, N. L. J. Org. Chem. 1969, 34, 1808–
1816.
Acknowledgement
We thank K. Sekhar, Director, DRDE, Gwalior, for his
keen interest and encouragement.
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