3446 J. Org. Chem., Vol. 42, No. 21,1977
Notes
Improved Reduction of Nitrimines to Nitramines Using Sodium Borohydride and Acetic Acid Michael J. Haire Contribution Ncl2456 from the Central Research and Development Department, E. I . du Pont de Nemours and Co., Wilmington, Delaware 19898 lieceived April 1 , 1977
Imines can generally be reduced efficiently with sodium borohydride, lithium aluminum hydride, catalytic hydrogenation, or dissolving metal reductions. However, in the presence of many functional groups (e.g., esters, ketones, nitro groups, and double bonds), these methods often cannot be employed for imine reduction due to concomitant reduction of the functional group.' In such cases, sodium borohydride is usually the reagent of choice,2 but even it will not always reduce nitro-substituted imines in good yield. The present study provides a significant improvement in the reduction of nitrimines to nitramines by the addition of acid to the reaction mixture (Table I). The procedure is simple and general, yet provides greatly improved yields over the usual sodium borohydride reduction procedures. When 38acetoxy-5a-chloro-6-nitriminocholestane(1) was treated with sodium borohydride in dioxane and ethanol, the nitramine 2 was obtained in only 15% yield regardless of reaction time; no nitrimine was recovered. Addition of glacial acetic acid to the reaction mixture dramatically increased the yield of recrystallized product to 76%. Similarly, sodium borohydride (3) without reduction of 3-chloro~3-methyl-2-nitriminobutane acid gave only a trace of the nitramine 4, but when the reduction was run in the presence of acetic acid, the yield of nitramine again jumped to 76%. Although a mechanistic study of the role of acetic acid was not undertaken, the presumed reducing agent is an acyloxyborohydride species formed by the initial reaction of acetic acid and sodium borohydride. Sodium triacetoxyborohydride is known to reduce aldehydes under mild conditions.3 That this reduction is general for a variety of structurally different nitrimines and can be accomplished without conNitrimine
Ad3
4Fy JP61 NH
m p 206 (dec)
76
bp 60/0.15 m m
70
m p 126-127
41
m p 84-85
\
/NO>
kNH 4
p /
N I'
OiN
6
5
NO,
& 7
76
2
NO,
w
O
NO,
1
3
Experimental Section
All melting points were uncorrected. NMR spectra were recorded on a Varian A-60 spectrometer using Me4Si as an internal standard. Infrared spectra were recorded on a Perkin Elmer 137 spectrometer. General Procedure for Nitramine Reduction. a solution of 23.2 mmol of nitrimine in 165 mL of dioxane, 165 mL of ethanol, and 0.5 mL of glacial acetic acid was stirred at 0 "C while 229 mmol of sodium borohydride was added as fast as possible while still controlling frothing. The mixture was stirred for 30 minat 0 "C, and 1.5mL of glacial acetic acid was added (totalof 35.0 m o l of HOAc). After stirring for 1h at 0 "C followed by 1h at room temperature, the mixture was diluted with 700 mL of 3% aqueous acetic acid and extracted with methylene chloride. The extracts were washed with water, dried, and concentrated in vacuo to give the crude nitramine which was either recrystallized or distilled. 3~-Acetoxy-5a-chloro-6~-nitraminocholestane (2). Sodium borohydride reduction as above of l6gave a white solid which was recrystallized from acetone to give a 76% yield of 2: mp 206-206.5 OC (dec); IR (Nujol) 5.85 (s) and 6.20 (8) rcm; NMR ((CD&SO) 6 5.504.90 (m, 1H, -COOCH
