A Practical Reagent for the Synthesis of Substituted Hydrazines

A practical, inexpensive triprotected hydrazine reagent, 2-benzyl-oxycarbonyl-1-tert-butoxycarbonyl-1-(4-methylphenylsulfonyl)-hydrazine, 1-Boc-1-Tos-2-Z-hydrazine (2), has been prepared on a 100 mmol scale and examined with respect to application in stepwise synthesis of unsymmetrically substituted hydrazines. The use of three protective groups excludes undesired substitution on the nitrogens even under forcing conditions. The initial alkylation which can be accomplished quantitatively is followed by the removal of the tosyl moiety. Due to the presence of a Boc group on the sulfonamide nitrogen atom, the otherwise rather stable sulfonamide function can be cleanly and efficiently cleaved reductively by magnesium in dry methanol to provide a second alkylation site. Such intermediates have recently been converted to tetrasubstituted hydrazines. With sonication this reduction is generally complete within 30 minutes. The new reagent exhibits increased stability to base in comparison with its predecessor and is more suitable and economical for work on a larger scale.

hydrazine reagent - magnesium reduction - stepwise synthesis - substituted hydrazine - tosyl cleavage