Convenient Methodology for the Synthesis of Trialkylhydrazines

Abstract

A convenient methodology, based on the addition of organolithium compounds to N-nitrosamines, was developed for the synthesis of substituted hydrazones and trialkyl hydrazines. The reaction is very sensitive to the reaction conditions, particularly the [RLi]–[nitrosamine] ratio. For molar ratios of 1–1.2, an almost quantitative conversion to the N = O bond addition products (i.e., alkylhydrazones) can be obtained in very good yields, with any remaining nitrosamine. Using greater molar ratios (in the range of 3–5), a second addition occurs, and branched trialkyl hydrazines are obtained, in good yields, with variable amounts of hydrazone remaining. Substituted hydrazines are known to have useful commercial applications and remarkable biological activities. A wide diversity of trialkyl hydrazines could be synthesized by using two different organolithiums.

Keywords:

• Addition to the N = O bond
• hydrazines
• hydrazones
• nitrosamines
• organolithiums

ACKNOWLEDGMENTS

A.V. and C.R. are grateful recipients of the National Research Council (CONICET) fellowships. The authors are indebted to the United Nations Environmental Program (Project PNUD/ARG 02/18 Subproj. B-C-53) and to CONICET (PIP no. 6019) for financial support.

Notes

^a Temp. 20–25°C. Reaction time 2 h.

^b 2 = (c-C₆H₁₁)₂NN = CHR¹.

^c 3 = (c-C₆H₁₁)₂NNH-CH(R¹)R.

^d Main product = (c-C₆H₁₁)₂NN = CHCH₃.

^e Lateral products in minor yields.

^a Reaction time: 2 h.

^b [RLi]:[1]: 1.05–1.2.

^c 2 = (c-C₆H₁₁)₂NN = CHR¹.

^d 7 = (c-C₆H₁₁)₂NNH-CHR¹R².

^e 15% of 3c observed.

^f This compound is called 3c in Table 1.