Synthesis of Hydrazines via Radical Generation and Addition of

Letter pubs.acs.org/OrgLett

Cite This: Org. Lett. XXXX, XXX, XXX−XXX

Synthesis of Hydrazines via Radical Generation and Addition of Azocarboxylic tert-Butyl Esters Chen-Hao Ru, Shi-Huan Guo, Gao-Fei Pan, Xue-Qing Zhu, Ya-Ru Gao, and Yong-Qiang Wang* Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of Chemistry & Materials Science, Northwest University, Xi’an 710069, P. R. China S Supporting Information *

ABSTRACT: A new chemistry of azo compounds that is a radical generation and addition in situ of azocarboxylic tert-butyl esters to synthesize hydrazines has been described. The protocol provides a novel strategy for the synthesis of various hydrazines. The advantages of the transformation include broad substrate scope, benign conditions, and convenient operation. ince Griess first discovered the diazo compounds in 1858,1 and in the following year Martius and Griess prepared commercial azo dyes,2 azo compounds have attracted intense attention due to their interesting physical and chemical properties.3 Besides being the most important and versatile class of colored organic compounds used as dyes and pigments,4 azo compounds (e. g., methyl orange) can be employed as acid−base indicators. Azo compounds [e.g., azobis(isobutyronitrile) (AIBN)] are also widely utilized as initiators in free-radical polymerizations and other radicalinduced reactions.5 Recently, azo-based molecules were found to be powerful tools for the fabrication of multi-stimuliresponsive degradable materials.6 Herein, we disclose a new chemistry of azo compounds, the first radical generation, and addition in situ to synthesize various hydrazines. It is well-known that hydrazines are a kind of valuable organic compounds.7 Many hydrazines show remarkable biological activities.8 Several similar molecules to hydrazines are effective for treatment of tuberculosis, hypertension, and Parkinson’s disease.7b Hydrazine-based petidomimetics are found to be potent agents against diseases such as SARS, AIDS, and hepatitis.9 Additionally, in the field of organic synthesis, hydrazines are essential amino acid precursors10 and versatile synthetic building blocks for heterocycle syntheses.11 In the hydrazine family, N-Boc-protected N,N′-disbstituted hydrazines are interesting molecules. Typically, they can be synthesized via transition-metal-catalyzed (e.g., Pd and Cu)12 or base-promoted (e.g., n-BuLi)13 amination reactions of hydrazines with haides or boronic acids. In this paper, we reported a novel synthetic method for such hydrazines. The research originated from the reaction where phenylazocarboxylic tert-butyl ester 1a was in the presence of hexafluoroisopropanol (HFIP) at room temperature for 24 h to afford the intriguing hydrazine compound 2a (the structure was confirmed by single-crystal X-ray analysis) in 26% yield. We realized this would be a new chemistry for azo compounds, and if the reaction conditions had been optimized, a novel strategy for the synthesis of hydrazines from azo compounds would be developed. Accordingly, we chose phenylazocarbox-

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ylic tert-butyl ester 1a as a model substrate to seek the optimal reaction conditions for the development of a new chemistry of azo compounds to synthesize hydrazines (Table 1). First, we Table 1. Optimization of the Reaction Conditionsa

entry

solvent

temp (°C)

time (h)

conv (%)

yieldb (%)

1 2 3 4 5 6 7 8 9

HFIP CF3CH2OH other solventsc solventd HFIP HFIP HFIP HFIP HFIP

25 25

24 24 24 24 28 4 1.5 1 1

30 9 0