The Use of Tosylhydrazone Salts as a Safe Alternative for Handling Diazo Compounds and Their Applications in Organic Synthesis

Abstract

Diazo compounds are useful synthetic intermediates in organic synthesis but, due to their toxicity and unpredictable explosive behaviour, their unique reactivity has not been fully exploited and their use on large scale has been avoided. We have developed a reliable method that generates diazo compounds in situ. Our approach is based on the BamfordStevens reaction, which utilizes tosylhydrazone salts as diazo precursors. In the presence of phase-transfer-catalysts (PTC), we found that tosylhydrazone salts can be cleanly converted to diazo compounds under mild reaction conditions and in a wide range of solvents. These diazo compounds can then be

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

“…In situ generation of diazo compounds from tosylhydrazone salts, [27] was briefly investigated and promising yields of cycloadduct 24 were obtained from reaction of benzylidene hydrazone salt 23 (57%, Scheme 8). This benign reactivity and broad range of possible tosylhydrazones encourages detailed future investigation.…”

Inserção C-H de carbenóides de ródio em água e reutilização do catalisador

“…Neste passo da síntese pretende-se que os alunos sejam alertados relativamente às normas de segurança na manipulação do hidreto de sódio (justificando o uso da dispersão em óleo mineral) e da azida 2, que justifiquem a elevada reactividade da azida e proponham um mecanismo para a reacção de formação da unidade diazo. Apesar das azidas serem conhecidas pela sua instabilidade, a p-TsN 3 (2) tem sido utilizada no nosso laboratório em condições bastante agressivas (60 ºC) sem nunca terem ocorrido acidentes e o seu uso é justificado pela não existência de métodos alternativos acessíveis 45,46 . Apesar da diazo acetamida 6 ser obtida com elevado grau de pureza, já que a p-toluenossulfonil amida formada é extraída com água, o produto da reacção pode ser ainda recristalizado num sistema éter etílico/hexano.…”

Two-Step Flow Synthesis of Biarylmethanes by Reductive Arylation of Tosylhydrazones

“…Both type of by-products can not further undergo reductive coupling. [10] A third type of by-products formed under the reaction conditions was biaryl 11 that resulted from homocoupling of the boronic acid. Its formation could not completely be suppressed because the boronic acid had to be employed in excess without necessarily reducing the yields of arylation products 3.…”