Hydrazone synthesis

JAPP KLINGEMANN Hydrazone Synthesis Synthesis ot hydrazones trom diazonum saKs and an activated methylene group (or enamlne)... 

The Buchwald group exploited the Pd-catalyzed hydrazone synthesis for the efficient preparation of indoles. While removal of the benzophenone moiety and isolation of the free hydrazine did not proceed cleanly, the MIT workers found that Fischer indole synthesis could be effected by in situ exchange of the ketone group. The desired indoles could thus be isolated in good to excellent yield over two steps,Eq. (149) [121]. 

JAPP Oxazole synthesis 187 JAPP KLINGEMANN Hydrazone synthesis 188 JAROUSSE MAKOSZA Phase transler 189 JEGERTetrahyikoturan synthesis 190 JOHNSON Phenol aHcynylation 191 Johnson 168,197,240 JONES Oxidation reagent 192 JULIA BRUYLANTS Cyclopropyl earbinol rearrangement 193... 

The esters also react readily with aryl hydrazines to give aryl hydrazone derivatives. Examples of the latter were first synthesized (prior to the availability of tetraalkyl carbonylphosphonates) from tetraalkyl methylenebisphosphonates and aryl diazonium salts, analogously to the phosphonoglyoxylate hydrazone synthesis described in a previous section. First made as possible precursors in a ketone synthesis, several of these compounds, converted to free acid salts by treatment with BTMS followed by dicyclohexylamine in methanol, proved to have unexpected inhibitory activity vs the pyrophosphate-dependent phospho-fructokinase of the parasite T. gondii, which causes a potentially lethal opportunistic infection in immunocompromised persons such as AIDS patients [94]. In fact, the 2,4-dinitrophenylhydrazone of carbonylbisphosphonic acid (as the tetrasodium salt) dramatically abated toxoplasmosis lesions in infected human foreskin fibroblasts [94]. Animal toxicity in this compound, probably arising from in vivo hydrolysis to the highly toxic hydrazine, precluded its future development, but the result remains an interesting lead. 

Scheme 8.27 MW-assisted hydrazone synthesis of furaldehyde and flavanone.

Hydrazone synthesis In a typical example, a mixture of benzophenone and hydrazine hydrate in toluene resulted in 95% yield of the hydrazone within 20 min [104] (Eq. 20) ... 

A better understanding of this mechanism aids our appreciation of how the reaction works, and helps us design novel reactions. The Japp-Klingemann hydrazone synthesis is sueh an example. A hydrazone is an... 

Li, J. Japp-Klingemann Hydrazone Synthesis in Name Reactions for Functional Group Transformations, Li, J. J. Corey, E. J., Eds., Wiley Hoboken, NJ, 2007, pp 630-634. 

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