Unprecedented, highly convergent, high yielding, one-pot synthesis of phenylhydrazones 7, acylhydrazones 8 and thiosemicarbazones 9 (most of them obtained as Z-isomers) was carried out starting from 1,2,3 by in situ condensing isolable key intermediate iminium chlorides 4,5,1a 61b with nitrogen nucleophiles (R-NHNH2) in the presence of N,N-dimethylaniline (Scheme 1). The reaction of 4,5,6 with hydrazine gave azines instead of hydrazones, while with primary aromatic amines (e.g., aniline) the reaction afforded the corresponding benzamides, rather than imines. At present, synthetic procedures for thioureidic derivatives 7 and 8 are unknown, while indole products 9 are obtainable from the corresponding aldehyde. Recently, metal ion chelation therapy has attracted much attention. In this context, hydrazones, acylhydrazones, and thiosemicarbazones show a variety of relevant biological activity, especially as bioavailable metal (iron, copper, zinc) chelators, potentially useful in cancer2. and neurodegenerative3. diseases. Derivatives 7, 8, and 9 are currently under biological screening.

Unprecedented one-pot synthesis of pharmaceutical interest derivatives via in situ condensation of heterocyclic iminium salts with nitrogen nucleophiles

CANEVA, CHIARA;ALFEI, SILVANA;SPALLAROSSA, ANDREA;RANISE, ANGELO
2013

Abstract

Unprecedented, highly convergent, high yielding, one-pot synthesis of phenylhydrazones 7, acylhydrazones 8 and thiosemicarbazones 9 (most of them obtained as Z-isomers) was carried out starting from 1,2,3 by in situ condensing isolable key intermediate iminium chlorides 4,5,1a 61b with nitrogen nucleophiles (R-NHNH2) in the presence of N,N-dimethylaniline (Scheme 1). The reaction of 4,5,6 with hydrazine gave azines instead of hydrazones, while with primary aromatic amines (e.g., aniline) the reaction afforded the corresponding benzamides, rather than imines. At present, synthetic procedures for thioureidic derivatives 7 and 8 are unknown, while indole products 9 are obtainable from the corresponding aldehyde. Recently, metal ion chelation therapy has attracted much attention. In this context, hydrazones, acylhydrazones, and thiosemicarbazones show a variety of relevant biological activity, especially as bioavailable metal (iron, copper, zinc) chelators, potentially useful in cancer2. and neurodegenerative3. diseases. Derivatives 7, 8, and 9 are currently under biological screening.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/625154
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