Chemistry and heterocyclization of carbohydrazides

Mlostoń

Heimgartner

2012

The reaction of 1H-imidazole-4-carbohydrazides 1, which are conveniently accessible by treatment of the corresponding esters with NH2NH2·H2O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (= hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4-dihydro-3H-1,2,4-triazole-3-thiones 5, the reaction in concentrated H2SO4 at room temperature gave 1,3,4-thiadiazol-2-amines 6. Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7, which, under basic conditions, undergo cyclization to give 2,4-dihydro-3H-1,2,4-triazol-3-ones 8 (Scheme 3). Treatment of 1 with Ac2O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol-2-ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N-oxide residue is retained. Furthermore, it was shown that imidazole N-oxides bearing a 1,2,4-triazole-3-thione or 1,3,4-thiadiazol-2-amine moiety undergo the S-transfer reaction to give bis-heterocyclic 1H-imidazole-2-thiones 11 by treatment with 2,2,4,4-tetramethylcyclobutane-1,3-dithione (Scheme 5).

“…[5]. A typical procedure for the preparation of unsubstituted hydrazides is the treatment of the corresponding carboxylic ester with NH 2 NH 2 ·H 2 O [1] [5].…”

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confidence: 99%

“…[5]. A typical procedure for the preparation of unsubstituted hydrazides is the treatment of the corresponding carboxylic ester with NH 2 NH 2 ·H 2 O [1] [5]. In a recent publication we have reported on the application of this method for the preparation of diverse types of unsubstituted hydrazides containing in their structure the imidazole ring [6].…”

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confidence: 99%

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

Mlostoń

Heimgartner

2012

“…In the case of carbohydrazides, only a few reactions with isoselenocyanates have been reported to date [4a][4b] [5]. Whereas, to the best of our knowledge, carbohydrazides derived from heterocyclic carboxylic acids have not yet been used in such reactions [6], reactions of benzohydrazide with aliphatic and aromatic isoselenocyanates are known [4a][4c], and in a recent study, selenosemicarbazides obtained thereby were shown to form 1,3,4-oxadiazole derivatives upon heating in DMF solution to 100° in the presence of air-oxygen [5]. This reaction was accompanied by the formation of elemental Se.…”

Section: Introduction -Isoselenocyanates Are Well Known As Versatilementioning

confidence: 99%

New Selenosemicarbazides Derived from Imidazole‐Based Carbohydrazides

Ciepielowski

Cebulska

et al. 2013

Imidazole-based carbohydrazides, i.e., 3-oxidoimidazole-4-carbohydrazides 1 and 2-[(imidazol-2-yl)sulfanyl]acetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7, respectively, in good yields. On heating 7b in DMF in the presence of air to 100°, 1,3,4-oxadiazole 8a was formed via cyclization and formal elimination of H2Se. Product 8a was also obtained after heating of a mixture of 4a and 6b under the same conditions. On the other hand, on heating of a solution of 7c in MeOH at reflux, a cyclization occurred to give the corresponding 1,2,4-triazole-3-selone 9b. Again, the same product was formed when a mixture of 4b and 6b was heated in MeOH. Surprisingly, analogous cyclizations of selenosemicarbazides of type 5 under the same conditions failed, and only decomposition was observed. The structures of 7a, 7d, and 9b have been established by X-ray crystallography. and 2-(imidazol-2-yl)sulfanylacetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7, respectively, in good yields. On heating 7b in DMF in the presence of air to 100°, 1,3,4-oxadiazole 8a was formed via cyclization and formal elimination of H 2 Se. Product 8a was also obtained after heating of a mixture of 4a and 6b under the same conditions. On the other hand, on heating of a solution of 7c in MeOH at reflux, a cyclization to give the corresponding 1,2,4-triazole-3-selone 9b occurred. Again, the same product was formed when a mixture of 4b and 6b was heated in MeOH. Surprisingly, analogous cyclizations of selenosemicarbazides of type 5 under the same conditions failed, and only decomposition was observed. The structures of 7a, 7d, and 9b have been established by X-ray crystallography.

“…In the case of the bis-heterocycle 8, treatment with HCOONH 4 and Pd/C in MeOH gave the debenzylated product 12.…”

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confidence: 99%

“…On the other hand, carbohydrazides are known as versatile starting materials for the synthesis of five-and six-membered heterocycles containing N, O, and S-atoms [4]. In our recent publications, the preparation and reactivity of 3-oxidoimidazole-4-carbohydrazides 1 as well as prolinehydrazides 2 were described [5][6][7][8].…”

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confidence: 99%

New Optically Active Bis‐Heterocycles Derived from (S)‐Proline

Mlostoń

Linden

et al. 2012

Enantiomerically pure bis-heterocycles containing a (S)-proline moiety have been prepared starting from (S)-N-benzylprolinehydrazide (2b). The reactions with isothiocyanates or butyl isocyanate in refluxing MeOH led to the corresponding thiosemicarbazide 5 and semicarbazide 9 with a N-benzylprolinoyl residue. The structure of the tert-butyl derivative 5d was established by X-ray crystallography. Basecatalyzed cyclization of 5 and 9 led to (S)-3-(pyrrolidin-2-yl)-1H-1,2,4-triazole-5(4H)-thiones 6 and the corresponding 5(4H)-one 8, respectively, whereas, in concentrated H2SO4, compounds 5 undergo cyclization to give (S)-5-amino-2-(pyrrolidin-2-yl)-1,3,4-thiadiazoles 7. Furthermore, 2b reacted with hexane-2,5-dione in boiling iPrOH to yield the (S)-N-(2,5-dimethylpyrrol-1-yl) prolinamide 10. In the case of the bis-heterocycle 8, treatment with HCOONH4 and Pd/C in MeOH gave the debenzylated product 12.