Synthesis of Masked Vicinal Amino Aldehydes of Pyrrolizine and Pyrrolo [1,2-c]thiazole Series

Abstract

Acylation of (1,3-dihydro-1,3-dimethyl-2H-benzimidazol-2-ylidene)acetonitrile with mixed anhydrides of N-Boc proline and 4-thiazolidinecarboxylic acid was found to proceed at the exocyclic carbon atom yielding the corresponding C-acyl derivatives. Removal of the protecting group with equimolar amount of hydrochloric acid effected simultaneous cyclization affording 2-(3-amino-5,6,7,7a-tetrahydro-1-oxo-1H-pyrrolizin-2-yl)- and 2-(5-amino-7,7a-dihydro-7-oxo-1H,3H-pyrrolo[1,2-c]thiazol-6-yl)-1,3-dimeth­ylbenzimidazolium chlorides. Reduction of the prepared salts with sodium borohydride resulted in 3-amino-2-(2,3-dihydro-1,3-di­methyl-1H-benzimidazol-2-yl)-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one and 5-amino-6-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-1,7a-dihydro-3H,7H-pyrrolo[1,2-c]thiazol-7-one, respectively. These compounds were shown to be masked aldehydes. Their reactions with phenylhydrazine and hydroxylamine yielded corresponding hydrazones and oximes, whereas condensation with malononitrile furnished 2-amino-5a,6,7,8-tetrahydro-5-oxo-5H-pyrido[3,2-b]pyrrolizine-3-carbonitrile and 2-amino-5a,6-dihydro-5H,8H-thiazolo[3′,4′:1,5]pyrrolo[2,3-b]pyridine-3-carbonitrile.

Key words

acylations - amino aldehydes - heterocycles - nitriles - reduction

References

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17

To be precise, the material recovered from the reaction exhibited the same ^¹H and ^¹³C NMR spectra as that of compound 6b, but differed in melting point and elemental analysis, having significant lack of Cl. Probably, it was a mixture of the salts 6b with different counterions, namely chloride, hydroxide, and, maybe, borate. Treatment of this material with HCl afforded compound 6b identical with the authentic sample in all parameters.

20

Full crystallographic parameters have been deposited at the Cambridge Crystallographic Data Centre under reference number CCDC 702208. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; e-mail: [e-mail]].