Iminophosphorane‐mediated synthesis of mesoionic 1,3,4‐Oxadiazolo‐[3,2‐ a ]pyridinylium‐2‐aminides

Abstract

Reaction of iminophosphorane 2 with methyl isocyanate yields the mesoionic 1,3,4-oxadiazolo[3,2-u Jpyridinylium-2-methylaminide 3, which undergoes N-methylation with CF3SO3CH3 to give the 1,3,4-oxadiazolo[3,2-a]pyridinium cation 4. The structure of compound 4 has been established by means of X-ray crystallography. Mesoionic aminide 3 undergoes rearrangement by the action of base to give the isomeric mesoionic compound 1,3,4-triazolo[3,2-u Jpyridinylium-2-olate 11. Compound 3 by the action of (ary1imino)triphenylphosphoranes is converted into the corresponding 1,3,4-oxadiazolo[3,2-a]pyridinylium-2-arylaminides 12, which can be also prepared from iminophosphorane 2 and hydroxirnoyl chlorides.Mesoionic compounds of the general formula 1 are an interesting family of heterocycles because of their unique structure, reaction behaviour, and pharmaceutical activity'! In spite of much work on the synthesis of mesoionic compounds possessing 6 x electrons in a heterocyclic five-membered ring and with the negative charge associated with a nitrogen atom (f = NAr; NCOR; NSO,Ar), no methods for the preparation of this kind of compounds, in which the exocyclic nitrogen atom is attached to an alkyl group (f = NR) has hitherto been reported. This fact could be due to the unstability of these compounds associated with the high negative charge density on the exocyclic nitrogen atom. As a part of our study on the chemistry of fused mesoionic compounds" we describe here the first synthesis of the mesoionic 5,7-diphenyl-1.3.4-oxadiazolo[3,2-a]-pyridinylium-2-methylaminide (3) and its unusual reactivity.The first reported synthesis of 1,3,4-oxadiazoliurn-2-arylaminidcs involves sequential treatment of N-benzoyl-N-methylhydrazine with isocyanide dichlorides and diazomethane'). Recently we have found that the reaction products of iminophosphoranes derived from N-aminoheterocycles with isocyanates are strongly dependent on the nature both of the heteroaromatic ring and the isocyanate4! Results and DiscussionIminophosphorane 2, readily available from l-amino-4,6-diphenyl-2(1 If )-pyridinone and triphenylphosphane dibromide4a', reacts with methyl isocyanate in dry benzene at room temperature to give crystalline 5,7-diphenyl-l,3,4-oxadiazolo[3,2-a]pyridinylium-2-methylaminide (3) in 64% yield. A similar result is obtained with methyl isothiocyanate. We believe that the 2 + 3 conversion involves an initial aza-Wittig reaction between the iminophosphorane 2 and the isocyanate to give a carbodiimide as a highly reactive intermediate which cyclizes spontaneously to the valence tautomer 3. Reaction of 2 with ethyl and tert-butyl isocyanate failed to give the corresponding mesoionic aminides, and only complex mixtures were obtained in which the mesoionic compounds could not be detected.The IR spectrum of 3 shows a strong absorption band at 1687 cm--' which can be attributed to the exocyclic C = N stretching, this value being in good agreement with those reported for the monocyclic systems3'. The absence of carbodiimide bands provides support for its...

Synthetic Strategies for Preparing Bicyclic Guanidines

“…[68] The synthesis of iminophosphorane intermediate 117 and subsequent treatment with isocyanate leading to 6+6 BGs 118 was performed under mild reaction conditions and afforded the target compounds in high yields of greater than 70 %. For this alternative, a diverse variety of starting materials and reagents have been used, with carbodiimides being one the most frequently applied building blocks (Scheme 32).…”