Diazetidine synthesis

Uretidinedione — see l,3-Diazetidine-2,4-dione 2-Uretidinone, 1,3-diphenyl-4-(phenylimino)-synthesis, 7, 474 Urgothianine, 5, 498 Urie acid... 

A recent review on four-membered heterocycles formed from imino-phosphoranes concentrates on the preparation and the reactivity of 2,4-diimino-l,3-diazetidine and related compounds (93JPR305). As an example, the synthesis via bisiminophosphorane 85 is described in Scheme 42. The bisiminophosphorane has both a heteroaryl and a styryl site. From a mechanistic view, the reaction of the bisiminophosphorane proceeds with aryl isocyanate formation via an aza-Wittig mechanism. Intermediate car-bodiimide formation (86) occurs directly on the iminophosphorane moiety... 

Beckert and co-workers reported the synthesis of 1,2-diazetidine derivatives 246 by the reaction of bis-imidoyl choloride 244 with amidrazone 245 <2002H(57)1257>. The product underwent decomposition during the isolation. Thus, they carried out the isolation at lower temperature to furnish 246a (38%) and 246b (48%). On the other hand, reaction of hydrazine 247 with bis-imidoyl chloride 244 gave 1,2-diazetidines derivatives 248 (Scheme 37). Some of the structures were confirmed by X-ray crystallography (Section 2.13.3.1) The reaction is expected to proceed via the formation of a C-N bond with the displacement of a chlorine atom. 

The dimerization of aryl isocyanates to l,3-diarylazetidin-2,4-diones is one of the classical methods for the synthesis of 1,3-diazetidinones. In 1993 trimerization of phenyl isocyanate catalyzed by a fluoride ion was also reported, and a small amount of l,3-diazetidin-2,4-dione was obtained at room temperature <1993JOC1932>. 

Aoyama et al. have reported the synthesis of a number of l,3-diazetidine-2,4-dione analogues with a view to studying their enzyme inhibition activities (Scheme 46) <2001BML1691>. 

Komatsu and co-workers reported the synthesis of l,3-diazetidine-2,4-diones by the ring-expansion reaction of diaziridinones <1999H(50)67> Thus, a ring-expansion reaction of l,2-di-/-butyl-l,2-diaziridinone 298 was carried out by a transition metal-mediated carbonylation reaction to furnish l,3-diazetidine-2,4-dione 299 (Equation 38). 

In this volume, we have already examined some alternatives to the synthesis in situ and/or to the use of methyl isocyanate. We thought that 1,3-dimethyl diazetidine dione (XII) (methyl isocyanate dimer) should be a suitable methyl isocyanate precursor which can release methyl isocyanate in safe conditions. This dimer was prepared from N-chlorocarbonyl-N-methyl N -methyl urea (XI) obtained by phosgenation of N,N -dimethyl urea as previously described in scheme 156, section 3-3-4. Cyclization of (XI) in a suitable solvent and in presence of a base such as DABCO afforded the expected dimer (XII) as depicted in scheme 220. 

Cyclization attendant by coupUng from molecules containing both an amino group and an allene unit has apparent utility in synthesis. Formation of five- or six-membered rings is subject to change of the substituent pattern of the allene moiety. The bond distance between the nitrogen atom and the unsaturation is of necessity important. Diazetidines have been acquired from 4-hydrazinyl-l,2-alkadienes. ... 

A new synthesis of 6-arylamino-2-heteroarylimino-l,2-dihydro-l,3,5-triazines from 2,4-bis-(heteroarylimino)-l,3-diazetidines and amidines has been developed by Molina et al. The formation of the triazines was explained as an initial addition of the imino nitrogen of the amidine to the exocyclic C=N bond, followed by formation of an open chain intermediate. This intermediate cyclized, followed by elimination of 4-amino-6-methyl-3-methylthio-l,2,4-triazin-5(47/)-one to give the triazine product (Scheme 62) <87S150>. 1,3,5-Triazines (207) and (208) have been prepared from 2-acylimino-l,3-thiazetidines (204) by treatment with iso thioureas or guanidines respectively (Scheme 63) <91JHC177>. 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

For reviews on the synthesis of p-lactams, see a) Sheehan JC, Corey EJ (1957) Org Reac 9 Chapt 6 b) Mukerjee AK, Srivastava, RC Synthesis 1973 373 b) Isaacs NS (1976) Chem Soc Rev 76 181 c) Bose AK, Manhas MS (1976) Lect Heterocycl Chem 3 43 d) Mukerjee AK, Singh AK (1978) Tetrahedron 34 1731 e) Koppel GA (1983) In Hassner A (ed) Small ring heterocycles-azetidines, p-lactams, diazetidines and diaziridines, Wiley, New York, Chapt 2 f) From azetidiniminium salts, see Ghosez L, Bogdan S, Ceresiat M, Frydrych C, Brynaert J, Portuguez MM, Huber I (1987) Pure Appl Chem 59 393... 

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