1.2- Diazetidin-4-ones

Cyclohexylamine is reported to react with formaldehyde giving a 60% yield of 1,3-diazetidine. One additional example reports a photochemical closure of iV-cyclohexylben-zaldehydeimine (68JA1666). An excellent review covers much of the earlier work on dimerizations of isocyanates (69ACR186). Aromatic isocyanates readily dimerize to uretidinediones (l,3-diazetidine-2,4-diones) when catalyzed by trialkyl phosphites or pyridine presumably by a dipolar intermediate AH = 2.1 to 4.2 kJ mol-1, AS = -251 to -293 JK-1 mol- (Scheme 86) (66JA3582, 76JGU799). 

Making use of the same reaction principle, disubstituted ketenes 66 have been reacted with aldehydes 80 to form p-lactones 81 [100], with diazo-compounds 82 to form 1,2-diazetidin-3-ones 83 [101] and with nitroso-compounds 84 to form 1,2-oxazetidin-3-ones 85 as precursors of a-hydroxy carboxylic acids (Fig. 42) [102],... 

Simple aliphatic imines are often considered as being photounreactive. One of the few reported examples of a 1,3-diazetidine formation concerns an imine of difluoroacetone (4.30)433). 

Disubstituted hydrazines and semicarbazones react with a-haloacyl halides under two-phase catalytic conditions to produce l,2-diazetidin-3-ones (20-85%) [35], whereas (3-haloacyl halides react with hydrazines to form pyrazolin-3-ones (ca. 30%). 

Four-membered heterocycles containing more than one heteroatom Dithietanes, dithietes, diazetidines... 

The carbonyl absorption for l,2-diazetidin-3-one is higher than that of (3 -lactams, 1780-1790 cm versus 1730-1760 cm-1, and indicates less resonance interaction with the... 

The carbonyl band at 1785 cm-1 for N-substituted 4,4-diphenyl-l,2-oxazetidin-3-ones is higher than that of /3-lactams. Here, as with l,2-diazetidin-3-ones, the additional heteroatom reduces amide conjugation (68JOC3619). 

The addition of cis-azobenzenes to ketenimines gives 3-imino-l,2-diazetidines which cleave to give carbodiimides and imines upon thermolysis (Scheme 4) (67JHC155, 72JHC555, 74JHC409). l,2-Diphenyl-l,2-diazetidin-3-one has similarly been reported to fragment to isocyanate and imine (56AG71). 

Carbonyl-substituted isocyanates have been reported to add [2 + 2] to carbodiimides, although in one case the reported 4-imino-l,3-diazetidin-2-one (64AP623) was reassigned an oxadiazine structure (72BCJ1534). It is clear that the initially formed [2 + 2] kinetically favored adducts are thermally unstable and ultimately form more stable [4 + 2] products, oxadiazines (Scheme 13) (79BSF(2)499). 

An interesting ortho semidine-type rearrangement of a l,2-diazetidin-3-one has been reported. However, it is probably not general for other derivatives that are unable to stabilize positive charge (Scheme 20) (63JCS674), and a different course has been reported for l,2,4-triphenyl-l,2-diazetidin-3-one (67AG(E)630). 

While l,3-diazetidine-2,4-diones are well known and readily prepared by dimerization (vide infra), very few closures from ureas are documented. One simple dialkyl derivative stable enough to be isolated is illustrated in Scheme 60. Smaller alkyl groups like isopropyl are much less stable (71JOC3056). 

One example of an a -chloro acid chloride conversion to a diazetidinone has been reported (Scheme 74) (63JCS674). Similarly, oxalyl chloride and di-f-butylhydrazine give 1,2-di-f-butyl-l,2-diazetidine-3,4-dione which is moderately stable in absence of air. The corresponding diisopropyl is much less stable (67JOC2360). 

One patent describes the inhibition of growth of six strains of Mycobacterium tuberculosis by l,3-dicycIohexyl-l,3-diazetidine (78MIP51500) and the corresponding diphenyl derivative shows similar activity (80MIP51500). 

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