Azetidin-2-thione

Reaction of /3-lactams with phosphorus pentasulfide affords the corresponding azetidine-2-thiones (c/. Section 5.09.4.3.1) (68JHC433). 

O-Alkylation of the readily available iV-unsubstituted azetidin-2-ones (/3-lactams) constitutes a versatile route to 2-alkoxy-l-azetines (cf. Section 5.09.3.2.3). Thus treatment of the /3-lactams (266) with trialkyloxonium tetrafluoroborates followed by basification affords the 2-alkoxy-l-azetines (267) in moderate yields (67JHC619,69LA(725)124). Similar treatment of the azetidine-2-thiones (268) (available from thiation of the corresponding /3-lactams with phosphorus pentasulfide) affords the analogous 2-ethylthio-1-azetines (269) (67JHC619), which are generally more stable than their 2-alkoxy analogues. 

Powdered crystals of 1, well ground and sandwiched by Pyrex glass plates, were irradiated with 500-W Hg lamp at 0°C for 2h, which led to the exclusive production of optically active j5-thiolactam, l-benzyl-4-phenyl-azetidine-2-thione-3-spiro-T-cyclohexane 2, in 96% yield at 58% conversion. The material was purified by column chromatography, and the structure was determined by spectroscopy. As expected, the thiolactam 2 showed optical activity ([a]o+109° c 1.0 CHCI3, 94% ee). 

Azetidiniminiutn salts have also been converted into azetidine-thiones, -imines or -hydrazones (Scheme 36). Yields of imine derivatives are high when the azetidiniminium salts bear no hydrogen atom at C-3. Otherwise the reaction is best effected by first forming the corresponding 2-azetidinethione which is further treated with an amine in the presence of mercury(II) acetate (Scheme 37). 

A. 1 -(2-Carbethoxyethyl)azetidine. A solution of 150 g. (2.0 mol es) of 3-amino-1-propanol in 500 g. (5.0 moles) of ethyl acrylate (Note 1) is refluxed for 2 hours in a 1-1. round-bottomed flask. Subsequent vacuum stripping of the excess ethyl acrylate at steam temperature furnishes 548 g. (99%) of crude diethyl 3-N-(3-h ydroxypropyl)iminodipropionate. A stirred, cooled solution of this material (548 g.) in 1 1. of chloroform and 10 ml. of dimethjrlformamide is treated dropwise with 262 g. (2.2 moles) of thion yl chloride. By cooling with an ice bath and controlling the addition rate, the reaction temperature is maintained below 40° (Note 2). After the addition is complete, the reaction m i xture is stirred for 30 minutes at room temperature and poured... 

A new reaction of iV-acyl thiazolidinethione enolates with enolizable aldoxime ethers has been reported to give 2-(thiazolidine-2-thione)-l-azetines 608 with excellent diastereoselectivity (Equation 235) <2003JA3690>. The absence of either a methoxy or a carbonyl group in the 1-azetines indicated a complex mechanism rather than a simple addition reaction. The formation of azetines has been rationalized by combination of the oxime and TiCh to give a highly electrophilic trichlorotitanium iminium intermediate 609, which adds onto enolate 610 to form intermediate 611, which cyclizes to azetidines 612 (Scheme 81). An irreversible elimination of bis-trichlorotitanium oxide provides the ultimate driving force to produce azetines. 

Azetidin-2-ones, 3-hydroxy-, conversion into tetramic acids, 57, 167 Azetine-2-thione, 4-dimethylamino-3-... 

A complex hydrolysis-elimination-rearrangement of 2-oxo-azetidin-4-thiones induced by silica (e.g. equation 4.17) is used in the synthesis of thiazolines [92]. 

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