Thiazetidines synthesis

A stereoselective one-pot synthesis of substituted 1,2-thiazetidine 1,1-dioxides (P-sultams) 55 started from heterocyclic pentafluorophenyl (PFP) sulfonates <06OL5513>. 

A novel synthesis in which diazoketones are thermolyzed with JV-sul-finylamines leads to cyclic S-oxides such as 3,4-dihydro-1,2,3-oxathiazine and 1,2-oxazetidine derivatives. A similar synthesis utilizing diazodiketones yields, via a 4 -f 2 cycloaddition, oxathiazines (165) and, via 2 -F 2 cycliza-tion, thiazetidines (166). When sulfonyldiazoketones were used, thiazetidines 167 were the only isolated products (Eq. 33). 

A sulfonylimine that is formed in situ as a reactive intermediate by interaction of the corresponding aminosulfonyl chloride and triethylamine has proved to be a popular cycloaddition reagent in the synthesis of 1,1-thiazetidines. 

Four-membered ring adducts from 2n + 2n cycloaddition of keten-imines to sulfur dioxide. Isolation of l,2-thiazetidin-3-one 1-oxides. jS-Sultames. Simple method for synthesis of substituted 1,2-thia-zetidin 1,1-dioxide. ... 

Freund and Wolf10 reported that 2,4-diphenyl-l,2,4-thiadiazolidine-3,5-dithione was formed by heating l,3-diphenyl-2-thiourea with thiophosgene in benzene whereas, a 1,3-thiazetidine was produced at lower temperatures in ether (see Section II). Ohande181 has reported that 3,5-diamino-l,2,4-thiadiazoles are formed by the reaction of thiopseudoureas with carbon disulfide in the presence of bromine. Use has also been made of thioureas in the synthesis of 1,3,4-thiadiazolines (79) via reaction with the halohydrazones 78.185,186 The analogous reaction with solenoureas was recently reported by Bulka and Ehlers187 to yield 1,3,4-selenadiazolines. 

The synthesis of 3-alkyl-substituted 1,2-thiazetidine 1,1-dioxides starts by transformation of the amino acids L-Val, L-Leu, L-Ile, and L-Phe into amino alcohols. These ate converted via the bromides to the corresponding thiols 161. Immediate oxidative chlorination affords either sulfonyl chloride hydrochlorides or sulfonic acids 162 which are transformed into the parent /3-sultams 163 <2004HCA90>. Similarly, L-cystine derivatives 164 have also been transformed into the parent /3-sultams 165 by oxidative chlorination followed by cyclization (Scheme 50) C1997LA1261, 2004HCA90>. 

In the synthesis of these compounds, the 2-(l-chloro-2-fluoroethyl)thio compound 200 has been debenzylated and intramolecular cyclization was carried out to afford the 1,3-thiazetidine ring in compound 201 (Scheme 65). The alternative /3-elimination reaction is inhibited because the lone pair of electrons on the sulfur atom of the anion is delocalized on the quinolone ring and so cannot attack the cr-carbonatom of the chlorosulfenyl group <1999CPB1765>. 

Concerning developments in the synthesis of 1,3-thiazetidine derivatives, it was recently shown that cyclothiomethyl-ation of phenyl hydrazine with formaldehyde and hydrogen sulfide in sodium butoxide medium produced A-phenyl(perhydro-l,3-thiazetidin-3-yl)amine in 22% yield <2006RCB1824>. 

A convenient synthesis of benzo[z]-l,2-thiazetidine 1,1-dioxides (1,2-benzosultams) 191 is based on a demethylative intramolecular cyclization of the sulfonic acid 190 (Scheme 116) <1998JOC2348, CHEC-III(2.15.8.2.2)755>. 

Intramolecular cyclization of 2-aminoethanesulfonyl halides gives 1,2-thiazetidine 1,1-dioxides ((3 sultams), as exemplified in the synthesis of 429. ° Treatment of 2-halosulfonylethanoyl halides with ammonia or primary amines yields 1,2-thiazetidin-3-one 1,1-dioxides, which are mixed sulfonic-carboxylic imides 430. A 3-imino derivative has also been obtained. ... 

Substances alleged to be A-aryl-l,3-thiazetidines have mycobacteriostatic and fungistatic properties. 3-Arylsulfonyl-l,3-thiazetidines are claimed to be useful in the synthesis of dye developers in color photography. ... 

Thioketenes, for example, 463, add to imines, carbodiimides, and azines to give 1,3-thiazetidines with exocyclic double bonds, as exemplified by the synthesis of 464. A novel ring contraction of 464a gives 1,3-thiazetidine 464b. 1,3-Thiazetidlnes are postulated as intermediates in the photochemical addition of thiobenzophenone to imines. They fragment to the two possible thiocarbonyl components and imines. ... 

The synthesis and reactions of imino-1,3-thiazetidine-2-ones, 2-thiones, and exomethylene derivatives have been discussed in Sections XXVI and... 

Treatment of A -substituted thioureas with diiodomethane yields 2-imino-l,3-thiazetidines, as exemplified by the synthesis of 477. Ethylene thiourea... 

Because of their structural similarity to the fi-lactams, the solid-phase synthesis of 3-sultams (1,2-thiazetidine-l,1-dioxides) is of relevance. However, in spite of their structural analogy to the fi-lactams, very little is known about the biological activity of P-sultams. Thus far, the P-sultams examined have shown disappointingly weak P-lactamase inhibition activity [49], although by using combinatorial technologies... 

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>. 

Kano, N. Daicho, Y Kawashima, T. A potential intermediate for the aza-Corey-Chaykovsky reaction synthesis, structure, and thermolysis of a pentacoordinate 1,2-thiazetidine 1-oxide. Org. Lett. 2006, 8, 4625. 

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