1.3.4- Thiadiazoline

The Hurd-Mori synthesis of 1,2,3-thiadiazoles from a-methylene ketones developed in 1955 is, even today, the method of choice for a number of 1,2,3-thia-diazole derivatives. Both the mechanism and the regiochemistry have been extensively studied, but since the isolation of the intermediate by Hurd and Mori (84CHEC-I(6)460), there has been no further work supporting the formation of this intermediate or its conversion into the aromatization product. In 1995 Kobori and coworkers published the isolation of several 1,2,3-thiadiazolin-1-oxides 186, finally demonstrating their participation in the formation of 1,2,3-thiadiazoles. Substituents R and R play an important role in the isolation of 1,2,3-thiadiazolin-1-oxide (95H(41)2413). 

There have been some reports of the use of N-sulfinyl compounds to transfer both a nitrogen and a sulfur atom. An example is the reaction of N-sulfinylcyclohexylamine (59 R = cyclohexyl) with diphenylcyclopropenone in the presence of nickel tetracarbonyl. An isothiazolinone S-oxide (62) was the product.80 Similarly, A-sulfinyl-/>-toluenesulfonamide (59 R = tosyl) and the Wittig reagent triphenylphosphonium phenylbenzoylmethylide give 1,2,3-thiadiazoline (63).8 ... 

A new method for the synthesis of 1,2,3-thiadiazoles has been reported. The method starts with the thioanilide derivative 72, which is converted into the hydrazone 73. Oxidative heterocyclization by treatment with hydrogen peroxide gave exclusively the 1,2,3-thiadiazoline 74 (Scheme 8) <2003S2559>. 

Rising polarity of the solvent favors the production of 1,2,3-thiadiazolines 120 whereas increasing steric demand of the thione assists formation of the 1,3,4-isomer 119. 

The preference for the 1,2,3-thiadiazoline structure in more polar solvents is explained by the higher dipole moment (ca 5 D as compared to ca 2 D) of the transition structure452. Extensive ab initio calculations on the reaction of diazomethane with thioformaldehyde concluded that both regioisomers should be formed via concerted pathways452, but some semiempirical methods (AMI, MNDO-PM3) suggest that the reaction takes place in a stepwise manner. 

The only isolated and characterized fused-ring thiirenes are those resulting from [4 + 2] cycloaddition chemistry as discussed in Section 1.06.6.3. Both photolysis (or thermolysis) of benzo-1,2,3-thiadiazolines and internal halide displacement from 2-halothiophenoxides have previously been reported <83HC(42/l)333, 84CHEC-i(7)i3i> to give dimeric bis-sulfides via initial formation of a fused-ring thiirene. 

Sustmann et al. (1993) applied both semiempirical MNDO-AMl and -PM3 calculations and ab initio RHF and CASSCF calculations on different levels (3-21G 6-31G ). Most interesting are the results on the cyclization mechanism with thioformaldehyde (R = H) The ab initio techniques suggest that both regioisomers should be formed in a concerted way, but with MNDO-AMl and -PM3 a concerted cyclization is predicted only for the 1,3,4-thiadiazoline 6.35. The 1,2,3-thiadiazoline 6.36 should be formed via a planar intermediate of type 6.37 in which the distance between the two C-atoms is calculated to be 327 pm (PM3) or 366 pm (AMI). ... 

C11H13NO5S, 3-Methyl-2,4-dicarbomethoxy-A -cephem, 40B, 348 Cl1H13N3O2S2, 2,4-Dimethy1-5-tosylimino-A -1,2,3-thiadiazoline, 44B, 359... 

Thermolysis of 5-sulfonyliminothiatriazoles 397 proceeds similarly and trapping with phenyl isocyanate gives the 1,2,3-thiadiazolines 398. ... 

The action of diazoalkanes on thiocarbonyl compounds provides a versatile route to thiirans 1,2,3-thiadiazole derivatives, which function as intermediates, are isolable in suitable cases. Thus, diazomethane reacts with thionesters (1) yielding 5-alkoxy-5-methyl-A -l,2,3-thiadiazolines (2) (ca. 60%) together with the next higher homologous thionester (3) (ca. 30%). Aromatic members (2 R = Ar) decompose readily to the alkenes (5). Ethyl thioformate (1 R = H, R = Et) gives rise, by methylation and aromatiza-tion, to (4), and to linear products. Comparable observations involving diazoethane and diazopropane are also on record. The formulation of the products as 1,2,3-thiadiazolines (2) in preference to the possible A -1,3,4-thiadiazoline structures (6) is supported by the results of n.m.r. studies. However, both isomers, (8) (20%) and (9) (45%), are obtained when diazomethane acts on methyl dithioacetate (7) at —70 C (compare also these Reports, Vol. 1. p. 450). ... 

A -l,3,4-Thiadiazolines.—The cycloaddition of aromatic sulphines to nitril imines is a regiospecific non-stereospecific reaction resulting in the formation of A -l,3,4-thiadiazoline derivatives. Interaction of the sulphines (137) and diphenylnitrilimine [generated in situ by the action of triethylamine on N-a-chlorobenzylidene-N -phenylhydrazine (138) in boiling benzene] gave uniform 1 1 adducts that were identified as the A -l,3,4-thiadiazoline S-oxides (139), the alternative 1,2,3-thiadiazoline structure (141) being conclusively eliminated on the basis of chemical and spectroscopic evidence. The non-stereo specific nature of the reaction was demonstrated and its significance discussed. ... 

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

A/-Chloroamidines are usehil for preparation of biocidal imidazoles (106) and thiadiazolines (107). Ai-Chloroguanidines, RNHC(=NC1)NHR, serve as starting materials for synthesis of imidazoles, oxadiazoles, and thiadiazoles (108,109). 

Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

A -1,3,4-Thiadiazoline-2-thione, 5-mercapto-3-phenyl-— see Bismuthiol II Thiadiazoline-5-thiones tautomerism, 6, 552... 

Early IR- and UV-spectroscopic studies [76AHC(S1), p. 481] of 5-amino-l,2,4-thiadiazolin-3-one and 5-amino-l,3,4-thiadiazolin-2-one indicate structures 236 and 237, respectively. 

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