2.5- Dihydro-l ,3,4-thiadiazoles

Thermolysis of 2,5-dihydro-l,3,4-thiadiazole 30 in CgDsCl solution at 20-35 °C gave spirothiiranes 43 and 44, O-hydrogen 0,0,A-ortholactone 45, the thio-A-ester 46, and 0,A,A-ortholactone 47 (Scheme 4) <1997HCA1260>. The ratio of these thermolysis products did not significantly vary between 23 and 35 °G. 

The 2,5-dihydro-l,3,4-thiadiazole 79 reacts with a range of acetylenic dipolarophiles to afford the 2,5-dihydrothio-phenes 80 in 25-75% yields (Equation 19) <2002HCA451>. The thermal extrusion of dinitrogen from the thiadia-zole affords a thiocarbonyl ylide, which reacts with the dipolarophiles to form the thiophenes. 

Over the past two decades, important contributions to the chemistry of thiocarbonyl ylides were made by Huisgen et al. (27). By carrying out the reaction of thiobenzophenone with diazomethane at low temperature, formation of 2,5-dihydro-l,3,4-thiadiazole (15) with subsequent elimination of N2 was established as the route to the reactive thiobenzophenone (S)-methylide (16) (17,28). In the absence of intercepting reagents, 16 undergoes electrocyclization to give 17 or head-to-head dimerization to yield 1,4-dithiane 18 (Scheme 5.3). 

In some instances, sterically encumbered 2,5-dihydro-l,3,4-thiadiazoles do not eliminate nitrogen. Instead, cycloreversion leading to the starting materials or a new pair of diazo- and thiocarbonyl compounds was reported. Thus, a crystalline product of type 20, obtained from di(ferf-butyl)diazomethane and 2-benzyl-4,4-dimethyl-l,3-thiazole-5(477)-thione, was found to dissociate in solution to give the starting materials (42). In the case of (ferf-butyl)(trimethylsilyl)thioketone and... 

Acidic compounds of type R—XH, which are able to protonate thiocarbonyl ylides, also undergo 1,3-addition leading to products of S,S-, S,0-, or 5,A-acetal type (Scheme 5.20). Thiophenols and thiols add smoothly to thiocarbonyl ylides generated from 2,5-dihydro-l,3,4-thiadiazoles (36,38,86,98,99). Thiocamphor, which exists in solution in equilibrium with its enethiol form, undergoes a similar reaction with adamantanethione (5)-methylide (52) to give dithioacetal 53 (40) (Scheme 5.21). Formation of analogous products was observed with some thiocarbonyl functionalized NH-heterocycles (100). 

In some cases, aliphatic thiocarbonyl (5)-methylides can be protonated by 2,5-dihydro-l,3,4-thiadiazoles, which are their precursors, to give a thioxonium ion (e.g., 56). Carbanion 57 undergoes a ring opening to thiolate 58, which subsequently combines with 56 to give (5,5)-acetal 59 (40,103) (Scheme 5.22). 

As mentioned previously, 2,5-dihydro-l,3,4-thiadiazoles obtained from aromatic thioketones and diazomethane readily eliminate N2 at -45 °C. (53-Methylides... 

Fragmentation of 2,5-dihydro-l,3,4-thiadiazole derivatives is summarized in Scheme 104. When comparable... 

Reaction of thioketones 317 with an excess of diazomethane 318 gave 2,5-dihydro-l,3,4-thiadiazoles 319. Thermolysis of 319 in refluxing benzene for 2h gave thiocarbonyl 3 -methylides 320, which underwent electro-cyclization to give corresponding thiiranes 321 (Scheme 92) <2005EJ01519>. 

Some interesting spiro jS-lactams (22) are obtained from the reaction of 2-imino-2,5-dihydro-l,3,4-thiadiazoles and ketones. The products presumably arise via a [27t + 27t] cycloaddition followed by elimination of a molecule of nitrogen. 

Kagi et al., 1993). The thiirane 6.44 loses sulfur easily, as found earlier in the similar reaction sequence with 2-diazopropane (6-24). With di( e/ butyl)diazo-methane the spiro compound corresponding to the 2,5-dihydro-l,3,4-thiadiazole 6.39 is sufficiently stable to be analyzed by NMR spectroscopy and by X-ray diffraction (Mlostoh et al., 1994). 

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