Thiadiazol-3-imines

4-Thiadiazol-2-imines (Anhydro-2-amino-l,3,4-thiadiazolium Hydroxides) (247) 

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The reaction of compound 90 with imidoyl halides without added base gives the hydrochloride salts of 1,2,4-thiadiazol-5-imines 95. The corresponding free bases can be liberated from the salts 95 with weak bases such as bicarbonate, but these imines are labile and decompose readily to form the W-cyanamide 96 and sulfur. The free base can be treated in situ with a second electrophile, such as an acid chloride, imidoyl chloride, or aryldiazonium salt, affording pentalene derivatives 97-99. It should be noted that the compound 98 cannot be prepared in a one-pot procedure from compound 90 and 2 equiv of imidoyl chloride in the presence of base, in contrast to the corresponding dioxa compound 91 (Scheme 22) <1981BSB89, 1992JHC1317>. 

The sulfide groups in mesoionic 1,3,4-thiadiazolium salts are activated toward nucleophilic substitution. The mercapto substituent of the thiadiazolium salt 117 can be displaced by cyclohexylamine to afford the 2//-thiadiazol-imine 118 (Equation 37) <2004BML4607>. 

Scheme 41 A Reaction mechanism for the generation of fused dihydro-1,2,4-thiadiazol-imines 209, B Some dihydro-1,2,4-thiadiazolimines (210-213) that have been synthesized from an appropriate cyano-substituted azide and an acyl isothiocyanate [ 144]...

The synthesis of meso-ionic 1,3,4-thiadiazole-imines described by Grashey et al. (see Vol. 3, p. 698) has been independently described by a Russian group of workers. The conversion of meso-ionic 4,5-diphenyl-l,3,4-thiadiazole-2-thiones into meso-ionic l,2,4-triazole-3-thiones under the influence of amines has also been further exemplified. ... 

The action of carbon disulphide on substituted amidrazones (180) fu-nishes the meso-ionic l,3,4-thiadiazole-2-thiones (181) nearly quantitatively. Substituted thioacylhydrazides (182) react with acyl or arylsulphonyl isothiocyanates, yielding stable crystalline meso-ionic 1,3,4-thiadiazole-imines (184), also formed by the deprotonation of (185)." ... 

This method has been extended to include arylhydrazono thioacetamides, such as 75, which undergo oxidative cyclization using bromine to afford 2-aryl-1,2,3-thiadiazol-5(277)imines 76 (Equation 23) <2004RJ0818>. 

Heating of a solution of 5-ethyl-3-phenyl-l,3,4-thiadiazol-2(377)-imine 85 in aq. NaOH to 80°C for 5h gave the 5-ethyl-2,3-dihydro-2-phenyl-l/7-l,2,4-triazole-3-thione 86 via Dimroth rearrangement (Scheme 7) <2002HCA1883>. Nucleophilic attack of the hydroxide on the electrophilic C-5 resulted in ring opening and, after rotation around the C(2)-N(3) bond and subsequent recyclization, triazole thione 86 formed. 

Thiadiazolin-2-imines can also be converted to thiadiazolin-2-ones in two steps <2004PS601, 2003HAC421, 2003PS1101>. The nitrosation of the thiadiazol-2-imines 87 with saturated nitrite in acetic acid at 0-5°C gave the iV-nitroso-l,3,4-thiadiazol-2(37/)imines 88 in 72% yield. Thermolysis of the latter in refluxing xylene gave the 1,3,4-thiadiazolin-2-one 89 in 78% yield (Scheme 8) <2003HAC421>. 

The reaction of imines with thiohydrazides gives 1,3,4-thiadiazole via a thioacylimidohydrazine intermediate. The imidoyl chloride 148 when treated with the IV-phenyl thiosemicarbazide 149 gave the 1,3,4-thiadiazole hydrochloride 150 (Equation 53) <2002MI1241>. 

Bakulev et al. reported the synthesis of 5//-[l,2,3]triazolo[5,l-i>] [l,3,4]thiadiazines starting from 5-N-nitrosylamino-l,2,3-thiadiazole 68. Reduction of 68 with SnCh and 1A/HC1 and then subsequent reaction with a ketone gave the imine 69. Treatment of 69 with thionyl chloride at -80 °C led to the formation of the isolable triazolothiazine 70 which on further reaction with thionyl chloride at room temperature gave the corresponding chloro derivative 71 <00MC19>. 

Two other results should be reviewed here, too. The substituted thiadiazolo[3,2-trifluoromethyl groups) was described by Sokolov and Aksinenko <2003IZV2053> 2-amino-5-methyl[l,3,4]thiadiazole 165 was heated with iV-ethoxycarbonyl-bis-trifluoroacetone imine in DMF in the presence of />-toluenesulfonic acid to yield the cyclized product 166 in good yield (77%). 

An overall strategy for the synthesis of 1,2,5-thiadiazoles from the acyclic N-C-C-N grouping and sulfur monochloride was proposed in 1967 (1967JOC2823). The N-C function could vary over oxidation levels of amine, imine, cyanide, oxime and nitroso derivatives. Aliphatic and aromatic compounds having these functionalities in many combinations reacted with sulfur monochloride to form appropriately substituted or fused 1,2,5-thiadiazoles. Based on this model, a large... 

The reaction of tetrasulfur tetranitride with phenylacetylene affords the imine (338), which can be oxidized to the monoxide (339). The monoxide (339) then undergoes facile hydrolysis to 3,5-dibenzoyl-1,2,4-thiadiazole (340) probably, by the mechanism shown in Scheme 75 <89CC1134>. 

Nitriles undergo 1,3-cycloaddition to 5-amino-l,2,4-dithiazoline-5-imines (79) across N=C—S grouping with rupture of the SS bond to give 1,2,4-thiadiazoles (80) regiospecifically. Electron-accepting substituents in (79) decrease the reactivity (Equation (4)) <85CB324i>. 

The A-acetyl derivatives of the 2-alkylthio-l,3-thiadiazol-4-imines (124, R = SR, R = Ac) undergo nucleophilic displacement reaction with amines (benzylamine, cyclohexylamine, morpholine, or aniline) giving the 2-amino derivatives (124, R = NRj, R = Ac). The salt (126, R = R = Ph, R = R = H, X = Cl) reacts with aniline at room temperature giving 4-anilino-2-phenyl-l,3-thiazole (128), presumably by a mechanism involving cleavage of the heterocyclic ring. ... 

A second type of synthetic route to meso-ionic l,3,4-thiadiazol-2-imines (247) is based on the acid-catalyzed reaction of N-thioacylhydrazines (232) with aryl isothiocyanates (Ar-NCS). " This reaction yields the s ts (248) as precursors of the meso-ionic heterocycles (247). An interesting variant upon this route involves the reaction between IV-thioacylhydrazines (232) and acyl isothiocyanates (RCO-NCS). This leads to the meso-ionic heterocycles 247, R = COzEt, CONMej, COMe, COCMe, COAr, and SOjPh. The investigation of these compounds by X-ray photoelectron spectroscopy is a good example of the application of this physical method for the examination of meso-ionic compounds. 

Thiadiazol-3-imines (Anhydro-3-amino-l,2,4-thiadiazolium Hydroxides) (268)... 

Only one representative of this class has been described. 3-Amino-5-phenyl-l,2,4-thiadiazole (269) and methyl iodide gave the iodide (270) which with silver oxide gave the meso-ionic l,2,4-thiadiazol-3-imine (268, R = Ph, R2 = Me, R = H). ... 

Ph, R = NHj, with phosgene gives a novel bicyclic heterocyclic system which can be represented as a bicyclic meso-ionic l,3,4-thiadiazol-2-one (493) (Section VII,H,1). A similar reaction using A -benzoyl isocyanide dichloride (PhCO.N=(i Cl2) gives the novel meso-ionic 1,3,4-thiadiazol-2-imine (494) (Section VII,H,2). ... 

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

Sowell and co-workers proposed that this may have begun with acid hydrolysis of the imine group to produce hydrazine 188 (Scheme 19), followed by condensation to give the hydrated thienothiadiazole 189. Pummerer-type dehydration then leads to thiadiazole 190. The validity of this proposal, however, has not been investigated. 

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