1.2.5- Thiadiazole, chloromethylation

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

Benzylamino-4-iV-benzyl-5-imino-4,5-dihydro-l,2,4-thiadiazole 5-[(l-Aminoethylidene)amino]-3-chloromethyl-l,2,4-thiadiazole... 

Chloromethyl-substituted 1,2,4-thiadiazoles can be substituted by nucleophiles (see CHEC-II(1996) for more details) <1996CHEC-II(4)307>. 

The hydroxymethyl side chain of 3-(2-benzofuranyl)-5-(hydroxymethyl)[l,2,4]triazolo[3,4-A][l,3,4]thiadiazole-6(5//)-thione 41 can be converted to chloromethyl derivative upon treatment with thionyl chloride amines can displace this chloride to provide the corresponding aminal 43 (Scheme 2) <1992IJB167>. 

A reverse Michael reaction took place when 5-(methoxycarbonylethylthio)-1,2,3-thiadiazole (220) was heated in the presence of DBU in ethanol (79JHC1295). The salt formed (221) was alkylated in situ with ethyl iodide. When 2,5-bis(chloromethyl)selenacyclopentane (222) was treated with... 

Methyl(and phenyl)-5-mercapto-l,2,4-thiadiazoles are converted by chloromethyl thiocyanate to the thiomethyl thiocyanates (RSCH2SCN) and are thence oxidized to the corresponding sulfinyl and sulfonyl thiocyanates with 3-chloroperoxybenzoic acid or hydrogen peroxide.347 3-Alkyl-... 

The non-classical system (182) has been synthesized, starting from 4,5-bis(chloromethyl)-l,2,5-thiadiazole, and characterized by the isolation of its dimer and adducts. The more complex but stable non-classical thiophens (183)—(185) have been prepared, starting from azomethine imine ylides, generated in situ from 1-aminopyridinium, 1-aminoquinolinium, or... 

The Delepine reaction appears to be the most favourable procedure for converting 2-arylamino-5-chloromethyl-l,3,4-thiadiazoles into the corresponding 5-aminomethyl compounds. Thus, treatment of (164) with urotropine produces the hexamethylenetetramino-salts (165) which afford (166) under the influence of ethanolic hydrochloric acid at room tanperature. ... 

Chloracetyl chloride dropped rapidly at 10-30° into isopropyl dithiocarbazate in anhydrous benzene, and refluxed vigorously for 1 hr. with azeotropic water entrainment -> 2-isopropylthio-5-chloromethyl-l,3,4-thiadiazole. Y 77%. F. e. s. K. Riifenacht, Helv. 55, 1979 (1972). 

Chemical Properties.—Alkylation. Treatment of 3,5-diethoxy-l,2,4-thiadiazole (67) with benzyl bromide in boiling acetonitrile ( Hilbert-Johnson reaction ) slowly yields a monoalkylation product (68). Chloromethyl benzyl ether effects the alkylation rapidly in good yield. The use of ribosyl halides should make novel nucleosides accessible. ... 

Thiadiazole, previously thought to be resistant to electrophilic substitution, is in fact as aromatic as thiophen, and undergoes chloromethylation to the bis(chloromethyl)-derivative. This is also obtained as the principal product of the chlorination of 3,4-dimethyl-l,2,5-thiadiazole with JV-chlorosuccinimide. NBS gives comparable results. ... 

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