Imidazo thiadiazole bromination

Highly functionalized imidazo[2,l-A][l,3,4]thiadiazoles 166 react with bromine in acetic acid to give the corresponding monobrominated derivatives 167 (Equation 6) <2003IJC(B)1463, 2001IJC(B)303, 2003IJH33, 2002IJH125>. 

Compound 185 can also be obtained by direct bromination of the corresponding thiazolo[3,2-ft][l,2,4]triazole (Bt2, acetie acid) (91AP49). Bromination at C-5 can also be affected by bromine/NBS in chloroform (72YZ935). Thiocyanation, which was possible in the imidazo[2,l-b]thia-zole and -[l,3,4]thiadiazole series (see Sections VI,B,l,a and VII,B,l) failed (72YZ935). 

Bromination is usually performed with bromine in a suitable solvent, but in a few cases where this is ineffective (e.g., 415197b and 414143b), N-bromosuccinimide has been employed. In the case of 414, bromination was found to be successful only when R1 = Me. Chlorination of 410 has been achieved with sulfuryl chloride (Table III). Thiocyanations have been carried out either with bromine and ammonium thiocyanate307 or bromine and thiourea236,242,414 though the structures of the products (thiocyanates or isothiocyanates) have not been established with certainty. Kano242 showed that imidazo[2,1-6]-1,3,4-thiadiazole 411 undergoes bromination and thiocyanation preferentially at C-5 (position a, Scheme 18) when this position is free. C-5-substituted derivatives are brominated at C-6 (position b), but thiocyanation fails. Electrophilic substitution reactions in 1 //-pyrrolol 1,2-6]-s-triazole have also been studied.289 ... 

The imidazo[l,2-electrophilic substitution, but nitration (and bromination) is reported to give 5-substituted products (77G1). 

Reaction of an amino-substituted heterocyclic thiol such as 84 with acylating agents gives compounds 85, which are cyclized by POCl3 to form the respective imidazo[2,l- ][l,3,4]thiadiazoles 86 (Scheme 51) (for a review see <1998CHE1003>). Bromine oxidation of the cyclic thiourea 87 forms 2,3,5,6-tetrahydroimidazo[l,2- /][l,2,4]thiadia-zol-3-ones 88 (Scheme 52) <1973JPR539>. 

Copper(I) cyanide in dimethylformamide displaces bromine in positions 5 or 6 of disubstituted imidazo[2,l-i][l,3,4]thiadiazoles (56) forming the corresponding heteroaromatic nitriles (Table 18) <83JHC1003, 88ZOR199). 

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