1.2.3- Thiadiazole lithiation

Chemical Properties of 1,2,5-Thiadiazoles. Lithiation and carbonylation of one methyl of 3,4-dimethyl-1,2,5-thiadiazole were described, followed by subsequent transformation into alcohol, mesylate, and vinyl derivatives. The reaction of 2,5-dicyclohexyl-l,2,5-thiadiazole-3,4-dione with RC6H4-SO2N3 gave the compounds (294 R = 4-MeO or 3-O2N). ... 

Thieno[2,3 -h]selenophenes lithiation, 4, 950 Thienospirans synthesis, 4, 760 Thieno[3,4-c][l,2,5]thiadiazoles cycloaddition reactions, 6, 534 reactions, 6, 1036 synthesis, 6, 1042, 1044 Thieno[2,3-d]thiazole, 2-acylamino-synthesis, 6, 1010 Thieno[2,3-d]thiazoles synthesis, 5, 116 6, 988, 994 Thieno[3,2-d]thiazoles synthesis, 5, 135 6, 1015 Thieno[3,4-d]thiazolidine-2-thione, perhydro-... 

However, lithiation of 5-phenyl-1,2,3-thiadiazole has been achieved using methyllithium, and reaction with a variety of electrophiles has given good yields of 4-substituted derivatives (Scheme 101)(68CJC1057 85S945). 

Different functional groups can be introduced at the 5-position of thieno[2,3- / -l,2,3-thiadiazole-6-carbo-xylates 43a and 43b by lithiation and subsequent reaction with the desired electrophile <1999JPR341>. For example, reaction of carboxylic acid 43a with lithium diisopropylamide (LDA) followed by CI3CCCI3 produced the 5-chloro product 44a while amide 43b treated with -BuLi then dimethylformamide (DMF) gave aldehyde 44b (Equations 4 and 5). 

Lithiation of the methyl derivatives of such five-membered heteroaromatics as pyrrole , thiophene , l,3-thiazole ° , 1,3-oxazole , isoxazole , 1,3,4-thiadiazole , 1,3,4-oxadiazole and imidazole also occurs. For the sulfur heterocyclics, ring metallations and ring opening after lithiation are complications. 

The fragmentation of lithiated isoxazoles 265 opens an access to lithium ynolates (Scheme 1-212). Lithiated 1,2,3-thiadiazoles 266 and 1,2,3-triazoles 267 provide lithium ynethiolates and yneamides by fragmentation (Scheme 1-212). 

Dimerization. The lithio-l,3,4-thiadiazole (120), formed by lithiation at —78 C, is methylated at low temperatures to give the 2-ethyl derivative, but it dimerizes at ambient temperatures to give (121). The open-chain thioimine (119) is isolable... 

---