Imidazo thiadiazole

With diethyl oxalate the diamide (150) is produced which easily cyclizes to the imidazo-thiadiazole (151) (81ZC185). 

In a more recent example of a type B synthesis, the imidazolium-O-sulfate salt 81 reacts with CS2 to afford the imidazo[2,l-f][l,2,4]thiadiazole 82 (Equation 22) <2003JOC4791>. 

SN/N Imidazo[2,l- ][l,3,4]thiadiazole 135 <2004S1067> (Figure 20), 136 and 137 (Table 44) <2004BMC5651> 6-aryl-2-aryloxymethylimidazo[2,l- ][l,3,4]thiadiazoles 120 (Table 45) <2005SC2881> NN/N 4-methyl-3-phenyl-2-phenylcarbamoyloxy-37/,47/-imidazo[l,2- ][l,2,4]triazole-3a-carboxylic acid ethyl ester 125 and 4,3a-dimethyl-3-phenyl-2-phenylcarbamoyloxy-37/,4/7-imidazo[l,2- ][l,2,4]triazole-6-carboxylic acid methyl ester 126 (Table 46) <2001JOC8528>. 

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>. 

Mannich reaction of 2-cyloalkyl(heteroaryl)-6-aryl-imidazo[2,l-A][l,3,4]thiadiazoles 161 with formaldehyde in the presence of cyclic bases (piperidine and pyrrolidine), in methanol with a catalytic amount of acetic acid, gives the corresponding C-alkylated derivatives 172 (Equation 8) <2006BMC3069>. 

When compound 241 is refluxed with hydrazine hydrate, 2,6-dimethyl-imidazo[2,l- ][l,3,4]thiadiazole-5-carbohy-drazide 242 was isolated. This product, after reaction with the appropriate aldehydes, yields the corresponding... 

Condensation of 3-amino-5-(l,2,3,4-tetrahydrocarbazol-9-ylmethyl)-l,3,4-thiadizole with chloroacetic acid affords compound 339 that on treatment with phosphoryl chloride cyclizes to 2-( 1,2,3,4-tetrahy drocarbazol-9-ylmethyl)-imidazo[2,l- ][l,3,4]thiadiazole-5-(67/)-one 340 (Equation 62) < 1998IJH231 >. 

When solutions of iminophosphorane 366 in anhydrous DMF are treated with an aromatic isocyanate at room temperature, 2-arylamino-imidazo[2,TA][l,3,4]thiadiazol-5(67/)-ones 135 are isolated (Equation 70) <2004S1067>. 

Substituted (ethyl, -propyl, benzyl), cyclohexyl, 2-furyl, and 2-thienyl) 2-amino-l,3,4-thiadiazoles 451 react with a-bromoarylketones to give imidazo[2,l- ][l,3,4]thiadiazoles 161 in good yields (Equation 103) (Table 59) <2006BMC3069, 2006TL2811>. 

The reaction of 2-amino-l,3,4-thiadiazole 470 and 3-amino-l,2,4-triazole 472 with benzaldehyde and fe/V-butylisoni-trile gives imidazo[2,l-A [l,3,4]thiadiazoles 471 and imidazo[l,2- ][l,2,4]triazoles 473, respectively, in a one-pot process (Equation 110) <1998AG(E)2234>. 

The molluscicidal activity of imidazo[2,l-/][l,3,4]thiadiazoles and imidazo[2,l-/][l,3,4]oxadiazoles, such as compounds 112 and 109 (Figure 25), have been evaluated against the snail Lymnaea acumiata, which is a vector of the giant liver flukes, Fasciola gigantica and Fasciola hepatica <2004IJC(B)901>. 

Imidazo[2,l-/][[l,3,4]thiadiazoles 161 (Figure 33), containing practically planar and rigid heteroaromatic systems with two condensed heterocycles, which have different Tt-conjugation, have been identified as useful fragments for liquid crystal molecules <2002MI6>. 

From the reaction of imidazole 161 and aromatic acid halides (Scheme 63), imidoyl chlorides 162 are obtained, which eliminate methyl chloride to form imidazo[2,l-6]l,3,4]thiadiazoles 163 upon extended heating (88H1935). 

Different mp s have been reported for 2-methyl-6-(4 -nitrophenyl)imidazo[2,l-h] [l,3,4]thiadiazole (241-2°C [52YZ610], 255°C [75G777]). 

The a-halo ketone has also been prepared in situ (NBS, benzoyl peroxide, light) [89IJC(B)500]. Similarly, imidazo[2,l-b][l,3,4]thiadiazoles are accessible from 2-amino-l,3,4-thiadiazoles and acetophenones in the presence of hydroxy(tosyloxy)iodobenzene (HTIB). This latter method has been proposed as more convenient and versatile than the reaction of 2-amino-1,3,4-thiadizoles with a-halo ketones [94IJC(B)686, 94JCR(S)38, 94MI5],... 

In contrast to imidazo[2,l-h][l,3,4]oxadiazoles (see Section III), im-idazo[2,l-h][l,3,4]thiadiazoles form stable salts (hydrohalides, perchlorates, picrates, picronolates). Hydrohalides are often the primary products of the cyclization reaction. 

Because of analytical and spectral data these compounds were formulated as salts 108. As others (e.g., 52YZ610 75G777) succeeded in preparing imidazo[2,l-h][l,3,4]thiadiazoles with H, Me, or Et in position 2 using exactly the same procedure, this discrepancy remains to be clarified. 

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