Imidazo thiazole

The substituted imidazo-thiazole, dexamisole, has antidepressant properties and its isomer, levamisole, possesses anthelmintic and immunostimulant properties. Enantiomers of HA-966 (3-amino-l-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects (+)-HA-966 is a selective glycine/A-methyl-o-aspartate receptor antagonist, but (-)-HA-966 is a potent i-butyrolactone-Uke sedative." A comparison of (+) and (-)-3-methoxycypro-heptadine shows that aU of the anticholinergic activity of the ( )-3-methoxycyproheptadine resides solely in the dextrorotatory enantiomer, while the antiserotonin activity resides in the levorotatory enantiomer." ... 

Imidazo[2,l-6]thiazole, 3-aryl-5,6-dihydro-biological activity, 6, 1024 Imidazo[2,l-6]thiazole, 5,6-bis(4-... 

Imidazo[2,l-6]thiazole, 2-phenyl-azo dyes from, 1, 325-326 Imidazo[2,l-6]thiazole, 2,3,5,6-tetrahydro-synthesis, 6, 993 Imidazo[2,l-6]thiazole,... 

H-Imidazo[4,5-d]thiazole, 4,6-dihydro-2,4,6-triphenyl-synthesis, 6, 990 Imidazothiazoles structure 6 977... 

Imidazo[ 1,2-e]thiazoles biological activity, 6, 1024 reactions, 6, 1041 synthesis, 6, 1048 Imidazo[2, l-6]thiazoles electrophilic substitution, 6, 979 synthesis, 6, 992, 993, 1010, 1018 Imidazo[3,l-6]thiazoles synthesis, 6, 986 Imidazo[5,l-6]thi azoles biological activity, 6, 1024 synthesis, 6, 1017 Imidazo[2,l-6]thiazolium chloride synthesis, 6, 1013... 

Treatment of 6-(2 -furanyl)imidazo[2,l-b]thiazole (65) with bromine in chloroform gave rise to products of bromination of both furan and imidazole moieties (80MI1). In the unsubstituted imidazothiazole, bromination in dimethylformamide at 80°C, or in dichloromethane at 0°C, occurred in the 5-position. Even when there are such reactive groups as 2 -furanyl or... 

A ,A"-/i/. s,(dimcthylaminomcthylenc)thiourea (prepared by double condensation of AAY-dimethylformamide dimethyl acetal with thiourea) has been reacted with a-haloketones or acrylic dienophiles to give thiazolic and thiazinic diazadienes, respectively. These undergo cyclization reactions to yield imidazo[2,1-/ ][1,3] thiazoles, 5H-1,3-thiazolo[3,2-a]pyrimidines, 72/-imidazo[2,1 -/ ][ 1,3]thiazines and 2//,6//-pyrimido[2,l -/)][1,3]thiazines without any regioisomeric ambiguity (Scheme 61).144,145... 

The chlorodifluoromethylated ketone 130 proved to be a valuable substrate for promoting SrnI subtitution reaction with sodium phenylthiolate and to generate a new a-(phenylthio)-a,a-difluoroacetophenone derivative 131 (Equation 57) <2001TL3459>. Upon treatment with nitronate anions under classical SrnI reaction conditions or MW irradiation, 6-chloromethyl-5-nitro-imidazo[2,l- ]thiazole 132 yielded 5-nitroimidazothiazoles bearing a trisubstituted ethylenic double bond at the 6-position (Equation 58) <2001SC1257>. 

An access to iV-substituted 4,6-dioxo-imidazo[3,4-c]thiazoles 185 was developed considering first the reaction of 2-chloroethylisocyanate with methyl thiazolidine 4-carboxylate 183 that generated the ureide 184. Cyclization of the imidazole ring occurred in acidic medium via an addition-elimination mechanism and delivered the imidazothiazole 185 (Equation 81) <2001MI1117>. 

Diazadienes have been used in organic synthesis for the preparation of various heterocyclic compounds. Alkylation of 1,3-diazadienes 207 and the benz-fused analog 210 at the nitrogen atom by aryl acyl bromides provided the iV-alkyl amidinium bromides 208 and 211, which underwent annulation to the 2,3-dihydro-imidazo[2,l-A]thiazole 209 and imidazo[2,l- ]benzothiazoles 212, respectively (Equations 92 and 93) <2001S741, 2002J(P1)741>. 

Acetic anhydride-promoted ring-closure reaction of 2-phenylimino-thiazoles 259 and 2-amino-benzoimidazolium salts 261 give the corresponding imidazo[2,l+]thiazolium 260 and imidazo[l,2- ]benzimidazole 262 compounds (Equations 114 and 115) <1997CHE728, 1999PCJ361 >. A similar cyclocondensation was reported for the elaboration of pyrazolo [l,5- ]benzimidazoles <2004RJ0221>. 

With a-hydroxy ketones and their related tosyloxy derivatives. The imidazo [2,T ]thiazole 364 was prepared by acetic acid-catalyzed cyclocondensation of 2-hydroxy-l,2-diphenyl-ethanone with thiophenyl-substituted 2-aminothiazole 363 (Equation 163) <2002MI110>. Under MW irradiation and in the presence of montmorillonite K-10 clay, a mixture of a-tosyloxyketones 365 and 2-imidazolidinethione led to the substituted 5,6-dihydro-imidazo[2,l- ]thiazoles 366 (Equation 164) <1998J(P1)4093>. When using a-tosyloxyacetophenone, prepared by reaction of acetophenone with [hydroxyl(tosyloxy)iodo]benzene (HTIB), 5-aminopyrazole 367 could be converted to imidazo[l,2- ]pyrazole 368 in basic medium (Equation 165) <2005JHC209>. 

With a-A3-iodanyl ketone precursors. Exposure of (2-acetoxyvinyl)phenyl-A3-iodanes 369 to 2-imidazolidinethione and triethylamine in methanol produced the bridgehead heterocycle 370 of type 5,6-dihydro-imidazo[2,l-3]thiazoles (Equation 166) <2003JOC7887>. 

With a-trifluoromethyl oxiranes. cr-Opening oxirane ring of the 2-benzenesulfonyl-2-trifluoromethyl-oxirane 374 by nucleophilic attack with 2-aminothiazole followed by Mannich cyclocondensation of the intermediate trifluoroketone gave the 6-trifluoromethyl-imidazo[2,l-A]thiazole 375 (Equation 168) <1995JFC83>. The same transformation was conducted with 2-isopropoxy-2-trifluoromethyl-3-phenyloxirane 376 and 2-imidazolidinethione and furnished the 2,3,5,6-tetrahydro-imidazo[2,l-A]thiazole 377 in good yield (Equation 169) <1999RJ0741>. 

With ketones. The 17/-imidazole-2(377)-thione 378 and 2-mercaptobenzoimidazole 380 reacted separately with cycloheptanone to form the tetrahydro-imidazo[2,l- ]thiazole 379 and the dihydro-thiazolo[3,2-tf]benzimidazole 381, respectively (Equations 170 and 171) <2000JHC943, 2001RJ0564>. 

Some work was carried out to investigate the reaction of 1,2-diaza-l,3-butadienes 409 with 2-imidazolidinethione in methanol at room temperature. 5,6-Dihydro-imidazo[2,l-3]thiazol-3-ones 410 were formed in 27-62% yield (Equation 186) <1999T13423>. 

With a.-bromo Michael acceptors. Condensation reaction of 2-aminothiazoline with a-bromo-a,/3-unsaturated compounds, commercially available or generated in situ, provided a route to functionalized 2,3,5,6-tetrahydro-imidazo[2,l-3]thiazoles 411 (Equation 187) <1994H(38)2593>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

Under basic conditions, A -acridinylmethyl-substituted thiourea 449 placed in the presence of bromoacetonitrile gave rise to the unexpected formation of the spiro[dihydro-acridine-9(10//),2 -(2, 7 -dihydro-3 //-imidazo[l,2-c]thiazol-5 -ylidene-/>-nitrophenyl)amine] 450 in 67% yield. The reaction involved displacement of the bromine atom of... 

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