Methyl-2- Methylthio Imidazole

Aus Methylamino-essigsaure-ethylester (Sarkosin-ethylester) bzw. 2-Methylamino-l-oxo-l-phenyl-ethan werden mit Dithiocarbonsaure-cyanimid-dimethylester 4-Amino-5-methoxycar-bonyl-l-methyl-2-methylthio-imidazol bzw. 4-Amino-5-benzoyl-l-methyl-2-methylthio-imidazol hergestellt303. 

Zur Losung von 30 mg (0,011 mmol) 4-Brom-5-methoxycarbonyl-l-methyl-2-methylthio-imidazol in 5 ml Tetrahydrofuran gibt man bei 0° 10 mg feuchtes Raney-Nickel (W-2). Dann ruhrt man 30 min. bei 20°, filtriert das Nickelsulfid ab und dampft zur Trockcne ein Ausbeute 24 mg (93%) Schmp. 91 94°. 

Mit Trifluormethansulfenylchlorid konnen auch Trifluormethylthio-Reste direkt am C-Atom des Imidazol-Rings eingefuhrt werden637 639. Auf diese Weise wird bei — 10° aus 1-Methyl-2-methylthio-imidazol in 42% Ausbeute l-Methyl-2-methylthin-4-triflunrmethylthio-imidazol erhalten637. 

Condensation of 1,2-dimethylimidazole <32LA(498)l) or l-methyl-2-(methylthio)imidazole (316) (74HCA750) gave a dihydroimidazo[l,2-a]pyridine (317), which in the case of the methylthio compound rearranged to (318), and the latter compound could be desulfurized. 

A real example of the effects of polymorphism on the Raman spectra is demonstrated by the polymorphs of A-cyano-IVM 1-[5-methyl-1H-imidazol-4-yl)methylthio]ethyl -guanidine, which is referred to as Cimetidine. 

Internal standard N-cyano-N - 2-[(5-methyl-lH-imidazol-4-yl)-methylthio]ethyl -S-me-thyl-isothourea... 

CloHisNeS H2O, 2-Cyano-1-methyl-3- 2-[(5-methyl-1H-imidazol-4-yl)-methylthio]ethyl guanidine monohydrate, 46B, 205 C1oH1sNgS, N -Cyano-N-methyl-N -(2-((5-methyl-1H-imidazol-4-yl)-methylthio)ethyl)guanidine, 44B, 192... 

Imidazole, 1 -cyano-4-methyl-2-methylthio-synthesis, 5, 494 Imidazole, 4-cyano-2-phenyl-synthesis, 5, 494... 

To a solution of methyl 3-oxobutanoate 127 (580 mg, 5 mmol) and l-methyl-2-methylthio-l//-imidazole-5-carboxaldehye 128 (390 mg, 2.5 mmol) in 5 mL of absolute methanol was added a solution of ammonium hydroxide (25%, 0.4 mL). The reaction was heated at reflux overnight before cooling to room temperature and removing the solvent. The crude product was purified by preparative TLC to afford 526 mg of dimethyl l,4-dihydro-2,6-dimethyl-4-(l-methyl-2-methylthio-5-imidazolyl)-3,5-pyridine-dicarboxylate 129 (60%) as a solid, mp = 200-201 °C (MeOH). 

A mixture of l-methyl-2-methylthio-4,5-dihydro-l //-imidazole and diethyl malonate was heated for 54 hr to give diethyl (1 -methyl-2-imidazolidi-nylidene)malonate (471, R = H, R1 = Et) in 56% yield (86CB2208). 

Several novel IOji bicyclic imidazoles (63 or 65), obtained from polysubstituted imidazoles, were reported during this period. The first synthesis of an imidazo[4 ,5 4,5]thieno[3,2-d]pyri-midine commences with l-benzyl-2-(methylthio)-4-bromo-5-cyanoimidazole (62) [95TL12807]. Sequential metallation, sulfurization, S-alkyiation, and Thorpe cyclization of 62 afforded the thienoimidazole intermediate 63. Precursor 62 was obtained from 1 -benzyl-2,4,5-tribromoimida-zole in a series of metallation-electrophile trapping protocols. Nitroimidazo[l,5-a]imidazoles (65) were readily obtained from l-(acylmethyl)-2-methyl-4-nitro-5-bromoimidazoles (64) by sequential amination and cyclization [94KGS490]. 

Chloro-4,5-diaminopyridazine, when treated with sodium methylmer-captide, did not afford the anticipated 3-methylthio derivative, but rather, a mixture of imidazo[4,5-pyridazine derivatives. The extra carbon atom needed for the formation of the imidazole ring originated from DMF, which was used as solvent (81JHC303). In an alternative approach, 4,5-diamino-3(2//)-pyridazinethione was treated with methyl iodide, but in this case, 4,5-diamino-l-methyl-3-(methylthio)pyridazinium iodide was formed. The required 3-methylthio compound was obtained only when an exact amount of methyl iodide was used (81JOC2467). 

Diphenylamino- 874 2-(l,2-Diphenyl-ethcnyl)- 969, 934 2-(2,2-Diphenyl-ethenyl)- 986 2,4-Diphenyl-1 -ethcnyl-5-(4-oxo-butyl)- 994 2-(1,2-Diphenyl-ethyl)- 960, 969 2-(2,2-Diphenyl-l-fluor-ethenyl)- 986 2-(l, 2-Diphenyl-2-hydroxy-ethyl)- 994 2-[Diphenyl-(l H-imidazol-1 -yl)-methyl]- 991 2-(l, 2-Diphenyl-2-methylthio-ethyl)- 934 2-(2,3-Diphenyl-4-oxo-4-subst.-butyl)- 992 2-(l,3-Diphenyl-ureido)- 965 2-Ethansulfonyl- 979... 

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