Imidazole 4-methylthio

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). 

CN ( ()-l-[2-(Methylthio)-l-[2-(pentyloxy)phenyl]ethenyl]-l//-imidazole monohydrochloride... 

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). 

Imidazole units have been substituted on poly(vinyl alcohol) chains to the extent of 19-51% as shown in Equation 14 (54). This reaction was run 1-5 days as a 1% solution in DMF at 85°C. Using the sequence of reactions outlined in Equation 15, 6-methylthio-purine units have been placed on the poly(vinyl alcohol) backbone (55). These polymers might be useful in treating cancer or leukemia since the parent compound, 6-mercaptopurine, is used in this way. 

There are many heterocyclic molecules in which 1,3,4-thiadiazoles are fused to other ring systems. For example, Molina et al. developed a procedure for building a thiadiazole ring on to a properly substituted imidazole moiety (Scheme 29). Reaction of l-amino-2-methylthio-4-phenylimidazole (161) with triphenylphosphine dibromide in dry benzene furnished the 2-methylthio-4-phenyl-l-triphenylphosphoranylidenamino imidazole (162) in a 95% yield. With aroyl chlorides at elevated temperature, this gave the 2-aryl-6-phenylimidazo[2,l-Z ][l,3,4]thiadiazoles (164) in yields between 50% and 70% via the imidoyl chloride intermediate (163) which could be isolated and shown to cyclize to the thiadiazole. The method developed for the imidazole ring was also applicable to the thiadiazolotriazine ring system <88H(27)1935). 

Quinazoline alkylthio derivatives are frequently made by S-alkylation of the corresponding quinazolinethiones. The conditions required are very mild, and S-alkylation can be performed in the presence of other groups capable of undergoing alkylation. For example, 777-imidazo[4,5-, ]quinazoline-6(777)-thione 209 was converted to the 4-methylthio derivative 210 at room temperature, without any alkylation of the nitrogen atoms of the imidazole ring <1996JME918>. 

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. 

An 1-Benzyl-2,4,5-tribrom-imidazol gelingt mit zwei Aquivalenten Butyl-lithium und Dime-thyldisulfan in einem Schritt ein Austausch der beiden Brom-Atome in 2- und 5-Stellung zu ]-Benzyl-2,5-bis-[methylthio]-4-brom-imidazol (72%). 

Aus l-Benzyl-2,4,5-tribrom-irnidazol erhalt man in einer Eintopfsynthese durch Umsetzung mit zunachst zwei Aquivalenten Butyl-lithium und Dimethyldisulfan und anschlieBender noch-maliger Umsetzung mit je einem Aquivalent dieser Reagentien 1-Benzyl-2,4,5-tris-[methylthio]-imidazol (67%)1040 ... 

Dimethyl-2-(2-methoxy-4-methylthio-phenyl)-6-oxo-1,5,6,7-te trahydro-(pyrrolo[2,3-J]benz-imidazol> 81% Schmp. 293-295°... 

Knoth et al. [48] studied the electrochemical behavior of omeprazole with the aid of the direct-current and differential-pulse polarography. Omeprazole was determined in Britton-Robinson buffers pH 7-9 up to a concentration of 10 5 M. The mechanism of the reduction process on the dropping mercury electrode is elucidated. With the consumption of two electrons and two protons, omeprazole will be reduced to 5-methoxy-2-[(3,5-dimethyl-4-methoxypyridin-2-yl)methylthio]-lH-benzimidazole which will be cleaved with the uptake of two further electrons and two protons into 4-methoxy-2,3,5-trimethyl pyridine and 2-mercapto-5-methoxybenz imidazole. 

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]. 

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