L-Methyl-4-methylthio

When thioxo (or thiol) derivatives (as part of a thiourea function incorporated into the heterocyclic system) are present, effective. Y-alkylation is observed. Thus, the 3-heteroaryl-substituted [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazole-6(5//)-thiones 37 dissolved in sodium hydroxide solution react with alkyl halides to afford the corresponding 6-alkylthio derivatives 38 (Equation 4) <1992IJB167>. The mesoionic compounds 39, inner salts of anhydro-7-aryl-l-methyl-3-methylthio-6-sulfonyl-[l,2,4]triazolo[4,3-A [l,2,4]triazolium hydroxides, are methylated with methyl iodide to give the corresponding quaternary salts 40 (Equation 5) <1984TL5427, 1986T2121>. 

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). 

A series of compounds with a 2,1-benzisothiazol-basis were easily available from 2, 1-benzisothiazol-3(2//)-one 180. The treatment of 1-methyl-2, l-benzisothiazol-3 (2//)-one 180 with phosphorus pentasulfide in pyridine gave the 1-methyl 2,1-benz-isothiazol-3(2//)-thione 181 in 28% yield. The preparation of l-methyl-3-methylthio-... 

Pyridazinium iodide, 4,5-diamino- l-methyl-3-(methylthio)-analysis, 3, 2... 

The isolable potassium salts (74) (available from the nucleophilic addition of 4-amino-l-methyl-3-methylthio-l -l,2,4-triazole-5(4//)-thiones (73) to aromatic nitriles in the presence of base) upon acidification with hydrochloric acid cyclize to give 7/7-[l,2,4]triazolo[4,3-fc][l,2,4]triazole-3(2//)-thiones (75) (Scheme 5) <85BCJ735>. 

A(-benzoylamino)-4,5-dihydro-l-methyl-3-methylthio-1 H-[ 1,2,4]triazole-5-thione (91) upon treatment with trifluoracetic anhydride and trifluoromethanesulfonic acid is converted into the [l,2,4]triazolo[3,4-()][l,3,4]thiadiazolium trifluoromethanesulfonate (92) (Equation (21)) <86LA1540>. 

The A -arylidene derivatives (96) of 4-amino-4,5-dihydro-l-methyl-3-methylthio-l/f-[l,2,4]tri-azole-5-thione, when treated with phosphorus pentachloride, are cyclized to give the 3-methylthio[l,2,4]triazolo[3,4-6][l,3,4]thiadiazolium chlorides (97). This conversion is envisaged to involve the initial formation of an iminium salt (98) which by attack of the chloride ion gives the intermediate imidoyl chloride (99) subsequent cyclization by intramolecular nucleophilic attack of the thiocarbonyl sulfur atom turns it into the fused bicyclic product (97) (Scheme 7) <86LA1540>. 

The reaction of 4-amino-l-methyl-3-methylthio-l//-[l,2,4]triazol-5(4/7)-one (143) with aromatic nitriles under basic conditions furnishes 6-aryl-2-methyl-77/-[l,2,4]triazolo[4,3-f)][l,2,4]triazol-3(27f)-ones (144) (Equation (39)) <85BCJ735>. 

Methoxy-4-methyl-3-methylthio I Methyl methylthioacetate, SO2CI2 2 2-Methoxy-5-methylaniline 3 l,8-W.s-(Dimethylammo)naphthalene 81, [14]... 

Quatemization of various pyridazinethiones and pyridazinyl sulfides is dependent on the substituents attached to the pyridazine ring. For example, 3-methylthiopyridazine and 6-methyl-3-methylthiopyridazine react with methyl iodide to form the corresponding 1-methyl-3-methylthio and l,6-dimethyl-3-methylthio derivatives (85). On the other hand, if a larger group, such as methoxy or phenyl, is attached at the 6-position, quaterniza-tion takes place at position 2 to give 6-substituted 2-methyl-3-methylthiopyridazines (86 Scheme 24). 

Indole, l-methyl-2-sulfonamido-tautomerism, 4, 200 Indole, l-methyl-3-sulfonamido-tautomerism, 4, 200 Indole, (methylthio)-synthesis, 4, 368 Indole, 3-(methylthio)-synthesis, 4, 338, 368 Indole, l-methyl-3-vinyl-oxidation, 4, 280 Indole, nitro-rearrangement, 4, 297 Indole, 3-nitro-nitration, 4, 211, 213 reduction, 4, 362 synthesis, 4, 210, 363 Indole, 5-nitro-synthesis, 4, 211, 363 Indole, nitroso-rearrangement, 4, 297 Indole, 1-nitroso-reduction, 4, 362 Indole, 3-nitroso-reduction, 4, 362 Indole, nitrovinyl-... 

Pteridin-2-one, l-methyl-4-(methylthio)-methylation, 3, 299 Pteridin-2-one, 4-methylthio-synthesis, 3, 299... 

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). 

Fig. 4.2 Hydrolytic activity of cauxin on 3-MBCG and proposed metabolic pathways for the conversion of 3-MBG to felinine in the cat kidney. The 3-MBCG (20 mM) was incubated with or without cauxin (1.5 mg/ml) at 38°C for 6 h, and the reaction mixtures were analyzed by thin layer chromatography with ninhydrin staining. y-GTP, y-glutamyl transferase RDP, renal dipeptidase a, 3-mercapto-3-methylbutyl formate b, 3-mercapto-3-methyl-l-butanol c, 3-methyl-3-methylthio-1-butanol and d, 3-methyl-3-(2-methyldisulfanyl)-l-butanol...

Both the inner salts 6 of anhydro 177-[l,2,4]triazolo[4,3-6][l,2,4]triazolium hydroxides and their methylation products 7, when heated above the melting points, suffer loss of sulfur or of methyl iodide and sulfur, respectively, and concomitant ring opening into 1-methyl-3-methylthio-5 (arylcyanamino)[l,2,4]triazoles 8 takes place (Equation 1) <1984TL5427,1986T2121>. 

Alkylation or acylation takes place at the nitrogen in position 1 when l/7-[l,2,4]triazolo[4,3-A][l,2,4]triazole 9 is treated with methyl iodide or acetyl chloride, furnishing compound 10 or 11, respectively <1983S415>. The 7-methyl isomers 13 are obtained after conversion of compounds 9 into the 1-acetyl derivatives 11 followed by methylation with methyl trifluoromethanesulfonate to give the l-acetyl-6-aryl-7-methyl-3-methylthio-17/-[l,2,4]triazolo[4,3-A]-[l,2,4]triazol-7-ium-trifluoromethanesulfonates 12, which upon treatment with aqueous sodium carbonate afford the 7-methyl derivatives 13 <1985BCJ735>. 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

Methyl 2-methyl-3-methylthio-4,6-benzylidene-/S-i>-idoside to methyl 2-methyl-3-de8Oxy-4,6-benzylidene-0-D-idoside Methyl 3-methylthio-5-L-xyloside to methyl 3-desoxy-/J-o-xyloside Ethyl thiol-D-ribonate tetraacetate to aldehydo-D-ribose tetraacetate Methyl thiol-D-gluconate pentaacetate to D-glucitol hexaacetate Ethyl tetraacetyl-0-D-glucopyranosyl xanthate to 1,5-anhydro-D-glucitol tetraacetate... 

The pyrido[3,4- pyridazine 40 was also reacted with l-methyl-2-methylthio-2-pyrroline, at room temperature within 30 min, to give the two isomeric pyrroline-annulated isoquinolines 49 and 50, in an overall yield of 65% with ratio 1 2.3, via elimination of nitrogen and methanethiol from the initially formed cycloadducts <1994H(38)1845>. 

III 5-Chlor-6-(2,3-dichlor-phenoxy)-l-methyl-2-methylthio-... 8% Schmp. 132-134°... 

Heating sulfur ylide 236 in 10% hydrochloric acid at 80°C for 13 h yielded 4-methyl-3-methylthio-2//-pyrimido[2,l-a]isoquinolin-2-one (156) (80YZ1261). 

In 2-methyl-3-methylthio-5,6-diphenyl-2,5-dihydro-l,2,4-triazine (19) the heterocyclic ring is folded at N-2 and C-5 to take a boat form with a dihedral angle between the two planes of 146.5°. The 6-phenyl ring is parallel to the plane to which it is attached, while the 3-methylthio group lies in the other plane. 

T = 0.0004 jUg L ) and 3-mercapto-2-pentanone. The methylfuran moiety of 2-methyl-3-(methylthio)furan also originates in the ribose, but the methylthio carbon comes partly from ribose and partly from cysteine. All the carbons of 3-mercapto-... 

Ethan- -S,S-dibutylester E2, 408 Ethan- -S.S-diethylester E2, 408 Ethan- -S-[ l-(2,2-dimethyl-hydra7inocarbonyl)-ethylesterj-O-ethylester E2, 452 Ethan- -S-(ethoxycarbonyl-isopropyloxy-methyl-estem)-0-ethy[ester E2, 452 Ethan- -0-[(ethoxy-methylthio-methylen)-amin-ester)-S-propargylester E2, 457 Ethan- -O-ethylester E2, 452, 453, 455 Ethan- -O-ethylester-S-(2-ethylthio-ethylester) XII/1, 591 E2, 420, 449 Ethan- -S-ethvlester-0-(2-methoxycarbonyl-l-methyl-vinyiester) E2, 456 Ethan- -0-ethylester-S-(4-methyl-3-methylthio-5-oxo-4,5-dihydro-1,2,4-triazolomethylester)... 

---