1.3- Dimethyl-2-methylthio-iodid

Frejd and co-workers utilized a different tactic for aniline cyclization by first employing a Heck-Jeffery protocol under solvent-free conditions to prepare o-amino dehydrophenylalanine derivatives from o-aminoaryl iodides with the former undergoing a spontaneous la cyclization-elimination sequence to afford 2-methoxycarbonyl indoles <06S1183>. Dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST) was used by the Okuma group to promote the cyclization of o-vinyl-A-p-toluenesulfonylanilide to N-tosylindole <06CL1122>. 

Benzimidazolium 5,6-Dimethyl-2-methylthio- -iodid Elba, 769 (S-Methyl.)... 

Abbreviations Ac acetyl Bn benzyl BSP 1-benzenesulfinyl piperidine BTIB bis(trifluoroacetoxy)iodobenzene DAST (diethylamino)sulfur trifluoride DDQ 2,3-dichloro-5,6-dicyano-/)-benzoquinone DMDO dimethyldioxirane DMTSF dimethyl(methylthio)sulfonium tetrafluoroborate DMTST dimethyl(methylthio)sulfonium triflate DTBMP 2,6-Ai-tert-butyl-4-methylpyridine DTBP 2,6-di-tert-butylpyridine DTBPl 2,6-di-tert-butylpyridinium iodide FDCPT l-fluoro-2,6-dichloropyridinium triflate FTMPT l-fluoro-2,4,6-trimethylpyridinium triflate IDCP iodonium dicollidine perchlorate IDCT idonium dicollidine triflate LPTS 2,6-lutidinium p-toluenesulfonate LTMP lithium tetramethylpiperidide Me methyl MPBT S-(4-methoxyphenyl) benzenethiosulflnate NBS A-bromosuccinimide NIS A-iodosuccinimide NlSac A-iodosaccharin PPTS pyridinium p-toluenesulfonate TBPA tris(4-bromophenyl)ammoniumyl hexachloroantimonate Tf trifluoromethanesulfonyl TMTSB methyl-bis(methylthio)sulfonium hexachloroantimonate TMU tetramethylurea Tr trityl TTBP 2,4,6-tri-tert-butylpyrimidine. 

Related Reagents. Methyl Iodide Methyl Sulfate 1-Benzene-sulfinyl Piperidine Diphenyl Sulfoxide Dimethyl(methylthio) Sulfonium Tetrafluoroborate. 

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). 

Methylation of the 6,7-dimethyl derivative of 133 with methyl iodide in sodium hydroxide or sodium ethoxide gave two S,N-dimethyl derivatives, whereas in sodamide or ammonia, only the 5-methyl derivative was obtained. Methylation with diazomethane gave four methyl derivatives and with methyl chloride two di-jV-methyl and one 5,/V-dimethy] derivative were obtained (80H1139). Methylation of 153, obtained from 152, gave 4-methyl-3-methylthio-triazinoindole 155, whose hydrolysis or oxidation gave 154 (76T1735). On the other hand, methylation of 156 gave methiodide... 

Dimethyl malonate was first treated dropwise with phenyl isothiocyanate in the presence of sodium hydride in N,7V-dimethylacetamide at 0°C. The reaction mixture was stirred at ambient temperature for 1.5 hr and then cooled to 0°C, and methyl iodide was added dropwise. After stirring for 4 hr at room temperature, (methylthio)(phenylamino)methy-lenemalonate (341) was obtained in 79% yields (69T4649). 

Dimethyl malonate was added to a suspension of sodium hydride in THF at room temperature, and after 10 min, 2-methylthio-l-methylquinolinium iodide was added. The reaction mixture was stirred for 1.5 hr at ambient temperature to give dimethyl (1 -methyl-1,2-dihydro-2-quinolinyIidene)ma-lonate in 95% yield [81 H( 15)277]. 

Chloro- and 2-methylthio-l-methylquinolinium iodides were reacted with dimethyl malonate in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in DMF at 80°C for 1 hr, or in the presence of triethylamine for 5 hr, to afford dimethyl (1 -methyl-l,2-dihydro-2-quinolinylidene)malonate (86MI3). The use of DBU and the 2-methylthio derivative gave a better yield than that from triethylamine and the 2-chloro derivative. 

Pyrimido[4,5-d]pyrimidine-4-thiones are also formed by reaction of pyrimido[4,5-d]-pyrimidin-4-ones with phosphorus pentasulfide. Methylation of these thiones with dimethyl sulfate or methyl iodide gives the corresponding methylthio derivatives (60JA5711). 5-Amino-l,3-dimethyl-7-methylthiopyrimido[4,5-d]pyrimidine-2,4(l//,3iy,)-dione (121) undergoes... 

The 4-imino group of 3-cyano-4-imino-2-methylthio-4//-pyrido[ 1,2-a]-pyrimidine was transformed to the 4,4-diamino group with amines and to the 4-methylimino group with methyl iodide in dimethylformamide in the presence of potassium carbonate.268 On the action of dimethyl acetylenedi-carboxylate in dimethylformamide at 150°C, the 1,4-diazacycl [3,3,3] azine (234 R = CH3S) was formed.314... 

Ammonium Dimethyl-[(2-furyl)-methylthio-methylen]- (iodid) E5, 85 (N-Alkylier.)... 

Dimethyl-(a-methylthio-benzyliden)-(iodid) E5, 82 (R CS-NR2 S-Alkylier.), 85 (N-Methylier.) Methyl-(l-methyllhio-ethyliden)-phenyl- (iodid) ES, 83 (R —S —NR2 - S Methylier.)... 

Alkylation of the thioxopurines may lead to both S- and A-alkylation but in many examples the 5-alkyl derivative is probably first formed under mild conditions and then rearranges to the A-substituted derivative under more fordng conditions. An exception appears to be 6-thioxo-l,6-dihydropurine (123) which with dimethyl sulfate in alkaline solution produces the relatively stable 6-methylthiopurine (124) (22LA(426)306). Similar methylation of 6-thiotheobromine in alkali with methyl iodide at room temperature furnishes the methylthio derivative (125) whereas, in contrast, the 6-thiocaffeine derivative (126) is produced with dimethyl sulfate and alkali at 40 °C (62JCS1863) and corresponding 5- and A-methyl derivatives are produced from the 6-thio analogue of theophylline. 

Piperazine-2,5-dione treated with sodium hydride in A,A-dimethylacetamide and carbon disulfide followed by esterification with methyl iodide gave l-methylthio(thio-carbonyl)piperazine-2,5-dione (methyl 2,5-dioxopiperazine-l-dithiocarboxylate) and l,4-bis[methylthio(thiocarbonyl)]piperazine-2,5-dione (107), but when the reaction was carried out in dimethyl sulfoxide containing tetrahydrofuran it afforded (107) plus 3-[bis(methylthio)methylene]-l-methylthio(thiocarbonyl)piperazine-2,5-dione (108) (1630). 

Methylthio-l,2-dithiolium salts are useful intermediates for synthesis and are generally obtained by reaction of methyl iodide or of dimethyl... 

Coupling reactions are observed when treating 2-methylthio-l, 3-dithiolium iodides with zinc. The intermediates 143 are not isolated they spontaneously lose dimethyl disulfide to give TTF derivatives. ... 

In contrast, (chloromercurl)-2V, iV -dimethyl-2-(methylthio)adenine (47) gave only the A -nucleoside (48). However, alkylation of the sodium salt of this purine with ethyl iodide gave a mixture of 7- and 9-isomers. ... 

This synthesis of sulfenyl chlorides can also be used in the aliphatic series although here the limitation applies that most alkylsulfur halides are too unstable to be isolated from solution. In general, and also in the aromatic series, sulfenyl chlorides are easier to prepare than the bromides, whilst the iodides are known only in a few cases and the fluorides not at all. As an example, Schneider,665 chlorinating methanethiol in anhydrous carbon tetrachloride at —15°, obtained dimethyl disulfide dichloride [chloro(methyl)(methylthio)-sulfonium chloride] which passed into methanesulfenyl chloride when allowed to warm slowly to room temperature ... 

---