1- Methylthio

Methyl-5-2-(methylthio)ethyl, 209 Cyclic Monothio Acetals and Ketals... 

Keywords 5-(2-methylthio-4-methylpyrimidin-5-yl)penta-2,4-diyn-l-ol, polymerization... 

Chemical Name Dihydro-5-(l-methylbutyl)-5-[2-(methylthio)ethyl]-2-thioxo-4,6-(lH,5H)pyrimidinedione monosodium salt... 

O-Trimethylsilyl-5-alkyl, 501 O-Alkyl-5-alkyl or -5-phenyl, 501 O-Methyl-5-2- (methylthio) ethyl, 503... 

Wasser midyl)-methyl -4-meth-yl-5- ( 2-methylthio-ethylj-... -chlorid-Hydrochlorid ... 

Since the 3,5-disubstituted 2-thiohydantoins may be produced in isothiocyanate-containing foods and in the human digestive tract, we evaluated their antimutagenic activities with a Salmonella test using S. typhimurium TA98 [79], The MTBI-derived 2-thiohydantoins, i.e., 3-[4-(methylthio)-3-butenyl]-5-isobutyl-2-thiohydantoin, 3-[4-(methylthio)-3-butenyl]-5-benzyl-2-thiohydantoin, and 3-[4-(methylthio)-3-butenyl]-5-[2-(methylthio)ethyl]-2-thiohydantoin were studied for their antimutagenicity against the food bom-heterocyclic amine, IQ. 

Phosphorothioic acid, 0,0- dimethyl-5-(2- (methylthio)ethyl)ester 500 500... 

A suspension of 0.35 mol of sodium amide in 400 ml of liquid ammonia was prepared in the usual way (e./. Chapter II, Exp. 11) (note 1). To this suspension was added with swirling 0.30 mol of 1-methylthio-l-propyne, in portions of about 10 g, waiting about 10 s after the addition of each portion. Swirling was continued for 1.5 min after the addition of the last portion. Immediately thereafter the... 

A mixture of 0.15 mol of 1-methylthio-1,2-pentadiene (see Chapter IV, Exp. 26), 100 ml of water, 40 ml of methanol (note 1) and 0.18 mol of NalO., was vigorously stirred. The temperature rose gradually, but was kept between 30 and 35°C by occasional cooling. After 1.5 h 500 ml of water were added to the white suspension and ten extractions with 30-ml portions of chloroform were carried out. The extracts were dried (without previous washing) over magnesium sulfate. Evaporation of the solvent in a water-pump vacuum (the last traces at 0.5-1 mmHg) gave the... 

Thioglycosides can be activated for gfycosylation reactions with sulfur electrophiles, e.g., with dimethyl(methylthio)sulfonium triflate or with methanesulfenyi bromide and silver(l +) to form reactive sulfonium intermediates (F. Dasgupta, 1988). 

Gassman and co-workers developed a synthetic route from anilines to indoles and oxindoles which involves [2.3]-sigmatropic rearrangement of anilinosul-fonium ylides. These can be prepared from Ai-chloroanilines and ot-thiomcthyl-ketones or from an aniline and a chlorosulfonium salt[l]. The latter sequence is preferable for anilines with ER substituents. Rearrangement and cyclizalion occurs on treatment of the anilinosulfonium salts with EtjN. The initial cyclization product is a 3-(methylthio)indole and these can be desulfurized with Raney nickel. Use of 2-(methylthio)acetaldehyde generates 2,3-unsubstituled indoles after desulfurization[2]. Treatment of 3-methylthioindoles with tri-fiuoroacetic acid/thiosalieylie acid is a possible alternative to Raney nickel for desulfurization[3]. 

When longer chain a-methylthio substituents or a-methylthiocycloalkanones are used, 3-methylthio-37/-indole intermediates are isolated. These can be converted to 2,3-disiibstitutcd indoles by reduction with LiAlH4[4],... 

The Gassman synthesis has been a particularly useful method for the synthesis of oxindolcs[lb,8]. Use of methylthioacetate esters in the reactions leads to 3-(methylthio)oxindoles which can be desulfurized with Raney nickel. Desulfurization can also be done by reduction with zinc or tin[10,ll]. 

A solution of 2-aminobenzophenone (98 g, 0.50 mol) and methyl 2-(methyl-thio)propanoate (74 g, 0,50 mol) in CH Clj (21) was cooled to —70 C and 95% 7-butyl hypochlorite (56 g, 0.5 mol) was added dropwise at such a rate that the temperature did not rise above — 65 C. One hour after the addition was complete, EtjN was added and the mixture was allowed to come to room temperature. The solution w as mixed with 3 N HCl (800 ml) and stirred for 1 h. The organic layer was separated, dried (Na2S04 ) and filtered. The solution was evaporated in vacuo and the residue triturated with ether. Filtration gave the 3-(methylthio)oxindole intermediate (92 g) in 62% yield. 

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

Chloro-4-(triHuoromethyl)phenoxy)-3- methylthio 1 CI2. Ethyl methylthioacetate 2 4-[2-Chloro-4-(trifluoromethyl)phcnoxyl]aniline 3 Et,N 49, [16]... 

The photochemical rearrangement of the mesolonic thiazole (33) provides an original synthesis of the 4-methylthio-derivatives of the A-4-thia2oline-2-one (34) (Scheme 15) (33). 

COMPARISON OF TYPICAL PHYSICOCHEMICAL PROPERTIES OF A-4-THIAZOLINE-2-THJONE (Ii WITH THOSE OF 2-(METHYLTHIO)THIAZOLE (II) AND 3-METHYL-A-4-TH1AZO-LINE-2-THIONE (UIF... 

Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

A 2-methylthio substituent decreases the basicity of thiazole pK = 2.52) by 0.6 pK unit (269). The usual bathochromic shift associated with this substituent in other heterocycles is also found for the thiazole ring (41 nm) (56). The ring protons of thiazole are shielded by this substituent the NMR spectrum of 2-methylthiothiazole is (internal TMS, solvent acetone) 3.32 (S-Me) 7.3 (C -H) 6.95 (Cj-H) (56, 270). Typical NMR spectra of 2-thioalkylthiazoles are given in Ref. 266. 

The kinetics of the reaction between 2-methylthiothiazoles and methyl iodide show that the nucleophilic center is the ring nitrogen. The 2-methylthio group decreases the nucleophilicity of the this atom (269). 

The methylthio group is removed by treatment with zinc powder in HCl (276) to give the 2-unsubstituted thiazole. The action of aluminum-mercury amalgam in methanol on various thioethers is reported to yield the expected thiazole (108) when Rj is an alkyl group and the corresponding A-4-thiazoline-2-thione (109) when Rj PhCH - (Scheme 55) (169). 

Methylthio- and 2-ethylthio-4-methylthiazoles undergo reductive ring opening when treated by sodium in liquid ammonia (204). The first step of this reaction consists of the formation of the A-4-thiazoline anion (80). The next steps are analogous to those given for 80a to 83. 

The methylthio group in 12 can be replaced with OH. Subsequent deprotonation affords a 2.4-dioxothiazole (5). 

Methylthio-5-aminothiazolium salts (28) are accessible through me-thylation of thiazolethiones (27), which are, in turn, obtained from alkylaminoacetonitriles and carbondisulfide (Scheme 27). 

A large number of variously 2-, 4-, and 5-substituted thiazoles with alkyl, aryl, hydroxy, methylthio, mercapto, halo, and nitro groups have been analyzed by thin-layer chromatography on silica and alumina by the Stahl s technique (167, 170, 172). Among the many systems recommended for the elution of these compounds are the following ... 

Methylthio)cyclopentane Thiirane Cyclopentyl methyl sulfide... 

Substitutive lUPAC name 1 (Methylthio)hexane Functional class name Hexyl methyl sulfide... 

The prefix thioxo- is used for naming =S in a thioketone. Sulfur analogs of acetals are named as alkylthio- or arylthio-. For example, CH3CH(SCH3)OCH3 is l-methoxy-l-(methylthio)ethane. Prefix forms for -carbothioic acids are hydroxy(thiocarbonyl)- when referring to the O-substituted acid and mercapto(carbonyl)- for the S-substituted acid. 

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