2- Methylthio-2-thiazoline

The one-step synthesis of further tri- and tetracyclic pteridine derivatives from 2-aminopyrazine 153 has also been described <2001JHC1173>. Cyclic analogues of A -[bis(methylthio)methylene]amino reagents such as 2-(methylthio)-2-thiazoline, 5,6-dihydro-2-(methylthio)-4//-l,3-thiazine, 2-(methylthio)-2-imidazoline, 2-(methylthio)-l,4,5,6-tetrahydro-pyrimidine, 2-(methylthio)-2-pyrazine, and 2-chloropyrimidine reacted with aminopyrazine 153 to afford thiazolo/thia-zino[2,3-3]- 159 ( = 1 (53%), n = 2 (42%)), imidazo/pyrimidino[2,l-/ ]- 160 ( = 1 (53%), = 2 (57%)), pyrazino[2,l-/ ]-161 (21%), and pyrimido[2,l-/ ]-pteridine 162 (42%) derivatives, respectively. 

Reactions between substituted allylic Grignard reagents and cyclic iminothioethers or iminoethers have been tried with 2-methylthio-2-thiazolines or 2-oxazolines. Interestingly, only one addition-elimination reaction is observed [77 Eq. (38)] ... 

A mixture of 2-methylthio-2-thiazoline and ethyl cyanoacetate stirred and heated 7-9 hrs. at 100-120° in the presence of a catalytic amount of ZnClg or triethylene-diamine 2-(carbethoxycyanomethylene)thiazolidine. Y 80%. F. e. s. K. Hirai, H. Matsuda, and Y. Kishida, Chem. Pharm. Bull. 20, 97 (1972). 

The 2-(methylthio)thiazoline (46) reacts with a variety of heteroaromatic aminoesters, for example (47) to give tricyclic hctcro ring systems such as (48). The thiazoline (46) is classed as a cyclic BMMA (iV-[bis(methylthio)methylene]amino) reagent <97M503>. 

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). 

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. 

Thiazoline, 2-methylthio [Thiazole, 4,5-dihydro-2-(methylthio)-], 82 2-Thiazolme, 2-(4-phenyl 1 buten-3-yl)thio-[Thiazole, 4,5-dihydro-2-[ [ l-(phenyl-methyl)-2-propenyl] thio] -], 78 Tluazolium,. V-inethyl-2-methylthio-,... 

Thiazolidine-2-thione, 3-allyl-, 56, 79 2-Thiazohne, 2-allylthio-, 56, 77 2-Thiazoline, 2-benzylthio-, 56, 82 2-Thiazoline, 2-cmnamylthio-, 56, 82 2 Thiazoline, 2 ethylthio, 56, 82 2-Thiazohne 2-mercapto-, 56, 77 2-Thiazoline, 2-methylthio-, 56, 82 2-Thiazohne, 2-(4-phenyl-l-buten-3-yl)-thio-, 56, 78... 

The reaction of azetidine-3-thiol hydrochloride 20 with 2-methylthio-l,3-thiazoline 21 in the presence of a catalytic amount of triphenylphosphine afforded 2-(3-mercaptoazetidin-l-yl)-l,3-thiazoline hydrochloride 22 (Equation 2), which is useful for the pendant moiety of new oral 1/3-methylcarbapenem antibiotic L-084 <2002H(56)433>. 

Alkylthiothiazoles (114) when treated with catalytic amounts of iodine or of 2-methylthio-3-methylthiazolium salts 115 rearrange to the isomeric N-alkvl-A-4-thiazoline-2-thione (116) (Scheme 58). The... 

Methyl iodide, reactions with dialkyl-amino-thiazoles, 32. See also Alkylation 4-Methylthiazole, preparation of, from Na/NH3 reduction of 4-methyl-A-4-thiazoline-2-thione, 397 2-Methylthio-3-methylthiazolium salts, as catalyst for methylthiothiazole rearrangement, 406 Methylvinylketone, reaction of, with... 

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

ALDEHYDES 1,3-Bis(methylthio)alIyI-litl1lum. 2,4-DimethyIthiazole. Ethyl vinyl ether. Methyl methylthlomethyl sulfoxide. 2-Methyl-3-thiazoline. NickcF aluminum alloy. Sodium tetracaibonylfer-rate(-II). 1,1,3,3-Tetramethy Ibutyl isocyanide. 2,4,4,6-Tettamethyl-S,6-dihydro-1,3-(4H)-oxazine. Thallium(III) nitrate. 

These reactions, coupl with the alkylations of sulfides and selenides, allow the homologation of primary alkyl halides - - - and the transformation of allyl halides to homoallyl halides. A related process, employing 2-methylthio- and 2-allylthio-thiazoline, allows the iodomeAylation (ICH2—) and the iodopropenylation (ICH2CH=CH—) of alkyl halides (Scheme 54).i3iii,i32.i7i... 

ALDEHYDES Bis(4-methylpiperazinyl)aluminum hydride. Di(r) -cyclopentadienyl)-(chloro)hydridozitconium(IV). Dihalobis(triphenylphosphine)paIIadium(H). 7,8-Dimethyl-l,5-dihydro-2,4-benzodithiepin. Grignard reagents. Lithium bis(ethylene-dioxyboryOmethide. 3-Methyl-I-phenyl-2-phospholene. 2-Methyl-2-thiazoline. Methylthioacetic acid. 3-Methylthio-l,4-diphenyl-s-triazium iodide. Sodium meth-oxide. Methylthiomethyl N,N-dimethyldithiocarbamate. Sodium tetracarbonylferrate(II). Tetra-n-butylammonium borohydride. Triethylallyloxysilane. N,4,4-Trimethyl-2-oxazolinium iodide. 

The substitution of a halide atom by an iodomethyl or iodopropenyl group can be performed with 2-methylthio- or 2-allylthio-thiazoline-lithium respectively thus extending the chain by 1 or 3 carbon atoms. 

Sulfur-containing heterocyclic compounds are associated with meaty characteristics. Two compounds with the most potent meaty impact include 2-methyl-3-furanthiol (1 ppt) and the corresponding dimer, -(2-methyl-3-furyl) disulflde (0.02 ppt) (18). Both substances have been identified in cooked beef and chicken broth and have a strong meaty quality upon dilution. The disulflde has a recognizable aroma character of rich aged-beef, prime-rib (15). Interestingly, both compounds are produced from the thermal degradation of thiamin (63). A related compound, 2-methyl-3-(methylthio)furan, is the character impact compound for roast beef (18). Other potent modifiers, such as 2-acetyl-2-thiazoline, impart a potent roasty, popcorn note, which enhances the meaty and roast flavor (64). 2-Ethyl-3,5-dimethylpyrazine and 2,3-diethyl-5-methylpyrazine also contribute potent roasty notes to roast beef flavor (65). A summary of character impact compounds for meat and seafood flavors is presented in Table 6. 

Lithium derivatives of 2-substituted A -thiazolines continue to be of interest in synthesis. Thus the organolithium compounds (70 R = H or Ph), prepared by metallation of 2-methylthio- or 2-benzylthio-AMhiazoline, react with aldehydes or ketones R R CO to yield the corresponding carbinols, which are useful because they decompose on being heated, or in the presence of base, to give episulphides (70a) in high yields. A -Thiazolines have been employed to prepare aldehydes, as shown in Scheme 1. A major feature of this process is... 

Meso-ionic Thiazoles.—Successive treatment of 5-acylamino-AMhiazoline-2-thiones (73) with methyl iodide and alkali yields products that have been recognized as meso-ionic 5-acylimino-2-methylthio-thiazoles (75) (see also these Reports, Vol. 2, p. 614). This formulation supersedes the thiazolium salt structure by which certain members of this series have previously been represented. The methylthio-group of (75) is readily replaced on treatment with nucleophilic reagents such as potassium hydrosulphide, di-cyanomethide ion, amines, etc., with formation of 2-substituted 5-acyl-amino-A -thiazolines [e.g. (76)]. ... 

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