L,3-Thiazin-2-ones

The [Rh(COD)Cl]2- and Kl-mediated carbonylation of substituted A -alkylisothiazolidines 257 occurs regiospeci-fically at the S-N bond (Equation 23) <2004OL3489>. The most favorable solvent for this ring expansion of the A -alkylisothiazolidines to give tetrahydro-2/7-l,3-thiazin-2-ones 258 is toluene. The yields were dependent on the nature of the aryl group. A range of alternative metal catalysts were also screened, however carbonylation was observed with Co(CO)8, and Pd(OAc)2 only. 

Benzylmercapto-5-methoxycarbonyl-6//-l,3-thiazine (177) slowly hydrates with atmospheric moisture which leads, after elimination of benzyl mercaptan, to the 3,6-dihydro-2//-l,3-thiazine-2-one (178) (Scheme 70)... 

AP833>, and 3-acyl-3,4,5,6-tetrahydro-l,3-thiazine-2-thiones (59) are formed in the same way from the parent 3,4,5,6-tetrahydro-l,3-thiazine-2-thiones (60) (Equation (7)) <84AP74>. Both types of product are unstable and can be used as transacylating agents for amines and thiols. Thiocarbamoyl chlorides also react with 3,4,5,6-tetrahydro-l,3-thiazin-2-ones, but here both N- and (9-thio-carbamoylation can occur <86LA1140>. 

Dihydro-2/f-l,3-thiazin-2-ones and 2-imines can be synthesized in a number of ways. Thus,... 

Cyclization of 3-(3-butynyl)-4-ethoxy-6,6-dimethyl- and 3-(3-alkenyl)-4-ethoxy-6-phenyltetrahydro-l,3-thiazin-2-ones in formic acid at room temperature afforded 3,3-dimethylperhydropyrido[l,2-c][l,3]thiazine-l,6-dione and ci5-3,4a,5,6-//-5-alkyl-7-formyloxy-3-phenylperhydropyrido[l,2-c][l,3]thiazin-l-ones (85T2(X)7). In the latter cases, the reaction proceed via a double chair transition state (180) containing a phenyl ring in an equatorial position. 

Since cystamine is one of the most effective radiation prophylactics known, the preparation and polymerization of S-vinyl-N-vinylthio-carbamates (37) (XXI) was utilized in an attempt to prepare alternating poly(vinylamine-vinylmercaptan)copolymers (Scheme III). The divinyl monomers were prepared by dehydrochlorination of the respective S-2-dhloroethyl-N-2-chloroethylthiocarbamates (XX). Polymerization of these monomers under a variety of conditions yielded terpolymers (XXII) composed of the tetrahydro-l,3-thiazin-2-one moiety as well as poly-S-vinyl and poly-N-vinyl units. Attempts to isolate polymeric a-amino y-thiols (XXIII) formed by hydrolysis of the resultant terpolymers (XXII) proved unsuccessful. 

A molecular mechanics prediction of the conformation of trans-%,9a-V - ,-phenyl-perhydropyrido[2,l-Z)][l,3]thiazin-6-one gave similar data as NMR experiments (00BAP19). 

Cyclocondensation of pyridine-2-thione 100 with cinnamonitriles 101 in the presence of a catalytic amount of NEts afforded 4,6-dihydropyrido[2,l-Z)][l,3]thiazine-6-ones 102 (98MI10, 99MI26). 

Phenyl-l,2,3,6-tetrahydropyrido[2,l- ][l,3]thiazino[3,2- ]quinolin-6-ones were prepared by the reaction of 2-mercapto-5-phenyl-l,4-dihydroquinolin-4-ones with 1,3-dihalopropane <1997JAK97/278780>. 7-Acetyl-2-aryl-9-cyano-6-methyl-8-phenyl-3,4-dihydro-277,877-pyrido[2,l- ][l,3]thiazin-4-ones were obtained from 5-acetyl-3-cyano-6-methyl-4-phenyl-l,2,3,4-tetrahydropyridine-2-thione with 3-aryl-2-propenoyl chloride <2002CHE761>. Reaction... 

Mass spectra of the cis- and /ram-isomers of the pyrimido[2,TA [l,3]thiazin-6-ones 294 and 295 were studied. Retro-Diels-Alder fragmentation of the hydrocarbon ring was of medium to low stereospecificity. A number of highly selective processes were discovered allowing differentiation between stereoisomers <1996RCM721>. The mass spectral fragmentation pattern of 296 was studied in detail <1996PS(113)67>. 

The following syntheses all proceeded regioselectively 4,6-diaryl-3,4-dihydropyrimidine-2-thiones with 3-bromopropionic acid in a Ac20/AcOH system <2001MI407, 2000IJH49>, or with acrylonitrile in pyridine followed by hydrolysis <1996IJB915> resulted 6,8-diaryl-2,3-dihydro+//,6//-pyrirnido[2,l+][l,3]thiazin-4-ones in good yield 4-phenyl-5-carbethoxy-3,4-dihydropyrimidine-2-thiones with benzylidenemalonitrile in a NaOAc/AcOH system... 

Dihydro-4//,8//-pyrimido[2,l-3][l,3]thiazine-7-carboxylic esters and amides exhibited high activity on antiinflammatory and antipyretic tests <1996EJM663>. 8-(Benzoylbenzyloxy) and (benzoylbenzylthio)-7-methyl-3,4-dihydro-2//,6//-pyrimido[2,l-3][l,3]thiazin-6-ones exhibit antitumor activity <1996EPP0733633>. 9-Amino- or 9-methyl-3.4-dihydro-2//,6//-pyrimido[2,l -3, 1,3]thiazin-6-oncs have anticorrosive effect <2003RUP2198245>. 

Alicyclic 2-isocyanato-l-carboxylic acids 214 synthesized from alicyclic trimethylsilyl 2-amino-l-carboxylates 213 were cyclized to the unstable 2-thioxoperhydro-l,3-oxazin-4-ones, which isomerize to the thermodynamically more stable perhydro-l,3-thiazine-2,4-diones 215 (cm, X = CH2 — CH2, CH = CH trans, X = CH2-CH2) (74MI2). 

The reaction of thiourea with acetylenic esters has been variously reported to give a thiazolin-4-one (372), an imidazolinethione (373), or a l,3-thiazin-4-one (374) " derivative. However, recent studies have shown that in fact it is the thiazolin-4-one (372) that is formed in this reaction [Eq. (55)]. In the light of this observation, it may now be necessary to revise the structures of products obtained from the reaction of A -methylthiourea, M -dimethylthiourea, and thiosemicarbazides with acetylenic esters. The reaction of a thiourea derivative such as A(-thiocarbamoylpiperidine with DMAD is reported to give 5-(carbomethoxymethylene)-2-piperidino-A -1,3-thiazolin-4-one (375) [Eq. (56)]. °... 

The thiazin-2,6-diones 49 lose one molecule of COS in boiling dimethylformamide (DMF) to afford l-substituted-6-alkyl uracils 98 (Scheme 2) <2005RJC134,2003TL5279>. The same products are obtained when 5-acyl-4-hydroxy-3,6-dihydro-2//-l,3-thiazine-2,6-diones 61 are heated together with the corresponding primary amine in hoiling DMF. The dimeric compound 99 and the nitrophenyl hydroxylated example 100 are produced by the same route <2005RJC134>. 

When the 5-phenyltetrahydro-l,3-thiazine-2,4-dione 155 is treated with NaBH4, the thiazine ring fragments to produce (3 )-3-mercapto-3-phenylpropan-l-ol in 45% yield and the oxazolidin-2-ones 156 and 157 as a mixture of diastereomers (Equation 11) <2006TL1153>. 

The spiro compound 15 is obtained in excellent yield by the cycloaddition of 3-(4-fluorophenylimino)indolin-2-one with mercaptopropionic acid under microwave irradiation <2003SUL201>. Treatment under basic conditions of 2,3-dihalopropylamines with carbon disulfide results in the formation of two isomeric products 5-halotetrahydro-l,3-thiazine-2-thione 204 and 5-(halomethyl)thiazolidine-2-thione 205 <2002CHE1533>. 

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