1.3- Thiazine-4-thion-6-ones

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... 

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... 

Hexahydropyrido[2,l-h][l,3]thiazin-4-one (99) and its 9-pent-4-enyl or 9-(6-trimethylsilanylhex-4-enyl) derivatives were prepared when the appropriate piperidine-2-thione reacted with acryloyl chloride in 1,2-dimethoxyethane [94H(37)441]. 

Reaction of piperidine-2-thione and diphenylcyclopropenone in acetonitrile gave 2,3-diphenyl-2,3,4,6,7,8-hexahydropyrido[2,l-b][l,3]thiazin-4-one in 88% yield [71LA(752)136], 2,6,7,llb-Tetrahydro[l,3]thiazino[2,3-a]iso-quinolines (214) were obtained from 1-substituted 3,4-dihydroisoquino-... 

We also note the chemical shifts at C-2 and C-4 for two 2-aryl-4,4-bis(trifluoromethyl)-4//-thiazines (24) (83CC945) along with the chemical shifts of four carbons for twelve 4//-thiazine-4-ones (102) (86PS327). The chemical shifts of four carbons from two 4,6-diphenyl-2//-thiazine-2-thiones (103) [82JCS(P1)2149] and the chemical shifts of the carbons from 2-substituted-4-methyl-6//-thiazine-6-thiones (104) are also shown (81BSB75). (See structures 24,102-104.)... 

Similarly, reaction of 3-chloroacylthio-3-isothiazoline-5-thiones (333) with reactive alkynic compounds proceeds with formation of the 1,3-dithiole derivatives (334) which contain thiazolone or 5,6-dihydro-l,3-thiazin-4-one rings (81H(16)595). 

Proton and C NMR data has proved useful in establishing that 2-benzyl-l,3-thiazin-4-ones (21) exist preferentially as the 2-benzylidene forms (22) (Equation (3)) <83CPB1929>, and in demonstrating the existence of ring-chain tautomerism between l,2,3,4-tetrahydro-6-hydroxy-6-methyl-l,3-thia-zine-2-thiones (23) and acyldithiocarbamic acids (24) (Equation (4)), although the reasons for this are not entirely clear <92KGS985>. 

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>. 

Amino-l, 3-thiazin-4-ones (245) (X = O), or thiones (245) (X = S), are obtainable via the cycloadditions of l-(A,A-diethylamino)propyne (246) and thioacyl isocyanates, or isothiocyanates, respectively (Equation (30)) <85ZC324>. A less common approach utilizes nitriles as the C—N component in [4 - - 2] constructions of l,3-thiazin-4-ones thus, the cyclization of the ( )-thiohemi-acetal (247) with (248) gives the 2-phenoxy-l,3-thiazin-4-one (249) (Equation (31)) <85ZC430>. 

CftHgN2S3, 2,4-Dimethyl-1,2,4-thiadiazolidine-3,5-dithione, 40B, 338 CftH6Nft03S2, 5-Acetamido-1,3,4-thiadiazole-2-sulphonamide, 40B, 338 Ci,H7N02S, (R)-Thiazolidene-4-carboxylic acid, 45B, 368 C5H5NO3S, 4-Hydroxymethylisothiazole-3-carboxylic acid, 44B, 353 C5H5N3OS, [1,2,4]Triazolo[3,2-b][1,3]thiazin-5-one, 46B, 390 C5H5N3OS2 f 2,3,6,7-Tetrahydro-4H-thiazolo[3,2-a]s-triazin-2-on-4-thione, 40B, 263... 

In a weakly alkaline solution, isothiocyanate reacts with the a-amino group of cysteine (Figure 2.64). The reaction of isothiocyanates with cystine leads to the cleavage of disulfide bond (-S-S-) with the formation of cysteine sulfenic acid and a dithiocarbamic acid ester. Dehydration of this ester yields 5-amino-l,3-thiazine-4-one-3-thione derivative and elimination of hydrogen sulfide produces a cyclic 2-thiazoline-4-carboxylic acid derivative (Figure 2.65). Reaction of cystine with thiocyanates (R-S-C=N), formed by spontaneous isomerisation of isothiocyanates, produces disulfide Cys-S-S-R and -thiocyanoalanine, which cyclises to 2-thiazoline derivative (Figure 2.66). 

There have been reports of various 3-cyano-l-p-D-glucopyranosyl- and -1-P-D-galactopyranosyl-pyridin-2-ones and pyridin-2-thiones, along with o-l-arabinopyranosyl- and P-D-xylopyranosyl-3-cyano-2-pyridinethiones. 5-Amino-6-aryl-3-(P-D-gluco-or -galacto-pyranosyl)tetrahydro-2-thioxo-4H-1,3-thiazin-4-ones have been made by elaboration of the appropriate tetra-O-acetyl-P-D-hexopyranosyliso thiocyanates, and l-(2-acetamido-2-deoxy-P-D-glucopyra-... 

Nayak observed" that l-(2-pyridyl)thiourea reacted with chloroacetic acid in ethanolic solution in the presence of sodium acetate to yield 2-(2-pyridyl-imino)thiazolidin-4>one, whereas the same reaction afforded 3-(2-pyridyl)-thiohydantoin when performed in pyridine solution. On treatment with chloroacetic acid in pyridine, p-bis(thioureido)biphenyl (323) similarly yielded p-bisCthiohydantoin-S-yObiphenyl." The reactions of monosubsti-tuted thioureas with -unsaturated /3 -dichlorocarbonyl compounds and 2-(l-chlorocyclohexyl)cyclohexanone afforded 1,3-thiazine- thiones and the spiro-compounds (324), respectively. 

As with five-membered heterocycles, phosphorus pentasulfide may replace a ring oxygen atom by sulfur, or it may effect replacement in an acyclic precursor and then bring about cyclization. Thus isochroman-l-one (99) is converted into thioisochroman-l-thione (100) under the same conditions a 3-arylisocoumarin( 101) produces a 3-ary 1-1-thioisocoumarin (102) only, with no replacement of the ring oxygen atom.122 A typical example of thiation, followed by cyclization, is the formation of 2-alkyl- or 2-aryl-3,l-benzo-thiazine-4-thiones (103) from /V-acylanthranilic acid esters (104) by treatment with phosphorus pentasulfide in boiling xylene.122... 

Rearrangement reactions involving 1,3-thiazines are often very facile. For example, reaction of 2-imino-4-phenyl-2/7-1,3-thiazinium perchlorate 957 with NaOH at room temperature gave 4-phenylpyrimidine-2(l//)-thione 958 <2004CHE1595>, while treatment of 6-amino-2,3-dihydro-l,3-thiazin-4(l// )-ones 959 with KOH readily gave the potassium salt of the dihydropyrimidinone 960 <2005HAC426>. 

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>. 

C-Enamino-imines obtained by photolysis of l//-pyrimidin-2-ones have been treated with carbon disulfide, giving 2//-l,3-thiazine-2-thiones (22) and/or l-aryl-l//-pyrimidine-2-thiones (23) (Scheme 13) [82JCS(P1)2149]. 

In the case of thiazine-4,6-diones, in contrast to the spectrum of the unsubstituted compound 92 (C=0,1640 cm ), there are three absorption bands. One is at 1640 cm-1, corresponding to the enol form, and two are at 1690 and 1730 cm"1, corresponding to the diketo form. In this example, the H-NMR spectrum suggests the presence of three tautomeric forms 93,94 and 95. In conclusion, we record a few absorptions bands for two thiazine-2-thiones (96) [82JCS(P1)2149]. 

A number of methods employ an imidazole-2-thione or related compound with a bifunctional reagent to build the thiazine ring in one or two steps. Treatment of (682) with acrylyl chloride directly produced (683) (64JOC1720). Substituting acrylic acid under catalysis allows isolation of the S-alkylated intermediate, which cyclized to (683) upon heating (64JOC1715). 

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