Thiazine-2-thiones

Gaertner, V. R. Fungicidal 3-amino-2,3-dihydro-1,3-thiazine-2-thiones, (Monsanto Chem. Corp.) U.S. Patent 2,909,460. Chem. Abstracts 54,3463 (i960). 

C5H6N2O2S, 4-Carboxylato-L-thiazolidinehydantoin, 46B, 391 C5H6N2O3S, 2-Amino-4-thiazolidinone-5-acetic acid, 38B, 386 CsH7NOS2r 3-Methyl-4-oxo-1,3-thiazine-2-thione, 38B, 386 C5H7N5O2S, 7-Amino-3-methyl-4H-imidazo[2,3-c](1,2,6)thiadiazine 5,5-dioxide, 43B, 471... 

The conformational distribution of all possible diastereomeric thiazine-thiones 183a and their N-alkyl derivatives 183b-e (cf. Scheme 64) was... 

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. 

Disubstituted derivatives of 4-mercaptoquinazolines were obtained in good yields by reaction of 5,6-benzo-l,3-thiazine-4-thione with amines (see 7b). 

The mesomeric effect of the C=S linkage is very pronounced and is responsible for the facile quaternization of heterocyclic N-alkylated thiones (159) this effect is operative even when such a shift does not increase the aromaticity of the ring. Thione derivatives of pyridazine, benzothiazole, quinazoline, 1,3-thiazine, triazole,and isoindole are examples of compounds which readily form quaternary salts. 

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... 

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... 

Basic hydrolysis of the [l,2,4]triazolo[5,l-3][l,3]thiazine derivative 77 was described to yield triazole-thione 78, the reaction proceeding in 59% yield <2005ZOR1092>. Related partially saturated triazolothiazines 79 were also subjected to ring-opening reaction aqueous hydrolysis afforded the acid 80 <2004KGS1256>, whereas reaction of 79 with hydrazine hydrate yielded the acid hydrazine 81 <2004ZOR260>. Both transformations took place in high yields. 

A general route to [l,2,4]triazolo[3,2-A][l,3]thiazines was discovered by Britsun etal. <2001ZOR1102, 2004KGS1256, 2004ZOR260>. In these publications, reaction of triazole thiones 332 with various substituted acrylic chlorides was reported to yield a series of ring-closed products 333 with the substituent of the reagent in the six-membered ring at the position adjacent to the sulfur atom. 

The reaction of tetrahydro-l,3-thiazine-2-thione and diethyl 2-chloro-malonate in the presence of triethylamine in boiling methylene chloride for 1.5 hr gave tetrahydro-1,3-thiazin-2-ylidenemalonate (508) in 33% yield via 507 through Eschenmoser sulfur elimination, together with traces of the mesoionic derivative (509) [77JCS(P 1) 1107]. In a similar reaction, diethyl 2-bromomalonate afforded the mesoionic compound (509) in 80% yield. Tetrahydro-l,3-thiazin-2-ylidenemalonate (508) was also obtained in 42% yield from 509 by irradiation in the presence of tributylphosphine in ethanol for 15 hr under argon [77JCS(P1)1107]. 

In the reaction of 2-isopropylidene-l-cyclopentanone 201 with carbon disulfide and ammonia, the perhydrocyclopenta[e][l,3]thiazine-2-thione derivative 204 was formed. The probable intermediates of the reaction are the Michael adduct 202 and the 2-imino-l-cyclopentanedithiocarbamic acid derivative 203. Under similar conditions, the related alkylidene derivatives gave the corresponding 3-substituted-2-imino-l-cyclopentanedithio-carbamic acid derivatives. Further substituted derivatives and homologs of 204 were also synthesized (74AKZ319), but the stereochemistry of these compounds was not investigated [73JCS(P1)1009]. 

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 solid-state structures of the benzo derivatives (Z)-4-benzylidene-6,8-dichloro-4//-benzo[, ( )-4-(3,4-dichlorobenzylidene)-2-methyl-4//-benzo[< ][l,3]thiazine 20 <2004JOC4545>, and 7-amino-l/7-benzoM[l,3]thiazine-2,4-dithione 21 <2005AXEo387> have been determined. As expected, they possess planar structures, and the thiazine-2,4-dithione 21 molecules pack in the solid state through amino-thione hydrogen bonds <2005AXEo387>. 

Three absorption bands are found in the UV spectra of 6//-l,3-thiazine-6-thiones 33 and 34. The spectrum of the 2-phenyl derivative contains bands at A ax = 253, 314, and 425 nm. A blue shift is seen when the 2-phenyl substituent is replaced by the dimethylamino group and the bands are observed at Aniax= 240.5, 288, and 428 nm <1997S573>. 

Intramolecular thermal rearrangement of /ra r-4//-5,6-dihydro-l,3-thiazines 93 affords /ra r-4,5-dihydro-l,3-thiazoles 94 (Equation 2) <1997JPP09136881>. 5-Halotetrahydro-l,3-thiazine-2-thiones 95 undergo facile rearrangement when heated with methanol, ethanol, or isopropanol, probably via intermediate 96, to give 5-(halomethyl)thiazoli-dine-2-thiones 97 (Scheme 1). No solvolysis products are observed <2002CHE1533>. 

The discussion will follow the trend thiazines, thiazinones and thiones, dihydrothiazines, dihydrothiazinones and thiones, perhydrothiazines and perhydrothiazinones, and thiones. Discussion on 1,3-benzothiazines and 3,1-benzothiazines is incorporated within the appropriate section, depending on the oxidation state of the heterocyclic ring. 

The 2-substituted l,3-thiazin-6-thiones 33 and 34 and 160 and 161 are accessible by reacting 3,3-dichloroprop-2-ene iminium salts (vinylogous Viehe salts) with thiobenzamide or WA -disubstituted thioureas (Scheme 11) <1997S573>. The ring closure occurs with loss of amine as the hydrochloride salt and the thiones are generated after a reaction with another thioamide molecule. 

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>. 

Thionation of 3-Wacylamino ketones with Lawesson s reagent (LR) gives the 3-Wthioacylamino thiones which cyclize to the 1,3-thiazines 216 with loss of H2S (Equation 20) <2000H(52)111, 2001HGA2347>. 

When the ruthenium complex 247 is reacted with an excess of isothiocyanates, the 2-imino-l,3-thiazine-4-thione ruthenium complexes 248 and 10 are formed by a [2+2+2] cycloaddition together with the [2+2] adduct 249, formed from cycloaddition of C C with the C=S (Scheme 32) <19980M2534, 2002JOM(660)127>. Treatment of 247 with an excess of isothiocyanate gives the six-membered ring directly and in improved yields. 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

Similarly the thione 172 is formed from the dithioester 171, which is obtained from the thiazine derivative 170 (71JCS(C)1610). 

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