Thiazines, preparation

The bis[l,2]-dithiolo[l,4]thiazines prepared by Rees and co-workers are nonplanar, with the thiazine ring 34° out of plane for the W-ethyl compound. This gives a scorpion-like conformation with the N-substituent as the scorpion tail, seen in the crystal structure of this and other analogues <1998JOC2189>. 

Hydroxy group of rru -7,9u-H-7-(prepared from 7-formyl-2-(2-pyrimidyl)perhydropyrido[l,2-u]pyrazine by the treatment with MeOCH2P(Ph)3Cl in the presence of -Pr2NH in THF at 0°C, than with BuLi at room temperature (99MIP6). 

Looking for novel 1,3-thiazines with biological interest, Dandia and coworkers have recently prepared fused pyrido-1,3-thiazine derivatives by treatment of in situ generated 3-indolyHmine derivatives with 2-mercaptonicotinic... 

The thiazine dyes used in the preparation of this type of leuco are obtained through oxidative coupling of phenothiazine with an active methylene compound or an aniline. The reduction of the dye 23 with zinc powder in acetic acid is straightforward.9 Treatment of the leuco 24 with acetic anhydride at 40°C yields a more air stable leuco 25.9 Addition of arylsulfinic acid to thiazine dyes such as 26 produces directly leuco dyes such as 27.Sb... 

The majority of nonsteroidal antiinflammatory agents contain an acidic carboxyl group. A series of experimental agents in this class have been prepared in which the acidic proton is supplied by a highly enolizable proton from a function such as a p-dicarbonyl incorporated into a heterocyclic system. As an example, an acylated, highly oxidized isoquinoline moiety can fulfill this function (see also the benzo-thiazines below). Toward this end, reaction of... 

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... 

Benzyl-9-phenyl-3,4-dihydro-27/,677-pyrimido[6,l-A [l,3]thiazine-6,8-(7//)-dione was prepared from 3-benzyl-6-chloro-l-(3-chloropropyl)-5-phenylpyrimidine-2,4-(17/,3//)-dione and NaSH hydrate in DMF in 27% yield <1995W035296>. 

Sulfonyl imides (78) are, like sulfenes, prepared by dehydrohalogenation of the corresponding sulfonyl chlorides (79) (usually called sulfamoyl chlorides). Like sulfenes, they take part in [2 + 2] and [4 + 2] cycloaddition reactions with electron-rich alkenes or with 1,3-dienes, yielding 1,2-thia-zetidine 1,1-dioxides (80)104 or dihydro-1,2-thiazines (81),105 respectively. 

Similar ring systems were prepared <97JHC1693> by Coppo and Fawzi from the reaction of substituted ethyl 5-[methyl(methylsulfonyl)amino]-l 7/-pyrazole-4-carboxylates 119 with sodium hydride. This gave the 7-substitued 1,7-dihydro-l-methylpyrazolo[3,4-c][l, 2]thiazin-4(37/)-one 2,2-dioxides 120 in fair to good yield (Scheme 30). They also extended this synthesis by treating methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate 121 with sodium hydride in dimethylformamide to yield l-methyl-7-(trifhioromethyl)-l//-pyrido[2,3-c][l,2]thiazin-4(3//)-one 2,2-dioxide 122 in 79% yield (Scheme 31) <98JHC499>. 

Reaction of isothiocyanate with amine gives the corresponding thioureas. Many reports are appeared.102 111 The thiourea derivatives have been prepared by reactions of isothiocyanates with arylamines (Scheme 39) and reacted with some substrates to afford heterocyclic compounds, such as 2-amino-4//-ben-zothiazine, 1,3-thiazine, 1,3-thiazinone and l,3-thiazolidin-4-one.112 115... 

A ,A"-/i/. s,(dimcthylaminomcthylenc)thiourea (prepared by double condensation of AAY-dimethylformamide dimethyl acetal with thiourea) has been reacted with a-haloketones or acrylic dienophiles to give thiazolic and thiazinic diazadienes, respectively. These undergo cyclization reactions to yield imidazo[2,1-/ ][1,3] thiazoles, 5H-1,3-thiazolo[3,2-a]pyrimidines, 72/-imidazo[2,1 -/ ][ 1,3]thiazines and 2//,6//-pyrimido[2,l -/)][1,3]thiazines without any regioisomeric ambiguity (Scheme 61).144,145... 

L-Perhydro-l,4-thiazine-3-carboxylic acid 1-oxide is a natural AA found in some red and brown algae. It was synthesized from L-cystine in several steps. The heterocyclic ring was prepared by cyclization of 5-(2-chloro- or bromoethyl)-L-Cys in the presence of triethylamine. Perhydro-l,4-thiazine-3-carboxylic acid was then oxidized with H2O2/ACOH to give the sulfoxide (64JOC2203). Cystine also reacted with ethyl a-bromopropionate in liquid ammonia to give 5-oxoperhydro-l,4-thiazine-3-carboxylic acid [76JCS(P2)203],... 

For the preparation of cephems from a protected t-butyl ce-methoxygly-cinate thioamide and an orthoamide, an azathiadiene was formed which afforded the 1,3-thiazine derivative after cycloaddition of acrolein (Scheme 42) (89JOC2889). 

Perhydropyrido[l,2-h][l,2]thiazine-l,1-dioxide was prepared in 70% yield by the cyclization of 2-(3-chlorosulfonylpropyl)piperidine hydrochloride, obtained from 5-[3-(2-piperidyl)propyl]isothiourea dihydrochlorides with chlorine gas, on heating in toluene (62AP615). 

Thiazine compounds 830, prepared from 829 by the Lawesson reagent, were converted to the corresponding (2-acetoxyethoxymethyl)imidazothia-... 

Four regioisomeric dihydrothiazine 1,1-dioxides are possible depending upon the position of the double bond. The most common examples of this subclass include 5,6-dihydro-4//-l,2-thiazine 1,1-dioxides 5, 3,4-dihydro-2//-l,2-thiazine 1,1-dioxides 6, and 3,6-dihydro-2//-l,2-thiazine 1,1-dioxides 7. Scant interest has been paid to 5,6-dihy-dro-2/7-l,2-thiazine 1,1-dioxides 8 or their substituted derivatives. Related 3,6-dihydro-2//-l,2-thiazine 1-oxides 9 are also an important subclass of compounds due to their ease of preparation via [4-f2] cycloaddition reactions. 

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