Tetrahydro- 1,4-thiazin

Tetrahydro-1,4-oxazines are normally prepared by the cyclization of diethanolamines in the presence of acids, although an alternative route employs the reaction of diQS-chloroethyl) ethers with ammonia or amines (Scheme 124) (12JCS1788). Similar procedures can be adapted to the syntheses of tetrahydro-1,4-thiazines, their 1-oxides and 1,1-dioxides (25JA282). 

The majority of syntheses of 1,4-thiazines involve the elimination of HL from species of type 11. Precursors of type 11a are not usually isolable compounds but are generated as intermediates. Two methods for the formation of such intermediates have been described one utilizes tetrahydro-1,4-thiazine-3,5-diones as starting materials, and the other requires diacyl sulfides and ammonia. Thus the synthesis of 2/f-l,4-thiazine (6), reported in 1948, was achieved by heating compound 16 at 450°C in the presence of powdered aluminum. Potentially, the procedure may be applied to the preparation of thiazines variously substituted at positions 2 and 6 however, the low yield (13%) achieved for the parent compound is a detraction. It was initially claimed that the reaction of diphenacyl sulfide with ammonia gave 3,5-diphenyl-4H-l,4-thiazine subsequent studies, however, revealed that the product was the 2//-tautomer 3,5-Diaryl-2/f-l,4-thiazines and... 

Quantitation of the oral bronehodilator 2,5-diethyl-7-(tetrahydro-l,4-thiazin-4-yl)-l,2,4-triazolo[l,5-c]pyrimidine (R-836) (195) in plasma and urine of humans and experimental animals utilized reversed-phase HPLC and UV deteetion (88MI1). 

Chemical Name 2-(4-Chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide Common Name Chloromethazanone Structural Formula ... 

Dihydro-4H-l,3-thiazine werden durch Natriumboranat bei 0-10° in schwach sau-rer athanolischer Losung zu den Tetrahydro-1,3-thiazinen reduziert (vgl. S. 348)2 z.B. ... 

Thiazolidine, 2,5-Dihydro- 1,3-thiazole, Tetrahydro-l,3-thiazine und 5,6-Dihydro- 1,3-thiazine werden durch Lithiumalanat6,7 und meist auch durch Natriumboranat7 zu den (w-Mercapto-aminen aufgespalten. 1,3-Thiazolidine lassen sich mit einem Lithi-umalanat-OberschuB ahnlich den 4,5-Dihydro-1,3-oxathiolanen zu Athylaminen wei-terreduzieren7,8 ... 

A potential insecticide that is a derivative of tetrahydro-l,3-thiazine undergoes a number of reactions resulting in some 43 products of which the dimeric azo compound is the principal one in aqueous solutions (Figure 1.6) (Kleier et al. 1985). 

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]. 

The exocyclic double bond of (tetrahydro-l,3-thiazin-2-ylidene)malo-nate (527) was saturated by reduction with Hg/Al in methanol at ambient... 

The reaction of 3-methyl-2-oxo-3-butenoates and dimethyl (amino-thiocarbonyl)malonate afforded (dihydro-1,3-thiazin-2-ylidene)malonate (1684) under acidic conditions, while in the presence of triethylamine, (tetrahydro-l,3-thiazin-2-ylidene)malonates (1685) were the products (88SC1043). 

The reaction mode depends mainly on the choice of the base and reaction conditions, but route B is usually more common. Thus, tetrahydro-l,4-thiazine derivative 157 the structure of which was proved by X-ray crystal structure analysis (Fig. 7) [22b] was obtained in the reaction of the chloro ester 1-Me with 2-aminoethanethiol (156) using K2CO3 or EtgN as a base in 43 and 20% yield, respectively (Scheme 49) [22b, 26]. In the latter case, the secondary amino group in the primary tetrahydrothiazine product 157 underwent Michael addition to a second molecule of 1-Me to give 2-[r-(spirocyclopropanetetrahydrothiazinyl) cyclopropyl]-2-chloroacetate 158 (14% yield). When KOH in the presence of di-benzo-18-crown-6 was employed, however, the seven-membered heterocycles 155 (42%) and 159 (48%) were obtained upon reaction of 1-Me with 1,3-pro-panedithiol and 2-aminoethanethiol, respectively (Scheme 49) [26]. 

The biology and chemistry of 3,4,5,6-tetrahydro-l,2-thiazine 1,1-dioxides, such as 10 (or 1,2-thiazinane 1,1-dioxides), has garnered significant attention in the past 10 years. For instance, interest in the tetrahydro-l,2-thiazine... 

Two methods have been described for the catalytic A -arylation of tetrahydro-l,2-thiazine 1,1-dioxides (Equation 22 Table 1) <2004TL3305>. The first involves the copper-catalyzed N-arylation of sulfonamide 151 in the presence of 2,2 -bipyridine and K3PO4 in A -methyl-2-pyrrolidone (NMP) at 120°C. A variety of aryl bromides/iodides and... 

A facile synthesis of 2,4-disubstitued-tetrahydro-l,3-thiazines 40 involves reduction of the 5,6-dihydro-4//-l,3-thiazine 130 with NaBH3CN to give the ty -isomers (Equation 5) <2004TL1503>. 

The Michael attack of the enamine moiety in the 3,6-dihydro-2//-l,3-thiazine 149 on a-phthalimido acrylic acid affords the cyclic product 152, most probably through the intermediate 150. Support for the mechanisms comes from the isolation of the 5,6,7,8-tetrahydro-la//-thiireno[2,3-f]indolizine 151 in 10% yield (Scheme 10) <1999J(P1)3565>. 

Treatment of the 1,3-thiazine 153 with 3equiv of NaI04 and catalytic OSO4 results in oxidation at the C-C double bond to give the (2-methyl-4-oxopentan-3-yl)tetrahydro-l,3-thiazine-2,4-dione 154 in moderate yield (Equation 10) <2006TL1153>. 

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. 

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