Thiazinium chloride

Thi abut azide 358 Thialbarbital 1, 275 Thiamphenicol 2 45 Thiamprine 2, 464 Thiamylal I, 274 Thiazinium chloride 3, 240 Thi azolsul Tone 14T Thi ethyl perazi ne 1, 382 Thiobarbital 1, 275 Thiofuradene T, 231 Thioguanine 464... 

Dialkyl and isopropylidene malonates were reacted with 2-chloro-l,3-thiazinium chlorides (1686) in methylene chloride in the presence of triethylamine to give (1,3-thiazin-2-ylidene)malonates (1687) in 5-13% yields (89AP593, 89GEP3803783). 

Since many of the uses of antihistamines involve conditions such as rashes, which should be treatable by local application, there is some rationale for developing drugs for topical use. The known side effects of antihistamines could in principle be avoided if the drug were functionalized so as to avoid systemic absorption. The known poor absorption of quaternary salts make such derivatives attractive for nonabsorbable antihistamines for topical use. Thus, reaction of the well-known antihis-taminic drug promethazine (104) with methyl chloride leads to thiazinium chloride (105). 

Although the dehydrogenation of dihydrothiazines of type lib, which are readily available compounds (Section V,B), may provide a useful route to thiazines, few examples have been reported. However, studies in the author s laboratory have shown that the compound 18a was converted into the thiazine 19 in good yield by lead tetraacetate in benzene. A further example is provided by the transformation, in boiling toluene, of the dihydrothiazine 18b into the bis(thiazine) 20 the product, however, was isolated only in 12% yield. The formation of the thiazinium chloride 23, from the reaction of the penicillin sulfoxide 21 with phenylacetyl chloride in acetone exposed to the air, constitutes a remarkable oxidative rearrangement. It seems likely that the dihydrothiazine 22, formed by the route suggested in Scheme 1,... 

The C =N bond of 2/f-l,4-thiazinium salts is expected to be particularly susceptible to attack by nucleophilic reagents. Two examples involving the compound 23 are known thus, with diazomethane and triethyl phosphite, the thiazinium chloride 23 afforded the derivatives 28a and 28b, respectively. ... 

In principle, acidic hydrolysis of a 1,4-thiazine may lead to the formation of ammonia and a dicarbonyl compound. In the case of 3,5-diaryl-2H-l,4-thiazines, this hydrolysis occurred under very mild conditions thus the thiazine 17 was converted into ammonia and diphenacyl sulfide by dilute hydrochloric acid at ambient temperature. In aqueous acetone at pH 7, the thiazinium chloride 23 underwent an interesting hydrolytic cleavage to give the thioamide 30 a possible reaction pathway is suggested in Scheme 3. 

There are two reports of X-ray diffraction studies involving 1,4-thiazines. Thus the meso configuration of the bis(thiazine) 24 was established by the observation that the molecule possessed a center of symmetry. The crystal structiu-e of the thiazinium chloride 23 has also been described however. 

Cyclization of 2-oxo-3-(2-pyridylthio)propyl chloride on the action of excess potassium iodide afforded 3,3-dihydroxy-3,4-dihydro-2//-pyrido[2,1- >][l,3]thiazinium iodide, from which the 3-oxo derivative 89 was obtained in quantitative yield by heating in vacuo (80CL947). 

Thiazinium oxides (131) are formed in a two-step sequence from enol ethers (130) and sulfoximines (129 Scheme 52) (78CC197), whereas alkylsulfamoyl chlorides and triethyl-amine react with activated dienes to afford diketosulfonamides (132) which on heating afford 1,1-dioxides (133 Scheme 53) (79JOC305). 

The usual routes to 1,3-oxazinium salts consist of 1,4-cycloadditions between either a,/3-unsaturated /3-chlorocarbonyl compounds and nitriles or between N-acylimidoyl chlorides and alkynes. Stannic chloride is an effective catalyst for both reactions (c/. Scheme 62). 1,3-Thiazinium perchlorates are synthesized by reacting oxazinium salts with hydrogen sulfide in absolute acetonitrile and then treating the product amides (185) with perchloric acid (Scheme 69) (72S333). 

The 1,1-dioxide of 3-halomethyl-2,3-dihydropyrido[l,2,3-de]-l,4-benzo-thiazinium triiodide and bromide were prepared by cyclization of 8-allyl-sulfonylquinoline with I2 in 2-PrOH, and with Br2 in CHCI3 (93MI9). When 8-[(l-chloro-2-mercapto-2-propyl)thio]quinoline HC1 was left to stand in EtOH at 20°C 2-mercapto-2-methyl-2,3-dihydropyrido[l,2,3-de]-l,4-benzothiazinium chloride was obtained (94ZOR636). 8-[2-Chloro-l-(un)-substituted ethylthio]quinolines could easily cyclized to 2,3-dihydropyrido-... 

The l,3-thiazinium-4,6-diolates 493, which are made by condensation of thiobenzamides (PhCSNHR ) with malonyl chlorides [CHR(COCI)2] or carbon suboxide, react with aryl isocyanates giving the pyrimidinium-... 

H-1,4-Thiazines are weak bases (Section 11,D,5), and the parent compound is reported to form salts with picric acid, chloroplatinic acid, and hydrogen chloride. Alkylation, to give the thiazinium iodide 25, occurred when the thiazine 15 was treated with methyl iodide the derivative 25 is the only known example of a 4//-l,4-thiazinium salt. 

Chloro-5,6-dihydro-4//-l,3-thiazinium salts (134) are strongly electrophilic and react with enamines and other nucleophiles by displacement of the chlorine atom as the chloride ion and the formation of 2-substituted derivatives. With the pyrrole (135) and indole this leads to the 2-(pyrrol-... 

The normal acidic rearrangement of penicillin sulfoxide derivatives is the well-known one discussed at length previously (Cooper and Spry, 1972). The usage of some alternative acidic reagents has resulted in totally different reaction pathways. The reaction of penicillin sulfoxide (349) with phenylacetyl chloride furnished the thiazinium salt (350)... 

A new route to 1,3-thiazinethiones with a wide variety of substituents is provided by the reaction of j8j8-dichlorovinyl aryl ketones with primary thioamides in a molar ratio of 1 2. Thus (9) reacts with thiobenzamide in boiling acetic acid to give (10), which, by sequential treatments with mercuric acetate and oxalyl chloride, can be converted into the thiazinium salt (11)... 

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