Spiro thiazines

Interesting observations were made on the cyclization reactions of N-benzoyl-CM- and fram-2-aminomethyl-l-cyclanols 216 and 217 with P4S10. From the cm isomers the spiro derivatives 219 were the main products, while the cm thiazines 220 were the minor products. In the cyclization of... 

Calculations by PM3 methods have been carried out on molecules such as the diastereomers of methyl 4-(dimethyl-amino)-5-methyl-2-phenyl-5,6-dihydro-4//-l,3-thiazine-5-carboxylate, and the /ra j-diastereomer 3 was shown to be significantly more stable than the corresponding m-diastereomer 4 <2002TL6067>. The structure of the spiro compound 5, which acts as a charge-transfer dye, was calculated by PM3 methods <1996JA1471>. 

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>. 

Reaction of pyrido[2,l-6][l,3]thiazine-2,4-dione (105) with p-tosyl azide in the presence of triethylamine in acetonitrile at 0°C gave a 3-diazo derivative (106), which reacted with cyclohexene in the presence of a catalytic amount of rhodium acetate under reflux to yield a spiro derivative (107) [94H(39)219 95H(41)1631]. 

Simple alkyl-substituted dihydro-1,4-thiazines are readily converted into the corresponding 5-monoxides atmospheric oxidation is sometimes sufficient, although side reactions may also occur. The cyclohexene derivative (99), for instance, affords not only the oxide (100) but also the spiro compound (101) probably generated by ring contraction of a hydroperoxide intermediate (Scheme 42) <73US(B)(8)34l>. 

Two modes of dimerization of the 2-alkyl-6-methyl-4//-l,3-thiazine-4-one (249) have been observed (83CC56). One mode gave the linearly combined dimer 250, and the other led to a spiro compound (251). The structure of one of the spiro compounds was confirmed by X-ray crystallography (Scheme 101). The reactions occurred when the 2-alkyl group was methyl, ethyl, or n-propyl, but not when it was isopropyl. 4-Acyloxy-and 4-p-tosyloxy-l,3-thiazine-6-ones (253) have been prepared by acylation and sulfonylation starting from thiazine-4,6-diones (252), in a solvent, at temperatures from room temperature to reflux (Scheme 102) (79KGS44). 

In an analogous series of reactions utilizing polycyclic bis-l,2-dithiole-3-thiones 124 or 125 and DMAD, depicted in Scheme 12, the type of major product, bis-spiro-l,3-dithiolethiopyranepyrrole 126a from 124, and bis-spiro-1,3-dithiolethiopyrane-l,4-thiazine 127 and bisdithiafulvenyl-l,4-thiazine 128 from 125, depends on the control of the reaction conditions <2004JOC3672>. 

Alkyl-l,3-thiazin-4-ones (161) undergo self-addition when allowed to stand at room temperature. This process can be considered to involve the tautomerism of the alkylthiazinone into its alkylidene isomer (162), which acts as an enamine and adds to the enone system of another molecule of the alkylthiazinone. The adducts (163) can be converted into the very unusual spiro derivatives (164) when they are treated with chlorosulfonic acid (Scheme 29) <83CPB1936>. 

A detailed account of condensation reactions used in heterocyclic chemistry can be found in Section 8.2.6, in Chapter 10 [97], and, for cycloaddition reactions, in Chapter 11 [98]. A previously unknown class of compounds, spiro[3H-indole-3,2 -[41-f] pyrido[3,2-e]-l,3-thiazine]-2,4 (ll-f) diones, can be synthesized by reaction of in situ-generated 3-indolylimine with 2-mercaptonicotinic acid under the action of MW in the absence of solvent. Both neat reactions and reactions on solid supports such as silica gel, alumina etc., effectively promote the reaction whereas reactions under thermal heating conditions failed to proceed (Scheme 8.31) [99]. 

Scheme 8.31. MW-promoted synthesis of spiro[indole-pyrido] thiazines.

Scheme 2.2-33 MW-promoted synthesis of novel spiro[indole-pyrido thiazines].

Spiro-6 -l,3-thiazines from carboxylic acid thioamides O... 

Ketenes are mostly used as common starting materials for structurally diverse mono-spiro- and fused six-membered heterocycles such as lactones, pyrans, pyronones, pyridines, quinolines, isoquinolines, oxazine, quinoxalines, thiazines, oxathines, etc. 

C20H19NOS2, 2-Phenylcyclopropane-1-spiro-4 -(2 -benzylthio-4, 5 -di-hydro-6 H-1, 3 -thiazine)-5 -spiro-2 -oxirane, 436, 463 C20H22N2O8, 2,2 -(m2"(1,4,7-Trioxahepta-1,7-diyl)-5,5 -(M2 (1r9-di-oxo-2,5,8-trioxanona-1,9-diyl))bis(pyridine), 466, 385 C20H2 36rN202, 2-6enzylamino-2-(1-bromoethyl)-3-benzyl-5-methyloxazo-lidin-4-one, 466, 385... 

K. Arya, D.S. Rawata, H. Sasaib, Zeolite supported Bronsted-add ionic liquids an eco approach for synthesis of spiro[indole-pyrido[3,2-e] thiazine] in water under ultrasonication. Green Chem. 14 (2012) 1956-1963. 

Thermal decomposition of ( >-azidophenylthio)uracil (299) furnishes a 2 1 mixture of the dihydro-5-thia- (300) and dihydro-10-thia-isoalloxazines (301). The formation of the former product is analogous to the preparation of pheno-thiazines from o-azidodiphenyl sulphides, and presumably involves rearrangement via a Spiro-intermediate. However, the direct insertion of the nitrene intermediate derived from azide (299) into the uracil ring to give the 1,4-benzothiazine system (301) is unique. More surprising is the production of the unrearranged 10-thiaisoalloxazine (301) (70%) as the only product from the photolysis of (299) in methanol solution. 

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. 

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