9- thiazine, ring opening

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. 

Novel ring opening reactions of the 1,3-thiazinone moiety of triazolo[5,l- ][l,3]thiazines (13) have been studied Britsun et al. <2005CHE1334>. The experienced transformations are reminiscent of formation of 81 from 79 (Section 11.16.5.1.1). In the frame of this research activity, ring contraction of the thiazine moiety to a thiazole was also observed by the same team <2005CHE782>. 

One notable advance in this chemistry since the publication of CHEC-II(1996) is the use of enantiomerically enriched 3,6-dihydro-l,2-thiazine 1-oxides in the rearrangement sequence. For instance, iV-Cbz-protected bicyclic 1,2-dihydrothiazine 44 undergoes ring opening upon treatment with phenylmagnesium bromide (Scheme 16). The synthesis of allylic amino alcohol 129 is completed in excellent yield upon exposure of the intermediate sulfoxide 130 to trimethyl phosphite and methanol at 80 °C <2002TA2407, 2000TL3743>. 

Thiazine 283 has been prepared through the nucleophilic ring opening of fused bicyclic aziridine isothiazoli-dine 1,1-dioxide 284 with MeOH in the presence of BF3-OEt2 (Equation 40) <20000L2327, 2004JOC6377>. 

A variety of N,S-bis(nucleophiles) react with unsaturated 5(47/)-oxazolones to produce triazolo-l,3-thiazin -ones 570 and 1,3-thiazin-4-ones 572. Mechanistically, Michael addition of the bis(nucleophile) to 569 and 571 followed by ring opening with concomitant cyclization leads to the observed products. 

Oxazines and thiazines are unstable with respect to ring-opened isomers (cf. 30—>31). l,2,3-Benzotriazin-4-ones on protonation undergo ring-chain tautomerism to yield diazonium ions (Scheme 8 see CHEC 2.18). 

Treatment of 81 with chlorine afforded a ring-opened product (82) [80CPB1131, 80JAP(K)8D/127372], A ring-opened product (84) was obtained when 9-[3-(2-methyl[l, 3]dioxolan-2-yl)ethyl]-2,3,4,6,7,8-hexahy-dropyrido [2,l-fo][l,3]thiazine (83) was treated with trifluoroacetic acid in boiling THF [94H(37)441]. 

The electrophilic properties of substituted 6//-l,3-thiazine-6-ones (208) in solution also shows reactivity at C-2 in acidic conditions and at C-6 in basic conditions. The regioselective reaction of 4-ethoxycarbonyl-2-phenyl-6//-l,3-thiazine-6-one with dimethylamine leads, after ring opening and reclosure, to two diasteriomeric 5-dimethylcarboxamido-4-ethoxy-carbonyl-2-phenyl-A2-thiazolines 209 and 210, whose structures were confirmed by X-ray diffraction studies on 210 (Scheme 84) (88BSF897). Com-... 

Thermolysis of 4//-l,3-thiazines (271) leads to thioamide vinylogues (272) by ring opening (Scheme 110) (86SC79). At more elevated temperature (toluene reflux), compound 273 is not isolated. A heterocyclic isomer (274) with a 3,4-dihydro-2//-l,3-thiazine structure is obtained (Scheme 111). 

Rhodanines have been obtained from 3-formyI-lO-methylpheno-thiazine and its 5,5-dioxide. From these two aldehydes and also from 2-formyl- and 2-formyl-lO-methylphenothiazine, azlactones have been prepared, and their physical properties and oxazolone ring-opening reactions have been investigated. ° ... 

Ring Opening of 3,6-Dihydro-l,2-thiazine 1-Oxides Obtained by Diels-Alder Addition36... 

Ring expansion of the bicyclic isothiazole (698) occurred upon treatment with cyanide ion to give the imidazo[l,2-c][l,3]thiazine (699). The mechanism involves initial ring opening by attack on sulfur, and then ring closure. The anion of methyl propiolate also causes the same type of rearrangement (79TL1281). 

Several related reactions involve reduction of cyclic carboxylic acid derivatives to masked aldehydes which resist further reduction but can be converted into the required aldehydes by acid hydrolysis. In a series of papers, it was established that carboxylic acids could be converted into dihydro-1,3-thiazines or dihydro-1,3-oxazines which could be reduced by NaBH4 in weakly acidic ethanol. Thus, as shown in Scheme 20, dihydro-1,3-thiazines (41) were reduced to tetrahydro-1,3-thiazines (42) in yields of 66-84%. The resulting tetrahydro compounds could be hydrolyzed to aldehydes by aqueous acid. - In a later publication, these workers showed that there was little evidence for ring opening during reduction and that other methods of reduction e.g. hydrogenation over Pt, Pd or Rh or use of dissolving metals such as Zn, Sn or Na) were totally unsuccessful. In closely similar work, reduction of 5,6-dihydro-4W-... 

---