2- Amino-1,3-thiazines, tautomerism

Another example of 1,3-thiazine formation is afforded by the acid-catalysed ring-opening and ring-closure of a 3,6-dihydro-2(li/)-pyrimi-dinethione to the isomeric 2-amino-4fr-l,3-thiazine thus, in hydrochloric acid solution the thione (32) is smoothly converted into (33), which appears to exist predominantly in the amino tautomeric form (u.v. and i.r. evidence). The sequence of reactions in Scheme 7 is suggested to account for the formation of (33). 

At present no systematic study of the factors which influence tautomeric behaviour in 1,3-oxazines and thiazines has been undertaken. All three types of 1,3-oxazines are known and both 2-amino-4-thioxo- and 2-imino-4-mercapto-l,3-thiazines exist in equilibrium with each other (74MI22700). When, however, the 4-position is disubstituted the amino isomer predominates (71KGS946). 

Examples of both 2-amino-4 f-1,3-thiazines and 2-amino-6H-1,3-thiazines are known, and in the case of 2-amino-4/f-1,3-thiazines these seem to be favored over their imino tautomers, at least in solution. Thus, 4,4,6-trimethyl-2-(A-methyl-7V-phenylamino)-4H-l,3-thiazine (I), which cannot tautomerize, absorbs at = 264 nm, and 4,4,6-trimethyl-2-(iV-phenylamino)-4H-l,3-thiazine (2), which can, shows = nm. 3,4,4-Trimethyl-2-(7V-phenylimino)-4//-l,3-thiazine (3), which is locked into the imino form, shows a main UV band at = 236 nm with a shoulder at 280 nm. Many 2-amino-6/f-1,3-thiazines are known where there is an unsaturated (acyl) group at C-5. This group serves to extend the delocalization of the chromophore, and 5-ethoxycarbonyl-2-(V-methylamino)-6//-l,3-thiazine (4), for example, exhibits UV bands at A iax = 240 nm, 266 nm, and 330 nm (Figure 1) <90AHC(50)85>. 

Condensation of ethyl /3-aminocrotonate (29) with the 3-keto-isothiocyanate (30) in hydrocarbon solvents results in the formation of the 2-thioio-pyrimidine (32) as the major product and the 2-amino-1,3-thiazine (33) as the minor component. However, the use of ether, chloroform, or acetonitrile as solvents reverses the product ratio. This observation points towards the feasibility of formation of the tautomeric intermediate (31), which through attack of nitrogen (31a) or sulphur (31b) at the carbonyl followed by dehydration and enamine hydrolysis leads to (32) and (33), respectively (cf. Scheme 3). Thus, in solvents of higher dielectric constant. 

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