ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 4, pp. 553–558. © Pleiades Publishing, Ltd., 2007. Original Russian Text © V.A. Sukach, N.G. Chubaruk, M.V. Vovk, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 4, pp. 555–560. 553 Heterocyclizations of Functionalized Heterocumulenes with C,N-, C,O-, and C,S-Binucleophiles: VII.* Reaction of 1-Chloroalkyl Isocyanates with N,N-Disubstituted Cyanothioacetamides. A New Synthetic Route to 6-Dialkylamino-4-oxo-3,4-dihydro- 2H-1,3-thiazine-5-carbonitriles V. A. Sukach, N. G. Chubaruk, and M. V. Vovk Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine e-mail: mvovk@i.com.ua Received May 4, 2006 Abstract—Reactions of α-chlorobenzyl isocyanates and 1-aryl-2,2,2-trifluoro-1-chloroethyl isocyanates with N,N-disubstituted cyanothioacetamides gave 3,4-dihydro-2H-1,3-thiazin-4-ones and 3-aryl-2-cyano-4,4,4-tri- fluorobut-2-enethioamides. The effect of substituents in the reactant molecules on the reaction course and product ratio was studied. * For communication VI, see [1]. We previously performed a detailed study on the cyclocondensation of 1-chloroalkyl isocyanates with N-substituted β-aminocrotonates [2, 3] and β-diketones [1, 4] and developed new methods for the synthesis of isomeric 2,3- and 3,4-dihydro-1,3-azine (pyrimidine and oxazine) systems. The revealed general relations holding in these reactions prompted us to involve in analogous transformations C,S-binucleophiles with a view to obtain compounds of the 1,3-thiazine series. As C,S-binucleophiles we selected accessible (from the preparative viewpoint) cyanothioacetamides having a cyclic amine fragment. It should be noted that, depending on the substituents on the nitrogen atom and methyl carbon atom, thioacetamides are capable of acting as both N,S- [6], and C,S-binucleophiles [7]. In particular, we showed in [8] that N-monosubstituted alkanethioamides behave as N,S-binucleophiles in reactions with 1-chloroalkyl isocyanates and that the products of these reactions are 1,3,5-thiadiazine derivatives. Taking into account different regioselectivities in the reactions of 1-chloroalkyl isocyanates with amino- crotonates [3] and β-diketones [4], as starting com- pounds we used both α-chlorobenzyl isocyanates Ia–Ic and 2,2,2-trifluoro-1-chloroethyl isocyanates IIa–IId. We found that α-chlorobenzyl isocyanates Ia–Ic react with N,N-disubstituted cyanothioacetamides IIIa and IIIb on heating in methylene chloride to give 6-(pyr- rolidin-1-yl or morpholino)-4-oxo-3,4-dihydro-2H-1,3- thiazine-5-carbonitriles IVa–IVf in 31–52% yield. The most probable reaction scheme includes initial nucleo- philic substitution of the chlorine atom in I by the S-nucleophilic center of thioamide III with formation of intermediate A which undergoes spontaneous cyclization to final product IV (Scheme 1). Less electrophilic α-chlorobenzyl isocyanates I (R 1 = Ph, 4-BrC 6 H 4 ) are incapable of effectively alkylating the sulfur atom in III, and they give rise to mixtures of unidentified products. 3,4-Dihydro-1,3-thiazin-4-ones IV thus obtained are structural analogs of 6-alkyl(aryl)- amino-5-cyano-3,4-dihydro-2 H-1,3-thiazin-4-ones which were synthesized by us previously via [5+1]-cy- clocondensation of 2-alkyl(aryl)amino-2-sulfanyl-1- cyanoacrylamides with aldehydes and ketones [9]. We can state that the proposed alternative approach on the basis of [3 + 3]-cyclocondensation of difunctional nu- cleophiles III and bielectrophilic isocyanates I opens a way to difficultly accessible derivatives of the dihy- dro-1,3-thiazine system. The structure of 3,4-dihydro-2H-1,3-thiazin-4-ones IVa–IVf was proved by IR and 1 H and 13 C NMR spectroscopy. The IR spectra of IVa–IVf contained DOI: 10.1134/S1070428007040112