Monatsh Chem 139, 939–943 (2008) DOI 10.1007/s00706-008-0860-1 Printed in The Netherlands Regioselective synthesis of 4-aryl-3,4-dihydro-1,3,5-triazino[2,1-a]- isoindol-2-ones Angelina V. Biitseva 1 , Olha V. Hordiyenko 1 , Volodymyr A. Sukach 2 , Myhailo V. Vovk 2 , Konstantin A. Pichugin 3 , Irina S. Konovalova 3 , Oleg V. Shishkin 3 1 Chemistry Department, Kyiv National Taras Shevchenko University, Kyiv, Ukraine 2 Institute of Organic Chemistry, National Academy of Sciences, Kyiv, Ukraine 3 STC ‘‘Institute for Single Crystals’’, National Academy of Sciences, Kharkiv, Ukraine Received 31 October 2007; Accepted 24 November 2007; Published online 18 February 2008 # Springer-Verlag 2008 Abstract The condensation of binucleophilic 3-amino- 1-arylimino-1H-isoindoles with bifunctional 1-chloro- benzylisocyanates occurs regioselectively resulting in 3,4-dihydro-1,3,5-triazino[2,1-a]isoindol-2-one deriva- tives. The structures of the synthesized compounds were unambiguously established by NOE experiments. Keywords Heterocycles; Cyclizations; NMR Spectroscopy; 3-Amino-1-arylimino-1H-isoindoles; 4-Aryl-3,4-dihydro- 1,3,5-triazino[2,1-a]isoindol-2-ones. Introduction In the last few years compounds possessing a broad spectrum of biological activity have been found among derivatives of 1H-isoindole [1] and 1,3,5-tri- azine [2–4]. Therefore, the development of efficient synthesis approaches to the compounds bearing iso- indole and triazine units in the same molecule be- came of considerable interest. A limited number of fused 1,3,5-triazinoisoindoles, that were described to date includes 4-amino-2,6-diimino-2,6-dihydro[1,3,5]- triazino[2,1-a]isoindole, which was synthesized by interaction of 3-amino-1-imino-1H-isoindole and N-cyanoguanidine and was used in the dye synthesis [5, 6]. A few (3R)-3,4-dihydro[1,3,5]triazino[2,1-a]- isoindol-6-ones are known to be prepared by reaction of 3-imino-1H-isoindol-1-one with formaldehyde and amines [7]. A simple approach to fused 1,3,5-triazines which is based on the reaction of 2-aminoazoles and 2-ami- noazines with 1-chloroalkylisocyanates has been elaborated earlier [8]. Upon exploring the interaction of 1-aryl-1-chloro-2,2,2-trifluoroethylisocyanates and 3-amino-1-arylimino-1H-isoindoles as binucleophi- lic aminoazole system two isomeric [1,3,5]triazino- isoindolones A and B have been isolated (Fig. 1). It has been found that the regioselectivity of this re- action depends on both reaction temperature and nature of substituents in Ar and Ar 0 [9]. The ap- proach mentioned above seems to be one of the most efficient ways to the fused [1,3,5]triazino[2,1-a]- isoindolones. Fig. 1 Isomeric triazinoisoindolones obtained from 1-aryl-1- chloro-2,2,2-trifluoroethylisocyanates and 3-amino-1-aryl- imino-1H-isoindoles Correspondence: Olha V. Hordiyenko, Chemistry Depart- ment, Kyiv National Taras Shevchenko University, 01033 Kyiv, Ukraine. E-mail: ov_hordiyenko@univ.kiev.ua