Please cite this article in press as: K. Justyna, et al., New, simple and efficient method for the synthesis of imidazo-azines by flash vacuum thermolysis of tert-butylimines of pyrimidine-2-, pyrazine-2-, quinoline-2-, quinoxaline-2- and isoquinoline-1-carbaldehydes, J. Anal. Appl. Pyrol. (2017), http://dx.doi.org/10.1016/j.jaap.2017.02.028 ARTICLE IN PRESS G Model JAAP-3994; No. of Pages 12 Journal of Analytical and Applied Pyrolysis xxx (2017) xxx–xxx Contents lists available at ScienceDirect Journal of Analytical and Applied Pyrolysis journal homepage: www.elsevier.com/locate/jaap New, simple and efficient method for the synthesis of imidazo-azines by flash vacuum thermolysis of tert-butylimines of pyrimidine-2-, pyrazine-2-, quinoline-2-, quinoxaline-2- and isoquinoline-1-carbaldehydes Katarzyna Justyna a,b , Anna Chrostowska b,∗ , Stanisław Le´ sniak a,∗ , Clovis Darrigan b , Patrick Baylère b , Saïd Khayar b , Curt Wentrup c,∗ a University of Łód´ z, Faculty of Chemistry, Department of Organic and Applied Chemistry, Tamka 12, 91-403 Łód´ z, Poland 1 b Université de Pau et des Pays de l’Adour, Institut des Sciences Analytiques et de Physico-Chimie pour l’Environnement et les Matériaux, UMR CNRS 5254, 64000 Pau, France 2 c School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia 3 a r t i c l e i n f o Article history: Received 9 December 2016 Received in revised form 8 February 2017 Accepted 27 February 2017 Available online xxx Keywords: Flash vacuum thermolysis Aza-heterocycles Photoelectron spectroscopy Density functional calculations a b s t r a c t Flash vacuum thermolysis reactions of N-(tert-butyl)-N-(pyrimidin-2-ylmethylidene)amine (1), N-(tert- butyl)-N-(pyrazin-2-ylmethylidene)amine (2), N-(tert-butyl)-N-(quinolin-2-ylmethylidene)amine (3), N-(tert-butyl)-N-(quinoxalin-2-ylmethylene)amine (4) and N-(tert-butyl)-N-(isoquinolin- 2-ylmethylidene)amine (5) have been investigated. The formation of 3-methyl-imidazo[1,5- a]pyrimidine(6), 3-methyl-imidazo[1,5-a]pyrazine (7), 1-methyl-imidazo[1,5-a]quinoline (8), 3-methyl-imidazo[1,5-a] quinoxaline (9) and 3-methyl-imidazo[5,1-a]isoquinoline (10) as reac- tion products was observed. Excellent yields of imidazoazines from monocyclic imines 1 and 2 were found, whereas from bicyclic imines 3–5 slightly lower yields (50–75%) of the major products and formation of byproducts such as quinolone and isoquinoline were observed. These cyclizations were found to occur fully regioselectively onto the nitrogen atom of the adjacent ring. UV-photoelectron spectroscopy combined with FVT and quantum chemical calculations were applied for direct monitoring and characterization of the thermolysis products. The proposed mechanism of these reactions are substantiated by DFT calculations. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Heteroaromatic N-fused bicyclic systems containing the imidazo[1,5-a]azine motif (Fig. 1) have many applications in mate- rials chemistry [1,2] and as potent pharmacophores [3–7]. For example, the imidazo[1,5-a]pyridine skeleton has poten- tial applications in organic light-emitting diodes (OLEDs) and organic thin layer field-effect transistors (FETs) [8–14]. This aza-heteroaromatic system embedded in biologically active molecules also plays an important role as cardiotonic agents [15], ∗ Corresponding authors. E-mail addresses: anna.chrostowska@univ-pau.fr (A. Chrostowska), slesniak@chemia.uni.lodz.pl (S. Le´ sniak), wentrup@uq.edu.au (C. Wentrup). 1 http://iprem-ecp.univ-pau.fr/live/personnel/anna chrostowska. 2 http://www.chemia.uni.lodz.pl/professors/lesniak.html. 3 http://researchers.uq.edu.au/researcher/3606. aromatase inhibitors in estrogen-dependent diseases [16], throm- boxane A2synthetase inhibitors [17] and angio-tensin II receptor antagonist [18]. Imidazopyridinyl-1,3,4-oxadiazole conjugates are apoptosis inducers and topoisomerase II inhibitors [19]. Imidazopyrazine is an important pharmacophore [20–27] prevalent in a number of biologically active molecules. For exam- ple, imidazo[1,2-a]pyrazine is used as a potent inhibitor of the gastric acid pump [20], kinase aurora inhibitors [21], phospho- diesterase inhibitors [22] and can be used in the treatment of schizophrenia [23]. Imidazo[1,5-a]pyrazines are orally efficacious inhibitors of mTORC1 and mTORC2 [24]. They are used as corti- cotropin releasing hormone receptor ligands [25] and as an agent for the treatment of acute ischaemic stroke [26]. Morever, 1,3- disubstituted imidazo[1,5-a]pyrazine may be applied as inhibitors of insulin-like growth-factor IGF-IR [27]. Imidazo[1,5-a]pyrimidines exhibit biological activities such as treatment and prevention of diseases mediated by GABA receptors http://dx.doi.org/10.1016/j.jaap.2017.02.028 0165-2370/© 2017 Elsevier B.V. All rights reserved.