A new route towards dithienoquinazoline and benzo[ f ]thieno[3,2-h ]quinazoline systems using Pd-catalyzed intramolecular cyclization under microwave irradiation

A novel synthetic route to novel thienoacene systems bearing a fused pyrimidine ring is proposed. The commercially available 5-bromopyrimidine is used as the starting material to obtain various dithienoquinazoline and benzo[ f ]thieno[3,2-h ]quinazoline systems through the Suzuki cross-coupling, nucleophilic aromatic substitution of hydrogen (the S NH reaction), and finally palladium-catalyzed intramolecular cyclization under microwave irradiation. Redox properties of some of the new compounds have been investigated. The data obtained show that these systems have plausible potential for use in organic electronic applications.


Introduction
2][3] In our previous publications, we have reported the synthesis of a series of dithienoquinazolines and benzo[f]thieno [3,2-h]quinazolines featuring a pyrimidine core fused with phenyl and thiophene rings, and have described some of their photophysical and electrochemical properties (Figure 1). 4,5Compounds I-III were obtained using oxidative photocyclization over long reaction times (from 20 to 70 hours) under UV irradiation (450 W).
The direct arylation of arenes via C-H bond activation and halogen exchange catalyzed or mediated by transition metals has received significant attention.[8][9][10] Palladium-catalyzed C-H intermolecular and/or intramolecular arylation offers one of the most efficient and reliable methods for the construction of different polycyclic structures. 11 In this communication, we present a new and simple route to dithienoquinazoline and benzo[f]thieno [3,2-h]quinazoline systems I-III, based on Pd-catalyzed intramolecular cyclization, proceeding under microwave irradiation.
The low yields (41-55%) of SN H -products 5a-g can be explained by the steric hindrance due to the presence of the (hetero)aryl substituent at C(5) of the pyrimidine ring.Thus, incomplete conversion of the starting reagents 3 and 4 into target products 5 was observed even after long reaction times (up to 2 weeks).In all cases, the starting reagent 3a-g was partially recovered after the reaction was stopped (see Table 1, entries 8-15).a For the reaction mixtures, the solvent was distilled off and the residue was analyzed by GC-MS; n.d.-not determined.
For the synthesis of the desired thienoacene derivatives 6a-g the best (so far as we are aware) protocol 26 for direct arylation has been used.The reactions proceed in DMF under microwave irradiation at 180 °C in the presence of mixture 10 mol % of Pd(OAc)2 and 20 mol % PCy3 as catalyst, and 3 equiv of K2CO3 as base.All reaction mixtures were analyzed by GC-MS and several by-products were identified (Scheme 2, Table 2).Unfortunately, yields of compounds 6a-g were relatively low due to prevailing debromination side reactions.For this reason the formation of bromo-substituted benzo[f]thieno [3,2-h]quinazolines and dithienoquinazolines 8a-g could not be observed, and the major by-products proved to be 5-(hetero)aryl-4-(thien-2-yl)pyrimidines 7a-g.We mention that purification of thienoacenes 6a-g is a difficult task, because of their poor solubility in common organic solvents.

Experimental Section
General.All reagents and solvents were obtained from commercial sources and dried by using standard procedures before use.N,N-Dimethylformamide for the microwave-assisted reaction was degassed by bubbling argon for 1h. 1 H, 19 F, and 13 C NMR spectra were recorded on a Bruker DRX-400 and Avance-500 instruments using Me4Si and C6F6 as an internal standards.Elemental analysis was carried on a Eurovector EA 3000 automated analyzer.Melting points were determined on Boetius combined heating stage.Flash column chromatography was carried out using Alfa Aesar silica gel 0.040-0.063mm (230-400 mesh), eluting with ethyl acetate-hexane.The progress of reactions and the purity of compounds were checked by TLC on Sorbfil plates (Russia), in which the spots were visualized with UV light (λ 254 or 365 nm).Semi-preparative HPLC was performed with ZORBAX Eclipse XDB-C18 PrepHT (21.2×150 mm, 5 μm) column, with flow rate 20 mL/min.Mixture of MeCN-H2O was used as mobile phase.Microwave heating was carried out in a Discover unimodal microwave system (CEM, USA) with a working frequency of 2.45 GHz and the power of microwave radiation ranged from 0 to 300 W. The reactions were carried out in a 10 mL reaction tube with hermetic Teflon cork.The temperature of the reaction was monitored using an inserted IR sensor by the external surface of the reaction vessel.A suitable crystal of 5a was selected and XRD analysis was performed on a Xcalibur diffractometer using standard procedure (MoKα graphite-monochromated irradiation, ω-scanning with 1º steps).Compound 5a was solved and refined by using Olex2 program. 27Non-hydrogen atoms were refined in anisotropic approximation; H-atoms were refined in isotropic approximation in riding model.The X-ray crystallography data for structure 5a reported in this paper have been deposited with Cambridge Crystallography Data Centre as supplementary publications CCDC no.1469706 for 5a.These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Cyclic voltammetry was carried out on a Metrohm Autolab PGSTAT128N potentiostat with a standard three-electrode configuration.Typically, a three electrodes cell equipped with a platinum working electrode, a Ag/AgCl reference electrode with two membranes (the interior volume contents KCl saturated water solution; exterior volume 0.1 M LiClO4 in CH2Cl2), and a glassy carbon rod counter electrode were employed.The measurements were performed in anhydrous CH2Cl2 solution containing the compound (2 mM) and tetrabutylammonium perchlorate (0.1 M) as the supporting electrolyte at a scan rate of 100 mV/s.The potential of reference electrode was calibrated by using the ferrocene/ferrocenium redox couple (Fc/Fc + ), which has a known oxidation potential of +5.1 eV vs. vacuum for ferrocene. 28The HOMO energy values were estimated from the onset potentials (Eox onset ) of the first oxidation event according to the following equations: where E1/2(Fc/Fc + ) is the half-wave potential of the Fc/Fc + couple against the Ag/AgCl electrode.

Figure 2 .
Figure 2. Mercury 25 representation of the X-ray crystal structure of 5a with thermal ellipsoids of 50% probability.

Table 1 .
Reaction conditions and yields of compounds 3a-g and 5a-g