Synthesis of 5-thiocarbomoyl-and 5-(thiazole-2-yl)-2,3,4,4a,5,6-hexahydro-1Н-pyrido[1,2-a]quinoline-5-carbonitriles

The tert -amino effect cyclizations are an efficient and convenient route to synthetically as well as biologically important ring-fused tetrahydroquinolines. The method is operationally simple and highly diastereoselective. Herein we represent our studies of the tert -amino effect reaction ortho -dialkylaminoben- zaldehydes and cyanthioacetamide or [4-aryl-1,3-thiazole-2yl]acetonitrile. It was found 9-chloro-5-(4-phenylthiazole-2-yl)-2,3,4,4a,5,6-hexahydro-1Н-pyrido[1,2-a]quinoline-5-carbinitrile can easily be obtained from 9-chloro-5-cyano-2,3,4,4а,5,6-hexahydro-1H-pyrido[1,2-a] quinoline-5-carbothioamide and α-bromoacetophenone by condensation.


Introduction
Reactions on tert-amino mechanism are of interest to organic chemists in terms of the directed synthesis of a wide variety of nitrogen-containing heterocycles 1,2 . These include the cyclization of conjugate N, N-disubstituted amines, a key stage in which is the transfer of hydrogen from the formally non-activated α-carbon atom of the dialkylamino group to one of the atoms of an unsaturated substituent such as, for ex-ample, C = C, C = N, N = O , C = O, etc. Depending on the nature of the unsaturated substituent, there are Met-Kon. 3 and Reynhoudt 4 reactions. We are interested in the transformations of the first type, which resulted in converting the new C-C bond. The general scheme of transformations which we study is shown below.
According to the analysis of literature data, there were mainly investigated cyclizations of compounds in which the № 2 | 2015 Chimica Techno Acta Synthesis of 5-thiocarbomoyl-and 5-(thiazole-2-yl)-2,3,4,4a,5,6hexahydro-1Н-pyrido[1,2-a]quinoline-5-carbonitriles terminal carbon atom of the vinyl group has two cyano or ester groups. Cyclization of compounds in which β-carbon atom of the vinyl group has two different substituents was investigated to a lesser extent. Besides, the only example of such transformation with cyanacetamide was described by our group. Analogous reactions of [4-aryl-1,3-thiazole-2-yl] acetonitrile has not previously been performed.

The experimental part
Monitoring of the progress of the reaction and the individuality of the synthesized compounds was performed by TLC plates 254 SolufolUV system: chloroform (Manifestation UV lamp). IR spectra were recorded on a spectrophotometer Bruker Alpha. 1 H NMR and 13 C recorded on a spectrometer Bruker AvanceII (400 and 100 MHz, respectively), internal standard -TMS, in the laboratory of comprehensive research and expert assessment of organic materials in the CCU UFU. Mass spectra were recorded on a spectrometer MAT 11 (EI, 70 eV). Reactions under microwave irradiation were performed in reactors AntonPaarMonowave 300. Melting points were determined on the instrument StuartSMP3 and are uncorrected. Elemental analysis was performed on a CHNS-analyzer PE 2400 SeriesII.
The starting ortho-dialkylaminobenzaldehydes 1 and 5 were obtained in yields of 60-80 % by nucleophilic substitution of fluorine atoms in the respective 2-fluoro-benzaldehyde with piperidine as by described previously method 7 , 2-fluoro-benzaldehyde -commercial preparations of Acros firm.

Procedure for the preparation of compound 2
To a solution of 2.0 mmol cyanacethioamide in 8.0 ml of ethanol was added 2.0 mmol of α-bromoacetophenone. This solution was boiled for 1-3 hours. Reaction completion is determined by TLC. The reaction mass is cooled down to room temperature. Solvent was removed in vacuo. The resulting solid precipitate was recrystallized from ethanol.

Method for producing 2-vinyl-N, Ndialkyl anilinium 3
To a solution of 1.0 mmol of benzaldehyde in 10 5 mL of toluene was added 1.0 mmol of [4 (4-chlorophenyl)-1,3-thiazole-2-yl] acetonitrile 6 and the reaction mixture refluxed for 10-30 h. End of the reaction is determined by TLC. The reaction mixture was cooled to room temperature. The solvent was removed in vacuo, the residue was crystallized from ethanol. Technique to obtain tetrahydroquinoline 7

3-[2-(Piperidine-4-yl)phenyl]-2-[4-(4-chlorophenyl)-1,3-thiazole-2-yl] prop-2-ennitrile (3)
To a solution of 0.5 mmol of benzaldehyde in 5 mL of 2-butanol 1 in a vessel equipped with an anchor stir-ring was added 0.5 mmol cyanacethioamide. The vessel was sealed with a roof perforated with septum and heated in a microwave reactor at 200 °C for 10 minutes. Closing of the reactions is determined by TLC. The reaction mixture was cooled to room temperature. The solvent was removed in vacuo. Obtained solid residue is recrystallized from ethanol. Technique to obtain tetrahydroquinoline 8 To a solution of 0.5 mmol of 9-chloro-5-cyano-2,3,4,4а,5,6-hexahydro-1Нpiride[1,2-а]quinoline-5-carbothiamide 7 in 2 mL of ethanol in a vessel equipped with an anchor for remixing is added 0.5 mmol of α-bromoacetophenone. The vessel is capped with a perforated septum and heated in a microwave reactor at temperature of 150 °C for 25 minutes. The end of the reaction is determined by TLC. Then repromotional mass is cooled to room temperature. The solvent was removed in vacuo. The resulting solid precipitate was recrystallized from ethanol.