Synthesis and Cyclizations of N-(2,3-, 3,4- and 3,5-Dimethylphenyl)-β-alanines

Abstract

A series of 1-aryl substituted dihydro-, 5-methyldihydro- and 6-methyl-dihydro-2,4(1H,3H)pyrimidinediones and their 2-thio analogues were obtained by reaction of the corresponding β-alanines or α-methyl- and β-methyl-β-alanines with urea or potassium thiocyanate. The reaction of N-(2,3- and 3,5-dimethylphenyl)-α-methyl-β-alanines with ethyl acetoacetate gave 1-(2,3- or 3,5-dimethylphenyl)-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)pyridones. The combined spectral data obtained by ¹H-, ¹³C-, ¹H/¹³C (HETCOR) NMR and IR provided useful information about the structure of the products synthesized in this work.

Introduction

N-Aryl-β-alanines can be obtained in different ways. The most convenient method is the reaction of aromatic amines with α,β-unsaturated acids, their esters and nitriles. Acidic or basic catalysts are needed in the reactions of amines with the unsaturated acid derivatives, but the reactions of amines with the unsaturated acids take place much easier than with the other derivatives as the acid itself acts as a catalyst. N-Substituted β-alanines have been shown to be versatile starting materials for the synthesis of a variety of heterocyclic systems, for example, the pyrimidine skeleton that is commonly found in pharmaceuticals, fungicides and herbicides. We have recently described the synthesis of N-(2-substituted phenyl)dihydro-2,4(1H,3H) pyrimidinediones and 2-thiones with substituents at the 5- and 6-positions [1,2]. Their structures were confirmed by their NMR spectra and it was shown that most of 5- and 6-methyldihydropyrimidindiones and their 2-thio analogues formed two atropisomers due to the restricted rotation about the N₍₁₎-C_(1’) bond. The problems of structure determination and the energetic characteristics of this process have been discussed.

Results and Discussion

We now report the synthesis of new N-aryl-β-alanines and their cyclization products. The N-aryl-β-alanines, N-aryl-α-methyl- and N-aryl-β-methyl-β-alanines described in this work were synthesized from aromatic amines reacted with acrylic, methacrylic and crotonic acids and were obtained in either the free form or as the corresponding HCl salts. Scheme 1 illustrates the approach used in the synthesis of substituted dihydropyrimidinone and hydropyridone derivatives from N-substituted β-alanines.

Scheme 1.

Scheme 1.

a R¹ = R² = CH₃; R³ = R⁴ = H; b R¹ = R⁴ = H; R² = R³ = CH₃; c R¹ = R³ = H; R² = R⁴ = CH₃; 6, 8, 10, 12, 14, 16 X = O; 7, 9, 11, 13, 15, 17 X = S

1-Aryldihydro-2,4(1H,3H)pyrimidindiones 12, 14, 16 and their 2-thioanalogues 13, 15, 17 were prepared by condensation of N-aryl-β-alanines or their hydrochlorides 3-5 with urea or potassium thiocyanate in acetic acid under reflux, followed by cyclization by hydrochloric acid of the intermediate N-aryl-N-carbamoyl-β-alanines 6, 8, 10 and N-aryl-N-thiocarbamoyl-β-alanines 7, 9, 11 to give the more stable dihydropyrimidinediones 12, 14, 16 and their 2-thioanalogues 13, 15, 17.

The dihydropyrimidindiones and their 2-thio analogues are acid-resistant, but in basic medium they easily cleave forming the respective salts of N-aryl-N-carbamoyl- and N-aryl-N-thiocarbamoyl-β-alanines. Compound 14b was cleaved in 10 % sodium hydroxide solution by heating the reaction mixture to boiling temperature. N-Carbamoyl-β-alanine 8b was separated from reaction mixture by acidifying this solution with acetic acid. Condensation of N-(2,3-dimethylphenyl)-α-methyl-β-alanine (4a) and N-(3,5-dimethylphenyl)-α-methyl-β-alanine (4c) with ethyl acetoacetate gave the corresponding 1-aryl-3-ethoxycarbonyl-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)pyridones 18.

The structure of the studied compounds was investigated using ¹H-, ¹³C-, ¹H/¹³C (HETCOR) NMR and IR spectroscopy. The NMR spectra were assigned unambiguously through consideration of the features of ¹H-NMR spectral characteristics, the signal intensity arguments and the additivity rules of the ¹³C-NMR spectra, including DEPT ¹³C-NMR spectral characteristics [3,5].

The substituent increments used in this work were available in literature [3] and were obtained during the interpretation of spectra of the respective compounds [4]. ¹H/¹³C (HETCOR)-NMR spectra [5] were used to assist the assignments of the studied compounds, particularly to check the identification of the resonances of methyl groups located on the benzene and on the heterocyclic ring as well.

The presence of characteristic splitting of the resonances was observed during the spectroscopic analysis of compounds 12-18. The c-type compounds presented a single set of the resonances in their ¹H- and ¹³C-NMR spectra. A double set of the resonances for the C-4 atoms was only found in compounds 12b and 13b. Meanwhile, all a-type compounds produced NMR spectra with split resonances. Moreover, compounds 14a and 15a showed some additional splitting of the resonances of the C-2 and C-4 atoms. It has been suggested that such splitting of the resonances of the aforementioned compounds possessing methyl groups in different locations was caused by the restricted rotation of benzene and heterocyclic rings around the C(1’)-N(1) bond and the possibility of the existence of diastereomers.

Conclusions

We have presented the synthesis of new N-aryl-β-alanines and their cyclization products. The structure elucidation of the representative series of the study compounds was carried out using ¹H-, ¹³C-, ¹H/¹³C (HETCOR) NMR and IR spectroscopy. The examination in detail of the structural features of the reported compounds was not the aim of this study and will be performed in the planned subsequent work.

Experimental

General

The ¹H- and ¹³C-NMR spectra were recorded on a Jeol FX 100 (100 MHz) or Bruker DRX 500 (500 MHz) instruments; chemical shifts are reported in ppm on the δ scale with tetramethylsilane as the internal reference. The IR spectra were measured in a Perkin-Elmer Spectrum GX FT-IR system. Silica gel plates (Silufol UV-254) were used for analytical tlc. Spectroscopic data for the prepared compounds is given in Table 1. Physical properties, analytical data and yields for the prepared compounds are given in Table 2.

N-Carboxyethyl-N-(2,3- and 3,4-dimethylphenyl)-β-alanine hydrochlorides (2a,b). A solution of the corresponding dimethylanilines 1a,b (3.03 g, 0.025 mol), water (20 mL) and acrylic acid (5.4 g, 0.075 mol) was heated with stirring for 6 h at 90-100 °C. At the end of reaction period the reaction mixture was treated with 5 % sodium hydroxide solution (50 mL), cooled and extracted with diethyl ether (3 x 50 mL). The alkaline solution was neutralized with hydrochloric acid and extracted with diethyl ether (3 x 50 mL). The ethereal solution dried by cooling for 1 h at -20 °C, filtered and saturated ethereal-hydrogen chloride solution was added. The resulting precipitate was filtered off.

N-(2,3-Dimethylphenyl)-β-alanine (3a). A solution of 2,3-dimethylaniline (1a, 30.3 g, 0.1 mol), acrylic acid (7.2 g, 0.1 mol) and toluene (100 mL) was stirred for 24 h at 20 °C. Afterwards 5 % sodium hydroxide (200 mL) was added to the reaction mixture and non-reacted amine was extracted with diethyl ether (3 x 100 mL). The alkaline solution was neutralized with hydrochloric acid. The obtained oily residue of β-alanine 3a was washed with water to give a precipitate, which was filtered off and washed with water.

N-(3,4- and 3,5-Dimethylphenyl)-β-alanine hydrochlorides (3b,c). These compounds were synthesized from arylamines 1b,c by the procedure described for 3a and were obtained as oily residues. These oily residues were dissolved in diethyl ether (150 mL), dried by cooling at -20 °C for 1 h filtered and saturated ethereal – hydrogen chloride solution was added, resulting in a precipitate, which was filtered off.

N-(2,3- and 3,5-Dimethylphenyl)-α-methyl-β-alanines (4a,c). A solution of the 2,3-dimethylaniline 1a,c (30.3 g, 0.25 mol), methacrylic acid (23.7 g, 0.275 mol), toluene (100 mL) and hydroquinone (1 g) was heated with stirring for 24 h at 70 °C. The solution was then allowed to cool and 5 % sodium hydroxide (200 mL) was added and non-reacted arylamine was isolated by extraction with toluene (1 x 100 mL) and diethyl ether (2 x 100 mL). The alkaline solution was neutralized with hydrochloric acid, giving an oily residue of the α-methyl-β-alanines 4a,c, which was washed with water to give a precipitate that was filtered and washed with water.

N-(3,4-Dimethylphenyl)-α-methyl-β-alanine hydrochloride (4b). A solution of 3,4-dimethylaniline (1b, 30.3 g, 0.25 mol), methacrylic acid (23.7 g, 0.275 mol), toluene (100 mL) and hydroquinone (1 g) was heated with stirring for 24 h at 70 °C. The solution was allowed to cool and 5 % sodium hydroxide solution (200 mL) was added and non-reacted arylamine was isolated by extraction with toluene (1 x 100 mL) and diethyl ether (2 x 100 mL). The alkaline solution was neutralized with hydrochloric acid and extracted with diethyl ether (3 x 100 mL). To the ethereal solution saturated ethereal-hydrogen chloride solution was added and resulting precipitate was filtered off.

N-(2,3- and 3,5-Dimethylphenyl)-β-methyl-β-alanine hydrochlorides (5a,c). A mixture of the corresponding arylamine 1a, c (23.7 g, 0.275 mol), crotonic acid and toluene (100 mL) was refluxed for 10 h cooled and 5 % sodium hydroxide solution (200 mL) was added. The toluene layer was isolated, alkaline solution was extracted with diethyl ether (2 x 100 mL) and neutralized with hydrochloric acid. The oily residue of β-methyl-β-alanines 5a,c thus obtained was washed with water, dissolved in diethyl ether (200 mL), dried by cooling 1 h at -20 °C, filtered and saturated ethereal-hydrogen chloride solution was added, resulting in a precipitate of the corresponding salt which was filtered off.

N-Carbamoyl-(3,4-dimethylphenyl)-α-methyl-β-alanine (8b). A mixture of dihydropyrimidinedione 14b (2.32 g, 0.01 mol) and 10 % sodium hydroxide (20 mL) was heated up to boiling temperature, filtered and kept at room temperature for 0.5 h. After that the mixture was acidified with 20 % acetic acid, the residue filtered off and washed with water.

1-(2,3-, 3,4- and 3,5-dimethylphenyl)dihydro-2,4(1H, 3H)pyrimidinediones (12a-c) and 5-methyl- and 6-methyldihydro-2,4(1H,3H)pyrimidindiones (14a-c, 16a,c). A mixture of the corresponding N-aryl-β-alanine or hydrochloride 3,4,5 (0.01 mol), urea (2.4 g, 0.02 mol) and acetic acid (10 mL) was heated under reflux for 14 h, then concentrated hydrochloric acid (5 mL) was added and refluxing was continued for 0.5 h. The reaction mixture was diluted with water (30 mL) and was kept in cold for crystallization. The dihydropyrimidinedione precipitates were filtered and washed with water.

1-(2,3-, 3,4- and 3,5-Dimethyl)dihydro-4(1H,3H)pyrimidinon-2-thiones (13a-c), 5-methyl- and 6-methyldihydro-4(1H,3H)pyrimidinon-2-thiones (15a-c, 17a,c). These compounds were obtained using the method for preparing 1-arylsubstituted dihydropyrimidinediones 12,14,15 using potassium thiocyanate instead of urea.

Preparation of 3-ethoxycarbonyl-1-(2,3- and 3,5-dimethylphenyl)-2,5-dimethyl-1,4,5,6-tetrahydro-4(1H)pyridones (18a,c). A reaction mixture of the corresponding N-aryl-α-methyl-β-alanine 4 (0.05 mol) and ethyl acetoacetate (30 mL) was refluxed for 8 h then cooled down to 20 °C, suspended in 5 % sodium carbonate solution (200 mL) and boiled. The reaction mixture was cooled down and extracted with diethyl ether (2 x 100 mL). The ethereal solution was dried with sodium carbonate (20 g) for 30 min, filtered, solvent was evaporated in vacuo, and the residue was washed with cold diethyl ether and hexane (10 mL).

Table 1. Spectroscopic data of the prepared compounds

Compounds	1H-NMR (solvent)	13C-NMR (solvent)	IR (KBr tabl.)
2a	(d6-DMSO) 2.35 (s, 3H, 2’-CH3Ar), 2.45 (s, 3H, 3’-CH3Ar), 2.30-2.65 (m, 4H, CH2CO), 3.65-3.95 (m, 4H, CH2NCH2), 7.30-7.90 (m, 3H, Ar), 11.14 (bs, 2H, COOH).	–	–
2b	(d6-DMSO) 2.30 (s, 6H, 3’,4’-CH3Ar), 2.44-2.80 (m, 4H, CH2CO), 3.66-3.98 (m, 4H, CH2NCH2), 7.40-7.70 (m, 3H, Ar), 10.60 (bs, 2H, COOH).	–	–
3a	(d6-acetone) 1.98 (s, 3H, 2’-CH3Ar), 2.18 (s, 3H, 3’-CH3Ar), 2.50-2.72 (m, 2H, CH2CO), 3.32-3.51 (m, 2H, NCH2), 6.40-7.10 (m, 3H, Ar).	–	–
3b	(d6-DMSO) δ: 2.29 (s, 6H, 3’,4’-CH3Ar), 2.74-3.45 (m, 2H, CH2CO), 3.40-3.62 (m, 2H, NCH2), 7.45-7.60 (m, 3H, Ar), 9.66 (bs, 1H, COOH).	–	–
3c	(d6-DMSO) 2.30 (s, 6H, 3’,5’-CH3Ar), 2.70-2.95 (m, 2H, CH2CO), 3.34-3.60 (m, 2H, NCH2), 7.02-7.25 (m, 3H, Ar), 10.25 (bs, 1H, COOH).	–	–
4a	(d6-acetone) 1.24 (d, J = 6.9 Hz, 3H, CH CH3), 2.02 (s, 3H, 2’-CH3Ar), 2.21 (s, 3H, 3’-CH3Ar), ), 2.65-3.06 (m, 1H, CH), 3.13-3.60 (m, 2H, NCH2), 6.50-7.10 (m, 3H, Ar).	–	–
4b	(d6-DMSO) 1.29 (d, J = 6.9 Hz, 3H, CH CH3), 2.28 (s, 6H, 3’,4’-CH3Ar), 2.75-3.10 (m, 1H, CH), 3.16-3.65 (m, 2H, NCH2), 7.25-7.50 (m, 3H, Ar), 10.66 (bs, 1H, COOH).	–	–
4c	(CDCl3) 1.25 (d, J = 7.02 Hz, 3H, CHCH3), 2.23 (s, 6H, 3’,5’-CH3Ar), 2.74-2.90 (m, 1H, CH), 3.14-3.27 (m, 2H, CH2N), 6.25-6.45 (m, 3H, Ar), 7.5 (bs, 1H, COOH).	(CDCl3) 14.84 (CHCH3), 21.47 (3’,5’-CH3Ar), 39.23 (CH), 47.09 (CH2), 111.39 (Ar-C-2’,6’), 120.22 (Ar-C-4’), 139.01 (Ar-C-3’,5’), 147.44 (Ar-C-1’), 181.17 (CO).	–
5a	(d6-DMSO) 1.36 (d, J = 6.5 Hz, 3H, CH CH3), 2.34 (s, 3H, 2’-CH3Ar), 2.37 (s, 3H, 3’-CH3Ar), 2.60-3.25 (m, 2H, CH2CO), 3.65-4.15 (m, H, CH), 7.45-7.65 (m, 3H, Ar), 10.67 (bs, 1H, COOH).	–	–
5c	(d6-DMSO) 1.35 (d, J = 6.6 Hz, 3H, CH CH3), 2.36 (s, 6H, 3’,5’-CH3Ar), 2.50-3.15 (m, 2H, CH2CO), 3.65-4.10 (m, 1H, CH), 7.02-7.32 (m, 3H, Ar), 10.70 (bs, 1H, COOH).	–	–
8b	(d6-DMSO) 1.01 (d, J = 7.0 Hz, 3H, CHCH3), 2.31 (s, 6H, 3’, 4’-CH3Ar), 2.37-2.56 (m, 1H, CHCO), 3.58-3.79 (m, 2H, CH2N), 6.99-7.23 (m, 3H, Ar), 12.20 (bs, 1H, NH).	(d6-DMSO) 14.58 (5-CH3), 18.84 (4’-CH3), 19.35 (3’-CH3), 38.33 (C-5), 51.23 (C-6), 125.16 (Ar-C-6’), 128.80 (Ar-C-2’), 130.33 (Ar-C-5’), 134.83 (Ar-C-4’), 137.37, (Ar-C-3’), 139.90 (Ar-C-1’), 157.41 (C-2), 175.93 (C-4).	3328.16 (NH), 1692.11 (C=O), 1631.71 (C=O).
12a	(d6-DMSO) 2.01 (s, 3H, 2’-CH3Ar), 2.21 (s, 3H, 3’-CH3Ar), 2.60-2.89 (m, 2H, CH2CO), 3.40-3.82 (m, 2H, CH2N), 7.07-7.19 (m, 3H, Ar), 10.32 (bs, 1H, NH).	(d6-DMSO) 13.81 (2’-CH3), 19.92 (3’-CH3), 30.98 (C-5), 44.69 (C-6), 124.68 (Ar-C-6’), 125.94 (Ar-C-5’), 128.63 (C-4’), 134.01 (Ar-C-2’), 137.38 (Ar-C-3’), 140.79 (Ar-C-1’), 151.70, 151.78 (C-2), 170.54, 170.63 (C-4).	3191.75 (NH), 1719.25 (C=O), 1689.35 (C=O).
12b	(d6-DMSO) 2.21 (s, 6H, 3’4’-CH3Ar), 2.72 (t, J = 6.7 Hz, 2H, CH2CO), 3.76 (t, J = 6.7 Hz, 2H, CH2N), 7.00-7.18 (m, 3H, Ar), 10.26 (bs, 1H, NH).	(d6-DMSO) 18.75 (4’-CH3), 19.28 (3’-CH3), 31.03 (C-5), 44.66 (C-6), 122.60 (Ar-C-6’), 126.39 (Ar-C-2’), 129.45 (Ar-C-5’), 133.86 (Ar-C-4’), 136.37 (Ar-C-3’), 139.68 (Ar-C-1’), 152.04 (C-2), 170.41, 170.50 (C-4).	3221.93 (NH), 1737.02 (C=O), 1689.56 (C=O).
12c	(d6-DMSO) 2.26 (s, 6H, 3’,5’-CH3Ar), 2.67 (t, J = 6.7 Hz, 3H, CH2CO), 3.76 (t, J = 6.7 Hz, 2H, CH2N), 6.87-6.93 (m, 3H, Ar), 10.32 (s, 1H, NH).	(d6-DMSO) 20.73 (3’,5’-CH3), 31.01 (C-5), 44.59 (C-6), 122.98 (Ar-C-2’, Ar-C-6’), 127.26 (C-4’), 137.64 (Ar-C-3’, Ar-C-5’), 141.86 (Ar-C-1’), 151.98 (C-2), 170.50, (C-4).	3207.49 (NH), 1727.61 (C=O), 1690.82 (C=O).
13a	(d6-DMSO) 2.07 (s, 3H, 2’-CH3Ar), 2.27 (s, 3H, 3-CH3Ar), 2.78-2.92 (m, 2H, CH2CO), 3.66-4.00 (m, 2H, CH2N), 7.05-7.16 (m, 3H, Ar), 11.22 (bs, 1H, NH).	(d6-DMSO) 13.79 (2’-CH3), 19.26 (3’-CH3), 30.20 (C-5), 47.91 (C-6), 124.46 (Ar-C-6’), 126.27 (Ar-C-5’), 129.09 (Ar-C-4’), 133.08 (Ar-C-2’), 137.56 (Ar-C-3’), 143.78 (Ar-C-1’), 166.74, 166.84 (C-4), 178.44, 178.57 (C-2).	3184.28 (NH), 1702.01 (C=O), 1213.70 (>N−CS−N< ).
13b	(d6-DMSO) 2.20 (s, 6H, 3’,4’-CH3Ar), 2.78 (t, J = 6.9 Hz, 2H, CH2CO), 3.85 (t, J = 6.9 Hz, 2H, CH2N), 7.00-7.22 (m, 3H, Ar), 11.13 (bs, 1H, NH).	(d6-DMSO) 18.88 (4’-CH3), 19.26 (3’-CH3), 30.32, 31.02 (C-5), 48.85 (C-6), 124.03 (Ar-C-6’), 127.53 (Ar-C-2’), 129.85 (Ar-C-5’), 135.47 (Ar-C-4’), 136.89 (Ar-C-3’), 142.80 (Ar-C-1’), 166.74, 166.83 (C-4), 179.14(C-2).	3176.11 (NH), 1717.41 (C=O), 1209.38 (>N−CS−N< ).
13c	(d6-DMSO) 2.28 (s, 6H, 3’,5’-CH3Ar), 2.78 (t, J = 6.9 Hz, 2H, CH2CO), 3.85 (t, J = 6.9 Hz, 2H, CH2N), 6.85-7.00 (m, 3H, Ar), 11.20 (bs, 1H, NH).	(d6-DMSO) 20.67 (3’,5’-CH3), 30.32 (C-5), 48.76 (C-6), 124.32 (Ar-C-2’, Ar-C-6’), 128.80 (Ar-C-4’), 138.16 (Ar-C-3’, Ar-C-5’), 144.94 (Ar-C-1’), 166.84 (C-4), 179.00 (C-2).	3186.44 (NH), 1736.13 (C=O), 1219.63 (>N−CS−N< ).
14a	(d6-DMSO) 1.12, 1.15 (2d, J = 6.8 Hz, 3H, 5-CH3), 2.04, 2.08 (2s, 3H, 2’-CH3Ar), 2.26 (s, 3H, 3’-CH3Ar), 2.80-2.99 (m, 1H, CHCO), 3.38-3.64 (m, 2H, CH2N), 7.05-7.20 (m, 3H, Ar), 10.29, 10.30 (2bs, 1H, NH).	(d6-DMSO) 12.01, 12.65 (5-CH3), 13.84 (2’-CH3), 19.86 19.95 (3’-CH3), 34.80 (C-5), 51.01, 51.10 (C-6), 124.18, 125.14 (Ar-C-6’), 125.13, 126.08 (Ar-C-5’), 128.51, 128.76 (Ar-C-4’), 133.87, 134.22 (Ar-C-2’), 137.34, 137.38 (Ar-C-3’), 140.67 (Ar-C-1’), 151.83, 151.92, 152.65 (C-2), 173.08, 173.17, 173.27, 173.36 (C-4).	3244.38 (NH), 1732.98 (C=O), 1694.97 (C=O).
14b	(CDCl3) 1.31 (d, J = 7.0 Hz, 3H, 5-CH3), 2.26 (s, 6H, 3’,4’-CH3Ar), 2.73-3.00 (m, 1H, CH), 3.51-4.05 (m, 2H, CH2N), 7.03-7.40 (m, 3H, Ar), 7.81 (s, 1H, NH).	–	–
14c	(d6-DMSO) 1.12 (d, J = 7.0 Hz, 3H, 5-CH3), 2.26 (s, 6H, 3’,5’-CH3Ar), 2.74-2.92 (m, 3H, CH2CO), 3.50-3.75 (m, 2H, CH2N), 6.86, 6.93 (2s, 3H, Ar), 10.30 (bs, 1H, NH).	(d6-DMSO) 12.16 (5-CH3), 20.74 (3’,5’-CH3), 34.89 (C-5), 50.88 (C-6), 122.88 (Ar-C-2’, Ar-C-6’), 127.22 (Ar-C-4’), 137.66 (Ar-C-3’, Ar-C-5’), 141.81 (Ar-C-1’), 151.97 (C-2), 173.17, (C-4).	3201.75 (NH), 1724.34 (C=O), 1682.58 (C=O).
15a	(d6-DMSO) 1.15 (d, J = 6.9 Hz. 3H, 5-CH3), 2.05, 2.09 (2s, 3H, 2’-CH3Ar), 2.26, 2.27 (2s, 3H, 3’-CH3Ar), 2.98-3.20 (m, 1H, CHCO), 3.65-3.90 (m, 2H, CH2N), 7.00-7.16 (m, 3H, Ar), 11.19, 11.23 (2s, 1H, NH).	(d6-DMSO) 11.86, 12.05 (5-CH3), 13.85 (2’-CH3), 19.78, 19.86 (3’-CH3), 33.93, 34.06 (C-5), 53.77, 53.84 (C-6), 124.16, 124,72 (Ar-C-6’), 126.20, 126.43 (Ar-C-5’), 129.04, 129.15 (Ar-C-4’), 133.04, 133.24 (Ar-C-2’), 137.56 (Ar-C-3’), 143.65 (Ar-C-1’), 169.62, 169.71, 169.84, 169.93 (C-4), 178.31, 178.44, 178.66 (C-2).	3177.51 (NH), 1701.97 (C=O), 1210.30 (>N−CS−N< ).
15b	(d6-DMSO) 1.16 (d, J = 6.9 Hz, 3H, 5-CH3), 2.27 (s, 6H, 3’,4’-CH3Ar), 2.91-3.07 (m, 1H, CHCO), 3.72-3.91 (m, 2H, CH2N), 7.00-7.26 (m, 3H, Ar), 11.24 (s, 1H, NH).	(d6-DMSO) 11.95 (5-CH3), 18.89 (4’-CH3), 19.26 (3’-CH3), 34.17 (C-5), 54.67 (C-6), 123.99 (C-6’), 127.46 (Ar-C-2’), 129.85 (Ar-C-5’), 135.46 (Ar-C-4’), 136.93 (Ar-C-3’), 142.70 (Ar-C-1’), 169.84 (C-4), 179.02 (C-2).	3174.29 (NH), 1703.01 (C=O), 1211.74 (>N−CS−N< ).
15c	(d6-DMSO) 1.14 (d, J = +6.9 Hz, 3H, 5-CH3), 2.33 (s, 6H, 3’,5’-CH3Ar), 2.88-3.17 (m, 3H, CHCO), 3.69-3.99 (m, 2H, CH2N), 6.85-7.00 (2s, 3H, Ar), 11.20 (s, 1H, NH).	(d6-DMSO) 11.92, 14.74 (5-CH3), 20.67, 20.74 (3’,5’-CH3), 34.17 (C-5), 54.60 (C-6), 124.28,124.87 (Ar-C-2’, Ar-C-6’), 128.77, 129.38 (C-4’), 138.18, 139.06 (Ar-C-3’, Ar-C-5’), 144.84 (Ar-C-1’), 169.83 (C-4), 178.93 (C-2).	3252.42 (NH), 1730.95 (C=O) 1207.11 (>N−CS−N< ).
16a	(d6-DMSO) 0.99, 1.17 (2d, J = 5.0 Hz, J = 5.1 Hz, 6-CH3), 2.04, 2.09 (2s, 3H, 2’-CH3Ar), 2.27 (s, 3H, 3’-CH3Ar), 2.40-3.15 (m, 2H, CH2CO), 3.60-4.10 (m, 1H, CHN), 6.95-7.20 (m, 3H, Ar), 10.37 (2bs, 1H, NH).	(d6-DMSO) 13.78, 14.50 (2’-CH3), 18.17, 18.70 (6-CH3), 19.96 19.98 (3’-CH3), 37.64, 38.16 (C-5), 50.18, 51.23 (C-6), 125.24, 125,43 (Ar-C-6’), 125.99, 127.26 (A-C-5’), 128.62, 128.89 (Ar-C-4’), 134.20,135.42 (Ar-C-2’), 137.16, 137,76 (Ar-C-3’), 138,81, 139.16 (Ar-C-1’), 151.16, 151.37 (C-2), 169, 94 (C-4).	3185.92 (NH), 1714.33 (C=O), 1678.05 (C=O).
16c	(d6-DMSO) 1.16 (d, J = 6.6 Hz, 3H, 6-CH3), 2.27 (s, 6H, 3’,5’-CH3Ar), 2.37-3.15 (m, 3H, CH2CO), 3.90-4.10 (m, 1H, CHN), 6.93 (s, 3H, Ar), 10.35 (bs, 1H, NH).	(d6-DMSO) 18.48 (6-CH3), 20.69 (3’,5’-CH3), 37.76 (C-5), 51.31 (C-6), 125.02 (Ar-C-2’, Ar-C-6’), 128.10 (Ar-C-4’), 137.91 (Ar-C-3’, Ar-C-5’), 140.51 (Ar-C-1’), 151.29 (C-2), 169.95 (C-4).	3205.99 (NH), 1728.28 (C=O), 1690.29 (C=O).
17a	(d6-DMSO) 1.01, 1.18 (2d, J = 6.7 Hz, 3H, 6-CH3), 2.07 (s, 3H, 3’-CH3Ar), 2.26, 2.28 (2s, 3H, 2’-CH3Ar), 2.50-3.25 (m, 2H, CH2CO), 3.80-4.25 (m, 1H, CHN), 6.99-7.20 (m, 3H, Ar), 11.27, 11.32 (2s, 1H, NH).	(d6-DMSO) 13.78, 15.00 (2’-CH3), 17.52 18.01 (6-CH3), 19.88 (3’-CH3), 36.90, 37.37, 37.62 (C-5), 53.69, 55.12 (C-6), 124.73, 125.60 (Ar-C-6’), 126.41, 126.50 (Ar-C-5’), 129.00, 129.20 (Ar-C-4’), 133.18, 134.54 (Ar-C-2’), 137.32, 137.86 (Ar-C-3’), 142.01, 142.15 (Ar-C-1’), 166.35, 166.51 (C-4), 177.92, 178.05 (C-2).	3221.61 (NH), 1702.49 (C=O), 1209.98 (>N−CS−N< ).
17c	(d6-DMSO) 1.23 (d, J = 6.7 Hz, 3H, 6-CH3), 2.34 (s, 6H, 3’,5’-CH3Ar), 2.45-3.30 (m, 3H, CH2CO), 3.96-4.12 (m, 1H, CHN), 6.96, 7.04 (2s, 3H, Ar), 11.29 (s, 1H, NH.	(d6-DMSO) 17.63 (6-CH3), 20.66 (3’,5’-CH3), 36.90 (C-5), 55.18 (C-6), 125.01, 125.39 (Ar-C-2’, Ar-C-6’), 129.07 (Ar-C-4’), 138.20 (Ar-C-3’, Ar-C-5’), 143.62 (Ar-C-1’), 166.34, 166.43 (C-4), 177.96 (C-2).	3219.94 (NH), 1734.70 (C=O), 1220.85 (>N−CS−N< ).
18a	(CDCl3) 1.24 (d, J = 6.8 Hz. 3H, 5-CH3), 1.39 (t, J = 7.1 Hz, 3H, COOCH2CH3), 1.96, 1.98 (2s, 3H, 2-CH3), 2.19, 2.25 (2s, 3H, 2’-CH3Ar), 2.33, 2.34 (2s, 3H, 3’-CH3), 2.60-2.82 (m, 1H, CHCO), 3.42-3.70 (m, 2H, CH2N), 4.30 (k, J = 7.1 Hz, COOCH2CH3), 6.90-7.30 (m, 3H, Ar).	(CDCl3) 12.88, 13.19 (5-CH3), 14.41 (COOCH2CH3), 14.21, 14.25 (2’-CH3), 19.17, 19.33 (2-CH3), 20.36, 20.43 (3’-CH3), 60.49 (COOCH2CH3), 106.02 (C-3), 38.40, 38.49 (C-5), 57.08, 57.28 (C-6), 124,44, 125.15 (Ar-C-6’), 127.00, 127.08 (Ar-C-5’), 130.11, 130.17 (Ar-C-4’), 133.64, 133.70 (Ar-C-2’), 139.20, 139.25 (Ar-C-3’), 142.75, 142.81 (Ar-C-1’), 163.47, 163.61 (C-2), 167.99, 168.03 (COOCH2CH3), 190.25, 190.36 (C-4).	1663.80 (C=O), 1249.25 (C−O−).
18c	(CDCl3) 1.18 (d, J = 6.9 Hz. 3H, 5-CH3), 1.34 (t, J = 7.1 Hz, 3H, COOCH2CH3), 2.00 (s, 3H, 2-CH3), 2.34 (s, 6H, 3’,5’-Ar), 2.54-2.73 (m, 1H, CHCO), 3.53-3.83 (m, 3H, CH2N), 4.28 (k, J = 7.1 Hz, 2H, COOCH2CH3), 6.77, 6.99 (2s, 3H, Ar).	(CDCl3) 12.99 (5-CH3), 14.39 (COOCH2CH3), 19.74 (2-CH3), 21.20 (3’,5’-CH3), 38.75 (C-5), 58.06, (C-6), 60.53 (COOCH2CH3), 106.70 (C-3), 124.11 (Ar-C-2’, C-6’), 129.75 (C-4’), 139.87 (C-3’,C-5’), 144.05 (Ar-C-1’), 162.54 (C-2), 168.06 (COOCH2CH3), 190.52 (C-4).	1726.31 (C=O), 1258.74 (C−O−).

Table 1. Spectroscopic data of the prepared compounds

Compounds	1H-NMR (solvent)	13C-NMR (solvent)	IR (KBr tabl.)
2a	(d6-DMSO) 2.35 (s, 3H, 2’-CH3Ar), 2.45 (s, 3H, 3’-CH3Ar), 2.30-2.65 (m, 4H, CH2CO), 3.65-3.95 (m, 4H, CH2NCH2), 7.30-7.90 (m, 3H, Ar), 11.14 (bs, 2H, COOH).	–	–
2b	(d6-DMSO) 2.30 (s, 6H, 3’,4’-CH3Ar), 2.44-2.80 (m, 4H, CH2CO), 3.66-3.98 (m, 4H, CH2NCH2), 7.40-7.70 (m, 3H, Ar), 10.60 (bs, 2H, COOH).	–	–
3a	(d6-acetone) 1.98 (s, 3H, 2’-CH3Ar), 2.18 (s, 3H, 3’-CH3Ar), 2.50-2.72 (m, 2H, CH2CO), 3.32-3.51 (m, 2H, NCH2), 6.40-7.10 (m, 3H, Ar).	–	–
3b	(d6-DMSO) δ: 2.29 (s, 6H, 3’,4’-CH3Ar), 2.74-3.45 (m, 2H, CH2CO), 3.40-3.62 (m, 2H, NCH2), 7.45-7.60 (m, 3H, Ar), 9.66 (bs, 1H, COOH).	–	–
3c	(d6-DMSO) 2.30 (s, 6H, 3’,5’-CH3Ar), 2.70-2.95 (m, 2H, CH2CO), 3.34-3.60 (m, 2H, NCH2), 7.02-7.25 (m, 3H, Ar), 10.25 (bs, 1H, COOH).	–	–
4a	(d6-acetone) 1.24 (d, J = 6.9 Hz, 3H, CH CH3), 2.02 (s, 3H, 2’-CH3Ar), 2.21 (s, 3H, 3’-CH3Ar), ), 2.65-3.06 (m, 1H, CH), 3.13-3.60 (m, 2H, NCH2), 6.50-7.10 (m, 3H, Ar).	–	–
4b	(d6-DMSO) 1.29 (d, J = 6.9 Hz, 3H, CH CH3), 2.28 (s, 6H, 3’,4’-CH3Ar), 2.75-3.10 (m, 1H, CH), 3.16-3.65 (m, 2H, NCH2), 7.25-7.50 (m, 3H, Ar), 10.66 (bs, 1H, COOH).	–	–
4c	(CDCl3) 1.25 (d, J = 7.02 Hz, 3H, CHCH3), 2.23 (s, 6H, 3’,5’-CH3Ar), 2.74-2.90 (m, 1H, CH), 3.14-3.27 (m, 2H, CH2N), 6.25-6.45 (m, 3H, Ar), 7.5 (bs, 1H, COOH).	(CDCl3) 14.84 (CHCH3), 21.47 (3’,5’-CH3Ar), 39.23 (CH), 47.09 (CH2), 111.39 (Ar-C-2’,6’), 120.22 (Ar-C-4’), 139.01 (Ar-C-3’,5’), 147.44 (Ar-C-1’), 181.17 (CO).	–
5a	(d6-DMSO) 1.36 (d, J = 6.5 Hz, 3H, CH CH3), 2.34 (s, 3H, 2’-CH3Ar), 2.37 (s, 3H, 3’-CH3Ar), 2.60-3.25 (m, 2H, CH2CO), 3.65-4.15 (m, H, CH), 7.45-7.65 (m, 3H, Ar), 10.67 (bs, 1H, COOH).	–	–
5c	(d6-DMSO) 1.35 (d, J = 6.6 Hz, 3H, CH CH3), 2.36 (s, 6H, 3’,5’-CH3Ar), 2.50-3.15 (m, 2H, CH2CO), 3.65-4.10 (m, 1H, CH), 7.02-7.32 (m, 3H, Ar), 10.70 (bs, 1H, COOH).	–	–
8b	(d6-DMSO) 1.01 (d, J = 7.0 Hz, 3H, CHCH3), 2.31 (s, 6H, 3’, 4’-CH3Ar), 2.37-2.56 (m, 1H, CHCO), 3.58-3.79 (m, 2H, CH2N), 6.99-7.23 (m, 3H, Ar), 12.20 (bs, 1H, NH).	(d6-DMSO) 14.58 (5-CH3), 18.84 (4’-CH3), 19.35 (3’-CH3), 38.33 (C-5), 51.23 (C-6), 125.16 (Ar-C-6’), 128.80 (Ar-C-2’), 130.33 (Ar-C-5’), 134.83 (Ar-C-4’), 137.37, (Ar-C-3’), 139.90 (Ar-C-1’), 157.41 (C-2), 175.93 (C-4).	3328.16 (NH), 1692.11 (C=O), 1631.71 (C=O).
12a	(d6-DMSO) 2.01 (s, 3H, 2’-CH3Ar), 2.21 (s, 3H, 3’-CH3Ar), 2.60-2.89 (m, 2H, CH2CO), 3.40-3.82 (m, 2H, CH2N), 7.07-7.19 (m, 3H, Ar), 10.32 (bs, 1H, NH).	(d6-DMSO) 13.81 (2’-CH3), 19.92 (3’-CH3), 30.98 (C-5), 44.69 (C-6), 124.68 (Ar-C-6’), 125.94 (Ar-C-5’), 128.63 (C-4’), 134.01 (Ar-C-2’), 137.38 (Ar-C-3’), 140.79 (Ar-C-1’), 151.70, 151.78 (C-2), 170.54, 170.63 (C-4).	3191.75 (NH), 1719.25 (C=O), 1689.35 (C=O).
12b	(d6-DMSO) 2.21 (s, 6H, 3’4’-CH3Ar), 2.72 (t, J = 6.7 Hz, 2H, CH2CO), 3.76 (t, J = 6.7 Hz, 2H, CH2N), 7.00-7.18 (m, 3H, Ar), 10.26 (bs, 1H, NH).	(d6-DMSO) 18.75 (4’-CH3), 19.28 (3’-CH3), 31.03 (C-5), 44.66 (C-6), 122.60 (Ar-C-6’), 126.39 (Ar-C-2’), 129.45 (Ar-C-5’), 133.86 (Ar-C-4’), 136.37 (Ar-C-3’), 139.68 (Ar-C-1’), 152.04 (C-2), 170.41, 170.50 (C-4).	3221.93 (NH), 1737.02 (C=O), 1689.56 (C=O).
12c	(d6-DMSO) 2.26 (s, 6H, 3’,5’-CH3Ar), 2.67 (t, J = 6.7 Hz, 3H, CH2CO), 3.76 (t, J = 6.7 Hz, 2H, CH2N), 6.87-6.93 (m, 3H, Ar), 10.32 (s, 1H, NH).	(d6-DMSO) 20.73 (3’,5’-CH3), 31.01 (C-5), 44.59 (C-6), 122.98 (Ar-C-2’, Ar-C-6’), 127.26 (C-4’), 137.64 (Ar-C-3’, Ar-C-5’), 141.86 (Ar-C-1’), 151.98 (C-2), 170.50, (C-4).	3207.49 (NH), 1727.61 (C=O), 1690.82 (C=O).
13a	(d6-DMSO) 2.07 (s, 3H, 2’-CH3Ar), 2.27 (s, 3H, 3-CH3Ar), 2.78-2.92 (m, 2H, CH2CO), 3.66-4.00 (m, 2H, CH2N), 7.05-7.16 (m, 3H, Ar), 11.22 (bs, 1H, NH).	(d6-DMSO) 13.79 (2’-CH3), 19.26 (3’-CH3), 30.20 (C-5), 47.91 (C-6), 124.46 (Ar-C-6’), 126.27 (Ar-C-5’), 129.09 (Ar-C-4’), 133.08 (Ar-C-2’), 137.56 (Ar-C-3’), 143.78 (Ar-C-1’), 166.74, 166.84 (C-4), 178.44, 178.57 (C-2).	3184.28 (NH), 1702.01 (C=O), 1213.70 (>N−CS−N< ).
13b	(d6-DMSO) 2.20 (s, 6H, 3’,4’-CH3Ar), 2.78 (t, J = 6.9 Hz, 2H, CH2CO), 3.85 (t, J = 6.9 Hz, 2H, CH2N), 7.00-7.22 (m, 3H, Ar), 11.13 (bs, 1H, NH).	(d6-DMSO) 18.88 (4’-CH3), 19.26 (3’-CH3), 30.32, 31.02 (C-5), 48.85 (C-6), 124.03 (Ar-C-6’), 127.53 (Ar-C-2’), 129.85 (Ar-C-5’), 135.47 (Ar-C-4’), 136.89 (Ar-C-3’), 142.80 (Ar-C-1’), 166.74, 166.83 (C-4), 179.14(C-2).	3176.11 (NH), 1717.41 (C=O), 1209.38 (>N−CS−N< ).
13c	(d6-DMSO) 2.28 (s, 6H, 3’,5’-CH3Ar), 2.78 (t, J = 6.9 Hz, 2H, CH2CO), 3.85 (t, J = 6.9 Hz, 2H, CH2N), 6.85-7.00 (m, 3H, Ar), 11.20 (bs, 1H, NH).	(d6-DMSO) 20.67 (3’,5’-CH3), 30.32 (C-5), 48.76 (C-6), 124.32 (Ar-C-2’, Ar-C-6’), 128.80 (Ar-C-4’), 138.16 (Ar-C-3’, Ar-C-5’), 144.94 (Ar-C-1’), 166.84 (C-4), 179.00 (C-2).	3186.44 (NH), 1736.13 (C=O), 1219.63 (>N−CS−N< ).
14a	(d6-DMSO) 1.12, 1.15 (2d, J = 6.8 Hz, 3H, 5-CH3), 2.04, 2.08 (2s, 3H, 2’-CH3Ar), 2.26 (s, 3H, 3’-CH3Ar), 2.80-2.99 (m, 1H, CHCO), 3.38-3.64 (m, 2H, CH2N), 7.05-7.20 (m, 3H, Ar), 10.29, 10.30 (2bs, 1H, NH).	(d6-DMSO) 12.01, 12.65 (5-CH3), 13.84 (2’-CH3), 19.86 19.95 (3’-CH3), 34.80 (C-5), 51.01, 51.10 (C-6), 124.18, 125.14 (Ar-C-6’), 125.13, 126.08 (Ar-C-5’), 128.51, 128.76 (Ar-C-4’), 133.87, 134.22 (Ar-C-2’), 137.34, 137.38 (Ar-C-3’), 140.67 (Ar-C-1’), 151.83, 151.92, 152.65 (C-2), 173.08, 173.17, 173.27, 173.36 (C-4).	3244.38 (NH), 1732.98 (C=O), 1694.97 (C=O).
14b	(CDCl3) 1.31 (d, J = 7.0 Hz, 3H, 5-CH3), 2.26 (s, 6H, 3’,4’-CH3Ar), 2.73-3.00 (m, 1H, CH), 3.51-4.05 (m, 2H, CH2N), 7.03-7.40 (m, 3H, Ar), 7.81 (s, 1H, NH).	–	–
14c	(d6-DMSO) 1.12 (d, J = 7.0 Hz, 3H, 5-CH3), 2.26 (s, 6H, 3’,5’-CH3Ar), 2.74-2.92 (m, 3H, CH2CO), 3.50-3.75 (m, 2H, CH2N), 6.86, 6.93 (2s, 3H, Ar), 10.30 (bs, 1H, NH).	(d6-DMSO) 12.16 (5-CH3), 20.74 (3’,5’-CH3), 34.89 (C-5), 50.88 (C-6), 122.88 (Ar-C-2’, Ar-C-6’), 127.22 (Ar-C-4’), 137.66 (Ar-C-3’, Ar-C-5’), 141.81 (Ar-C-1’), 151.97 (C-2), 173.17, (C-4).	3201.75 (NH), 1724.34 (C=O), 1682.58 (C=O).
15a	(d6-DMSO) 1.15 (d, J = 6.9 Hz. 3H, 5-CH3), 2.05, 2.09 (2s, 3H, 2’-CH3Ar), 2.26, 2.27 (2s, 3H, 3’-CH3Ar), 2.98-3.20 (m, 1H, CHCO), 3.65-3.90 (m, 2H, CH2N), 7.00-7.16 (m, 3H, Ar), 11.19, 11.23 (2s, 1H, NH).	(d6-DMSO) 11.86, 12.05 (5-CH3), 13.85 (2’-CH3), 19.78, 19.86 (3’-CH3), 33.93, 34.06 (C-5), 53.77, 53.84 (C-6), 124.16, 124,72 (Ar-C-6’), 126.20, 126.43 (Ar-C-5’), 129.04, 129.15 (Ar-C-4’), 133.04, 133.24 (Ar-C-2’), 137.56 (Ar-C-3’), 143.65 (Ar-C-1’), 169.62, 169.71, 169.84, 169.93 (C-4), 178.31, 178.44, 178.66 (C-2).	3177.51 (NH), 1701.97 (C=O), 1210.30 (>N−CS−N< ).
15b	(d6-DMSO) 1.16 (d, J = 6.9 Hz, 3H, 5-CH3), 2.27 (s, 6H, 3’,4’-CH3Ar), 2.91-3.07 (m, 1H, CHCO), 3.72-3.91 (m, 2H, CH2N), 7.00-7.26 (m, 3H, Ar), 11.24 (s, 1H, NH).	(d6-DMSO) 11.95 (5-CH3), 18.89 (4’-CH3), 19.26 (3’-CH3), 34.17 (C-5), 54.67 (C-6), 123.99 (C-6’), 127.46 (Ar-C-2’), 129.85 (Ar-C-5’), 135.46 (Ar-C-4’), 136.93 (Ar-C-3’), 142.70 (Ar-C-1’), 169.84 (C-4), 179.02 (C-2).	3174.29 (NH), 1703.01 (C=O), 1211.74 (>N−CS−N< ).
15c	(d6-DMSO) 1.14 (d, J = +6.9 Hz, 3H, 5-CH3), 2.33 (s, 6H, 3’,5’-CH3Ar), 2.88-3.17 (m, 3H, CHCO), 3.69-3.99 (m, 2H, CH2N), 6.85-7.00 (2s, 3H, Ar), 11.20 (s, 1H, NH).	(d6-DMSO) 11.92, 14.74 (5-CH3), 20.67, 20.74 (3’,5’-CH3), 34.17 (C-5), 54.60 (C-6), 124.28,124.87 (Ar-C-2’, Ar-C-6’), 128.77, 129.38 (C-4’), 138.18, 139.06 (Ar-C-3’, Ar-C-5’), 144.84 (Ar-C-1’), 169.83 (C-4), 178.93 (C-2).	3252.42 (NH), 1730.95 (C=O) 1207.11 (>N−CS−N< ).
16a	(d6-DMSO) 0.99, 1.17 (2d, J = 5.0 Hz, J = 5.1 Hz, 6-CH3), 2.04, 2.09 (2s, 3H, 2’-CH3Ar), 2.27 (s, 3H, 3’-CH3Ar), 2.40-3.15 (m, 2H, CH2CO), 3.60-4.10 (m, 1H, CHN), 6.95-7.20 (m, 3H, Ar), 10.37 (2bs, 1H, NH).	(d6-DMSO) 13.78, 14.50 (2’-CH3), 18.17, 18.70 (6-CH3), 19.96 19.98 (3’-CH3), 37.64, 38.16 (C-5), 50.18, 51.23 (C-6), 125.24, 125,43 (Ar-C-6’), 125.99, 127.26 (A-C-5’), 128.62, 128.89 (Ar-C-4’), 134.20,135.42 (Ar-C-2’), 137.16, 137,76 (Ar-C-3’), 138,81, 139.16 (Ar-C-1’), 151.16, 151.37 (C-2), 169, 94 (C-4).	3185.92 (NH), 1714.33 (C=O), 1678.05 (C=O).
16c	(d6-DMSO) 1.16 (d, J = 6.6 Hz, 3H, 6-CH3), 2.27 (s, 6H, 3’,5’-CH3Ar), 2.37-3.15 (m, 3H, CH2CO), 3.90-4.10 (m, 1H, CHN), 6.93 (s, 3H, Ar), 10.35 (bs, 1H, NH).	(d6-DMSO) 18.48 (6-CH3), 20.69 (3’,5’-CH3), 37.76 (C-5), 51.31 (C-6), 125.02 (Ar-C-2’, Ar-C-6’), 128.10 (Ar-C-4’), 137.91 (Ar-C-3’, Ar-C-5’), 140.51 (Ar-C-1’), 151.29 (C-2), 169.95 (C-4).	3205.99 (NH), 1728.28 (C=O), 1690.29 (C=O).
17a	(d6-DMSO) 1.01, 1.18 (2d, J = 6.7 Hz, 3H, 6-CH3), 2.07 (s, 3H, 3’-CH3Ar), 2.26, 2.28 (2s, 3H, 2’-CH3Ar), 2.50-3.25 (m, 2H, CH2CO), 3.80-4.25 (m, 1H, CHN), 6.99-7.20 (m, 3H, Ar), 11.27, 11.32 (2s, 1H, NH).	(d6-DMSO) 13.78, 15.00 (2’-CH3), 17.52 18.01 (6-CH3), 19.88 (3’-CH3), 36.90, 37.37, 37.62 (C-5), 53.69, 55.12 (C-6), 124.73, 125.60 (Ar-C-6’), 126.41, 126.50 (Ar-C-5’), 129.00, 129.20 (Ar-C-4’), 133.18, 134.54 (Ar-C-2’), 137.32, 137.86 (Ar-C-3’), 142.01, 142.15 (Ar-C-1’), 166.35, 166.51 (C-4), 177.92, 178.05 (C-2).	3221.61 (NH), 1702.49 (C=O), 1209.98 (>N−CS−N< ).
17c	(d6-DMSO) 1.23 (d, J = 6.7 Hz, 3H, 6-CH3), 2.34 (s, 6H, 3’,5’-CH3Ar), 2.45-3.30 (m, 3H, CH2CO), 3.96-4.12 (m, 1H, CHN), 6.96, 7.04 (2s, 3H, Ar), 11.29 (s, 1H, NH.	(d6-DMSO) 17.63 (6-CH3), 20.66 (3’,5’-CH3), 36.90 (C-5), 55.18 (C-6), 125.01, 125.39 (Ar-C-2’, Ar-C-6’), 129.07 (Ar-C-4’), 138.20 (Ar-C-3’, Ar-C-5’), 143.62 (Ar-C-1’), 166.34, 166.43 (C-4), 177.96 (C-2).	3219.94 (NH), 1734.70 (C=O), 1220.85 (>N−CS−N< ).
18a	(CDCl3) 1.24 (d, J = 6.8 Hz. 3H, 5-CH3), 1.39 (t, J = 7.1 Hz, 3H, COOCH2CH3), 1.96, 1.98 (2s, 3H, 2-CH3), 2.19, 2.25 (2s, 3H, 2’-CH3Ar), 2.33, 2.34 (2s, 3H, 3’-CH3), 2.60-2.82 (m, 1H, CHCO), 3.42-3.70 (m, 2H, CH2N), 4.30 (k, J = 7.1 Hz, COOCH2CH3), 6.90-7.30 (m, 3H, Ar).	(CDCl3) 12.88, 13.19 (5-CH3), 14.41 (COOCH2CH3), 14.21, 14.25 (2’-CH3), 19.17, 19.33 (2-CH3), 20.36, 20.43 (3’-CH3), 60.49 (COOCH2CH3), 106.02 (C-3), 38.40, 38.49 (C-5), 57.08, 57.28 (C-6), 124,44, 125.15 (Ar-C-6’), 127.00, 127.08 (Ar-C-5’), 130.11, 130.17 (Ar-C-4’), 133.64, 133.70 (Ar-C-2’), 139.20, 139.25 (Ar-C-3’), 142.75, 142.81 (Ar-C-1’), 163.47, 163.61 (C-2), 167.99, 168.03 (COOCH2CH3), 190.25, 190.36 (C-4).	1663.80 (C=O), 1249.25 (C−O−).
18c	(CDCl3) 1.18 (d, J = 6.9 Hz. 3H, 5-CH3), 1.34 (t, J = 7.1 Hz, 3H, COOCH2CH3), 2.00 (s, 3H, 2-CH3), 2.34 (s, 6H, 3’,5’-Ar), 2.54-2.73 (m, 1H, CHCO), 3.53-3.83 (m, 3H, CH2N), 4.28 (k, J = 7.1 Hz, 2H, COOCH2CH3), 6.77, 6.99 (2s, 3H, Ar).	(CDCl3) 12.99 (5-CH3), 14.39 (COOCH2CH3), 19.74 (2-CH3), 21.20 (3’,5’-CH3), 38.75 (C-5), 58.06, (C-6), 60.53 (COOCH2CH3), 106.70 (C-3), 124.11 (Ar-C-2’, C-6’), 129.75 (C-4’), 139.87 (C-3’,C-5’), 144.05 (Ar-C-1’), 162.54 (C-2), 168.06 (COOCH2CH3), 190.52 (C-4).	1726.31 (C=O), 1258.74 (C−O−).

Table 2. The physical, analytical and yield data of the studied compounds

Compounds	M. p., °C; (Solv.*)	Molecular Formula	Elemental analysis data (Calculated / Found) %			Yield, %
			C	H	N
2a	168-195	C14H19NO4·HCl	55.71 / 55.48	6.69 / 6.58	4.64 / 4.32	62.7
2b	194-195	C14H19NO4·HCl	55.71 / 55.41	6.69 / 6.42	4.64 / 4.79	54.9
3a	101-102	C11H15NO2	68.37 / 68.24	7.82 / 7.68	7.25 / 7.14	25.7
3b	151-158	C11H15NO2·HCl	57.51 / 57.29	7.03 / 7.31	6.10 / 6.34	26.7
3c	186-187	C11H15NO2·HCl	57.51 / 57.28	7.03 / 7.29	6.10 / 6.26	37.5
4a	100-101	C12H17NO2	69.54 / 69.67	8.27 / 8.35	6.76 / 6.92	38.0
4b	185-186	C12H17NO2·HCl	59.14 / 59.02	7.46 / 7.64	5.75 / 5.49	34.1
4c	129-130	C12H17NO2	69.54 / 69.22	8.27 / 8.11	6.76 / 6.36	58.3
5a	166-167	C12H17NO2·HCl	59.14 / 58.98	7.46 / 7.31	5.75 / 5.36	66.7
5c	170-172	C12H17NO2·HCl	59.14 / 58.96	7.46 / 7.28	5.75 / 5.61	69.6
8b	184-186	C13H18N2O3	62.38 / 62.16	7.25 / 7.38	11.19 / 11.32	75.4
12a	204-206	C12H14N2O2	66.04 / 65.89	6.47 / 6.64	12.84 / 12.66	57.6
12b	179-181	C12H14N2O2	66.04 / 66.24	6.47 / 6.31	12.84 / 12.61	41.4
12c	179-180	C12H14N2O2	66.04 / 66.31	6.47 / 6.67	12.84 / 12.65	29.4
13a	242-244	C12H14N2OS	61.51 / 61.32	6.02 / 5.84	11.96 / 11.72	51.3
13b	247-249	C12H14N2OS	61.51 / 61.44	6.02 / 5.87	11.96 / 11.79	50.9
13c	263-264	C12H14N2OS	61.51 / 61.39	6.02 / 5.79	11.96 / 11.75	60.5
14a	196-197	C13H16N2O2	67.22 / 67.05	6.94 / 6.77	12.06 / 12.27	60.3
14b	135-136	C13H16N2O2	67.22 / 67.41	6.94 / 6.78	12.06 / 12.20	78.3
14c	155-156	C13H16N2O2	67.22 / 67.38	6.94 / 6.81	12.06 / 12.34	33.2
15a	187-188	C13H16N2OS	62.87 / 62.69	6.49 / 6.65	11.28 / 11.47	39.5
15b	188-190	C13H16N2OS	62.87 / 62.64	6.49 / 6.35	11.28 / 11.41	38.7
15c	206-208	C13H16N2OS	62.87 / 62.69	6.49 / 6.62	11.28 / 11.05	47.8
16a	214 -216	C13H16N2O2	67.22 / 67.32	6.94 / 6.75	12.06 / 12.32	31.4
16c	181-182	C13H16N2O2	67.22 / 67.07	6.94 / 6.72	12.06 / 12.28	38.4
17a	224 -226	C13H16N2OS	62.87 / 62.45	6.49 / 6.58	11.28 / 11.11	26.6
17c	254-255	C13H16N2OS	62.87 / 62.45	6.49 / 6.31	11.28 / 11.40	38.5
18a	109-110	C18H23NO3	71.73 / 71.55	7.69 / 7.49	4.65 / 4.41	17.0
18c	111-112	C18H23NO3	71.73 / 71.46	7.69 / 7.82	4.65 / 4.47	6.6

*Solvents for crystallization: 2a,b, 3b,c, 4b, 5a,c – acetic acid, rest – ethanol.

Table 2. The physical, analytical and yield data of the studied compounds

Compounds	M. p., °C; (Solv.*)	Molecular Formula	Elemental analysis data (Calculated / Found) %			Yield, %
			C	H	N
2a	168-195	C14H19NO4·HCl	55.71 / 55.48	6.69 / 6.58	4.64 / 4.32	62.7
2b	194-195	C14H19NO4·HCl	55.71 / 55.41	6.69 / 6.42	4.64 / 4.79	54.9
3a	101-102	C11H15NO2	68.37 / 68.24	7.82 / 7.68	7.25 / 7.14	25.7
3b	151-158	C11H15NO2·HCl	57.51 / 57.29	7.03 / 7.31	6.10 / 6.34	26.7
3c	186-187	C11H15NO2·HCl	57.51 / 57.28	7.03 / 7.29	6.10 / 6.26	37.5
4a	100-101	C12H17NO2	69.54 / 69.67	8.27 / 8.35	6.76 / 6.92	38.0
4b	185-186	C12H17NO2·HCl	59.14 / 59.02	7.46 / 7.64	5.75 / 5.49	34.1
4c	129-130	C12H17NO2	69.54 / 69.22	8.27 / 8.11	6.76 / 6.36	58.3
5a	166-167	C12H17NO2·HCl	59.14 / 58.98	7.46 / 7.31	5.75 / 5.36	66.7
5c	170-172	C12H17NO2·HCl	59.14 / 58.96	7.46 / 7.28	5.75 / 5.61	69.6
8b	184-186	C13H18N2O3	62.38 / 62.16	7.25 / 7.38	11.19 / 11.32	75.4
12a	204-206	C12H14N2O2	66.04 / 65.89	6.47 / 6.64	12.84 / 12.66	57.6
12b	179-181	C12H14N2O2	66.04 / 66.24	6.47 / 6.31	12.84 / 12.61	41.4
12c	179-180	C12H14N2O2	66.04 / 66.31	6.47 / 6.67	12.84 / 12.65	29.4
13a	242-244	C12H14N2OS	61.51 / 61.32	6.02 / 5.84	11.96 / 11.72	51.3
13b	247-249	C12H14N2OS	61.51 / 61.44	6.02 / 5.87	11.96 / 11.79	50.9
13c	263-264	C12H14N2OS	61.51 / 61.39	6.02 / 5.79	11.96 / 11.75	60.5
14a	196-197	C13H16N2O2	67.22 / 67.05	6.94 / 6.77	12.06 / 12.27	60.3
14b	135-136	C13H16N2O2	67.22 / 67.41	6.94 / 6.78	12.06 / 12.20	78.3
14c	155-156	C13H16N2O2	67.22 / 67.38	6.94 / 6.81	12.06 / 12.34	33.2
15a	187-188	C13H16N2OS	62.87 / 62.69	6.49 / 6.65	11.28 / 11.47	39.5
15b	188-190	C13H16N2OS	62.87 / 62.64	6.49 / 6.35	11.28 / 11.41	38.7
15c	206-208	C13H16N2OS	62.87 / 62.69	6.49 / 6.62	11.28 / 11.05	47.8
16a	214 -216	C13H16N2O2	67.22 / 67.32	6.94 / 6.75	12.06 / 12.32	31.4
16c	181-182	C13H16N2O2	67.22 / 67.07	6.94 / 6.72	12.06 / 12.28	38.4
17a	224 -226	C13H16N2OS	62.87 / 62.45	6.49 / 6.58	11.28 / 11.11	26.6
17c	254-255	C13H16N2OS	62.87 / 62.45	6.49 / 6.31	11.28 / 11.40	38.5
18a	109-110	C18H23NO3	71.73 / 71.55	7.69 / 7.49	4.65 / 4.41	17.0
18c	111-112	C18H23NO3	71.73 / 71.46	7.69 / 7.82	4.65 / 4.47	6.6

*Solvents for crystallization: 2a,b, 3b,c, 4b, 5a,c – acetic acid, rest – ethanol.