There are few known methods for the synthesis of 3-sulfanylpyridin-2(1H)-ones. They are based on the transformations of thiazolo[4,5-b]pyridines1 or the introduction of a thio group via diazonium salts obtained from the hard to access 3-amino-2-methoxypyridines.2 3-Sulfanylpyridin-2(1H)-ones and 3-sulfanylquinolin-2(1H)-ones are used for the synthesis of 2-pyridones or 2-quinolones containing a divalent sulfur atom at the C-3 position bonded to alkyl, aryl groups, or a heterocyclic ring.2,3,4,5,6,7,8,9 Interest in such compounds is primarily owed to their biological activity.10,11,12,13,14,15,16,17,18,19 Among them, compounds that are effective in the treatment of erectile dysfunction,3,4,5,6 cancers,7, 8 possess antiviral activity9 including antiHIV,2, 20 exhibit the properties of cannabinoid receptor antagonists21 were found.

We proposed a strategy22 for the synthesis of 3-substituted pyridin-2(1H)-ones and their hydrogenated derivatives based on nucleophilic substitution of halogen in 2-chloro-N-(3-oxoalkenyl)- or 2-chloro-N-(3-oxoalkyl)-acetamides by a functional group with subsequent intramolecular cyclization of the resulting intermediate. This strategy makes it possible on the basis of a single substrate and several nucleophiles to obtain pyridin-2(1H)-ones or their hydrogenated derivatives with various substituents at position C-3.23,24,25,26,27,28,29 The rules of this cyclization were studied30 and it was shown that the replacement of the amide group by the thioamide31 or the introduction of a divalent sulfur atom into the α-position with respect to the carbamoyl group leads to an increase in acidity sufficient for intramolecular cyclization.32

A divalent sulfur atom can be introduced into the molecule by S-alkylation of thiols3, 6, 21 or cyclic thiocarbamates, dithiocarbamates, and thioureas.27 The latter compounds are crystalline and, unlike thiols, do not have an unpleasant odor. We previously reported on the possibility of such an approach (Scheme 1).27

scheme 1

Scheme 1

The reaction of the readily available23 2-chloro-N-(3-oxoalkenyl) acetamides 1a–c with 1,3-benzothiazole-2(3H)-thione (2), 1,3-benzoxazole-2(3H)-thione (3), and 1-methyl-1,3-dihydro-2H-benzimidazole-2-thione (4) afforded compounds 5a–c, 6a, 7a in 60–90% yields. Alkylation of thiones with chloroacetamides 1a–с was carried out in anhydrous Me2CO at room temperature in the presence of K2CO3 and a catalytic amounts of KI. Earlier,27 DMF was used as a solvent for the synthesis of compound 5а. Replacing DMF with Me2CO led to a reduction in the reaction time from several days to 4 h, as well as to an increase in the yield of compound 5а from 78 to 90% (Scheme 2).

scheme 2

Scheme 2

Previously, N-(3-oxoalkyl)amides of heteroarylsulfanylacetic acids were used by us for the synthesis of substituted 5,6-dihydropyridin-2(1H)-ones.27, 33 The possibility of intramolecular cyclization of N-(3-alkenyl)amides was demonstrated only by a single example.27 Compounds 5a–c, 6a, 7a were reacted with potassium tert-butylate in THF, the products being pyridin-2(1H)-ones 8a–c, 9a, 10a containing a divalent sulfur atom at position C-3 bonded to a heterocyclic ring. Pyridones 8a–c were obtained in 60–88% yields. In the case of compounds 9а and 10а, the reactions proceeded with low yields (25–27%) and were accompanied by the formation of byproducts (Scheme 3).

scheme 3

Scheme 3

We studied the transformations of 3-(1,3-benzothiazol-2-ylsulfanyl)-4,6-dimethylpyridin-2(1H)-one (8а) in alkylation and electrophilic substitution reactions. Alkylation of compound 8а with methyl iodide led to N-methylsubstituted pyridin-2(1Н)-one 11а. By the action of bromine on compound 8а in 1,4-dioxane, electrophilic substitution proceeded with the formation of 3-(1,3-benzothiazol-2-ylsulfanyl)-5-bromo-4,6-dimethylpyridin-2(1H)-one (12а). The yield of bromo derivative 12а was 70%. At the same time, nitration of 3-(1,3-benzothiazol-2-yl-sulfanyl)-4,6-dimethylpyridin-2(1H)-one (8а) with a mixture of KNO3 and H2SO4 proceeded at the benzothiazole ring. It is known that the treatment of 2-(alkylsulfanyl)benzothiazoles with the nitrating mixture leads to 2-(alkylsulfanyl)-6-nitro-1,3-benzothiazoles.34, 35 Apparently, in our case the reaction proceeds in the same position with the formation of product 13a, as evidenced by the spin-spin interaction between protons in the benzene ring of the benzothiazole fragment. Using a nitrating mixture (HNO3–H2SO4, 1: 4), dinitro derivative 14а was obtained from compound 8а in 49% yield. In this case, both the pyridine and benzothiazole rings were nitrated (Scheme 4).

scheme 4

Scheme 4

It was previously shown that 2-quinolones containing a divalent sulfur atom bonded to a heterocycle at the C-3 position upon heating with morpholine are converted into 3-mercapto-substituted derivatives in 31–35% yields.36 At the same time, 3-(1,3-benzothiazol-2-ylsulfanyl)pyridin-2(1H)-one 8а does not enter into the reaction under similar conditions. In order to obtain 3-sulfanylpyridin-2(1Н)-ones 15а–с, we studied the reaction of compounds 8а–с with zinc in AcOH leading to the reduction of the C=N bond in benzothiazole and subsequent cleavage of the heterocycle.37 Yields of 3-sulfanylpyridin-2(1H)-ones 15а–с amounted to 63–85% (Scheme 5).

scheme 5

Scheme 5

The structure of all the obtained compounds was confirmed by IR, 1Н, 13С NMR spectroscopy and elemental analysis. The NMR spectra are quite easy to interpret; however, one should take into account the features of prototropic tautomeric transformations characteristic to pyridin-2(1H)-ones. The position of the pyridone-pyridol tautomeric equilibrium depends on a number of factors: the concentration of the solution, the type of solvent, temperature, the structure of the compound, etc.38 If the rate of proton exchange is high enough, an averaged signal of two tautomeric forms is observed. As the rate decreases, the signals broaden, and at a low rate, both tautomeric forms are recorded.39 The rate of tautomeric transformations of compounds 8a–c, 10–14 a, 15a–c on the NMR time scale is rather high, therefore, the spectra contain narrow averaged signals of both tautomeric forms. At the same time, in the 13C NMR spectrum of compound 9a recorded in DMSO-d6 at room temperature, part of the signals of carbon atoms appears as broadened peaks, which are distinguishable only after long accumulation (Fig. 1). This indicates an average exchange rate.

Figure 1.
figure 1

13С NMR spectra of compound 9а recorded in а) CDCl3 and b) DMSO-d6.

Full size image

A decrease in the viscosity of the solvent should lead to an increase in the equilibrium rate. Indeed, after replacing DMSO-d6 with the less viscous CDCl3, the signals of carbon nuclei in the 13C NMR spectra looked like narrow peaks even at low temperatures. However, in deuterated chloroform solution, compound 9a, unlike compounds 8, 10 a, apparently exists mainly in the form of pyridin-2-ol. In the IR spectra of compounds 8, 10 a, stretching vibrations of the NH bond are in the range of 3425–3475 cm–1 in the form of a broadened signal, while the signal of the OH group of compound 9a is recorded at 3273 cm–1. In the 13С NMR spectrum of compound 9a, the signals of the С-3 and С-5 atoms are observed at 131.5 and 131.3 ppm, while in the spectra of pyridin-2(1H)-ones 8a and 10a they are in the 113.7–115.3 and 107.6–109.6 ppm ranges, respectively. In the 1Н NMR spectrum of compound 9а, the signal of the H-5 proton is observed further downfield at 6.63 ppm as compared to the signals of the same proton in the spectra of compounds 8, 10 a which resonate at 5.92–6.19 ppm. For compounds 8, 10 a, 1H–13C HMBC 2D NMR spectra were also recorded. The signals of the C atoms of these compounds were assigned based on the correlation with the protons of the methyl groups (1.74–2.53 ppm) and the proton at position C-5. In the 1H–13C HMBC spectrum of compound 9a, cross peaks 13C {1H}: 128.6 {12.45}, 142.8 {12.45}, 160.5 {12.45} ppm are recorded, indicating interaction of the proton of the OH group of pyridin-2-ol with carbon atoms C-7a, C-3a of 1,3-benzoxazole and the C-2 atom of pyridin-2-one.

To conclude, it has been shown that intramolecular cyclization of 2-(heteroarylsulfanyl)-N-(3-oxoalkenyl)-acetamides leads to pyridin-2(1H)-ones containing a divalent sulfur atom at position C-3 bonded to the heterocyclic ring. The reactions of alkylation, bromination, nitration have been studied by the example of 3-(1,3-benzothiazol-2-ylsulfanyl)-substituted pyridin-2(1H)-ones, and a new method for the preparation of hard-to-access 3-sulfanylpyridin-2(1H)-ones has been developed.

Experimental

IR spectra were registered on a FT-801 FT-IR spectrometer in KBr pellets. 1H and 13C NMR spectra and 1H–13C HMBC two-dimensional NMR spectra were acquired on a Bruker DRX 400 spectrometer (400 and 100 MHz, respectively), with TMS as internal standard. 13C NMR spectra were recorded in J-modulation (J-MOD) mode. Elemental analysis was performed on a Carlo Erba EA 1106 CHN-analyzer. Melting points were determined on a Kofler bench and a Reach devices RD-MP apparatus. Monitoring of the reaction progress and assessment of the purity of synthesized compounds were done by TLC on Sorbfil UV-254 plates, visualization under UV light. Purification by column chromatography was carried out using silica gel as a sorbent.

Synthesis of the starting 2-chloro-N-[(1Z)-3-oxoalkyl-1-en-1-yl]acetamides 1a–c was described by us earlier.24

Synthesis of 2-(heteroarylsulfanyl)-N-[(1Z)-3-oxoalk-1-en-1-yl]acetamides 5a–c, 6a, 7a (General method). A solution of compound 1а–с (1.0 mmol), K2CO3 (207 mg, 1.5 mmol), compound 2–4 (1.0 mmol), and KI (17 mg, 0.1 mmol) in anhydrous Me2CO (3 ml) was stirred at room temperature for 2–4 h. The solvent was removed under reduced pressure. The precipitate was treated with H2O (10 ml) and neutralized with 5% aqueous AcOH. It was then filtered off, washed with H2O, and crystallized from the EtOH–H2O system.

(Z)-2-(1,3-Benzothiazol-2-ylsulfanyl)-N-(4-oxopent-2-en-2-yl)acetamide (5a). Yield 276 mg (90%), paleyellow crystals, mp 112–113°С (EtOH–H2O). IR spectrum, ν, cm–1: 1592 (NC=O), 1649 (C=O), 1698 (C=O), 3200–3645 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.13 (3H, s, COCH3); 2.37 (3H, d, 4J = 1.0, =C–CH3); 4.19 (2H, s, SСH2); 5.36 (1H, q, 4J = 1.0, =СH); 7.27–7.32 (1Н, m, H-6 benzothiazole); 7.38–7.43 (1Н, m, H-5 benzothiazole); 7.73–7.77 (1Н, m, H-7 benzothiazole); 7.88–7.92 (1Н, m, H-4 benzothiazole); 12.84 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 21.8 (CH3); 30.5 (CH3); 37.8 (CH2S); 106.6 (=CH); 121.0 (C-7 benzothiazole); 121.9 (С-4 benzothiazole); 124.4 (C-6 benzothiazole); 126.0 (C-5 benzothiazole); 135.7 (C-7a benzothiazole); 154.0 (=C–NH); 152.8 (C-3a benzothiazole); 164.2 (C-2 benzothiazole); 167.3 (C=O); 199.4 (NC=O). Found, %: С 54.96; H 4.67; N 9.03. C14H14N2O2S2. Calculated, %: С 54.88; H 4.61; N 9.14.

(Z)-2-(1,3-Benzothiazol-2-ylsulfanyl)-N-(4-oxo-4-phenylbut-2-en-2-yl)acetamide (5b). Yield 283 mg (77%), pale-yellow powder, mp 80–81°С (EtOH–H2O). IR spectrum, ν, cm–1: 1600 (NC=O), 1622 (C=O), 1699 (C=O), 3305–3628 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.51 (3H, d, 4J = 1.0, =CCH3); 4.46 (2H, s, SСH2); 6.07 (1H, q, 4J = 1.0, =СH); 7.24–7.30 (1H, m, H-6 benzothiazole); 7.34–7.40 (1H, m, H-5 benzothiazole); 7.41–7.46 (2H, m, H-3,5 Ph); 7.50–7.54 (1H, m, H-4 Ph); 7.72–7.75 (1Н, m, H-7 benzothiazole); 7.91–7.94 (1Н, m, H-4 benzothiazole); 7.87–7.90 (2H, m, H-2,6 Ph); 13.26 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 22.5 (CH3); 38.1 (CH2S); 102.9 (=CH); 121.0 (C-7 benzothiazole); 122.0 (C-4 benzothiazole); 124.5 (C-6 benzothiazole); 126.1 (C-5 benzothiazole); 127.8 (2C); 128.6 (C-2,3,5,6 Ph); 132.5 (C-4 Ph); 135.8 (C-7a benzothiazole); 138.6 (C-1 Ph); 152.9 (C-3a benzothiazole); 156.3 (=C–NH); 164.3 (C-2 benzothiazole); 167.5 (C=O); 191.2 (NC=O). Found, %: С 62.04; H 4.31; N 7.55. C19H16N2O2S2. Calculated, %: С 61.93; H 4.38; N 7.60.

N-(2-Acetylcyclohex-1-en-1-yl)-2-(1,3-benzothiazol-2-ylsulfanyl) acetamide (5c). Yield 209 mg (60%), pale-brown crystals, mp 97–98°С (EtOH–H2O). IR spectrum, ν, cm–1: 1576 (NC=O), 1634 (C=O), 1691 (C=O), 3305–3630 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.57–1.65 (4H, m, CH2CH2); 2.19 (3H, s, COCH3); 2.34–2.42 (2H, m, =CCH2); 2.95–3.02 (2H, m, =CCH2); 4.16 (2H, s, SСH2); 7.25–7.31 (1Н, s, H-6 benzothiazole); 7.36–7.42 (1Н, m, H-5 benzothiazole); 7.71–7.75 (1Н, m, H-7 benzothiazole); 7.87–7.91 (1Н, m, H-4 benzothiazole); 13.23 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 21.5 (CH2); 22.0 (CH2); 26.5 (CH2); 28.5 (CH2); 28.9 (CH3); 38.3 (CH2S); 113.0 (=C); 121.0 (C-7 benzothiazole); 122.0 (C-4 benzothiazole); 124.4 (C-6 benzothiazole); 126.0 (C-5 benzothiazole); 135.7 (C-7a benzothiazole); 151.4 (C-3a benzothiazole); 153.0 (=C–NH); 164.7 (C-2 benzothiazole); 167.8 (C=O); 202.3 (NC=O). Found, %: С 59.06; H 5.31; N 7.99. C17H18N2O2S2. Calculated, %: С 58.93; H 5.24; N 8.09.

(Z)-2-(1,3-Benzoxazol-2-ylsulfanyl)-N-(4-oxopent-2-en-2-yl)acetamide (6a). Yield 235 mg (81%), pale-brown crystals, mp 123–124°С (EtOH–H2O). IR spectrum, ν, cm–1: 1600 (NC=O), 1647 (C=O), 1701 (C=O), 3276 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.13 (3H, s, COCH3); 2.38 (3H, d, 4J = 1.0, =CCH3); 4.16 (2H, s, SСH2); 5.38 (1H, q, 4J = 1.0, =СH); 7.22–7.30 (2H, m, H-5,6 benzoxazole); 7.42–7.748 (1Н, m, H-7 benzoxazole); 7.58–7.64 (1Н, m, H-4 benzoxazole); 12.85 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 21.8 (CH3); 30.5 (CH3); 37.2 (CH2S); 106.8 (=CH); 110.1 (C-5 benzoxazole); 118.8 (C-6 benzoxazole); 124.2, 124.4 (C-4,7 benzoxazole); 141.8 (C-3a benzoxazole); 152.3 (C-3a benzoxazole); 154.1 (=C–NH); 162.9 (C-2 benzoxazole); 166.7 (C=O); 199.6 (NC=O). Found, %: С 57.81; H 4.97; N 9.65. C14H14N2O3S. Calculated, %: С 57.92; H 4.86; N 9.56.

(Z)-2-[(1-Methyl-1H-benzimidazol-2-yl)sulfanyl]-N-(4-oxopent-2-en-2-yl)acetamide (7a). Yield 201 mg (66%), pale-brown crystals, mp 127–128°С (EtOH–H2O). IR spectrum, ν, cm–1: 1600 (NC=O), 1645 (C=O), 1701 (C=O), 3000–3350 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.08 (3H, s, COCH3); 2.34 (3H, d, 4J = 1.0, =CCH3); 3.37 (1H, s, NCH3); 4.25 (2H, s, SСH2); 5.32 (1H, q, 4J = 1.0, =СH); 7.17–7.29 (2H, m, H-5,6 benzimidazole); 7.61–7.69 (2H, m, H-4,7 benzimidazole); 12.76 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 21.8 (СH3); 30.1 (CH3); 30.4 (NCH3); 37.2 (CH2S); 106.6 (=CH); 108.5 (C-4 benzimidazole); 118.6 (C-7 benzimidazole); 121.8 (C-6 benzimidazole); 121.9 (C-5 benzimidazole); 137.2 (C-3a benzimidazole); 143.4 (C-3a benzimidazole); 150.0 (C-2 benzimidazole); 154.0 (=C–NH); 167.5 (C=O); 199.1 (NC=O). Found, %: С 59.46; H 5.76; N 13.72. C15H17N3O2S. Calculated, %: С 59.38; H 5.65; N 13.85.

Synthesis of 3-(heteroarylsulfanyl)pyridin-2(1H)-ones 8a–c, 10a and 3-(1,3-benzoxazol-2-ylsulfanyl)-4,6-dimethylpyridin-2-ol (9a) (General method). t-BuOK (168 mg, 1.5 mmol) was added with stirring and cooling in an ice bath to a solution of acetamide 5a–c, 7a, 6a (1.0 mmol) in anhydrous THF (5 ml). The mixture was stirred with cooling for 15 min and then at room temperature for 1 h. The solvent was removed under reduced pressure, the residue was treated with H2O (5 ml), neutralized with 5% AcOH solution, filtered off, washed with H2O, and recrystallized from EtOH.

3-(1,3-Benzothiazol-2-ylsulfanyl)-4,6-dimethylpyridin-2(1H)-one (8a). Yield 238 mg (88%), pale-yellow crystals, mp >250°С (EtOH). IR spectrum, ν, cm–1: 1649 (C=O), 3200–3300 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.24 (3H, s, CH3); 2.35 (3H, s, CH3); 6.19 (1H, s, H-5); 7.29 (1H, dd, 3J = 7.8, 3J = 7.4, H-6 benzothiazole); 7.41 (1H, dd, 3J = 8.0, 3J = 7.4, H-5 benzothiazole); 7.79 (1H, d, 3J = 8.0, H-7 benzothiazole); 7.88 (1H, d, 3J = 7.8, H-4 benzothiazole); 12.08 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 18.5 (CH3); 21.3 (CH3); 107.8 (C-5); 113.7 (C-3); 121.0 (C-7 benzothiazole); 121.5 (C-4 benzothiazole); 124.0 (C-6 benzothiazole); 126.2 (C-5 benzothiazole); 134.7 (C-7a benzothiazole); 148.7 (C-4); 153.8 (C-3a benzothiazole); 160.1 (C-6); 161.3 (C-2); 169.7 (C-2 benzothiazole). Found, %: С 58.24; H 4.27; N 9.83. C14H12N2OS2. Calculated, %: С 58.31; H 4.19; N 9.71.

3-(1,3-Benzothiazol-2-ylsulfanyl)-6-methyl-4-phenylpyridin-2(1H)-one (8b). Yield 210 mg (60%), beige crystals, mp 205–206°С (EtOH). IR spectrum, ν, cm–1: 1640 (C=O), 3225–3660 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.33 (3H, s, CH3); 6.26 (1H, s, H-5); 7.26–7.35 (1H, m, H-6 benzothiazole); 7.35–7.40 (1H, m, H-5 benzothiazole); 7.37–7.46 (5H, m, H Ph); 7.77 (1H, d, 3J = 8.0; H-7 benzothiazole); 7.91 (1H, d, 3J = 7.9, H-4 benzothiazole); 12.35 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 18.6 (CH3); 107.3 (C-5); 112.9 (C-3); 121.0 (C-7 benzothiazole); 121.4 (C-4 benzothiazole); 124.0 (C-6 benzothiazole); 126.1 (C-5 benzothiazole); 127.8, 128.0 (C-2,3,5,6 Ph); 128.7 (C-4 Ph); 134.7 (C-7a benzothiazole); 138.5 (C-1 Ph); 149.3 (C-4); 153.5 (C-3a benzothiazole); 160.9 (C-6); 161.4 (C-2); 169.5 (C-2a benzothiazole). Found, %: С 64.99; H 4.11; N 8.08. C19H14N2OS2. Calculated, %: С 65.12; H 4.03; N 8.53.

3-(1,3-Benzothiazol-2-ylsulfanyl)-4-methyl-5,6,7,8-tetrahydroquinolin-2(1H)-one (8c). Yield 259 mg (78%), paleyellow crystals, mp 147–148°С (EtOH). IR spectrum, ν, cm–1: 1638 (C=O), 3250–3600 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.46–1.54 (2H, m, 7-CH2); 1.62–1.71 (2H, m, 6-CH2); 2.41(3H, s, CH3); 2.37–2.45 (4H, m, 5,8-CH2); 7.21–7.26 (1H, m, H-6 benzothiazole); 7.38–7.45 (1H, m, H-5 benzothiazole); 7.64 (1H, d, 3J = 8.0, H-7 benzothiazole); 7.85 (1H, d, 3J = 7.9, H-4 benzothiazole); 12.98 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 18.5 (CH3); 21.0 (CH2); 22.5 (CH2); 25.0 (CH2); 27.3 (CH2); 115.3 (C-5); 116.1 (C-3); 120.7 (C-7 benzothiazole); 121.8 (C-4 benzothiazole); 124.0 (C-6 benzothiazole); 125.9 (C-5 benzothiazole); 135.7 (C-7a benzothiazole); 146.3 (C-4); 154.2 (C-3a benzothiazole); 160.1 (C-6); 162.6 (C-2); 169.4 (C-2a benzothiazole). Found, %: С 62.03; H 4.83; N 8.61. C17H16N2OS2. Calculated, %: С 62.16; H 4.91; N 8.53.

3-(1,3-Benzoxazol-2-ylsulfanyl)-4,6-dimethylpyridin-2-ol (9a). Yield 68 mg (25 %), beige crystals, mp >250°С. IR spectrum, ν, cm–1: 1607 (Ar), 3273 (O–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 2.44 (3H, s, CH3); 2.53 (3H, s, CH3); 6.63 (1H, s, H-5); 7.16–7.27 (3H, m, H-6 benzoxazole); 7.35–7.45 (1H, m, H-6 benzoxazole); 12.30 (1H, br. s, OH). 13C NMR spectrum (CDCl3, –35°C), δ, ppm: 15.8 (CH3); 16.5 (CH3); 110.6 (C-6 benzoxazole); 111.1 (С-5 benzoxazole); 124.0 (C-4 benzoxazole); 125.0 (C-7 benzoxazole); 128.6 (C-7a benzoxazole); 131.3 (C-5); 131.5 (C-3); 142.8 (C-3a benzoxazole); 145.3 (С-6); 145.8 (C-4); 160.5 (C-2); 172.9 (C-2 benzoxazole). Found, %: С 61.60; H 4.51; N 10.36. C14H12N2O2S. Calculated, %: С 61.75; H 4.44; N 10.29.

4,6-Dimethyl-3-[(1-methyl-1H-benzimidazol-2-yl)sulfanyl]pyridin-2(1H)-one (10a). Yield 77 mg (70%), beige crystals, mp >250°С (EtOH). IR spectrum, ν, cm–1: 1634 (C=O), 3305–3645 (N–H). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.74 (3H, s, CH3); 2.44 (3H, s, CH3); 3.90 (3H, s, NCH3); 5.92 (1H, s, H-5); 7.16–7.30 (3H, m, H-4,5,6 benzimidazole); 7.65 (1H, d, 3J = 7.4, H-7 benzimidazole); 12.92 (1H, br. s, NH). 13C NMR spectrum (CDCl3), δ, ppm: 18.0 (CH3); 22.0 (CH3); 30.8 (NCH3); 108.8 (C-4 benzimidazole); 109.6 (C-5); 115.3 (C-3); 119.1 (C-7 benzimidazole); 121.7 (C-5 benzimidazole); 122.1 (C-6 benzimidazole); 136.3 (C-7a benzimidazole); 143.3 (C-3a benzimidazole); 145.6 (C-6); 149.5 (C-2 benzimidazole); 157.5 (C-4); 163.5 (C-2). Found, %: С 63.03; H 5.39; N 14.42. C15H15N3OS. Calculated, %: С 63.13; H 5.30; N 14.37.

3-(1,3-Benzothiazol-2-ylsulfanyl)-1,4,6-trimethylpyridin-2(1H)-one (11a). t-BuOK (168 mg, 1.5 mmol) was added with stirring and cooling in an ice bath to a solution of compound 8a (288 mg, 1.0 mmol), methyl iodide (110 μl, 1.75 mmol), and tetramethylammonium iodide (0.1 mg, 50 μmol) in anhydrous THF (2.0 ml). The mixture was stirred at room temperature for 3 h, then poured into H2O, neutralized, and extracted with CHCl3 (3×5 ml). CHCl3 was removed under reduced pressure, the residue was purified by column chromatography (silica gel 60–100 μm, eluent CHCl3–EtOAc, 1:1). Yield 179 mg (59%), paleyellow crystals, mp >250°С. IR spectrum, ν, cm–1: 1642 (C=O). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.40 (3H, s, CH3); 2.42 (3H, s, CH3); 3.57 (3H, s, NCH3); 6.13 (1H, s, H-5); 7.19–7.25 (1H, m, H-6 benzothiazole); 7.33–7.37 (1H, m, H-5 benzothiazole); 7.61–7.65 (1H, d, 3J = 8.0, H-7 benzothiazole); 7.82–7.85 (1H, d, 3J = 7.9, H-4 benzothiazole). 13C NMR spectrum (DMSO-d6), δ, ppm: 21.1 (CH3); 21.7 (CH3); 32.3 (NCH3); 109.6 (C-5); 115.8 (C-3); 120.7 (C-7 benzothiazole); 121.8 (C-4 benzothiazole); 123.9 (C-6 benzothiazole); 125.8 (C-5 benzothiazole); 135.6 (C-3a benzothiazole); 148.6 (C-4); 154.2 (C-3a benzothiazole); 157.8 (C-6); 162.2 (C-2); 168.8 (C-2 benzothiazole). Found, %: С 59.49; H 4.37; N 9.31. C15H14N2OS2. Calculated, %: С 59.57; H 4.67; N 9.26.

3-(1,3-Benzothiazol-2-ylsulfanyl)-5-bromo-4,6-dimethylpyridin-2(1H)-one (12a). A solution of Br2 (248 mg, 1.0 mmol) in 1,4-dioxane (6 ml) was added to a solution of compound 8a (288 mg, 1.0 mmol) in 1,4-dioxane (6 ml). The mixture was stirred at room temperature until the reaction was complete (TLC control, 8–10 h), then poured into ice cold H2O and neutralized with 2 N aqueous NaHCO3. The precipitate was filtered off, washed with H2O, and crystallized from EtOH. Yield 258 mg (70%), pale-yellow crystals, mp >250°С (EtOH). IR spectrum, ν, cm–1: 1647 (C=O), 3200–3650 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.44 (3H, s, CH3); 2.59 (3H, s, CH3); 7.31–7.34 (1H, m, H-5 benzothiazole); 7.42–7.46 (1H, m, H-6 benzothiazole); 7.82 (1H, d, 3J = 8.0, H-4 benzothiazole); 7.92 (1H, d, 3J = 7.9, H-7 benzothiazole); 12.59 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 20.7 (CH3); 23.3 (CH3); 99.4 (C-5); 121.1 (C-7 benzothiazole); 121.5 (C-4 benzothiazole); 124.1 (C-6 benzothiazole); 126.2 (C-5 benzothiazole); 134.7 (C-3, C-3 benzothiazole); 153.6 (C-4, C-7a benzothiazole); 158.2 (C-6); 159.8 (C-2); 168.3 (C-2 benzothiazole). Found, %: С 45.84; H 2.98; N 7.71. C14H11BrN2OS2. Calculated, %: С 45.78; H 3.02; N 7.63.

4,6-Dimethyl-3-[(6-nitro-1,3-benzothiazol-2-yl)sulfanyl]pyridin-2(1H)-one (13a). KNO3 (252 mg, 2.5 mmol) was added to a solution of compound 8a (288 mg, 1.0 mmol) in concentrated H2SO4 (3 ml). The mixture was stirred at room temperature for 4 h, then poured onto ice and neutralized with 2 N aqueous NaHCO3. The precipitate was filtered off, washed with H2O, and recrystallized from AcOH. Yield 165 mg (49%), yellow crystals, mp >250°С (AcOH). IR spectrum, ν, cm–1: 1332 (NO2), 1515 (NO2), 1656 (C=O), 3305–3677 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.27 (3H, s, CH3); 2.38 (3H, s, CH3); 6.25 (1H, s, H-5); 7.96 (1H, d, 3J = 9.0, H-4 benzothiazole); 8.27 (1H, dd, 3J = 9.0, 4J = 2.5, H-5 benzothiazole); 8.94 (1H, d, 4J = 2.5, H-7 benzothiazole); 12.18 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 18.5 (CH3); 21.2 (CH3); 107.9 (C-5); 112.9 (C-3); 118.4 (C-4 benzothiazole); 121.1, 121.8 (C-5,7 benzothiazole); 135.3 (C-7a benzothiazole); 143.3 (C-6 benzothiazole); 149.3 (C-4); 157.7 (C-3a benzothiazole); 160.4 (C-6); 161.1 (C-2); 177.5 (C-2 benzothiazole). Found, %: С 50.52; H 3.27; N 12.71. C14H11N3O3S2. Calculated, %: С 50.44; H 3.33; N 12.60.

4,6-Dimethyl-5-nitro-3-[(6-nitro-1,3-benzothiazol-2-yl)-sulfanyl]pyridin-2(1H)-one (14a). A mixture of fuming HNO3 (0.4 ml) and concentrated H2SO4 (0.6 ml) was added dropwise to a solution of compound 8a (288 mg, 1.0 mmol) in concentrated H2SO4 (1 ml) at –3°С. The mixture was stirred at room temperature for 1 h, then poured onto ice and neutralized with 2 N aqueous NaHCO3. The precipitate was filtered off, washed with H2O, and recrystallized from AcOH. Yield 179 mg (59%), paleyellow crystals, mp >250°С (AcOH). IR spectrum, ν, cm–1: 1332 (NO2), 1515 (NO2), 1656 (C=O), 3305–3670 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.46 (3H, s, CH3); 2.51 (3H, s, CH3); 8.01 (1H, d, 3J = 9.0, H-4 benzothiazole); 8.29 (1H, dd, 3J = 9.0, 4J = 2.4, H-5 benzothiazole); 9.01 (1H, d, 4J = 2.4, H-7 benzothiazole); 13.01 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 17.0 (CH3); 18.4 (CH3); 118.6 (C-4 benzothiazole); 121.5, 121.9 (5,7-CH benzothiazole); 135.2 (C-3); 135.4 (C-7a benzothiazole); 143.6 (C-6 benzothiazole); 148.0 (C-4); 152.0 (C-5); 157.3 (C-3a benzothiazole); 159.3 (C-6); 171.9 (C-2); 177.8 (C-2 benzothiazole). Found, %: С 44.56; H 2.54; N 14.81. C14H10N4O5S2. Calculated, %: С 44.44; H 2.54; N 14.92.

Synthesis of 3-sulfanylpyridin-2(1Н)-ones 15a–c (General method). Activated zinc dust (317 mg, 5.0 mmol) was added to a solution of compound 8а–с (1.0 mmol) in AcOH (8.0 ml). The mixture was heated under reflux for 2 h, cooled, and filtered to remove residual zinc. The filtrate was neutralized with 2 N aqueous NaHCO3, the formed precipitate was filtered off, washed with H2O, and recrystallized from EtOH.

4,6-Dimethyl-3-sulfanylpyridin-2(1H)-one (15a). Yield 132 mg (85%), pale-yellow powder, mp >250°С (EtOH). IR spectrum, ν, cm–1: 1634 (C=O), 3150–3300 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm: 2.22 (3H, s, CH3); 2.25 (3H, s, CH3); 6.31 (1H, s, H-5); 12.61 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 17.7 (CH3); 22.2 (CH3); 111.8 (CH); 130.6 (C); 134.6 (C); 148.2 (C); 164.2 (C). Found, %: С 54.02; H 5.86; N 9.13. C7H9NOS. Calculated, %: С 54.17; H 5.84; N 9.02.

6-Methyl-4-phenyl-3-sulfanylpyridin-2(1H)-one (15b). Yield 150 mg (69%), yellow powder, mp >250°С. IR spectrum, ν, cm–1: 1628 (C=O), 3150–3300 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 2.25 (3H, s, CH3); 6.32 (1H, s, H-5); 7.35 (1H, t, 3J = 7.2, H-4 Ph); 7.42 (2H, dd, 3J = 7.2, 3J = 7.2; H-3,5 Ph); 7.61 (2H, d, 3J = 7.2, H-2,6 Ph); 12.75 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 17.8 (CH3); 111.3 (CH); 127.7 (CH); 127.8 (2CH); 128.5 (2CH); 130.7 (C); 135.2 (C); 140.6 (C); 149.2 (C); 165.2 (C). Found, %: С 54.02; H 5.91; N 9.13. C12H11NOS. Calculated, %: С 54.17; H 5.84; N 9.02.

4-Methyl-3-sulfanyl-5,6,7,8-tetrahydroquinolin-2(1H)-one (15с). Yield 123 g (63%), pale-yellow powder, mp >250°С. IR spectrum, ν, cm–1: 1632 (C=O), 3200–3350 (N–H). 1H NMR spectrum (DMSO-d6), δ, ppm: 1.95–1.97 (4H, m, 6,7-СH2); 2.63–2.80 (7H, m, 5,8-СH2, CH3); 12.66 (1H, br. s, NH). 13C NMR spectrum (DMSO-d6), δ, ppm: 18.2 (CH3); 21.0 (CH2); 21.9 (CH2); 24.3 (CH2); 25.9 (CH2); 117.1 (CH); 131.2 (C); 132.9 (C-4); 147.7 (C-6); 162.5 (C-2). Found, %: С 61.61; H 6.66; N 7.23. C10H13NOS. Calculated, %: С 61.50; H 6.71; N 7.17.