Synthesis and characterization of some new S-substituted sulfanylpyridines, thieno[2,3-b]pyridines and related heterocycles

Ethyl (3-cyano-5-ethoxycarbonyl-6-methyl-4-styryl-2-pyridylsulfanyl)acetate was prepared and reacted with hydrazine hydrate in ethanol to give a mixture of (3-cyano-5-ethoxycarbonyl-6-methyl-4-styryl-2pyridylsulfanyl)acetohydrazide and diethyl 3-amino-6-methyl-4-styrylthieno[2,3-b]pyridine-2,5-dicarboxylate. The latter compound was reacted with 2,5-dimethoxytetrahydrofuran to give 3-(1H-pyrrol-1-yl)thieno[2,3b]pyridine analogue which on treatment with hydrazine hydrate in ethanol furnished 5-ethoxycarbonyl-6methyl-3-(1H-pyrrol-1-yl)-4-styrylthieno[2,3-b]pyridine-2-carbohydrazide. Both acetohydrazide and carbohydrazide were used as precursors for the title compounds.

It is noteworthy that the intramolecular cyclizations of compounds 2 and 6a-d to the corresponding thieno[2,3-b]pyridines 3 and 7a-d obey Thorpe-Ziegler reaction which its mechanism is reviewed before. 4 Scheme 3. Synthesis of compounds 5, 6a-d, 7a-d and 8a-d.
IR spectrum of 5 exhibited three absorption bands in the region 3280 to 3200 characteristic for (NH) groups. Its 1 HNMR spectrum showed three singlet signals at δ values 9.80, 9.19 and 8.40 corresponding to three (NH) groups beside the other signals. IR spectra of 6a-d showed characteristic absorption bands in the regions 3190 to 3208 for (NH), 2221 to 2224 for (C≡N), 1719 to 1725 for (C=O, ester) and 1655 to 1679 for (C=O, acetohydrazide). Their 1 H NMR spectra showed a singlet at δ value ranged from 10.12 to 11.48 corresponds to (NH) group and a singlet signal at δ value ranged from 4.15 to 4.57 equivalent to SCH 2 group. IR spectra of compounds 7a-d showed characteristic absorption bands in the regions 3450 to 3461, 3303 to 3311, 3215 to 3132 for (NH 2 ) and (NH) groups, 1716 to 1724 for (C=O, ester) and 1628 to 1640 1 for (C=O, carbohydrazide). Their 1 HNMR spectra exhibited a singlet signal at δ value ranged from 9.51 to 10.85 corresponds to (NH) group and a singlet signal at δ value ranged from 6.74 to 6.93 equivalent to NH 2 group. IR spectra of compounds 8a-d showed characteristic absorption bands in the regions 1705 to 1670 for (C=O, ester) and 1670 to 1687 for (C=O, pyrimidinone). Their 1 H NMR spectra exhibited a singlet at δ value ranged from 9.26 to 9.63 corresponds to (CH) of pyrimidinone moiety. 13 C NMR and Dept 135 spectral data of 6a and 6c and 7b are in accordance with their structures.
The IR spectrum of 9 revealed the disappearance of ν NH2 . Its 1 H NMR spectrum showed a doublet at δ value ranged from 6.94 to 6.95 for 2CH (pyrrole) and a doublet signal at δ value 6.22 for 2CH (pyrrole). IR spectrum of compound 10 showed absorption bands at 3418, 3334, 3278 for (NHNH 2 ), 1723 for (C=O, ester group attached to pyridine ring) and 1657 for (C=O, carbohydrazide). Its 1 HNMR spectrum showed a singlet at δ 8.06 ( NH) and a singlet signal at δ 4.53 (s, 2H, NH 2 ). IR spectra of compounds 11a-c showed an absorption band in the regions 3290 to 3299 for (NH), 1716-1724 for (C=O, ester) and 1664-1673 for (C=O, carbohydrazide). IR spectrum of compound 12 showed absorption bands at 2142 for (N 3 ), 1724 for (C=O, ester) and 1691 for (C=O, carbonylazide). MS of compounds 9, 10 and 11b are in agreement with their structures.
Heating carbonylazide 12 in ethanol at reflux temperature for two hours provided a mixture of the corresponding carbamate 14 and the fused pyrazinone 15. This reaction may proceed via Curtius rearrangement of the carbonyl azide 13 affording the reactive isocyanate intermediate 13 which underwent in situ either reaction with ethanol giving the carbamate 14, or an intramolecular cycloaddition reaction affording pyrazinone 15, respectively (Scheme 5). In contrast, heating carbonylazide 12 in an inert solvent such as toluene furnished pyrazinone 15 as the sole product (Scheme 5). It is noteworthy that the double bond of the styryl group (2-phenylethenyl group) of all prepared compounds possesses E-configuration since we start with E-cinnamaldehyde and all entire sequence of reactions took place far away from this double bond. This fact was further supported via our previous publication 27 in which the crystal structure of compound 3 was studied and proved the E-configuration of the styryl group.

Experimental Section
General. Melting points were determined on a Gallenkamp apparatus. The IR spectra were recorded on a Shimadzu 470 IR-spectrophotometer (KBr; ν max in cm -1 ). The 1 H NMR spectra were recorded on a Bruker 400 MHz spectrometer using CDCl 3 or DMSO-d 6 as a solvent and tetramethylsilane (TMS) as internal reference. 13 C NMR and Dept 135 spectra were recorded on on a Bruker 100 MHz spectrometer using CDCl 3 or DMSO-d 6 as a solvent and tetramethylsilane (TMS) as internal reference. Coupling constants (J values) are given in Hertz (Hz). Elemental analyses were performed on Perkin Elmer 2400 LS Series CHN/O analyzer. MS analyses were performed on a Thermo Scientific single quadrupole mass spectrometer Model: ISQ 7000.