Yb(OTf)₃ catalysed regioselective synthesis of unusual di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives through a pseudo four-component hetero-Diels–Alder reaction

Abstract

An efficient and facile regioselective synthesis of di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives was reported from 4-hydroxydithiocoumarin, ammonium acetate/primary amines and aldehydes involving a ytterbium triflate catalysed pseudo four component hetero-Diels–Alder reaction. The significant features of the present protocol are: mild reaction conditions, shorter reaction time, good yields, and unusual ring closure leading to the formation of C–C, C–N and C–S bonds in a single step operation.

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Introduction

Heterocyclic compounds containing sulfur and nitrogen are pharmacologically potent molecules.¹ Amongst them, 1,3-thiazine structural motifs are of considerable research interest exhibiting a wide range of biological activities spanning from antibacterial,^2a anti-inflammatory,^2b antimicrobial,³ antitumor,^4a antipyretic,^4b to being the active core of cephalosporin to anabolic agents in medicine.⁵ Furthermore, 1,3-thiazine core moieties are used in various organic synthesis and transformations as reaction intermediates^6a,b and they also shows significant potential as anti-radiation agents^6b and cell growth inhibitors.^6c Therefore, the development of new efficient and practical strategies for synthesis of 1,3-thiazines skeleton has kindled the interest of synthetic organic chemists. To the best of our knowledge, most of the previously reported methods⁷ for the synthesis of 1,3-thiazines skeleton involves the employment of thiourea as one of the major reactant where the nitrogen and the sulphur atom of thiourea gets incorporated into the 1,3-thiazine nucleus with different other reactants to produce a variety of 1,3-thiazine derivatives. Recently Jarvis et al.⁸ reported the synthesis of thiazine derivatives by the reaction of secondary amines with thiosalicylaldehydes in the presence of catalytic amount of acetic acid. Similarly, Sathiyanarayanan et al.⁹ accomplished the synthesis of 1,3-thiazines using iodine catalysed four component reaction from β-naphthol, aldehydes, amines and carbon disulphide. In this context the synthesis of various 1,3-thiazine derivatives by finding an alternative to thiourea is highly desirable using multicomponent reactions (MCRs). Multicomponent reactions are the convergent approach to synthesize selective final products from three or more starting materials in a highly atom economic manner.¹⁰ The MCRs have already proven a powerful synthetic strategy in diversity-oriented synthesis of complex molecules with immense biomedical application,¹¹ as well as for natural product synthesis.¹² It also offers that intermolecular C–N and C–S bond formation in hetero-Diels–Alder reaction for the synthesis of particularly attractive bimolecular scaffolds.^13a The hetero-Diels–Alder reaction is a powerful tool for carbon–carbon and carbon-hetero bond formation leading to the creation of complex structural motifs thus finding its application in the synthesis of various asymmetric heterocyclic compounds.^13b The improvement of prominent hetero-Diels–Alder reactions¹⁴ gives a platform to develop new multicomponent reactions, which is an extensive area of research interest in modern organic synthesis.

In 1987, Anderson-McKay and his co-worker first accomplished the synthesis of 4-hydroxydithiocoumarin using 2′-chloroacetophenones with carbon disulfide in the presence of sodium hydride.¹⁵ It has been utilized for the synthesis of new heterocyclic molecules¹⁶ and we envisaged that it can be further explored for the synthesis of 1,3-thiazine derivatives through hetero-Diels–Alder reaction.

An extensive literature survey reveals that ytterbium triflate catalyses a wide range of carbon–carbon and carbon-hetero atom bond forming reactions,¹⁷ which led us to believe that it can be used to facilitate hetero-Diels–Alder reaction leading to the synthesis of novel 1,3-thiazine derivatives.

In continuation to our efforts to synthesis novel heterocycles through MCRs using 4-hydroxydithiocoumarin,¹⁸ herein we report the synthesis of hitherto unreported 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives through pseudo four component hetero-Diels–Alder reaction involving 4-hydroxydithiocoumarin, ammonium acetate/primary amines and aldehydes in the presence of 5 mol% ytterbium triflate as shown in Scheme 1.

Scheme 1 Synthesis of di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives.

Results and discussion

Initially, the reaction was performed with 4-hydroxydithiocoumarin (1, 0.5 mmol), benzaldehyde (2a, 1.0 mmol) and ammonium acetate (3, 1.0 mmol) in ethanol as the model substrates to find out the optimum reaction conditions. At 60 °C temperature in absence of any catalyst, the reaction is unsuccessful to produce any desired product (Table 1, entry 1). To our delight the product 4a was isolated in 41% yield (Table 1, entry 2) when the same reaction was carried out with acetic acid as catalyst. The isolated product 4a was fully characterized by IR, ¹H and ¹³C NMR spectra and HRMS. With an effort to improve the yield, the reaction was again performed separately in trifluoromethanesulfonic acid and iodine as catalyst but no significant improvement in yield was observed (Table 1, entries 3–4). Next, we turned our attention to examine the reaction using metal catalysts. While carrying out the reaction with In(OTf)₃ at room temperature it do lead to the formation of trace amount of product 4a, when the same set of reaction was carried at 60 °C temperature the product 4a was obtained in only 22% yield (Table 1, entry 5–6), but after long time it resulted in multiple spot in TLC which were difficult to isolate. Subsequently the reaction was examined using 2.5 mol% Yb(OTf)₃ in ethanol at 60 °C temperature (Table 1, entry 7) and the product was obtained in 80% yield. The yield of the product was increased further when the reaction was executed with 5 mol% Yb(OTf)₃ in ethanol at 60 °C and the reaction time was also reduced to 15 min. (Table 1, entry 8). This increase could be in accordance with the general trend of a catalyst. In order to obtain more better results, the reaction was scrutinized using 10 mol% catalyst, but the yield was not increased (Table 1, entry 9) which might be due to the deactivation of reactants in the presence of excess catalyst.

Table 1 Optimization of the reaction conditions^a

S. no.	Catalyst (mol%)	Solvent	Time/h	Yield^c (%)
a All the reactions were carried out using 4-hydroxy-2H-thiochromene-2-thione (1, 0.5 mmol), benzaldehyde (2a, 1 mmol) and ammonium acetate (3, 1.0 mmol).b Reaction was carried out at room temperature.c Isolated yield.
1	—	EtOH	12.0	NR
2	AcOH (5)	EtOH	0.75	41
3	TfOH (5)	EtOH	0.50	52
4	I2 (5)	EtOH	1.00	38
5	In(OTf)3 (5)^b	EtOH	2.00	Trace
6	In(OTf)3 (5)	EtOH	2.00	22
7	Yb(OTf)3 (2.5)	EtOH	0.50	80
8	Yb(OTf)3 (5)	EtOH	0.25	86
9	Yb(OTf)3 (10)	EtOH	0.25	82
10	Yb(OTf)3 (5)	MeOH	1.00	65
11	Yb(OTf)3 (5)	^nBuOH	1.50	56
12	Yb(OTf)3 (5)	CH3CN	0.50	58

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To check the feasibility of the reaction in other solvents, we investigated a range of solvents like methanol, butanol, acetonitrile (Table 1, entries 10–12). All these solvents are required longer reaction time and also provide lower yields. It was noted that the optimum reaction condition for this reaction was 5 mol% catalysts in ethanol under heating condition (60 °C) in terms of yield and reaction time.

After optimization of the reaction condition, the scope of the reaction was investigated with various aromatic aldehydes having substituents on the aromatic ring. The aromatic aldehydes having substituent at the para position such as Me, Cl, Br and OMe group gave the product 4b–e in the 75–84% yield (Table 2, entries 2–5). Interestingly, while moving on to aromatic aldehydes having ortho substituents such as Cl, Br, F, NO₂ groups, the reaction proceeded much faster as compared to their para analogues giving the product 4f–i in 78–84% yield (Table 2, entries 6–9). Moreover, the present protocol was well applied to 4-CN and 2-naphthaldehyde giving the product 4j and 4k in 72–80% yields (Table 2, entries 10–11). All these products were characterized by IR, ¹H and ¹³C NMR spectra as well as HRMS.

Table 2 Synthesis of 2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives using as Yb(OTf)₃ a catalyst^a

S. no.	R (2)	Product (4)	Time (min)	Yield^b (%)
a All the reactions were carried out using 4-hydroxydithiocoumarin (1, 0.5 mmol), aldehyde (2, 1.0 mmol) and ammonium acetate (3, 1.0 mmol) in ethanol (2 mL).b Isolated yield.
1	C6H5(2a)	4a	15	86
2	4-Me-C6H4 (2b)	4b	15	84
3	4-Cl-C6H4 (2c)	4c	30	78
4	4-Br-C6H4 (2d)	4d	30	80
5	4-OMe-C6H4 (2i)	4e	35	75
6	2-Cl-C6H4 (2e)	4f	10	80
7	2-Br-C6H4 (2f)	4g	10	82
8	2 F-C6H4 (2g)	4h	10	84
9	2-NO2-C6H4 (2h)	4i	20	78
10	4-CN-C6H4 (2j)	4j	20	80
11	2-Napthyl (2k)	4k	25	72

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Finally, the structure of the compound 4f was confirmed by single-crystal X-ray crystallographic data (Fig. 1(I)). Unfortunately, the present protocol was unsuccessful for aliphatic and heteroaromatic aldehydes to obtain the anticipated product.

Fig. 1 (I) XRD structure of 4f (ESI) and (II) XRD structure of 6b (ESI†).

Inspired with the success of the above transformation, we further explored the generality of the reaction with various alkyl/benzyl amines as a substitute of NH₄OAc for the synthesis of tri-substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives. When the reaction was carried out with 4-hydroxydithiocoumarin (0.5 mmol, 1), benzaldehyde (1.0 mmol, 2) and benzyl amine (0.5 mmol, 5a) under the same set of reaction conditions, it furnished the product 6a with moderate yield (65%), which was characterized by IR, ¹H and ¹³C NMR spectra and HRMS. However, it was observed that the time taken for the completion of the reaction was significantly longer i.e. 24 h as compared to the earlier reaction time. Therefore, the need to optimize the reaction conditions aroused again. Surprisingly, just changing the solvent from ethanol to acetonitrile worked wonder and the same reaction took only 2 h instead of 24 h as taken in ethanol medium with the significant improvement in the yield to 84% (Table 3, entry 1). Next, 4-hydroxydithiocoumarin (0.5 mmol, 1) participated in the hetero-Diels–Alder reaction with benzyl amine (0.5 mmol, 5a) and various aromatic aldehydes (1.0 mmol, 2) showing good tolerance from electron-donating to electron-withdrawing group at ortho-, meta- and para-position on the aromatic ring in presence of 5 mol% of Yb(OTf)₃ in acetonitrile at 60 °C and the desired products 6b–f were obtained in 74–82% yields (Table 3, entries 2–6). The reaction was further assessed with various other amines such as 4-methyl benzyl amine (5b) and butyl amine (5c) under identical reaction conditions and the expected products 6g–n were obtained in good yields (Table 3, entries 7–14). Furthermore, the reaction of 4-hydroxydithiocoumarin with 2-naphthaldehyde (2k) and benzyl amine (5a) afforded the product 6o in 70% yield (Table 3, entry 15). All the products were characterized by recording IR, ¹H and ¹³C NMR spectra as well as from their HRMS. The structure of the compound 6b was further confirmed by single-crystal X-ray crystallographic data (Fig. 1(II)).

Table 3 Synthesis of 3-alkyl-2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives using as Yb(OTf)₃ a catalyst^a

S. no.	R (2)	R^1 (5)	Product (6)	Time (h)	Yield^b (%)
a All the reactions were carried out using 4-hydroxydithiocoumarin (1, 0.5 mmol), aldehyde (2, 1.0 mmol) and alkyl amine (5, 0.5 mmol) in acetonitrile (2 mL).b Isolated yield.
01	C6H5 (2a)	5a	6a	1.5	84
02	4-Me-C6H4 (2b)	5a	6b	2.0	82
03	4-Cl-C6H4 (2c)	5a	6c	2.0	78
04	4-Br-C6H4 (2d)	5a	6d	2.0	76
05	2-F-C6H4 (2g)	5a	6e	1.5	80
06	3-F-C6H4 (2l)	5a	6f	2.0	74
07	4-NO2-C6H4 (2m)	5b	6g	2.5	75
08	4-Cl-C6H4 (2c)	5b	6h	2.0	80
09	2-Cl-C6H4 (2e)	5c	6i	3.0	76
10	2-Br-C6H4 (2f)	5b	6j	1.5	80
11	2-F-C6H4 (2g)	5c	6k	2.5	78
12	2-Cl-C6H4 (2e)	5b	6l	2.0	80
13	4-Cl-C6H4 (2c)	5c	6m	3.0	75
14	3-F-C6H4 (2l)	5c	6n	3.0	72
15	2-Napthyl (2k)	5a	6o	2.5	70

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Unfortunately, we were unable to obtain any desired product with aromatic amines, aliphatic and heteroaromatic aldehydes thus somewhat limiting the scope of the reaction.

In addition, the XRD structure of compounds 4f and 6b showed that the position of Ha and Hb are anti to each other respectively which indicates the formation of single anti-diastereoisomer. The anti-diastereoselectivity was also confirmed through NOEs spectra of compound 6f, which shows the absence of any cross peak between the (Ha & Hb) and (Hb & Hc) region that proves (Ha & Hb) and (Hb & Hc) are anti to each other i.e. trans-orientation respectively, it is also shown that the presence of cross peak in the highlighted region that proves Hb and Hd are in cis-orientation as shown in Fig. 2.

Fig. 2 (I) Selected NOEs enhancements of compound 6f and (II) expanded NOEs spectra of compound 6f.

A plausible mechanism for the formation of products 4 and 6 in this unusual ring closure reaction may be drawn as follow (Scheme 2).

Scheme 2 Plausible mechanism for the formation of 3-alkyl-2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives.

Initially, ytterbium triflate reacted with the aldehyde 2 to form active species A which further undergoes reaction with 4-hydroxydithiocoumarin 1 to form Knoevenagel product B. At the same time the species A reacted with amine 5 to form an imine C which was further activated in the presence of ytterbium triflate to serve as a dienophile E. There are two possibilities which may lead to the formation of two different hetero-Diels–Alder products (products 6 and 7) either ‘pathway a’ or ‘pathway b’. However, the isolation of only product 6 shows that the reaction proceeds mainly through ‘pathway a’. In ‘pathway a’ the diene D undergoes concomitant regioselective cyclization through hetero-Diels–Alder reaction with the dienophile E to give the final product 6. The regioselective formation of product 6 can be rationalized in terms of the following points (i) the presence of soft sulfur atom which decreases HOMO–LUMO gap when the thioester acts as heterodine D, (ii) the empty d-orbitals in sulfur makes it more polarizable as compared to oxygen thus serving as an efficient reaction core, (iii) the steric hindrance faced by R group with the sulfur of the heterodiene F might have also prevented the reaction to proceed via ‘pathway b’.

Conclusion

In conclusion, we have developed a novel protocol for the synthesis of 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives through hetero-Diels–Alder reaction in high yields with a wide substrates scope. The present protocol is user-friendly, operationally simple, regioselective and shows unusual ring closure leading to the formation of C–C, C–N and C–S bond in a single step reaction. Moreover, these unusual di- and tri- substituted 3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives were reported first time in the literature from 4-hydroxydithiocoumarin. In addition, the biological activities of these compounds would be reported elsewhere.

Experimental section

I. General procedure for the synthesis of compound (1)

The key starting material 4-hydroxydithiocoumarin (1) was prepared by following the previous reported procedure.¹⁵

II. General procedure for the synthesis of 2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives (4)

To a mixture of 4-hydroxydithiocoumarin (1, 0.5 mmol), aromatic aldehyde (2, 1.0 mmol) and ammonium acetate (3, 1.0 mmol) in 2 mL ethanol was added 5 mol% ytterbium triflate (15.5 mg). Then the reaction mixture was kept for stirring in a pre-heated oil-bath at 60 °C and the progress of the reaction was monitored by TLC. After a stipulated period of time precipitation was occurred and then the reaction mixture was cooled to room temperature. After that, the precipitate was filter off through a Büchner funnel, washed with EtOH and finally dried over vacuum pump to obtain the pure products 4 in good yields.

III. General procedure for the synthesis of 3-alkyl-2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one derivatives (6)

Into an oven dried 25 mL round bottomed flask was taken a mixture 4-hydroxydithiocoumrin (0.5 mmol, 1), aromatic aldehyde (1.0 mmol, 2), alkyl amine (0.5 mmol, 5) in 2 mL of acetonitrile. Then, 5 mol% ytterbium triflate (15.5 mg) was added into the above reaction mixture and it was kept for stirring at 60 °C and the progress of the reaction was monitored by TLC. After the completion of the reaction, it was concentrated under reduced pressure. Then, the obtained residue was extracted with DCM (15 mL × 2), and dried over anhydrous Na₂SO₄ and evaporated in vacuo. After that, the crude residue was purified over a silica gel column chromatography eluted with 3% ethyl acetate in hexane to afford the desired products 6 in good yields.

2,4-Diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4a). White solid (0.167 g, 86%), mp 163–164 °C, ¹H NMR (600 MHz, CDCl₃): δ 5.67 (s, 1H), 5.96 (s, 1H), 7.28–7.29 (m, 1H), 7.33–7.36 (m, 4H), 7.38–7.40 (m, 5H), 7.45–7.48 (m, 2H), 7.54–7.57 (m, 1H), 8.41 (d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 56.5, 65.2, 124.3, 124.7, 126.8, 127.1, 127.4, 127.8, 128.5, 128.7, 128.8, 129.1, 129.2, 129.5, 129.9, 131.0, 131.3, 136.9, 137.8, 140.1, 154.1, 175.2; IR (KBr)ν_max 1122, 1169, 1229, 1301, 1314, 1346, 1437, 1448, 1479, 1491, 1505, 1557, 1573, 1597, 2852, 2924, 3023, 3061, 3271 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₈NOS₂ 388.0825 (M + H⁺); found 388.0825.

2,4-Di-p-tolyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4b). White solid (0.174 g, 84%), mp 161–162 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.31 (s, 3H), 2.34 (s, 3H), 5.65 (s, 1H), 5.90 (s, 1H), 7.12–7.18 (m, 4H), 7.24–7.28 (m, 5H), 7.43–7.46 (m, 1H), 7.53–7.56 (m, 1H), 8.39 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.3, 21.4, 56.5, 65.6, 124.6, 124.7, 126.8, 127.4, 128.6, 129.5, 129.6, 129.8, 129.9, 130.0, 131.1, 131.2, 134.9, 137.1, 137.2, 137.4, 139.2, 154.2, 175.1; IR (KBr)ν_max 1167, 1241, 1307, 1350, 1404, 1435, 1467, 1489, 1504, 1554, 1583, 1601, 2848, 2922, 3306 cm⁻¹; HRMS (ESI) calcd for C₂₅H₂₂NOS₂ 416.1138 (M + H⁺); found 416.1139.

2,4-Bis(4-chlorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4c). White solid (0.178 g, 78%), mp 201–202 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.51 (b s, 1H), 5.55 (s, 1H), 5.87 (s, 1H), 7.30–7.34 (m, 8H), 7.46–7.48 (m, 2H), 7.56–7.58 (m, 1H), 8.40 (d, J = 7.6 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 52.2, 54.4, 121.6, 123.9, 124.7, 124.9, 126.9, 127.1, 127.6, 127.9, 128.4, 129.1, 129.2, 130.1, 130.5, 131.9, 133.4, 133.8, 136.1, 139.5, 140.5, 173.9; IR (KBr)ν_max 1121, 1161, 1241, 1285, 1308, 1349, 1401, 1432, 1465, 1489, 1505, 1561, 1582, 1600, 2845, 2923, 3059, 3298 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆Cl₂NOS₂ 456.0045 (M + H⁺); found 456.0044.

2,4-Bis(4-bromophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4d). White solid (0.218 g, 80%), mp 208–209 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.47 (s, 1H), 5.54 (s, 1H), 5.86 (s, 1H), 7.23 (s, 2H), 7.28 (s, 1H), 7.46–7.51 (s, 7H), 7.53–7.58 (s, 1H), 8.40 (d, J = 7.2 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 55.7, 63.5, 122.1, 123.4, 123.9, 124.9, 127.7, 128.6, 129.6, 130.4, 131.1, 131.6, 132.0, 132.4, 136.7, 136.8, 139.2, 153.7, 175.3; IR (KBr)ν_max 1162, 1241, 1304, 1350, 1393, 1432, 1465, 1485, 1499, 1581, 1596, 2850, 2923, 2950, 3296 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆Br₂NOS₂ 543.9035 (M + H⁺); found 543.9027.

2,4-Bis(4-methoxyphenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4e). White solid (0.168 g, 75%), mp 159–160 °C, ¹H NMR (400 MHz, CDCl₃): δ 3.78 (s, 3H), 3.81 (s, 3H), 5.68 (s, 1H), 5.94 (s, 1H), 6.85–6.91 (m, 4H), 7.30 (d, J = 8.0 Hz, 2H), 7.35–7.39 (m, 2H), 7.43–7.65 (m, 2H), 7.52–7.56 (m, 1H), 8.39 (d, J = 8.0 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 55.4, 55.6, 56.6, 114.2, 114.5, 124.6, 124.7, 125.6, 127.4, 128.1, 128.4, 129.4, 129.5, 129.8, 129.9, 130.1, 131.2, 131.3, 131.9, 132.3, 137.2, 159.2, 160.4, 175.0; IR (KBr)ν_max 1112, 1175, 1245, 1288, 1306, 1437, 1462, 1509, 1581, 1609, 2834, 2933, 3278, 3311 cm⁻¹; HRMS (ESI) calcd for C₂₅H₂₂NO₃S₂ 448.1036 (M + H⁺); found 448.1036.

2,4-Bis(2-chlorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4f). White solid (0.182 g, 80%), mp 168–169 °C, ¹H NMR (600 MHz, CDCl₃): δ 6.02 (s, 1H), 6.17 (s, 1H), 7.10–7.13 (m, 1H), 7.15–7.18 (m, 3H), 7.19–7.22 (m, 1H), 7.24–7.27 (m, 1H), 7.35–7.39 (m, 3H), 7.45–7.48 (m, 1H), 7.56–7.57 (m, 1H), 8.28 (d, J = 7.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 54.1, 60.8, 123.7, 124.8, 126.5, 127.6, 127.8, 128.4, 129.2, 129.3, 129.5, 130.3, 130.4, 130.7, 131.2, 131.5, 133.5, 134.9, 136.8, 137.7, 153.6, 175.1; IR (KBr)ν_max 1128, 1161, 1241, 1301, 1346, 1439, 1458, 1500, 1582, 1600, 2836, 2931, 3045, 3325 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆Cl₂NOS₂ 456.0045 (M + H⁺); found 456.0045.

2,4-Bis(2-bromophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4g). White solid (0.223 g, 82%), mp 188–189 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.61 (b s, 1H), 6.07 (d, J = 11.2 Hz, 1H), 6.18 (s, 1H), 7.17–7.19 (m, 1H), 7.25–7.26 (m, 3H), 7.36–7.40 (m, 1H), 7.44–7.52 (m, 2H), 7.54–7.58 (m, 2H), 7.63–7.68 (m, 2H), 8.38 (d, J = 8.0 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 56.1, 63.4, 122.7, 124.3, 124.8, 126.5, 126.9, 127.8, 128.3, 128.4, 128.7, 128.8, 130.1, 130.4, 130.9, 132.7, 133.2, 135.8, 136.1, 138.9, 153.2, 174.2; IR (KBr)ν_max 119, 1132, 1159, 1190, 1230, 1288, 1307, 1343, 1435, 1463, 1513, 1560, 1580, 1595, 2844, 2939, 3059, 3313 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆Br₂NOS₂ 543.9035 (M + H⁺); found 543.9039.

2,4-Bis(2-fluorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4h). White solid (0.178 g, 84%), mp 173–174 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.86 (b s, 1H), 5.92 (d, J = 12.0 Hz, 1H), 6.19 (s, 1H), 7.07–7.09 (m, 2H), 7.14–7.21 (m, 3H), 7.31–7.33 (m, 2H), 7.40–7.47 (m, 3H), 7.54–7.55 (m, 1H), 8.37 (d, J = 6.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 50.1, 58.4, 115.4, 115.6, 115.7, 122.5, 123.3, 124.1, 124.2, 124.4, 126.9, 127.1, 128.1, 128.5, 128.9, 129.3, 130.4, 130.9, 136.1, 153.2, 158.2, 159.1, 160.7, 161.6, 174.2; IR (KBr)ν_max 1146, 1170, 1230, 1276, 1344, 1452, 1488, 1507, 1559, 1576, 1607, 2845, 2925, 2961, 3067, 3109, 3273 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆F₂NOS₂ 424.0636 (M + H⁺); found 424.0635.

2,4-Bis(2-nitrophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4i). White solid (0.186 g, 78%), mp 184–185 °C, ¹H NMR (600 MHz, CDCl₃): δ 2.87 (d, J = 8.4 Hz, 1H), 6.15 (d, J = 12.0 Hz, 1H), 6.63 (s, 1H), 7.23–7.24 (m, 1H), 7.47–7.54 (m, 5H), 7.59 (t, J = 7.8 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 7.2 Hz, 1H), 8.41 (d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, DMSO): δ 51.7, 59.9, 122.7, 125.1, 125.5, 125.9, 128.4, 128.9, 129.5, 129.8, 130.4, 130.6, 130.9, 131.1, 132.5, 132.8, 133.5, 134.5, 136.3, 148.0, 149.6, 154.0, 174.5; IR (KBr)ν_max 1172, 1239, 1344, 1438, 1475, 1522, 1574, 1599, 2848, 2948, 3059, 3301 cm⁻¹; HRMS (ESI) calcd for C₂₃H₁₆N₃O₅S₂ 478.0526 (M + H⁺); found 478.0526.

4,4′-(5-Oxo-2,3,4,5-tetrahydrothiochromeno[3,2-e][1,3]thiazine-2,4-diyl)dibenzonitrile (4j). White solid (0.175 g, 80%), mp 204–205 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.66 (d, J = 13.6 Hz, 1H), 5.52 (d, J = 13.6 Hz, 1H), 5.93 (s, 1H), 7.48–7.53 (m, 6H), 7.59–7.61 (m, 1H), 7.64–7.66 (m, 2H), 7.69–7.71 (m, 2H), 8.39 (d, J = 7.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 55.9, 62.6, 110.1, 112.1, 113.5, 118.2, 118.8, 123.0, 125.1, 127.6, 128.1, 129.6, 130.9, 131.9, 132.8, 133.1, 136.7, 142.3, 145.3, 153.5, 175.4; IR (KBr)ν_max 1118, 1235, 1290, 1313, 1348, 1399, 1438, 1468, 1499, 1515, 1554, 1575, 1598, 2227, 2845, 2923, 3289 cm⁻¹; HRMS (ESI) calcd for C₂₅H₁₆N₃OS₂ 438.0730 (M + H⁺); found 438.0728.

2,4-Di(naphthalen-2-yl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (4k). White solid (0.175 g, 72%), mp 144–145 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.79 (b s, 1H), 5.83 (s, 1H), 6.15 (s, 1H), 7.45–7.52 (m, 7H), 7.57–7.61 (m, 1H), 7.67–7.71 (m, 2H), 7.78–7.82 (m, 5H), 7.85–7.89 (m, 2H), 8.43 (d, J = 8.4 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 56.8, 65.2, 124.2, 124.4, 124.9, 126.1, 126.2, 126.3, 126.9, 127.1, 127.5, 127.6, 127.8, 127.9, 128.3, 128.4, 126.8, 128.9, 129.1, 129.3, 129.6, 131.2, 131.4, 133.3, 133.4, 133.6, 135.0, 137.1, 137.6, 154.4, 175.3; IR (KBr)ν_max 1121, 1159, 1205, 1241, 1272, 1291, 1324, 1339, 1360, 1435, 1507, 1525, 1563, 1588, 1613, 2838, 2929, 3046, 3302 cm⁻¹; HRMS (ESI) calcd for C₃₁H₂₂NOS₂ 488.1138 (M + H⁺); found 488.1139.

3-Benzyl-2,4-diphenyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6a). Yellow solid (0.200 g, 84%), mp 173–174 °C, ¹H NMR (600 MHz, CDCl₃): δ 3.38 (d, J = 13.8 Hz, 1H), 3.87 (d, J = 13.8 Hz, 1H), 5.49 (s, 1H), 6.11 (s, 1H), 7.15–7.19 (m, 7H), 7.22–7.26 (m, 4H), 7.29–7.31 (m, 2H), 7.35–7.37 (m, 2H), 7.39–7.40 (m, 1H), 7.43–7.44 (m, 1H), 7.49–7.51 (m, 1H), 8.30 (d, J = 7.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 50.8, 59.7, 68.9, 121.1, 124.8, 127.5, 127.6, 127.7, 127.9, 128.7, 128.8 (2), 129.0, 129.2, 129.7, 131.2, 131.4, 136.8, 137.0, 137.9, 141.5, 152.7, 176.0; IR (KBr)ν_max 1102, 1158, 1235, 1261, 1308, 1333, 1354, 1432, 1449, 1490, 1508, 1560, 1580, 1604, 2853, 2917, 2953, 3017 cm⁻¹; HRMS (ESI) calcd for C₃₀H₂₄NOS₂ 478.1294 (M + H⁺); found 478.1294.

3-Benzyl-2,4-di-p-tolyl-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6b). Yellow solid (0.207 g, 82%), mp 141–142 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.29 (s, 3H), 2.33 (s, 3H), 3.42 (d, J = 14.0 Hz, 1H), 3.95 (d, J = 14.0 Hz, 1H), 5.50 (s, 1H), 6.19 (s, 1H), 7.12 (s, 3H), 7.16–7.18 (m, 2H), 7.26–7.33 (m, 7H), 7.44–7.51 (m, 3H), 7.55–7.59 (m, 1H), 8.37 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.3, 50.6, 59.4, 68.9, 121.3, 124.7, 127.4, 127.5, 127.8, 128.6, 129.1, 129.4, 129.7, 131.2, 131.4, 133.8, 137.0, 137.2, 138.1, 138.5, 138.8, 152.6, 175.9; IR (KBr)ν_max 1113, 1161, 1174, 1232, 1310, 1330, 1402, 1436, 1454, 1510, 1587, 1611, 1646, 2839, 2917, 3028 cm⁻¹; HRMS (ESI) calcd for C₃₂H₂₈NOS₂ 506.1607 (M + H⁺); found 506.1611.

3-Benzyl-2,4-bis(4-chlorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6c). Yellow solid (0.213 g, 78%), mp 182–183 °C, ¹H NMR (400 MHz, CDCl₃): δ 3.41 (d, J = 14.0 Hz, 1H), 3.86 (d, J = 14.0 Hz, 1H), 5.48 (s, 1H), 6.05 (s, 1H), 7.14–7.16 (m, 2H), 7.20–7.22 (m, 2H), 7.26–7.34 (m, 6H), 7.36 (s, 3H), 7.47–7.53 (m, 2H), 7.59–7.62 (m, 1H), 8.37 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 50.7, 59.1, 67.9, 120.5, 124.9, 127.7, 127.9, 128.4, 128.9, 129.0, 129.1, 129.2, 129.3, 129.6, 130.1, 131.0, 131.7, 133.7, 135.0, 135.1, 136.8, 137.4, 139.9, 152.5, 175.9; IR (KBr)ν_max 1117, 1161, 1181, 1244, 1314, 1327, 1341, 1400, 1436, 1453, 1487, 1511, 1584, 1607, 2845, 2925, 3024, 3060 cm⁻¹; HRMS (ESI) calcd for C₃₀H₂₂Cl₂NOS₂ 546.0515 (M + H⁺); found 546.0515.

3-Benzyl-2,4-bis(4-bromophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6d). Yellow solid (0.241 g, 76%), mp 172–173 °C, ¹H NMR (400 MHz, CDCl₃): δ 3.41 (d, J = 13.6 Hz, 1H), 3.85 (d, J = 14.0 Hz, 1H), 5.46 (s, 1H), 6.03 (s, 1H), 7.09 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 7.2 Hz, 2H), 7.26–7.34 (m, 5H), 7.43 (d, J = 8.4 Hz, 2H), 7.48 (s, 1H), 7.52 (d, J = 8.0 Hz, 3H), 7.60 (t, J = 7.2 Hz, 1H), 8.36 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 50.7, 59.2, 67.9, 123.3, 124.9, 127.7, 127.9, 128.8, 128.9, 129.1, 129.2, 129.4, 129.5, 129.6, 129.7, 130.4, 130.5, 131.0, 131.7, 131.9 (2), 132.0, 132.1, 135.5, 136.8, 137.3, 140.5, 152.5, 175.9; IR (KBr)ν_max 1162, 1261, 1324, 1396, 1435, 1482, 1511, 1587, 1606, 2853, 2924, 2961, 3059 cm⁻¹; HRMS (ESI) calcd for C₃₀H₂₂Br₂NOS₂ 633.9504 (M + H⁺); found 633.9510.

3-Benzyl-2,4-bis(2-fluorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6e). Yellow solid (0.205 g, 80%), mp 126–127 °C, ¹H NMR (400 MHz, CDCl₃): δ 3.51 (d, J = 14.0 Hz, 1H), 4.06 (d, J = 14.0 Hz, 1H), 5.76 (s, 1H), 6.54 (s, 1H), 6.99–7.05 (m, 2H), 7.09–7.16 (m, 5H), 7.20–7.22 (m, 3H), 7.28 (b s, 2H), 7.45 (t, J = 7.6 Hz, 1H), 7.49–7.51 (m, 1H), 7.56–7.62 (m, 1H), 7.64–7.65 (m, 1H), 8.34 (d, J = 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 51.5, 55.8, 63.8, 116.1, 116.3, 120.2, 123.4, 123.5, 123.6 (2), 123.9, 124.0, 124.8, 127.4, 127.6, 127.7, 127.8, 128.2, 129.1, 129.5, 129.6, 129.8, 129.9, 130.1, 131.1, 131.2, 131.5, 136.9, 137.2, 153.1, 159.6, 160.1, 162.1, 162.6, 175.6; IR (KBr)ν_max 1117, 1163, 1232, 1304, 1334, 1452, 1487, 1514, 1614, 2841, 2925, 3063 cm⁻¹; HRMS (ESI) calcd For C₃₀H₂₂F₂NOS₂ 514.1106 (M + H⁺); found 514.1107.

3-Benzyl-2,4-bis(3-fluorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6f). Yellow solid (0.190 g, 74%), mp 70–71 °C, ¹H NMR (600 MHz, CDCl₃): δ 3.44 (d, J = 13.8 Hz, 1H), 3.89 (d, J = 13.2 Hz, 1H), 5.51 (s, 1H), 6.01 (s, 1H), 6.93–6.96 (m, 2H), 7.01 (d, J = 7.8 Hz, 1H), 7.06 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 10.2 Hz, 1H), 7.22–7.25 (m, 3H), 7.28–7.30 (m, 2H), 7.32–7.34 (m, 2H), 7.35–7.39 (m, 1H), 7.47–7.50 (m, 1H), 7.52–7.53 (m, 1H), 7.60 (t, J = 7.2 Hz, 1H), 8.37 (d, J = 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 50.7, 58.9, 67.7, 114.6, 114.8, 114.9, 115.4, 115.6, 115.9, 116.1, 120.3, 123.3, 124.2, 124.7, 127.5, 127.7, 128.7, 129.0, 129.4, 130.1, 130.2, 130.3, 130.4, 130.8, 131.5, 136.6, 137.1, 138.8, 138.9, 143.8, 143.9, 152.4, 161.6, 164.1, 164.2, 175.8; IR (KBr)ν_max 1199, 1227, 1260, 1293, 1328, 1340, 1368, 1439, 1484, 1519, 1586, 1611, 2850, 2920, 3017, 3061 cm⁻¹; HRMS (ESI) calcd for C₃₀H₂₂F₂NOS₂ 514.1106 (M + H⁺); found 514.1107.

3-(4-Methylbenzyl)-2,4-bis(4-nitrophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6g). Yellow solid (0.218 g, 75%), mp 188–189 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.35 (s, 3H), 3.47 (d, J = 13.6 Hz, 1H), 3.75 (d, J = 13.6 Hz, 1H), 5.57 (s, 1H), 6.03 (s, 1H), 7.09–7.11 (m, 2H), 7.14–7.16 (m, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.52–7.55 (m, 1H), 7.57–7.59 (m, 2H), 7.62–7.66 (m, 2H), 8.17–8.20 (m, 2H), 8.28 (d, J = 8.8 Hz, 2H), 8.37 (d, J = 7.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.3, 50.9, 59.0, 67.5, 119.9, 124.1, 124.3, 124.9, 126.0, 128.0, 128.1, 128.5, 128.7, 129.1, 129.4, 129.6, 129.7, 129.8, 130.8, 132.0, 132.2, 133.2, 136.6, 138.1, 143.3, 147.6, 148.4, 148.7, 152.3, 175.9; IR (KBr)ν_max 1119, 1162, 1224, 1319, 1346, 1415, 1437, 1515, 1605, 1624, 2852, 2922, 3015, 3069 cm⁻¹; HRMS (ESI) calcd for C₃₁H₂₄N₃O₅S₂ 582.1152 (M + H⁺); found 582.1130.

2,4-Bis(4-chlorophenyl)-3-(4-methylbenzyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6h). Yellow solid (0.224 g, 80%), mp 183–184 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.26 (s, 3H), 3.30 (d, J = 13.6 Hz, 1H), 3.74 (d, J = 14.0 Hz, 1H), 5.40 (s, 1H), 5.97 (s, 1H), 7.04–7.08 (m, 7H), 7.19–7.21 (m, 4H), 7.41–7.45 (m, 3H), 7.51–7.53 (m, 1H), 8.29 (d, J = 7.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.3, 50.4, 58.8, 67.9, 120.6, 124.8, 127.7, 128.9, 129.0, 129.1, 129.2, 129.5, 129.4, 130.1, 131.0, 131.6, 133.6, 134.1, 135.0, 135.1, 136.8, 137.5, 140.1, 152.5, 175.9; IR (KBr)ν_max 1119, 1160, 1235, 1260, 1321, 1346, 1397, 1436, 1462, 1488, 1516, 1587, 1611, 2852, 2923, 2958, 3021, 3051 cm⁻¹; HRMS (ESI) calcd for C₃₁H₂₄Cl₂NOS₂ 560.0671 (M + H⁺); found 560.0667.

3-Butyl-2,4-bis(2-chlorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6i). Yellow solid (0.195 g, 76%), mp 131–132 °C, ¹H NMR (400 MHz, CDCl₃): δ 0.61 (t, J = 7.6 Hz, 3H), 0.83–0.89 (m, 2H), 1.42–1.53 (m, 2H), 2.45–2.52 (m, 1H), 2.78–2.83 (m, 1H), 6.04 (s, 1H), 6.48 (s, 1H), 7.15–7.19 (m, 1H), 7.23–7.31 (m, 5H), 7.45–7.48 (m, 3H), 7.53–7.55 (m, 1H), 7.57–7.71 (m, 1H), 8.37 (d, J = 7.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 13.7, 20.2, 29.6, 47.2, 59.6, 67.6, 121.2, 124.7, 126.3, 126.5, 127.6, 129.3, 129.4, 130.1, 130.2, 130.3, 130.5, 130.7, 131.2, 131.4, 133.3, 135.4, 135.9, 136.9, 137.5, 153.8, 175.7; IR (KBr)ν_max 1122, 1161, 1239, 1263, 1299, 1329, 1438, 1468, 1489, 1517, 1588, 1608, 2853, 2925, 2955, 3059 cm⁻¹; HRMS (ESI) calcd for C₂₇H₂₄Cl₂NOS₂ 512.0671 (M + H⁺); found 512.0665.

2,4-Bis(2-bromophenyl)-3-(4-methylbenzyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6j). Yellow solid (0.259 g, 80%), mp 122–123 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.36 (s, 3H), 3.61–3.64 (m, 1H), 4.18–4.21 (m, 1H), 6.02 (s, 1H), 6.69 (s, 1H), 7.06 (s, 4H), 7.35–7.39 (m, 4H), 7.64–7.69 (m, 6H), 7.85 (s, 1H), 8.50 (s, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.2, 51.9, 61.7, 69.2, 121.4, 124.8, 125.4, 126.8, 127.1, 127.6, 128.6, 129.5, 129.6, 129.8, 129.9, 130.4, 130.6, 130.9, 131.2, 131.5, 133.9, 134.1, 134.2, 134.6, 136.7, 136.9, 138.9, 153.0, 175.5; IR (KBr)ν_max1163, 1261, 1302, 1343, 1436, 1466, 1505, 1585, 1603, 2853, 2924, 2963, 3018, 3057 cm⁻¹; HRMS (ESI) calcd for C₃₁H₂₄Br₂NOS₂ 647.9661 (M + H⁺); found 647.9661.

3-Butyl-2,4-bis(2-fluorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6k). Yellow semi-solid (0.187 g, 78%), ¹H NMR (600 MHz, CDCl₃): δ 0.66 (t, J = 7.2 Hz, 3H), 0.92–0.99 (m, 1H), 1.19–1.26 (m, 1H), 1.42–1.45 (m, 1H), 1.52–1.56 (m, 1H), 2.49–2.53 (m, 1H), 2.75–2.80 (m, 1H), 6.00 (s, 1H), 6.44 (s, 1H), 6.97 (t, J = 9.0 Hz, 1H), 7.05 (t, J = 9.0 Hz, 1H), 7.13–7.18 (m, 3H), 7.29–7.33 (m, 2H), 7.45–7.48 (m, 2H), 7.55–7.58 (m, 1H), 7.60–7.62 (m, 1H), 8.37–8.39 (m, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 13.7, 20.0, 29.5, 46.6, 55.7, 64.1, 116.0, 116.1, 116.2, 116.3, 120.4, 123.6, 123.9, 124.7, 127.1, 127.6, 129.4, 129.7, 129.8, 130.5, 130.9, 131.0, 131.2, 131.5, 136.9, 153.8, 160.0, 160.5, 161.7, 162.2, 175.8; IR (KBr)ν_max 1149, 1202, 1228, 1331, 1455, 1487, 1516, 1610, 2853, 2925, 2961, 3024, 3066 cm⁻¹; HRMS (ESI) calcd for C₂₇H₂₄F₂NOS₂ 480.1262 (M + H⁺); found 480.1262.

2,4-Bis(2-chlorophenyl)-3-(4-methylbenzyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6l). Yellow solid (0.224 g, 80%), mp 173–174 °C, ¹H NMR (400 MHz, CDCl₃): δ 2.24 (s, 3H), 3.47 (d, J = 13.6 Hz, 1H), 4.03 (d, J = 13.6 Hz, 1H), 5.88 (s, 1H), 6.58 (s, 1H), 6.90–6.97 (m, 4H), 7.16 (d, J = 7.2 Hz, 1H), 7.20–7.24 (m, 3H), 7.31–7.33 (m, 1H), 7.36–7.38 (m, 1H), 7.45–7.50 (m, 2H), 7.52 (s, 1H), 7.56–7.58 (m, 1H), 7.71–7.73 (m, 1H), 8.37 (d, J = 7.6 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 21.0, 51.4, 58.8, 66.8, 120.7, 124.6, 125.9, 126.4, 127.4, 128.4, 129.0, 129.1, 129.6, 129.9, 130.2, 130.5, 130.9, 131.3, 132.9, 133.7, 134.9, 135.8, 136.5, 136.6, 137.2, 152.9, 175.2; IR (KBr)ν_max 1129, 1241, 1302, 1346, 1440, 1500, 1583, 1601, 2851, 2919, 2967, 3016, 3058 cm⁻¹; HRMS (ESI) calcd for C₃₁H₂₄Cl₂NOS₂ 560.0671 (M + H⁺); found 560.0669.

3-Butyl-2,4-bis(4-chlorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6m). Yellow solid (0.192 g, 75%), mp 138–139 °C, ¹H NMR (600 MHz, CDCl₃): δ 0.70 (t, J = 7.2 Hz, 3H), 1.03–1.08 (m, 1H), 1.18–1.24 (m, 1H), 1.44–1.49 (m, 2H), 2.34–2.38 (m, 1H), 2.49–2.55 (m, 1H), 5.64 (s, 1H), 5.85 (s, 1H), 7.16–7.19 (m, 3H), 7.20–7.21 (m, 2H), 7.25–7.26 (m, 3H), 7.42 (d, J = 7.2 Hz, 2H), 7.50–7.53 (m, 1H), 8.34 (d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 14.3, 20.4, 30.3, 46.1, 59.7, 69.0, 120.9, 124.2, 124.8, 127.7, 128.9, 129.1, 129.2, 129.6, 130.2, 131.0, 131.6, 133.6, 134.8, 135.2, 137.0, 140.1, 153.4, 176.2; IR (KBr)ν_max 1101, 1240, 1302, 1330, 1436, 1470, 1518, 1588, 1607, 2856, 2926, 2954, 3021, 3065 cm⁻¹; HRMS (ESI) calcd for C₂₇H₂₄Cl₂NOS₂ 512.0671 (M + H⁺); found 512.0674.

3-Butyl-2,4-bis(3-fluorophenyl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6n). Yellow solid (0.172 g, 72%), mp 128–129 °C, ¹H NMR (600 MHz, CDCl₃): δ 0.78 (t, J = 7.8 Hz, 3H), 1.13–1.19 (m, 1H), 1.28–1.34 (m, 1H), 1.54–1.59 (m, 2H), 2.43–2.47 (m, 1H), 2.60–2.65 (m, 1H), 5.76 (s, 1H), 5.98 (s, 1H), 6.96–6.99 (m, 1H), 7.01–7.07 (m, 3H), 7.11–7.15 (m, 2H), 7.31–7.34 (m, 2H), 7.48–7.51 (m, 2H), 7.58–7.60 (m, 1H), 8.42 (d, J = 8.4 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃): δ 13.9, 20.4, 29.9, 46.2, 59.8, 68.9, 114.7, 114.8, 115.0, 115.7, 115.8, 115.9, 120.8, 123.3, 124.5, 124.8, 127.1, 127.5, 127.7, 129.5, 130.3, 130.4, 131.0, 131.6, 136.9, 139.2, 144.2, 153.4, 162.1, 162.5, 163.8, 164.1, 176.2; IR (KBr)ν_max 1132, 1241, 1261, 1297, 1328, 1435, 1486, 1513, 1586, 1613, 1650, 1723, 2817, 2955, 3059 cm⁻¹; HRMS (ESI) calcd For C₂₇H₂₄F₂NOS₂ 480.1262 (M + H⁺); found 480.1262.

3-Benzyl-2,4-di(naphthalen-2-yl)-3,4-dihydrothiochromeno[3,2-e][1,3]thiazin-5(2H)-one (6o). Yellow solid (0.202 g, 70%), mp 110–111 °C, ¹H NMR (400 MHz, CDCl₃): δ 3.54 (d, J = 14.4 Hz, 1H), 4.08 (d, J = 14.4 Hz, 1H), 5.79 (s, 1H), 6.56 (s, 1H), 6.98–6.99 (m, 1H), 7.02–7.06 (m, 2H), 7.09–7.13 (m, 3H), 7.15–7.20 (m, 3H), 7.22–7.25 (m, 5H), 7.26–7.73 (m, 2H), 7.32–7.46 (m, 1H), 7.46–7.49 (m, 2H), 7.51 (s, 1H), 7.55–7.59 (m, 1H), 7.65 (t, J = 7.6 Hz, 1H), 8.36 (d, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 50.8, 59.8, 68.8, 120.9, 124.8, 125.8, 126.1, 126.2, 126.7, 126.9, 127.1, 127.5, 127.6, 127.7, 127.8, 127.9, 128.3, 128.4, 128.7, 128.9, 129.3, 129.7, 131.2, 131.5, 132.9, 133.2, 133.3, 133.5, 134.0, 137.0, 137.8, 138.9, 152.8, 176.0; IR (KBr)ν_max 1162, 1233, 1306, 1343, 1455, 1437, 1510, 1587, 1616, 2851, 2924, 2962, 3067 cm⁻¹; HRMS (ESI) calcd for C₃₈H₂₈NOS₂ 578.1607 (M + H⁺); found 578.1613.

Acknowledgements

A.T.K gratefully acknowledges Council of Scientific and Industrial Research (CSIR) 02(0181)/14/EMR-II) for financial assistance. KM and PRB acknowledges UGC, New Delhi for their research fellowships. The authors are also thankful to the Department of Science and Technology (DST) for providing single XRD facility under FIST programme to the Department of Chemistry as well as to the Director, IIT Guwahati for providing general facility.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Spectral data (¹H and ¹³C NMR copies) of all the synthesized compounds. CCDC 1029813 and 1029814. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra06905j

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