Synthesis of benzylic thioether containing α-substituted thio compounds via carbene insertion into an S–H bond: expeditious access to a new C–S bond

Abstract

Considering the importance of thioethers in biological systems, we developed a strategy to achieve these target molecules. In this regard, an efficient copper(II)-catalyzed synthesis of highly biologically relevant thioethers is realized, employing readily available and inexpensive starting precursors under ambient conditions. The developed new methodology is very useful to selectively synthesize a C–S bond via carbene insertion into an S–H bond. Our strategy also paved the way to produce a wide range of α-thio substituted benzylic esters in a single-pot method in very good yields under short reaction times. All the synthesized compounds have been fully characterized using spectroscopic and analytical techniques. The best features of the developed strategy are S–H insertion, mild reaction conditions, wide substrate scope, and excellent functional group tolerance.

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Introduction

Nitrogen, oxygen, and sulphur-containing organic scaffolds are highly useful in the field of pharmaceuticals due to their wide spectrum of biological activity.¹ Among the different hetero-atoms, sulfur is one of the most essential elements found in living systems in the form of proteins and amino acids. Particularly, organosulfur compounds play significant roles in the fields of biology and chemistry due to their ubiquitous biological activity.² Beyond amino acids (methionine and cysteine), the C–S bond is present in several natural products, significant drug molecules and functional materials from the pharmaceutical industry,³ and in products in the food industry.⁴ These motifs also play a vital role in photoelectric materials⁵ due to the higher resonance energy of the sulphur atoms. Among the different organosulfur compounds, α-substituted thioethers, in particular, possess a significant role because they act as suitable precursors in the synthesis of biologically active benzothiophenes and Julia reagents.⁶ Moreover, organosulfur-based structural frameworks are present in various biologically active compounds and synthetic intermediates. Sulphur-containing heterocycles exhibit many pharmacological activities. Particularly, thioethers of benzoxazoles and benzothiazoles have been important targets due to their biological activities. They are extensively useful as antibacterial, antifungal, anti-inflammatory, anticancer, antiviral, antagonizing, and antituberculosis agents and as fungicides^7–12 (Fig. 1).

Fig. 1 Some biologically active compounds containing thioethers of the benzoxazole scaffold.

Additionally, in recent years, transition metal catalysis has dramatically changed the face of modern organic chemistry by introducing novel synthetic routes. Using these facile catalytic systems, construction of several carbon–heteroatom bond formations, such as C–O, C–N and C–P, as well as other carbon–element bonds based on B, Si, Ge, and Sn, was developed. Until now, the effective construction of C–S bonds has been highly challenging or very rarely explored compared with the formation of other carbon–heteroatom bonds in the field of organic synthesis due to its own limiting factors, such as harsh reaction conditions (higher temperature, toxic and higher boiling solvents, and longer reaction times), deactivation of the catalytic system due to its strong affinity with metals, expensive starting precursors, and usage of high loading metal catalysts. Therefore, we need to develop an alternate, greener and efficient protocol for the construction of organosulphur compounds via C–S bond formation over existing conventional methodologies. In this study, we overcame all these drawbacks by using a new catalytic system to produce biologically relevant organosulfur compounds containing a C–S bond in an effective manner.

Generally, metal-catalysed reactions have been useful synthetic tools to access the target molecules in organic transformations. Particularly, copper-catalysed organic reactions are a promising methodology for synthesizing an important class of organic molecules used in medicinal chemistry and material science.¹³ For example, diazo compounds are very useful precursors in organic transformations to construct complex organic molecular frameworks using C–C and C–X bond formations via transition metal catalysis. It is well known that reactive intermediates, such as metal carbenes or carbenoids, which are in situ formed from diazo compounds, can undergo various synthetic organic transformations and are sometimes ideal for initiating domino sequences, leading to the generation of structural complexity.¹⁴ Moreover, diazo compounds are useful precursors, including C–H and X–H (X= N, O, S, P, and Si) insertion,¹⁵ cyclopropanation¹⁶ and ylide formation.¹⁷ The tandem or cascade construction of biologically relevant organosulphur compounds, such as thioethers/thioesters, via the formation of a new C–S bond by S–H insertion through cross-coupling reactions under metal catalysis via a single pot process is very less due to its synthetic challenges. Particularly, the formation of C–S bonds using heterocyclic compounds containing thiols and diazo compounds is known but has not been explored much in the literature so far. Beller and coworkers have reported S–H insertion into benzoxazole–thiol to afford the product using an exotic Cu-NC/Al₂O₃ as catalyst.¹⁸ Ollevier et al. have reported the synthesis of α-thioesters using α-diazocarbonyl compounds with organo-sulphur compounds via S–H insertion under copper(I) catalysis (Scheme 1a).¹⁹ Huo and co-workers have utilized α-diazoesters and thiols to form α-thioethers under ambient temperature in the presence of visible light (Scheme 1b).²⁰ Eosin-Y-catalysed sulfenylation of hydrazones with thiols under visible light to produce the thioether derivatives was developed by the Krishna group (Scheme 1c).²¹ Chens and coworkers have reported S–H insertion into benzoxazole–thiol to yield the expected product using TfOH as a catalyst (Scheme 1d).²²

Scheme 1 Synthesis of thioethers using a carbene source (a–e).

Inspired by these reports on the significance of thioethers and their biological applications and by our ongoing research program in the field of metal carbenes,^23–25 we studied the construction of biologically relevant organic molecular frameworks using a new C–S bond formation via a simple reaction strategy. In this line, we investigated the development of an efficient reaction strategy to construct new C–S bonds, along with chiral centers, using copper-carbenoids with heterocyclic compounds containing thiols at ambient temperature with shorter reaction times.

Results and discussion

In our investigation, initially, we tested the reaction between 2-mercaptobenzoxazole (1a) and methyl 2-diazo-2-phenylacetate (2a) in the presence of 5 mol% of CuI under MeCN solvent at ambient temperature for 12 h. To our delight, we isolated the expected product methyl 2-(benzo[d]oxazol-2-ylthio)-2-phenylacetate (3a) in 76% yield and the desired product was confirmed through spectroscopic techniques such as ¹H-NMR, ¹³C-NMR and mass spectrometry. An interesting feature of this intermolecular organic transformation is generating a new C–S bond, along with one chiral centre, in a single-pot reaction. Encouraged by these interesting results, we attempted to improve the yield of the desired product 3a using optimised reaction conditions. Accordingly, we screened the following metal catalysts, CuCl₂·2H₂O, CuSO₄·5H₂O and Cu(OAc)₂ of 5 mol%, in MeCN solvent at room temperature for 12 h; the yield of the anticipated product 3a was not improved and the desired product 3a was formed in 66%, 72% and 75%, respectively (Table 1, entries 2–4). Further, the yield of the anticipated product 3a was increased from 71% to 78% when we used 5 mol% of CuBr and Cu(CH₃CN)ClO₄ as a metal catalyst under the same reaction conditions (Table 1, entries 5 and 6). Further, to improve the yield of product 3a, we used 2 mol% of the metal catalyst Cu(OTf)₂; surprisingly, we obtained product 3a with 80% yield (Table 1, entry 7). Further, in order to increase yield, we screened different solvent systems, ranging from MeCN to polar aprotic solvents, such as THF, CHCl₃, C₂H₄Cl₂ and CH₂Cl₂, using 5 mol% of Cu(OTf)₂ at ambient temperature with varying reaction times (Table 1, entries 8–12). To our delight, we observed that the yield of 3a was 77% when 5 mol% of Cu(OTf)₂ was used in MeCN as a solvent for 12 h (Table 1, entry 13). Further, the reaction was conducted by loading the metal catalyst, 5 mol% Cu(OTf)₂, in DCM for 2 h, and the yield of 3a gradually increased to 85% (Table 1, entry 14). Finally, we tested the reaction using 2 mol% Cu(OTf)₂ in DCM, and the yield of 3a was 89% (Table 1, entry 15). We tested the reaction in the absence of a metal catalyst in DCM for 5 h, and in this case, the product 3a was not observed (Table 1, entry 16). When we used TfOH as a catalyst, we observed a trace amount of the product (Table 1, entry 17). A control experiment with TfOH confirmed that the reaction is not fully acid-promoted; however, it proceeds with poor selectivity and significant decomposition. Nevertheless, the Cu(OTf)₂ effectively accelerated the transformation via the formation of a Cu(II)–carbene intermediate, yielding the required α-thio-substituted benzylic esters in high yield. Therefore, the Lewis acidity of Cu(OTf)₂ prevents the excessively acidic conditions associated with TfOH and ensures controlled activation of the diazo molecule. From these optimisation studies, we finally concluded that the selective S–H insertion into the C–S bond is effective in the presence of Cu(OTf)₂ (2 mol%) using dichloromethane as the solvent at ambient temperature for 2 h, and TfOH is not suitable for this S–H insertion reaction with α-aryl diazoester.

Table 1 Optimization studies for the reaction of S–H insertion^a

S. no.	Catalyst (mol%)	Solvent	Time (h)	Isolated^b yield (%)
a All reactions were carried out with (1.0 mmol, 1 equiv.) of 2-mercaptobenzoxazole (1a) and (1.0 mmol, 1 equiv.) of α-diazo compound (2a).b Isolated yield of the pure product obtained after column chromatography purification.
1	CuI (5)	CH3CN	12	76
2	CuCl2·2H2O (5)	CH3CN	12	66
3	CuSO4·5H2O (5)	CH3CN	12	72
4	Cu(OAc)2 (5)	CH3CN	12	75
5	CuBr (5)	CH3CN	12	71
6	Cu(CH3CN)4ClO4 (5)	CH3CN	12	78
7	Cu(OTf)2 (2)	CH3CN	12	80
8	Cu(OTf)2 (2)	THF	12	70
9	Cu(OTf)2 (2)	Toluene	10	64
10	Cu(OTf)2 (2)	CHCl3	5	82
11	Cu(OTf)2 (2)	DCE	5	84
12	Cu(OTf)2 (2)	DCM	5	89
13	Cu(OTf)2 (5)	MeCN	12	77
14	Cu(OTf)2 (5)	DCM	2	85
15	Cu(OTf)2(2)	DCM	2	89
16	No catalyst	DCM	5	nr
17	TfOH	CH3CN	5 min	Trace

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Herein, we report the developed methodology for the synthesis of α-thioether derivatives via carbene insertion into an S–H bond to form a C–S bond, along with one chiral centre. The highlight of this reaction is the high selectivity to produce the C–S bond through S–H insertion. It is important to note that metal carbenoids can be inserted into S–H bond to create thioethers utilising 2-mercaptobenzoxazole as a sulfur source. The scope of the reaction was tested by utilizing different substituted 2-mercaptobenzoxazoles 1a with different α-aryl-α-diazoacetates 2a in the presence of a copper catalyst to form the corresponding α-thioethers (3a–l) in very good to excellent yields, and the results and conditions^a,b are summarized in Scheme 2. The reaction between the substrates 1a and 2a, containing different ester functionalities, viz. methyl 2a, ethyl 2b, isopropyl 2c, and benzyl 2d, produced the corresponding products 3a, 3b, 3c and 3d in 89%, 90%, 92%, and 89% yields, respectively (Scheme 2). The aryl ring of α-diazoester 2a, containing electron-withdrawing groups, such as chloro, bromo and fluoro, furnished the anticipated products 3e–3j in very good to excellent yields. The electron-donating groups, such as methyl and methoxy substituted diazoesters 2a, reacted well with 2-mercaptobenzoxazole derivatives to provide the desired products 3k–3n in excellent yields. The aryl ring of ethyl diazoacetate 2b, having electron-withdrawing groups, such as 4-chloro, 2,4-dichloro and 3-Br substituents, also smoothly reacted with compound 1a to furnish the corresponding products 3o–3q in 85%, 81%, and 79% yield, respectively (Scheme 2).

Scheme 2 Substrate scope of methyl/ethyl phenyl diazoacetate 2a with 2-mercaptobenzoxazole derivatives. ^aAll the reactions were conducted using 2-mercaptobenzoxazole (1.0 mmol, 1 equiv.) and α-aryl diazoester 2 (1.0 mmol, 1 equiv.) with 2 mol% of Cu catalyst in 3 mL of DCM solvent at ambient temperature. ^bIsolated yield of the pure products 3.

To further explore the substrate scope of the reaction, we carried out the reaction between substituted 2-mercaptobenzoxazole derivatives and methyl phenyl diazoacetate using the optimized reaction conditions, and the results and conditions^a,b are summarised in Scheme 3. The reaction between methyl phenyl diazoacetate (2) and 2-mercaptobenzoxazole, whose aryl ring has halogen groups (F, Cl, and Br) at the para position, smoothly reacted and afforded the corresponding products 4a–c in 79%, 80%, and 83% yields, respectively (Scheme 3). 2-Mercaptobenzoxazole, containing a strong electron-withdrawing group, such as NO₂, also reacted well with compound (2) to furnish the desired product 4d in 78% yield. 2-Mercaptobenzoxazole, bearing electron-donating functionalities like Me and OMe groups at the para position, also reacted smoothly with methyl phenyl diazoacetate (2) to produce the anticipated products 4e and 4f in 81% and 82% yields, respectively (Scheme 3). Both substrates (1) and (2) have aryl rings that contain halogen substituents, such as chloro, bromo and fluoro, at ortho and para positions to afford the respective products 4g–i in very good yields (Scheme 3). 2-Mercaptobenzoxazole containing NO₂ substituent at the para position and similarly, compound (2) having OMe group at the para position, smoothly reacted and formed the corresponding product 4j in 88% yield. 4k and 4l are also produced in good yields of 83% and 85%.

Scheme 3 Substrate scope of 2-mercaptobenzoxazoles with methyl/ethyl diazoacetate derivatives. ^aAll the reactions were conducted using 2-mercaptobenzoxazole (1.0 mmol, 1 equiv.) and α-aryl diazoester 2 (1.0 mmol, 1 equiv.) with 2 mol% of Cu catalyst in 3 mL of DCM solvent at ambient temperature. ^bIsolated yield of the pure products 4.

Still, to further assess the substrate scope, we tested the reactions of 2-mercapto benzoxazole (1a) and ethyl 2-((6-chlorobenzo[d]thiazol-2-yl) thio) acetate (1a) with ethyl 2-diazoacetate (2b) under standard reaction conditions.^a,b Interestingly, the reactions provided the desired products 5a and 5b in 93% and 89% yields, respectively. Additionally, the reaction between ethyl 2-((6-chlorobenzo[d]thiazol-2-yl)thio) acetate (1a) and ethyl 2-diazo-2-phenylacetate, ethyl 2-diazo-2-(3,4-dichlorophenyl)acetate (2b) formed the corresponding desired products 5c and 5d in 81% and 78% yields, respectively (Scheme 4).

Scheme 4 Substrate scope of 2-mercaptobenzoxazoles/ethyl 2-((6-chlorobenzo[d]thiazol-2-yl)thio)acetate with α-diazoester derivatives. ^aAll the reactions were conducted using 2-mercaptobenzoxazole/ethyl 2-((6-chlorobenzo[d]thiazol-2-yl)thio)acetate (1.0 mmol, 1 equiv.) and α-aryl diazoester 2 (1.0 mmol, 1 equiv.) with 2 mol% Cu catalyst in 3 mL of DCM solvent at ambient temperature. ^bIsolated yield of the pure products 5.

To study the scalability of our optimized reaction conditions, we carried out a large scale reaction between 2-mercaptobenzoxazole (1a) (378 mg, 2.5 mmol, 1 equiv.) and isopropyl phenyl diazoacetate (2a) (510 mg, 2.5 mmol, 1 equiv.) in 10 mL DCM (0.33 M) at rt in the presence of the Cu(OTf)₂ catalyst (18 mg, 2 mol%). The scale-up reaction afforded the anticipated product 3c in 86% yield (708 mg, 2.1 mmol), confirming the large-scale applicability of the method (Scheme 5).

Scheme 5 Larger scale synthesis of α-thio substituted benzylic ester.

A plausible mechanism has been proposed below for the formation of α-thio-substituted benzylic esters (III) from I and II, as shown in Fig. 2. Initially, the active catalyst Cu(OTf)₂ (A) would react with α-diazoester (I) to generate the intermediate (B) via the formation of a copper-carbenoid with the evolution of nitrogen gas. Simultaneously, 2-mercaptobenzoxazole (II) undergoes nucleophilic addition with the intermediate (B) to generate the intermediate (C). Eventually, the intermediate (C) would undergo hydrogen migration to afford the desired product (III) with the regeneration of the active catalyst Cu(OTf)₂.

Fig. 2 Proposed reaction mechanism for the reaction of 2-mercaptobenzoxazole and α-diazoesters.

Conclusion

We successfully developed an efficient protocol to access biologically relevant α-thio substituted benzylic esters from 2-mercaptobenzoxazoles and α-diazoesters in the presence of a copper catalyst. Using this newly developed protocol, we synthesized a variety of α-thioester derivatives at ambient temperature. During this organic transformation, a new C–S bond is formed with a new chiral center. These overall organic transformations proceed via cascade metal-carbenoid formation and S–H insertion, followed by reductive elimination to produce the anticipated product in very good yields. A wide substrate scope, shorter reaction times and excellent functional group tolerance are the best features of this reaction. The synthesized α-thioester derivatives may be useful in the pharmaceutical and chemical industry.

Experimental section

General experimental information

Commercial reagents were used without further purification. IR spectra were recorded on a PerkinElmer FTIR spectrometer using solid samples pressed into KBr pellets. For compounds, ¹H NMR (400 MHz, CDCl₃) and ¹³C NMR (100 MHz, CDCl₃) spectra were recorded in deuterochloroform (CDCl₃) on a Bruker 400 MHz spectrometer using tetramethylsilane (TMS, δ = 0) as an internal standard at room temperature. HR-MS was recorded on a UHD Q-TOF mass spectrometer. All the reagents were purchased from Sigma-Aldrich. Reactions were monitored by thin-layer chromatography (TLC) on silica gel 60 F₂₅₄ aluminium plates. TLC plates were visualized using ultraviolet (UV) light at 254 nm. Column chromatography was performed with silica gel 60 Å (100–200 mesh) from Aldrich using the stated mixture of solvents. Based on the literature procedure, different types of α-aryl diazoesters were synthesized (see SI).

General procedure for the synthesis of compounds (3a–3q), (4a–4l). Double-distilled dry DCM (3 mL) (0.33 M) solvent was added to a mixture of 2-mercapto benzoxazoles (1.0 mmol, 1 equiv.), α-aryl diazoesters (1.0 mmol, 1 equiv.), and Cu(OTf)₂ (2 mol%) catalyst. The reaction mixture was allowed to stir at room temperature for 2 h under a nitrogen atmosphere. After the reaction was completed, it was monitored by TLC. The reaction mixture was filtered through Celite, and the filtrate was concentrated. To the crude reaction mixture, water (10 mL) and EtOAc (10 mL) were added, and the mixture was extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (eluted with 5% EtOAc/hexane) to give the desired product 3a in a pure form.

Analytical data.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-phenylacetate (3a). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (266 mg, 89% yield). Mp 79–80 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.53–7.48 (m, 1H), 7.47–7.43 (m, 2H), 7.34–7.31 (m, 1H), 7.30–7.26 (m, 2H), 7.25 (dd, J = 3.9, 1.3 Hz, 1H), 7.21–7.11 (m, 2H), 5.62 (s, 1H), 3.68 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.05, 162.99, 151.97, 141.82, 134.09, 129.24, 129.18, 128.54, 124.48, 124.29, 118.85, 110.12, 53.75, 53.50. IR (KBr): 1738, 1505, 1472, 1453, 1130 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₃NO₃S 299.0616, found: 300.0693.
Ethyl 2-(benzo[d]oxazol-2-ylthio)-2-phenylacetate (3b). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (282 mg, 90% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.47 (m, 3H), 7.32–7.26 (m, 2H), 7.26–7.22 (m, 2H), 7.18–7.09 (m, 2H), 4.13 (m, 2H), 1.13 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.43, 163.00, 151.88, 141.77, 134.14, 129.12, 129.05, 128.48, 124.41, 124.20, 118.72, 110.03, 62.47, 53.87, 14.05. IR (KBr): 1742, 1505, 1452, 1020, 806 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅ NO₃S 313.0773, found: 314.0859.
Isopropyl 2-(benzo[d]oxazol-2-ylthio)-2-phenylacetate (3c). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (301 mg, 92% yield). Mp 63–64 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.51–7.43 (m, 3H), 7.33 (dd, J = 7.9, 1.4 Hz, 1H), 7.31–7.26 (m, 2H), 7.26–7.11 (m, 3H), 5.55 (s, 1H), 4.99 (p, J = 6.3 Hz, 1H), 1.20 (d, J = 6.2 Hz, 3H), 1.05 (d, J = 6.2 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.00, 163.17, 151.96, 141.87, 134.25, 129.15, 129.06, 128.54, 124.48, 124.24, 118.78, 110.10, 70.29, 54.11, 21.72, 21.51. IR (KBr): 1738, 1505, 1453, 1241, 1130 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₈H₁₇NO₃S 327.0929, found: 328.1011.
Benzyl 2-(benzo[d]oxazol-2-ylthio)-2-phenylacetate (3d). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (334 mg, 89% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.57–7.53 (m, 3H), 7.38–7.26 (m, 8H), 7.26–7.17 (m, 3H), 5.77 (d, J = 1.4 Hz, 1H), 5.31 (d, J = 12.3 Hz, 1H), 5.11 (d, J = 12.4 Hz, 1H). ¹³C NMR (101 MHz, chloroform-d) δ 169.31, 162.85, 151.86, 141.72, 135.24, 133.74, 129.13, 129.10, 128.52, 128.48, 128.31, 128.07, 124.36, 124.16, 118.72, 110.02, 67.87, 53.81. IR (KBr): 1740, 1510, 1450, 1246, 1134 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₂₂H₁₇NO₃S 375.0929, found: 376.0995.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(2-chlorophenyl)acetate (3e). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (257 mg, 77% yield). Mp 80–81 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.52–7.48 (m, 1H), 7.46–7.42 (m, 2H), 7.35–7.27 (m, 2H), 7.26–7.11 (m, 3H), 5.61 (s, 1H), 3.68 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.07, 163.00, 151.98, 141.82, 134.07, 129.25, 129.20, 128.55, 124.49, 124.30, 118.86, 110.13, 53.74, 53.53. IR (KBr): 1738, 1505, 1453, 1275, 1130 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂ClNO₃S 333.0226, found: 334.0299.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(3-chlorophenyl)acetate (3f). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (270 mg, 81% yield). Mp 97–98 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.56–7.53 (m, 1H), 7.50 (d, J = 2.1 Hz, 1H), 7.40–7.35 (m, 2H), 7.27–7.16 (m, 4H), 5.63 (s, 1H), 3.74 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.52, 162.49, 152.03, 141.73, 136.27, 135.00, 130.42, 129.41, 128.74, 126.81, 124.58, 124.43, 118.91, 110.19, 53.72, 53.21. IR (KBr): 1742, 1502, 1453, 1128, 1096 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂ClNO₃S 333.0226, found: 334.0301.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(4-chlorophenyl)acetate (3g). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (277 mg, 83% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.53–7.49 (m, 1H), 7.44–7.40 (m, 2H), 7.35–7.31 (m, 1H), 7.27–7.23 (m, 2H), 7.21–7.12 (m, 2H), 5.63 (s, 1H), 3.70 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.57, 162.48, 151.94, 141.69, 135.13, 132.94, 129.90, 129.32, 124.49, 124.34, 118.82, 110.09, 53.54, 53.07. IR (KBr): 1743, 1503, 1453, 1132, 1095 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂ClNO₃S 333.0226, found: 334.0277.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(2,4-dichlorophenyl)acetate (3h). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (266 mg, 75% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.50–7.44 (m, 2H), 7.27 (d, J = 4.7 Hz, 1H), 7.14–7.04 (m, 4H), 6.11 (s, 1H), 3.68 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.58, 162.18, 151.82, 141.43, 135.28, 134.75, 131.27, 130.85, 129.73, 127.57, 124.27, 124.11, 118.61, 109.86, 53.45, 50.29. IR (KBr): 1746, 1587, 1503, 1453, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₁Cl₂NO₃S 366.9837, found: 367.9939.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(2-bromophenyl)acetate (3i). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (302 mg, 80% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.49–7.44 (m, 3H), 7.29–7.25 (m, 1H), 7.19–7.13 (m, 1H), 7.13–7.01 (m, 3H), 6.10 (s, 1H), 3.65 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.26, 162.62, 151.98, 141.71, 134.02, 133.55, 130.43, 129.98, 128.13, 124.63, 124.40, 124.22, 118.81, 110.03, 53.56, 53.28. IR (KBr): 1747, 1504, 1452, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂BrNO₃S 376.9721, found: 377.9770.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(4-fluorophenyl)acetate (3j). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (257 mg, 81% yield). Mp 59–60 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.59–7.52 (m, 3H), 7.37 (dd, J = 8.0, 1.3 Hz, 1H), 7.26–7.17 (m, 2H), 7.05–6.99 (m, 2H), 5.73 (s, 1H), 3.75 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.66, 164.13, 162.51, 161.66, 151.80, 141.59, 130.34, 130.26, 130.11, 130.08, 124.36, 124.20, 118.67, 116.12, 115.91, 109.95, 53.32, 52.86. IR (KBr): 1742, 1603, 1509, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂FNO₃S 317.0522, found: 318.0572.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(o-tolyl)acetate (3k). Purified by column chromatography (hexane : EtOAc, 95 : 5). Pale yellow liquid (285 mg, 91% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.67–7.62 (m, 1H), 7.60–7.55 (m, 1H), 7.44 (dd, J = 7.7, 1.3 Hz, 1H), 7.31–7.23 (m, 5H), 6.03 (s, 1H), 3.80 (s, 3H), 2.61 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.03, 163.12, 151.79, 141.63, 136.79, 132.07, 130.97, 128.97, 127.80, 127.31, 126.76, 124.25, 124.04, 118.58, 109.88, 77.36, 53.19, 50.29, 38.89, 19.48. IR (KBr): 1747, 1503, 1453, 1132, 1097 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅NO₃S 313.0773, found: 314.0823.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(p-tolyl)acetate (3l). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (291 mg, 93% yield). Mp 69–70 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.62–7.58 (m, 1H), 7.44–7.41 (m, 3H), 7.29 (dd, J = 7.5, 1.5 Hz, 1H), 7.25–7.17 (m, 3H), 5.68 (s, 1H), 3.78 (s, 3H), 2.34 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.17, 163.11, 151.96, 141.86, 139.19, 131.03, 129.92, 128.41, 124.45, 124.24, 118.83, 110.09, 53.52, 53.43, 21.30. IR (KBr): 1747, 1503, 1453, 1132, 1097 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅NO₃S 313.0773, found: 314.0842.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(4-methoxyphenyl)acetate (3m). Purified by column chromatography (hexane : EtOAc, 95 : 5). Pale yellow liquid (303 mg, 92% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.44 (dd, J = 7.6, 1.5 Hz, 1H), 7.33 (d, J = 8.7 Hz, 2H), 7.26–7.21 (m, 1H), 7.07 (m, 2H), 6.72 (d, J = 8.7 Hz, 2H), 5.56 (s, 1H), 3.61 (s, 3H), 3.59 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.01, 162.89, 160.03, 151.71, 141.63, 129.61, 125.67, 124.26, 124.06, 118.59, 114.41, 109.88, 55.14, 53.16, 53.08. IR (KBr): 1738, 1609, 1511, 1481, 1031 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅NO₄S 329.0722, found: 330.0795.
Methyl 2-(benzo[d]oxazol-2-ylthio)-2-(3,5-dimethoxyphenyl)acetate (3n). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (309 mg, 86% yield). Mp 101–102 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.52 (dd, J = 7.2, 1.7 Hz, 1H), 7.35 (dd, J = 7.4, 1.7 Hz, 1H), 7.19 (qt, J = 7.6, 3.7 Hz, 2H), 6.60 (d, J = 2.3 Hz, 2H), 6.36 (s, 1H), 5.56 (s, 1H), 3.71 (s, 9H). ¹³C NMR (101 MHz, chloroform-d) δ 169.89, 163.06, 161.31, 152.04, 141.89, 136.05, 124.51, 124.30, 118.87, 110.14, 106.60, 101.25, 55.58, 53.95, 53.53. IR (KBr): 1738, 1609, 1511, 1481, 1031 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₈H₁₇NO₅S 359.0827, found: 360.0894.
Ethyl 2-(benzo[d]oxazol-2-ylthio)-2-(4-chlorophenyl)acetate (3o). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (295 mg, 85% yield). Mp 60–61 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.52–7.47 (m, 1H), 7.45–7.40 (m, 2H), 7.33 (dd, J = 7.8, 1.4 Hz, 1H), 7.25 (d, J = 8.5 Hz, 2H), 7.21–7.12 (m, 2H), 5.59 (s, 1H), 4.16 (m, 2H), 1.16 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.08, 162.61, 151.97, 141.74, 135.10, 133.10, 129.94, 129.32, 124.52, 124.35, 118.82, 110.12, 62.72, 53.29, 14.09. IR (KBr): 1742, 1504, 1451, 1232, 1015 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₄ClNO₃S 347.0383, found: 348.0441.
Ethyl 2-(benzo[d]oxazol-2-ylthio)-2-(3,4-dichlorophenyl)acetate (3p). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (309 mg, 81% yield). Mp 61–62 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.55 (d, J = 2.0 Hz, 1H), 7.45–7.41 (m, 1H), 7.30–7.22 (m, 3H), 7.13–7.03 (m, 2H), 5.53 (s, 1H), 4.10 (m, 2H), 1.10 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.47, 162.09, 151.87, 141.53, 134.85, 133.23, 133.03, 130.85, 130.46, 127.84, 124.45, 124.32, 118.72, 110.01, 62.81, 52.77, 13.98. IR (KBr): 1739, 1504, 1452, 1096, 1032 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₃Cl₂NO₃S 380.9993, found: 382.0070.
Ethyl 2-(benzo[d]oxazol-2-ylthio)-2-(3-bromophenyl)acetate (3q). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (310 mg, 79% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.60–7.57 (m, 1H), 7.52–7.48 (m, 3H), 7.46–7.41 (m, 3H), 7.31–7.26 (m, 2H), 5.65 (s, 1H), 4.30–4.18 (m, 2H), 1.25 (t, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.02, 162.59, 151.99, 141.75, 133.65, 132.30, 131.71, 130.24, 129.93, 124.54, 124.38, 123.30, 118.84, 110.14, 62.76, 53.37, 14.11. IR (KBr): 1747, 1504, 1452, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₄BrNO₃S 390.9878, found: 391.9950.
Methyl 2-((4-fluorobenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4a). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (250 mg, 79% yield). Mp 89–90 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.48–7.42 (m, 2H), 7.30 (td, J = 5.2, 3.2 Hz, 2H), 7.28–7.17 (m, 3H), 6.87 (td, J = 9.1, 2.6 Hz, 1H), 5.61 (s, 1H), 3.70 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.81, 164.95, 161.22, 158.82, 148.21, 142.60, 142.47, 133.84, 129.18, 129.16, 128.45, 111.66, 111.40, 110.24, 110.14, 105.61, 105.35, 53.75, 53.44. IR (KBr): 1742, 1603, 1509, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂FNO₃S 317.0522, found: 318.0589.
Methyl 2-((4-chlorobenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4b). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (267 mg, 80% yield). Mp 100–101 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.49–7.46 (m, 1H), 7.44–7.40 (m, 2H), 7.28–7.21 (m, 4H), 7.16–7.08 (m, 1H), 5.58 (s, 1H), 3.68 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.87, 164.83, 150.57, 142.92, 133.91, 130.07, 129.29, 128.56, 124.46, 118.92, 110.76, 53.90, 53.57. IR (KBr): 1743, 1503, 1453, 1132, 1095 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂ClNO₃S 333.0226, found: 334.0299.
Methyl 2-((4-bromobenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4c). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (314 mg, 83% yield). Mp 90–91 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.66 (d, J = 2.0 Hz, 1H), 7.48–7.43 (m, 2H), 7.34–7.26 (m, 4H), 7.24–7.18 (m, 1H), 5.61 (s, 1H), 3.71 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.86, 164.70, 151.00, 143.37, 133.90, 129.29, 128.56, 127.20, 121.89, 117.34, 111.28, 53.92, 53.58. IR (KBr): 1747, 1504, 1452, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂BrNO₃S 376.9721, found: 377.9795.
Methyl 2-((4-nitrobenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4d). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (268 mg, 78% yield). ¹H NMR (400 MHz, CDCl₃) δ 8.38 (d, J = 2.3 Hz, 1H), 8.13 (dd, J = 8.9, 2.3 Hz, 1H), 7.48–7.41 (m, 3H), 7.33–7.29 (m, 3H), 5.63 (s, 1H), 3.72 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.58, 167.15, 155.34, 145.34, 142.22, 133.53, 129.42, 129.33, 128.89, 128.54, 120.42, 114.89, 110.17, 54.16, 53.65. IR (KBr): 1742, 1510, 1460, 1131, 1085 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₂N₂O₅S 344.0467, found: 345.0477.
Methyl 2-((4-methylbenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4e). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (253 mg, 81% yield). Mp 75–76 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.56–7.50 (m, 2H), 7.41–7.33 (m, 4H), 7.29 (d, J = 8.3 Hz, 1H), 7.04 (dd, J = 8.4, 1.7 Hz, 1H), 5.70 (s, 1H), 3.78 (s, 3H), 2.43 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 170.09, 162.84, 150.28, 142.04, 134.34, 134.24, 129.22, 129.15, 128.57, 125.27, 118.94, 109.48, 53.76, 53.46, 21.55. IR (KBr): 1747, 1503, 1453, 1132, 1097 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅NO₃S 313.0773, found: 314.0839.
Methyl 2-((4-methoxybenzo[d]oxazol-2-yl)thio)-2-phenylacetate (4f). Purified by column chromatography (hexane : EtOAc, 95 : 5). Pale yellow liquid (270 mg, 82% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.56–7.50 (m, 2H), 7.37–7.30 (m, 3H), 7.26 (d, J = 8.9 Hz, 1H), 7.09 (d, J = 2.5 Hz, 1H), 6.80 (dd, J = 8.9, 2.6 Hz, 1H), 5.70 (s, 1H), 3.78 (s, 3H), 3.75 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.87, 163.33, 157.21, 146.50, 142.54, 134.06, 129.09, 129.02, 128.39, 112.20, 110.01, 102.26, 55.84, 53.66, 53.29. IR (KBr): 1738, 1609, 1511, 1481, 1031 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₅NO₄S 329.0722, found: 330.0795.
Ethyl 2-((4-chlorobenzo[d]oxazol-2-yl)thio)-2-(4-chlorophenyl)acetate (4g). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (291 mg, 79% yield). Mp 74–75 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J = 2.0 Hz, 1H), 7.55–7.51 (m, 2H), 7.40–7.35 (m, 3H), 7.25 (ddd, J = 8.7, 2.1, 0.9 Hz, 1H), 5.68 (s, 1H), 4.35–4.20 (m, 2H), 1.31–1.27 (m, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.94, 164.48, 150.57, 142.83, 135.25, 132.87, 130.13, 129.95, 129.40, 124.54, 118.88, 110.78, 62.84, 53.45, 14.13. IR (KBr): 1743, 1503, 1453, 1132, 1095 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₃Cl₂NO₃S 380.9993, found: 382.0058.
Methyl 2-((4-bromobenzo[d]oxazol-2-yl)thio)-2-(2,4-dichlorophenyl)acetate (4h). Purified by column chromatography (hexane : EtOAc, 95 : 5). Orange liquid (344 mg, 77% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.69 (d, J = 2.0 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 2.2 Hz, 1H), 7.32 (ddd, J = 8.6, 1.9, 0.6 Hz, 1H), 7.25–7.19 (m, 2H), 6.10 (s, 1H), 3.76 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.82, 164.16, 151.15, 143.26, 135.81, 135.11, 131.26, 131.07, 130.17, 127.94, 127.34, 122.00, 117.45, 111.33, 53.86, 50.64. IR (KBr): 1746, 1587, 1503, 1453, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₀BrCl₂NO₃S 444.8942, found: 445.8997.
Methyl 2-((4-chlorobenzo[d]oxazol-2-yl)thio)-2-(4-fluorophenyl)acetate (4i). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (285 mg, 81% yield). Mp 70–71 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.57 (d, J = 2.0 Hz, 1H), 7.53 (dd, J = 8.5, 5.2 Hz, 2H), 7.33 (d, J = 8.6 Hz, 1H), 7.21 (dd, J = 8.6, 2.1 Hz, 1H), 7.06 (t, J = 8.5 Hz, 2H), 5.68 (s, 1H), 3.79 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.68, 164.52, 164.40, 161.92, 150.58, 142.86, 130.50, 130.42, 130.14, 130.02, 129.99, 124.54, 118.93, 116.38, 116.16, 110.77, 53.60, 53.15. IR (KBr): 1742, 1603, 1509, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₆H₁₁ClFNO₃S 351.0132, found: 352.0199.
Methyl 2-((4-methoxybenzo[d]oxazol-2-yl)thio)-2-(4-nitrophenyl)acetate (4j). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (329 mg, 88% yield). Mp 121–122 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.46 (d, J = 2.3 Hz, 1H), 8.21 (dd, J = 8.9, 2.4 Hz, 1H), 7.48 (dd, J = 20.7, 8.6 Hz, 3H), 6.90 (d, J = 8.2 Hz, 2H), 5.67 (s, 1H), 3.80 (s, 6H). ¹³C NMR (101 MHz, chloroform-d) δ 169.80, 167.33, 160.44, 155.36, 145.39, 142.32, 129.87, 125.33, 120.40, 114.89, 114.74, 110.15, 55.46, 53.72, 53.58. IR (KBr): 1742, 1510, 1460, 1131, 1085 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₄N₂O₆S 374.0573, found: 375.0645.
Methyl 2-(3,5-dimethoxyphenyl)-2-((4-methylbenzo[d]oxazol-2-yl)thio)acetate (4k). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (310 mg, 83% yield). ¹H NMR (400 MHz, CDCl₃) δ 7.22 (dt, J = 39.6, 5.6 Hz, 2H), 6.93 (t, J = 7.5 Hz, 1H), 6.62–6.54 (m, 2H), 6.32 (t, J = 7.2 Hz, 1H), 5.53 (s, 1H), 3.68 (s, 10H), 2.32 (s, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.84, 162.78, 161.20, 150.18, 141.94, 136.00, 134.24, 125.18, 118.80, 109.38, 106.49, 101.10, 55.46, 53.82, 53.41, 21.44. IR (KBr): 1747, 1503, 1453, 1132, 1097 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₉H₁₉NO₅S 373.0984, found: 374.1046.
Ethyl 2-((4-bromobenzo[d]oxazol-2-yl)thio)-2-(p-tolyl)acetate (4l). Purified by column chromatography (hexane : EtOAc, 95 : 5). Orange liquid (345 mg, 85% yield). ¹H NMR (400 MHz, CDCl₃) 7.69 (d, J = 1.9 Hz, 1H), 7.38 (d, J = 8.2 Hz, 2H), 7.31 (dd, J = 8.6, 1.9 Hz, 1H), 7.23 (d, J = 5.9 Hz, 1H), 7.14 (d, J = 7.8 Hz, 2H), 5.59 (s, 1H), 4.20 (m, 2H), 2.31 (s, 3H), 1.22 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.46, 164.94, 151.00, 143.47, 139.25, 130.98, 129.94, 128.45, 127.14, 121.84, 117.32, 111.24, 62.58, 53.89, 21.33, 14.17. IR (KBr): 1747, 1504, 1452, 1096, 1002 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₈H₁₆BrNO₃S 405.0034, found: 406.0037.
Ethyl 2-(benzo[d]oxazol-2-ylthio)acetate (5a). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (221 mg, 93% yield). ¹H NMR (400 MHz, chloroform-d) δ 7.59 (d, J = 7.6 Hz, 1H), 7.46–7.41 (m, 1H), 7.31–7.21 (m, 2H), 4.25 (q, J = 7.1 Hz, 2H), 4.12 (s, 2H), 1.29 (t, J = 7.2 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 167.90, 163.32, 152.11, 141.78, 124.42, 124.13, 118.65, 110.01, 62.21, 34.28, 14.11. IR (KBr): 1735, 1502, 1470, 1450, 1130 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₁H₁₁NO₃S 237.0460, found: 238.0526.
Ethyl 2-((6-chlorobenzo[d]thiazol-2-yl)thio)acetate (5b). Purified by column chromatography (hexane : EtOAc, 95 : 5). White solid (288 mg, 89% yield). ¹H NMR (400 MHz, chloroform-d) δ 7.81 (d, J = 2.1 Hz, 1H), 7.63 (dd, J = 8.5, 1.7 Hz, 1H), 7.25 (dq, J = 8.4, 2.5, 2.0 Hz, 1H), 4.24 (q, J = 7.1 Hz, 2H), 4.15 (s, 2H), 1.29 (t, J = 7.2 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.13, 167.13, 153.70, 133.80, 132.25, 124.87, 121.75, 121.61, 62.18, 35.18, 14.21. IR (KBr): 1741, 1501, 1452, 1130, 1095 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₁H₁₀ClNO₂S₂ 286.9841, found: 287.9917.
Ethyl-2-((6-chlorobenzo[d]thiazol-2-yl)thio)-2-phenylacetate (5c). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (295 mg, 81% yield). ¹H NMR (400 MHz, chloroform-d) δ 7.75 (s, 1H), 7.51 (d, J = 8.6 Hz, 1H), 7.45 (dd, J = 7.8, 1.8 Hz, 2H), 7.29 (d, J = 6.1 Hz, 2H), 7.24 (d, J = 1.0 Hz, 1H), 7.16 (dd, J = 8.5, 2.1 Hz, 1H), 5.70 (s, 1H), 4.15 (m, 2H), 1.17 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 169.46, 166.85, 153.75, 134.18, 133.77, 132.22, 129.15, 129.11, 129.07, 129.00, 128.62, 124.91, 121.78, 121.59, 62.38, 54.76, 14.16. IR (KBr): 1740, 1500, 1450, 1130, 1090 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₄ClNO₂S₂ 363.0154, found: 364.0224.
Ethyl-2-((6-chlorobenzo[d]thiazol-2-yl)thio)-2-(3,4-dichlorophenyl)acetate (5d). Purified by column chromatography (hexane : EtOAc, 95 : 5). White liquid (377 mg, 78% yield). ¹H NMR (400 MHz, chloroform-d) δ 7.83 (s, 1H), 7.67 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.45–7.37 (m, 2H), 7.27 (d, J = 8.7 Hz, 1H), 5.77 (s, 1H), 4.25 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, chloroform-d) δ 168.70, 165.86, 153.64, 134.90, 133.80, 133.32, 133.19, 132.43, 130.97, 130.67, 128.03, 125.19, 121.87, 121.72, 62.84, 53.54, 14.16. IR (KBr): 1741, 1504, 1455, 1133, 1096 cm⁻¹. HRMS (ESI) m/z: [M + H] calcd for C₁₇H₁₂Cl₃NO₂S₂ 430.9375, found: 431.9447.

Author contributions

Arumugam Jayarani contributed majorly to this work. The corresponding author developed the methodology, supervised the work, helped in fund generation and analysed the data, and the other co-author contributed to data collection.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data underlying this study are available in the published article and its supplementary information (SI). Supplementary information: experimental details and spectroscopic data (¹H and ¹³C NMR). See DOI: https://doi.org/10.1039/d5ra06843f.

Acknowledgements

C. S. gratefully acknowledges the Anusandhan National Research Foundation (ANRF), New Delhi, India, for the financial support (ANRF/PAIR/2025/000021/PAIR). A. J gratefully acknowledges the University Grants Commission (UGC). We thank the Central Instrumentation Facility for NMR, Pondicherry University and the Department of Science and Technology-Fund for Improvement of Science and Technology (DST-FIST).

Notes and references

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