Sunlight Induced and Recyclable g-C3N4 Catalyzed C-H Sulfenylation of Quinoxalin-2(1H)-Ones

A sunlight-promoted sulfenylation of quinoxalin-2(1H)-ones using recyclable graphitic carbon nitride (g-C3N4) as a heterogeneous photocatalyst was developed. Using the method, various 3-sulfenylated quinoxalin-2(1H)-ones were obtained in good to excellent yields under an ambient air atmosphere. Moreover, the heterogeneous catalyst can be recycled at least six times without significant loss of activity.

As a part of our continuing interest in functionalized quinoxalines [30,37,85,86], herein, we wish to report sunlight induced and g-C 3 N 4 catalyzed sulfenylation of quinoxalin-2(1H)ones under air conditions (Scheme 1d). The current reaction provides a highly attractive and practical approach to selectively access various 3-sulfenylated quinoxalin-2(1H)-ones in good to excellent yields. Furthermore, the heterogeneous catalyst can be easily recycled up to six times, while maintaining its high catalytic activity.
Next, we investigated the substrate generality with respect to thiols as evaluated in Scheme 3, various thiols (2b-2m) charged with different aliphatic chains and steric branched chains reacted smoothly to deliver products 3ab-3af in excellent yields. Other linear thiols bearing a phenyl ring or a furan group also proceeded well to provide 3ag-3ai in good yields. In addition, diverse cyclic substituted thiols were all compatible with the reaction, respectively, giving 3aj-3al in good yields. Unfortunately, thiophenol (2m) failed to give the desired product (3am) and a remarkable dimerization product 1,2-diphenyldisulfane was detected in the reaction mixture. Next, we investigated the substrate generality with respect to thiols as evaluated in Scheme 3, various thiols (2b-2m) charged with different aliphatic chains and steric branched chains reacted smoothly to deliver products 3ab-3af in excellent yields. Other linear thiols bearing a phenyl ring or a furan group also proceeded well to provide 3ag-3ai in good yields. In addition, diverse cyclic substituted thiols were all compatible with the reaction, respectively, giving 3aj-3al in good yields. Unfortunately, thiophenol (2m) failed to give the desired product (3am) and a remarkable dimerization product 1,2-diphenyldisulfane was detected in the reaction mixture. To illustrate the synthetic application, a gram-scale experiment between 1a and 2a was carried out (Scheme 4). As anticipated, when the reaction was scaled up to 6 mmol, 3aa was obtained in 84% isolated yield, suggesting the current reaction is a practical method for the synthesis of 3-thioquinoxalinones.
Recycling studies were performed for the reaction between 1a and 2a under the standard conditions. After the reaction was complete, the g-C 3 N 4 catalyst was recycled from the reaction mixture by simple filtration and rinsing with reaction solvent. The recovered photocatalyst was dried and then directly reused in the next round. As shown in Figure 1, the reaction was repeated up to six times, and no obvious losses in its catalytic activity were observed. To illustrate the synthetic application, a gram-scale experiment between 1a and 2a was carried out (Scheme 4). As anticipated, when the reaction was scaled up to 6 mmol, 3aa was obtained in 84% isolated yield, suggesting the current reaction is a practical method for the synthesis of 3-thioquinoxalinones. Recycling studies were performed for the reaction between 1a and 2a under the standard conditions. After the reaction was complete, the g-C3N4 catalyst was recycled from the reaction mixture by simple filtration and rinsing with reaction solvent. The recovered photocatalyst was dried and then directly reused in the next round. As shown in Figure 1, the reaction was repeated up to six times, and no obvious losses in its catalytic activity were observed. To illustrate the synthetic application, a gram-scale experiment between 1a and 2a was carried out (Scheme 4). As anticipated, when the reaction was scaled up to 6 mmol, 3aa was obtained in 84% isolated yield, suggesting the current reaction is a practical method for the synthesis of 3-thioquinoxalinones. Recycling studies were performed for the reaction between 1a and 2a under the standard conditions. After the reaction was complete, the g-C3N4 catalyst was recycled from the reaction mixture by simple filtration and rinsing with reaction solvent. The recovered photocatalyst was dried and then directly reused in the next round. As shown in Figure 1, the reaction was repeated up to six times, and no obvious losses in its catalytic activity were observed. To better understand the mechanism, some control experiments were performed (Scheme 5). The reaction was completely suppressed by addition of two equiv. of TEMPO or BHT (Scheme 5a), suggesting that radical intermediates might be involved in this transformation. Conducting the reaction using phenylmethanethiol 2g as a substrate under the standard conditions, 3ag was isolated in 81% yield and the 1,2-dibenzyldisulfane 5a was detected by GC-MS (Scheme 5b). In addition, in the absence of 1-methylquinoxalin-2(1H)one 1a, phenylmethanethiol 2g underwent a quick dimerization to generate 5a in 78% yield (Scheme 5c). To confirm whether disulfides participate in the sulfenylation process, the reaction between 1a and 5a was performed, and no product 3ag was detected (Scheme 5d), indicating that disulfides should not be the effective intermediates for the sulfenylation. Moreover, performing the template reaction under N2 atmosphere (Scheme 5e), no To better understand the mechanism, some control experiments were performed (Scheme 5). The reaction was completely suppressed by addition of two equiv. of TEMPO or BHT (Scheme 5a), suggesting that radical intermediates might be involved in this transformation. Conducting the reaction using phenylmethanethiol 2g as a substrate under the standard conditions, 3ag was isolated in 81% yield and the 1,2-dibenzyldisulfane 5a was detected by GC-MS (Scheme 5b). In addition, in the absence of 1-methylquinoxalin-2(1H)-one 1a, phenylmethanethiol 2g underwent a quick dimerization to generate 5a in 78% yield (Scheme 5c). To confirm whether disulfides participate in the sulfenylation process, the reaction between 1a and 5a was performed, and no product 3ag was detected (Scheme 5d), indicating that disulfides should not be the effective intermediates for the sulfenylation. Moreover, performing the template reaction under N 2 atmosphere (Scheme 5e), no product 3aa was observed, which demonstrates that dioxygen was crucial for the present transformation.
To better understand the mechanism, some control experiments were performed (Scheme 5). The reaction was completely suppressed by addition of two equiv. of TEMPO or BHT (Scheme 5a), suggesting that radical intermediates might be involved in this transformation. Conducting the reaction using phenylmethanethiol 2g as a substrate under the standard conditions, 3ag was isolated in 81% yield and the 1,2-dibenzyldisulfane 5a was detected by GC-MS (Scheme 5b). In addition, in the absence of 1-methylquinoxalin-2(1H)one 1a, phenylmethanethiol 2g underwent a quick dimerization to generate 5a in 78% yield (Scheme 5c). To confirm whether disulfides participate in the sulfenylation process, the reaction between 1a and 5a was performed, and no product 3ag was detected (Scheme 5d), indicating that disulfides should not be the effective intermediates for the sulfenylation. Moreover, performing the template reaction under N2 atmosphere (Scheme 5e), no product 3aa was observed, which demonstrates that dioxygen was crucial for the present transformation. Based on the above control experiment and related precedents in the literature [36][37][38], a possible reaction mechanism is proposed (Scheme 6). Initially, under the irradiation of visible light, g-C 3 N 4 is excited and generates holes in the valence band (VB) and electrons in the conduction band (CB). Then, the holes obtain an electron from thiol 2 to generate thiyl radical cation 5 via a single electron transfer (SET) process. Simultaneously, the electrons in the CB were transferred to O 2 (air) to generate O 2 •− . Next, O 2 •− abstracted hydrogen from thiyl radical cation 5 to form HO 2 • species and thiyl radical 6, which would add to C=N of 1a giving nitrogen radical intermediate 7. trons in the conduction band (CB). Then, the holes obtain an electron from thiol 2 to generate thiyl radical cation 5 via a single electron transfer (SET) process. Simultaneously, the electrons in the CB were transferred to O2 (air) to generate O2 •− . Next, O2 •− abstracted hydrogen from thiyl radical cation 5 to form HO2• species and thiyl radical 6, which would add to C=N of 1a giving nitrogen radical intermediate 7.

General Information
Unless otherwise noted, all reagents and solvents were used as received from commercial suppliers. The 1 H, 13 C and 19 F NMR spectra were recorded at 400, 100 and 376 MHz by using a German Bruker Avance spectrometer. Chemical shifts were calibrated using residual undeuterated CDCl3 as an internal reference ( 1 H NMR is calibrated at 7.26 ppm and 13 C NMR at 77.0 ppm). Mass spectra were performed on a spectrometer operating on ESI-TOF. The catalyst g-C3N4 was purchased from JiangSu XFNANO Materials Tech Co., Ltd., China.

General Procedure for the Preparation of 3-Thioquinoxalinones
A glass tube equipped with a magnetic stirrer bar was charged with quinoxalin-2(1H)-ones 1 (0.3 mmol), thiols 2 (0.9 mmol), g-C3N4 (10 mg) and EtOAc (1.5 mL). The reaction mixture was open to the air and stirred at room temperature under the irradiation of sunlight (sunny or cloudy weather) for about 8 h. After completion of the reaction, g-C3N4 was filtered out of the mixture. Then filtrate was extracted three times with ethyl acetate (5 mL × 3). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (petroleum ether/ethyl acetate = 10/1-6/1) to give the desired products 3. Scheme 6. Possible mechanism.

General Information
Unless otherwise noted, all reagents and solvents were used as received from commercial suppliers. The 1 H, 13 C and 19 F NMR spectra were recorded at 400, 100 and 376 MHz by using a German Bruker Avance spectrometer. Chemical shifts were calibrated using residual undeuterated CDCl 3 as an internal reference ( 1 H NMR is calibrated at 7.26 ppm and 13 C NMR at 77.0 ppm). Mass spectra were performed on a spectrometer operating on ESI-TOF. The catalyst g-C 3 N 4 was purchased from JiangSu XFNANO Materials Tech Co., Ltd. (JiangSu, China).

General Procedure for the Preparation of 3-Thioquinoxalinones
A glass tube equipped with a magnetic stirrer bar was charged with quinoxalin-2(1H)ones 1 (0.3 mmol), thiols 2 (0.9 mmol), g-C 3 N 4 (10 mg) and EtOAc (1.5 mL). The reaction mixture was open to the air and stirred at room temperature under the irradiation of sunlight (sunny or cloudy weather) for about 8 h. After completion of the reaction, g-C 3 N 4 was filtered out of the mixture. Then filtrate was extracted three times with ethyl acetate (5 mL × 3). The combined organic layers were dried over anhydrous Na 2 SO 4 . After filtration, the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (petroleum ether/ethyl acetate = 10/1-6/1) to give the desired products 3.

Gram-Scale Synthesis of 3aa
A glass tube equipped with a magnetic stirrer bar was charged with quinoxalin-2(1H)-ones 1a (0.96 g, 6 mmol), pane-2-thiol 2a (1.37 g, 18 mmol), g-C 3 N 4 (200 mg) and EtOAc (30 mL). The reaction mixture was open to the air and stirred at room temperature under the irradiation of sunlight for about 8h. After completion of the reaction, g-C 3 N 4 was filtered out of the mixture. Then filtrate was extracted three times with ethyl acetate (30 mL× 2). The combined organic layers were dried over anhydrous Na 2 SO 4 . After filtration, the solvent was evaporated in vacuo. The crude product was purified by silica gel chromatography (petroleum ether/ethyl acetate = 8/1) to give 1.18 g of 3aa, yield 84%.

Recycling Experiments
A glass tube equipped with a magnetic stirrer bar was charged with quinoxalin-2(1H)ones 1a (0.048 g, 0.3 mmol), pane-2-thiol 2a (0.068 g, 0.9 mmol), g-C 3 N 4 (10 mg) and EtOAc (1.5 mL). The reaction mixture was open to the air and stirred at room temperature under the irradiation of sunlight for about 8h. After completion of the reaction, the g-C 3 N 4 previously used was simply filtered and washed with EtOAc (2 mL), and then the recyclable g-C 3 N 4 was dried under vacuum and directly reused for the next reaction cycle without    277.1012. The compound spectra data is in agreement with the report [37].

Conclusions
In summary, we have developed a visible-light induced sulfenylation of quinoxalin-2(1H)-ones employing g-C 3 N 4 as a heterogeneous photocatalyst and ambient air as the sole oxidant. The process was chemo-, regioselective and provided direct access to a series of 3-sulfenylated quinoxalin-2(1H)-ones in good to excellent yields. Importantly, the photocatalyst can be easily recycled up to six times by simple filtration without the significant loss of its reaction efficiency. The environmentally friendly oxidant, recyclable photocatalyst and operation simplicity make this protocol highly attractive in organic synthesis and pharmaceutical chemistry.

Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.