English

• 1.   Introduction

  Disulfide is an important moiety for the construction of various chemically and biologically significant molecules.^[1] Pharmaceutically important examples are biocefalin for cognition disorders and disulfiram for chronic alcoholism. For numerous native proteins, such as oxytocin, vasopressin, insulin and somatostatin, disulfide bridge plays a critical role in the formation of secondary and tertiary structures to maintain the biologically active conformation.^[2] Furthermore, it is also widely applied in the organic reactions, such as the sulfenylation of a variety of organic substrates including indoles, ^[3] diazooxindoles, ^[4] arenes, ^[5] alkynes, ^[6] ketones, ^[7] pyrroles^[8] and sulfoximines.^[9] Moreover, disulfide is frequently used as vulcanizing agent for rubbers and elastomers.^[10]

  Figure 1

  

  Figure 1.  Represented drugs with a disulfide motif

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  Due to all these special characteristics and applications, numerous useful methods have been developed for the synthesis of disulfides, the most frequently used is the direct oxidation of thiols because a great many of thiols are commercially available or are easily synthesized. Peroxides, ^[11] heterogeneous catalysts, ^[12] photocatalysts, ^[13] nitrates, ^[14] halogenating agents, ^[15] and other oxidizing reagents^[16] have been utilized for this transformation. Although these reagents can afford disulfides in good yields, they still suffer from several drawbacks. For instance, the use of bases or expensive metal-based oxidizing reagents, special treatment for the activation of reagents and low selectivity because of over oxidation of the final products into sulfoxides/sulfones. Therefore, the development of a simple and efficient method for disulfides formation under mild reaction conditions remains highly desirable.

  N-Fluorobenzenesulfonimide (NFSI) has been widely used as an electrophilic fluorinating agent since 1990s.^[17] Subsequently, it has been successfully applied as a strong oxidant for organometallic intermediates, ^[18] an amination reagent, ^[19] and a phenylsulfonyl group transfer reagent.^[20] In the course of our study on C—H fluorination, we found that it failed to provide the fluoro product, instead delivered a symmetrical disulfide when the substrate containing a thiol. To the best of our knowledge, oxidative coupling of thiols into disulfides with NFSI is rare in literature. In this context, a great deal of interest has been focused on this phenomenon. We find that NFSI is an ideal choice for the conversion of thiols to the corresponding disulfides at room temperature without any contamination by over oxidation. This new method has the advantages of straightforward workup, mild reaction conditions, high yields of the products, as well as short reaction times.

  2.   Results and discussion

  Our initial experiment was carried out with benzenethiol (1a, 0.5 mmol), N-fluorobenzenesulfonimide (NFSI) (0.75 mmol) in N, N-dimethylformamide (DMF) (1 mL) stirred at room temperature for 1 h. Gratifyingly, the desired product 2a was obtained in 90% yield under this condition (Table 1, Entry 1). Encouraged by this result, we further optimized the reaction conditions, and the results were showed in Table 1. Firstly, different solvents were examined, and ethyl acetate showed optimal influence on the reaction to give the product 2a in 93% isolated yield (Entry 7). Other solvents, such as DMF, dichloromethane (DCM), acetone, MeCN, dimethyl sulfoxide (DMSO), EtOH were less effective (Entries 1~6). Then we focused our attention on the equi-valent amounts of the oxidant. When the amount of NFSI was decreased from 1.2 equiv. to 1.0 equiv., an identical yield was still obtained, but further decrease resulted in only 86% of desired product (Entry 8). To our delight, shortening the reaction time from 1 h to 10 min did not reduce the efficiency of the reaction (Entry 9). Therefore, the optimized conditions for the oxidation of thiols to disulfides can be summarized as follows: 0.5 mmol of substrate, 0.5 mmol of NFSI in ethyl acetate stirred at room temperature for 10 min.

  Table 1

  

  Table 1.  Optimization of reaction conditions^a

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  Entry	NFSI/equiv.	Solvent	Time/min	Yieldb/%
  1	1.2	DMF	60	90
  2	1.2	DCM	60	55
  3	1.2	Acetone	60	64
  4	1.2	Acetonitrile	60	67
  5	1.2	DMSO	60	69
  6	1.2	Ethanol	60	81
  7	1.0	Ethyl acetate	60	93
  8	0.8	Ethyl acetate	60	86
  9	1.0	Ethyl acetate	10	93
  10	0	Ethyl acetate	60	Trace
  a Reaction conditions: benzenethiol (1a, 0.5 mmol), NFSI, solvent (1 mL), r.t.; b Isolated yield.

  Once the efficient conditions had been established, we then performed further investigation to examine the application scope of the present protocol. As shown in Table 2, both electron donating (1b~1d, 1g~1j) and electron withdrawing substituents (1e, 1f, 1k) on the aromatic ring were provided the corresponding disulfides in good to excellent yields. For example, thiosalicylic acid (1k) was smoothly derivatised to give the corresponding disulfide 2k in 97% yield. The scope of this protocol was further extended to heteroaromatic thiols. As shown from the results, reaction of 2-mercaptobenzoxazole (1m) and 2-mercapto-benzothiazole (1n) proceeded smoothly to deliver the desired products 2m and 2n in 82% and 85% yields, respectively. Besides aromatic thiols, aliphatic thiols (1o~1u) also showed good reactivity in this novel transformation. For instance, 3-mercapto-propanoic acid (1s) gave the desired disulfide product 2s in 96% yield under the optimum conditions. But the yield of di-tert-butyl disulfide (2p) was only 43%, presumably due to steric reasons. It is noteworthy that all these reactions showed high chemoselectivity in the case of bi-functional thiols, and a wide spectrum of synthetically variable functional group, such as halogen, methyl, amino and carboxyl were well tolerated, offering valuable synthetic handles for further derivatization of the disulfides. Moreover, conversion of the biologically important L-cysteine (1t) and N-acetylcysteine (1u) into the corresponding disulfides was also investigated. Although the oxidation in protic solvents required prolonged reaction times, the desired products 2t and 2u were obtained in good yields (97% and 84% respectively).

  Table 2

  

  Table 2.  Reaction scope of thiols^{a, b}

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  The mechanism for this reaction is still not clear. When radical scavenger, 2, 2, 6, 6-tetramethyl-piperidine1-oxyl (TEMPO), was added in the reaction of piperidine (1a) and NFSI under the optimized reaction conditions, the reaction was not evidently affected, which indicated that this transformation might not be a radical process. Based on the experimental results and the previous literature, ^[21] a plausible mechanistic pathway is depicted in Scheme 1 with 1a as the model substrate. The fluorosulfonium ion A is attacked by benzenethiol (1a) to deliver intermediate B, which undergo elimination to release intermediate C. Final nucleophilic addition of imide anion to C gives diaryl disulfide 2a and byproduct 3 (compound 3 was confirmed by ¹H NMR and ¹³C NMR spectra).

  Scheme 1

  

  Scheme 1.  Proposed reaction mechanism for the synthesis of disulfides from thiols

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  3.   Conclusions

  In summary, we have demonstrated a simple and rapid method for oxidative coupling of thiols into the symmetrical disulfides using NFSI as an efficient oxidant for the first time. This protocol proceeded successfully under base-and metal-free conditions with the advantages of simple operation, high efficiency of transformation, broad functional group tolerance as well as short reaction times (as brief as 10 min). We believe that this method has potential applications in the synthesis of related bioactive compounds and intermediates.

  4.   Experimental section

  4.1   General considerations

  Starting materials were purchased from commercial suppliers and used without further purification. All the solvents were treated according to general methods. Thin layer chromatography (TLC) was performed using precoated silica gel GF₂₅₄ (0.2 mm), while column chromatography was performed using silica gel (100~200 mesh). The melting point was measured on an YRT-3 melting point apparatus (Shantou Keyi instrument & Equipment Co. Ltd, Shantou, China). The optical rotation was measured on an Anton Paar MCP 200 polarimeter (k＝589 nm). NMR spectra were taken on a Varian INOVA 400 or 600 MHz (Varian, Palo Alto, CA, USA) using CDCl₃ or DMSO-d₆ as solvent. Chemical shifts were expressed in δ, with tetramethylsilane (TMS) functioning as the internal reference. Infrared (IR) spectra were recorded on a PerkinElmer Spectrum Two instrument. High resolution mass spectroscopy data of the products were collected on a Waters Micromass GCT or a Bruker Apex IV FTMS instrument.

  4.2   General procedure for the synthesize of disulfides

  In a flask, NFSI (0.5 mmol) was dissolved in ethyl acetate (1mL), then thiol 1 (0.5 mmol) was added, and the entire mixture was magnetically stirred at room temperature and monitored by TLC. After completion of reaction as indicated by TLC, the crude mixture was concentrated and directly purified by flash column chromatography [V(petroleum ether)/V(ethyl acetate)＝20/1~5/1] to give the desired product 2 with indicated yields.

  1, 2-Diphenyldisulfane (2a): Yield 93%. White solid, m.p. 60~62 ℃ (Lit.^[16e] m.p. 59~60 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.52 (d, J＝4.0 Hz, 4H), 7.39 (t, J＝4.0 Hz, 4H), 7.30 (t, J＝4.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ: 137.1, 129.2, 127.6, 127.2; IR ν: 3072, 1552, 1385, 894 cm^－1; HRMS (EI) calcd for C₁₂H₁₀S₂ 218.0224, found 218.0222.

  1, 2-Di-p-tolyldisulfane (2b): Yield 95%. Yellow solid, m.p. 47~48 ℃ (Lit.^11b m.p. 47~48 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.39 (d, J＝8.0 Hz, 4H), 7.19 (d, J＝8.0 Hz, 4H), 2.28 (s, 6H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 137.6, 132.8, 130.2, 128.3, 20.8; IR ν: 3019, 2915, 2852, 1487, 1376, 1014, 816, 798 cm^－1; HRMS (EI) calcd for C₁₄H₁₄S₂ 246.0537, found 246.0537.

  1, 2-Bis(4-(tert-butyl)phenyl)disulfane (2c): Yield 92%. White solid, m.p. 86~87 ℃ (Lit.^[16e] m.p. 88~89 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.44 (d, J＝8.0 Hz, 4H), 7.32 (d, J＝8.0 Hz, 4H), 1.29 (s, 18H); ¹³C NMR (100 MHz, CDCl₃) δ: 150.5, 134.0, 127.7, 126.1, 34.5, 31.3; IR ν: 2958, 2865, 2744, 1484, 1394, 1360, 838 cm^－1; HRMS (EI) calcd for C₂₀H₂₆S₂ 330.1476, found 330.1475.

  1, 2-Bis(4-methoxyphenyl)disulfane (2d): Yield 88%. White solid, m.p. 44~45 ℃ (Lit.²² m.p. 42~44 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 7.41 (d, J＝8.0 Hz, 4H), 6.95 (d, J＝8.0 Hz, 4H), 3.75 (s, 18H); ¹³C NMR (100 MHz, CDCl₃) δ: 159.9, 132.7, 128.4, 114.6, 55.4; IR ν: 2967, 2840, 1489, 1236, 831 cm^－1; HRMS (EI) calcd for C₁₄H₁₄O₂S₂ 278.0435, found 278.0436.

  1, 2-Bis(4-chlorophenyl)disulfane (2e): Yield 89%. Yellow solid, m.p. 68~69 ℃ (Lit.^11b m.p. 71~73 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.40 (d, J＝8.0 Hz, 4H), 7.28 (d, J＝8.0 Hz, 4H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 134.7, 132.7, 129.7, 129.4; IR ν: 3077, 1469; 812, 737 cm^－1; HRMS (EI) calcd for C₁₂H₈Cl₂S₂ 285.9444, found 285.9444.

  1, 2-Bis(4-bromophenyl)disulfane (2f): Yield 96%. White solid, m.p. 90~92 ℃ (Lit.^[16f] m.p. 94~95 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.42 (d, J＝8.0 Hz, 4H), 7.33 (d, J＝8.0 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 135.8, 132.3, 129.4, 121.6; IR ν: 3073, 1465, 807, 493 cm^－1; HRMS (EI) calcd for C₁₂H₈Br₂S₂ 373.8434, found 373.8434.

  N, N'-(Disulfanediylbis(4, 1-phenylene))diacetamide (2g): Yield 91%. White solid, m.p. 192~193 ℃ (Lit.^[23] m.p. 192~193 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 10.09 (s, 2H), 7.66 (d, J＝8.0 Hz, 2H), 7.59 (d, J＝8.0 Hz, 2H), 7.43 (d, J＝8.0 Hz, 2H), 7.37 (d, J＝8.0 Hz, 2H), 2.04 (s, 6H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 169.0, 139.9, 130.6, 129.9, 120.2, 24.5; IR ν: 3292, 3111, 1646, 1534, 1395, 812 cm^－1; HRMS (EI) calcd for C₁₆H₁₆N₂O₂S₂ 332.0653, found 332.0650.

  N, N'-(Disulfanediylbis(4, 1-phenylene))bis(2, 2, 2-trifluoroacetamide) (2h): Yield 89%. Yellow solid, m.p. 181~183 ℃ (Lit.^[24] m.p. 181~183 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 11.37 (br, 2H), 7.70 (d, J＝8.0 Hz, 4H), 7.57 (d, J＝8.0 Hz, 4H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 154.8 (q, J＝30.0 Hz), 136.4, 132.6, 129.1, 128.3, 126.4, 122.1, 116.9; IR ν: 3291, 3138, 1700, 1493, 1150, 817 cm^－1; HRMS (EI) calcd for C₁₆H₁₀F₆N₂O₂S₂ 440.0088, found 440.0089.

  Di-tert-butyl(disulfanediylbis(4, 1-phenylene))dicarbamate (2i): Yield 52%. Yellow solid, ¹H NMR (400 MHz, DMSO-d₆) δ: 9.53 (s, 2H), 7.46 (d, J＝8.0 Hz, 4H), 7.38 (d, J＝8.0 Hz, 4H), 1.47 (s, 18H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 168.1, 139.0, 129.6, 128.9, 119.2, 79.6, 23.5; IR ν: 3291, 3127, 1699, 1529, 1399, 1360, 1157, 817 cm^－1; HRMS (EI) calcd for C₂₂H₂₈N₂O₄S₂ 448.1490, found 448.1488.

  N, N'-(Disulfanediylbis(4, 1-phenylene))bis(4-methylbenzenesulfonamide) (2j): Yield 74%. White solid, m.p. 171~173 ℃ (Lit.^[25] m.p. 171 ℃); ¹H NMR (600 MHz, DMSO-d₆) δ: 10.43 (s, 2H), 7.64 (d, J＝7.8 Hz, 4H), 7.32 (m, 8H), 7.07 (d, J＝7.8 Hz, 4H), 2.33 (s, 6H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 143.9, 138.5, 136.9, 131.0, 130.7, 130.2, 127.2, 120.7, 21.4; IR ν: 3271, 2921, 1511, 1334, 1187, 1175, 921, 810, 767 cm^－1; HRMS (EI) calcd for C₂₆H₂₄N₂O₄S₄ 556.0619, found 556.0619.

  2, 2'-Disulfanediyldibenzoic acid (2k): Yield 97%. White solid, m.p. 282~283 ℃ (Lit.^[26] m.p. 283~285 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 13.56 (br, 2H), 8.02 (dd, J＝4.0, 0.8 Hz, 2H), 7.62 (d, J＝4.0 Hz, 2H), 7.56 (dt, J＝4.0, 0.8 Hz, 2H), 7.34 (t, J＝4.0 Hz, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 139.2, 133.5, 131.9, 128.3, 126.2, 125.3; IR ν: 3091, 2814, 1676, 1561; 1415, 1310, 1258, 737, 696 cm^－1; HRMS (EI) calcd for C₁₄H₁₀O₄S₂ 306.0021, found 306.0022.

  1, 2-Di(naphthalen-2-yl)disulfane (2l): Yield 99%. White solid, m.p. 134~135 ℃ (Lit.^[16f] m.p. 135~138 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 7.98 (s, 2H), 7.78 (d, J＝8.0 Hz, 4H), 7.13 (d, J＝8.0 Hz, 2H), 7.62 (d, J＝8.0 Hz, 2H), 7.45 (s, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 134.2, 133.4, 132.5, 128.9, 127.7, 127.4, 126.7, 126.5, 126.2, 125.6; IR ν: 3050, 2918, 1584, 868, 735 cm^－1; HRMS (EI) calcd for C₂₀H₁₄S₂ 318.0537, found 318.0539.

  1, 2-Bis(benzo[d]oxazol-2-yl)disulfane (2m): Yield 82%. White solid, m.p. 110~111 ℃ (Lit.^[27] m.p. 111~113 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.07 (d, J＝8.0 Hz, 2H), 7.94 (d, J＝8.0 Hz, 2H), 7.53 (t, J＝8.0 Hz, 2H), 7.44 (t, J＝8.0 Hz, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 159.7, 152.9, 142.5, 129.6, 128.9, 119.2, 111.2; IR ν: 3214, 1657, 1458, 1234, 800, 739 cm^－1; HRMS (EI) calcd for C₁₄H₈N₂O₂S₂ 300.0027, found 300.0027.

  1, 2-Bis(benzo[d]thiazol-2-yl)disulfane (2n): Yield 85%. White solid, m.p. 181~182 ℃ (Lit.^[28] m.p. 177~179 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 8.07 (d, J＝8.0 Hz, 2H), 7.94 (d, J＝8.0 Hz, 2H), 7.53 (t, J＝8.0 Hz, 2H), 7.44 (t, J＝8.0 Hz, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 160.4, 151.7, 135.2, 126.5, 124.3, 121.7, 121.0; IR ν: 3109, 1651, 1458, 810, 797, 729 cm^－1; HRMS (EI) calcd for C₁₄H₈N₂S₄ 331.9570, found 331.9568.

  1, 2-Dibenzyldisulfane (2o)^[16f]: Yield 82%. Colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 7.28 (m, 10H), 3.60 (s, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 137.3, 129.4, 128.5, 127.4, 63.2; IR ν: 3027, 2964, 2910, 1493, 1452, 757, 692 cm^－1; HRMS (EI) calcd for C₂₀H₁₄S₂ 318.0537, found 318.0539.

  1, 2-Di-tert-butyldisulfane (2p)^[16g]: Yield 43%. Colorless oil. ¹H NMR (400 MHz, CDCl₃) δ: 1.41 (s, 18H); ¹³C NMR (100 MHz, CDCl₃) δ: 45.7, 30.5; IR ν: 2960, 2922, 2895, 1455, 1388, 1360, 1160 cm^－1; HRMS (EI) calcd for C₂₀H₁₄S₂ 318.0537, found 318.0539.

  1, 2-Dioctyldisulfane (2q): Yield 81%. White solid, m.p. 183~185 ℃ (Lit.^[29] m.p. 185~187 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 2.68 (t, J＝7.2 Hz, 4H), 2.54 (m, 4H), 1.31 (m, 20H), 0.79 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ: 39.2, 31.8, 29.3, 29.2, 29.2, 28.6, 22.7, 14.1; IR ν: 2957, 2909, 2824, 1457, 1358 cm^－1; HRMS (EI) calcd for C₁₆H₃₄S₂ 290.2102, found 290.2103.

  2, 2'-Disulfanediylbis(ethan-1-amine) (2r): Yield 95%. Yellow solid, m.p. 133~135 ℃; ¹H NMR (400 MHz, DMSO-d₆) δ: 8.26 (br, 4H), 3.09 (t, J＝4.0 Hz, 4H), 3.01 (t, J＝4.0 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 37.9, 34.0; IR ν: 3112, 2952, 1601, 1402, 1243, 1096, 813 cm^－1; HRMS (EI) calcd for C₄H₁₂N₂S₂ 152.0442, found 152.0442.

  3, 3'-Disulfanediyldipropionic acid (2s): Yield 96%. White solid, m.p. 152~154 ℃ (Lit.^[30] m.p. 156 ℃); ¹H NMR (400 MHz, DMSO-d₆) δ: 12.34 (br, 2H), 2.88 (t, J＝8.0 Hz, 4H), 2.61 (t, J＝8.0 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.8, 33.7, 33.1; IR ν: 2968, 2916, 1620, 1483, 1404, 1296, 1193 cm^－1; HRMS (EI) calcd for C₆H₁₀O₄S₂ 210.0021, found 210.0021.

  (2R, 2'R)-3, 3'-Disulfanediylbis(2-aminopropanoic acid) (2t): Yield 97%. White solid, m.p. 202~204 ℃ (dec.); [α]_D²⁰－197.53 (c 1.00, 1 mol·L^-1 HCl) [Lit.^[31] m.p. 216~220 ℃ (dec.), [α]_D²⁰－205.17 (c 1.02, 1 mol·L^-1 HCl)]; ¹H NMR (400 MHz, DMSO-d₆) δ: 12.19 (br, 2H), 8.57 (br, 4H), 4.17 (t, J＝8.0 Hz, 2H), 3.42 (d, J＝8.0 Hz, 2H), 3.20 (d, J＝8.0 Hz, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 169.5, 51.4, 37.5; IR ν: 2880, 2633, 1918, 1726, 1590, 1431, 1362, 1090, 1133, 1082, 955, 868, 756, 541 cm^－1; HRMS (EI) calcd for C₆H₁₂N₂O₄S₂ 240.0238, found 240.0235.

  (2R, 2'R)-3, 3'-Disulfanediylbis(2-acetamidopropanoic a-cid) (2u): Yield 67%. White solid, m.p. 270~272 ℃ (Lit.^{[13d, 32]} m.p. 273~275 ℃); [α]_D²⁴－95.98 (c 1.00, D₂O) [Lit.^[13d] [α]_D²⁴ －102.95 (c 1.06, D₂O)]; ¹H NMR (600 MHz, DMSO-d₆) δ: 12.91 (br, 2H), 8.30 (d, J＝4.0 Hz, 4H), 4.46 (m, 2H), 3.12 (dd, J＝8.0, 4.0 Hz, 2H), 2.90 (dd, J＝8.0, 4.0 Hz, 2H), 1.85 (s, 6H); ¹³C NMR (100 MHz, DMSO-d₆) δ: 172.5, 169.9, 51.7, 39.4, 22.8; IR ν: 3297, 2941, 2886, 1739, 1646, 1431, 1395, 957, 775 cm^－1; HRMS (EI) calcd for C₁₀H₁₆N₂O₆S₂ 324.0450, found 324.0450.

  Supporting Information The ¹H NMR and ¹³C NMR spectra of products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

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• 

  Figure 1  Represented drugs with a disulfide motif

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  Scheme 1  Proposed reaction mechanism for the synthesis of disulfides from thiols

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  Table 1.  Optimization of reaction conditions^a

  Entry	NFSI/equiv.	Solvent	Time/min	Yieldb/%
  1	1.2	DMF	60	90
  2	1.2	DCM	60	55
  3	1.2	Acetone	60	64
  4	1.2	Acetonitrile	60	67
  5	1.2	DMSO	60	69
  6	1.2	Ethanol	60	81
  7	1.0	Ethyl acetate	60	93
  8	0.8	Ethyl acetate	60	86
  9	1.0	Ethyl acetate	10	93
  10	0	Ethyl acetate	60	Trace
  a Reaction conditions: benzenethiol (1a, 0.5 mmol), NFSI, solvent (1 mL), r.t.; b Isolated yield.

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  Table 2.  Reaction scope of thiols^{a, b}

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•