Synthesis method of 1,2-disulfide ethane compound and 1,4-dithiane

Abstract

The invention discloses a synthetic method of 1,2-disulfide ethane compounds and 1,4-dithiane, belongs to the field of organic synthesis technology, including S1, dissolving iodine in an organic solvent; S2, adding 1,4-dioxane and thiol or thiol compound R-SH or ethanedithiol to the solution of step S1, sealing, heating and stirring until the reaction is completed; S3, adding Na2S2O3 to the solution at the end of the S2 reaction to reduce the remaining I2; S4, extracting with dichloromethane, drying and concentrating the organic phase, and purifying the crude product by silica gel column chromatography to obtain a final product. The present invention uses 1,4-dioxane as "-CH2CH2-" precursor, and realizes the ring-opening substitution reaction of 1,4-dioxane under the synergistic effect of iodine and S-H bonds. The synthesis step of the reaction is simple, cost-effective, and the reaction process is safe.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing a 1,2-dithioethane compound and a 1,4-dithiane compound. Background Art

[0002] The product, 1,2-dithioethane, is a sulfide organic compound with numerous applications as a neutral ligand in the synthesis of metal-organic complexes. Oxidation of the sulfide to a sulfoxide compound serves as a ligand in White's catalyst. 1,4-Dithiane is a food flavoring.

[0003]

[0004] 1,2-Dithioethane is a sulfide compound. Its synthesis methods mainly include the following categories: transition metal ruthenium-catalyzed addition reaction of disulfides with alkenes (eq 1), substitution reaction of thiophenols, thiols and 1,2-dichloroethane under transition metal ruthenium or rhodium catalyst conditions (eq 2); substitution reaction of thiophenols, thiols and halogenated alkanes in strong alkaline solution (eq 3-4), reaction of potassium benzenethiophenolate with dichloroethyl ether (eq 5); in addition, there are substitution reactions of thiophenols, thiols and halogenated alkanes under metal-free conditions (eq 6-8).

[0005]

[0006] While all of the above methods are highly efficient for synthesizing 1,2-dithioethane and 1,4-dithiane, they also have certain drawbacks. The high prices of the transition metals ruthenium and rhodium increase the synthesis cost; the use of strong alkaline solutions is hazardous in practice; and polyhalogenated alkanes are toxic, resulting in significant pollution from reaction byproducts. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a synthesis method of 1,2-dithioethane compounds and 1,4-dithiane, which has simple reaction, convenient operation, low cost and is more in line with the concept of green chemistry.

[0008] In order to solve the above technical problems, the technical solution adopted by the present invention is:

[0009] The synthesis method of 1,2-dithioethane compound and 1,4-dithiane comprises the following steps:

[0010]

[0011] S1, dissolving iodine in an organic solvent;

[0012] S2, adding 1,4-dioxane and thiol or thiol compound R-SH or ethanedithiol to the solution of step S1, sealing, heating and stirring until the reaction is completed;

[0013] S3, adding Na2S2O3 to the solution where the reaction in S2 is completed to reduce the remaining I2;

[0014] S4, extract with dichloromethane, dry and concentrate the organic phase, and purify the crude product by silica gel column chromatography to obtain the final product.

[0015] A further improvement of the technical solution of the present invention is that the iodine element in step S2 can be replaced by HI.

[0016] A further improvement of the technical solution of the present invention is that: when the raw material in S1 is HI, 1,4-dioxane and a disulfide compound R1-SS-R1 are added to the solution in step S1 in S2 for reaction.

[0017]

[0018] A further improvement of the technical solution of the present invention is that: in the thiol or thiol compound R-SH, R is an aryl group with or without a first substituent, or a C1-30 straight-chain alkyl group with or without a second substituent, the first substituent includes a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxy group, or a halogen substituent, and the second substituent includes a straight-chain C1-30 alkyl group. The number of the first substituent and the second substituent is not limited.

[0019] A further improvement of the technical solution of the present invention is that the disulfide compound R1-SS-R1 is a symmetrical disulfide, wherein R1 is selected from an aromatic group containing a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxy group, a halogen substituent, or a straight-chain C1-30 alkyl group.

[0020] A further improvement of the technical solution of the present invention is that the organic solvent is a non-polar solvent, including one or more of toluene, n-hexane, and cyclohexane.

[0021] A further improvement of the technical solution of the present invention is that the reaction temperature in step S2 is 80-100°C.

[0022] A further improvement of the technical solution of the present invention is that the molar ratio of 1,4-dioxane: R-SH: I2 in the reaction is 2:1:1.1, and when synthesizing 1,4-dithiane, the molar ratio of 1,4-dioxane: ethanedithiol: I2 is 1:1:1.

[0023] A further improvement of the technical solution of the present invention is that the molar ratio of 1,4-dioxane:R-SH:HI in the reaction is 2:1:1.1, and when synthesizing 1,4-dithiane, the molar ratio of 1,4-dioxane:ethanedithiol:HI is 1:1:1.

[0024] A further improvement of the technical solution of the present invention is that the molar ratio of 1,4-dioxane:R1-SS-R1:HI in the reaction is 2:1:2.2.

[0025] Due to the adoption of the above technical solution, the technical advancements achieved by the present invention are:

[0026] In the preparation method of the present application, elemental iodine reacts with SH bonds to generate HI and a vicinal disulfide compound in situ. The strongly acidic HI then cleaves the CO bond of 1,4-dioxane, which then undergoes a substitution reaction with the vicinal disulfide compound to produce 1,2-dithioethane. Simultaneously, ethanedithiol is used in the reaction to produce 1,4-dithiane. The synthesis method of the present application is simple, low-cost, and the reaction process is safer. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 The present invention relates to the structural formula of a 1,2-dithioethane compound prepared by the method of the present application. DETAILED DESCRIPTION

[0028] The present invention is further described in detail below with reference to specific embodiments:

[0029] Implementation steps

[0030] Method 1: I2 (419 mg, 1.65 mmol) was weighed into a 25 mL reaction flask and dissolved in 3 mL of toluene. 1,4-dioxane (264 mg, 3.0 mmol), arylthiophenol, or alkylthiol (1.5 mmol) was then added to the flask. The flask was sealed and heated with stirring for 48 h. After the reaction, Na2S2O3 (0.2 M, 20 mL) was added to reduce the remaining I2. The mixture was then extracted three times with dichloromethane (10 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, and then spin-dried. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate mobile phase) to obtain the desired product.

[0031] Method 2: 1,4-dioxane (264 mg, 3.0 mmol) and an arylthiophenol or alkylthiol (1.5 mmol) were weighed into a 25 mL reaction flask and dissolved in 2 mL of toluene. HI (55% aqueous solution, 381 mg, 1.65 mmol) was then added. The flask was sealed and heated with stirring for 48 h. After the reaction, Na₂S₂O₃ (0.2 M, 10 mL) was added to quench the reaction. The mixture was then extracted three times with dichloromethane (10 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, and then spin-dried to dryness. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate mobile phase) to obtain the desired product.

[0032] Method 3: 1,4-dioxane (89 mg, 1.0 mmol) and a disulfide (0.5 mmol) were weighed into a 25 mL reaction flask, dissolved in 2 mL of toluene, and then HI (55% aqueous solution, 254 mg, 1.1 mmol) was added. The flask was then sealed and heated with stirring for 48 h. After the reaction, Na2S2O3 (0.2 M, 10 mL) was added to quench the reaction. The mixture was then extracted three times with dichloromethane (10 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, and then spin-dried to dryness. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate mobile phase) to obtain the desired product.

[0033] Example 1

[0034] Preparation of 1,2-bis(4-methylphenylthio)ethane (Ⅱ-1)

[0035]

[0036] According to method 1: 4-methylthiophenol (186 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-methylphenylthio) ethane (Ⅱ-1), (167 mg, 81%).

[0037] According to method 2: 4-methylthiophenol (186 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-methylphenylthio) ethane (II-1), (148 mg, 72%).

[0038] According to method three: 1,2-bis(4-methylphenyl)disulfide (125 mg, 0.5 mmol), 1,4-dioxane (89 mg, 1.0 mmol), HI (254 mg, 1.1 mmol), react at 95°C for 48 h to obtain the product 1,2-bis(4-methylphenylthio)ethane (Ⅱ-1), (110 mg, 80%).

[0039] A known compound, white solid, melting point 80-81°C. 1 H NMR (400MHz, CDCl3) δ7.25–7.18(m,4H),7.12–7.06(m,4H),3.02(s,4H),2.33(s,6H). 13 C NMR (101MHz, CDCl3) δ136.9,131.4,130.9,129.9,34.1,21.2.

[0040] Example 2

[0041] Preparation of 1,2-bis(3-methylphenylthio)ethane (Ⅱ-2)

[0042]

[0043] According to method 1: 3-methylthiophenol (186 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (3-methylphenylthio) ethane (Ⅱ-2), (128 mg, 62%).

[0044] A known compound, white solid, melting point 50-51°C. 1 H NMR (400MHz, CDCl3) δ7.19–7.05(m,6H),7.12–7.06(m,2H),3.06(s,4H),2.29(s,6H). 13 C NMR (101MHz, CDCl3) δ138.9,134.9,130.7,128.9,127.5,127.0,33.4,21.4.

[0045] Example 3

[0046] Preparation of 1,2-bis(2-methylphenylthio)ethane (Ⅱ-3)

[0047]

[0048] According to method 1: 2-methylthiophenol (186 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (2-methylphenylthio) ethane (Ⅱ-3), (109 mg, 53%).

[0049] A known compound, white solid, melting point 51-52°C. 1 H NMR (400MHz, CDCl3) δ7.25–7.18(m,4H),7.18–7.11(m,4H),3.09(s,4H),2.40(s,6H). 13 C NMR (101MHz, CDCl3) δ138.6,134.4,130.5,129.2,126.6,126.5,32.6,20.6.

[0050] Example 4

[0051] Preparation of 1,2-bis(4-methoxyphenylthio)ethane (Ⅱ-4)

[0052]

[0053] According to method 1: 4-methoxythiophenol (210 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 80 ° C for 48 hours to obtain the product 1,2-bis (4-methoxyphenylthio) ethane (Ⅱ-4), (165 mg, 72%).

[0054] According to method 2: 4-methoxythiophenol (210 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 80 ° C for 48 hours to obtain the product 1,2-bis (4-methoxyphenylthio) ethane (Ⅱ-4), (201 mg, 88%).

[0055] A known compound, white solid, melting point 108-109°C. 1 H NMR (400MHz, CDCl3) δ7.38–7.29(m,4H),6.91–6.81(m,4H),3.85(s,6H),2.99(s,4H). 13 C NMR (101MHz, CDCl3) δ159.3, 133.8, 125.3, 114.7, 55.4, 35.3.

[0056] Example 5

[0057] Preparation of 1,2-bis(2-methoxyphenylthio)ethane (Ⅱ-5)

[0058]

[0059] According to method 1: 2-methoxythiophenol (210 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 80 ° C for 48 hours to obtain the product 1,2-bis (2-methoxyphenylthio) ethane (Ⅱ-5), (117 mg, 51%).

[0060] Unknown compound, white solid, melting point 71-72℃. 1 H NMR (400MHz, CDCl3) δ7.27–7.18(m,4H),6.90–6.82(m,4H),3.83(s,6H),3.05(s,4H). 13 C NMR(101MHz, CDCl3)δ157.9,130.9,128.0,122.9,121.0,110.7,55.78,31.6.HRMS(EI,m / z):Calcd.for C 16 H 18 O2S2[M] + 306.0748,found 306.0738.

[0061] Example 6

[0062] Preparation of 1,2-bis(phenylthio)ethane (Ⅱ-6)

[0063]

[0064] According to method 1: thiophenol (165 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (phenylthio) ethane (Ⅱ-6), (144 mg, 78%).

[0065] According to method 2: thiophenol (165 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (phenylthio) ethane (II-6), (110 mg, 60%).

[0066] According to method three: diphenyl disulfide (109 mg, 0.5 mmol), 1,4-dioxane (89 mg, 3.0 mmol), HI (254 mg, 1.1 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (phenylthio) ethane (Ⅱ-6), (92 mg, 78%).

[0067] A known compound, white solid, melting point 70-71°C. 1 H NMR (400MHz, CDCl3) δ7.33–7.23(m,8H),7.23–7.17(m,2H),3.08(s,4H). 13 C NMR (101MHz, CDCl3) δ135.1, 130.2, 129.2, 126.7, 33.5.

[0068] Example 7

[0069] Preparation of 1,2-bis(4-ethylphenylthio)ethane (Ⅱ-7)

[0070]

[0071] According to method 1: 4-ethylthiophenol (207 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-ethylphenylthio) ethane (Ⅱ-7), (166 mg, 73%).

[0072] Unknown compound, white solid, melting point 49-50℃. 1 H NMR(400MHz, CDCl3)δ7.28–7.20(m,4H),7.14–7.07(m,4H),3.03(s,4H), 1 H NMR (400MHz, CDCl3) δ7.23 (m, 4H), 7.11 (m, 4H), 3.03 (s, 4H), 2.62 (m, 4H), 1.22 (t, J = 7.6Hz, 6H). 13 C NMR(101MHz, CDCl3)δ143.2,131.7,130.9,128.7,77.5,77.2,76.8,34.1,28.6,15.6.HRMS(EI,m / z):Calcd.for C 18 H 22 S2[M] + 302.1163, found 302.1153.

[0073] Example 8

[0074] Preparation of 1,2-bis(4-isopropylphenylthio)ethane (Ⅱ-8)

[0075]

[0076] According to method 1: 4-isopropylthiophenol (229 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-isopropylphenylthio) ethane (Ⅱ-8), (186 mg, 75%).

[0077] According to method 2: 4-isopropylthiophenol (229 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-isopropylphenylthio) ethane (II-8), (201 mg, 81%).

[0078] Unknown compound, white solid, melting point 45-46℃. 1 H NMR (400MHz, CDCl3) δ7.26–7.19(m,4H),7.16–7.09(m,4H),3.03(s,4H),2.87(m,2H),1.23(d,J=6.9Hz,12H). 13 C NMR(101MHz, CDCl3)δ147.78,131.80,130.77,127.29,34.02,33,83,24.05.HRMS(EI,m / z):Calcd.forC 20 H 26 S2[M] + 330.1476,found 330.1469.

[0079] Example 9

[0080] Preparation of 1,2-bis(4-tert-butylphenylthio)ethane (Ⅱ-9)

[0081]

[0082] According to method 1: 4-tert-butylthiophenol (249 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-tert-butylphenylthio) ethane (Ⅱ-9), (210 mg, 78%).

[0083] A known compound, white solid, melting point 107-108°C. 1 H NMR (400MHz, CDCl3) δ7.31–7.26(m,4H),7.26–7.20(m,4H),3.04(s,4H),1.30(s,18H). 13 C NMR (101MHz, CDCl3) δ150.0,131.6,130.3,126.2,34.6,33.9,31.4.

[0084] Example 10

[0085] Preparation of 1,2-bis(4-fluorophenylthio)ethane (Ⅱ-10)

[0086]

[0087] According to method 1: 4-fluorobenzenethiol (192 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-fluorophenylthio) ethane (Ⅱ-10), (131 mg, 62%).

[0088] According to method 2: 4-fluorobenzenethiol (192 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-fluorophenylthio) ethane (Ⅱ-10), (68 mg, 32%).

[0089] A known compound, white solid, melting point 71-72°C. 1 H NMR (400MHz, CDCl3) δ7.34–7.27(m,4H),7.02–6.95(m,4H),2.98(s,4H). 13 C NMR(101MHz,CDCl3)δ162.2(d,J (C-F) =247.5Hz),133.3(d,J (C-F) =8.1Hz),129.9(d,J (C-F) =3.3Hz),116.3(d,J (C-F) =22.2Hz),34.7. 19 F NMR (376MHz, CDCl3): δ-114.50.

[0090] Example 11

[0091] Preparation of 1,2-bis(3-fluorophenylthio)ethane (Ⅱ-11)

[0092]

[0093] According to method 1: 3-fluorobenzenethiol (192 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (3-fluorophenylthio) ethane (Ⅱ-11), (112 mg, 53%).

[0094] Unknown compound, white solid, melting point 38-39℃. 1 H NMR (400MHz, CDCl3) δ7.27–7.19(m,2H),7.11–6.82(m,6H),3.10(s,4H). 13 C NMR(101MHz,CDCl3)δ163.0(d,J (C-F) =249.7Hz),137.5(d,J (C-F) =7.8Hz),130.5(d,J (C-F) =8.6Hz),125.2(d,J (C-F) =3.0Hz),116.4(d,J (C-F) =23.0Hz),113.7(d,J (C-F) =21.3Hz),33.0. 19 F NMR (376MHz, CDCl3): δ-112.17.HRMS (EI, m / z): Calcd.for C 14 H 12 F2S2[M] + 282.0348,found 282.0337.

[0095] Example 12

[0096] Preparation of 1,2-bis(2-fluorophenylthio)ethane (Ⅱ-12)

[0097]

[0098] According to method 1: 2-fluorobenzenethiol (192 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (2-fluorophenylthio) ethane (Ⅱ-12), (97 mg, 46%).

[0099] Unknown compound, white solid, melting point 41-42℃. 1H NMR (400MHz, CDCl3) δ7.36–7.29(m,2H),7.27–7.21(m,2H),7.09–7.02(m,4H),3.05(s,4H). 13 C NMR(101MHz,CDCl3)δ161.9(d,J (C-F) =246.7Hz),133.1(d,J (C-F) =1.5Hz),129.2(d,J (C-F) =7.9Hz),124.6(d,J (C-F) =3.8Hz),121.7(d,J (C-F) =17.8Hz),116.0(d,J (C-F) =22.7Hz),33.2(d,J=2.5Hz). 19 F NMR (376MHz, CDCl3): δ-108.70.HRMS (EI, m / z): Calcd.for C 14 H 12 F2S2[M] + 282.0348,found 282.0339.

[0100] Example 13

[0101] Preparation of 1,2-bis(4-chlorophenylthio)ethane (Ⅱ-13)

[0102]

[0103] According to method 1: 4-chlorobenzenethiol (217 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-chlorophenylthio) ethane (Ⅱ-13), (189 mg, 80%).

[0104] According to method 2: 4-chlorobenzenethiol (217 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-chlorophenylthio) ethane (Ⅱ-13), (200 mg, 85%).

[0105] According to method three: 1,2-bis(4-chlorophenyl)disulfide (144 mg, 0.5 mmol), 1,4-dioxane (89 mg, 1.0 mmol), HI (254 mg, 1.1 mmol), react at 95°C for 48 h to obtain the product 1,2-bis(4-chlorophenylthio)ethane (Ⅱ-13), (79 mg, 50%).

[0106] A known compound, white solid, melting point 94-95°C. 1 H NMR (400MHz, CDCl3) δ7.29–7.27(m,4H),7.27–7.23(m,4H),3.06(s,4H). 13 C NMR (101MHz, CDCl3) δ133.6, 133.0, 131.7, 129.4, 33.8.

[0107] Example 14

[0108] Preparation of 1,2-bis(3-chlorophenylthio)ethane (Ⅱ-14)

[0109]

[0110] According to method 1: 3-chlorobenzenethiol (217 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (3-chlorophenylthio) ethane (Ⅱ-14), (156 mg, 66%).

[0111] Unknown compound, white solid, melting point 57-58℃. 1 H NMR (400MHz, CDCl3) δ7.30–7.25(m,2H),7.24–7.11(m,6H),3.08(s,4H). 13 C NMR(101MHz, CDCl3)δ137.2,134.9,130.2,129.6,127.7,126.8,33.1.HRMS(EI,m / z):Calcd.for C 14 H 12 Cl2S2[M] + 313.9757,found 313.9752.

[0112] Example 15

[0113] Preparation of 1,2-bis(2-chlorophenylthio)ethane (Ⅱ-15)

[0114]

[0115] According to method 1: 2-chlorobenzenethiol (217 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (2-chlorophenylthio) ethane (Ⅱ-15), (125 mg, 53%).

[0116] Unknown compound, white solid, melting point 75-76℃. 1 H NMR (400MHz, CDCl3) δ7.41–7.35(m,2H),7.28–7.22(m,2H),7.22–7.10(m,4H),3.14(s,4H). 13 C NMR(101MHz, CDCl3)δ134.7,134.3,130.1,129.8,127.5,127.3,31.9.HRMS(EI,m / z):Calcd.for C 14 H 12 Cl2S2[M] + 313.9757, found 313.9749.

[0117] Example 16

[0118] Preparation of 1,2-bis(4-bromophenylthio)ethane (Ⅱ-16)

[0119]

[0120] According to method 1: 4-bromobenzenethiol (284 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-bromophenylthio) ethane (Ⅱ-16), (249 mg, 81%).

[0121] According to method 2: 4-bromobenzenethiol (284 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (4-bromophenylthio) ethane (Ⅱ-16), (83 mg, 27%).

[0122] According to method three: 1,2-bis(4-bromophenyl)disulfide (188 mg, 0.5 mmol), 1,4-dioxane (89 mg, 1.0 mmol), HI (254 mg, 1.1 mmol), react at 95°C for 48 h to obtain the product 1,2-bis(4-bromophenylthio)ethane (Ⅱ-16), (106 mg, 52%).

[0123] A known compound, white solid, melting point 109-110°C. 1 H NMR (400MHz, CDCl3) δ7.50–7.31(m,4H),7.21–7.04(m,4H),3.03(s,4H). 13 C NMR (101MHz, CDCl3) δ134.6, 132.6, 132.1, 121.1, 33.9.

[0124] Example 17

[0125] Preparation of 1,2-bis(3-bromophenylthio)ethane (Ⅱ-17)

[0126]

[0127] According to method 1: 3-bromobenzenethiol (284 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (3-bromophenylthio) ethane (Ⅱ-17), (212 mg, 70%).

[0128] Unknown compound, white solid, melting point 78-79℃. 1 H NMR (400MHz, CDCl3) δ7.48–7.40(m,2H),7.37–7.29(m,2H),7.23–7.08(m,4H),3.07(s,4H). 13 C NMR(101MHz, CDCl3)δ137.5,132.3,130.5,129.8,128.2,123.1,33.2.HRMS(EI,m / z):Calcd.for C 14 H 12 Br2S2[M] + 403.8727, found 403.8718.

[0129] Example 18

[0130] Preparation of 1,2-bis(2-bromophenylthio)ethane (Ⅱ-18)

[0131]

[0132] According to method 1: 3-bromobenzenethiol (284 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 95 ° C for 48 hours to obtain the product 1,2-bis (2-bromophenylthio) ethane (Ⅱ-18), (170 mg, 56%).

[0133] A known compound, white solid, melting point 84-85°C. 1 H NMR (400MHz, CDCl3) δ7.70–7.40(m,2H),7.29–7.19(m,4H),7.16–6.99(m,2H),3.15(s,4H). 13 C NMR (101MHz, CDCl3) δ136.4,133.4,129.4,128.0,127.6,124.9,32.2.

[0134] Example 19

[0135] Preparation of 1,2-bis(2,4-dimethylphenylthio)ethane (Ⅱ-19)

[0136]

[0137] According to method 1: 2,4-dimethylthiophenol (207 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 90 ° C for 48 hours to obtain the product 1,2-bis (2,4-dimethylphenylthio) ethane (Ⅱ-19), (139 mg, 61%).

[0138] Unknown compound, white solid, melting point 57-58℃. 1 H NMR (400MHz, CDCl3) δ7.14–7.07(m,2H),7.02–6.96(m,2H),6.95–6.86(m,2H),2.97(s,4H),2.33(s,6H),2.27(s,6H). 13 C NMR(101MHz, CDCl3)δ138.9,136.6,131.3,130.6,130.3,127.3,33.1,20.99,20.5.HRMS(EI,m / z):Calcd.for C 18 H 22 S2[M] + 302.1163, found 302.1155.

[0139] Example 20

[0140] Preparation of 1,2-bis(2,4-dimethylphenylthio)ethane (Ⅱ-20)

[0141]

[0142] According to method 1: 2,5-dimethylthiophenol (207 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 90 ° C for 48 hours to obtain the product 1,2-bis (2,5-dimethylphenylthio) ethane (Ⅱ-20), (121 mg, 53%).

[0143] According to method 2: 2,5-dimethylthiophenol (207 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), HI (381 mg, 1.65 mmol), react at 90 ° C for 48 h to obtain the product 1,2-bis (2,5-dimethylphenylthio) ethane (II-20), (154 mg, 68%)

[0144] Unknown compound, white solid, melting point 74-75℃. 1 H NMR (400MHz, CDCl3) δ7.11–7.01(m,4H),6.99–6.89(m,2H),3.07(s,4H),2.36(s,6H),2.29(s,6H). 13 C NMR(101MHz, CDCl3)δ136.2,135.5,134.0,130.3,130.01,127.4,32.8,21.1,20.1.HRMS(EI,m / z):Calcd.for C 18 H 22 S2[M] + 302.1163, found 302.1155.

[0145] Example 21

[0146] Preparation of 1,2-bis(2,6-dimethylphenylthio)ethane (Ⅱ-21)

[0147]

[0148] According to method 1: 2,6-dimethylthiophenol (207 mg, 1.5 mmol), 1,4-dioxane (264 mg, 3.0 mmol), I2 (419 mg, 1.65 mmol), react at 90 ° C for 48 hours to obtain the product 1,2-bis (2,6-dimethylphenylthio) ethane (Ⅱ-21), (104 mg, 46%).

[0149] Unknown compound, white solid, melting point 155-157℃. 1 H NMR (400MHz, CDCl3) δ7.18–7.06(m,6H),2.76(s,4H),2.48(s,12H). 13 C NMR(101MHz, CDCl3)δ143.5,132.9,128.7,128.6,34.9,22.5.HRMS(EI,m / z):Calcd.for C 18 H 22 S2[M] + 302.1163, found 302.1153.

[0150] Example 22

[0151]

[0152] Preparation of 1,2-bis(butylthio)ethane (Ⅱ-22)

[0153] According to method 1: decanethiol (135 mg, 1.5 mmol), 1,4-dioxane (264 mg, 2.0 mmol), I2 (419 mg, 1.65 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (butylthio) ethane (Ⅱ-22), (78 mg, 46%).

[0154] Known compound, colorless liquid. 1 H NMR (400MHz, CDCl3) δ2.70 (s, 4H), 2.58–2.51 (m, 4H), 1.60–1.52 (m, 4H), 1.44–1.34 (m, 4H), 0.90 (t, J = 7.4Hz, 6H). 13 C NMR (101MHz, CDCl3) δ32.27,31.99,31.90,22.08,13.78.

[0155] Example 23

[0156] Preparation of 1,2-bis(decylthio)ethane (Ⅱ-23)

[0157]

[0158] According to method 1: decanethiol (174 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), I2 (279 mg, 1.1 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (decylthio) ethane (Ⅱ-23), (93 mg, 50%).

[0159] Unknown compound, white solid, melting point 41-42℃. 1 H NMR (400MHz, CDCl3) δ2.70 (s, 4H), 2.57–2.47 (m, 4H), 1.61–1.52 (m, 4H), 1.39–1.32 (m, 4H), 1.30–1.16 (m, 24H), 0.87 (t, J = 6.8Hz, 6H). 13 C NMR(101MHz, CDCl3)δ32.3,32.2,32.0,29.8,29.7,29.7,29.4,29.4,29.0,22.8,14.2.HRMS(EI,m / z):Calcd.for C 22 H 46 S2[M] + 374.3041,found 374.3034.

[0160] Example 24

[0161] Preparation of 1,2-bis(dodecylthio)ethane (Ⅱ-24)

[0162]

[0163] According to method 1: dodecyl mercaptan (202 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), I2 (279 mg, 1.1 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (dodecylthio) ethane (Ⅱ-24), (132 mg, 61%).

[0164] According to method 2: dodecyl mercaptan (202 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), HI (254 mg, 1.1 mmol), react at 90 ° C for 48 h to obtain the product 1,2-bis (2,5-dimethylphenylthio) ethane (II-24), (140 mg, 65%)

[0165] According to method three: bis(dodecyl) disulfide (201 mg, 0.5 mmol), 1,4-dioxane (89 mg, 1.0 mmol), HI (254 mg, 1.1 mmol), react at 100°C for 48 hours to obtain the product 1,2-bis(4-bromophenylthio)ethane (Ⅱ-24), (144 mg, 67%).

[0166] Unknown compound, white solid, melting point 54-55℃. 1H NMR (400MHz, CDCl3) δ2.71 (s, 4H), 2.59–2.49 (m, 4H), 1.62–1.53 (m, 4H), 1.40–1.32 (m, 4H), 1.31–1.18 (m, 32H), 0.88 (t, J = 6.8Hz, 6H). 13 C NMR(101MHz, CDCl3)32.4,32.3,32.0,29.9,29.80,29.77,29.74,29.67,29.5,29.394,22.8,14.3.HRMS(EI,m / z):Calcd.for C 26 H 54 S2[M] + 430.3667,found 430.3659.

[0167] Example 25

[0168] Preparation of 1,2-bis(tetradecylthio)ethane (Ⅱ-25)

[0169]

[0170] According to method 1: tetradecyl mercaptan (230 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), I2 (279 mg, 1.1 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (tetradecylthio) ethane (Ⅱ-25) (132 mg, 54%).

[0171] Unknown compound, white solid, melting point 60-61°C. 1 H NMR (400MHz, CDCl3) δ2.70 (s, 4H), 2.57–2.49 (m, 4H), 1.62–1.52 (m, 4H), 1.41–1.33 (m, 4H), 1.31–1.20 (m, 41H), 0.87 (t, J = 6.8Hz, 6H). 13 C NMR(101MHz, CDCls3)δ32.33,32.25,32.1,29.83,29.82,29.79,29.75,29.7,29.5,29.4,29.0,22.8,14.27.HRMS(EI,m / z):Calcd.for C 30 H 62 S2[M] + 486.4293,found486.4284.

[0172] Example 26

[0173] Preparation of 1,2-bis(hexadecylthio)ethane (Ⅱ-26)

[0174]

[0175] According to method 1: hexadecyl mercaptan (259 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), I2 (279 mg, 1.1 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (hexadecylthio) ethane (Ⅱ-26), (154 mg, 57%).

[0176] According to method 2: hexadecyl mercaptan (259 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), HI (254 mg, 1.1 mmol), react at 100 ° C for 48 h to obtain the product 1,2-bis (2,5-dimethylphenylthio) ethane (II-26), (160 mg, 59%)

[0177] According to method three: bis(hexadecyl) disulfide (257 mg, 0.5 mmol), 1,4-dioxane (89 mg, 1.0 mmol), HI (254 mg, 1.1 mmol), react at 100°C for 48 h to obtain the product 1,2-bis(4-bromophenylthio)ethane (Ⅱ-26), (154 mg, 57%).

[0178] White solid, unknown compound, melting point 68-69℃. 1 H NMR (400MHz, CDCl3) δ2.70 (s, 4H), 2.53 (t, J = 7.4Hz, 4H), 1.60–1.54 (m, 4H), 1.40–1.34 (m, 5H), 1.25 (s, 47H), 0.87 (t, J = 6.7Hz, 6H). 13 C NMR(101MHz, CDCl3)δ32.4,32.3,32.1,29.9,29.80,29.75,29.7,29.5,29.4,29.0,22.8,14.3.HRMS(EI,m / z):Calcd.for C 34 H 70 S2[M] + 542.4919,found 542.4915.

[0179] Example 27

[0180] Preparation of 1,2-bis(octadecylthio)ethane (Ⅱ-26)

[0181]

[0182] According to method 1: octadecyl mercaptan (287 mg, 1.0 mmol), 1,4-dioxane (176 mg, 2.0 mmol), I2 (279 mg, 1.1 mmol), react at 100 ° C for 48 hours to obtain the product 1,2-bis (octadecylthio) ethane (Ⅱ-27) (193 mg, 64%).

[0183] Unknown compound, white solid, melting point 72-73℃. 1 H NMR (400MHz, CDCl3) δ2.71 (s, 4H), 2.54 (t, J = 7.3Hz, 4H), 1.57 (m, 6H), 1.37 (s, 8H), 1.31–1.11 (m, 52H), 0.92–0.83 (m, 6H). 13 C NMR(101MHz, CDCl3)δ32.3,32.2,32.0,29.7,29.68,29.63,29.55,29.4,29.3,28.9,22.7,14.1.HRMS(EI,m / z):Calcd.for C 38 H 78 S2[M] + 598.5545, found 598.5539.

[0184] Example 28

[0185] Preparation of 1,4-dithiane (Ⅱ-28)

[0186]

[0187] Method 1: I2 (508 mg, 2.0 mmol) was weighed into a 25 mL reaction flask and dissolved in 3 mL of toluene. 1,4-Dioxane (176 mg, 2.0 mmol) and ethanedithiol (188 mg, 2.0 mmol) were then added to the flask, which was then sealed and heated and stirred at 100°C for 24 h. After the reaction, Na2S2O3 (0.2 M, 20 mL) was added to reduce the remaining I2. The mixture was then extracted three times with dichloromethane (10 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, and then spin-dried to dryness. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate mobile phase) to obtain 1,4-dithiane (II-28) as a white solid (212 mg, 88%).

[0188] Method 2: 1,4-dioxane (176 mg, 2.0 mmol) and ethanedithiol (188 mg, 2.0 mmol) were weighed into a 25 mL reaction flask and dissolved in 3 mL of toluene. HI (55% aqueous solution, 924 mg, 4.0 mmol) was then added, sealed, and heated and stirred at 100°C for 24 h. After the reaction, Na₂S₂O₃ (0.2 M, 20 mL) was added to quench the reaction. The mixture was then extracted three times with dichloromethane (10 mL). The organic phases were combined, dried over anhydrous magnesium sulfate, and then spin-dried to dryness. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate mobile phase) to obtain 1,4-dithiane (II-28) as a white solid (193 mg, 80%).

[0189] A known compound, white solid, melting point 110-111°C. 1 H NMR (400MHz, CDCl3) δ2.85 (s, 8H). 13 CNMR (101MHz,CDCl3)δ29.1.

[0190] Other embodiments

[0191] 1,2-bis(4-methylphenylthio)ethane (II-1) was prepared using 4-methylthiophenol as a raw material. Some reaction conditions were changed, and the remaining operations were the same as in Example 1, as shown in Table 1-3.

[0192] Table 1 Effects of accelerators and epoxy compounds on yield, reaction temperature 80°C, time 24h.

[0193] Example Accelerator (1.0 equiv.) Epoxide Yield (%) 29 <![CDATA[I2]]> 1,4-Dioxane 48 30 LiI 1,4-Dioxane 0 31 NaI 1,4-Dioxane 0 32 KI 1,4-Dioxane 0 33 HI 1,4-Dioxane 40 34 HCl 1,4-Dioxane 0 35 HBr 1,4-Dioxane 0 36 <![CDATA[I2]]> 1,3-Dioxolane 16 37 <![CDATA[I2]]> 1,4-Benzodioxin 0

[0194] Table 2 Effect of solvent on yield, I2 (1.0 equiv.), 1,4-dioxane (2.0 equiv.), time 24 h.

[0195] Example Solvent (3 mL) Temperature (℃) Yield (%) 38 n-hexane 80 26 39 Toluene 80 53 40 N,N-Dimethylformamide 80 0 41 Dimethyl sulfoxide 80 0 42 Tetrahydrofuran 70 0 43 Ether 40 0

[0196] Table 3 Effect of temperature on yield, 1,4-dioxane (2.0 equiv.), toluene (3.0 mL), time 24 h.

[0197]

[0198]

[0199] Table 4 Effect of the dosage and reaction time of I2 on the yield, 1,4-dioxane (2.0 equiv.), toluene (3.0 mL), reaction temperature 95°C.

[0200] Example Accelerator Time (h) Yield (%) 50 <![CDATA[I2(1.1equiv.)]]> 24 75 51 <![CDATA[I2(1.3equiv.)]]> 24 76 52 <![CDATA[I2(1.5equiv.)]]> 24 75 53 <![CDATA[I2(1.1equiv.)]]> 48 81 54 <![CDATA[I2(1.1equiv.)]]> 72 82

Claims

1. A method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane, characterized by: The following steps are involved: ； S1, dissolving elemental iodine in an organic solvent; the organic solvent is one or both of toluene and n-hexane; S2, adding 1,4-dioxane and thiol or thiol compound R-SH or ethanedithiol to the solution of step S1, sealing, heating and stirring until the reaction is completed; In the thiol or thiol compound R-SH, R is an aryl group with or without a first substituent, or a C1-30 linear alkyl group with or without a second substituent, the first substituent includes a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxy group, or a halogen substituent, and the second substituent includes a linear C1-30 alkyl group. The number of the first substituent and the second substituent is not limited; S3, adding Na2S2O3 to the solution where the reaction in S2 is completed to reduce the remaining I2; S4, extract with dichloromethane, dry and concentrate the organic phase, and purify the crude product by silica gel column chromatography to obtain the final product.

2. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 1, characterized in that: The iodine in step S1 is replaced by HI; in step S3, Na2S2O3 is added to the solution after the reaction in S2 to quench the reaction.

3. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 2, characterized in that: When the raw material in S1 is HI, 1,4-dioxane and a disulfide compound R1-SS-R1 are added to the solution in step S1 in S2 to react: ； The vicinal disulfide compound R1-SS-R1 is a symmetrical vicinal disulfide, wherein R1 is selected from an aromatic group containing a methyl group, an ethyl group, an isopropyl group, a tert-butyl group, a methoxy group, or a halogen substituent.

4. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 3, characterized in that: In the reaction, the molar ratio of 1,4-dioxane:R1-SS-R1:HI is 2:1:2.

2.

5. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 1, characterized in that: The reaction temperature in step S2 is 80-110°C.

6. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 1, characterized in that: In the reaction, the molar ratio of 1,4-dioxane: R-SH: I2 is 2:1:1.

1. When synthesizing 1,4-dithiane, the molar ratio of 1,4-dioxane: ethanedithiol: I2 is 1:1:

1.

7. The method for synthesizing 1,2-dithioethane compounds and 1,4-dithiane according to claim 2, characterized in that: In the reaction, the molar ratio of 1,4-dioxane: R-SH: HI is 2:1:1.

1. When synthesizing 1,4-dithiane, the molar ratio of 1,4-dioxane: ethanedithiol: HI is 1:1:1.

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