Thiobenzoic acid ethyl ester compound containing thiocarbonyl and preparation method of thiobenzoic acid ethyl ester compound

Abstract

The invention discloses a thiocarbonyl-containing ethyl thiobenzoate compound and a preparation method thereof.According to the preparation method, benzoylformic acid and elemental sulfur which are cheap and easy to obtain serve as reaction raw materials, the thiocarbonyl-containing ethyl thiobenzoate compound with potential application value is synthesized in one step, and the thiocarbonyl-containing ethyl thiobenzoate compound has the advantages of being high in reaction efficiency and the like. In the generation reaction of the thiocarbonyl-containing ethyl thiobenzoate compound, acetonitrile or acetone can be used as a solvent and a substrate of the reaction, and the use of a transition metal catalyst can be avoided, so that the requirement of green chemistry is met.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a thiobenzoic acid ethyl ester compound containing a thiocarbonyl group and a preparation method thereof. Background Art

[0002] Organic sulfur-containing compounds are an important class of heteroatom-containing compounds, which contain SC bonds and at least one organic group directly connected to the sulfur atom. They have broad application prospects in synthetic chemistry, medicinal chemistry and materials science. The reaction scope involved in building SC bonds is limited, and the synthesis of raw materials may be difficult. Moreover, the raw materials generally use thiols, which have a strong odor, are relatively expensive, and have more by-products that are not environmentally friendly. Therefore, it is of great significance to explore a new method for synthesizing thiobenzoic acid ethyl ester compounds containing thiocarbonyl groups under mild reaction conditions. In order to solve the above problems, the present invention provides the following technical solutions. Summary of the invention

[0003] The technical problem solved by the present invention is as follows: In the prior art method for synthesizing a series of ethyl thiobenzoate compounds, the raw materials are difficult to synthesize and are expensive, requiring harsh reaction conditions and high costs.

[0004] In view of the above problems, the object of the present invention is to provide a method for preparing thiobenzoic acid ethyl ester compounds containing thiocarbonyl groups. Using cheap and readily available benzoylformic acid compounds and sulfur as raw materials, tetrabutylammonium decatungstate (TBADT) as a visible light catalyst, thiobenzoic acid ethyl ester compounds containing thiocarbonyl groups are synthesized under visible light irradiation. The method has readily available raw materials, a wide range of substrates, mild reaction conditions, convenient operation, high atom economy, and is suitable for industrial production.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] Thiobenzoic acid ethyl ester compounds containing thiocarbonyl, the chemical formula of the compound is:

[0007]

[0008] R1 is a phenyl group, a phenyl group substituted by a halogen, a nitro group, an alkoxy group, or an alkyl group having 2 to 3 carbon atoms;

[0009] The structural formula of R2 is

[0010] As a further embodiment of the present invention, the preparation method of the compound is:

[0011] Adding carbonyl-containing benzoylformic acid compounds, S8 and visible light catalyst tetrabutylammonium decatungstate into an organic solvent, stirring and reacting under visible light irradiation, synthesizes thiobenzoic acid ethyl ester compounds containing thiocarbonyl groups;

[0012] The organic solvent is acetone or acetonitrile.

[0013] As a further embodiment of the present invention, the molar ratio of the carbonyl-containing benzoylformic acid compound to S8 is 1:1.

[0014] As a further embodiment of the present invention, the molar ratio of the solvent to the benzoylformic acid compound containing a carbonyl group is (200-300):1.

[0015] As a further embodiment of the present invention, the reaction temperature is room temperature.

[0016] As a further embodiment of the present invention, the reaction time is 15 hours.

[0017] Beneficial effects of the present invention:

[0018] 1. The present invention uses cheap and readily available benzoylformic acid and sulfur as reaction raw materials to synthesize thiocarbonyl-containing ethyl thiobenzoate compounds with potential application value in one step, and has the advantages of high reaction efficiency.

[0019] 2. In the formation reaction of ethyl thiobenzoate compounds containing thiocarbonyl groups, acetonitrile or acetone can be used as both a solvent and a substrate for the reaction, and the use of transition metal catalysts can be avoided, which meets the requirements of green chemistry.

[0020] 3. The synthesis method of the present invention is simple to operate, has mild reaction conditions, and has a wide substrate range. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The present invention will be further described below in conjunction with the accompanying drawings.

[0022] Figure 1 is the thiocarbonyl-containing ethyl thiobenzoate compound (4a) in Example 1 1 H NMR spectra.

[0023] Figure 2 is the thiocarbonyl-containing ethyl thiobenzoate compound (4a) in Example 1 13 C NMR spectrum.

[0024] Figure 3 is the thiobenzoic acid ethyl ester compound (4b) containing a thiocarbonyl group in Example 2 1 H NMR spectra.

[0025] Figure 4is the thiobenzoic acid ethyl ester compound (4b) containing a thiocarbonyl group in Example 2 13 C NMR spectrum.

[0026] Figure 5 is the thiobenzoic acid ethyl ester compound (4c) containing a thiocarbonyl group in Example 3 1 H NMR spectra.

[0027] Figure 6 is the thiobenzoic acid ethyl ester compound (4c) containing a thiocarbonyl group in Example 3 13 C NMR spectrum.

[0028] Figure 7 is the thiobenzoic acid ethyl ester compound (4c) containing a thiocarbonyl group in Example 3 19 F NMR spectrum.

[0029] Figure 8 is the thiobenzoic acid ethyl ester compound (4d) containing a thiocarbonyl group in Example 4 1 H NMR spectra.

[0030] Fig. 9 is the thiobenzoic acid ethyl ester compound (4d) containing a thiocarbonyl group in Example 4 13 C NMR spectrum.

[0031] Fig.10 is the thiocarbonyl-containing ethyl thiobenzoate compound (4e) in Example 5 1 H NMR spectra.

[0032] Fig.11 is the thiocarbonyl-containing ethyl thiobenzoate compound (4e) in Example 5 13 C NMR spectrum.

[0033] Fig.12 is the thiocarbonyl-containing ethyl thiobenzoate compound (4e) in Example 5 19 F NMR spectra

[0034] Fig.13 is the thiobenzoic acid ethyl ester compound (4f) containing a thiocarbonyl group in Example 6 1 H NMR spectra.

[0035] Fig.14 is the thiobenzoic acid ethyl ester compound (4f) containing a thiocarbonyl group in Example 6 13 C NMR spectrum.

[0036] Fig.15 is the thiobenzoic acid ethyl ester compound (4f) containing a thiocarbonyl group in Example 6 19F NMR spectrum.

[0037] Fig.16 is the thiobenzoic acid ethyl ester compound (4 g) containing a thiocarbonyl group in Example 7 1 H NMR spectra.

[0038] Fig.17 is the thiobenzoic acid ethyl ester compound (4 g) containing a thiocarbonyl group in Example 7 13 C NMR spectrum.

[0039] Fig.18 is the thiobenzoic acid ethyl ester compound (4h) containing a thiocarbonyl group in Example 8 1 H NMR spectra.

[0040] Fig.19 is the thiobenzoic acid ethyl ester compound (4h) containing a thiocarbonyl group in Example 8 13 C NMR spectrum.

[0041] Fig. 20 is the thiocarbonyl-containing ethyl thiobenzoate compound (4i) in Example 9 1 H NMR spectra.

[0042] Fig.21 is the thiocarbonyl-containing ethyl thiobenzoate compound (4i) in Example 9 13 C NMR spectrum. DETAILED DESCRIPTION

[0043] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0044] A method for preparing ethyl thiobenzoate compounds containing a thiocarbonyl group, the reaction route of which is shown in the following figure:

[0045]

[0046] The specific steps are as follows:

[0047] At room temperature, a benzoylformic acid compound of formula 1, elemental sulfur 2 and catalyst TBADT are added to a quartz photoreaction tube, anhydrous solvent acetone (2.0 mL) is added to the reaction tube, and then irradiated and stirred for 15 hours at room temperature and at a wavelength of 365 nm for visible light. After the reaction is completed, the remaining solvent is removed by a rotary evaporator, and then separated and purified by column chromatography, and the eluent used is petroleum ether / ethyl acetate (v / v=100:1-20:1), and after purification, ethyl thiobenzoate compounds containing thiocarbonyl groups are obtained.

[0048] The present invention uses green and pollution-free visible light induced reaction, which is environmentally friendly, has high atomic utilization rate and little environmental pollution. The organic solvent can also be used as one of the reaction substrates.

[0049] The present invention selects elemental sulfur as the sulfur source, which has good stability, is cheap, is easily available and is easy to operate.

[0050] Unless otherwise specified, the various reagents / instruments used in the examples and comparative examples of the present invention are conventional commercially available products. The experimental materials and instrument information used in the present invention are shown in the following table:

[0051] Table 1 Experimental materials / instruments and manufacturers

[0052]

[0053]

[0054] Example 1

[0055] The reaction route is shown in the figure below:

[0056]

[0057] At room temperature, p-methylbenzoylformic acid compound 1a (0.10mmol), elemental sulfur (0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (2.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 15h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4a was obtained with a yield of 86%. Figure 1 , Figure 2 As shown, the structural characterization data of compound 4a are as follows:

[0058] 1H NMR (600MHz, CDCl3) δ7.88–7.86(m,2H),7.28–7.24(m,2H),3.91(s,2H),2.41(s,3H),2.33(s,3H);

[0059] 13 C NMR (150MHz, CDCl3) δ202.15,189.85,144.76,133.49,129.31,127.42,39.29,28.77,21.61;

[0060] HRMS(ESI)m / z calcd for C 11 H 13 O2S + (M+H) + 209.0631, found 209.0631.

[0061] Example 2

[0062]

[0063] At room temperature, p-chlorobenzoylformic acid compound 1b (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (2.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 15h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4b was obtained with a yield of 82%. Figure 3 , Figure 4 As shown, the structural characterization data of compound 4b are as follows:

[0064] 1 H NMR (600MHz, CDCl3): δ7.92 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.6 Hz, 2H), 3.94 (s, 2H), 2.35 (s, 3H);

[0065] 13 C NMR (150MHz, CDCl3): δ201.54,189.27,140.29,134.43,129.05,128.75,39.59,28.96;

[0066] HRMS(ESI)m / z calcd for C 10 H 10 ClO2S+ (M+H) + 229.0085, found 229.0085.

[0067] Example 3

[0068]

[0069] At room temperature, trifluoromethylbenzoylformic acid compound 1c (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (2.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 15h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4c was obtained with a yield of 76%. Figure 5 , Figure 6 , Figure 7 As shown, the structural characterization data of compound 4c are as follows:

[0070] 1 H NMR (600MHz, CDCl3): δ8.08(d,J=8.1Hz,2H),7.74(d,J=8.1Hz,2H),3.99(s,2H),2.36(s,3H);

[0071] 13 C NMR (150MHz, CDCl3): δ201.10, 189.58, 138.81, 134.96 (q, J = 32.7Hz), 127.71, 125.75 (q, J = 3.7Hz), 123.35 (q, J = 272.9Hz), 39.69, 28.93;

[0072] 19 F NMR (565MHz, CDCl3): δ-63.22;

[0073] HRMS(ESI)m / z calcd for C 11 H 10 F3O2S + (M+H) + 263.0348, found 263.0346.

[0074] Example 4

[0075]

[0076] At room temperature, m-methylbenzoylformic acid compound 1d (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (3.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 22h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4d was obtained with a yield of 71%. Figure 8 , Fig. 9 As shown, the structural characterization data of compound 4d are as follows:

[0077] 1 H NMR (600MHz, CDCl3): δ7.79–7.77(m,2H),7.41–7.40(m,1H),7.36–7.33(m,1H),3.92(s,2H),2.41(s,3H),2.33(s,3H);

[0078] 13 C NMR (150MHz, CDCl3): δ202.05,190.48,138.63,136.09,134.59,128.58,127.87,124.63,39.43,28.84,21.23;

[0079] HRMS(ESI)m / z calcd for C 11 H 13 O2S + (M+H) + 209.0631, found 209.0630.

[0080] Example 5

[0081]

[0082] At room temperature, m-fluorobenzoylformic acid compound 1e (0.10 mmol), elemental sulfur (2, 0.1 mmol) and catalyst TBADT (5 mol%, 16.5 mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (2.0 mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365 nm for 20 hours. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography, and the eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4e was obtained, and the yield was 73%. Fig.10 , Fig.11 and Fig.12As shown, the structural characterization data of compound 4e are as follows:

[0083] 1 H NMR (600MHz, CDCl3): δ7.78 (ddd, J=7.8, 1.7, 1.0Hz, 1H), 7.64 (ddd, J=9.2, 2.6, 1. 6Hz,1H),7.45(td,J=8.0,5.5Hz,1H),7.31–7.28(m,1H),3.96(s,2H),2.35(s,3H);

[0084] 13 C NMR (150MHz, CDCl3): 201.28, 189.18 (d, J = 2.7Hz), 162.50 (d, J = 248.6Hz), 137.91 (d, J = 6.9Hz), 13 0.34(d,J=7.7Hz), 123.12(d,J=2.9Hz), 120.65(d,J=21.3Hz), 114.06(d,J=23.1Hz), 39.52, 28.82;

[0085] 19 F NMR (565MHz, CDCl3): δ-111.28;

[0086] HRMS(ESI)m / z calcd for C 10 H 10 FO2S + (M+H) + 313.0380, found 313.0381.

[0087] Example 6

[0088]

[0089] At room temperature, o-fluorobenzoylformic acid compound 1f (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetone (2.5mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 15h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4f was obtained with a yield of 80%. Fig.13 , Fig.14 and Fig.15 The structural characterization data of compound 4f are as follows:

[0090] 1 H NMR (600MHz, CDCl3): δ7.90(td,J=7.5,1.8Hz,1H),7.57–7.53(m,1H),7.26–7.23(m,1H),7.19–7.16(m,1H),3.93(s,2H),2.35(s,3H);

[0091] 13 C NMR (150MHz, CDCl3): (ppm): δ201.64, 187.21 (d, J = 5.3Hz), 160.62 (d, J = 258.7Hz), 134.91 (d, J = 8.8Hz) ,129.82,124.40(d,J=11.0Hz),124.32(d,J=3.8Hz),116.92(d,J=22.3Hz),39.77(d,J=3.8Hz),28.94;

[0092] 19 F NMR (565MHz, CDCl3): δ-109.77;

[0093] HRMS(ESI)m / z calcd for C 10 H 10 FO2S + (M+H) + 313.0380, found 313.0380.

[0094] Example 7

[0095]

[0096] At room temperature, add 1g (0.10mmol) of fused-ring 2-naphthobenzoylcarboxylic acid compound, elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) to a quartz photoreaction tube, add anhydrous solvent acetone (2.0mL) to the reaction tube, and irradiate and stir for 15h under visible light wavelength of 365nm. After the reaction is completed, remove the remaining solvent with a rotary evaporator, separate and purify by column chromatography, and the eluent used is petroleum ether / ethyl acetate (v / v=100:1~20:1), and obtain 4g of white solid target product with a yield of 69%. Fig.16 , Fig.17 As shown, the structural characterization data of compound 4g are as follows:

[0097] 1H NMR (600MHz, CDCl3): δ8.56(s,1H),7.99–7.96(m,2H),7.90–7.87(m,2H),7.62–7.55(m,2H),3.99(s,2H),2.37(s,3H);

[0098] 13 C NMR (150MHz, CDCl3): δ202.01,190.28,135.90,133.37,132.34,129.57,129.09,128.73,128.62,127.80,127.04,123.03,39.59,28.92;

[0099] HRMS(ESI)m / z calcd for C 14 H 13 O2S + (M+H) + 245.0631, found 245.0630.

[0100] Example 8

[0101]

[0102] At room temperature, unsubstituted benzoylformic acid compound 1h (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetonitrile (2.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 15h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and the target product 4h was obtained as a colorless oily liquid with a yield of 84%. Fig.18 , Fig.19 As shown, the structural characterization data of compound 4h are as follows:

[0103] 1 H NMR (600MHz,CDCl3):δ 1 H NMR (600MHz, Chloroform-d) δ7.96–7.94(m,2H),7.66–7.64(m,1H),7.52–7.49(m,2H),3.87(s,2H);

[0104] 13C NMR (150MHz, CDCl3): δ187.90,135.19,134.53,129.00,127.51,115.83,14.33;

[0105] HRMS(ESI)m / z calcd for C9H8NOS + (M+H) + 178.0321, found 178.0320.

[0106] Example 9

[0107]

[0108] At room temperature, p-methylbenzaldehyde compound 1a (0.10mmol), elemental sulfur (2, 0.1mmol) and catalyst TBADT (5mol%, 16.5mg) were added to a quartz photoreaction tube, and anhydrous solvent acetonitrile (2.0mL) was added to the reaction tube, and then irradiated and stirred at a visible light wavelength of 365nm for 10h. After the reaction was completed, the remaining solvent was removed by rotary evaporator, and then separated and purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v=100:1~20:1), and a colorless oily liquid target product 4i was obtained with a yield of 89%. Fig. 20 , Fig.21 As shown, the structural characterization data of compound 4i are as follows:

[0109] 1 H NMR (600MHz, CDCl3): δ7.84(d,J=8.2Hz,2H),7.29(d,J=8.0Hz,2H),3.85(s,2H),2.44(s,3H);

[0110] 13 C NMR (150MHz, CDCl3): δ187.39,145.72,132.68,129.66,127.61,115.96,21.78,14.24;

[0111] HRMS(ESI)m / z calcd for C 10 H 10 NOS + (M+H) + 192.0478, found 192.0478.

[0112] Comparative Example 1

[0113]

[0114]

[0115]

[0116] Comparative Example 2

[0117]

[0118]

[0119] The above contents are merely examples and explanations of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in a similar manner. As long as they do not deviate from the invention or exceed the scope defined by the claims, they shall all fall within the protection scope of the present invention.

Claims

1. A thiobenzoic acid ethyl ester compound containing a thiocarbonyl group, characterized in that: The chemical formula of this compound is: R1 is a phenyl group, a phenyl group substituted by a halogen, a nitro group, an alkoxy group, or an alkyl group having 2 to 3 carbon atoms; The structural formula of R2 is 2. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 1, characterized in that: The R1 is ethyl, n-butyl, n-hexyl, cyclohexyl, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl or 4-nitrophenyl.

3. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 1, characterized in that: Benzoylformic acid compounds containing a carbonyl group include:

4. The thiocarbonyl-containing ethyl thiobenzoate compound according to any one of claims 1 to 3, characterized in that: The preparation method of the compound is: Adding carbonyl-containing benzoylformic acid compounds, S8 and visible light catalyst tetrabutylammonium decatungstate into an organic solvent, stirring and reacting under visible light irradiation, synthesizes thiobenzoic acid ethyl ester compounds containing thiocarbonyl groups; The organic solvent is acetone or acetonitrile.

5. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 4, characterized in that: The molar ratio of the carbonyl-containing benzoylformic acid compound to S8 is 1:

1.

6. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 5, characterized in that: The molar ratio of the solvent to the benzoylformic acid compound containing a carbonyl group is (200-300):

1.

7. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 6, characterized in that: The reaction temperature is 10-50°C.

8. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 6, characterized in that: The reaction temperature is room temperature.

9. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 7, characterized in that: The reaction time is 10 to 24 hours.

10. The thiocarbonyl-containing ethyl thiobenzoate compound according to claim 9, characterized in that: The reaction time is 15h.

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