Synthesis method of chlorinated alcohol compound

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a chlorinated alcohol compound. The method comprises the following steps: adding an acetonitrile solution of a compound 1 into 1, 1, 2, 2-tetrachloroethane in a nitrogen atmosphere, then adding tert-butyl hydroperoxide, alkali and trimethylsilyl cyanide, stirring at room temperature, heating, stirring and reacting, removing a solvent under reduced pressure after the reaction is completed, and then performing silica gel column chromatography on a crude product to obtain a product, namely the chlorohydrin compound. According to the synthesis method disclosed by the invention, by regulating and controlling reaction conditions and optimizing raw material selection, the yield of the chlorinated alcohol compound is effectively improved, the atom economy is improved, the raw materials are efficiently utilized, and the emission of wastes is reduced.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for synthesizing chlorinated alcohols. Background Technology

[0002] Chlorools, as a class of organic compounds containing both hydroxyl (-OH) and chlorine (-Cl) atoms in their molecular structure, occupy a pivotal position in the field of chemistry. Their unique structure endows them with diverse chemical properties, making them key raw materials in many fields such as medicine, agriculture, and synthetic methodology. In the pharmaceutical field, chlorools play an irreplaceable role. The synthesis of many drugs relies on chlorools as key intermediates. For example, in the preparation of the nonsteroidal anti-inflammatory drug fenprofen calcium, chlorools are converted into nitrile compounds through nucleophilic substitution reactions, thereby constructing the core framework of the drug. Furthermore, chlorool derivatives, such as α-chlorools, are used in the preparation of rodenticides, controlling rodent populations by disrupting the coagulation mechanism and endocrine system of rats. Despite their high toxicity and the need for strict management, they remain an effective biological control method in agriculture and public health, demonstrating the importance of chlorools in protecting human health and environmental safety.

[0003] In agriculture, chloroalcohols are also widely used. Besides being a core component of rodenticides, they play a crucial role in pesticide synthesis. With the increasing demand for highly effective and low-toxicity pesticides in agriculture, chloroalcohols, as intermediates, provide strong support for the development of novel pesticides. For example, certain chloroalcohol derivatives can be used to synthesize pesticides with specific biological activities, which can target pests and diseases while reducing environmental and non-target organism impacts. The application of chloroalcohols not only improves agricultural production efficiency but also promotes sustainable agricultural development.

[0004] At the level of synthetic methodology, the preparation of chloroethanol is a classic paradigm of organic synthesis, and its research has driven the development of green chemistry. The chloroethanol method, using ethylene as a raw material, generates chloroethanol through the addition reaction of chlorine and water, followed by alkali treatment to close the ring and yield ethylene oxide. Although this process has relatively low atom utilization, it provides a historical reference for modern catalytic oxidation methods (such as silver-catalyzed direct oxidation of ethylene). The molecular weight calculation of chloroethanol is based on the combination of the alcohol skeleton and chlorine atoms, achieved through atomic mass accumulation. This fundamental skill is crucial for understanding their physicochemical properties. Furthermore, the synthesis of chloroethanol involves green chemistry concepts such as atom economy, emphasizing the importance of efficient use of raw materials and reduced waste emissions. In summary, chloroethanol is not only a catalyst for pharmaceutical and agricultural innovation but also a microcosm of the progress in synthetic chemistry. Its importance extends from laboratory research to industrial production, continuously driving scientific frontiers. However, how to improve the yield and atom utilization of chloroethanol compounds and reduce waste emissions by controlling reaction conditions and optimizing raw material selection remains a pressing technical problem to be solved. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, this invention provides a method for synthesizing chlorohydrin compounds. In this invention, an acetonitrile solution of compound 1 is added to 1,1,2,2-tetrachloroethane under a nitrogen atmosphere, followed by the addition of tert-butyl hydroperoxide, a base, and trimethylcyanosilane. After stirring at room temperature, the reaction is heated and stirred. Once the reaction is complete, the solvent is removed under reduced pressure. The crude product is then subjected to silica gel column chromatography to obtain the chlorohydrin compound. This synthesis method effectively improves the yield of chlorohydrin compounds, enhances atom economy, efficiently utilizes raw materials, and reduces waste emissions by controlling reaction conditions and optimizing raw material selection.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a method for synthesizing chlorohydrin compounds, comprising the following steps: An acetonitrile solution of compound 1 was added to 1,1,2,2-tetrachloroethane, followed by the addition of tert-butyl hydroperoxide, a base, and trimethylcyanosilane. The mixture was stirred at room temperature and then heated and stirred to react. After the reaction was completed, the solvent was removed under reduced pressure, and the crude product was subjected to silica gel column chromatography to obtain the product, which is a chlorohydrin compound.

[0007] Furthermore, compound 1 is any one of the following structural formulas: .

[0008] Furthermore, the molar ratio of compound 1, tert-butyl hydroperoxide, base, and trimethylcyanosilane is 1:2~6:4:3~5.

[0009] Furthermore, the molar ratio of compound 1, tert-butyl hydroperoxide, base, and trimethylcyanosilane is 1:6:4:4.

[0010] Furthermore, the base is any one of triethylamine, diethylamine, diisopropylethylamine, DBU, and triethylenediamine.

[0011] Furthermore, the base is triethylamine or diethylamine.

[0012] Furthermore, the tert-butyl hydroperoxide is specifically a 70% aqueous solution.

[0013] Furthermore, the temperature of the heating and stirring reaction is 60 °C.

[0014] Furthermore, the heating and stirring reaction time is 24 hours.

[0015] Compared with the prior art, the beneficial effects of the present invention are: In this invention, an acetonitrile solution of compound 1 is added to 1,1,2,2-tetrachloroethane under a nitrogen atmosphere, followed by the addition of tert-butyl hydroperoxide, a base, and trimethylcyanosilane. The mixture is stirred at room temperature, then heated and stirred until the reaction is complete. The solvent is removed under reduced pressure, and the crude product is then subjected to silica gel column chromatography to obtain the chlorohydrin compound. This synthetic method effectively improves the yield of chlorohydrin compounds, enhances atom economy, efficiently utilizes raw materials, and reduces waste emissions by controlling reaction conditions and optimizing raw material selection. Detailed Implementation

[0016] The specific embodiments of the present invention will be further described below. It should be noted that these descriptions are for the purpose of aiding understanding the present invention, but do not constitute a limitation thereof. Furthermore, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0017] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods, and the experimental materials used in the following embodiments are all available through conventional commercial channels.

[0018] Example 1: A method for synthesizing a chlorohydrin compound 4a A solution of compound 1a (0.5 mmol, 1.0 equivalent) in acetonitrile (0.5 mL) was placed in 1,1,2,2-tetrachloroethane (0.5 mL). Then, tert-butyl hydroperoxide (3.0 mmol, 6.0 equivalent), triethylamine (2.0 mmol, 4.0 equivalent), and trimethylcyanosilane (2 mmol, 4.0 equivalent) were added, and the mixture was stirred at room temperature. The mixture was then stirred at 60 °C for 24 hours. After the reaction was complete, the solvent was removed under reduced pressure, and the crude product was subjected to silica gel column chromatography to give a yellow oily product 4a in 67% yield.

[0019] The structural formula of compound 1a is: The reaction equation is: The NMR data for compound 4a are as follows: R f = 0.36 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.98-7.76 (m, 4H), 7.54 (dd, J = 6.3, 3.1 Hz, 3H), 5.27-5.12 (m, 1H), 4.16-3.98(m, 2H), 2.15 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 135.1, 133.4, 133.0, 128.9,128.1, 127.8, 127.0, 126.74, 126.66, 124.7, 67.8, 65.0. Example 2: A method for synthesizing a chlorohydrin compound 4a The difference between Example 2 and Example 1 is that the amount of tert-butyl hydroperoxide used in Example 2 is 1.0 mmol, while the rest remains the same as in Example 1. The final yield of the chlorohydrin compound 4a was 23%.

[0020] Example 3: A method for synthesizing a chlorohydrin compound 4a The difference between Example 3 and Example 1 is that the amount of tert-butyl hydroperoxide used in Example 3 is 2.0 mmol, while the rest remains the same as in Example 1. The final yield of the chlorohydrin compound 4a was 57%.

[0021] Example 4: A method for synthesizing a chlorohydrin compound 4a The difference between Example 4 and Example 1 is that the amount of trimethylcyanosilane used in Example 4 is 1.5 mmol, while the rest remains the same as in Example 1. The final yield of the chlorohydrin compound 4a was 58%.

[0022] Example 5: A method for synthesizing a chlorohydrin compound 4a The difference between Example 5 and Example 1 is that the amount of trimethylcyanosilane used in Example 5 is 2.5 mmol, while the rest remains the same as in Example 1. The final yield of the chlorohydrin compound 4a was 68%.

[0023] Example 6: A method for synthesizing a chlorohydrin compound 4a The difference between Example 6 and Example 1 is that in Example 6, triethylamine was replaced with diisopropylethylamine; otherwise, the results were the same as in Example 1. The final yield of the chlorohydrin compound 4a was 29%.

[0024] Example 7: A method for synthesizing a chlorohydrin compound 4a The difference between Example 7 and Example 1 is that in Example 7, triethylamine was replaced with diethylamine; otherwise, the results were the same as in Example 1. The final yield of the chlorohydrin compound 4a was 58%.

[0025] Example 8: A method for synthesizing a chlorohydrin compound 4a The difference between Example 8 and Example 1 is that in Example 8, triethylamine was replaced with DBU; otherwise, the results were the same as in Example 1. The final yield of the chlorohydrin compound 4a was 21%.

[0026] Example 9: A method for synthesizing a chlorohydrin compound 4a The difference between Example 9 and Example 1 is that in Example 9, triethylamine is replaced with triethylenediamine; otherwise, they remain the same as in Example 1. The final yield of the chlorohydrin compound 4a was 15%.

[0027] Example 10: A method for synthesizing a chlorohydrin compound 4a The difference between Example 10 and Example 1 is that in Example 10, trimethylcyanosilane was replaced with trimethylchlorosilane; otherwise, the results were the same as in Example 1. The final yield of the chloroalcohol compound 4a was 32%.

[0028] Comparative Example 1: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 1 and Example 1 is that in Comparative Example 1, triethylamine was replaced with potassium carbonate; otherwise, the results were the same as in Example 1. Ultimately, chlorohydrin compound 4a could not be obtained.

[0029] Comparative Example 2: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 2 and Example 1 is that triethylamine was not added in Comparative Example 2, while the rest remained the same as in Example 1. Ultimately, chlorohydrin compound 4a could not be obtained.

[0030] Comparative Example 3: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 3 and Example 1 is that trimethylcyanosilane was not added in Comparative Example 3, while the rest remained the same as in Example 1. Ultimately, chlorohydrin compound 4a could not be obtained.

[0031] Comparative Example 4: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 4 and Example 1 is that 1,1,2,2-tetrachloroethane was replaced with carbon tetrachloride in Comparative Example 4, while the rest remained the same as in Example 1. Ultimately, chlorool compound 4a could not be obtained.

[0032] Comparative Example 5: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 5 and Example 1 is that 1,1,2,2-tetrachloroethane was replaced with dichloromethane in Comparative Example 5, while the rest remained the same as in Example 1. Ultimately, chlorool compound 4a could not be obtained.

[0033] Comparative Example 6: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 6 and Example 1 is that 1,1,2,2-tetrachloroethane was replaced with N-chlorosuccinimide in Comparative Example 6, while the rest remained the same as in Example 1. Ultimately, chlorool compound 4a could not be obtained.

[0034] Comparative Example 7: A method for synthesizing a chlorohydrin compound 4a The difference between Comparative Example 7 and Example 1 is that 1,1,2,2-tetrachloroethane was replaced with potassium chloride in Comparative Example 7, while the rest remained the same as in Example 1. Ultimately, chlorool compound 4a could not be obtained.

[0035] Example 11: A method for synthesizing a chlorohydrin compound 4b The difference between Example 11 and Example 1 is that in Example 11, compound 1b is used instead of compound 1a, and the structural formula of compound 1b is: The structural formula of the synthesized compound 4b is: Compound 4b is a yellow oil with a yield of 70%.

[0036] The NMR data for compound 4b are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1H NMR (400 MHz, CDCl3) δ 7.49-7.32 (m, 5H), 5.02 (dd, J = 7.4, 5.7 Hz, 1H), 4.03-3.87 (m, 2H), 2.23 (s,1H). 13 C NMR (101 MHz, CDCl3) δ 137.8, 128.9, 128.8, 127.5, 67.9, 64.9. Example 12: A method for synthesizing a chlorohydrin compound 4c The difference between Example 12 and Example 1 is that in Example 12, compound 1c is used instead of compound 1a, and the structure of compound 1c is as follows: The structural formula of the synthesized compound 4c is: Compound 4c is a yellow oil with a yield of 74%.

[0037] The NMR detection data of compound 4c are as follows: Rf = 0.36 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.63-7.42 (m, 1H), 7.30-7.24 (m, 2H), 7.22 (dd, J = 9.9, 4.3 Hz, 1H), 5.31 (dd, J= 8.1, 5.0 Hz, 1H), 4.00 (qd, J = 12.1, 6.6 Hz, 2H), 2.44 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 135.9, 130.8, 128.7, 126.7, 67.0, 61.3, 19.2. Example 13: A method for synthesizing a chlorohydrin compound 4d The difference between Example 13 and Example 1 is that in Example 13, compound 1d is used instead of compound 1a, and the structure of compound 1d is as follows: The structural formula of the synthesized compound 4d is: Compound 4d is a yellow oil with a yield of 75%.

[0038] The NMR data for compound 4d are as follows: Rf = 0.38 (EtOAc / cyclohexane = 1 / 10). 1H NMR (400 MHz, CDCl3) δ 7.48-7.40 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 5.01 (dd, J = 7.5, 5.6 Hz, 1H), 4.00-3.88 (m, 2H), 2.34 (s, 1H), 1.35 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 152.0,134.8, 127.2, 125.8, 67.8, 64.8, 34.7, 31.3. Example 14: A method for synthesizing a chlorohydrin compound 4e The difference between Example 14 and Example 1 is that in Example 14, compound 1e is used instead of compound 1a, and the structure of compound 1e is as follows: The structural formula of the synthesized compound 4e is: Compound 4e is a yellow oil with a yield of 64%.

[0039] The NMR detection data for compound 4e are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.49-7.36 (m, 2H), 7.16-7.00 (m, 2H), 5.00 (dd, J = 7.3, 5.6 Hz, 1H), 4.00-3.83(m, 2H), 2.08 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 162.8 (d, J = 248.2 Hz), 133.8 (d, J = 3.4 Hz), 129.3 (d, J = 8.4 Hz), 115.8 (d, J = 21.7 Hz), 67.8, 64.0. 19 F NMR (376 MHz, CDCl3) δ -112.56. Example 15: A method for synthesizing a chlorohydrin compound 4f The difference between Example 15 and Example 1 is that in Example 15, compound 1f is used instead of compound 1a, and the structure of compound 1f is as follows: The structural formula of the synthesized compound 4f is: Compound 4f is a yellow oil with a yield of 69%.

[0040] The NMR data for compound 4f are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.53-7.27 (m, 4H), 5.07-.83 (m, 1H), 3.93 (dd, J = 5.4, 1.8 Hz, 2H), 2.23 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 136.4, 134.8, 129.0, 128.9, 67.7. Example 16: A method for synthesizing 4g of a chlorohydrin compound The difference between Example 16 and Example 1 is that in Example 16, compound 1g is used instead of compound 1a, and the structure of compound 1g is as follows: The structural formula of the synthesized compound 4g is: The compound was obtained in a yellow oily form (4g), with a yield of 63%.

[0041] The NMR detection data of compound 4g are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.63-7.46 (m, 2H), 7.33-7.19 (m, 2H), 5.03-4.87 (m, 1H), 4.01-3.82 (m, 2H), 2.18(s, 1H). 13 C NMR (101 MHz, CDCl3) δ 136.9, 132.0, 129.2, 122.9, 67.7, 63.9. Example 17: A method for synthesizing a chlorohydrin compound in 4 hours The difference between Example 17 and Example 1 is that in Example 17, compound 1h is used instead of compound 1a, and the structure of compound 1h is as follows: The structural formula of the synthesized compound 4h is: The compound was a yellow oil after 4 hours, with a yield of 53%.

[0042] The NMR data of compound 4h are as follows: Rf = 0.32 (EtOAc / cyclohexane = 1 / 8). 1H NMR (400 MHz, CDCl3) δ 8.15-8.02 (m, 2H), 7.59-7.43 (m, 2H), 5.09-4.97 (m, 1H), 4.00-3.95 (m, 2H), 3.95(s, 3H), 2.23 (t, J = 6.8 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 166.5, 142.7, 130.6, 130.0, 127.6, 126.1, 67.7, 63.9, 52.3. Example 18: A method for synthesizing a chlorohydrin compound 4i The difference between Example 18 and Example 1 is that in Example 18, compound 1i is used instead of compound 1a, and the structure of compound 1i is as follows: The structural formula of the synthesized compound 4i is: Compound 4i is a yellow oil with a yield of 39%.

[0043] The NMR data for compound 4i are as follows: Rf = 0.37 (EtOAc / cyclohexane = 1 / 5). 1 H NMR (400 MHz, CDCl3) δ 8.40-8.15 (m, 2H), 7.62 (dd, J = 7.9, 0.9 Hz, 2H), 5.06 (dd, J = 8.2, 3.4 Hz, 1H), 3.81 (dd, J = 11.4, 3.6 Hz, 1H), 3.67 (dd, J = 11.4, 8.2 Hz, 1H), 2.92 (s,1H). 13 C NMR (101 MHz, CDCl3) δ 147.9, 146.9, 127.0, 123.9, 73.0, 50.3. Example 19: A method for synthesizing a chlorohydrin compound 4j The difference between Example 19 and Example 1 is that in Example 19, compound 1j is used instead of compound 1a, and the structure of compound 1j is as follows: The structural formula of the synthesized compound 4j is: Compound 4j is a yellow oil with a yield of 42%.

[0044] The NMR data for compound 4j are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.67(d, J = 8.3 Hz, 2H), 7.57 (d, J = 8.1 Hz, 2H), 5.05 (t, J = 6.3 Hz, 1H), 3.97(t, J = 6.2 Hz, 2H), 2.22 (t, J = 6.6 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ141.9-141.7 (m),131.2, 130.9, 127.9, 126.0-125.6 (m), 125.2, 122.5, 67.7,63.6. 19 F NMR (376 MHz, CDCl3) δ -62.77. Example 20: A method for synthesizing a chlorohydrin compound 4k The difference between Example 20 and Example 1 is that in Example 20, compound 1k is used instead of compound 1a, and the structure of compound 1k is as follows: The structural formula of the synthesized compound 4k is: Compound 4K is a yellow oil with a yield of 70%.

[0045] The NMR detection data for compound 4k are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 8). 1 H NMR (400 MHz, CDCl3) δ 7.31(dd, J = 14.2, 6.3 Hz, 1H), 7.02-6.96 (m, 2H), 6.91 (ddd, J = 8.3, 2.6, 0.9Hz, 1H), 4.98 (dd, J = 7.1, 6.0 Hz, 1H), 3.98-3.92 (m, 2H), 3.84 (s, 3H), 2.20 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 159.8, 139.3, 129.9, 119.7, 114.3,113.2, 67.9, 64.7, 55.3. Example 21: A method for synthesizing a chlorohydrin compound 4l The difference between Example 21 and Example 1 is that in Example 21, compound 11 is used instead of compound 1a, and the structure of compound 11 is as follows: The structural formula of the synthesized compound 4l is: Compound 4l is a yellow oil with a yield of 68%.

[0046] The NMR detection data of compound 4l are as follows: Rf = 0.36 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.29(dd, J = 9.6, 5.3 Hz, 1H), 7.23 (d, J = 9.8 Hz, 2H), 7.18 (d, J = 7.5 Hz,1H), 4.98 (dd, J = 7.5, 5.7 Hz, 1H), 4.04-3.85 (m, 2H), 2.40 (s, 3H), 2.29 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 138.6, 137.8, 129.7, 128.7, 128.1, 124.5,67.9, 64.9, 21.4. Example 22: A method for synthesizing a chlorohydrin compound 4m The difference between Example 22 and Example 1 is that in Example 22, compound 1m is used instead of compound 1a, and the structure of compound 1m is as follows: The structural formula of the synthesized compound 4m is: Compound 4M is a yellow oil with a yield of 56%.

[0047] The NMR data for compound 4m are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.37(dd, J = 13.9, 7.8 Hz, 1H), 7.19 (dd, J = 12.3, 8.7 Hz, 2H), 7.12-6.98 (m,1H), 4.99 (t, J = 6.4 Hz, 1H), 3.95 (d, J = 6.3 Hz, 2H), 2.17 (s, 1H). 13C NMR(101 MHz, CDCl3) δ 162.8 (d, J = 247.1 Hz), 140.3 (d, J = 7.3 Hz), 130.4 (d,J = 8.2 Hz), 123.2 (d, J = 3.0 Hz), 115.9 (d, J = 21.1 Hz), 114.6 (d, J =22.7 Hz), 67.8, 63.8. 19 F NMR (376 MHz, CDCl3) δ -111.96. Example 23: A method for synthesizing a chlorohydrin compound 4n The difference between Example 23 and Example 1 is that in Example 23, compound 1n is used instead of compound 1a, and the structure of compound 1n is as follows: The structural formula of the synthesized compound 4n is: Compound 4n is a yellow oil with a yield of 60%.

[0048] The NMR detection data of compound 4n are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.50-7.40 (m, 1H), 7.37-7.28 (m, 3H), 5.06-4.90 (m, 1H), 3.94 (d, J = 6.5 Hz, 2H), 2.22 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 139.9, 134.7, 130.1, 129.0, 127.7,125.7, 67.7, 63.7. Example 24: A method for synthesizing a chlorohydrin compound 4o The difference between Example 24 and Example 1 is that in Example 24, compound 1o is used instead of compound 1a, and the structure of compound 1o is as follows: The structural formula of the synthesized compound 4o is: Compound 4o is a yellow oil with a yield of 59%.

[0049] The NMR detection data of compound 4o are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1H NMR (400 MHz, CDCl3) δ 7.60(t, J = 1.8 Hz, 1H), 7.50 (ddd, J = 7.9, 1.9, 1.1 Hz, 1H), 7.42-7.33 (m, 1H),7.31-7.24 (m, 1H), 4.95 (t, J = 6.4 Hz, 1H), 3.94 (t, J = 6.4 Hz, 2H), 2.19 (t, J = 6.8 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 140.1, 132.0, 130.6, 130.3,126.2, 122.8, 67.7, 63.6. Example 25: A method for synthesizing a chlorohydrin compound 4p The difference between Example 25 and Example 1 is that in Example 25, compound 1p is used instead of compound 1a, and the structure of compound 1p is as follows: The structural formula of the synthesized compound 4p is: Compound 4p is a yellow oil with a yield of 65%.

[0050] The NMR detection data for compound 4p are as follows: Rf = 0.36 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.50(dd, J = 6.5, 2.6 Hz, 1H), 7.29-7.25 (m, 2H), 7.24-7.19 (m, 1H), 5.31 (dd, J= 8.1, 5.0 Hz, 1H), 4.10-3.85 (m, 2H), 2.44 (s, 3H), 2.35 (s, 1H). 13 C NMR (101 MHz, CDCl3) δ 135.9, 130.8, 128.7, 126.9, 126.7, 67.0, 61.3, 19.2. Example 26: A method for synthesizing a chlorohydrin compound 4q The difference between Example 26 and Example 1 is that in Example 26, compound 1q is used instead of compound 1a, and the structure of compound 1q is as follows: The structural formula of the synthesized compound 4q is: Compound 4q is a yellow oil with a yield of 57%.

[0051] The NMR detection data of compound 4q are as follows: Rf = 0.35 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.55(t, J = 7.4 Hz, 1H), 7.39-7.31 (m, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.15-7.02(m, 1H), 5.38 (t, J = 6.3 Hz, 1H), 4.00 (d, J = 6.3 Hz, 2H), 2.27 (s, 1H). 13 CNMR (101 MHz, CDCl3) δ 159.8 (d, J = 248.3 Hz), 130.5 (d, J = 8.4 Hz), 129.1 (d, J = 3.1 Hz), 125.1 (d, J = 12.8 Hz), 124.6 (d, J = 3.6 Hz), 115.7 (d, J =21.8 Hz), 66.9, 57.7, 26.3. Example 27: A method for synthesizing a chlorohydrin compound 4r The difference between Example 27 and Example 1 is that in Example 27, compound 1r is used instead of compound 1a, and the structure of compound 1r is as follows: The structural formula of the synthesized compound 4r is: Compound 4r is a yellow oil with a yield of 60%.

[0052] The NMR detection data of compound 4r are as follows: Rf = 0.36 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.45(d, J = 7.5 Hz, 2H), 7.38 (dt, J = 16.6, 6.9 Hz, 3H), 4.83 (d, J = 5.9 Hz,1H), 4.18 (dq, J = 11.4, 5.7 Hz, 1H), 1.99 (d, J = 4.7 Hz, 1H), 1.31 (d, J =6.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 137.8, 128.7, 128.6, 128.1, 71.8,68.2, 19.0. Example 28: A method for synthesizing a chlorohydrin compound 4S The difference between Example 28 and Example 1 is that in Example 28, compound 1s is used instead of compound 1a, and the structure of compound 1s is as follows: The structural formula of the synthesized compound 4S is: Compound 4r is a yellow oil with a yield of 52%.

[0053] The NMR data for compound 4s are as follows: Rf = 0.38 (EtOAc / cyclohexane = 1 / 10). 1 H NMR (400 MHz, CDCl3) δ 7.38-7.32 (m, 8H), 7.30 (dd, J = 4.6, 3.1 Hz, 2H), 7.27-7.17 (m, 6H), 7.13 (dd, J= 6.8, 2.8 Hz, 2H), 5.11 (d, J = 6.5 Hz, 1H), 5.04 (d, J = 6.5 Hz, 1H), 5.03 (d, J = 3.1 Hz, 1H), 4.98 (d, J = 8.3 Hz, 1H), 3.09 (s, 1H), 2.40 (s, 1H). 13 CNMR (101 MHz, CDCl3) δ 139.5, 138.7, 137.7, 137.2, 128.7, 128.6, 128.5,128.39, 128.35, 128.3, 128.21, 128.19, 128.15, 128.0, 127.1, 127.0, 78.8,78.2, 70.7, 66.9. The embodiments of the present invention have been described in detail above, but the present invention is not limited to the described embodiments. For those skilled in the art, various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and these variations still fall within the protection scope of the present invention.

Claims

1. A method for synthesizing chlorohydrin compounds, characterized in that, Includes the following steps: An acetonitrile solution of compound 1 was added to 1,1,2,2-tetrachloroethane, followed by the addition of tert-butyl hydroperoxide, a base, and trimethylcyanosilane. The mixture was stirred at room temperature and then heated and stirred to react. After the reaction was completed, the solvent was removed under reduced pressure, and the crude product was subjected to silica gel column chromatography to obtain the product, which is a chlorohydrin compound.

2. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, Compound 1 is any one of the following structural formulas: 。 3. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, The molar ratio of compound 1, tert-butyl hydroperoxide, base, and trimethylcyanosilane is 1:2~6:4:3~5.

4. The method for synthesizing a chlorohydrin compound according to claim 3, characterized in that, The molar ratio of compound 1, tert-butyl hydroperoxide, base, and trimethylcyanosilane is 1:6:4:

4.

5. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, The base is any one of triethylamine, diethylamine, diisopropylethylamine, DBU, and triethylenediamine.

6. The method for synthesizing a chlorohydrin compound according to claim 5, characterized in that, The base is triethylamine or diethylamine.

7. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, The tert-butyl hydroperoxide is specifically a 70% aqueous solution.

8. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, The temperature for the heating and stirring reaction is 60 °C.

9. The method for synthesizing a chlorohydrin compound according to claim 1, characterized in that, The heating and stirring reaction time is 24 hours.

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