A method for preparing 2,2-dibromoacetophenone by C-S bond cleavage

Abstract

The present invention relates to the technical field of fine chemical engineering, and discloses a method for preparing 2,2-dibromoacetophenone by C-S bond cleavage. The specific steps are as follows: Using 1-phenylethyl methyl sulfide as the reaction raw material, dichlorodimethylhydantoin and water as important additives, heating and reacting in an organic solvent to obtain the target product 2,2-dibromoacetophenone. This method has the advantages of simple operation, avoiding the use of additional catalysts and the use of highly toxic and corrosive liquid bromine, and has potential application value.

Description

Technical Field

[0001] The present invention belongs to the field of fine chemicals and relates to a method for preparing 2,2-dibromoacetophenone by C-S bond cleavage. Background Art

[0002] 2,2-Dibromoacetophenone is not only an important chemical intermediate, but also can be used as an antifungal and antibacterial drug, and even can be used as a bactericide and algaecide.

[0003] Currently, the synthetic methods of 2,2-dibromoacetophenone that can be consulted mainly include the following two categories: (1) Using acetophenone as a raw material, 2,2-dibromoacetophenone is synthesized through continuous secondary bromination reactions. Generally, such reactions require the use of highly toxic and corrosive liquid bromine as a bromination reagent (Organic Letters, 2019, 21, 9681); (2) Using styrene as a raw material, 2,2-dibromoacetophenone is synthesized by adding additional catalysts such as perchloric acid, ferric chloride, and peroxidase (Monatshefte für Chemie, 2016, 147, 405; Tetrahedron Letters, 2015, 56, 4124; EP57562).

[0004] The present method uses 1-phenylethyl methyl sulfide as a raw material, and dibromohydantoin (DBDMH) and water as additives, and can rapidly and efficiently synthesize 2,2-dibromoacetophenone through a C-S bond cleavage reaction. Currently, the reaction for synthesizing 2,2-dibromoacetophenone by this method has not been reported. This method involves the cleavage of C-S bonds and C-H bonds and the formation of C-Br bonds. Summary of the Invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a simple, rapid, and efficient method for 2,2-dibromoacetophenone.

[0006] The steps for synthesizing 2,2-dibromoacetophenone involved in the present invention are as follows: 1-phenylethyl methyl sulfide, dibromohydantoin, and water are added to a sealed tube containing a reaction solvent and reacted. After the reaction is completed, the reaction solution is concentrated and column chromatography separation is carried out in sequence to obtain the target product 2,2-dibromoacetophenone.

[0007] The reaction solvent of the system in the present invention is one of 1,2-dichloroethane, acetonitrile, and dichloromethane. Further preferably, the reaction solvent is 1,2-dichloroethane.

[0008] In the invention, the molar ratio of 1-phenylethyl methyl sulfide, dibromohydantoin, and water is 1.0: 2.0-4.0: 5.0-50.0. Further preferably, the molar ratio of 1-phenylethyl methyl sulfide, dibromohydantoin, and water is 1.0: 3.0: 20.

[0009] The reaction temperature described in the present invention is 60 to 120 °C, and the reaction temperature is further preferably 60 to 100 °C.

[0010] The reaction time described in the present invention is 6 to 18 hours, and the reaction time is further preferably 18 hours.

[0011] The concentration of 1-phenylethyl methyl sulfide in the reaction solvent of the present invention is 0.05 to 0.1 mol / L.

[0012] Compared with the prior art, the beneficial effects of the present invention are as follows: The present invention uses 1-phenylethyl methyl sulfide as the reaction raw material, dibromohydantoin and water as important additives, and heats and reacts in an organic solvent to obtain 2,2-dibromoacetophenone. The preparation method of the present invention is simple, rapid and efficient, and avoids the use of additional catalysts and the use of highly toxic and corrosive liquid bromine, and has potential application value. Specific Embodiments

[0013] The following examples will help to illustrate the present invention, but are not limited to its scope.

[0014] Specific Example 1: Synthesis method of 2,2-dibromoacetophenone: 1,2-dichloroethane (3 mL), 1-phenylethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol) and water (4.0 mmol) were successively added to a 25 mL sealed tube, the reaction temperature was controlled at 100 °C, and the reaction was vigorously stirred for 18 hours. After the reaction was completed, the reaction solution was concentrated and column chromatographed in sequence to obtain 2,2-dibromoacetophenone, and the separation yield was 73%.

[0015]

[0016] NMR data and mass spectrometry data of the target product:

[0017] 1 H NMR(300MHz,CDCl3)δ8.01(d,J=8.1Hz,2H),7.57(t,J=7.4Hz,1H),7.44(t,J=7.7Hz,2H),6.64(s,1H). 13 C NMR(75MHz,CDCl3)δ185.97,134.47,130.87,129.73,128.95,39.67.MS(EI)=278.0[M] + .

[0018] Specific Example 2, Screening Experiment (Screening of Solvent Types): In a 25 mL sealed tube, successively add organic solvent (3 mL), 1-phenylethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol), and water (2.0 mmol). Control the reaction temperature at 100 °C and vigorously stir the reaction for 18 hours. After the reaction is completed, successively perform concentration of the reaction solution and column chromatography separation. The specific conditions are as follows:

[0019]

[0020] (1) Using acetonitrile as the solvent, the yield of the target product is 50%;

[0021] (2) Using dichloromethane as the solvent, the yield of the target product is 44%;

[0022] (3) Using 1,2-dichloroethane as the solvent, the yield of the target product is 51%;

[0023] (4) Using acetone, toluene, methanol, and tetrahydrofuran as solvents, the target product cannot be separated.

[0024] Specific Example 3, Screening Experiment (Screening of the Dosage of Dibromohydantoin): In a 25 mL sealed tube, successively add 1,2-dichloroethane (3 mL), 1-phenylethyl methyl sulfide (0.2 mmol), dibromohydantoin (0 - 0.8 mmol), and water (2.0 mmol). Control the reaction temperature at 100 °C and vigorously stir the reaction for 18 hours. After the reaction is completed, successively perform concentration of the reaction solution and column chromatography separation. The specific conditions are as follows:

[0025]

[0026] (1) When the dosage of dibromohydantoin is 0 mmol, the yield of the target product is 0%;

[0027] (2) When the dosage of dibromohydantoin is 0.2 mmol, the yield of the target product is 0%;

[0028] (3) When the dosage of dibromohydantoin is 0.4 mmol, the yield of the target product is 30%;

[0029] (4) When the dosage of dibromohydantoin is 0.6 mmol, the yield of the target product is 51%;

[0030] (5) When the dosage of dibromohydantoin is 0.8 mmol, the yield of the target product is 50%.

[0031] Specific Example 4, Screening Experiment (Screening of the Dosage of Water): In a 25 mL sealed tube, successively add 1,2-dichloroethane (3 mL), 1-phenethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol), and water (0 - 27.0 mmol). Control the reaction temperature at 100 °C and vigorously stir the reaction for 18 hours. After the reaction, successively perform concentration of the reaction solution and column chromatography separation. The specific conditions are as follows:

[0032]

[0033] (1) When the dosage of water is 0 mmol, the yield of the target product is 0%;

[0034] (2) When the dosage of water is 1.0 mmol, the yield of the target product is 27%;

[0035] (3) When the dosage of water is 2.0 mmol, the yield of the target product is 51%;

[0036] (4) When the dosage of water is 3.0 mmol, the yield of the target product is 66%;

[0037] (5) When the dosage of water is 4.0 mmol, the yield of the target product is 73%;

[0038] (6) When the dosage of water is 10.0 mmol, the yield of the target product is 70%;

[0039] (7) When the dosage of water is 27.0 mmol, the yield of the target product is 0%.

[0040] Specific Example 5, Screening Experiment (Screening of Temperature): In a 25 mL sealed tube, successively add 1,2-dichloroethane (3 mL), 1-phenethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol), and water (4.0 mmol). Control the reaction temperature at 25, 60, 100, and 120 °C respectively and vigorously stir the reaction for 18 hours. After the reaction, successively perform concentration of the reaction solution and column chromatography separation. The specific conditions are as follows:

[0041]

[0042] (1) When the reaction temperature is 25 °C, the yield of the target product is 0%;

[0043] (2) When the reaction temperature is 60 °C, the yield of the target product is 69%;

[0044] (3) When the reaction temperature is 100 °C, the yield of the target product is 73%;

[0045] (4) When the reaction temperature is 120 °C, the yield of the target product is 63%.

[0046] Specific Example 6, Screening Experiment (Screening of the Dosage of Solvent 1,2-Dichloroethane): In a 25 mL sealed tube, sequentially add 1,2-dichloroethane (2 - 4 mL), 1-phenethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol), and water (4.0 mmol). Control the reaction temperature at 100 °C and vigorously stir the reaction for 18 hours. After the reaction is completed, concentrate the reaction solution and perform column chromatography separation in sequence. The specific situations are as follows:

[0047]

[0048] (1) When the dosage of 1,2-dichloroethane is 2.0 mL, the yield of the target product is 70%;

[0049] (2) When the dosage of 1,2-dichloroethane is 3.0 mL, the yield of the target product is 73%;

[0050] (3) When the dosage of 1,2-dichloroethane is 4.0 mL, the yield of the target product is 58%.

[0051] Specific Example 7, Screening Experiment (Screening of Reaction Time): In a 25 mL sealed tube, sequentially add 1,2-dichloroethane (3 mL), 1-phenethyl methyl sulfide (0.2 mmol), dibromohydantoin (0.6 mmol), and water (4.0 mmol). Control the reaction temperature at 100 °C and vigorously stir the reaction for 6 - 24 hours. After the reaction is completed, concentrate the reaction solution and perform column chromatography separation in sequence. The specific situations are as follows:

[0052]

[0053] (1) When the reaction time is 6 hours, the yield of the target product is 58%;

[0054] (2) When the reaction time is 12 hours, the yield of the target product is 62%;

[0055] (3) When the reaction time is 18 hours, the yield of the target product is 73%;

[0056] (4) When the reaction time is 24 hours, the yield of the target product is 70%.

[0057] The above describes the optional implementation schemes of the present invention to teach those skilled in the art how to implement and reproduce the present invention. For teaching the present invention scheme, some conventional technical aspects have been simplified and omitted. Those skilled in the art should understand that the variations derived from this aspect are all within the protection scope of the present invention.

Claims

1. A method for preparing 2,2-dibromoacetophenone by C-S bond cleavage, which is characterized in that: 1-Phenylethyl methyl sulfide, dibromohydantoin and water are added into a sealed tube containing a reaction solvent, and the reaction is vigorously stirred at a reaction temperature of 60-120 °C for 6-18 hours. After the reaction is completed, the 2,2-dibromoacetophenone is obtained through separation and purification; Among them, the reaction solvent is one of 1,2-dichloroethane, acetonitrile, and dichloromethane; the molar ratio of 1-phenylethyl methyl sulfide, dibromohydantoin and water is 1.0: 2.0-4.0: 5.0-50.0; the concentration of 1-phenylethyl methyl sulfide in the reaction solvent is 0.05-0.1 mol / L.

2. The method according to claim 1, wherein After the reaction is completed, the reaction solution is concentrated and separated by column chromatography, and the target product is collected.

3. The method according to claim 1, characterized in that: The reaction temperature is 60-100 °C.

4. The method according to claim 1, wherein: The reaction time is 18 h.

5. The method according to claim 1, characterized in that: The molar ratio of 1-phenylethyl methyl sulfide, dibromohydantoin and water is 1.0: 3.0: 20.

Images