A preparation method of compound 3,5-dichloro-2-pentanone

Abstract

The invention discloses a method for preparing a compound 3,5-dichloro-2-pentanone, comprising the following steps: using α-acetyl-γ-butyrolactone (II) as a raw material, reacting with hypochlorite and hydrochloric acid, absorbing the dilute hydrochloric acid aqueous solution obtained by water with the generated hydrogen chloride gas, sampling and analyzing, α-acetyl-γ-butyrolactone (II) content ≤1%, the reaction solution is heated and continued to react, and compound (III) 3-chloro-4-oxygen-1-pentanol is generated; the dilute hydrochloric acid aqueous solution obtained in step (1) is added to compound (III) 3-chloro-4-oxygen-1-pentanol, and hydrochloric acid is added to react to obtain compound (I) 3,5-dichloro-2-pentanone. The inventive method has mild reaction conditions and simple process, and the two-step reaction can be operated continuously, and can also be realized by "one-pot method", and the obtained product content is high, which is of great significance to industrial production.

Description

Technical Field

[0001] The invention belongs to the field of chemistry and chemical engineering, and specifically relates to a method for preparing the compound 3,5-dichloro-2-pentanone. Background Art

[0002] 3,5-dichloro-2-pentanone is an important intermediate of the bactericide prothioconzale, and can also be used to synthesize the gamma-aminobutyric acid regulator clomethiazole, as well as to synthesize a series of medical compounds for inhibiting leukemia and anti-tumor. In the previously reported method for preparing similar compounds, α-acetyl-γ-butyrolactone is chlorinated with sulfonyl chloride, and then reacted under concentrated hydrochloric acid to obtain the target product. This is mentioned in J.Am.Chem.Soc.58, P1803 (1936) and Synthesis1977 (3) P189. The method is improved in patent CN109265329, but sulfonyl chloride is still used as the main raw material. A large amount of sulfur dioxide and hydrogen chloride gas are generated during the reaction. The sulfur dioxide and hydrogen chloride gas are difficult to separate, and most of the useful hydrogen chloride is lost. The equipment is corrosive. The amount of hydrochloric acid used in the later stage is large, and a large amount of waste acid is generated, which is not friendly to the environment. Similar compounds can also be prepared by reacting butenone and dichloromethane in the presence of a catalyst to obtain the target product, which is mentioned in the document J.Chem.Soc., Chem.Commun., P1446 (1983). This method has harsh conditions and is not suitable for industrialization. The starting material butenone used in this method is flammable and explosive, highly toxic, and has poor stability. For industrial production and storage, the risk is relatively high. The similar compound can also be obtained by chlorinating α-acetyl-γ-butyrolactone with chlorine gas, and then obtaining the target product under the conditions of hydrogen chloride gas or aqueous solution. This is mentioned in the document "Fine Chemical Intermediates" Vol51 (5), P27. Due to the high toxicity and high activity of chlorine gas, the amount of chlorine gas used in this method has a great influence on the product content, and impurities are difficult to separate. Summary of the invention

[0003] Purpose of the invention: In view of the problems existing in the prior art, the present invention proposes a new preparation method for synthesizing 3,5-dichloro-2-pentanone, in which α-acetyl-γ-butyrolactone is subjected to the action of hypochlorite and hydrochloric acid to complete the process of chlorination, decarboxylation and rechlorination to obtain the target product 3,5-dichloro-2-pentanone.

[0004] Technical solution: In order to achieve the above purpose, the method for preparing the compound 3,5-dichloro-2-pentanone of the present invention comprises the following steps:

[0005] (1) Using α-acetyl-γ-butyrolactone (II) as a raw material, reacting with hypochlorite and hydrochloric acid, and absorbing the generated hydrogen chloride gas with water to obtain a dilute hydrochloric acid aqueous solution. After the reaction, sampling and analysis are performed. When the content of α-acetyl-γ-butyrolactone (II) is ≤1% (gas chromatography analysis, instrument-normalized area ratio), the reaction solution is heated and the reaction is continued to generate compound (III) 3-chloro-4-oxo-1-pentanol;

[0006] (2) Adding the aqueous hydrochloric acid solution obtained in step (1) to compound (III) 3-chloro-4-oxo-1-pentanol, and then adding hydrochloric acid, to react to obtain compound (I) 3,5-dichloro-2-pentanone.

[0007] Wherein, in step (1), the molar ratio of the reaction raw materials α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:1.5-3.5:1.5-4.

[0008] Preferably, the molar ratio of α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:1.5-2.5:1.5-2.5.

[0009] In the step (1), α-acetyl-γ-butyrolactone (II) is used as a raw material and reacts with hypochlorite and hydrochloric acid at a reaction temperature of -20 to 40° C. and a reaction time of 1 to 10 hours.

[0010] Preferably, the reaction temperature is -10 to 30°C, and the reaction time is 4 to 8 hours.

[0011] In which, in step (1), sampling and analysis show that the content of α-acetyl-γ-butyrolactone (II) is ≤1%, the reaction solution is heated to a temperature of 60 to 110° C. and the reaction time is 1 to 4 hours.

[0012] Preferably, the reaction temperature is 60 to 90° C., and the reaction time is 1 to 2 hours.

[0013] Wherein, in step (1), the hypochlorite is sodium hypochlorite or calcium hypochlorite, or a mixture of the two.

[0014] Wherein, the solvent for the reaction in step (1) is one or a mixture of benzene, toluene, xylene, dichloroethane, tetrahydrofuran, methyltetrahydrofuran, cyclohexane, methylcyclohexane, water.

[0015] In the step (1), a hydrogen chloride tail gas absorption device is used, and α-acetyl-γ-butyrolactone (II) is used as a raw material to react with hypochlorite and hydrochloric acid. Hydrogen chloride gas will escape from the reaction solution and be absorbed by measured water. The obtained dilute hydrochloric acid aqueous solution can be directly used in the step (2), wherein all the hydrogen chloride recovered in the step (1) is added to the step (2).

[0016] Wherein, in step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:0.8-3.

[0017] Preferably, the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:1 to 1.5.

[0018] Wherein, in step (2), the reaction temperature is 80-120° C., and the reaction time is 6-14 hours.

[0019] Preferably, the reaction temperature in step (2) is 85-105° C., and the reaction time is 8-10 hours.

[0020] 3,5-dichloro-2-pentanone prepared by the preparation method of the present invention.

[0021] Preferably, the preparation method of the present invention is:

[0022] 1) using α-acetyl-γ-butyrolactone (II) as a raw material, reacting with hypochlorite and hydrochloric acid at -10 to 30°C, absorbing the generated hydrogen chloride gas with water, and using the obtained dilute hydrochloric acid aqueous solution in step 2); after the reaction of α-acetyl-γ-butyrolactone (II) is completed, heating to 60 to 90°C, releasing carbon dioxide gas, and after the reaction is completed, separating the organic layer, i.e., a solution of compound (III) 3-chloro-4-oxo-1-pentanol;

[0023] 2) Adding the dilute hydrochloric acid aqueous solution obtained in step 1) to the organic phase of compound (III) obtained in step 1), and then adding a measured amount of hydrochloric acid, the molar ratio of the added hydrochloric acid to α-acetyl-γ-butyrolactone (II) being 1 to 1.5:1, heating to 85 to 105° C., reacting for 8 to 10 hours, letting the reaction solution stand to separate the water layer, washing the organic phase with a sodium carbonate aqueous solution, and distilling to remove the solvent to obtain compound (I)

[0024] The reaction equation is as follows:

[0025]

[0026] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0027] The invention provides a new method for preparing 3,5-dichloro-2-pentanone (I), an intermediate of prothioconazole. Different raw materials are used, hypochlorite and hydrochloric acid are used instead of irritating reagent sulfonyl chloride, so that sulfur dioxide gas can be avoided from being generated by the reaction. According to the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization, sulfur dioxide belongs to Class 3 carcinogens, and corrosion to equipment can be reduced. The reaction is carried out at low temperature with the participation of water, so that the loss of hydrogen chloride gas is effectively reduced. Hydrogen chloride is captured by tail gas, so the amount of hydrochloric acid used in subsequent steps can be reduced, and the discharge of three wastes can be effectively reduced. Since inorganic salts are generated in the reaction of sodium hypochlorite and hydrochloric acid, the separation and recovery of organic products are more conducive. The method has easy-to-obtain raw materials, mild reaction conditions, simple and efficient process, economic feasibility, continuous operation, no need to take out intermediate products separately, simplified operation, shortened construction period, improved production capacity, and can be completed in one pot, so as to be suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 : is the NMR spectrum of the product prepared in Example. DETAILED DESCRIPTION

[0029] The technical solution of the present invention is described clearly and completely below in conjunction with the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention.

[0030] The experimental methods described in the examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0031] Example 1

[0032] Connect the hydrogen chloride tail gas absorption system at the reactor vent, open the hydrogen chloride tail gas absorption system, put 592g of 1mol sodium hypochlorite aqueous solution, 0.5mol α-acetyl-γ-butyrolactone and 100g toluene into the reaction bottle, cool to 10°C, drip 105g of 1mol hydrochloric acid, drip it within 2 hours, keep warm at 10°C for 3 hours (at this time, the content of α-acetyl-γ-butyrolactone (II) is ≤1%), heat to 80°C, keep warm for 1.5 hours, add hydrogen chloride absorption liquid, add 62.5g of 0.6mol hydrochloric acid, heat to 90°C, keep warm for 8 hours, let stand, separate the water layer, wash the organic phase with sodium carbonate aqueous solution, distill to remove toluene, and obtain the target product 3,5-dichloro-2-pentanone 75.5g, content 95.6%. Pale yellow liquid, bp.208.1°C (760mmHg), NMR spectrum see Figure 1 .

[0033] 1H NMR(CDCl3,400MHz)δ:2.382.(3H,s,CH3),2.167-2.283(2H,m,CH2),3.713-3.728(2H,t,CH2),4.486-4.543(H,m,CH)

[0034] Example 2

[0035] A hydrogen chloride tail gas absorption system was connected to the vent of the reactor, the hydrogen chloride tail gas absorption system was opened, 183 g of 0.8 mol of calcium hypochlorite, 0.5 mol of α-acetyl-γ-butyrolactone and 200 g of water were added to the reaction bottle, the temperature was lowered to 15° C., 115 g of 1.1 mol of hydrochloric acid was added dropwise, and the addition was completed within 2.5 hours. After the addition was completed, the temperature was kept at 15° C. for 3.5 hours (at this time, the content of α-acetyl-γ-butyrolactone (II) was ≤1%), the temperature was raised to 70° C., the temperature was kept for 1.5 hours, hydrogen chloride absorption liquid was added, 52 g of 0.5 mol of hydrochloric acid was added, the temperature was raised to 100° C., the temperature was kept for 8 hours, the reaction mixture was allowed to stand, the water layer was separated, the organic phase was washed with an aqueous sodium carbonate solution, and then dried with anhydrous sodium chloride to obtain 75.2 g of the target product 3,5-dichloro-2-pentanone with a content of 96.7%.

[0036] Example 3

[0037] The preparation method of Example 3 is the same as that of Example 1, except that: in step (1), the molar ratio of α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:1.5:1.5, the early reaction temperature is -20°C, and the reaction time is 10 hours; the late reaction temperature is 60°C; the reaction time is 4 hours; and the reaction solvent is benzene.

[0038] In step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:0.8; the reaction temperature is 80° C.; and the reaction time is 14 hours.

[0039] Example 4

[0040] The preparation method of Example 4 is the same as that of Example 1, except that: in step (1), the molar ratio of α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:3.5:4; the early reaction temperature is 40° C. and the reaction time is 1 hour; the late reaction temperature is 110° C. and the reaction time is 1 hour; and the reaction solvent is xylene.

[0041] In step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:3; the reaction temperature is 120° C., and the reaction time is 6 hours.

[0042] Example 5

[0043] The preparation method of Example 5 is the same as that of Example 1, except that: in step (1), the molar ratio of α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:2.5:2.5; the initial reaction temperature is 10° C.; the reaction time is 8 hours; the later reaction temperature is 60° C., and the reaction time is 2 hours; and the reaction solvent is ethylene dichloride.

[0044] In step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:1, the reaction temperature is 85° C., and the reaction time is 10 hours.

[0045] Example 6

[0046] The preparation method of Example 6 is the same as that of Example 1, except that: in step (1), the molar ratio of α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:1.5:2.5; the initial reaction temperature is 30°C and the reaction time is 4 hours; the later reaction temperature is 90°C and the reaction time is 1 hour; and the reaction solvent is tetrahydrofuran.

[0047] In step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:1.5; the reaction temperature is 105° C., and the reaction time is 8 hours.

Claims

1. A method for preparing the compound 3,5-dichloro-2-pentanone, characterized in that: The following steps are involved: (1) Using α-acetyl-γ-butyrolactone (II) as a raw material, reacting with hypochlorite and hydrochloric acid, and absorbing the generated hydrogen chloride gas with water to obtain a dilute hydrochloric acid aqueous solution. After the reaction, sampling and analysis are performed. When the content of α-acetyl-γ-butyrolactone (II) is ≤1%, the reaction solution is heated and the reaction is continued to generate compound (III) 3-chloro-4-oxo-1-pentanol; (2) adding the dilute hydrochloric acid aqueous solution obtained in step (1) to compound (III) 3-chloro-4-oxo-1-pentanol, and then adding hydrochloric acid to react to obtain compound (I) 3,5-dichloro-2-pentanone; the reaction is a one-pot process; In step (1), the molar ratio of the reaction raw materials α-acetyl-γ-butyrolactone (II), hypochlorite and hydrochloric acid is 1:1.5~3.5:1.5~4; Step (1) α-acetyl-γ-butyrolactone (II) is used as a raw material, reacted with hypochlorite and hydrochloric acid, the reaction temperature is -20 to 15°C, and the reaction time is 1 to 10 hours; In step (1), the hypochlorite is sodium hypochlorite or calcium hypochlorite, or a mixture of the two; α-acetyl-γ-butyrolactone (II) ≤ 1%, the reaction solution is heated to a temperature of 60-110° C., and the reaction time is 1-4 hours; In step (2), the molar ratio of α-acetyl-γ-butyrolactone (II) to the added hydrochloric acid is 1:0.8-3; in step (2), the reaction temperature is 80-120° C., and the reaction time is 6-14 hours.

2. The preparation method according to claim 1, characterized in that: The solvent for the reaction in step (1) is one or a mixture of benzene, toluene, xylene, dichloroethane, tetrahydrofuran, methyltetrahydrofuran, cyclohexane, methylcyclohexane, water.

3. The preparation method according to claim 1, characterized in that: In step (1), a hydrogen chloride tail gas absorption device is used to react α-acetyl-γ-butyrolactone (II) with hypochlorite and hydrochloric acid as a raw material. Hydrogen chloride gas will escape from the reaction solution and be absorbed by measured water. The obtained dilute hydrochloric acid aqueous solution can be directly used in step (2).

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