WO2024146006A1 - Preparation method and purification method for 2,2-dichloropropane - Google Patents

Abstract

Provided in the present invention are a preparation method and a purification method for 2,2-dichloropropane. The preparation method comprises: taking acetone and phosphorus pentachloride as substrates, and subjecting same to a chlorination reaction under the catalysis of an acid catalyst, so as to prepare 2,2-dichloropropane, wherein the acid catalyst comprises one or more of an alkali metal halide, an alkaline earth metal halide, boron halide, silicon halide, an aluminum salt, a ferric salt, a copper salt, a zinc salt, a titanium salt, a tin salt, a bismuth salt, an organosilicon halide, an acyl chloride or a protonic acid. The methods can solve the problem of there being difficulties in realizing scaled-up production of 2,2-dichloropropane in the prior art, and are applicable to the field of synthesis of 2,2-dichloropropane.

Description

Preparation method and purification method of 2,2-dichloropropane

This application is based on the Chinese application with application number CN202310000562.5 and application date January 3, 2023, and claims its priority. The disclosed content of the CN application is again introduced as a whole into this application.

Technical Field

The invention relates to the field of synthesis of 2,2-dichloropropane, and in particular to a preparation method and a purification method of 2,2-dichloropropane.

Background technique

Simmons-Smith cyclopropanation reaction is a very efficient reaction for preparing cyclopropane. Cyclopropane groups are mostly present in natural products, synthetic compounds, and pharmaceuticals that have physiological activity. Even now, the development of efficient cyclopropanation reactions is in great demand. The reaction of cyclopropanation of olefins with dihalomethanes is very extensive, but there are few reports on the preparation of geminal dimethyl substituted cyclopropane compounds using 2,2-dihalopropanes. One of the reasons is that the current commercially available 2,2-dihalopropanes, such as 2,2-dichloropropane, have high cost prices, high difficulty coefficients in the preparation process, and high risk coefficients. In the prior art, there are few reports on the synthesis of 2,2-dichloropropane.

Scheme 1: Marc Tordeux et al. (J. Org. Chem. 1993, 58, 1939-1940) reported in 1993 that dimethyloxime was chlorinated with chlorine and then hydrogen chloride was added to obtain the target product with a yield of 40%. The system contained chlorinated impurities at other positions, which were difficult to separate. The starting materials of this synthesis process were not bulk products, and the raw materials used were not easy to obtain, resulting in a difficult supply chain. In addition, chlorine and hydrogen chloride gases were used in the process, which increased the difficulty of equipment materials and production control. The production control difficulty coefficient was high and there were certain safety risks. This scheme was not suitable for scale-up.

Scheme 2: Griesbaum, K et al. (Chemische Berichte, 1973, vol. 106, p. 2001-2008) used hydrogen chloride and propyne for an addition reaction to obtain 2,2-dichloropropane, but a four-membered ring by-product was generated, which was difficult to separate, and the safety risk was high during the use of propyne.

Scheme 3: Kharasch et al. (Journal of Organic Chemistry, 1939, vol. 4, p. 431-434) used 2-chloropropene to react with hydrogen chloride under ferric chloride catalysis to obtain the target product. The operation is relatively simple, but 2-chloropropene is not available in bulk.

Scheme 4: A.T.MORSE et al. (Journal of Organic Chemistry, 1958, vol.23, p.990-994) reported the use of acetone and phosphorus pentachloride for a solvent-free solid-liquid two-phase reaction. The risk of scale-up is high. The reaction mainly produces 2-chloropropene and 2,2-dichloropropane as the main by-product, resulting in a very low yield of 2,2-dichloropropane, with a separation yield of less than 25%. The product separation is difficult and has no value for commercial scale-up production.

Therefore, the above four solutions in the prior art are all difficult to solve the problem of large-scale production of 2,2-dichloropropane.

Summary of the invention

The main purpose of the present invention is to provide a preparation method and a purification method of 2,2-dichloropropane, so as to solve the problem that 2,2-dichloropropane is difficult to scale up in production in the prior art.

In order to achieve the above object, according to a first aspect of the present invention, a method for preparing 2,2-dichloropropane is provided, which comprises: taking acetone and phosphorus pentachloride as substrates, carrying out a chlorination reaction under the catalysis of an acid catalyst to prepare 2,2-dichloropropane; the acid catalyst comprises one or more of alkali metal halides, alkaline earth metal halides, boron halides, silicon halides, aluminum salts, iron salts, copper salts, zinc salts, titanium salts, tin salts, bismuth salts, organic silicon halides, acyl chlorides or protonic acids.

Further, the acid catalyst preferably includes an iron salt, a zinc salt, an acid chloride or an organosilicon halide.

Further, the alkali metal halide includes lithium halide and/or sodium halide; preferably, the alkaline earth metal halide includes magnesium halide and/or calcium halide; preferably, the lithium halide includes lithium chloride and/or lithium bromide; preferably, the magnesium halide includes magnesium chloride and/or magnesium bromide; preferably, the calcium halide includes calcium chloride.

Further, the boron halide includes one or more of boron trichloride, boron trifluoride ether complex, boron tribromide or boron triiodide; preferably, the silicon halide includes silicon tetrachloride; preferably, the aluminum salt includes aluminum trichloride; preferably, the copper salt includes a divalent copper salt and/or a monovalent copper salt; preferably, the divalent copper salt includes cupric chloride; preferably, the monovalent copper salt includes cuprous chloride; preferably, the titanium salt includes titanium tetrachloride; preferably, the tin salt includes tin tetrachloride; preferably, the bismuth salt includes bismuth trichloride; preferably, the protonic acid includes hydrogen chloride and/or an aqueous solution of hydrogen chloride.

Further, the iron salt includes a ferric salt and/or a divalent iron salt; preferably, the ferric salt includes one or more of ferric chloride, ferric chloride hydrate, ferric bromide or ferric bromide hydrate; preferably, the divalent iron salt includes ferrous chloride and/or ferrous chloride hydrate; preferably, the zinc salt includes one or more of zinc chloride, zinc chloride hydrate, zinc bromide or zinc bromide hydrate.

Further, the organosilicon halide includes halogenated silane; preferably, the halogenated silane includes chlorosilane; preferably, the chlorosilane includes one or more of trimethylchlorosilane, triethylchlorosilane or tert-butyldimethylchlorosilane; preferably, the acyl chloride includes one or more of dichlorothionyl, acetyl chloride or oxalyl chloride.

Further, the substrate reacts in a reaction solvent, and the reaction solvent includes one or more of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, anisole, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dibromoethane, n-heptane, n-hexane or N-methylpyrrolidone.

Further, the molar ratio of phosphorus pentachloride to acetone is 1-10:1; preferably, the amount of phosphorus pentoxide is 1-5:1 of the total molar amount of acetone; preferably, the molar ratio of the acid catalyst to acetone is 1%-100%:1; preferably, the amount of the acid catalyst is 5%-50% of the total molar amount of acetone.

Furthermore, the reaction temperature of the chlorination reaction is -10 to 80°C; preferably, the reaction temperature is 5 to 40°C, and more preferably 20 to 25°C.

In order to achieve the above object, according to a second aspect of the present invention, a method for purifying 2,2-dichloropropane is provided. The method comprises: purifying the 2,2-dichloropropane prepared by the above preparation method by a distillation method.

By applying the technical scheme of the present invention, acetone and phosphorus pentachloride are used as substrates, and a chlorination reaction occurs under the action of an acid catalyst to prepare 2,2-dichloropropane. The reaction raw materials are cheap and readily available, the reaction yield is high, and high-efficiency and low-cost 2,2-dichloropropane can be enlarged for production.

Detailed ways

It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.

As mentioned in the background art, although there are reports on the synthesis method of 2,2-dichloropropane in the prior art, it is difficult to scale up the production of 2,2-dichloropropane in industry due to the limitations of reaction conditions and reaction costs. Therefore, in this application, the inventors tried to use bulk chemicals acetone and phosphorus pentachloride as substrates, and through the exploration of catalysts, found a variety of acid catalysts that can play a catalytic role, which can synthesize 2,2-dichloropropane with high efficiency and yield, and are suitable for industrial production. Therefore, a series of protection schemes of this application are proposed.

In a first typical embodiment of the present application, a method for preparing 2,2-dichloropropane is provided, wherein acetone and phosphorus pentachloride are used as substrates, and a chlorination reaction occurs under the action of an acid catalyst to prepare 2,2-dichloropropane; the acid catalyst comprises one or more of an alkali metal halide, an alkaline earth metal halide, a boron halide, a silicon halide, an aluminum salt, an iron salt, a copper salt, a zinc salt, a titanium salt, a tin salt, a bismuth salt, an organosilicon halide, an acyl chloride or a protonic acid.

In the prior art, Chinese patent application CN109678651A discloses a preparation method for generating α, α-dichloroethylcyclopropane by chlorination reaction of phosphorus pentachloride and cyclopropyl methyl ketone. However, for the raw material acetone, due to the difference in substituents, the carbonyl group of acetone is more chemically stable than the carbonyl group of cyclopropyl methyl ketone, and it is difficult to react with phosphorus pentachloride. In the above-mentioned preparation method of the present application, by using acid as a catalyst, the chlorination reaction between phosphorus pentachloride and acetone, which is originally difficult to occur, can be carried out normally, thereby preparing 2,2-dichloropropane. The raw materials used in the preparation method are all bulk chemicals, with high yield and low price, making large-scale industrial production of 2,2-dichloropropane possible for the first time. The above-mentioned acid catalyst is selected in various types, and the acid in the range of pH 0.01 to 7 can catalyze the above-mentioned chlorination reaction.

In a preferred embodiment, the acid catalyst comprises one or more of alkali metal halides, alkaline earth metal halides, boron halides, silicon halides, aluminum salts, iron salts, copper salts, zinc salts, titanium salts, tin salts, bismuth salts, organosilicon halides, acyl chlorides or protonic acids; preferably, the acid catalyst comprises iron salts, zinc salts, acyl chlorides or organosilicon halides.

The acid catalyst includes a variety of metal or non-metallic halides, metal salts, silicides, acyl chlorides or acid compounds. By using one or more of the above acid catalysts, the chlorination reaction can be catalyzed, and the preparation of 2,2-dichloropropane can be completed with high yield and efficiency. The acid catalyst can accept electron pairs, thereby exerting the activity of the catalyst in the chlorination reaction and promoting the reaction.

In a preferred embodiment, the alkali metal halide comprises lithium halide and/or sodium halide; preferably, the alkaline earth metal halide comprises magnesium halide and/or calcium halide; preferably, the lithium halide comprises lithium chloride and/or lithium bromide; preferably, the magnesium halide comprises magnesium chloride and/or magnesium bromide; preferably, the calcium halide comprises calcium chloride.

In a preferred embodiment, the boron halide includes one or more of boron trichloride, boron trifluoride etherate, boron tribromide or boron triiodide; preferably, the silicon halide includes silicon tetrachloride.

In a preferred embodiment, the aluminum salt comprises aluminum trichloride; preferably, the iron salt comprises a ferric salt and/or a divalent iron salt; preferably, the ferric salt comprises one or more of ferric chloride, ferric chloride hydrate, ferric bromide or ferric bromide hydrate; preferably, the divalent iron salt comprises ferrous chloride and/or ferrous chloride hydrate; preferably, the copper salt comprises a divalent cupric salt and/or a monovalent cupric salt; preferably, the divalent cupric salt comprises cupric chloride; preferably, the monovalent cupric salt comprises cuprous chloride; preferably, the zinc salt comprises one or more of zinc chloride, zinc chloride hydrate, zinc bromide or zinc bromide hydrate; preferably, the titanium salt comprises titanium tetrachloride; preferably, the tin salt comprises tin tetrachloride; preferably, the bismuth salt comprises bismuth trichloride.

In a preferred embodiment, the organosilicon halide comprises a halogenated silane; preferably, the halogenated silane comprises a chlorosilane; preferably, the chlorosilane comprises one or more of trimethylchlorosilane, triethylchlorosilane or tert-butyldimethylchlorosilane; preferably, the acyl chloride comprises one or more of dichlorothionyl, acetyl chloride or oxalyl chloride; preferably, the protonic acid comprises hydrogen chloride and/or an aqueous solution of hydrogen chloride.

In a preferred embodiment, the chlorination reaction is carried out by placing the substrate in a reaction solvent, wherein the reaction solvent includes but is not limited to tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, anisole, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, dichloromethane (DCM), chloroform, 1,2-dichloroethane, 1,2-dibromoethane, n-heptane, n-hexane or one or more of N-methylpyrrolidone.

The above reaction solvent is a commonly used solvent in chemical reactions, and can disperse phosphorus pentachloride. The use of the solvent can reduce the concentration of acetone and phosphorus pentachloride in the reaction system, prevent the direct high-concentration contact of phosphorus pentachloride solid with acetone liquid, and prevent the adverse effects such as too fast reaction rate, large amount of heat release, and generation of by-products. In addition, by dispersing the phosphorus pentachloride solid in the reaction solvent and then dropping acetone into the system, it is convenient for the operation and quantitative control of the specific reaction. The above reaction solvent also does not react with the raw materials, catalyst and reaction product, and has stable chemical properties.

In a preferred embodiment, the molar ratio of phosphorus pentachloride to acetone is 1-10:1, including but not limited to 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1; preferably, the amount of phosphorus pentoxide is 1-5:1 of the total molar amount of acetone; preferably, the molar ratio of the acid catalyst to acetone is 1%-100%:1, including but not limited to 1%:1, 2%:1, 3%:1, 5%:1, 10%:1, 20%:1, 30%:1, 40%:1, 50%:1, 60%:1, 70%:1, 80%:1, 90%:1 or 100%:1; preferably, the amount of the acid catalyst is 5%-50% of the total molar amount of acetone.

Although the reaction molar ratio of acetone to phosphorus pentachloride is 1:1 in the chlorination reaction, in the actual preparation method, by using the above molar ratio, keeping the phosphorus pentachloride equal to or in excess of acetone in the reaction system, the conversion rate of acetone can be increased and the reaction cost can be reduced. Preferably, the amount of phosphorus pentoxide used is 1 to 5:1 of the total molar amount of acetone, which can make the acetone conversion more complete. By using the above ratio of acid catalyst, the production cycle can be shortened and the production cost can be saved.

In a preferred embodiment, the reaction temperature of the chlorination reaction is -10 to 80°C; preferably, the reaction temperature is 5 to 40°C, more preferably 20 to 25°C.

In the above preparation method, the reaction temperature of the present application is appropriately adjusted according to different catalysts. By increasing or decreasing the reaction temperature, the reaction rate can also be controlled, and the reaction rate can be appropriately increased under the premise of safe production. The above preparation method can react at room temperature, which can further save reaction costs and reduce the equipment requirements required for production.

In a second typical embodiment of the present application, a method for purifying 2,2-dichloropropane is provided. The method utilizes a distillation method to purify the 2,2-dichloropropane prepared by the above preparation method.

Since the physical properties of the substrate, reaction solvent and product in the reaction system are quite different, the commonly used distillation method can be used after the reaction, such as a distillation tower and other conventional devices for separation, so as to obtain 2,2-dichloropropane with high purity. The purification cost is low, and no other reagents or fillers are introduced to prevent the introduction of exogenous impurities and affect the purification of the product. By using distillation, the reaction solvent in the above preparation method can also be separated and recovered, so as to be recycled in subsequent production, reducing production costs and pollution.

The beneficial effects of the present application will be further explained in detail below in conjunction with specific embodiments.

Example 1

At 20-25°C, add dichloromethane (5 vol., 665 kg) to a dry and clean 2000L enamel kettle, stir, add phosphorus pentachloride (1.2 eq., 430.24 kg), and control the temperature at 20-25°C. Add acid catalyst trimethylsilyl chloride (0.2 eq., 37.41 kg), acetone (1.0 eq., 100 kg) in dichloromethane (2 vol., 266 kg) solution successively, keep the temperature at 20-25°C for 20 hours after the addition, the system gradually changes from a light yellow suspension to a light yellow clear homogeneous system, and add it dropwise to purified water (5 vol., 500 kg) after the reaction, and control the temperature at 20-30°C. After quenching, separate the liquids, wash the organic phase with water once, and rectify the organic phase in a rectification tower to separate 167 kg of 2,2-dichloropropane (GC purity 99.2%, content 99%), with a separation yield of 85%. The separation yield is the yield of the high-purity target product separated from the mixture system, and the separation yield is ≤ the conversion rate.

Embodiment 2-14

The reaction steps are the same as those in Example 1, except that the reference material acetone feed amount is 10 kg (1.0 eq) and phosphorus pentachloride (1.2 eq). The data of the acid catalyst used in the example and the yield are shown in Table 1.

Table 1

Examples 15-20

The reaction steps are the same as those in Example 1, except that the solvent type in some examples is 1,2-dibromoethane (DBE), the base material acetone feed amount is 10 kg (1.0 eq), phosphorus pentachloride (1.2 eq), the reaction temperature is different, and the specific reaction conditions are shown in Table 2.

Table 2

Examples 21-24

The reaction steps are the same as those in Example 1, except that the feed amount of the reference material acetone is 10 kg (1.0 eq), and the feed ratios of the reference materials acetone and phosphorus pentoxide are different. For specific reaction conditions, see Table 3.

table 3

Embodiments 25 to 29

The reaction steps are the same as those in Example 1, except that the feed amount of the reference material acetone is 10 kg (1.0 eq), and the feed ratio of the reference material acetone and the acid catalyst is different. For specific reaction conditions, see Table 4.

Table 4

Comparative Example 1

The reaction steps are the same as those in Example 1, except that the amount of acetone added is 10 kg, and no acid catalyst is added.

7.54 kg of 2,2-dichloropropane (GC purity 99%, content 98%) was obtained, with a separation yield of 38%.

From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects: a variety of Lewis acids can be used to catalyze the reaction between acetone and phosphorus pentachloride, and the magnitude of the reaction can meet the needs of industrial production, thereby achieving industrial synthesis of 2,2-dichloropropane at a relatively low cost.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims (13)

A method for preparing 2,2-dichloropropane, characterized in that the method comprises: using acetone and phosphorus pentachloride as substrates, and carrying out a chlorination reaction under the catalysis of an acid catalyst, thereby obtaining the 2,2-dichloropropane; The acid catalyst includes one or more of alkali metal halides, alkaline earth metal halides, boron halides, silicon halides, aluminum salts, iron salts, copper salts, zinc salts, titanium salts, tin salts, bismuth salts, organic silicon halides, acyl chlorides or protonic acids. The preparation method according to claim 1, characterized in that the alkali metal halide comprises lithium halide and/or sodium halide; The alkaline earth metal halide comprises magnesium halide and/or calcium halide; The boron halide includes one or more of boron trichloride, boron trifluoride ether complex, boron tribromide or boron triiodide; The silicon halide claimed includes silicon tetrachloride; The aluminum salt includes aluminum trichloride; The copper salt includes a divalent copper salt and/or a monovalent copper salt; The titanium salt includes titanium tetrachloride; The tin salt includes tin tetrachloride; The bismuth salt includes bismuth trichloride; The protonic acid includes hydrogen chloride and/or an aqueous solution of hydrogen chloride; The iron salt includes ferric iron salt and/or ferrous iron salt; The zinc salt includes one or more of zinc chloride, zinc chloride hydrate, zinc bromide or zinc bromide hydrate; The organosilicon halide comprises a halosilane; The acyl chloride includes one or more of thionyl chloride, acetyl chloride or oxalyl chloride. The preparation method according to claim 2, characterized in that the lithium halide comprises lithium chloride and/or lithium bromide; The magnesium halide includes magnesium chloride and/or magnesium bromide; The calcium halide includes calcium chloride; The divalent copper salt includes copper chloride, and the monovalent copper salt includes cuprous chloride; The ferric iron salt includes one or more of ferric chloride, ferric chloride hydrate, ferric bromide or ferric bromide hydrate; The divalent iron salt includes ferrous chloride and/or ferrous chloride hydrate; The halogenated silane includes chlorosilane. The preparation method according to claim 3 is characterized in that the chlorosilane includes one or more of trimethylchlorosilane, triethylchlorosilane or tert-butyldimethylchlorosilane. The preparation method according to claim 1, characterized in that the substrate is placed in a reaction solvent for the chlorination reaction, and the reaction solvent includes one or more of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, anisole, methyl tert-butyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, dichloromethane, chloroform, 1,2-dichloroethane, 1,2-dibromoethane, n-heptane, n-hexane or N-methylpyrrolidone. The preparation method according to claim 1, characterized in that the molar ratio of the phosphorus pentachloride to the acetone is 1 to 10:1. The preparation method according to claim 6, characterized in that the amount of the phosphorus pentachloride is 1 to 5:1 of the total molar amount of the acetone. The preparation method according to claim 1, characterized in that the molar ratio of the acid catalyst to the acetone is 1% to 100%:1. The preparation method according to claim 8, characterized in that the amount of the acid catalyst is 5% to 50% of the total molar amount of the acetone. The preparation method according to claim 1 is characterized in that the reaction temperature of the chlorination reaction is -10 to 80°C. The preparation method according to claim 10 is characterized in that the reaction temperature of the chlorination reaction is -5 to 40°C. The preparation method according to claim 11, characterized in that the reaction temperature of the chlorination reaction is 20-25°C. A method for purifying 2,2-dichloropropane, characterized in that the purification method comprises: purifying the 2,2-dichloropropane prepared by the preparation method according to any one of claims 1 to 12 by a distillation method.