JP2019031485A - Manufacturing method of 2-(2-haloethyl)-1,3-dioxolane - Google Patents

Abstract

To provide a method for manufacturing 2-(2-haloethyl)-1,3-dioxolane from a commercially available raw material which can be easily obtained, without need for proper management or facility adapted thereto or the like.SOLUTION: There is provided a method of manufacturing a compound of the formula (II) by reacting a compound of the formula (I) with a hydrogen halide in a presence of a solvent.0012: X is a halogen atom.SELECTED DRAWING: None

Description

  The present invention relates to a method for producing 2- (2-haloethyl) -1,3-dioxolane, which is useful as a raw material for intermediates and polymers such as pharmaceuticals and agricultural chemicals.

  Patent Document 1 discloses a method for producing 2- (2-chloroethyl) -1,3-dioxolane from acrolein, ethylene glycol and hydrogen chloride. In the handling of acrolein used as a raw material in this method, Appropriate management and appropriate equipment are necessary.

  Non-Patent Document 1 discloses a method for producing 2- (2-bromoethyl) -1,3-dioxolane from readily available 2-vinyl-1,3-dioxolane using trimethylsilyl chloride and sodium bromide. Is disclosed, but the yield is only 55%. In addition, since this method requires the use of an excessive amount of expensive trimethylsilyl chloride, it is not preferable from a cost standpoint, and generation of waste water containing trimethylsilyl chloride and its derivatives is inevitable, so from the viewpoint of green chemistry. Is also not preferred.

  When 2- (2-haloethyl) -1,3-dioxolane is used industrially, high purity is desirable, but 2- (2-bromoethyl) -1,3-dioxolane has low stability, Since decomposition occurs during distillation purification and the yield decreases, it is difficult to obtain a high yield and high purity target product. On the other hand, 2- (2-chloroethyl) -1,3-dioxolane is stable during distillation purification, and it is easy to obtain a high-purity target product. In industrial production, 2- (2-bromoethyl) -1 This is superior to 3-dioxolane. However, there is no known method for producing 2- (2-chloroethyl) -1,3-dioxolane from 2-vinyl-1,3-dioxolane which is inexpensive and readily available.

U.S. Pat. No. 2,432,601

Synthetic Communications, 15 (2), 87-89, 1985

  The present invention has a low environmental impact, does not require appropriate management, equipment suitable for it, and the like, and can be easily obtained from commercially available raw materials by using 2- (2-haloethyl) -1,3-dioxolane, particularly 2 The object is to provide a process for producing-(2-chloroethyl) -1,3-dioxolane.

  As a result of studies to solve the above-mentioned problems, the present inventors have obtained 2- (2-haloethyl) -1,3-dioxolane from 2-vinyl-1,3-dioxolane available as a commercial product, The present invention has been completed by finding a method for producing a product with high selectivity, high yield and cost efficiency.

  That is, the present invention relates to the formula (I):

A compound of formula (II): wherein compound (hereinafter also referred to as compound (I)) is reacted with hydrogen halide in the presence of a solvent:

[Wherein X is a halogen atom]
A method for producing the compound (hereinafter also referred to as compound (II)) (hereinafter also referred to as the method of the present invention) is provided.

  According to the method of the present invention, 2- (2-haloethyl) -1,3-dioxolane (compound (II)), which is useful as a raw material for intermediates and polymers of pharmaceuticals, agricultural chemicals, and the like, is highly selective and has a high yield. And it can manufacture cost-effectively.

  The method of the present invention is a method for producing compound (II), characterized in that compound (I) is reacted with hydrogen halide in the presence of a solvent, as shown in the following reaction formula. According to the method of the present invention, halogen is selectively introduced at the β-position.

[Wherein X is as described above]

  Although a commercial item can be used for compound (I), it can also be manufactured by a well-known method in this field | area.

  In this specification, a halogen atom shows a chlorine atom, a bromine atom, or an iodine atom. As the hydrogen halide, any one of hydrogen chloride, hydrogen bromide or hydrogen iodide may be selected according to the desired compound (II). The hydrogen halide may be used as a gas as it is, or may be used as a solution obtained by dissolving in a solvent described later. The hydrogen halide gas is preferably dried.

  The amount of hydrogen halide to be used cannot be generally specified due to differences in reaction conditions and the like, but is usually 1 to 10 mol, preferably 1 to 2 mol, more preferably 1 to 1 mol per 1 mol of compound (I). .2 moles. Depending on the reaction conditions, amounts outside this range may be used.

  The process of the present invention is usually carried out in the presence of a solvent. Any solvent may be used as long as it does not adversely affect the reaction. Examples of the solvent include aromatic hydrocarbon solvents such as benzene, toluene and xylene; halogenated hydrocarbon solvents such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride and chlorobenzene; diethyl ether and t-butyl. Examples include ether solvents such as methyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxane; and one or more mixed solvents thereof. Solvents other than those described above may be used as long as they do not adversely affect the reaction.

  Although the amount of the solvent used cannot be defined unconditionally due to differences in the amount of raw materials used, the type of solvent, the reaction conditions, etc., it is usually 1 to 10 times the volume of the compound (I).

  The reaction form of the method of the present invention may be either batch type or continuous type. The order of mixing the raw materials in the case of performing the reaction in a batch system is not particularly limited. For example, (1) Compound (I) or a solution thereof is added to a solution of hydrogen halide gas. (2) Compound (I) Alternatively, hydrogen halide gas or a solution thereof may be added to the solution. Moreover, addition of a raw material may be performed at once or divided | segmented, and you may add continuously.

  The reaction temperature and reaction time in the method of the present invention vary depending on the reaction conditions and cannot be generally specified, but the reaction temperature is usually about -78 to 100 ° C, preferably about 0 to 50 ° C, more preferably 0 to 30. The reaction time is usually about 10 minutes to 48 hours, preferably about 30 minutes to 12 hours, and more preferably about 30 minutes to 1 hour.

  After completion of the reaction, the compound (II) can be isolated and purified by performing post-treatment by a conventional method such as neutralization, extraction, washing, drying, distillation and the like, if necessary. For example, when unreacted hydrogen halide is contained in the reaction mixture obtained by the reaction of compound (I) with hydrogen halide, a base (for example, carbonate such as sodium carbonate, potassium carbonate, cesium carbonate, hydrogen carbonate) By neutralizing with an aqueous solution of a hydrogen carbonate such as sodium or potassium hydrogen carbonate or a hydroxide such as sodium hydroxide or potassium hydroxide, or by introducing an inert gas such as nitrogen or argon into the reaction mixture. Can be removed and then purified, for example, by distillation, to give the desired compound (II).

  As a particularly preferred embodiment of the present invention, the method of the present invention comprises, after completion of the reaction, if necessary, removing unreacted hydrogen halide from the reaction mixture and / or removing the compound ( Further comprising purifying II). More specifically, the present invention also includes the following methods [A] to [C].

[A] (1) Formula (I):

Reacting with a hydrogen halide in the presence of a solvent;
(2) removing unreacted hydrogen halide from the reaction mixture obtained in (1);
Including formula (II):

[Wherein X is a halogen atom]
A method for producing the compound.

[B] (1) Formula (I):

Reacting with a hydrogen halide in the presence of a solvent;
(2) From the reaction mixture obtained in (1), formula (II):

[Wherein X is a halogen atom]
Purifying the compound of
A process for producing a compound of formula (II) comprising:

[C] (1) Formula (I):

Reacting with a hydrogen halide in the presence of a solvent;
(2) removing unreacted hydrogen halide from the reaction mixture obtained in (1);
(3) From the reaction mixture obtained in (2), formula (II):

[Wherein X is a halogen atom]
Purifying the compound of
A process for producing a compound of formula (II) comprising:

  From the viewpoint of reducing the environmental load, it is more preferable to remove the unreacted hydrogen halide by introducing an inert gas (nitrogen, argon, etc.) into the reaction mixture without generating waste water due to neutralization. In this case, the inert gas may be introduced by a method known to those skilled in the art. For example, the inert gas (nitrogen, argon, etc.) is added to the reaction mixture until the pH of the reaction mixture reaches about 3 to 5. Can be done by bubbling.

  The purification of compound (II) is preferably performed by distillation. In this case, purification by distillation of the compound (II) may be carried out by a method known to those skilled in the art, for example, under reduced pressure (about 30 to 80 hpa) at a tower top temperature of about 70 to 100 ° C. it can.

  Various components in the method of the present invention can be appropriately selected from the plurality of examples and conditions described above, and can be combined with each other. That is, each type, use form, or use amount of compound (I), hydrogen halide, and solvent; reaction temperature; reaction time; operation; and the like are examples of normal ranges and conditions described above, and examples of preferred ranges. And can be appropriately selected from the conditions and combined with each other.

Examples of preferred embodiments of the present invention are listed below, but the present invention is not limited to these.
[1] Formula (I):

The compound of formula (II) is reacted with a hydrogen halide in the presence of a solvent:

[Wherein X is a halogen atom]
A method for producing the compound.
[2] The method according to [1], wherein X is a chlorine atom.
[3] The above [1] or [2], wherein the solvent is one or more selected from the group consisting of an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, and an ether solvent. the method of.
[4] The method according to any one of [1] to [3], further comprising neutralizing the obtained reaction mixture with a base.
[5] The method according to [4], wherein the neutralization temperature is 0 to 10 ° C.
[6] The method according to any one of [1] to [3], further comprising introducing an inert gas into the obtained reaction mixture.
[7] The method according to [6], wherein the inert gas is nitrogen.
[8] The method according to any one of [1] to [7], further comprising purifying the compound of formula (II) by distillation.

  Next, examples of the present invention will be described, but the present invention should not be construed as being limited thereto.

Example 1
To a 500 ml four-necked flask, 238 g of dichloromethane was added and cooled to 5 ° C. with ice water. 19 g of hydrogen chloride gas was introduced, and then 36.4 g of 27.5% 2-vinyl-1,3-dioxolane in dichloromethane was added dropwise over 30 minutes. After stirring at the same temperature for 2 hours, an additional 4 g of hydrogen chloride gas was introduced, and the mixture was further stirred for 1 hour. The reaction solution was neutralized with 10% aqueous sodium carbonate solution and then separated, and the organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The obtained concentrated liquid was purified by distillation under reduced pressure (65 hPa, bath temperature 110 ° C.), 6.0 g (yield: 44%) of 2- (2-chloroethyl) -1,3-dioxolane, purity 99.0%. Got in.
The NMR spectrum data of the obtained 2- (2-chloroethyl) -1,3-dioxolane was as follows.
1H-NMR (CD ₃ Cl) δ 5.04 (t, J = 5.0 Hz, 1H), 4.00-3.95 (m, 2H), 3.90-3.85 (m, 2H), 3.65 (t, J = 6.5 Hz, 2H) , 2.14 (dt, J = 6.5, 5.0 Hz, 2H).

Example 2
To a 100 ml four-necked flask, 40 g of 95.3% 2-vinyl-1,3-dioxolane and 40 g of toluene were added and cooled to 5 ° C. with ice water. Hydrogen chloride gas 16.7g was introduce | transduced over 30 minutes under 10 to 20 degreeC, and it stirred for 30 minutes after that. At 20 ° C. or lower, the reaction solution was neutralized with a 1.5-fold volume of 10% aqueous sodium carbonate solution, and the organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The obtained filtrate was distilled under reduced pressure (65 hPa, top temperature 88 ° C.) to obtain 38.2 g (yield: 71%) of 2- (2-chloroethyl) -1,3-dioxolane with a purity of 96.6%. It was.

Example 3
20 g of 93.3% 2-vinyl-1,3-dioxolane and 20 g of toluene were added to a 100 ml four-necked flask and cooled to 5 ° C. with ice water. Hydrogen chloride gas 8.15g was introduce | transduced over 30 minutes under 10 to 20 degreeC, and it stirred after that for 1 hour (pH 2-3). Nitrogen gas was bubbled through the reaction solution for 1 hour (pH 3-4). The resulting solution was distilled under reduced pressure (65 hPa, top temperature 88 ° C.) to obtain 19.1 g (yield: 73%) of 2- (2-chloroethyl) -1,3-dioxolane with a purity of 96.8%. It was.

Example 4
To a 100 ml four-necked flask, 96.3% 2-vinyl-1,3-dioxolane (40 g) and toluene (20 g) were added and cooled to 5 ° C. with ice water. 16.8 g of hydrogen chloride gas was introduced at 12 ° C. to 20 ° C. over 45 minutes, and then stirred for 1 hour (pH 2). Nitrogen gas was bubbled through the reaction solution for 1 hour (pH 4). The resulting solution was distilled under reduced pressure (65 hPa, head temperature 88 ° C.) to obtain 41.1 g (yield: 77%) of 2- (2-chloroethyl) -1,3-dioxolane with a purity of 98.8%. It was.

Claims (8)

Formula (I):

The compound of formula (II) is reacted with a hydrogen halide in the presence of a solvent:

[Wherein X is a halogen atom]
A method for producing the compound.   The method according to claim 1, wherein X is a chlorine atom.   The method according to claim 1 or 2, wherein the solvent is one or more selected from the group consisting of an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, and an ether solvent.   The process according to any one of claims 1 to 3, further comprising neutralizing the resulting reaction mixture with a base.   The method of Claim 4 whose neutralization temperature is 0-10 degreeC.   The method according to claim 1, further comprising introducing an inert gas into the obtained reaction mixture.   The method of claim 6, wherein the inert gas is nitrogen.   8. A process according to any of claims 1 to 7, further comprising purifying the compound of formula (II) by distillation.