JP7227711B2 - Method for producing 2-(2-haloethyl)-1,3-dioxolane - Google Patents

Description

The present invention relates to a method for producing 2-(2-haloethyl)-1,3-dioxolane, which is useful as an intermediate for pharmaceuticals, agricultural chemicals, etc., or as a starting material for polymers.

Patent Document 1 discloses a method for producing 2-(2-chloroethyl)-1,3-dioxolane from acrolein, ethylene glycol and hydrogen chloride. , Appropriate management and suitable facilities are required.

Non-Patent Document 1 describes 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 remains at 55%. In addition, this method requires the use of an excessive amount of expensive trimethylsilyl chloride, which is not only undesirable from a cost standpoint, but also inevitably generates wastewater containing trimethylsilyl chloride and its derivatives. I don't like it either.

When 2-(2-haloethyl)-1,3-dioxolane is used industrially, it is desirable to have high purity, but 2-(2-bromoethyl)-1,3-dioxolane has low stability, Since decomposition occurs during purification by distillation and the yield decreases, it is difficult to obtain the desired product with high yield and high purity. On the other hand, 2-(2-chloroethyl)-1,3-dioxolane is stable during distillation purification, and it is easy to obtain a highly pure target product, and in industrial production, 2-(2-bromoethyl)-1 , 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 small environmental load, does not require appropriate management or suitable equipment, etc., and can be obtained from easily available commercially available raw materials. An object of the present invention is to provide a method for producing -(2-chloroethyl)-1,3-dioxolane.

The inventors of the present invention conducted studies to solve the above problems, and found that 2-(2-haloethyl)-1,3-dioxolane was selected from commercially available 2-vinyl-1,3-dioxolane, The inventors have found a highly selective, high-yield and cost-effective production method, and completed the present invention.

Thus, the present invention provides a compound of formula (I):

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

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

According to the method of the present invention, 2-(2-haloethyl)-1,3-dioxolane (compound (II)), which is useful as an intermediate for pharmaceuticals, agricultural chemicals, etc. and as a starting material for polymers, can be produced with high selectivity and high yield. and can be manufactured cost effectively.

The method of the present invention is a method for producing compound (II), characterized by reacting compound (I) 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 introduced in a β-selective manner.

[Wherein, X is as described above]

Compound (I) can be a commercially available product, but can also be produced by a method known in the art.

As used herein, a halogen atom represents a chlorine atom, a bromine atom, or an iodine atom. Hydrogen halide may be selected from hydrogen chloride, hydrogen bromide or hydrogen iodide depending on 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 it in a solvent to be described later. As the hydrogen halide gas, a dry one is preferable.

The amount of hydrogen halide to be used cannot be unconditionally defined due to differences in reaction conditions, etc., but it is usually 1 to 10 mol, preferably 1 to 2 mol, more preferably 1 to 1 .2 mol. Amounts outside this range may be used depending on the reaction conditions.

The method of the 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 solvents 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, t-butyl ether solvents such as methyl ether, tetrahydrofuran, 1,4-dioxane, 1,3-dioxane; and mixed solvents of one or more of these. Solvents other than those mentioned above may be used as long as they do not adversely affect the reaction.

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

The reaction mode of the method of the present invention may be either a batch system or a continuous system. The order of mixing raw materials when the reaction is carried out in batch mode is not particularly limited, but for example, (1) compound (I) or a solution thereof is added to a solution of hydrogen halide gas, (2) compound (I) Alternatively, a hydrogen halide gas or a solution thereof may be added to the solution. Moreover, the addition of the raw material may be performed at once or dividedly, or may be added continuously.

The reaction temperature and reaction time in the method of the present invention vary depending on the reaction conditions and the like, and cannot be categorically defined. ° C., and the reaction time is usually about 10 minutes to 48 hours, preferably about 30 minutes to 12 hours, more preferably about 30 minutes to 1 hour.

After completion of the reaction, compound (II) can be isolated and purified by post-treatment such as neutralization, extraction, washing, drying, distillation, and the like, if necessary. For example, when the reaction mixture obtained by the reaction of compound (I) and hydrogen halide contains unreacted hydrogen halide, a base (e.g., sodium carbonate, potassium carbonate, carbonate such as cesium carbonate, hydrogen carbonate sodium, hydrogen carbonate such as potassium hydrogen carbonate, hydroxide such as sodium hydroxide, potassium hydroxide), or by introducing an inert gas such as nitrogen, argon, etc. 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 removing, if necessary, unreacted hydrogen halide from the reaction mixture obtained after the completion of the reaction, 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):

with a hydrogen halide in the presence of a solvent;
(2) removing unreacted hydrogen halide from the reaction mixture obtained in (1);
Formula (II), comprising:

[Wherein, X is a halogen atom]
A method for producing a compound of

[B] (1) Formula (I):

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 method for preparing a compound of formula (II), comprising

[C] (1) Formula (I):

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 method for preparing a compound of formula (II), comprising

From the viewpoint of reducing the environmental load, it is more preferable to remove unreacted hydrogen halide by introducing an inert gas (nitrogen, argon, etc.) into the reaction mixture without generating wastewater due to neutralization. In this case, the inert gas may be introduced by a method known to those skilled in the art. This can be done by bubbling to

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

Various components in the method of the present invention can be appropriately selected from the multiple examples and conditions described above, and can be combined with each other. That is, the type, mode of use, or amount of use of compound (I), hydrogen halide, and solvent; reaction temperature; reaction time; and conditions, and can be 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):

A 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 a compound of
[2] The method according to [1] above, 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 aromatic hydrocarbon solvents, halogenated hydrocarbon solvents, and ether solvents. 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] above, 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 resulting reaction mixture.
[7] The method according to [6] above, wherein the inert gas is nitrogen.
[8] The method according to any one of the above [1] to [7], further comprising purifying the compound of formula (II) by distillation.

Examples of the present invention will be described below, but the present invention should not be construed as being limited to these.

Example 1
238 g of dichloromethane was added to a 500 ml four-necked flask and cooled to 5° C. with ice water. 19 g of hydrogen chloride gas was introduced, and then 36.4 g of a 27.5% 2-vinyl-1,3-dioxolane solution in dichloromethane was added dropwise over 30 minutes. After stirring at the same temperature for 2 hours, 4 g of hydrogen chloride gas was additionally introduced, and the mixture was further stirred for 1 hour. After the reaction solution was neutralized with a 10% aqueous sodium carbonate solution, the layers were separated, and the organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting concentrate was purified by vacuum distillation (65 hPa, bath temperature 110° C.) to give 6.0 g of 2-(2-chloroethyl)-1,3-dioxolane (yield: 44%), purity 99.0%. I got it in
The NMR spectrum data of the obtained 2-(2-chloroethyl)-1,3-dioxolane were 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
40 g of 95.3% 2-vinyl-1,3-dioxolane and 40 g of toluene were added to a 100 ml four-necked flask and cooled to 5° C. with ice water. 16.7 g of hydrogen chloride gas was introduced at 10° C. to 20° C. over 30 minutes, followed by stirring for 30 minutes. At 20° C. or lower, the reaction solution was neutralized with 1.5 volumes of 10% sodium carbonate aqueous solution, and the organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The resulting filtrate was distilled under reduced pressure (65 hPa, overhead temperature 88° C.) to obtain 38.2 g (yield: 71%) of 2-(2-chloroethyl)-1,3-dioxolane with a purity of 96.6%. rice field.

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. 8.15 g of hydrogen chloride gas was introduced at 10° C. to 20° C. over 30 minutes, followed by stirring for 1 hour (pH 2 to 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, overhead temperature 88° C.) to obtain 19.1 g (yield: 73%) of 2-(2-chloroethyl)-1,3-dioxolane with a purity of 96.8%. rice field.

Example 4
40 g of 96.3% 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. 16.8 g of hydrogen chloride gas was introduced at 12° C. to 20° C. over 45 minutes, followed by stirring 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, overhead temperature 88° C.) to obtain 41.1 g (yield: 77%) of 2-(2-chloroethyl)-1,3-dioxolane with a purity of 98.8%. rice field.

Claims (8)

- in a solution of hydrogen halide gas,
Formula (I):

adding a compound of or a solution thereof,
- adding a solution of hydrogen halide gas to the compound of formula (I) or a solution thereof, or
- adding a hydrogen halide gas to the solution of the compound of formula (I), and
thereby reacting said compound of formula (I) with a hydrogen halide in the presence of a solvent of said solution of said compound of formula (I) and/or said solution of hydrogen halide gas ,
Formula (II):

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