JPH1095760A - Production of cyanoacetic ester - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for efficiently recovering higher alkyl cyanoacetate which is produced by transesterification of a lower alkyl cyanoacetate with a higher alcohol in a high yield. SOLUTION: Before fractionation of cyanoacetic higher alkyl ester represented by the general formula: NCCH2 COOR' (R' means an alkyl group of 4-20 carbon atoms) prepared by catalytic transesterification of a cyanoacetic lower alkyl ester with a higher alcohol from the reaction mixture, the reaction mixture containing the higher alkyl cyanoacetate and the catalyst is subjected to the thin-layer evaporation under reduced pressure to remove the catalyst. Thus, the cyanoacetic higher alkyl ester can be recovered in high yield and the product is readily recovered without abnormal foaming during the distillation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a higher alkyl cyanoacetate useful as an intermediate for medical and agricultural chemicals and an intermediate for industrial products. In the present invention, a cyanoacetic acid higher alkyl ester is represented by the general formula NCCH ₂ COO
R '(wherein R' represents an alkyl group having 4 to 20 carbon atoms)
Means a cyanoacetic acid ester represented by

[0002]

2. Description of the Related Art As a method for producing cyanoacetate,
A method of reacting chloroacetic acid ester with NaCN or KCN, a method of reacting cyanoacetyl halide and alcohol in the presence of a base catalyst, an alkoxycarbonylation method of reacting chloroacetonitrile with CO and alcohol, an acid catalyst with cyanoacetic acid and alcohol A method of performing a dehydration reaction in the presence and a method of subjecting a cyanoacetate to transesterification with an alcohol are generally well known.

For example, as a method for producing t-butyl cyanoacetate, t-butyl chloroacetate and NaCN or K
Method for reacting CN [DE1951032; Hel
v. Chim. Acta. , 42 , 1214, 1222
(1959); Am. Chem. Soc. , 64 ,
2274 (1942)] cyanoacetyl halide and t
-A method of reacting butanol with N, N-dimethylaniline [J. Chem. Soc. , (1955) 423
426; Org. Synth. , Coll. Vol.
5,171] and chloroacetonitrile, CO and t-
An alkoxycarbonylation method in which butanol is reacted [DE2403483] and the like are known.

[0004] However, the method of
It is not easy to obtain -butyl and the raw material must be separately synthesized by a complicated method. Further, a large amount of waste such as NaCl is produced as a by-product of the reaction. In the method (1), it is necessary to use highly corrosive PCl ₅ or the like in order to obtain a starting material, cyanoacetyl halide, which greatly restricts the material of the apparatus. Further, N, N-dimethylaniline is required in an amount equal to or greater than that of cyanoacetyl halide, and the hydrochloride is by-produced as the reaction proceeds, so that a large amount of waste is generated. In the above method, CO must be reacted at a high pressure, so that equipment is restricted.

As a method for causing a dehydration reaction between cyanoacetic acid and an alcohol in the presence of an acid catalyst, for example, Ann. Ch
im. , (Paris), 9 (9) 69 (1918);
Tetrahedron, 305 (1967). However, this method is excellent in reactivity when an alcohol having a small number of carbon atoms, particularly a primary alcohol is used, but has a drawback that the reactivity is low when a higher alcohol or a tertiary alcohol is used. Furthermore, this method is not suitable for the case where the resulting cyanoacetate is an acid-labile tertiary ester.

As a method for transesterifying a cyanoacetate with an alcohol, a method using titanium alkoxide as a catalyst is known. [Org.
Synth. , 65 , 230 (1987); Helv.
Chim. Acta. , 65 , 1197 (1982);
Helv. Chim. Acta. , 65 , 495 (19
82); Synthesis (1982), 138] However, the methods described therein are described only when a primary or secondary alcohol such as methyl alcohol, ethyl alcohol, or isopropyl alcohol is used as the alcohol. In the case of a tertiary alcohol ester such as t-butanol, it is known that the exchange reaction hardly proceeds, so that it cannot be said to be an appropriate method.

Further, a method for producing a higher alkyl cyanoacetate by a transesterification reaction using a specific tin compound from a readily available raw material without causing the above-mentioned problems is disclosed in Japanese Patent Application Laid-Open No. -22856
No. 4 can be mentioned. In the case of using this method, after the reaction, unreacted higher alcohol is removed by vacuum distillation, which is commonly used, and then the higher alkyl cyanoacetate obtained by transesterification is distilled off. Had been separated.

[0008]

However, when higher alkyl cyanoacetates are distilled in the presence of a catalyst, there is a problem that thermal decomposition and thermal polymerization due to a long-term heat history cannot be avoided. However, there is a drawback that the amount is greatly reduced. Further, when ester distillation proceeds and the catalyst concentration in the bottom becomes relatively high, the viscosity of the liquid becomes extremely high, causing abnormal foaming due to evaporation, and the distillation operation must be abandoned on the way. Was.

The present invention overcomes the drawbacks of reduced product yield due to thermal decomposition or thermal polymerization during distillation in the conventional method, and abnormal foaming, and provides a simple and efficient method for removing the catalyst from the reaction solution. The present invention has been made to provide a method for producing a higher alkyl cyanoacetic acid ester which can be produced and is industrially advantageous.

[0010]

Means for Solving the Problems The present inventors have conducted intensive studies to solve various problems during the distillation of higher alkyl cyanoacetates, and as a result, have found that a reaction solution containing higher alkyl cyanoacetates and a catalyst. The low-boiling components containing the higher alkyl cyanoacetate are instantaneously evaporated by thin-film evaporation and separated from the reaction solution containing the catalyst, thereby suppressing the thermal decomposition and thermal polymerization of the higher alkyl cyanoacetate during subsequent distillation. The present inventors have found that the separation operation can be carried out as an industrially stable separation operation, and have reached the present invention.

That is, the present invention provides a compound represented by the general formula NCCH ₂ COO
R ¹ (wherein R ¹ represents an alkyl group having 1 to 3 carbon atoms) cyanoacetate lower alkyl ester of the general formula R'OH represented by (wherein R 'represents an alkyl group having 4 to 20 carbon atoms) The general formula NCCH ₂ COOR ′ obtained by transesterification using a catalyst from a higher alcohol represented by the formula:
Prior to fractionating the higher cyanoacetic acid alkyl ester represented by the formula (wherein R ′ represents an alkyl group having 4 to 20 carbon atoms) from the reaction solution, the reaction solution containing the higher cyanoacetic acid alkyl ester and the above catalyst is subjected to reduced pressure. And a method for producing higher alkyl cyanoacetate, wherein the catalyst is removed by subjecting the catalyst to thin film evaporation.

Hereinafter, the present invention will be described in detail. The lower alkyl cyanoacetate used as a raw material in the present invention is a compound represented by the general formula NCCH ₂ COOR ¹ (wherein R ¹ has ¹ carbon atom).
To 3), specifically, methyl cyanoacetate, ethyl cyanoacetate, propyl cyanoacetate, and isopropyl cyanoacetate.

Higher alcohol R'OH used in the present invention
(Wherein R ′ represents an alkyl group having 4 to 20 carbon atoms) as n-butanol, iso-butanol, t-butanol, 1-pentanol, 2-pentanol, 3-pentanol, 2-methyl -1-butanol, 3-methyl-1-butanol, 2-methyl-2-butanol, 3-
Methyl-2-butanol, 2,2-dimethyl-1-propanol, cyclopentanol, 1-hexanol,
-Hexanol, 3-hexanol, 4-methyl-1-
Pentanol, 4-methyl-2-pentanol, 3-methyl-3-pentanol, 2,3-dimethyl-2-butanol, 3,3-dimethyl-2-butanol, cyclohexanol, 1-heptanol, -Heptanol, 3
-Heptanol, 4-heptanol, 3-ethyl-3-
Pentanol, 2,4-dimethyl-3-pentanol,
2,3,3-trimethyl-2-butanol, 1-octanol, 2-octanol, 2-ethyl-1-hexanol, 1,1,3,3-tetramethyl-1-butanol, 1-nonanol, 2-nonanol , 2,6-dimethyl-4-heptanol, 1-decanol, 1-undecanol, 1-dodecanol, 1-tridecanol, 1-
Examples include tetradecanol, 1-pentadecanol, 1-hexadecanol, 1-heptadecanol, 1-octadecanol, and triphenylmethanol.

Particularly preferred are t-butanol, 1-pentanol, 1-hexanol, cyclopentanol,
Cyclohexanol and the like are used.

As a catalyst used in the reaction between the lower alkyl cyanoacetate and the higher alcohol, a tin compound is preferably used. As the tin compound, tin compounds shown in the following (1) to (4) are used.

[0016]

Embedded image [Wherein, R ² and R ³ are each independently an alkyl group having 1 to 18 carbon atoms, and X ¹ and X ² are each independently -H, -R ⁶ ,-
OR ⁶ , —OCOR ⁶ , —OCOCH ＝ CHCOOR ⁶ (where R ⁶ has 1 to 18 carbon atoms)
Represents an alkyl group) or represents a halogen]

[0017]

Embedded image [Wherein, R ² and R ³ each independently represent an alkyl group having 1 to 18 carbon atoms]

[0018]

Embedded image [Wherein, R ² and R ³ each independently represent an alkyl group having 1 to 18 carbon atoms, and A represents —COCH ＝ CHOC—]

[0019]

Embedded image [Wherein, R ² , R ³ , R ⁴ and R ⁵ are each independently an alkyl group having 1 to 18 carbon atoms, and X ³ and X ⁴ are each independently -R
⁶ or —OR ⁶ (R ⁶ represents an alkyl group having 1 to 18 carbon atoms), B represents —OCOCH ＝ CH—COO— or —O—
Shows]

Examples of the tin compound represented by the above formula (1) include dibutyltin dimethoxide, dibutyltin diethoxide, dioctyltin dimethoxide, dioctyltin diethoxide, dibutyltin di (t-butoxide), dioctyltin di (t-butoxide), and the like. Dibutyltin dihydride, dioctyltin dihydride, dibutyltin diacetate, dioctyltin diacetate, dibutyltin dioctate, dioctyltin dioctate, dibutyltin dilaurate, dioctyltin dilaurate, dibutyltin distearate, dioctyltin distearate, tributyltin acetate, trioctyltin Acetate, tributyltin octate, trioctyltin octate, tributyltin laurate, trioctyltin laurate, tributyltin stearate, Riokuchiru tin stearate, tributyltin methoxide, trioctyl tin methoxide, tributyltin ethoxide, trioctyl tin ethoxide, tributyltin t- butoxide, trioctyl tin t
-Butoxide, dibutyltin bis (monomethyl maleate), dioctyl tin bis (monomethyl maleate), dibutyl tin bis (monooctyl maleate), dioctyl tin bis (monooctyl maleate), dibutyl tin bis (monolauryl maleate) , Dioctyltin bis (monolauryl maleate), dibutyltin dichloride, dioctyltin dichloride and the like.

In particular, dibutyltin dimethoxide, dibutyltin diethoxide, dioctyltin dimethoxide, dioctyltin diethoxide, dibutyltin di (t-butoxide), dioctyltin di (t-butoxide), dibutyltin dihydride, dioctyltin dihydride,
Dibutyltin diacetate, dioctyltin diacetate,
Dibutyltin dioctate, dioctyltin dioctate,
Dibutyltin dilaurate, dioctyltin dilaurate,
It is preferable to use dibutyltin distearate, dioctyltin distearate, tributyltin methoxide, trioctyltin methoxide, tributyltin t-butoxide, trioctyltin t-butoxide, or the like.

As the tin compound represented by the above formula (2), dibutyltin oxide, dioctyltin oxide,
Dicyclohexyltin oxide and the like, in particular,
It is preferable to use dibutyltin oxide and dioctyltin oxide. Examples of the tin compound represented by the above formula (3) include dibutyltin maleate and dioctyltin maleate.

Examples of the tin compound represented by the above formula (4) include bis (tributyltin) oxide, bis (trioctyltin) oxide, bis (tributyltin) maleate, bis (trioctyltin) maleate, and bis (dibutylmethoxytin) Maleate, bis (dioctylmethoxytin) maleate, bis (dibutylmethoxytin) oxide, bis (dioctylmethoxytin) oxide, bis {dibutyl (t-butoxy) tin} maleate, bis {dioctyl (t-butoxy) tin} maleate, Bis dibutyl (t-butoxy) tin oxide, bis dioctyl (t-butoxy) tin oxide, bis (dibutyl lauroxy tin) maleate, bis (dioctyl lauroxy tin) maleate, bis (dibutyl lauroxy tin) oxide , Bis (diocti) , And the like Raurokishi tin) oxide.

In particular, bis (dibutylmethoxytin) maleate, bis (dioctylmethoxytin) maleate, bis (dibutylmethoxytin) oxide, bis (dioctylmethoxytin) oxide, bis (dibutyl (t-butoxy) tin) maleate, {Dioctyl (t-butoxy) tin} maleate, bis dibutyl (t-butoxy)
Tin oxide, bis dioctyl (t-butoxy)
It is preferable to use tin oxide.

In general, the transesterification reaction using the above-mentioned raw material and catalyst can be carried out under any of normal pressure, reduced pressure and increased pressure, but is carried out while distilling off by-product alcohol quickly out of the system.

The amount of the lower alkyl cyanoacetate and higher alcohol used as raw materials is usually 1.5 to 3 moles per mole of the lower alkyl cyanoacetate.
It may be used in a molar range of 0 times, preferably 2 to 20 times.

The amount of the catalyst used is in the range of 0.1 to 50 mol% with respect to the lower alkyl cyanoacetate.
Preferably, it is in the range of 0.5 to 25 mol%.

[0028] The reaction temperature is applied in the range of 40 to 250 ° C, preferably 60 to 200 ° C. The reaction time varies depending on the reaction conditions such as the molar ratio of the raw materials, the amount of the catalyst and the reaction temperature, but is usually applied within 12 hours and in the range of 3 to 10 hours.

It is efficient if the alcohol by-produced by the reaction is led to a distillation column and extracted out of the system at an appropriate reflux ratio.
In this case, the reflux ratio may be appropriately selected from 1: 1 to 30: 1, usually from 1: 1 to 15: 1.

After the reaction, prior to fractionating the produced higher alkyl cyanoacetate from the resulting reaction solution, the reaction solution is subjected to thin film evaporation under reduced pressure to remove low boiling components containing the higher alkyl cyanoacetate from the reaction solution. By distilling off, a tar-like residual liquid containing a catalyst and a high-boiling substance is separated from the low-boiling component.

The above-mentioned reaction solution contains unreacted starting materials, ie, lower alkyl cyanoacetic acid ester and higher alcohol. When these are present in excess, or when lower alcohol which is a by-product of the reaction is contained in the reaction solution. In order to promote thin film evaporation efficiently, at least most of them may be removed from the reaction solution by vacuum distillation or the like prior to thin film evaporation.

The pressure at the time of thin film evaporation is 0.1 to 50 mmH
g, preferably in the range of 1 to 10 mmHg.
The heating temperature is preferably lower within the temperature at which the reaction solution is quickly evaporated in order to suppress thermal decomposition or thermal polymerization, and a temperature higher by 0 to 50 ° C. than the boiling point of the reaction solution at the evaporation pressure is suitable.

The thin film evaporator used in the present invention may be of any type as long as it has a structure in which the supply liquid is formed into a thin film and the liquid is evaporated instantaneously. Examples of such an apparatus include a thin film descending concentrator, a stirring thin film evaporator, and a centrifugal thin film evaporator. Among these, a stirring type thin film evaporator that forms a thin film by mechanical stirring is preferably used. The stirring type thin film evaporator includes a Luwer type, a Smith type, a Sunbay type, a Hitachi control type and the like, and any of them can be used in the present invention.

In order to carry out the present invention continuously, it is desirable that the residual liquid has fluidity and is discharged without stagnation. Therefore, it is preferable to terminate the thin film evaporation in a state where the liquid component remains in the residual liquid, and the liquid component may be a liquid in which a higher alkyl cyanoacetic acid ester is partially left in the residual liquid, High-boiling substances derived from the reaction may remain. As the high-boiling substance derived from the reaction, any substance having a higher boiling point than that of the higher alkyl cyanoacetate and capable of substantially imparting fluidity to the residual liquid at the temperature at the end of the thin film evaporation may be used. Regardless.

In the present invention, in order to maintain the fluidity of the residual liquid, the following substances different from the above high boiling substances can be added to the above reaction liquid in advance. Such substances include a boiling point of 100 to 20 at a pressure of 1 to 50 mmHg.
It is an organic compound which is in the range of 0 ° C. and soluble in the above reaction solution. For example, triethylene glycol, 1-hexadecanol, 1-heptadecanol, 1-octadecanol, triethanolamine and the like can be mentioned.

The distillate obtained by the thin film evaporation contains a lower alkyl cyanoacetate as an impurity. By treating this with an aqueous alkali solution, the lower alkyl cyanoacetate is selectively hydrolyzed. As the alkali used here, any alkali can be used as long as it shows alkalinity in an aqueous solution, but hydroxides, carbonates, and ammonia of alkali metals can be preferably used. The amount of the alkali used is 0.4 to the lower cyanoacetic acid ester.
It is preferable to use 10 to 10 mol%. After the impurities are hydrolyzed with an aqueous alkali solution, the reaction solution is separated, the organic layer is separated, and distilled under reduced pressure to obtain purified higher alkyl cyanoacetic acid ester.

[0037]

EXAMPLES Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

Example 1 A flask equipped with a stirrer, thermometer and a McMahon packed column was charged with 73.9 g of methyl cyanoacetate and t-butanol4.
9.7 g and dibutyltin oxide 9.2 g were added, and 10
Heated to 0 ° C. and refluxed. After the reaction liquid was completely refluxed for 10 minutes, the reaction was performed while methanol generated at a reflux ratio of 15: 1 was flown out of the system. After the reaction, the reaction mixture was analyzed by gas chromatography. As a result, the conversion of methyl cyanoacetate was 80.7%, and the selectivity for t-butyl cyanoacetate was 80.6%.

Subsequently, the obtained reaction solution was subjected to distillation under reduced pressure to distill off low-boiling substances to a boiling point of 78 ° C./20 mmHg. The weight after distillation was 100.4 g, and the composition was as follows. Methyl cyanoacetate 14.2% by weight t-butyl cyanoacetate 68.2 {catalyst 9.2} high boiling point substance 8.4}

Subsequently, the outer cylinder diameter was 50 mm and the heating section length was 1
In a vertical stirring type thin film evaporator having a stirring blade of 50 mm, at a pressure of 5 mmHg, at a heating part temperature of 110 ° C., 100.4 g of the reaction solution obtained above after distilling off the low-boiling substance was obtained at a rate of 2.5 g / min. And thin film evaporation was performed. The amount of the obtained distillate was 80.7 g. As a result of analysis by gas chromatography, t-butyl cyanoacetate in the distillate was 60.7 g.
7.4 g and methyl cyanoacetate were 13.3 g. The recovery of t-butyl cyanoacetate in the thin film evaporation step represented by the following formula (5) was 98.4%.

The residual liquid composition was 0.5% by weight of methyl cyanoacetate, 1.4% of t-butyl cyanoacetate, 64.8% of dibutyltin oxide, and 35.2% of a high-boiling substance. there were. Equation (5)

To recover t-butyl cyanoacetate, 80.7 g of the distillate obtained by thin-film evaporation was placed in a flask equipped with a stirrer, thermometer and dropping funnel.
A 15% by weight aqueous sodium hydroxide solution at a temperature of 40 ° C.
0 g (the amount of sodium hydroxide is equimolar to methyl cyanoacetate) was added dropwise over 30 minutes, stirred for 5 minutes, allowed to stand for 10 minutes and separated into an organic layer and an aqueous layer. Under reduced pressure to obtain 64.0 g of purified t-butyl cyanoacetate. The yield of purified t-butyl cyanoacetate based on the charged methyl cyanoacetate was 60.8%.
At the time of distillation under reduced pressure of t-butyl cyanoacetate, there was no abnormal foaming, and the recovery was good.

Example 2 10.0 g of 1-hexadecanol was added to 90.0 g of the same reaction solution instead of subjecting 100.4 g of the reaction solution obtained by distilling off the low-boiling substance by vacuum distillation to a thin film evaporator. The procedure was the same as in Example 1 except that the mixture was applied to a thin film evaporator. Cyanoacetic acid t- in thin film evaporation
The recovery of butyl was 98.0%. The composition of the residue liquid is methyl cyanoacetate 0.6% by weight t-butyl cyanoacetate 1.3 {dibutyltin oxide 34.6} high-boiling substance 24.4 {1-hexadecanol 39.0}. The flowability was even better than in Example 1. Next, pure t-butyl cyanoacetate was obtained from the distillate obtained by thin-film evaporation in the same manner as in Example 1. The yield of purified t-butyl cyanoacetate based on the charged methyl cyanoacetate was 60.
6%. At the time of distillation under reduced pressure of t-butyl cyanoacetate, there was no abnormal foaming, and the recovery was good.

Comparative Example 1 100.1 g of a reaction solution obtained by distilling off low-boiling substances by vacuum distillation obtained in the same manner as in Example 1 was put into a mold flask, and the boiling point was 100 ° C./°C. The ester content was distilled off to 10 mmHg. Cyanoacetic acid t in simple distillation
The recovery of -butyl was 57.3%. Since thermal decomposition of t-butyl cyanoacetate occurs during the simple distillation, foaming was observed in the middle, and the foaming became intense as the distillation proceeded. Due to abnormal foaming, the recovery rate could not be further increased.

[0045]

According to the method of the present invention, the general formula NCCH
An alkyl lower cyanoacetate represented by ₂ COOR ¹ (wherein R ¹ represents an alkyl group having 1 to 3 carbon atoms) and a general formula R′OH (where R ′ represents an alkyl group having 4 to 20 carbon atoms) General formula NCCH ₂ COOR ′ obtained by transesterification using a catalyst from a higher alcohol represented by the formula:
(Wherein R ′ represents an alkyl group having 4 to 20 carbon atoms), prior to fractionating the higher alkyl cyanoacetate from the reaction mixture, the reaction mixture containing the higher alkyl cyanoacetate and the above catalyst is evaporated in a thin film. By removing the catalyst over a period of time, higher cyanoacetic acid alkyl ester can be recovered in high yield, and the product can be easily recovered without causing abnormal foaming during distillation.

Claims (1)

[Claims] 1. A cyanoacetic acid lower alkyl ester represented by the general formula NCCH ₂ COOR ¹ (wherein R ¹ represents an alkyl group having 1 to 3 carbon atoms) and a general formula R′OH (wherein R ′
Represents an alkyl group having 4 to 20 carbon atoms, which is obtained by a transesterification reaction using a catalyst from a higher alcohol represented by NCCH ₂ COOR ′ (wherein R ′ represents an alkyl group having 4 to 20 carbon atoms). Prior to fractionating the higher cyanoacetic acid alkyl ester represented by
A process for producing a higher alkyl cyanoacetate, comprising subjecting a reaction solution containing the higher alkyl cyanoacetate and the above catalyst to thin-film evaporation under reduced pressure to remove the catalyst.