JPH0142258B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing α-cyanoacrylate, and particularly to a method for producing α-cyanoacrylate in which a condensation polymer of cyanoacetate and formaldehyde is treated with an alkali and then depolymerized.

α-Cyanoacrylate compositions, which have strong anionic polymerizability and quickly polymerize at room temperature and without pressure without the use of specific catalysts to form strong bonds, are used for industrial and general purposes as so-called instant adhesives. , widely and commonly used in the pharmaceutical field.

α-Cyanoacrylate is generally synthesized by reacting cyanoacetate and formaldehyde in a solvent to obtain a condensation polymer, which is then depolymerized under reduced pressure in a stream of acidic gas. This manufacturing process is usually considered to be divided into the following three steps. That is,
(1) Addition condensation process - A process in which cyanoacetate and formaldehyde are reacted under a catalyst to obtain a condensation polymer; (2) Polymer treatment process - As a pretreatment step for depolymerization, solvent removal, dehydration, purification, etc. (3) Depolymerization step - This is a step in which the condensed polymer, which has been subjected to necessary treatments such as dehydration, is thermally depolymerized under reduced pressure in a stream of acidic gas to obtain a monomer. The present invention relates to the second step of polymer treatment.

The addition condensation process involves lower alcohols, hydrocarbons,
It is carried out at room temperature or under mild heating using a halogenated hydrocarbon, water, ether, or a mixture thereof as a solvent, usually with a basic compound, and in some cases a salt or acid as a catalyst. The method of the present invention is applicable to cyanoacetate and formaldehyde condensation polymers carried out under any conditions, and is also applicable to prior art acid-washed systems.

In addition to the solvent as a reaction medium and water as a reaction product, this condensation polymer contains a catalyst and its residues. In addition, unreacted substances such as cyanoacetate and formaldehyde naturally coexist. Catalysts and their residues tend to cause polymerization alteration of the product α-cyanoacrylate, so if depolymerization is carried out in the presence of large amounts of these catalysts, it will be difficult to complete the depolymerization reaction, resulting in low yields, and However, the quality of the product is often poor and unstable. Furthermore, unreacted raw materials,
Cyanoacetate, formaldehyde, or
When a large number of these low condensates coexist, it is difficult to separate the resulting product from α-cyanoacrylate (α-cyanoacrylate at this stage is often referred to as a crude synthetic monomer. The same applies hereinafter), resulting in adhesion. Since the drug composition requires a high degree of purification before commercialization, measures in the manufacturing process were also required.

Although there are many types of impurities contained in the coarsely synthesized monomer, water and solvents can be removed relatively easily.
However, other impurities have been difficult to separate because their boiling points and distillation behavior are similar to those of the target product, α-cyanoacrylate, and because they are bound together as polymerization initiators.

In order to overcome these inconveniences, methods have been proposed such as reacting with a slight excess of formaldehyde so that cyanoacetate does not remain during the addition reaction, and methods of washing the condensation polymer with water, washing with acid, or azeotropically treating the condensation polymer with a solvent. However, it is a well-known fact to those skilled in the art that it has not produced sufficient practical effects.

As is generally known, highly reactive α-
The purification methods that can be applied to cyanoacrylates are practically limited to distillation purification, so components that may be inconvenient to the depolymerization reaction or to subsequent products are removed in the previous process for depolymerizing the crude monomer. It is recognized that there is a need to maintain Therefore, the present inventors
As a result of considering a new treatment method based on the analysis results of the reaction mechanism, we found that a purification method in which the condensation polymer is treated with alkali before depolymerization is extremely rational and effective, leading to the present invention. Ivy.

Thus, the present invention provides a method for producing α-cyanoacrylate by depolymerizing a condensation polymer obtained by condensing cyanoacetate and formaldehyde, which is characterized in that the polymer is treated with an alkali and then depolymerized. A method for producing α-cyanoacrylate is provided.

To further explain the present invention, the reaction between cyanoacetate and formaldehyde is generally considered to involve activating cyanoacetate, which is an acidic substance, with a catalyst, converting it into methylol with formaldehyde, and then carrying out the subsequent condensation reaction. ing. Various catalysts such as bases, acids, and salts have been considered for this purpose, but the method using a base catalyst is most commonly used and is also easy to implement.

As mentioned above, basic compounds that are effective as catalysts in the addition reaction step, as well as their residues and salts, are extremely likely to alter α-cyanoacrylate, so acid treatment and water washing are recommended as purification methods that include their removal. Although this seems reasonable, it did not have the desired effect.

The present inventors previously conducted detailed research on the addition condensation reaction, condensation products, and depolymerization reaction of cyanoacetate and formaldehyde, and in the course of their research,
In the addition condensation reaction process, which starts in the alkaline range of pH 8 to 14 under a basic catalyst, the reaction occurs extremely rapidly.
We discovered a new phenomenon in which the pH decreases and becomes acidic at pH 4 to 6, elucidated the mechanism, and obtained new knowledge. One of the findings was based on the action of active methylene hydrogen. One reason why the acid water washing treatment was not as effective as expected was that the acid water washing treatment was performed on an acidified system. The present invention is based on new findings obtained by the inventors,
The present invention aims to propose a method for removing impurities by treating a polycondensation product with an alkali before depolymerization, and for facilitating the depolymerization and subsequent steps.

In the method of the present invention, a condensation product obtained by addition condensation of cyanoacetate and formaldehyde, a condensation product having the same structure obtained by another method, or a solution or dispersion thereof is treated with an alkali. As long as the treatment does not significantly decompose or alter the condensation product, similar effects can be expected under any conditions. Examples include a method of treating a condensation polymer solution with an aqueous solution or dispersion of an alkaline substance, a method of treating a condensation polymer solution with an inert alkaline substance and obtaining a purified solution by perfusion or phase separation, and a method of treating a condensation polymer solution with an inert alkaline substance and obtaining a purified solution by phase separation. An example is a method in which a basic ion exchange resin or an alkaline adsorbent is used to treat it in a conventional manner.

As the alkaline substance used in this alkaline treatment, either organic or inorganic compounds can be used, but care must be taken to ensure that as little as possible remains in the depolymerization process. It is desirable that there is no concern about generating water or volatile basic substances under depolymerization conditions, and if a large amount of degradable organic compounds such as lower amines and polyethyleneimine remain, it may have an adverse effect, so be sure to remove them thoroughly. It is desirable to do so. Particularly desirable compounds include lithium hydroxide,
hydroxides of alkali metals or alkaline earth metals such as sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, and magnesium hydroxide; carbonates and bicarbonates represented by sodium carbonate and magnesium carbonate; Examples include oxides represented by sodium oxide and calcium oxide, alkoxides represented by sodium methoxide and magnesium ethoxide, basic alumina, silicon alkali, alkali silicates, and basic ion exchange resins.

When sodium hydroxide is used as the alkaline substance, the alkali content is not particularly limited, but is 0.001 based on cyanoacetate during condensation polymer synthesis.
If it is less than g/mol, it is too small and has little effect, and
Even if the amount is larger than 20g/mol, no beneficial effect can be expected, so treat with 0.001 to 20g/mol of alkali so that the concentration during cleaning becomes an aqueous solution of about 0.001% (weight) to about 50%. A method in which the aqueous phase is separated and removed is desirable. At this time, it is recommended that the stirring treatment be carried out at room temperature or at a temperature below the boiling point of the system, usually at a temperature below 80°C. The processing time depends on the temperature,
It can be set taking into consideration various factors such as stirring speed, alkali concentration and amount, type of cyanoacetate, condensation polymer solution concentration, equipment shape, etc., but in reality it is 1 minute to 1 hour in relation to the overall working process time. A certain amount is sufficient.

Also effective is a method in which the condensation polymer solution is treated with a basic ion exchange resin column without washing with water. Note that acid water washing treatment before and after alkali treatment is also effective.

The method of the present invention, in which such condensation polymers or their solutions are treated with alkali by water washing, adsorption, etc., effectively removes unreacted cyanoacetate and other organic contaminants that are difficult to remove with simple water washing or acidic water washing. It is particularly useful industrially because it reduces impurities and also removes low-condensation polymers, making the molecular weight distribution of the condensation polymer uniform, making it easy to carry out the depolymerization reaction and obtaining commercial grade crude monomers. be.

Examples of the present invention are shown below. The middle part of the example represents parts by weight.

Example 1 Paraformaldehyde was added to the 4-necked flask from 1.
30.6 parts of toluene, 100 parts of toluene, and 0.5 parts of piperidine were added, and while stirring and heating to 70 to 85°C, 113 parts of ethyl cyanoacetate was added dropwise from the dropping funnel. After the addition, the mixture was reacted for 3 hours under reflux to complete the addition condensation step. 1 part of sodium hydroxide was dissolved in 100 parts of water, and the mixture was added to the reaction solution and stirred for 10 minutes, left to stand, the aqueous phase was separated and removed, and toluene was distilled off under heating and reduced pressure.

Add 0.5 parts of hydroquinone and 3 parts of phosphoric anhydride into a flask, and reduce the temperature to 170 to 205 under reduced pressure of 5 mmHg or less.
104 parts of crude monomer distilled off at a liquid temperature of °C (yield 83%)
I got it. The purity of this crude monomer was 98.1%, and ethyl cyanoacetate among impurities was 0.4%.
In the above reaction, when the same operation was performed without alkali treatment after the reaction was completed, the crude monomer was
106 parts (yield 85%) were obtained. The purity of this crude monomer was 91.9%, and ethyl cyanoacetate among impurities was 6.5%.

Example 2 Paraformaldehyde was added to the 4-necked flask from 1.
Prepare 61 parts, 250 parts of water, and 3 parts of sodium hydroxide.
While heating and stirring, 226 parts of cyanoacetate was added dropwise from the dropping funnel. After the dropwise addition, the mixture was reacted at 85 to 95°C for 3 hours, and then a solution of 5 parts of potassium hydroxide dissolved in 100 parts of water was added, stirred for 5 minutes, and allowed to stand, and the aqueous phase was separated and removed. Add 200 parts of toluene to the condensation polymer, remove water with azeotropy,
The remaining toluene was distilled off under reduced pressure.

Add 1 part of hydroquinone and 8 parts of phosphoric anhydride,
195 parts of crude monomer (yield 78%) was obtained by distillation at a liquid temperature of 170 to 205° C. under reduced pressure of 5 mmHg or less. The purity of this crude monomer was 98.7%, and ethyl cyanoacetate among impurities was 0.3%.

In the above reaction, when the same operation was performed without alkali treatment after the completion of the reaction, the crude monomer was
200 parts (yield 80%) were obtained. The purity of this crude monomer was 90.8%, and ethyl cyanoacetate among impurities was 7.4%.

Example 3 100 parts of water and 150 parts of toluene are placed in a 14-neck flask, and 3 parts of sodium hydroxide and 0.3 part of triethylbenzylammonium chloride are added and dissolved. Add 31 parts of paraformaldehyde to this, stir, and add ethyl cyanoacetate to this.
Drop 113 parts. After dropping, heat at 60-80°C for 15 minutes, then cool to room temperature.

After adding 2 parts of sodium hydroxide to this and stirring, the mixture is allowed to stand to separate the organic phase and the aqueous phase. This toluene solution of the polycondensation product is distilled at normal pressure and dehydrated by azeotropy. After the dehydration was completed, the remaining toluene was completely distilled off under normal pressure and reduced pressure to obtain a condensation product as a pale yellow viscous liquid.

2 parts of phosphoric anhydride and 0.6 parts of hydroquinone were added to this polymer, and the crude monomer was distilled out by depolymerizing the mixture at a liquid temperature of 170 to 210°C under a 5 mmHg vacuum in an SO ₂ stream.
Obtained 114 copies. The yield is 91.2% based on ethyl cyanoacetate. The purity of this crude monomer is
The amount of ethyl cyanoacetate in the crude monomer was 0.2%.

In the above reaction, when the same operation was performed without alkali treatment after the reaction was completed, the crude monomer was
111 parts were obtained (yield 88.8%). The purity of this crude monomer was 94.2% and the amount of ethyl cyanoacetate in this monomer was 4.3%.

Example 4 In Example 3, instead of treating with sodium hydroxide, a strongly basic ion exchange resin (trade name
After passing through a column of Amberlite IRA 400),
As a result of separating the aqueous phase and performing the same treatment,
A pale yellow viscous condensation product is obtained.

As a result of adding 2 parts of phosphoric anhydride and 0.6 parts of hydroquinone to this polymer and depolymerizing it in the same way, the result was 4 mmHg.
Crude monomer distilled under reduced pressure at a liquid temperature of 165℃ to 205℃
112 parts were obtained (yield 89.6%).

The purity of this crude monomer is 98.4% and the amount of ethyl cyanoacetate in this monomer is 0.3
It was %.

Example 5 100 parts of water and 150 parts of toluene are placed in a 14-necked flask, and 2 parts of anhydrous sodium carbonate is added thereto to dissolve it, followed by 32.5 parts of paraformaldehyde and stirred. 113 parts of ethyl cyanoacetate is added dropwise to this mixture, heated at 60 to 80°C for 20 minutes to complete the reaction, and then cooled to room temperature.

Three parts of potassium carbonate was added to this reaction solution, stirred for 10 minutes, and then allowed to stand to separate an aqueous phase and an organic phase. This organic phase was azeotropically dehydrated at normal pressure, and then residual toluene was completely distilled off at normal and reduced pressures to obtain a pale yellow viscous liquid.

2 parts of phosphoric anhydride and 0.6 parts of hydroquinone were added to this polymer, and the mixture was depolymerized at a liquid temperature of 168 to 215°C under a reduced pressure of 8 mmHg under a stream of SO ₂ to distill the crude monomer.
115 parts were obtained (yield 92.0%).

The purity of this crude monomer is 97.6% and the amount of ethyl cyanoacetate in this monomer is 0.2%
It was hot.

In the above reaction, when the same operation was performed without alkali treatment after the reaction was completed, 113 parts of crude monomer was obtained (yield 90.4%).

The purity of this crude monomer is 93.5% and the amount of ethyl cyanoacetate in this monomer is 5.4%
It was hot.

Example 6 According to the method of Example 3, 157 parts of 2-ethoxyethyl cyanoacetate was reacted instead of ethyl cyanoacetate to obtain 146 parts (yield: 86%) of a crude monomer.

The purity of this crude monomer was 97.4%, of which 2-
Ethoxyethylcyanoacetate was 0.3%.

After the completion of the reaction in the above reaction, the same operation was carried out without alkali treatment, and 88 parts of crude monomer (yield 52%) was obtained.

The purity of this crude monomer was 91.3%, and 2-ethoxyethylcyanoacetate among impurities was 5.8%.

Example 7 In Example 5, 6 parts of barium hydroxide was added instead of potassium carbonate and the same treatment was carried out, and the resulting condensation product was depolymerized to yield 114 parts (91%) of the crude monomer. Obtained.

The amount of ethyl cyanoacetate in this crude monomer was 0.4%, which was good.

Example 8 100 parts of water and 150 parts of toluene were placed in a 14-necked flask, and 3 parts of sodium hydroxide and 1 part of polyoxyethylene nonyl phenyl ether (10 mole adduct) were added to the solution. 31 parts of formaldehyde was added, and while stirring, 113 parts of ethyl cyanoacetate was added, heated at 60 to 80°C for 15 minutes to complete the reaction, and the mixture was returned to room temperature.

The toluene layer of the polycondensation product was separated by standing, and 20 parts of crushed magnesium carbonate was added thereto, stirred, filtered, and then treated in the same manner as in Example 3 for depolymerization. 113 parts (91%) of crude monomer was obtained which was distilled at a liquid temperature of 170 to 210°C. The amount of ethyl cyanoacetate in this crude monomer is 0.3
%, which was good.

Example 9 The same treatment as in Example 5 was carried out using 6 parts of No. 1 water glass instead of potassium carbonate, and the resulting condensation product was depolymerized to obtain 112 parts (89.6%) of crude monomer.

The amount of ethyl cyanoacetate in this crude monomer was 0.5%, which was good.

Claims (1)

[Claims] 1. A method for producing α-cyanoacrylate by depolymerizing a condensation polymer obtained by condensing cyanoacetate and formaldehyde, characterized in that the condensation polymer is treated with an alkali and then depolymerized. - Method for producing cyanoacrylate.