JPH0456823B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing N-(α-alkoxyethyl)formamide. N-(α-alkoxyethyl)formamide is
It is an important substance as an intermediate raw material that yields useful N-vinylformamide according to the reaction formula below. (In the above formula, R represents an alkyl group.) Conventional methods for producing N-vinylformamide include (1) using acetaldehyde cyanohydrin obtained by the reaction of acetaldehyde and hydrogen cyanide as a raw material, and adding formamide to this; A method of reacting to form N-(α-cyanoethyl)formamide, from which hydrogen cyanide is split to obtain an N-vinyl compound. (2) A method is known in which N-ethylformamide and methanol are reacted with an electrode to form N-(α-methoxyethyl)formamide, and methanol is split from this to obtain an N-vinyl compound. Neither method is industrially satisfactory in terms of safety of raw materials and reaction operations. A method of reacting α-chloroethyl methyl ether and formamide in the presence of an excess base is also known as a reaction to obtain N-(α-methoxyethyl)formamide, but this reaction is more This is not a practical method because -(α-methoxyethyl)formamide is predominantly produced. The method using the reaction product of N-(α-hydroxyethyl)formamide and alcohol as a raw material according to the above reaction formula is industrially more advantageous than these known methods, but there are no reports on this method. . Therefore, N-(α-
hydroxyethyl)formamide is prepared and then N by reaction with a primary or secondary alcohol.
It is not yet known to produce -(α-alkoxyethyl)formamide. There have been many reports on the reaction between formamide and formaldehyde for a long time, and an N-methylol compound is generally obtained through an equilibrium reaction between the two substances. Further, N-methylolamide produces N-methoxymethylamide by reaction with methanol. Therefore, even if a similar aldehyde reacts with formamide, formaldehyde and acetaldehyde behave differently, and the essence of the reaction is different. The present inventors, in view of the above circumstances, formamide,
As a result of intensive studies to industrially advantageously produce N-(α-alkoxyethyl)formamide from acetaldehyde and alcohol, we found that N-(α-hydroxyethyl)formamide was produced by reacting formamide and acetaldehyde in the presence of a basic catalyst. The inventors discovered that the desired product could be produced in an extremely high yield by reacting this with a primary or secondary alcohol in the presence of an acid catalyst, and completed the present invention. . That is, the gist of the present invention is to react formamide and acetaldehyde in the presence of a basic catalyst to obtain N-(α-hydroxyethyl)formamide, which is then reacted with primary or secondary formamide in the presence of an acid catalyst. N- characterized by reacting with alcohol
The present invention relates to a method for producing (α-alkoxyethyl)formamide. The present invention will be explained in detail below. As the catalyst used in the reaction of formamide and acetaldehyde in the present invention, any general basic compound can be used. Hydroxides of alkali metals, alkaline earth metals, quaternary ammonium, etc., tertiary amines, strong bases, ion exchange resins that act on weak bases, weak base salts consisting of strong bases and weak acids, etc. However, the preferred base catalyst is a weakly basic salt consisting of a strong base and a weak acid, particularly a weakly basic salt consisting of a strong base and a weak acid having a PKa value of 4 to 15. Here, the PKa value is
Means the value at 25°C of 0.01 mol/aqueous solution concentration. Such weakly basic salts include various substances, such as strong bases of hydroxides such as lithium, sodium, or potassium, and organic acids, phenols, sulfurous acid, phosphorous acid, hypophosphorous acid, and pyrroline. Examples include salts with weak acids such as phosphoric acid, carbonic acid, boric acid, and metasilicic acid. Particularly preferred weakly basic salts are potassium carbonate, sodium carbonate, potassium phosphate, sodium phosphate, potassium pyrophosphate, and sodium pyrophosphate. The ratio of the reaction raw materials, formamide and acetaldehyde, is usually 1:1.0 to 5.0 (molar ratio).
is selected from the range of, but the preferred usage ratio is
It depends on the mode of supply of acetaldehyde to the reaction system, for example, when acetaldehyde is supplied in gaseous form, it is 1:1.0 to 1.5 (molar ratio), and when it is supplied in liquid form, it is 1:1.5 to 4.0 (molar ratio). is within the range of The proportion of the weakly basic salt used as a catalyst for the reaction between formamide and acetaldehyde is usually 0.01 to 10 mol%, preferably 0.1% to formamide.
It is appropriately selected from the range of ~5 mol%. The reaction temperature between formamide and acetaldehyde can be selected from a wide range of -10 to 100°C, but from the viewpoint of acetaldehyde selectivity, it is preferably in the range of 0 to 40°C. The reaction between formamide and acetaldehyde can be carried out using any reaction apparatus according to various conventionally known formats, but the supply mode of acetaldehyde, if it is in a gaseous state, is as described above. It is economically advantageous because a high yield can be achieved at a usage rate of acetaldehyde close to the molar amount. A preferred reaction method is a method in which a catalyst and formamide are placed in a stirring tank, and gaseous acetaldehyde is continuously fed into the liquid little by little. Although the reaction can be carried out in the absence of a solvent, the product N-(α-hydroxyethyl)
Formamide is a crystalline substance with a melting point of 52.5 to 53.8°C, and if the reaction is carried out without a solvent at the preferred temperature of 0 to 40°C, the product will precipitate and solidify at the end of the reaction, forming a lump that is difficult to remove. So,
Preferably, the reaction is carried out in the presence of a solvent. The solvent is preferably a solvent that is inert to the reaction and does not inhibit the crystallization of N-(α-hydroxyethyl)formamide, in order to facilitate crystal precipitation during the reaction described later as a preferred reaction mode. Examples include aliphatic hydrocarbons such as hexane and heptane, and aromatic hydrocarbons such as benzene, toluene and xylene. The amount of the solvent used is usually appropriately selected from a range of 0.2 to 2 times the weight of formamide. Incidentally, the solvent may be added to the reaction system immediately before the crystal precipitation described below. N-(α-hydroxyethyl)formamide, the reaction product of formamide and acetaldehyde, is
Ultimately, as mentioned above, crystals are precipitated from the reaction system, but during the reaction, where crystal precipitation does not occur under normal conditions, specifically, when the conversion rate of formamide is 50
It is preferable to precipitate crystals by cooling or adding crystal nuclei within the range of 80 to 80 mol%, preferably 60 to 80 mol%, since the yield of the product can be increased. Cooling is carried out by lowering the reaction temperature to a range of -20 to 25°C, preferably -5 to 10°C, and the addition of crystal nuclei is carried out according to methods known in the art of crystallization. This is carried out by adding a small amount of N-(α-hydroxyethyl)formamide to the reaction system as crystal nuclei. In the method of feeding acetaldehyde gas into a solution of formamide and catalyst, the reaction occurs rapidly until the conversion rate of formamide reaches 60 mol%, and acetaldehyde reacts with formamide immediately after being supplied. However, the reaction rate decreases after that, but in the method of the present invention, under such conditions, the remaining amount of acetaldehyde determined in advance is fed into the liquid as a gas and dissolved, and then the above-mentioned Either precipitate N-(α-hydroxyethyl)formamide crystals according to the method and then continue the reaction, or precipitate the crystals in advance and then feed the remaining amount of acetaldehyde gas into the liquid to react. You may continue. After completion of the reaction, the N-(α-hydroxyethyl)formamide obtained as crystals can be taken out from the reaction system by an appropriate separation means such as a sieve.
However, the product is hygroscopic, unstable to heat, and easily decomposes into the raw materials formamide and acetaldehyde.
This decomposition is accelerated by the presence of acids and bases, so even if the crystals containing the reaction catalyst are carefully neutralized and passed under a nitrogen atmosphere at low temperatures, about 10% of the product will be lost. In contrast, N− obtained under cooling conditions
By reacting the (α-hydroxyethyl)formamide crystals with alcohol without isolating them, the decomposition reaction can be completely avoided and N-(α-alkoxyethyl)formamide can be obtained in an extremely high yield. . N-(α-hydroxyethyl)formamide obtained in a non-crystallized state can be converted into N-(α-hydroxyethyl)formamide with high selectivity by reacting with an alcohol from which it cannot be isolated. It can be extracted by known means such as distillation. The alcohol used in the reaction with N-(α-hydroxyethyl)formamide in the method of the present invention is generally a primary or secondary alcohol. From the viewpoint of solubility with (ethyl)formamide, alcohols having 1 to 8 carbon atoms are preferred. Polyhydric alcohols are undesirable because they give two or more types of reactants, resulting in complex products, but they do not pose an obstacle to obtaining N-vinylformamide by cleaving the alkoxy group. Examples of preferred alcohols include methanol, ethanol, n-propanol, n-
-butanol, isobutanol, n-pentanol, n-hexanol, n-heptanol, n-
Octanol, benzyl alcohol, sec-butanol, 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, 2-butoxyethanol, diethylene glycol monomethyl ether, ethylene glycol, propylene glycol, 1,4-butanediol, diethylene glycol, etc. It will be done. Particularly preferred are monovalent primary alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, 2-methoxyethanol, and 2-ethoxyethanol. The amount of alcohol to be used relative to N-(α-hydroxyethyl)formamide can be determined arbitrarily, but since N-(α-hydroxyethyl)formamide is a thermally unstable compound and difficult to recover after the reaction. It is preferable to use an equimolar or excess amount of alcohol, and usually 1.0 to 30 times the molar amount of alcohol is used. Since N-(α-hydroxyethyl)formamide is a crystalline compound, the alcohol used for the reaction is used as a solvent. In this case, the amount of alcohol used is preferably 2.0 to 20 times the mole. In order to minimize the amount of alcohol used, an inert solvent may be appropriately used in the reaction. Even if a portion of N-(α-hydroxyethyl)formamide exists as crystals in the reaction system, it becomes liquid due to the reaction with alcohol.
The inert solvent used here may be a substance that dissolves N-(α-hydroxyethyl)formamide, or a substance used simply for the purpose of dispersing it. When a solvent is used, the amount of alcohol used is preferably 1.0 to 5 times the mole of N-(α-hydroxyethyl)formamide. As the catalyst used for the reaction of N-(α-hydroxyethyl)formamide obtained from formamide and acetaldehyde with alcohol, any general acid catalyst can be used. These include mineral acids, organic acids, weak acids, ion exchange resins exhibiting strong acidity, solid acid catalysts, etc. Among these, strongly acidic substances are preferably used. Examples of preferred acid catalysts include sulfuric acid, hydrochloric acid, nitric acid, hydrobromic acid, sulfamic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and crosslinked polystyrenesulfonic acid. The amount of acid catalyst used is 0.001 to 10 mol%, preferably 0.1 to 10 mol%, based on N-(α-hydroxyethyl)formamide.
It is in the range of 5 mol%. Furthermore, when a heterogeneous catalyst such as an ion exchange resin is used, the raw material mixture can be passed through a column filled with the catalyst to cause the reaction. The reaction between N-(α-hydroxyethyl)formamide and alcohol is easily accomplished by adding an acid catalyst to a mixture of the two or bringing them into contact. The reaction temperature is -10 to 60℃ from the viewpoint of reactivity and stability of N-(α-hydroxyethyl)formamide.
A range of is preferred. Particularly preferably, the temperature is in the range of 0 to 40°C. The reaction product can also be isolated by a commonly known method such as concentration or distillation after neutralizing or separating the acid catalyst. The process of the invention also allows the N-(α-hydroxyethyl)formamide obtained by the reaction of formamide and acetaldehyde in the presence of a basic catalyst to be reacted with an alcohol without isolating the N-
-(α-alkoxyethyl)formamide is particularly effective. Although the present invention does not depend on the order in which alcohol and catalyst are added, for example, N-(α-hydroxyethyl)formamide obtained by the reaction of formamide and acetaldehyde contains a base catalyst, so alcohol is added to it; It is easy to neutralize by adding an acid equivalent to the base catalyst and then react by adding an acid catalyst, or by adding an excess amount of acid catalyst necessary to neutralize the base catalyst and causing the reaction. can get the desired object. In this case, depending on the type of alcohol, it can easily form acetal with unreacted acetaldehyde, so in addition to the amount of alcohol used above,
It is preferable to increase the amount of alcohol by twice the molar amount. As described above, according to the method of the present invention, it is possible to produce N-(α-hydroxyethyl)formamide from formamide, acetaldehyde, and alcohol in high yield, and the present invention contributes to the field of producing N-vinylformamide. It is important to do so. EXAMPLES The present invention will be explained in more detail with reference to examples below, but the present invention is not limited to the following examples unless it exceeds the gist thereof. Reference example Synthesis example of N-(α-hydroxyethyl)formamide A stirrer equipped with a stirring blade made of fluororesin, a gas inlet pipe, a thermometer, and an exhaust pipe connected to a trap containing a small amount of paraffin are attached. 270 g (6 moles) of formamide, 4.15 g (0.03 moles) of potassium carbonate, and 246 g of n-hexane were placed in a second four-necked flask equipped with an ice-cooled condenser, and the mixture was stirred vigorously while keeping the temperature at 25°C. with needle valve
After about 350 g of acetaldehyde was placed in a 500 ml pressure-resistant glass container, a needle valve and a gas introduction pipe were connected, and the pressure-resistant glass container was kept at a temperature of 40 to 45°C. The needle valve was opened, the trapped liquid paraffin was observed, and acetaldehyde was supplied in gaseous form to the maximum extent that would not cause the acetaldehyde to leak. Acetaldehyde 299g (6.79mol)
It took 195 minutes to supply the Furthermore, when a portion of the colorless and transparent viscous liquid produced after being left at 25°C for 1 hour was analyzed by liquid chromatography, the conversion rate of formamide was 83.7 mol%. The selectivity was 100 mol%. In addition, the conversion rate of acetaldehyde was 77 mol%, and the N of acetaldehyde was
The selectivity to -(α-hydroxyethyl)formamide was 96 mol%. When the flask was cooled to 10°C and held for 30 minutes, the product crystallized and the internal temperature rose to 42°C. After cooling to 5°C again and holding for 1 hour, a portion of the product was taken and analyzed in the same manner as above. The conversion rate of formamide was 99.2 mol%, and N-(α-hydroxyethyl)
The selectivity to formamide was 100 mol%.
After adding 500ml of cooled acetone, add concentrated sulfuric acid.
A solution of 3.03 g dissolved in 30 g of isopropanol was added at 5° C. to neutralize potassium carbonate. The product was filtered under cooling in a nitrogen gas stream, washed with ice-cooled acetone, and then dried under reduced pressure at room temperature to obtain 481 g of white crystals. This corresponds to 90% of the theoretical amount.
This was recrystallized with acetone and the melting point was 52.5-53.8.
℃ crystals were obtained. The elemental analysis value of this product is N-(α
-hydroxyethyl)formamide was in agreement with the calculated value. The structure was confirmed by IR and NMR spectra. Elemental analysis value; 40.18% H; 7.88% N; 15.59% Theoretical value C; 40.44% H; 7.92% N; 15.72% Examples 1 to 5 N obtained in the reference example was placed in a 100 ml pear-shaped flask equipped with a cooling tube. 17.8 g (0.2 mol) of -(α-hydroxyethyl)formamide and 0.6 mol of the alcohol shown in Table 1 were added, and stirred with a magnetic stirrer while keeping the temperature at 20°C. 98 mg of sulfuric acid dissolved in 2 g of each alcohol was added and reacted for 30 minutes. A portion of the product was taken and analyzed by liquid chromatography. Conversion rate of formamide and N-
The selectivity to (α-alkoxyethyl)formamide is shown in Table 1. After adding 0.25 ml of aqueous ammonia to neutralize the sulfuric acid, the resulting inorganic substances were separated and the liquid was concentrated using an evaporator. The concentrate was distilled under reduced pressure, and the product N-(α
-alkoxyethyl)formamide was obtained. The boiling points and yields are shown in Table 1.

[Table] Example 6 17.8 g (0.2 mol) of N-(α-hydroxyethyl)formamide obtained in the reference example and 40 g (1.25 mol) of methanol were placed in a 100 ml pear-shaped flask equipped with a cooling tube, and the mixture was heated with a magnetic stirrer. The temperature was maintained at 20°C while stirring. 0.68 g of dried Diaion PK208H (trademark of Mitsubishi Chemical Industries, Ltd., crosslinked polystyrene sulfonic acid resin) was added to the mixture and vigorously stirred at 20° C. for 30 minutes. After separating the ion exchange resin, the liquid is concentrated using an evaporator.
20.4 g of N-(α-methoxyethyl)formamide containing 0.8% formamide were obtained. This corresponds to 98% of the theoretical amount. Examples 7 to 13 A small amount of fluid was added to the exhaust pipe of a 500 ml four-necked flask equipped with a stirrer equipped with a stirring blade made of fluororesin, a gas inlet pipe, a thermometer, and an ice-cooled condenser with an exhaust pipe. A trap containing paraffin was connected. Approximately 65 g of acetaldehyde was collected in a 100 ml pressure-resistant glass container equipped with a needle valve, the needle valve was closed, and the container was connected to the gas inlet pipe of the flask with a fluororesin tube. 45g formamide in flask
(1 mol) and 0.005 mol of the catalyst shown in Table 2 were added and stirred vigorously while maintaining the temperature at 25°C. The pressure-resistant glass container was kept at a temperature of 40 to 45°C, the needle valve was opened, and acetaldehyde was blown into the reaction liquid in gas form from the gas introduction tube. The trap containing liquid paraffin was observed, and the needle valve was adjusted so that the maximum amount of acetaldehyde could be supplied without leaking from the trap in gaseous form. The feeding time and amount of acetaldehyde used are shown in Table 2.
Furthermore, the flask was cooled to 5°C while stirring, and N-
(α-Hydroxyethyl)formamide crystals approx.
50 mg was added as crystal nuclei to crystallize the reaction product. After cooling to 5℃ and holding for 30 minutes, sulfuric acid
Adding 96 g of methanol in which 0.005 mol was dissolved
Stir for 30 minutes. Next, the temperature of the flask was raised to 20°C, a solution of 0.005 mol of sulfuric acid dissolved in 2 g of methanol was added, and the temperature was maintained at 20°C for 30 minutes. product 1
A sample was taken and its composition was analyzed by liquid chromatography. Formamide conversion rate and formamide N-
The selectivity to (α-methoxyethyl)formamide is shown in Table 2.

【table】

Claims (1)

[Claims] 1 Formamide and acetaldehyde are reacted in the presence of a basic catalyst to obtain N-(α-hydroxyethyl)formamide, which is then reacted with a primary or secondary alcohol in the presence of an acid catalyst. A method for producing N-(α-alkoxyethyl)formamide, which comprises reacting with. 2. The method according to claim 1, wherein the basic catalyst is a weak basic salt consisting of a strong base and a weak acid having a PKa value of 4 to 15. 3. The method according to claim 1 or 2, wherein the reaction between formamide and acetaldehyde in the presence of a basic catalyst is carried out at a temperature in the range of 0 to 40°C. 4 Primary or secondary alcohol has 1 carbon atom
4. The method according to any one of claims 1 to 3, characterized in that the alcohol is alcohol of 1 to 8.