JPH0328412B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an improved method for producing N-alkyl substituted unsaturated amide compounds. More specifically, the present invention relates to an improved method for producing both N-mono-substituted and N,N-disubstituted amide compounds. In general, N-substituted amide compounds have a good balance between hydrophilic and hydrophobic groups in the molecule, so they have good compatibility with various substances and have strong resistance to hydrolysis. Because of its excellent advantages, it is suitable for adhesives, paints, paper processing agents, textile processing agents, emulsions, urethane curing agents, pigment dispersants, plastic additives,
It is known to be applied to a wide range of fields such as polymer flocculants and ion exchange resins. It is also a useful compound as a raw material, intermediate, and product for compounds with complex structures such as pharmaceuticals, agricultural chemicals, amino acids, and natural products, and also as a raw material for amino production. However, since an inexpensive industrial production method for N-substituted amide compounds has not been established, they have not been used in large quantities. Conventionally, industrially used methods for producing N-substituted amide compounds include the reaction of a carboxylic acid chloride with an amine and the use of the Ritter reaction, but these methods are expensive. Alternatively, the types of compounds that can be produced are limited, and their applications are currently limited to specific fields. In addition, as a general method for producing N-substituted amide compounds, an alkali metal-substituted amide compound is formed by the action of an amide compound and a strong basic substance such as an alkali metal alkoxide, and then a halogen-substituted compound such as an alkyl halide is reacted with the amide compound and a strong basic substance such as an alkali metal alkoxide. A method for producing N-substituted amide compounds is described, for example, in WJ
Written by Hickinbottom Reactions of Organic
Compounds 3rd edition, Longmans, Gren and
Co. (1957) p. 344 and US Pat. No. 3,084,191. However, these methods require the production process to consist of two steps, the use of protic solvents such as liquid ammonia or alcohol that are highly reactive with halogen-substituted compounds under basic catalysts, and the use of alkali metal amides. There are various disadvantages such as the use of highly basic substances such as hydrogen compounds, alkoxides, etc., which are difficult to handle. Therefore, as shown in Comparative Examples 1, 2, and 3 described later, the yield of the target product is low, the halogen-substituted compound to be reacted is not versatile, and the target products are all N-monosubstituted amide compounds.
When producing NN-disubstituted amide compounds, problems such as the need to repeat the same production process arise, and this method has come to be widely adopted industrially as a general method for producing N-substituted amide compounds. Not yet. Furthermore, in recent years, GLIsele, A. Luttringhous,
As disclosed in Synthesis 1971 (5), page 266, an amide compound is reacted with a strong basic substance in an aprotic polar solvent to form an alkali metal-substituted amide compound, and then an alkyl metal substituted amide compound such as an alkyl halide is prepared. A two-step process for producing N-alkyl-substituted amide compounds by reaction with halogen-substituted compounds is also known. However, even if such a method is employed, satisfactory results are not obtained, as shown in Comparative Example 2, which will be described later. Similarly, RAWJohnstone.MERose,
Tetrahedron, Vol. 35, pp. 2169-2173 (1979) describes the reaction of a saturated amide compound and a halogen-substituted compound in the presence of a large excess of a strong basic substance in an aprotic solvent to form an N-substituted saturated amide compound. A method of manufacturing is disclosed. However, as shown in Comparative Example 4, the unsaturated amide compound reacts with a strong basic substance and disappears even in the absence of a halogen-substituted compound. The organic substance and the unsaturated amide compound react with each other, making it impossible to carry out the N-substitution reaction of the unsaturated amide compound efficiently. Furthermore, in USSR Inventor's Certificate No. 667547, in a method for producing N-alkylated organic compounds in a polar solvent, a basic substance such as caustic soda is added as an aqueous solution, and the basic substance starts the reaction in a liquid state. A method is disclosed in which the presence of water in the reaction mixture is said to be highly advantageous for the progress of the reaction. However, according to the research conducted by the present inventors, as is clear from the comparison of Examples 1, 2, 3, and Comparative Example 3, which will be described later, when this method is used, the formation of side reactants is significant, and the desired N- It has been found that the selectivity to alkyl-substituted unsaturated amide compounds is low, and the yield is significantly reduced depending on the target N-substituted amide compound. In view of the actual situation regarding the production of the above-mentioned N-substituted saturated amide compound, the present inventors aimed to improve the production method by considering the quantitative relationship between the strong basic substance and the raw material unsaturated amide compound and the presence of water in the reaction system. As a result of intensive studies on the relationship between quantity and reactivity, it was discovered that the influence on selectivity to N-alkyl-substituted unsaturated amide compounds is extremely large, and the present invention was achieved. In other words, the quantitative relationship between a strong basic substance and an amide compound, which did not pose much of a problem with a saturated amide compound, has a large effect on the reaction selectivity with an unsaturated amide compound. The presence of water in the reaction system causes side reactions contrary to expectations and inhibits the production of the target N-alkyl-substituted unsaturated amide compound;
In addition, in order to suitably carry out the N-alkyl substitution reaction, instead of the conventional method of reacting an amide compound with a strong basic substance and then reacting with a halogen-substituted compound, it is necessary to use a strong basic substance, an amide compound, and a halogen-substituted compound. The present invention was achieved by discovering that it is necessary to cause a catalytic reaction of compounds at the same time. That is, the present invention provides a method for producing an N-alkyl-substituted unsaturated amide compound by simultaneously contacting and reacting a strongly basic substance, an unsaturated amide compound, and an alkyl halide in an aprotic polar solvent. , the amount of the basic substance added is 0.5 per hydrogen atom of the amide group.
This is a method for producing an N-alkyl-substituted unsaturated amide compound, characterized in that the reaction is started at ~1.5 times the molar amount and while the basic substance is suspended. In the present invention, a specific method for starting the reaction while suspending a strong basic substance is a method of simultaneously supplying and mixing the three substances in an aprotic polar solvent to suspend the strong basic substance and causing the reaction. , a method in which a strong basic substance is suspended in an aprotic polar solvent, and then an unsaturated amide compound and a halogen-substituted compound are simultaneously supplied and reacted; An appropriate method may be employed, such as dissolving or suspending the compound and then adding and suspending a strong basic substance. The unsaturated amide compounds that are the object of the present invention are roughly divided into unsaturated monoamide compounds and polyunsaturated amide compounds that are higher than unsaturated diamide compounds. Examples of unsaturated monoamide compounds include aliphatic unsaturated carboxylic acid amides. Aliphatic unsaturated carboxylic acid amides have the general formula C _o
A compound represented by H _2o+1-2n CONH ₂ (in the formula, n is an integer of 2 to 20, m is an integer of 1 to 5), and has one or more carbon-carbon double bonds and/or triple bonds in the molecule. include. Also, nitro group, cyano group, amino group,
One or more substituents such as carboxylic acid group, sulfonic acid group, alkoxy group, carboxylic acid ester group, etc.
Items that have been introduced more than once are also eligible. Examples of aliphatic unsaturated carboxylic acid amides include acrylamide, methacrylamide, vinylacetamide, crotonamide, decenamide, nonadesenamide, propiolamide, putinamide, hexadiene carboxamide, pentinamide, heptinamide, ethoxyacrylamide, ethoxymethacrylamide, cyanobutenamide, nitrobutinamide, aminobutinamide, Carbamoyl propene These include sulfonic acid, carbamoyl crotonic acid, and methyl carbamoyl crotonate. Among these exemplified unsaturated amide compounds,
Unsubstituted unsaturated amide compounds are preferred in that the reaction can be carried out efficiently. More preferred are conjugated unsaturated amide compounds in which the amide group of the unsaturated amide compound is conjugated to a double bond, such as aliphatic unsaturated amide compounds such as acrylamide, methacrylamide, crotonamide, and the like. On the other hand, polyunsaturated amide compounds include aliphatic unsaturated polycarboxylic acid amides. Aliphatic unsaturated polycarboxylic acid amide has the general formula C _o H _2o+2-n-2r
(CONH ₂ ) is represented by _n , where n, m and r are integers,
n is 2-20, m is 2-4, and r is 1-4. Furthermore, those into which one or more of a nitro group, a cyano group, an amino group, a carboxylic acid group, a sulfonic acid group, an alkoxy group, a carboxylic acid ester group, etc. have been introduced are also targeted. Aliphatic unsaturated polycarboxylic acid amides include, for example, maleamide, fumaramide, citraconamide, mesaconamide, decenedicarboxamide, tetradecenedicarboxamide, octadecenedicarboxamide, butenetetracarboxamide, hexadienedicarboxamide, pentinedicarboxamide, methoxybutenedicarboxamide , cyanobutine dicarboxamide, nitrobutene dicarboxamide, aminobutene dicarboxamide, dicarbamoylbutenesulfonic acid, dicarbamoylbutenoic acid, methyl dicarbamoylbutenoate, and the like. Among these exemplified unsaturated amide compounds,
Unsubstituted unsaturated amide compounds are preferred in that the reaction can be carried out efficiently. More preferred are conjugated amide compounds conjugated to the double bond of the amide group of the unsaturated amide compound, such as aliphatic unsaturated polyamide compounds such as fumaramide, maleamide, citraconamide, and the like. The halogen-substituted compound reacted with the unsaturated amide compound is an alkyl halide. Alkyl halides have the general formula C _o H _2o+1
is represented by halogen), and n is an integer from 1 to 20. In the following examples of alkyl halides, chlorine-substituted, bromine-substituted, and iodine-substituted compounds are all subject to the present invention, but chlorine-substituted compounds are shown as representative. Examples of alkyl halides include chloromethane, chloroethane, chloropropane, chlorobutane, chloropentane, chlorohexane, chloroheptane, chlorodecane, chlorododecane, chlorotetradecane, and chlorooctadecane. Among these compounds, the reactivity differs depending on the structure of the carbon in which the halogen atom is substituted. Compounds in which a halogen atom is substituted with a primary or secondary carbon are suitable for the reaction of the present invention. The reaction solvent used in the present invention may be any aprotic polar medium, such as acetonitrile, dioxane, nitromethane, nitroethane, nitrobenzene, pyridine, dimethoxyethane, tetrahydrofuran, tetrahydropyran, 2-methyl-tetrahydr Furan, benzonitrile,
N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide, dimethylsulfoxide, N-methylpyrrolidone, hexamethylphosphoramide, sulfolane,
Glymes such as oxepane, monoglyme, diglyme, triglyme, tetraglyme, tetramethylurea, tetraethylurea, 1,3-dimethyl-2-imidazolidinone, 1,3-dimethyl-3,4,5,6-tetrahydro -2(1H)-
Alkylureas such as pyrimidinone can be used. Among the above-mentioned solvents, more preferable solvents include acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide,
Dimethyl sulfoxide, sulfolane, tetraglyme, 1,3-dimethyl-2-imidazolidinone, etc. can be used. Since these solvents generally have a strong affinity for water, care must be taken as water may be mixed in due to water absorption or water may be mixed in during circulation and reuse. In the reaction system of the method of the present invention, it is necessary to start the reaction in a state where at least a part of the strong basic substance is suspended, and the amount of water in such a state is equal to the amount of water in the reaction system. It is usually about 6% by weight. If the amount of water in this case exceeds this, side reactions such as hydrolysis of halogen-substituted compounds or unsaturated amide compounds tend to occur, resulting in a significant decrease in yield. In order to carry out the reaction efficiently and increase the yield of the target product, as will be understood from the descriptions of Examples 2 and 3 and Comparative Example 3, the water content of the reaction system should be at least 5% by weight or less. The content is preferably 2.5% by weight or less, particularly preferably 10,000 ppm or less. The amount of the solvent to be used is not particularly limited, but is in the range of 5 to 95% by weight, preferably 10 to 90% by weight, based on the total amount of reactants including the solvent. Next, the strong basic substance used in the present invention is a solid substance, and can be used as long as the pH of the aqueous solution when dissolved or suspended in water is 10 or more, preferably 11 or more. However, when using ion exchange resins and other ion exchangers, this condition is not applicable, and will be described later. Such strong basic substances include, for example, alkali metal oxides, alkaline earth metal oxides, the amount of water in the reaction system, alkali metal carbonates, alkali metal hydrides, alkaline earth metal hydrides, alkali metal These include amides, alkali metal alkoxides, ion exchange resins, and other ion exchangers. Examples of the above-mentioned substances include, as the alkali metal oxide, sodium oxide, potassium oxide, lithium oxide, rubidium oxide, and cesium oxide. Alkaline earth metal oxides are, for example,
They are beryllium oxide, magnesium oxide, calcium oxide, strontium oxide, and barium oxide. Examples of alkali metal hydroxides include sodium hydroxide, potassium hydroxide, lithium hydroxide, rubidium hydroxide, and cesium hydroxide. Examples of alkaline earth metal hydroxides include beryllium hydroxide, magnesium hydroxide, calcium hydroxide, strontium hydroxide, and barium hydroxide. Examples of alkali metal carbonates include sodium carbonate, potassium carbonate, and lithium carbonate. Rubidium carbonate and cesium carbonate. Examples of the alkali metal hydroxide include sodium hydride, potassium hydride, and lithium hydride. Examples of alkaline earth metal hydrides include beryllium hydride, magnesium hydride, and calcium hydride.
Alkali metal amides are alkali metal substituted compounds of ammonia, such as sodium amide, potassium amide, lithium amide, and the like. Alkali metal alkoxides are compounds in which the protons of the hydroxyl groups of alcohols are replaced with alkali metals, such as sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide, and potassium t-butoxide. As the ion exchange resin, OH type of strongly basic resin and free type of strongly basic resin can be used, and preferably resin containing water content is 15% or less. Other ion exchangers may be substances that exhibit an anion exchange phenomenon, such as anion exchange cellulose, anion exchange Cephadex, anion exchange liquid, basic dolomite, hydrated iron oxide, and hydrated zirconium oxide. You just need to be able to perform a sum reaction. Among the above-mentioned basic substances, those suitable for carrying out the method of the present invention are, for example, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal oxides, alkaline earth metal oxides, alkali metal carbonates, ion exchange resins, and other ion exchange resin bodies, and more preferred ones include, for example, alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal oxides, alkaline earth metal oxides, Alkali metal carbonates, ion exchange resins, and other on exchangers. However, among unsaturated amide compounds, unsaturated amide compounds with high polymerization activity such as acrylamide and methacrylamide tend to cause side reactions such as hydrogen transfer polymerization due to strong basic substances in addition to radical polymerization due to heat. In such a case, in order to suitably carry out the method of the present invention, it is preferable to use an alkali metal hydroxide, particularly sodium hydroxide or potassium hydroxide, as the strong basic substance. These strong basic substances are usually used in the reaction in solid form, and the reaction is initiated while at least a portion of them is suspended in the reaction solution. In carrying out the present invention, the relative amounts of the unsaturated amide compound, halogen-substituted compound, and strong basic substance used as raw materials are determined by the reactivity of the halogen-substituted compound and the unsaturated amide compound, or by Is it a substituted unsaturated amide compound?
It differs depending on whether the amide compound is an N,N-disubstituted unsaturated amide compound, and it is difficult to make a general rule, but in general, when producing an N-monosubstituted unsaturated amide compound, use of a halogen-substituted compound is required. The amount is 0.2-10 times the mole of the unsaturated amide compound, preferably 0.3
-7 times the molar range. When producing an N,N-disubstituted unsaturated amide compound, the amount of the halogen-substituted compound used is 1.0-20 mol, preferably 1.0 to 20 mol, based on the unsaturated amide compound.
The range is 1.5-15 times the mole. In any case, the strong basic substance is added in an amount of 0.5 to 1.5 times the molar amount of the hydrogen atom of the amide group, as shown in the examples below. If the amount of the strong basic substance exceeds 1.5 moles per hydrogen atom of the amide group in this reaction, the yield of the desired N-alkyl-substituted unsaturated amide compound will be extremely reduced. Furthermore, it is also possible to produce N,N-disubstituted unsaturated amide compounds having different substituents, in which case two types of halogen-substituted compounds may be reacted simultaneously. The relative amounts of the two types of halogen-substituted compounds vary depending on the reactivity of the halogen-substituted compounds, but in general, it is 1.0-20% for the one with high reactivity.
The amount is twice the molar amount, preferably 1.0 to 15 times the molar amount.
Another method for producing N,N-disubstituted unsaturated amide compounds having different substituents is to first react with a first halogen-substituted compound to obtain an N-monosubstituted unsaturated amide compound; It is also possible to react with a halogen-substituted compound of 2. When using an unsaturated amide compound, it is preferable to add a polymerization inhibitor to prevent polymerization of raw materials and products during the reaction and purification steps. There are no particular restrictions on the polymerization inhibitor in this case, but
Common examples include phenolic inhibitors, amine inhibitors, mercaptan inhibitors, and copper powder. For the reaction method, a normal reaction vessel may be used, or if a strongly basic substance with low solubility is used, it may be packed in a column and mixed with an unsaturated amide compound and a halogen-substituted compound. A flow type method in which the solution is passed through and circulated may also be used. However, a reaction vessel is more convenient for equipment maintenance and management. When producing in a reaction vessel, there is no restriction on the order in which raw materials are added, but when using a highly reactive halogen-substituted compound, it is better to add the halogen-substituted compound last and react to suppress side reactions. It is convenient in this respect. The reaction temperature depends on the reactivity of the unsaturated amide compound and halogen-substituted compound used, but if the reaction temperature is low, the reaction progresses slowly, while if the temperature is high, side reactions such as hydrolysis of the unsaturated amide compound may occur. This results in a decrease in product yield.
Therefore, usually -20 to 100°C, preferably -10 to 70°C
The reaction is carried out in a temperature range of 0 to 50°C, particularly preferably in a temperature range of 0 to 50°C, except for certain halogen-substituted compounds. As long as it is within this temperature range, it is not necessarily necessary to keep the temperature constant during the reaction, but it is sufficient to monitor the progress of the reaction and appropriately set the reaction temperature to carry out the reaction efficiently. Further, the reaction time also varies depending on the unsaturated amide compound and halogen-substituted compound used, as well as the reaction temperature, but it is at most 30 hours, and usually within 10 hours. The progress of the reaction can be understood by observing changes in the properties of the reaction system and the concentrations of raw materials and target products in the reaction solution by gas chromatography or high performance liquid chromatography. After the reaction, by-produced metal chlorides are filtered off and distilled under reduced pressure using a conventional method to obtain a highly pure target product. However, if the metal chloride is dissolved in the reaction solution or if a sublimable raw material unsaturated amide compound remains, two layers such as benzene-water and chloroform-water are formed after the solvent is distilled off. After removing the above substances using a combination of solvents, a highly pure target product can be obtained by distillation under reduced pressure. In addition, if the target product has a high boiling point or is thermally decomposable,
The desired product can be purified by methods such as solvent extraction and recrystallization. When the reaction solvent has a high affinity for water, such as dimethyl sulfoxide, and the target product is highly lipophilic, such as an N-alkyl-substituted unsaturated amide compound, water may be added to the reaction solution after the reaction. A method in which the target product is separated as an oil layer, or a method in which the target product is extracted and separated using a solvent that forms two layers with water, such as benzene, toluene, or chloroform, can also be applied. According to the present invention, N-alkyl-substituted unsaturated amide compounds having an extremely wide variety of functions can be produced in one step at low cost. In addition, it becomes possible to supply N-alkyl-substituted unsaturated amide compounds to various uses that could not be applied conventionally. Furthermore, since the present invention uses the same reaction pattern, it is possible to produce a wide variety of N-alkyl-substituted unsaturated amide compounds in the same reactor, which has the advantage of being suitable for producing a wide variety of products in small quantities. Next, the present invention will be further explained by examples. Example 1 Production of N-n-propylacrylamide 14 g of potassium hydroxide (0.6 times the mole relative to the hydrogen atom of the amino group) was added and suspended in 150 ml of N,N-dimethylformamide, and 14 g of acrylamide,
0.05 g of phenothiazine and 31 g of n-propyl bromide were added, and the reaction was carried out at 40° C. for 3 hours with stirring. After the reaction, the reaction solution was analyzed by gas chromatography using a 20M polyethylene glycol column, and as a result, it was confirmed that 21 g (yield: 92%) of Nn-propylacrylamide was produced in substantial amount. Further, after the reaction solution was filtered, N,N-dimethylformamide and unreacted n-propyl bromide were distilled off under reduced pressure. 100 ml of benzene and 50 ml of distilled water were added to the residue, and after thorough stirring, the layers were separated, and the aqueous layer was extracted twice with 50 ml of benzene. The benzene layer was collected and dried over magnesium sulfate. The benzene layer was distilled under reduced pressure, and 81−83
A C/1 mm fraction was collected to obtain 18 g of N-n-propylacrylamide (yield 79%). The amount of water in the reaction system in this reaction is 1000ppm
In this case, the conversion rate of acrylamide was 95%, and the selectivity to Nn-propylacrylamide was 97%. Comparative Example 1 Production of N-n-propylacrylamide 14 g of acrylamide was added at room temperature to 150 ml of t-butanol in which 22 g of potassium t-butoxide was dissolved. After leaving to stand until the precipitation of N-potassium acrylamide was completed, 31 g of n-propyl bromide and 0.05 g of phenothiazine were added at room temperature and reacted for 3 hours with stirring, and then the precipitated potassium bromide was filtered off. The filtrate was distilled under reduced pressure at 81-83℃/1mm.
The Hg fraction was collected to obtain 6.0 g of Nn-propylacrylamide (yield 2%5). Comparative Example 2 14 g of potassium hydroxide, 14 g of acrylamide, and 0.05 g of phenothiazine were added to 150 ml of NN-dimethylformamide, and a reaction was carried out at 40°C. Thirty minutes after the reaction, a white substance precipitated on the surface of the potassium hydroxide, and sufficient stirring became impossible. After reacting as it was for 1 hour, 31 g of n-propyl bromide was added and the reaction was continued for an additional 2 hours. When the post-reaction treatment was carried out in exactly the same manner as in the example, 2.0g of N-n-propylacrylamide was obtained.
(Yield: 9%). Example 2 Production of N-n-propylacrylamide The reaction and post-reaction treatment were carried out in exactly the same manner as in Example 1, except that N,N-dimethylformamide containing 3.5% by weight of water was used. The reaction was started in the same manner as in Example 1, with potassium hydroxide partially suspended. The conversion rate in this reaction was 93%, the selectivity was 90%, and the production rate was 84%. Note that the amount of water in this reaction system was 2.5% by weight. Example 3 Production of N-n-propylacrylamide The reaction and post-reaction treatment were carried out in exactly the same manner as in Example 1, except that N,N-dimethylformamide containing 7.0% by weight of water was used. The reaction was started in the same manner as in Example 1 with potassium hydroxide suspended. The conversion rate in the reaction is 87% and the selectivity is 81
%, and the production rate was 70%. Note that the amount of water in this reaction system was 5.0 weight. Comparative Example 3 Production of N-n-propylacrylamide 14 g of acrylamide, 0.05 g of phenothiazine and 31 g of n-propyl bromide were added to 150 ml of N,N-dimethylformamide, and after stirring and dissolving, the concentration was 47.5%.
19.9 ml of potassium hydroxide aqueous solution was added to start the reaction. At that time, the reaction solution formed two layers, and all of the potassium hydroxide was in a liquid state. Then Example 1
The operation was performed in exactly the same way. The conversion rate in this reaction was 63%, the selectivity was 48%, and the production rate was 30%. Note that the amount of water in this reaction system was 7.2% by weight. Example 4-7 A reaction was carried out using the combinations of raw materials, strong basic substances, and solvents listed in Table 1 under the conditions listed in Table 1. In addition,
In Example 4-5, the reaction was carried out by adding 0.05 g of phenothiazine. After the reaction, treatment was carried out in exactly the same manner as in Example 1, and the results shown in Table 2 were obtained. Example 8 Production of N,N,N',N'-tetramethylfumaramide 56g of potassium hydroxide (1.2 times the mole) and 23g of fumaramide were added to 150ml of N,N-dimethylformamide, and methylated at 40°C with stirring. 56 g of chloride was blown into the reactor, and the reaction was carried out for 4 hours. After the reaction, the insoluble matter was filtered out, the filtrate was distilled under reduced pressure, the solvent and unreacted raw materials were removed, and the distillation residue was recrystallized with ethanol.
27 g (yield 79%) of N,N,N',N'-tetramethylfumaramide with a melting point of 130-131°C was obtained. Example 9 A reaction was carried out using the combinations of raw materials, strong basic substances, and solvents listed in Table 1 under the conditions listed in Table 1. After the reaction, treatment was carried out in exactly the same manner as in Example 8, and the products listed in Table 2 were crystallized using the recrystallization solvents listed in Table 2.

【table】

【table】

[Table] Example 10 Production of N,N-dimethyl methacrylamide 17 g of methacrylamide, 0.005 g of phenothiazine, and 18 g (1.1 times the mole) of sodium hydroxide were added to 150 ml of dimethyl sulfoxide, and the mixture was heated at 40°C with stirring.
Then, 30 g of methyl chloride was blown into the solution, and the reaction was carried out for 3 hours. After the reaction, filter out the insoluble matter and add 150ml of benzene and water.
150 ml was added, thoroughly stirred and treated. After separation, the benzene layer was collected, and the aqueous layer was further extracted twice with 100 ml of benzene. After drying the benzene layer with magnesium sulfate, it was distilled under reduced pressure to give 65−67
A C/10 mmHg fraction was collected to obtain 19 g of N,N-dimethylmethacrylamide (yield: 86%). Example 11 Production of N,N-dimethylacrylamide 1.7g of potassium hydroxide (1.5 times the mole) was added to 20g of dimethyl sulfoxide, and after stirring at room temperature for 5 minutes, 0.7g of acrylamide and 5.7g of methyl iodide were added. The mixture was added and reacted for 5 minutes with stirring. After the reaction was completed, the reaction mixture was analyzed by gas chromatography using a 20M polyethylene glycol column. As a result, it was confirmed that 0.9 g of N,N-dimethylacrylamide was produced (yield: 92%). Comparative Examples 4 and 5 In the method of Example 11, the amount of potassium hydroxide was
The reaction was carried out in the same manner except that the amounts were changed to 0.3 g (0.3 times the mole) and 2.2 g (2.0 times the mole), resulting in a yield of 9% (56% conversion of acrylamide) and 41% (conversion of acrylamide), respectively. The conversion rate was 99%).

Claims (1)

[Claims] 1. A method for producing an N-alkyl-substituted unsaturated amide compound by simultaneously contacting and reacting a strong basic substance, an unsaturated amide compound, and an alkyl halide in an aprotic polar solvent. N-alkyl-substituted unsaturated, characterized in that the amount of the basic substance added is 0.5 to 1.5 times the molar amount to the hydrogen atom of the amide group, and the reaction is started under suspension of the basic substance. A method for producing an amide compound. 2. The method according to claim 1, wherein the amount of water in the reaction system at the start of the reaction is 5% by weight or less.