JPS5916861A - Preparation of n-substituted amide compound - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an adhesive, etc. inexpensively, by bringing an amide compound into contact with a halogen-substituted compound simultaneously in an aprotic polor solvent in the suspension of an alkali metal hydroxide having a specific surface area. CONSTITUTION:In preparing an N-substituted amide compound by bringing simultaneously a strongly basic substance and an amide compound (e.g., formamide) into contact with a halogen-substituted compound [e.g., alkyl halide (e.g., chloromethane)] in an aprotic polar solvent (e.g., acetonitrile), the reaction starts in the suspension of an alkali metal hydroxide (e.g., HaOH) having >=5cm<2>/g specific surface area. The surface shape of the strongly basic substance has great influence on the reaction, and has particularly great influence when the alkali metal hydroxide is used. When the alkali metal hydroxide having <=5cm<2>/ g specific surface area is used, the reaction rate becomes slow and may stop in the middle of the reaction.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an improved method for producing 1dNiff, converted amide compounds. More specifically, the present invention relates to an improved production method capable of producing both N-(6, substituted and N,N-disubstituted amide compounds).

In general, 14-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. , co-l (has advantages such as excellent adhesion properties, so it is used in adhesives, paints, paper processing agents, fiber processing agents, emulsions, urethane curing agents, pigment dispersants, plastic additives, polymer aggregation) Agent 1. It is known to have a wide range of applications such as ion exchange resins.
It is a compound useful as logs of compounds with complex structures such as dyes, amino acids, and natural products], intermediates, and products, and also as a raw material for amine production. However, N-
Since an inexpensive industrial production method for substituted amide compounds has not been established, they have not been used in large quantities.

In view of the above points, the present inventors have already made a
8441, an improved method for easily and inexpensively producing 19-substituted amide compounds is proposed.

According to the production method, an N-substituted amide compound is brought into contact with a strongly basic substance, an amide compound, and a halogen-substituted compound simultaneously in an aprotic polar solvent and a reaction is initiated under the influence of the basic substance. It has been found that during production, excess water present in the reaction system inhibits the production of the target N-substituted amide compound, and improvements have already been made.

In order to suitably carry out the method of the present invention, we have made extensive studies and found that
Table 111 The shape of the basic substance has a great influence on the reaction 1
・1 Alkali metal hydroxide f as a strong basic substance for scratches
I found that when using the proboscis, it becomes 31'1j.

In other words, it is a feature of the present invention that as the specific surface area of the alkali gold hydroxide increases, the formation of the converted amide compound, which is the target of N-1, becomes faster. Since the method is partly a homogeneous reaction, it is easy to produce 411t.
i! II can do it. On the contrary, the specific surface area 5 C7rb
/! If the following alkali metal hydroxides are used, regardless of the type of alkali metal, the reaction rate will slow down or the reaction will stop midway, making it difficult for the present invention to suitably carry out the process. is the specific surface area 5 ari/? We have discovered that it is essential to use an alkali metal hydroxide that satisfies the following two conditions, and have arrived at the present invention.

This book describes a method for producing a monosubstituted amide compound by simultaneously contacting a strong basic substance, an amide compound, and a chlorine-substituted compound in an aprotic bath medium, with a specific surface area of 5 cl(/ This is a method for producing an N-substituted amide compound, the key feature of which is to initiate a reaction under the influence of an alkali metal hydroxide having an alkali metal hydroxide.

The alkali metal hydroxides used in the method of the present invention include lithium hydroxide, sodium hydroxide, potassium hydroxide, etc., with preference given to the use of thorium hydroxide and potassium hydroxide.

Since the specific surface area of these alkali metal hydroxides is generally very small, it is extremely difficult to measure the specific surface area using techniques such as ordinary adsorption methods.

Therefore, the present inventors photographed the alkali metal hydroxide, enlarged its shape, created a simple model based on the photograph, and calculated the specific surface area. For example, the specific surface area was calculated using a hemisphere for a granular material, or a plate-like material for a flaky material, and the irregularities on the surface were ignored.

According to this method, there was no significant difference in specific surface area between sodium hydroxide and potassium hydroxide as long as the shapes were the same.

According to experiments by the present inventors, the specific surface area of pelleted alkali metal hydroxide is (already 4 cni/fi
Therefore, the specific surface area of the method of the present invention is 5'cn.
f/ri"-, and the method of the present invention can be carried out suitably. 1. If the specific surface area is thickened by crushing, it is generally 1.
Although it is possible to quickly generate the target 14-substituted amide compound, there are also problems such as dusting due to pulverization, blocking due to moisture absorption, and decreased activity due to absorption of carbon dioxide gas. However, increasing the specific surface area does not necessarily produce the same effect. Therefore, the optimum specific surface area depends on the combination of the base material 1 and the electric medium and cannot be uniformly discussed.

However, in the method of the present invention, at least the specific surface d<
An alkali metal hydroxide having a diameter of 5 orf/V or less is used, preferably 10 cnt/1 or more,
Even better is 10-1000 c1rt/f! The one with the following is used.

Next, regarding amide compounds, halogen-substituted compounds, and aprotic polar solvents that can be applied to the present invention, patent application No. 56
-198441 are applicable.

That is, among amide compounds, monoamide compounds include aliphatic saturated carboxylic acid amide, aliphatic unsaturated carboxylic acid amide, aromatic carboxylic acid amide, alicyclic carboxylic acid amide, urea and its derivatives. Examples of the polyamide compound include aliphatic saturated polycarboxylic acid amide, aliphatic unsaturated polycarboxylic acid amide, aromatic polycarboxylic acid amide, and alicyclic polycarboxylic acid amide.

Representative examples of these compounds include formamide, acetamide, propionamide, stearamide, ethoxyacetamide, acrylamide, methacrylamide, crotonamide, xyacrylamide, heptinamide, penzagodo, nitrobenzamide,
Toluamide, natutamide, phenylacetamide, nunnamite, cyclopentanecarboxamide, soclohegysancalfogizamide, / clohequinulgropioamide, bili/ncarbogizamide, urea, oxamide, malonacido, geltalamide, upamide, maleamide, fumaramito, Canforamide, / clohegizandicarphogizamide, fumaramide, maleamide, phthalamide I, inonotalamito, terephthalamide, etc. can be mentioned.

Reacting with a S-do compound... to form a logeno-substituted compound, and -1, a halogenated alkyl polyhalogenated alkyl,... a halogenated polycyclic compound,... a halogenated aryl, a halogenated alkylaryl, Alkenyl halides, alkenyl aryl halides, carbonic acid halides, sulfonate halides, halogen-substituted carboxylic acids and their esters, halokene i61-converted ethers, complex-containing halogenides, heteroatom-containing halogenides, etc. It can be opened.

Among these compounds, representative ones are exemplified as chlorine-substituted compounds: chloromethane, chloroethane, chloropropane, chlorobutane, chloroethane, chlorododecane, dichloromethane, dichloroethane, /chloropropane, cyclobutane, dichlorohebutane, cyclohexane, chloro Noclohexane, chloromethylcyclohexane, chlorobenzene, chlorotoluene, chlorostyrene, chloronitrobenzene, chloroacrylic, chloroallylbenzene, chloronaphthalene, benzyl chloride, phenethyl chloride, chloromethylnaphthalene,
Chloropenpyl chloride, allyl chloride, chloroallyl chloride, propargyl chloride, methallyl chloride, styryl chloride, cinnamyl chloride, formyl chloride, acetyl chloride, propionyl chloride, butyryl chloride, stearoyl chloride, adipoyl chloride, acryloyl chloride, methacryloyl chloride, crotonoyl chloride, fumaroyl chloride, benzoyl chloride, phenylacetyl chloride, phthaloyl chloride, ethanesulfonyl chloride, benzenesulfonyl chloride, chloroacetic acid, chloropropionic acid, chloroacrylic acid) , chloro]11'
Allyl 1 acid, chloro1norohyon fζ9 phenyl,
Chloroma product 7m no mini chill, l'M'l acid chlorine
lconityl, acrylic chloroethyl chloride, 21-ethyl benzoate, chloromethyl methyl needle, chloroethyl ethyl ether, chloromethyl vinyl chloride, chloroethyl piperi, chloropropylcarbasonope, epichlorohydrin, methyl epichlorohydri/,
Chloropropionitrile, chloroacrylny-'J
chloronitropropane, chloroethanesulfone i'
Iv. , N-(chloroethyl)dimethyl-amine J'A
i. z Chloromethylethyl sulfide, Biscro [j
Conityl sulfurate Next, there are no restrictions on the reaction medium as long as it is an aprotic solvent, but suitable ones for carrying out the reaction are acetonitrile, N,N-7 methylformago, ,N,
Examples include N-dimethylacetamide, dimethylsulfoginde, sulfolane, tetraglyme, 1-methyl-2-imidazolidinone, and the like. However, in the method of the present invention, it is necessary to start the reaction in a state where at least a portion of the substance is soaked in strong basicity, and the amount of water in such a state is determined by the water content of the reaction solution. The slope is usually about 6%. On the other hand, if the amount of JEJ combined water exceeds this amount, side reactions such as hydrolysis of rogane-substituted compounds or amide compounds are likely 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, the reaction system should be hydrated at least 5:t.
fft% or less, preferably d, 25 sandbars or less, and preferably 10,000 1) l]11 or less for ribs.

The amount of solvent to be used is not particularly limited, but is in the range of 5 to 95% by weight, preferably 10 to 9% by weight, based on the total amount of reactants including the solvent.

In carrying out the present invention, the reactivity of the amide compound as a raw material, the halogen-substituted compound, and the amide compound, or whether the desired product is an N-monosubstituted amide compound, N,N
-It depends on whether it is a disubstituted amide compound, -It is difficult to define in general, or it is convenient to use a 1-, halokene-substituted compound when producing an N--1-fΔ-substituted amide compound. [tJ The amount of the strong basic substance used is 0.2-10 times the mole of the amide compound, preferably 0.3-7 times the mole of the amide compound, and the amount of the strong basic substance used is 0.3-10 times the mole of the amide compound. The preferred range is 0.5 to 7 times the mole.

1. When producing an N-3-position 1″ substituted amide compound,
The amount of the halokene-substituted compound to be used is 4.0 to 20 times the mole of the -γ amide compound, preferably 1.5 to 15 times the mole, which is 111 times the amount of the -γ amide compound. The amount used is 15 to 20 times the mole of Agodo compound, 1 part per 2 parts.
．． 0 to 15 times the molar Kfij.

It is also possible to produce N-, N-, or amide compounds having different Nij substituents, and in that case, two halogen-substituted compounds may be reacted with 4[1]. 2
The relative use of the halogen-substituted compound varies depending on the reactivity of the halogen-substituted compound, but it is generally 10 to 20 times the amount of the reactive compound, 1li1.
It is in the range of 0 to 15 times the mole. Another method for producing N,N-disubstituted amide compounds having different substituents is to react with a first halogen-substituted compound and then react with a second halogen-substituted compound. It is also possible to produce N-
Anru cyclic imine compound can be prepared from bishaloalkyl ether compound J-, 1) Example, t Irf N-acylmorpholine can be prepared from bishaloalkyl sulfide compound, for example N-a/ruthiomorpholine.

When using an unsaturated amide compound, it is necessary to add a polymerization inhibitor to prevent polymerization of raw materials and products during the reaction and purification steps. The polymerization inhibitor in this case is not particularly limited, but generally includes phenol-based inhibitors, amine-based market inhibitors, mercaptan-based IE inhibitors, and copper powder.

Next, when producing an N-substituted amide compound according to the method of the present invention, it may be necessary to first grind the alkali metal hydroxide. In particular, when using a granular product, it is necessary to crush it, and even when using a flake-like product, pulverization may result in a smaller size. At that time, the grinding L to be used
As H and Q, any type of R structure such as d compression type, impact type, J umbrella type, and shear type can be used, but since alkali metal hydroxides are relatively easy to crush, roll crushers, Compression type or impact type crushing machines such as Edge Runner, Hammer Mino Tsutsu, and Rotary Crannon Yare are sufficient. Octopus, alkali metal hydroxide (the proboscis easily absorbs moisture and carbon dioxide gas, so it is better to crush it quickly and use it for the reaction).

Although the reaction is carried out using the alkali metal hydroxide thus ground, there is no particular restriction on the order in which the raw materials are added.

However, when using a highly reactive halogen-substituted compound, it is more convenient to add the halogen-16]-substituted compound after the preparation and react, in terms of suppressing side reactions.

The reaction temperature also depends on the reactivity of the 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 amide compound may occur. The yield of raw products is reduced. Therefore, it is usually -20 to 100℃, or -10 to 90℃.
The reaction is preferably carried out in the temperature range of 0 to 70'C, except for certain halogen-substituted compounds. As long as it is within this 7+'M degree range, it is not necessarily necessary to maintain a constant temperature of 6m degrees during the reaction, but it is necessary to keep track of the progress of the reaction and set the reaction temperature appropriately to carry out the reaction efficiently.
good.

Although the reaction time varies depending on the amide compound and halogen-substituted compound used as well as the reaction temperature, a time of 30 hours at the longest, usually within 101 hours is sufficient. The course of the reaction can be monitored by changing the conditions of the reaction system and by determining the concentration of IW of the raw materials and target product in the reaction solution by gas chromatography or high performance liquid chromatography.

After the reaction, the alkali metal chloride produced as a by-product is separated and distilled under reduced pressure by a conventional method to obtain a highly pure target product. However, if the alkali metal chloride is dissolved in the reaction solution or if a sublimable crude acid compound remains, after distilling off the layer line, benzene/cene-water, chloroform-
After removing the substances listed in - by combining the d agents that form two water-like layers and keeping the pressure at 7, the desired product of high-purity helmet j is obtained.
is obtained.

In cases where the desired product is highly (astigmatic or thermally decomposable), the desired product can be produced by solvent extraction and removal of the inner crystal layer.3. 1
The medium is 7 methyl sulfoxide θ11<, the mixture with water is 1' (total N-gataki<, the target product is N-argyl tM',
%J! A < l- Compound 1 of course 11 When the compound is highly lipophilic, dl, after the reaction, add water to the anti-LL, and separate the proboscis as an oil layer.
A method in which the target material is eroded using a agent that forms a two-layer with water, such as toluene or chloroform, can also be applied.

According to the present invention, as a strong basic substance, the specific surface area is 5o1/
By using an alkali metal hydroxide monomer north of Si', the N-1id-converted amide compound can be produced quickly and efficiently.

Next, the present invention will be explained to the prefecture based on the first implementation.

Example 1 Production of J→,N-dimethylacrylamide: 200+u of N,N-dimethylformamide (1
67, flaky potassium hydroxide (specific surface area 12 ar
f/'if) 28f and phenothianone [], [
157 was added thereto, and 35 g of methyl chloride was blown in at 4[]'C while blowing I'j#, and the reaction was carried out for 5 hours.

Against! After the core, filter out the impurities, LRF, distill the liquid, 80
-81℃, /20+qm, 1-1g fraction was collected,
N,N-dimethylacrylamide 17'i/(yield 76
(In charge) is (4).

N,N-dimethylacrylamide was produced in exactly the same manner as in Example 1, except that the reaction conditions for the strong basic substances listed in Comparative Example 1, Example 2, and Table 1 were applied. I got the results described.

Example 4 N, Ill, N: Production of rq'-tetraglycidyl terephthalamide Near methyl sulfoxide 20017+J, terephthalamide filter 01, epichlorohydrin 857, flaky sodium hydroxide (specific surface area 15 cnt/fl) 32
7 was added thereto, and the reaction was carried out at 60°C for 6 hours.

After incubation, after separating the insoluble matter by d°1, the raw materials and solvent were distilled off, and the remaining liquid was mixed with 100++ lJ of Pennanano and 50% of distilled water.
〃+6 was added, and after 1.4 liters were separated, 50 yte of the aqueous solution layer was collected and dried with magnesium sulfate.

After Bense and distillation, further 120℃/2 +++m'H
The remaining 'd' medium is distilled off at g, and the target N, Ill,
rq: ty'-tetraglycy/luterephthalamide 4
87 (yield: 7 filtration) was obtained.

Comparison 1+1.2, Examples 5 and 6 Same as Example 4 except that the strong basic substance and reaction conditions listed in Table 2 were reversely used. N, N, N; 14
'-detraglin/luterephthalamide was produced and the results shown in Table 2612 were obtained.

Example 7 +y, +<-/Manufacture of allyl acrylamide: N,
To + -Q methylformamide 200 + I + ff, acrylamide 167, allyl bromide 607, flaky potassium hydroxide (specification table to +,! quality 12 c1jt
/f) 287 and phenothiazino 0.05 i?
was added, and the reaction was carried out at 20°C for 6 hours.

After the reaction, after rinsing the unheavy part to d='M, the raw materials and solvent were distilled off, and the residual liquid was mixed with 10 omJ of benzene and 50 ml of distilled water.
dll was added, stirred thoroughly, separated, and stratified in a water bath for 5 minutes.
'O1lldN, I.j-/allylacrylamide 27
2 (yield 8%) was obtained.

Comparative example 6, practical examples 8 and 9 Fire treatment 117 and total < 11 except that strong J, I, :IJ:', appendix 'A, and reaction conditions described in Table 1 were applied.
fj+) N,N-/allylacrylamide was produced using the previous method, and the results of the threads shown in Table 6 and 1-1 were examined.

Claims (1)

[Claims] (1) A method for producing an N-1i'4-substituted amide compound by simultaneously contacting a strong basic substance, an amide compound, and a rogen-substituted compound in an aprotic polar solvent, with a specific surface area of 5 oa/Y 1. A method for producing an N-substituted amide compound, which comprises initiating a reaction under the influence of an alkali metal hydroxide having the following.