JPH0967299A - Production of acid halide - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a compound advantageously in terms of economic and environmental aspects by reacting a carboxlic acid with a haloiminium salt. SOLUTION: (A) A carboxlic acid containing a hydroxyl group and/or amino group (e.g. 5-amino-2,4,6-triiodoisophthalic acid) is reacted with (B) a haloiminium salt of the formula (R<1> and R<2> are each a lower alkyl; X is a halogen; (n) is 2 or 3) (e.g. 2-chloro-1,3-dimethylimidazolium chloride). The amount of the component B used based on the component A is equal to or more than stoichiometric amount (especially preferably 1.1-1.3 times as much as the stoichiometric amount of the compound A). The reaction is carried out at room temperature to 70 deg.C for several hours to tens hours. Lauric acid chloride may be cited as the compound.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing an acid halide.

[0002]

2. Description of the Related Art Recently, acid halides have become industrially important as reaction intermediates for the production of heat-resistant resins and the production of pharmaceuticals and agricultural chemicals. For example, lauric acid chloride is used industrially as an intermediate in the production of peroxides and surfactants, and terephthalic acid chloride is used industrially in the production of polyesters. Further, 5-amino-2,4,6-triiodoisophthalic acid dihalide obtained by acid-halogenating 5-amino-2,4,6-triiodoisophthalic acid (hereinafter abbreviated as TIPA) is a radiographic contrast agent. It is an important compound as a raw material.

As a method for producing an acid halide, a method of chlorinating a carboxylic acid with a chlorinating agent such as thionyl chloride, phosphorus pentachloride, phosphorus trichloride, phosphoryl chloride and phosgene is generally used. However, chlorinating agents such as thionyl chloride, phosphorus pentachloride, phosphorus trichloride, and phosphoryl chloride are expensive, and the treatment of sulfur oxides, phosphorus oxides, and by-products produced by the reaction is problematic, and economical. Also, from an environmental point of view, industrial scale manufacturing has various disadvantages and difficulties.
Also, phosgene is less reactive than the above chlorinating agents and requires the use of a catalyst. Examples of the catalyst include dimethylformamide (Japanese Patent Publication No. 43-10613), quaternary ammonium salts and phosphonium salts (Japanese Patent Publication No. 44-27363), and lower aliphatic amides such as dimethylformamide have high activity and can be obtained at low cost. So generally available.

However, even if it is used, the reactive species produced by phosgene and a lower aliphatic amide such as dimethylformamide are thermally unstable at high temperatures, and at a temperature of 100 ° C. or higher, the rate of formation of tar-like substances is high. However, there is a problem in that 2-Chloro-1,3-dimethylimidazolinium chloride is known as a halogenating agent for primary hydroxyl groups (JP-A-4-30853).
8), no example is known for use in the production of acid halides.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in order to solve the above-mentioned problems of the conventional method for producing an acid halide, and the first object thereof is excellent in economical aspect. The second purpose is to propose an excellent method from an environmental point of view.

[0006]

Means for Solving the Problems As a result of intensive studies to achieve these objects, the present inventors have arrived at the present invention having the following constitution.

That is, the present invention relates to 1) carboxylic acids represented by the general formula (1)

Embedded image (Wherein R ¹ and R ² are the same or different and each is a lower alkyl group, X is a halogen atom, and n is an integer of 2 or 3) and the haloiminium salt is reacted. Method for producing acid halide, 2) General formula (2) for carboxylic acids

Embedded image (Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, and n represents an integer of 2 or 3), and a cyclic urea compound represented by the formula (1) is blown with phosgene. )

[Chemical 6] (Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents an integer of 2 or 3), and a haloiminium salt represented by the formula:
A method for producing an acid halide, which comprises reacting the carboxylic acid with the haloiminium salt, 3) the method according to 2), wherein the cyclic urea compound is 1,3-dimethylimidazolidin-2-one, 4) carvone The method of 1) or 2) above, wherein the acid is a compound having a hydroxyl group and / or an amino group, 5) the method of 4) above, wherein the compound having a hydroxyl group and / or an amino group is an aromatic carboxylic acid having a hydroxyl group, 6 ) The method according to 4) above, wherein the compound having a hydroxyl group and / or an amino group is an aromatic carboxylic acid having an amino group, 7) the aromatic carboxylic acid having an amino group is 5-amino-
The method of 6) above which is 2,4,6-triiodoisophthalic acid, and 8) the method of 1) above wherein the haloiminium salt is 2-chloro-1,3-dimethylimidazolinium chloride.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The haloiminium salt used in the present invention is represented by the general formula (1), and as the lower alkyl group represented by R ¹ and R ² in the general formula (1), , Methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group and the like. The halogen atom represented by X is a fluorine atom,
Examples thereof include a chlorine atom, a bromine atom and an iodine atom, but a chlorine atom is particularly preferable. Moreover, among the haloiminium salts represented by the general formula (1), 2-chloro-1,3-dimethylimidazolinium chloride (hereinafter abbreviated as DMC) and 2-chloro-1,3-diisopropyl are preferable specific examples. Imidazolinium chloride, 2-chloro-1,
Examples thereof include 3-dimethyl-3,4,5,6-tetrahydropyrimidinium chloride.

The haloiminium salt is represented by the following general formula (2), which is known as an easily available solvent.

[Chemical 7] (Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents an integer of 2 or 3), an oxalylhalogenide, Phosphorus trihalide, phosphorus pentahalide,
It can be easily obtained by reacting a halogenating agent known per se such as phosphorus oxyhalide, phosgene, trichloromethyl chloroformate and the like. Of these, phosgene is used in large quantities at low cost in the urethane industry, is economically advantageous, and is preferable because it does not produce industrial waste such as phosphorus compounds.

In this reaction, either the compound of the general formula (2) or the halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride, and the other is added little by little, and the mixture is further heated at room temperature to 70 ° C. The reaction is carried out for several hours to several tens of hours. The haloiminium salt represented by the general formula (1) thus obtained can be isolated and used, but the reaction solution can also be used for the reaction of the present invention without isolation.

First, a method for reacting a carboxylic acid with a haloiminium salt will be described. The amount of haloiminium salt used relative to the carboxylic acid is at least a stoichiometric amount, preferably 1.0 to 2.0 times, more preferably 1.1.
~ 1.3 times. After the completion of the reaction, the haloiminium salt can be returned to the compound represented by the general formula (2) to react with the halogenating agent again to form a haloimimine salt.

The embodiment of the present invention is to prepare an iminium chloride in which X is chlorine in the general formula (1),
It includes a mode in which the generated iminium chloride is reacted with carboxylic acids. That is, the target acid chloride can be obtained by charging phosgene into a solution containing the starting carboxylic acids and the cyclic urea compound of the general formula (2) and reacting them. In this reaction, first, the cyclic urea of the general formula (2) reacts with phosgene to form an iminium chloride in which X is chlorine in the general formula (1), and then the carboxylic acid is halogenated by this iminium chloride. , The desired carboxylic acid chloride is produced. At this time, the iminium chloride in which X is chlorine in the general formula (1) returns to the original cyclic urea of the general formula (2). Therefore, the cyclic urea of the general formula (2) used in this case is 0.01 equivalent or more, especially 0.0
It is preferable to use 5 to 0.1 equivalent, and even if it is used more than this, the reaction rate does not increase.

The amount of phosgene used in this case is 1.0 to 2.0 equivalents, preferably 1.1 to 1.3 equivalents, based on the carboxylic acid, and this amount is maintained for 6 to 10 hours. , Preferably 7 to 8 hours are required for charging.

The carboxylic acids used in the present invention include, for example, formic acid, acetic acid, propionic acid, butanoic acid, isobutanoic acid, pentanoic acid, 3-methylbutanoic acid, pivalic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, Decanoic acid, myristic acid, palmitic acid, stearic acid, phenylacetic acid, diphenylacetic acid, acetoacetic acid, phenylpropionic acid, cinnamic acid, monochloroacetic acid, dichloroacetic acid,
Aliphatic monocarboxylic acids such as trichloroacetic acid, chloropropionic acid, α-bromoacetic acid, dibromoacetic acid, α-bromopropionic acid and oxalic acid, malonic acid, succinic acid,
Methylsuccinic acid, glutaric acid, adipic acid, 1,1-
Dimethyl-1,3-dicarboxypropane, 1,5-pentanecarboxylic acid, 1,6-hexanecarboxylic acid, 1,
Aliphatic dicarboxylic acids such as 7-heptanecarboxylic acid and 1,8-octanecarboxylic acid and benzoic acid, toluic acid,
4-isopropylbenzoic acid, 4-tert-butylbenzoic acid, methoxybenzoic acid, dimethoxybenzoic acid, 3,
4,5-trimethoxybenzoic acid, o-chlorobenzoic acid,
Aromatic monocarboxylic acids such as 2,6-dichlorobenzoic acid, 3,4-dichlorobenzoic acid, 2,3,6-trichlorobenzoic acid and 4-bromobenzoic acid, and phthalic acid, isophthalic acid, terephthalic acid, 2 -Chloroterephthalic acid,
Aromatic dicarboxylic acids such as 2,5-dibromoterephthalic acid and further aliphatic carboxylic acids having a secondary hydroxyl group in the same molecule such as lactic acid, butyric acid and 3-hydroxy-2,2-dimethylpropionic acid, salicylic acid, 5- Methoxysalicylic acid, 2-oxy-m-toluic acid, 3,5-di-ter
aromatic carboxylic acids having a hydroxyl group in the same molecule such as t-butylsalicylic acid and p-hydroxybenzoic acid, and β
-Alanine, 4-aminobenzoic acid, 3-aminobenzoic acid, N-methylaminobenzoic acid, m-dimethylaminobenzoic acid, 5-amino-2,4,6-triiodoisophthalic acid, etc. Examples thereof include a carboxylic acid having a group, and further, a carboxylic acid having a mercapto group in the same molecule such as 3-mercaptopropionic acid and o-mercaptobenzoic acid, but are not limited thereto. Incidentally, for carboxylic acids having an amino group in the same molecule, it is preferable to carry out the reaction using a hydrochloride or the like.

It should be noted that the above-mentioned carboxylic acids having a hydroxyl group or an amino group in the same molecule are effectively halogenated by the haloiminium salt of the general formula (1). For example, when the known chlorination reaction of carboxylic acids with phosgene using dimethylformamide as a catalyst is applied to aromatic carboxylic acids having an amino group in the same molecule, a formamidine derivative is produced to obtain a desired carboxylic acid chloride. However, according to the present invention, a desired carboxylic acid halide can be obtained from an aromatic carboxylic acid having an amino group in the same molecule without protecting the amino group.

The solvent used in the present invention is represented by the general formula (1):
There is no particular limitation as long as it is a known solvent that does not react with the haloiminium salt represented by and is used in the production of acid halides. For example, hydrocarbon solvents such as benzene, toluene, xylene, hexane, heptane, and cyclohexane,
1,2-dichloroethane, chloroform, carbon tetrachloride,
Examples thereof include halogenated hydrocarbon solvents such as chlorobenzene and dichlorobenzene, ester solvents such as ethyl acetate and butyl acetate, but are not limited thereto.

The reaction temperature of the present invention depends on the reaction substrate and solvent, but is generally selected from room temperature to 120 ° C.
For example, 1,2-dichloroethane is preferably 7
5 to 80 ° C., preferably 105 to 11 in the case of toluene
The temperature is 0 ° C., but is not limited thereto.

This reaction can also be carried out in the presence of a base. This makes it possible to increase the reaction rate and decrease the reaction temperature. As the base, pyridine, triethylamine, tributylamine or the like can be used.

The acid halide thus formed can be obtained by treating the mixture after the reaction according to a conventional method such as distillation or crystallization. The reaction between TIPA and the haloiminium salt can also be carried out by the method described above. In this case, a preferable aspect is shown below.

The amount of haloiminium salt used relative to TIPA is at least a stoichiometric amount, preferably 2.0 to 4.0 times mol, more preferably 2.1 to 2.5 times mol. After completion of the reaction, the haloiminium salt has the above general formula (2).
The haloiminium salt can be obtained by returning to the above compound and reacting with the halogenating agent again. The reaction temperature between TIPA and haloiminium salt is preferably 50 ° C. or higher, optimally 9
It is 0 to 110 ° C.

5-amino-2 from the reaction mass obtained,
The 4,6-triiodoisophthalic acid dihalide is taken out by removing the solvent from the reaction mass and adding hexane or the like to the residue to crystallize 5-amino-2,4,6-triiodoisophthalic acid dihalide. be able to.

[0022]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 Synthesis of lauric acid chloride 9.30 g (0.055 mol) of 2-chloro-1,3-dimethylimidazolinium chloride and 50.1 of toluene
g was added, and then 10.02 g (0.05 mol) of lauric acid was added and reacted at 110 ° C. for 4 hours. The reaction mixture was analyzed by gas chromatography and liquid chromatography to find that the conversion of lauric acid was 10
0% and lauric acid chloride was obtained in a yield of 100%.

Example 2 Synthesis of benzoic acid chloride 9.30 g (0.055 mol) of 2-chloro-1,3-dimethylimidazolinium chloride was added to 50.1 of toluene.
g, and then benzoic acid 6.11 g (0.05 mol)
Was added and reacted at 110 ° C. for 7 hours. When the reaction mixture was analyzed by gas chromatography and liquid chromatography, the conversion rate of benzoic acid was 100% and benzoic acid chloride was obtained in a yield of 100%.

Example 3 Synthesis of benzoic acid chloride To 9.72 g (0.0575 mol) of 2-chloro-1,3-dimethylimidazolinium chloride, 90 ml of 1,2-dichloroethane and 6.11 g of benzoic acid (0.05)
Mol) was added, the reaction mixture was kept at 15 to 20 ° C., 5.06 g (0.05 mol) of triethylamine was added dropwise over 30 minutes, and then the mixture was reacted at room temperature for 4 hours. When the reaction mixture was analyzed by gas chromatography, benzoic acid chloride was obtained in a yield of 93%.

Example 4 Synthesis of benzoic acid chloride In a four-necked flask equipped with a stirrer, gas inlet tube, thermometer and Dimroth condenser, 1,3-dimethyl-catalyst was added.
2-Imidazolidinone 3.42 g (0.03 mol), benzoic acid 36.64 g (0.3 mol) and toluene 14
6.56 g was charged. 4.2 with stirring phosgene
It was blown in at a rate of g / hour and reacted at 110 ° C. for 7 hours. When the reaction mixture was analyzed by gas chromatography, benzoic acid chloride was obtained in a yield of 95%.

Example 5 Synthesis of terephthalic acid chloride To 18.6 g (0.11 mol) of 2-chloro-1,3-dimethylimidazolinium chloride was added 83 g of toluene, and then 8.31 g (0.05 mol of terephthalic acid). ) Was added and reacted at 110 ° C. for 4 hours. When the reaction mixture was analyzed by gas chromatography, terephthaloyl chloride was obtained in a yield of 98%.

Example 6 Synthesis of succinic acid dichloride 19.44 g (0.115 mol) of 2-chloro-1,3-dimethylimidazolinium chloride and 83 g of toluene
Was added, and then 5.00 g (0.05 mol) of phthalic anhydride was added and reacted at 110 ° C. for 11 hours. When the reaction mixture was analyzed by gas chromatography,
Succinic acid dichloride was obtained in a yield of 90%.

Example 7 5-Amino-2,4,6-triiodoisophthalic acid dichloride
Synthesis of lolide 2-chloro-1,3-dimethylimidazolinium chloride 4.23 g (0.025 mol) and 5-amino-2,
5.56 g of 4,6-triiodoisophthalic acid (0.01
Mol) and 80 g of toluene are charged to a reaction flask,
The reaction was carried out at 105 to 110 ° C for 4 hours. Then, the reaction mass was cooled and toluene was removed under reduced pressure. 100 ml of hexane was added to the obtained concentrate to give 5-amino-2,4,6.
-Triiodoisophthalic acid dichloride was crystallized.
This is filtered off and dried under reduced pressure to give white 5-amino-2,4,4.
5.65 g of 6-triiodoisophthalic acid dichloride
(Yield / 95%) was obtained.

Example 8 5-amino-2,4,6-triiodoisophthalic acid and 2
Example 7 was repeated except that the reaction with -chloro-1,3-dimethylimidazolinium chloride was carried out at 90 to 95 ° C for 6 hours. 5.53 g of 5-amino-2,4,6-triiodoisophthalic acid dichloride (yield / 93
%) Was obtained.

Example 9 Synthesis of 4-hydroxybenzoic acid chloride To 9.72 g (0.0575 mol) of 2-chloro-1,3-dimethylimidazolinium chloride, 90 ml of 1,2-dichloroethane and 6-hydroxybenzoic acid 6 were added. .9
After adding 1 g (0.05 mol), reaction mixture 15-2
While maintaining the temperature at 0 ° C, 5.06 g (0.05 mol) of triethylamine was added dropwise over 30 minutes, and then reacted at 15 to 20 ° C for one day. When the reaction mixture was analyzed using liquid chromatography and gas chromatography,
Unreacted 4-hydroxybenzoic acid was 1.79 g (0.0
13 mol) remained and 4-hydroxybenzoic acid chloride was obtained in a yield of 72%.

Example 10 To 93 g (0.55 mol) of 2-chloro-1,3-dimethylimidazolinium chloride, 500 g of toluene was added, and then 100.2 g (0.5 mol) of lauric acid was added to the mixture at 110 ° C. The reaction was carried out for 4 hours. When the reaction mixture was analyzed by gas chromatography and liquid chromatography, the conversion rate of lauric acid was 100% and lauric acid chloride was obtained in a yield of 100%. Toluene was distilled off from this reaction mixture by vacuum distillation, followed by 1,3-dimethyl-2-imidazolidinone 5
6.5 g (0.495 mol) were recovered by vacuum distillation (106-108 ° / 17 mm). Subsequently, 102.8 g (0.47 mol) of lauric acid chloride was obtained (yield 94%) (142 to 144 ° / 15 mm).

Comparative Example 1 11.3 g (0.02 mol) of TIPA, 0.15 of DMF
g (0.002 mol) and 100 ml of toluene were charged into a reaction flask and the temperature was raised to 70 ° C. The temperature of the reaction mass is 70
Phosgene was blown in at a rate of 4 g / h for 2 hours while maintaining at -80 ° C. The reaction mass was then purged with nitrogen at 70-80 ° C for about 1 hour. After cooling, the crystals in the reaction mass were filtered off and dried under reduced pressure (9.53 g). The crystals were a mixture of unreacted TIPA and 2,4,6-triiodo-5- (N, N-dimethylaminomethylidene) aminoisophthalic acid dichloride.

[0034]

INDUSTRIAL APPLICABILITY According to the present invention, when the acid halide is produced, the use of the haloiminium salt represented by the general formula (1) is more efficient than the conventional method from the economical and environmental viewpoints. The target compound can be obtained. The cyclic ureas of the general formula (2) produced by the reaction of the haloiminium salt of the general formula (1) with a carboxylic acid are recovered and used again for the synthesis of the haloiminium salt of the general formula (1). Therefore, there is a great economic advantage.

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Claims (8)

[Claims] 1. A carboxylic acid having the general formula (1): (Wherein R ¹ and R ² are the same or different and each is a lower alkyl group, X is a halogen atom, and n is an integer of 2 or 3) and the haloiminium salt is reacted. Method for producing acid halide. 2. A carboxylic acid represented by the general formula (2): (Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, and n represents an integer of 2 or 3), and a cyclic urea compound represented by the formula (1) is blown with phosgene. ) [Chemical 3] (Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents an integer of 2 or 3), and a haloiminium salt represented by the formula:
A method for producing an acid halide, which comprises reacting the carboxylic acid with the haloiminium salt. 3. The method according to claim 2, wherein the cyclic urea compound is 1,3-dimethylimidazolidin-2-one. 4. The method according to claim 1, wherein the carboxylic acid is a compound having a hydroxyl group and / or an amino group. 5. The compound having a hydroxyl group and / or an amino group is an aromatic carboxylic acid having a hydroxyl group.
the method of. 6. The method according to claim 4, wherein the compound having a hydroxyl group and / or an amino group is an aromatic carboxylic acid having an amino group. 7. The aromatic carboxylic acid having an amino group is 5
The method of claim 6 which is -amino-2,4,6-triiodoisophthalic acid. 8. The haloiminium salt is 2-chloro-1,3.
-Dimethylimidazolinium chloride.
the method of.