JP3362458B2 - Method for producing aromatic amide compound - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a process for producing an aromatic amide compound which selectively acylates an amino group of an aromatic amine derivative.

[0002]

2. Description of the Related Art Conventionally, in the synthesis of an acid amide using an acid halide, a base is present in order to capture hydrogen halide generated as a result of the reaction. As the base,
Usually, a tertiary amine is used. For example, when an aliphatic amine such as triethylamine is used, acid amidation of an aromatic primary amine derivative in which an aromatic ring is substituted with a hydroxyl group results in acylation of the hydroxyl group. The converted compound becomes the main product, and the target compound cannot be obtained. When an unsubstituted or monoalkyl-substituted heterocyclic compound such as pyridine or picoline is used for capturing hydrogen halide, an acid amide compound is preferentially obtained.
For industrial use, since pyridine and picoline have high solubility in water, the recovery method is complicated, and the waste water generated in the manufacturing process has a large load on the environment.

[0003]

It is an object of the present invention to develop a method for producing an aromatic amide compound, which selectively acylates only the amino group of a hydroxyl group-substituted aromatic primary amine derivative by an industrially advantageous method. To aim.

[0004]

As a result of intensive studies, the present inventors have found that as a method for producing an aromatic amide compound by selective acylation of an amino group of a hydroxyl group-substituted aromatic primary amine derivative, an acid halogen compound is used. By using a compound and a dialkyl-substituted pyridine as a deoxidizing agent, an industrially advantageous production method has been found out. That is, the present invention provides: Ar-NH ₂ · (A) n (1) Here, X ₁ and X ₂ each represent a hydrogen atom, an alkyl group, an alkoxy group, an acyl group or a halogen atom, and A is any one selected from HCl, H ₂ SO ₄ , HBr, p-toluenesulfonic acid and methanesulfonic acid. Or n is 0 or 1. ) And an aromatic amine derivative represented by the general formula (2) (In the formula, R represents an alkyl group having 1 to 10 carbon atoms and 1 to 10 carbon atoms.
It represents an alkoxy group having 10 carbon atoms, an alkyl group having 1 to 10 carbon atoms substituted with phenyl, and an alkoxy group having 1 to 10 carbon atoms substituted with phenyl. Here, the alkyl group or the alkoxy group may be substituted with a halogen atom. Z represents a halogen atom. ) Is used as a deoxidizing agent represented by the general formula (3) (Wherein X ₃ and X ₄ each represent a lower alkyl group), and the reaction is carried out in the presence of a dialkyl-substituted pyridine. ) General formula (4) (Wherein Ar and R have the same meanings as described above), and a method for selectively producing the aromatic amide compound.

In the general formula representing the compounds of the present invention:
X ₁ and X ₂ are each an alkyl group such as methyl, ethyl, propyl and butyl, methoxy, ethoxy,
Represents an alkoxy group such as propoxy and butoxy, an acyl group such as acetyl, propionyl, butyryl and pentyl, and a halogen atom such as fluorine, chlorine and bromine, and R is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl. , Nonyl, decyl,
2,4-dimethylhexyl, 2,3,6-trimethylheptyl, isobutyl, isopropyl, s-butyl, t-
Alkyl groups such as butyl, 1-methylbutyl, cyclohexyl, methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy,
Alkoxy groups such as 2,4-dimethylhexyloxy, 2,3,6-trimethylheptyloxy, isobutyloxy, isopropyloxy, s-butyloxy, t-butyloxy and 1-methylbutyloxy, benzyl, 2
-Phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 7-phenylheptyl, 8-phenyloctyl, 9
-Phenylnonyl, 10-phenyldecyl, benzyloxy, 2-phenylethyloxy, 3-phenylpropyloxy, 4-phenylbutyloxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 7-phenylheptyloxy, 8- Phenyloctyloxy, 9-
Phenylnonyloxy, 10-phenyldecyloxy, halomethyl, 2-haloethyl, 3-halopropyl, 4-halobutyl, 5-halopentyl, 6-halohexyl, 7-
Haloheptyl, 8-halooctyl, 9-halononyl, 10
-A haloalkyl group such as halodecyl, halomethoxy,
2-haloethoxy, 3-halopropoxy, 4-halobutoxy, 5-halopentyloxy, 6-halohexyloxy, 7-haloheptyloxy, 8-halooctyloxy, 9-halononyloxy, 10-halodecyloxy and the like. Represents a haloalkoxy group. Here, halo is chlorine
> Represents an atom or bromine atom. Z represents a halogen atom such as a fluorine atom, a chlorine atom and a bromine atom.

Examples of the dialkyl-substituted pyridine (3) used in the present invention include 5-ethyl-2-methylpyridine, 2,3-dimethylpyridine, 2,4-dimethylpyridine, 2,5-dimethylpyridine and 2 , 6-dimethylpyridine, 3,4-dimethylpyridine, 3,5-dimethylpyridine, 2,6-diisopropylpyridine, 2,
6-di-t-butylpyridine and the like can be mentioned.

In the reaction for reacting the aromatic amine derivative (1) with the acid halide (2) to obtain the aromatic amide compound (4), the amount of the acid halide (2) used is the same as the amine derivative (1). On the other hand, it is usually 0.3 to 2 times equivalent, but preferably 0.9 to 1.5 times equivalent. Further, the amount of the dialkyl-substituted pyridine (3) used for capturing the hydrogen halide generated as a result of the reaction is 1 to 10 times equivalent, preferably 1 to 5 times equivalent. However, when a salt with an acid is used as the aromatic amine derivative (1), it is preferably 2 to 6 times equivalent.

When a solvent is used in the above reaction,
Examples of the solvent include hexane, toluene, benzene, chlorobenzene, dichloromethane, chloroform,
Solvents such as carbon tetrachloride, tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, methyl isobutyl ketone, and other aliphatic or aromatic hydrocarbons, halogenated hydrocarbons, ethers, ketones, and the like inert to the reaction may be used. Moreover, the amount used is not particularly limited.

The reaction temperature is usually -30 to 100 ° C, preferably 0 to 80 ° C. The reaction time is not particularly limited, and the time point when the raw material aromatic amine derivative (1) or acid halide (2) disappears can be the end point of the reaction. After completion of the reaction, usual separation means such as extraction,
Aromatic amide compound (4) is obtained by operations such as liquid separation and concentration.
Can be obtained in good yield and, if necessary, can be purified by recrystallization, distillation or the like.

[0010]

According to the production method of the present invention, an aromatic amide compound can be produced by selectively acylating only the amino group of a hydroxyl group-substituted aromatic primary amine derivative by an advantageous method. It is possible, and the load of drainage is small, which is extremely advantageous industrially.

[0011]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Example 1 A 4-necked flask equipped with a stirrer and a thermometer was charged with 2-amino-phenol (10.9 g), 5-ethyl-2-methylpyridine (35.4 g) and toluene (200 ml).
Cooled to ° C. 14.1 g of benzoic acid chloride was added dropwise thereto while keeping the temperature at 0 to 10 ° C, and the reaction was carried out for 10 hours. After the reaction was completed, the reaction mixture was mixed with 5
The mixture was washed with aqueous HCl (%), washed with water, and then concentrated under reduced pressure to give a brown residue, which was purified by recrystallization to obtain 17.9 g of benzoyl-2-hydroxyanilide (yield 90%).

Examples 2 to 10 The aromatic amide compound (3) can be obtained by using the starting materials shown in Table 1 and carrying out a reaction and a post-treatment in the same manner as in Example 1.

[0014]

[Table 1]

[0015]

[Table 2]

Comparative Example The reaction was carried out in the same manner as in Example 4 except that triethylamine was used instead of 5-ethyl-2-methylpyridine. The main product is a product in which both the hydroxyl group and the amino group are acylated, and the yield of the aromatic amide compound in which only the target amino group is acylated is 7%.
I only got a degree.

─────────────────────────────────────────────────── ─── Continued front page (72) Inventor Tsutomu Matsumoto 2-10-1 Tsukahara, Takatsuki City, Osaka Prefecture Sumitomo Chemical Co., Ltd. (72) Inventor Masayoshi Minai 2-1-1 Tsukahara, Takatsuki City, Osaka Sumitomo Chemical Industry Co., Ltd. (56) Reference JP-A-52-62234 (JP, A) JP-A-4-211674 (JP, A) JP-A 63-159342 (JP, A) JP-A-49-35303 ( JP, A) JP-B-49-35612 (JP, B1) UK patent application publication 1088295 (GB, A) US patent 4046905 (US, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) C07C 231/02 C07C 233/75 C07C 235/56 C07B 43/06

Claims (2)

(57) [Claims] 1. A general formula (1) Ar-NH _2. (A) n (1) Here, X ₁ and X ₂ each represent a hydrogen atom, an alkyl group, an alkoxy group, an acyl group or a halogen atom, and A is selected from HCl, H ₂ SO ₄ , HBr, p-toluenesulfonic acid and methanesulfonic acid. One of them is shown, and n is 0 or 1. ) And an aromatic amine derivative represented by the general formula (2) (In the formula, R represents an alkyl group having 1 to 10 carbon atoms and 1 to 10 carbon atoms.
It represents an alkoxy group having 10 carbon atoms, an alkyl group having 1 to 10 carbon atoms substituted with phenyl, and an alkoxy group having 1 to 10 carbon atoms substituted with phenyl. Here, the alkyl group or the alkoxy group may be substituted with a halogen atom. Z represents a halogen atom. ) Is used as a deoxidizing agent represented by the general formula (3) (Wherein X ³ and X ⁴ each represent a lower alkyl group), and the reaction is carried out in the presence of a dialkyl-substituted pyridine represented by the general formula (4). (In the formula, Ar and R have the same meanings as described above.) A method for producing an aromatic amide compound. 2. The method according to claim 1, wherein the dialkyl-substituted pyridines are 5-ethyl-2-methylpyridine.