JPH07138215A - Production of amides - Google Patents

Abstract

PURPOSE:To provide a method for efficiently producing an amide from an oxime under an approximately neutral and mild condition. CONSTITUTION:An oxime of formula 2 (R<3> and R<4> are each an organic group and may be bonded to form a ring) is reacted with a haloiminium salt of formula 1 (R<1> and R<2> are lower alkyl; X is halogen; n is 2 or 3) such as 2-chloro-1,3- dimethylimidazolium chloride in the presence of a base B to produce an amide of formula 5. In the reaction, since the compound of formula 1 is converted into a water-soluble compound of formula 6, the water-soluble compound is readily separated and purified. The objective amide is simply isolated from the reaction mixture by a conventional method such as distillation, recrystallization, etc. The compound of formula 1 can readily be obtained by reacting the compound of formula 6 with a halogenating agent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing amides, and more particularly to a method for producing amides from oximes using a specific haloiminium salt.

[0002]

BACKGROUND OF THE INVENTION Many organic compounds useful as pharmaceuticals or agricultural chemicals are amides having an amide bond, and amides are industrially used as intermediates in organic synthesis such as being used as a constitutional unit in heterocyclic ring construction. It is a useful compound.

As a method for producing amides, many methods have already been reported. Among them, the following four production methods can be mentioned as the method for producing amides from ketoxime by Beckmann rearrangement. (1) A method using an acid such as sulfuric acid, hydrochloric acid, polyphosphoric acid, formic acid, or boron trifluoride. (2) Phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, p
-A method using a halide such as toluenesulfonyl chloride. (3) Hexamethylphosphoric triamide (HMP
Method of heating in A). (4) A method using 1,1′-carbonyldiimidazole.

[0004]

However, the method (1) using an acid such as sulfuric acid or hydrochloric acid cannot be applied to oximes having a functional group weak against acid because the reaction system becomes strongly acidic. Even if it can be applied, it has a drawback that the yield is low. On the other hand, when polyphosphoric acid is used, there is a problem of wastewater treatment from the viewpoint of preventing water pollution.

Further, the method (2) using a halide such as phosphorus pentachloride or phosphorus oxychloride produces hydrogen halide having a strong corrosive property, so that it can be carried out on an industrial scale.
Since a special reaction vessel is required and equipment such as an alkali washing tower is also required, there is a drawback that the equipment must be large-scale.

Further, a method of heating in HMPA (3)
Requires high temperature heating of 225 to 240 ° C., and HMPA
Since it has carcinogenicity, it has a drawback that handling is complicated. Further, the method (4) using 1,1′-carbonyldiimidazole has a drawback that the yield of amides is low.

Therefore, an object of the present invention is to provide an industrially advantageous method for producing amides which is not affected by the properties of the starting oxime, does not require high temperature heating, and does not require special equipment.

[0008]

Under the circumstances, the inventors of the present invention have conducted diligent research on an industrially advantageous method for producing amides, and found that oximes in the presence of a base and water are The present invention has been completed by finding that if a haloiminium salt represented by the formula (1) is reacted, the reaction can proceed under almost neutral and mild conditions, and amides can be obtained in high yield. .

The present invention is shown by the following reaction formula.

[0010]

[Chemical 2]

[Wherein, R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, n represents an integer of 2 or 3, and R ³ and R ⁴ are the same or different. Differently, each represents an organic group, but R ³ and R ⁴ may combine to form a ring. B represents a base. ]

That is, the present invention relates to oximes (2),
The present invention provides a method for producing amides, which comprises reacting a haloiminium salt (1) in the presence of a base (4) and water (3).

The haloiminium salt used in the present invention is represented by the general formula (1). In the formula, the lower alkyl group represented by R ¹ and R ² is a methyl group, an ethyl group, an n-propyl group, Isopropyl group, n-butyl group,
Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms such as an isobutyl group. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly preferable. Specific preferred examples of the haloiminium salt (1) include 2-
Chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethyl-3,4,5,6-
Examples thereof include tetrahydropyrimidinium chloride.

This haloiminium salt (1) is obtained by, for example, adding a compound represented by the general formula (6), which is known as an easily available solvent, to oxalyl halogenide, phosphorus trihalide, phosphorus pentahalide, oxyhalogen. It can be easily obtained by reacting a halogenating agent known per se such as phosphorus bromide, phosgene, trichloromethyl chloroformate and the like. In this reaction, either compound (6) or a halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70 ° C. for several hours to several tens of hours. The haloiminium salt (1) thus obtained can be isolated, but the reaction solution can also be used in the reaction of the present invention without isolation.

In the production method of the present invention, the oxime which is a raw material compound is not particularly limited. For example, in the general formula (2), R ³ and R ⁴ may have a substituent, alkyl,
Examples thereof include alkenyl, aromatic and heterocyclic groups. Further, the oximes may have a substituent containing an ether bond or an olefin bond.

Examples of the base represented by B include 2,6-lutidine, pyridine, triethylamine and tributylamine.

To carry out the production method of the present invention, for example, to 1 mol of oximes (2), about 1 mol of water (3), about 1 mol of haloiminium salt (1) and about 2 mol of base (4). In addition, the reaction may be performed near room temperature.

The reaction solvent need not be used,
It is also possible to use a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or dichloroethane, a hydrocarbon, an ether, or an aromatic hydrocarbon. Further, even when the reaction apparatus is carried out on an industrial scale, it is possible to use an ordinary stainless steel reaction kettle instead of a special reaction kettle such as glass lining.

In the production method of the present invention, since the haloiminium salt (1) is changed to the water-soluble compound (6), separation and purification are easy. Therefore, the isolation of the desired amide from the reaction mixture can be easily performed by a conventional method such as distillation or recrystallization.

[0020]

According to the production method of the present invention, amides can be efficiently produced from oximes under mildly neutral conditions.

[0021]

The present invention will be further described below with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of acetanilide: 2.0 g (15 mmol) acetophenone oxime, 0.53 water in 50 ml acetonitrile.
g (29 mmol) and triethylamine 3.6 g (36 mm
ol) was dissolved therein, and 3.0 g (18 mmo of 2-chloro-1,3-dimethylimidazolinium chloride under ice cooling was dissolved therein.
A solution of l) in 20 ml of acetonitrile was slowly added dropwise. After the completion, the ice bath was removed, stirring was continued at room temperature for 2 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 1.9 g of a crystalline residue. This residue was subjected to silica gel chromatography (solvent n-hexane-
Purification with ethyl acetate) gave 1.6 g of the title compound (yield 8
0%) was obtained. IR ν _max ^KBr cm ^-1 : 1660

Example 2 Synthesis of benzanilide: 3.9 g (20 mmol) benzophenone oxime, 0.71 water in 50 ml acetonitrile.
g (40 mmol) and triethylamine 4.8 g (48 mm
ol) was dissolved therein, and under cooling with ice, 4.0 g (24 mmo of 2-chloro-1,3-dimethylimidazolinium chloride).
A solution of l) in 20 ml of acetonitrile was slowly added dropwise. After the completion of the reaction, the ice bath was removed, and stirring was continued at room temperature for another 16 hours. Then, brine was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give 4.1 g of a crystalline residue. The residue was purified by silica gel chromatography (solvent benzene-ethyl acetate) to give the title compound as 3.
3 g (yield 85%) was obtained. IR ν _max ^KBr cm ^-1 : 1650

Example 3 Synthesis of 4'-fluoroacetoanilide: 4-fluoroacetophenone oxime 3.0 in 50 ml of acetonitrile.
g (20 mmol), water 0.71 g (39 mmol) and triethylamine 4.8 g (47 mmol) were dissolved therein, and under ice cooling, 2-chloro-1,3-dimethylimidazolinium chloride 4.0 g (24 mmol) was dissolved. 20 ml of acetonitrile
The solution was slowly added dropwise. After the completion, the ice bath was removed, stirring was continued at room temperature for 2 hours, water was added to the reaction solution, and the mixture was extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 2.9 g of residue. The residue was purified by silica gel chromatography (solvent n-hexane-ethyl acetate) to obtain 2.3 g (yield 77%) of the title compound. IR ν _max ^KBr cm ^-1 : 1665

Example 4 Synthesis of 1-benzyl-5-oxohexahydro-1,4-diazepine: 2.0 g (9.8 mmol) N-benzyl-4-piperidone oxime, 0.35 g water in 50 ml acetonitrile. (19.6 mmol) and triethylamine 2.
Dissolve 4 g (23.5 mmol), and under ice cooling, 2-chloro-
2.0 g of 1,3-dimethylimidazolinium chloride
A solution of (11.8 mmol) in 20 ml of acetonitrile was slowly added dropwise. When finished, remove the ice bath and allow another 16 at room temperature.
After continuing stirring for an hour, an aqueous potassium carbonate solution was added to the reaction solution, and the mixture was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to obtain 3.5 g of residue. The residue is chromatographed on silica gel (solvent
Purification with chloroform-methanol) gave 1.7 g (yield 85%) of the title compound. IR ν _max ^KBr cm ^-1 : 1660

Claims (1)

[Claims] 1. An oxime in the presence of a base and water, represented by the following general formula (1): [In the formula, R ¹ and R ² are the same or different and each represents a lower alkyl group, X is a halogen atom, and n is 2 or 3
The method for producing amides is characterized by reacting a haloiminium salt represented by