JPH08143559A - Production of 5-imino-2(5h)-furanones - Google Patents

Abstract

PURPOSE: To efficiently obtain 5-imino-2(5H)-furanones from maleic acid monoamides under nearly neutral mild conditions without being influenced by properties of the raw materials. CONSTITUTION: These 5-imino-2(5H)-furanones of formula I (R3 is an organic group) are obtained by reacting 1mol of maleic monoamides expressed by formula II (R<3> is an organic group such as an alkyl or an alkenyl), e.g. 4-oxo-4- phenylamino-2-butenoic acid with 1mol of a haloiminium salt expressed by formula III [R<1> and R<2> are each independently a 1-6C alkyl group such as methyl; X is a halogen such as F or Cl; (n) is an integer of 2 or 3], e.g. 2-chloro-1,3- dimethylimidazolinium chloride and 2mol of a base such as 2,6-lutidine in a solvent such as dichloromethane at nearly room temperature.

Description

Detailed Description of the Invention

[0001]

The present invention relates to 5-imino-2 (5
The present invention relates to a method for producing H) -furanones, and more specifically to a method for producing 5-imino-2 (5H) -furanones from maleic acid monoamides using a specific haloiminium salt.

[0002]

BACKGROUND OF THE INVENTION 5-Imino-2 (5H) -furanones are easily polymerized or copolymerized, and therefore used as a raw material monomer for synthesizing functional oligomers and polymers, and as a rubber elasticity improver. Has been. Furthermore, the highly reactive imino group can be converted into β by reaction with ketene.
-Since it has characteristics such as generation of a lactam ring, 5-imino-2 (5H) -furanones are useful as raw materials for pharmaceuticals and pharmaceutical synthetic intermediates.

Conventionally, several methods have been known as a method for producing 5-imino-2 (5H) -furanones, and one of them is a method for producing a maleic acid monoamide by a ring-closing reaction. . Then, 5-imino-2 (5H)-by a conventional ring closure reaction of maleic acid monoamides.
As a method for producing furanones, 1) a method using acetic anhydride, 2) a method using acetic anhydride-sodium acetate, 3) a method using thionyl chloride, 4) a method using an acid halide such as acetyl chloride, 5) A method using trifluoroacetic anhydride, 6) a method using N, N′-dicyclohexylcarbodiimide, etc. are known.

[0004]

However, in the methods 1) and 2) using acetic anhydride, a large amount of reagents must be used in order to use acetic anhydride as a solvent. Further, the methods of using thionyl chloride and acid halides of 3) and 4) cannot be applied to maleic acid monoamides having a functional group weak to acid because the reaction system becomes strongly acidic, or the yield will decrease. There is a problem. Further, since hydrogen halide which is highly corrosive is generated, a special reaction vessel is required for implementation on an industrial scale, and equipment such as an alkali washing tower is required. The method of 5) using trifluoroacetic anhydride has low industrial utility because the trifluoroacetic anhydride is not commercially available as an industrial reagent and is expensive. The method using 6) N, N'-dicyclohexylcarbodiimide is not only a reagent having strong skin irritation but also produces a large amount of sparingly soluble N, N'-dicyclohexylurea as a by-product at the end of the reaction. It was difficult to do.

Therefore, an object of the present invention is to provide a method for producing 5-imino-2 (5H) -furanones industrially advantageously under mild conditions without being affected by the properties of raw materials. is there.

[0006]

Under such circumstances, the present inventor has conducted diligent research to find out a new method for producing 5-imino-2 (5H) -furanones, and as a result, the following general formula ( It was found that 5-imino-2 (5H) -furanones can be obtained from maleic acid monoamides in high yield under almost neutral and mild conditions by using the haloiminium salt represented by 1), and the present invention completed.

The method of the present invention is shown by the following reaction formula.

[0008]

Embedded image

[Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, n is an integer of 2 or 3, B represents a base, and R ³
Represents an organic group]

That is, according to the present invention, maleic acid monoamides (2) are reacted with a haloiminium salt to give 5-imino-
The 2 (5H) -furanones (4) are produced.

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 straight or branched chain having 1 to 6 carbon atoms. Alkyl group such as methyl group, ethyl group, n
-Propyl group, isopropyl group, n-butyl group, isobutyl group and the like can be mentioned. 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 these, a chlorine atom is particularly preferable. Preferred specific examples of the haloiminium salt (1) include 2-chloro-1,3-dimethylimidazolinium chloride and 2-chloro-1,3-dimethyl-3,4.
5,6-tetrahydropyrimidinium chloride and the like can be mentioned.

This haloiminium salt (1) is obtained by, for example, adding an oxalyl halogenide, a phosphorus trihalide, a phosphorus pentahalide, an oxyhalogen to a compound represented by the general formula (5) which is known as an available solvent. 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 (5) 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 maleic acid monoamides (2) which are the raw material compounds used in the present invention, the organic group represented by R ³ is an alkyl group which may have a substituent, an alkenyl group, an aromatic group or a heterocyclic group. Groups and the like. The substituent may have a substituent containing an ether bond, an olefin bond, or the like.

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

To carry out the method of the present invention, about 1 mol of a haloiminium salt (1) and about 2 mol of a base (3) are added to 1 mol of a maleic acid monoamide (2), and the reaction is carried out at around room temperature. Good. A reaction solvent may not be used, but a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or dichloroethane, an aliphatic hydrocarbon, an ether or an aromatic hydrocarbon, can be used. 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 method of the present invention, the haloiminium salt (1) is used.
Changes to the water-soluble compound (5), so separation and purification are easy. Therefore, the desired 5-imino-2 (5H) -furanones can be isolated from the reaction mixture simply by a conventional method such as distillation or recrystallization.

[0017]

According to the method of the present invention, maleic acid monoamides are converted to 5-imino-2 under mildly neutral conditions.
(5H) -furanones can be efficiently produced.

[0018]

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

Example 1 Preparation of 5-phenylimino-2 (5H) -furanone: 3.0 g (16 mmol) of 4-oxo-4-phenylamino-2-butenoic acid and 2 in 100 ml of dichloromethane.
3.2 g (19 mmol) of -chloro-1,3-dimethylimidazolinium chloride was added, 3.8 g (38 mmol) of triethylamine was slowly added dropwise thereto, and stirring was continued for another 19 hours after completion. Next, water was added to the reaction solution, extraction was performed with dichloromethane, the extract was washed with water, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain 4.2 g of a yellowish brown oily residue. The residue was purified by silica gel chromatography (solvent: n-hexane / ethyl acetate) to give 2.2 g of the title compound.
(Yield 81%) was obtained. IR; ν _max ^KBr (cm ^-1 ) 1780

Example 2 Preparation of 5-phenethylimino-2 (5H) -furanone:
To 100 ml of dichloromethane, 3.0 g (14 mmol) of 4-oxo-4-phenethylamino-2-butenoic acid and 3.4 g (20 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and triethylamine was added thereto. 4.1 g (40 mmol) was slowly added dropwise, and after completion, stirring was continued for 18 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 1.6 g (yield 57%) of the title compound. IR; ν _max ^neat (cm ^-1 ) 1795

Example 3 Preparation of 5-cyclohexylimino-2 (5H) -furanone: 3.0 g (15 mm) of 4-cyclohexylamino-4-oxo-2-butenoic acid in 100 ml of dichloromethane.
ol) and 3.5 g (21 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride, 4.2 g (41 mmol) of triethylamine was slowly added dropwise thereto, and stirring was continued for another 24 hours after completion. It was
Thereafter, the same operation as in Example 1 was repeated to give 1.
4 g (yield 53%) was obtained. IR; ν _max ^neat (cm ^-1 ) 1790

Claims (1)

[Claims] 1. A maleic acid monoamide is prepared by adding the following general formula (1): [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 is reacted. A method for producing 5-imino-2 (5H) -furanones.