JP2005239603A - Method for producing 2-imidazolidinones - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a 2-imidazolidinone from a 1,2-diamino compound in a high yield in excellent operability. <P>SOLUTION: A 1,2-diamino compound is reacted with phosgene in a two phase-based solvent composed of a nitrile and water to produce a 2-imidazolidinone. An aliphatic nitrile such as butyronitrile or isobutyronitrile is suitably used as the nitrile solvent. The reaction may be carried out in the presence of a base such as a metal hydroxide, a nitrogen-containing heteroaromatic compound, a tertiary amine, etc. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for producing 2-imidazolidinones from 1,2-diamino compounds. 2-Imidazolidinones are useful as pharmaceuticals, agricultural chemicals, electronic materials, raw materials or intermediates thereof, and the like.

As a method for producing 2-imidazolidinones, a method in which a 1,2-diamino compound and phosgene are reacted in an organic solvent or water is known (see, for example, Patent Documents 1 and 2). In addition, in US Pat. No. 5,151,525 (Patent Document 3), when an alkali metal salt of meso-2,3-bis (dibenzylamino) succinic acid and phosgene are reacted, xylene, toluene, The use of a two-phase solvent of dichloromethane or anisole and water is described.
JP 61-109772 A JP-A-62-265269 US Pat. No. 5,151,525

  As described in Patent Document 3, when an organic solvent / water two-phase solvent is used as a reaction solvent, the reaction is easier to proceed than when only an organic solvent is used, and compared with a case where only water is used. Although phosgene is difficult to hydrolyze, it is advantageous, but the yield of 2-imidazolidinones may not be sufficient depending on the type of raw materials and organic solvent. In addition, when a halogen-based solvent such as dichloromethane is used, environmental considerations are particularly necessary, which increases the operation burden. Accordingly, an object of the present invention is to provide a method capable of producing 2-imidazolidinones from a 1,2-diamino compound with good yield and good operability.

  As a result of intensive studies, the present inventors have found that the above object can be achieved by reacting a 1,2-diamino compound with phosgene using a nitrile / water two-phase solvent as a reaction solvent. The invention has been completed. That is, the present invention provides a method for producing 2-imidazolidinones by reacting a 1,2-diamino compound with phosgene in a two-phase solvent composed of nitrile and water.

According to the present invention, 2-imidazolidinones can be produced from 1,2-diamino compounds with good yield and good operability.

  The 1,2-diamino compound used as a raw material in the present invention has a structure in which one unsubstituted or monosubstituted amino group is bonded to each of adjacent two carbon atoms, and the two carbon atoms are bonded to the two carbon atoms. A total of four groups other than the amino group to be bonded can each be a hydrogen atom or an appropriate substituent.

  A typical example of a 1,2-diamino compound can be represented by the following formula (1).

(In the formula, R ^{1 to} R ⁶ each represent a hydrogen atom or a hydrocarbon group, but R ² and R ⁴ may be combined to form a ring with the carbon atom to which they are bonded.)

In the formula (1), when at least one of R ^{1 to} R ⁶ is a hydrocarbon group, the hydrocarbon group may be an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, or an aromatic hydrocarbon group. it can.

  Here, the aliphatic hydrocarbon group is a residue obtained by removing hydrogen from an aliphatic hydrocarbon, and its carbon number is usually about 1 to 20. Specific examples thereof include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-pentyl group, n-hexyl group, n- Examples thereof include alkyl groups such as octyl group, n-decyl group, n-dodecyl group and n-octadecyl group; alkenyl groups such as vinyl group and allyl group; alkynyl groups such as ethynyl group and propargyl group. .

  Moreover, an alicyclic hydrocarbon group is the residue remove | excluding hydrogen from alicyclic hydrocarbon, and the carbon number is about 3-20 normally. The alicyclic hydrocarbon group may be a residue obtained by removing hydrogen from the aliphatic ring of the alicyclic hydrocarbon, or remove hydrogen from the aliphatic chain of the alicyclic hydrocarbon having an aliphatic chain. It may be a residue. Specific examples thereof include a cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, a norbornyl group and an adamantyl group; a cycloalkylalkyl group such as a cyclopentylmethyl group and a cyclohexylmethyl group, etc. Can be mentioned.

  The aromatic hydrocarbon group is a residue obtained by removing hydrogen from an aromatic hydrocarbon, and the carbon number thereof is usually about 6 to 20. The aromatic hydrocarbon group may be a residue obtained by removing hydrogen from an aromatic ring of an aromatic hydrocarbon, or a residue obtained by removing hydrogen from the aliphatic chain of an aromatic hydrocarbon containing an aliphatic chain. It may be a group, or may be a residue obtained by removing hydrogen from an aliphatic ring of an aromatic hydrocarbon containing an aliphatic ring. Specific examples thereof include aryl groups such as phenyl, naphthyl and indenyl groups; arylalkyl groups (aralkyl groups) such as benzyl and 4-phenylbutyl groups.

The hydrocarbon group represented by R ^{1 to} R ⁶ may have a ring-setting group. Examples of the substituent include an alkoxy group, an acyl group, an alkoxycarbonyl group, a halogeno group, an oxo group. Group, silyl group, diazo group, cyano group and the like.

In the formula (1), when R ² and R ⁴ are combined to form a ring together with the carbon atom to which they are bonded, the number of rings is usually 5 to 12, and the type of ring is Examples thereof include aromatic hydrocarbon rings such as benzene ring and naphthalene ring; aliphatic hydrocarbon rings such as cyclohexane ring and cyclohexene ring.

  Typical examples of the 1,2-diamino compound include diaminosuccinic acids and derivatives thereof represented by the following formula (2).

[Wherein R ⁷ and R ¹⁰ each represent a hydrogen atom or a hydrocarbon group, and R ⁸ and R ⁹ each represent a cyano group or the following formula (3)
-COOR ¹¹ (3)
(In the formula, R ¹¹ represents a hydrogen atom, a hydrocarbon group, an alkali metal or ammonium.)
Represents a group represented by ]

In the formula (2), when at least one of R ⁷ and R ¹⁰ is a hydrocarbon group, at least one of R ⁸ and R ⁹ is a group represented by the formula (3), and R ¹¹ is a carbon group. When it is a hydrogen group, these hydrocarbon groups can be aliphatic hydrocarbon groups, alicyclic hydrocarbon groups or aromatic hydrocarbon groups. And, examples of these hydrocarbon groups are the same as examples of the hydrocarbon group represented by R ¹ to R ^6.

In the formula (2), when at least one of R ⁸ and R ⁹ is a group represented by the formula (3) and R ¹¹ is an alkali metal, the alkali metal may be, for example, lithium. It may be sodium, potassium, or potassium. Further, when R ¹¹ is ammonium, the ammonium may be ammonium ammonium or aliphatic, alicyclic or aromatic primary, secondary or tertiary amine ammonium. It may be quaternary ammonium.

  Specific examples of 1,2-diamino compounds include 1,2-diaminoethane, 1,2-diaminopropane, 2,3-diaminobutane, 3,4-diaminohexane, 4,5-diaminooctane, 1,2 -Diamino-1,2-diphenylethane, 2,3-diamino-2,3-dimethylbutane, 1,2-bis (methylamino) ethane, 2,3-bis (methylamino) butane, 3,4-bis (Methylamino) hexane, 1,2-bis (phenylamino) ethane, 1,2-bis (benzylamino) ethane, 1,2-diamino-1,2-dicyanoethane, 1,2-bis (methylamino) -1,2-dicyanoethane, 1,2-bis (benzylamino) -1,2-dicyanoethane, 1,2-diaminobenzene, 2,3-bis (methylamino) succinic acid, 2,3-bis Benzylamino) succinic acid, dimethyl 2,3-bis (benzylamino) succinate, dipotassium 2,3-bis (benzylamino) succinate, disodium 2,3-bis (benzylamino) succinate and the like. it can. Two or more kinds of 1,2-diamino compounds may be used as necessary.

  By reacting the 1,2-diamino compound with phosgene, the corresponding 2-imidazolidinones can be produced. The amount of phosgene used is usually about 0.8 to 6 moles of the 1,2-diamino compound.

  For example, by using a compound represented by the above formula (1) as a 1,2-diamino compound, as a 2-imidazolidinone, the following formula (4)

(In the formula, R ^{1 to} R ⁶ each have the same meaning as described above.)
The compound shown by these can be manufactured.

  Further, by using the compound represented by the above formula (2) as the 1,2-diamino compound, as the 2-imidazolidinones, the following formula (5)

(In the formula, R ^{7 to} R ¹⁰ each have the same meaning as described above.)
The compound shown by these can be manufactured.

  Examples of the obtained 2-imidazolidinones include 2-imidazolidinone, 4-methyl-2-imidazolidinone, 4,5-dimethyl-2-imidazolidinone, 4,5-diethyl-2-imidazolidone. Lidinone, 4,5-dipropyl-2-imidazolidinone, 4,5-diphenyl-2-imidazolidinone, 4,4,5,5-tetramethyl-2-imidazolidinone, 1,3,4, 5-tetramethyl-2-imidazolidinone, 1,3-dimethyl-2-imidazolidinone, 1,3-dimethyl-4,5-diethyl-2-imidazolidinone, 1,3-diphenyl-2-imidazolidone Lidinone, 1,3-bis (benzylamino) -2-imidazolidinone, 2-benzimidazolidinone, 4,5-dicyano-2-imidazolidinone, 1,3-dimethyl-4,5-dicyano- -Imidazolidinone, 1,3-bis (benzylamino) -4,5-dicyano-2-imidazolidinone, 1,3-dimethyl-2-imidazolidinone-4,5-dicarboxylic acid, 1,3- Dibenzyl-2-imidazolidinone-4,5-dicarboxylic acid, 1,3-dibenzyl-2-imidazolidinone-4,5-dicarboxylate dimethyl, 1,3-dibenzyl-2-imidazolidinone-4,5 -Dipotassium dicarboxylate, 1,3-dibenzyl-2-imidazolidinone-4,5-dicarboxylate disodium and the like.

  In the present invention, a two-phase solvent is constituted using a nitrile solvent that can be separated from water and water as the reaction solvent in the above reaction. By using such a solvent, the reaction can proceed smoothly, and 2-imidazolidinones can be produced in good yield.

  The nitrile solvent is substantially inert to the reaction and is liquid at room temperature, for example, butyronitrile, isobutyronitrile, valeronitrile, trimethylacetonitrile, isovaleronitrile, hexanenitrile, heptanenitrile, octanenitrile Aliphatic nitriles such as nonanenitrile, dodecanenitrile, pentadecanenitrile, adiponitrile; cycloaliphatic nitriles such as cyclopropylacetonitrile, cyclopentanecarbonitrile, cyclohexanecarbonitrile, cycloheptanecarbonitrile; benzonitrile, o-tolunitrile, m-tolunitrile, 2-ethylbenzonitrile, 4-ethylbenzonitrile, phenylacetonitrile, o-tolylacetonitrile, m-tolylacetonitrile, p-tolylaceto Tolyl, 2-phenyl-butyronitrile, aromatic nitriles such as 4-phenyl-butyronitrile and the like, the number of carbon atoms thereof is usually about 4 to 15. Of these, aliphatic nitriles such as butyronitrile and isobutyronitrile are preferable. These nitrile solvents may be used alone or in combination of two or more.

  The amount of the nitrile solvent used is usually 0.5 to 100 times by weight, preferably 1 to 20 times by weight of the 1,2-diamino compound. The amount of water used is usually 0.5 to 100 times by weight of the 1,2-diamino compound, preferably 1 to 20 times by weight, and usually 0.1 to 10 times by weight of the nitrile solvent. Preferably it is 0.2-5 weight times. If necessary, a solvent other than the nitrile solvent and water can be used in combination, but the amount of the solvent used is usually up to 20 parts by weight with respect to 100 parts by weight of the total amount of the nitrile solvent and water. is there.

  The reaction is preferably performed in the presence of a base (deoxidizing agent) that can neutralize hydrogen chloride generated by the reaction of a 1,2-diamino compound and phosgene. Examples of such base include sodium hydroxide, Metal hydroxides such as potassium hydroxide and calcium hydroxide; nitrogen-containing heteroaromatic compounds such as pyridine, 4-ethylpyridine and 4- (N, N-dimethylamino) pyridine; triethylamine, N, N-diethyl There may be mentioned tertiary amines such as aniline, and two or more of them may be used as necessary. The amount of such base used is usually 10 moles or less of the 1,2-diamino compound.

  The reaction is carried out by mixing 1,2-diamino compound, phosgene, the solvent and, if necessary, a base, etc., and the mixing method can be selected as appropriate, but a mixture of the 1,2-diamino compound and the solvent The reaction is preferably carried out while adding phosgene. Further, it is an effective method for maintaining the pH of the reaction solution in a predetermined range, for example, pH 6 to 12, by adding a base.

  The reaction temperature is usually about −10 to 150 ° C., preferably 0 to 80 ° C. The progress of the reaction can be followed by gas chromatography, high performance liquid chromatography, thin layer chromatography, nuclear magnetic resonance spectrum, or the like.

  The post-treatment operation after the reaction is appropriately selected. By separating the reaction mixture into oil and water, a nitrile solution of 2-imidazolidinones as an organic layer or an aqueous solution of 2-imidazolidinones as an aqueous layer is obtained. be able to. These solutions may be further subjected to separation and purification operations such as concentration, extraction, crystallization, and distillation. In the above oil-water separation, the oil-water distribution ratio of 2-imidazolidinones varies depending on the type and conditions of 2-imidazolidinones and nitrile solvents, but from the standpoint of separation and purification, there are many by-product salts. It is advantageous that the organic layer is more easily distributed than the water layer that can be contained.

The method of the present invention is a 1,3-dibenzyl-2-imidazolidinone-4,5-dicarboxylic acid or its alkali metal salt useful as a biotin intermediate [wherein R ⁷ and R ¹⁰ are benzyl And R ⁸ and R ⁹ are groups represented by the above formula (3) (—COOR ¹¹ ), and R ¹¹ is a hydrogen atom or an alkali metal], that is, 2,3-dibenzylbis (benzyl Amino) succinic acid or an alkali metal salt thereof [in the above formula (2), R ⁷ and R ¹⁰ are benzyl groups, R ⁸ and R ⁹ are groups (—COOR ¹¹ ) represented by the above formula (3); The compound wherein R ¹¹ is a hydrogen atom or an alkali metal] and phosgene can be suitably employed. Performing such a reaction in an oil-water two-phase solvent is also described in Patent Document 3 as described above. However, since the organic solvent is xylene, toluene, dichloromethane, or anisole, The desired 2,3-dibenzylbis (benzylamino) succinic acid or its alkali metal salt is more easily distributed to the aqueous layer than to the organic layer. On the other hand, according to the method of the present invention, by using a nitrile solvent, particularly butyronitrile or isobutyronitrile as the organic solvent, the desired 2,3-dibenzylbis (benzylamino) succinic acid or its alkali metal salt can be obtained. It is easier to distribute to the organic layer than the aqueous layer, which is advantageous in terms of operability in separation and purification.

  Examples of the present invention will be described below, but the present invention is not limited thereto.

Example 1
Into a 300 ml flask, 14.1 g of 1,2-diaminopropane, 15 g of water, and 40 g of butyronitrile were stirred, and 23.7 g of phosgene was blown into the flask at 30 ° C. over 4 hours. For 0.5 hour. Further, a 25 wt% aqueous sodium hydroxide solution was added so that the pH of the reaction solution was maintained at 8.5 during the blowing and holding. The obtained reaction solution was separated into an organic layer and an aqueous layer, and the aqueous layer was analyzed by liquid chromatography. As a result, the content of 4-methyl-2-imidazolidinone was 18.0 g (yield 94%). It was.

Example 2
In a 500 ml flask, 21.3 g of meso-2,3-bis (benzylamino) succinic acid, 18.1 g of 49% by weight potassium hydroxide aqueous solution and 30.3 g of water were stirred to obtain a homogeneous solution. .2 g was mixed. Into this, 20.3 g of phosgene was blown at 32 ° C. over 4 hours, and then held at 20 ° C. for 0.5 hour. Further, 79.8 g of a 49 wt% aqueous potassium hydroxide solution was added so that the pH of the reaction solution was maintained at 10.5 during the blowing and holding. The obtained reaction solution was separated into an organic layer and an aqueous layer, and the organic layer was analyzed by liquid chromatography. As a result, the content of dipotassium 1,3-dibenzyl-2-imidazolidinone-4,5-dicarboxylate was It was 25.0 g (yield 95%).

Comparative Example 1
In a 500 ml flask, 21.3 g of meso-2,3-bis (benzylamino) succinic acid, 18.1 g of 49% by weight potassium hydroxide aqueous solution, and 30.3 g of water were stirred to obtain a homogeneous solution. .2 g was mixed. Into this, 20.3 g of phosgene was blown at 32 ° C. over 4 hours, and then held at 20 ° C. for 0.5 hour. Further, 79.3 g of a 49 wt% potassium hydroxide aqueous solution was added so that the pH of the reaction solution was maintained at 10.5 during the blowing and holding. The obtained reaction solution was separated into an organic layer and an aqueous layer, and then the aqueous layer was filtered to remove 15 g of inorganic salt, and the filtrate was analyzed by liquid chromatography. As a result, 1,3-dibenzyl-2-imidazolidine was obtained. The content of non-potassium non-4,5-dicarboxylate was 20.9 g (yield 91%).

Claims (6)

  A process for producing 2-imidazolidinones, which comprises reacting a 1,2-diamino compound with phosgene in a two-phase solvent comprising nitrile and water. The 1,2-diamino compound is represented by the following formula (1)

(In the formula, R ^{1 to} R ⁶ each represent a hydrogen atom or a hydrocarbon group, but R ² and R ⁴ may be combined to form a ring with the carbon atom to which they are bonded.)
The manufacturing method of Claim 1 which is a compound shown by these. The 1,2-diamino compound is represented by the following formula (2)

[Wherein R ⁷ and R ¹⁰ each represent a hydrogen atom or a hydrocarbon group, and R ⁸ and R ⁹ each represent a cyano group or the following formula (3)
-COOR ¹¹ (3)
(In the formula, R ¹¹ represents a hydrogen atom, a hydrocarbon group, an alkali metal or ammonium.)
Represents a group represented by ]
The manufacturing method of Claim 1 which is a compound shown by these.   The production method according to claim 1, wherein the 1,2-diamino compound is 2,3-bis (benzylamino) succinic acid or an alkali metal salt thereof.   The method according to any one of claims 1 to 4, wherein the nitrile is butyronitrile or isobutyronitrile. The production method according to any one of claims 1 to 5, wherein the reaction is carried out in the presence of a metal hydroxide, a nitrogen-containing heteroaromatic compound or a tertiary amine.