JP5111787B2 - Method for producing 2-alkylimidazole - Google Patents

Description

The present invention is a manufacturing how the 2-alkyl imidazoles, specifically, it relates to how to produce high-purity 2-alkyl imidazoles having a needle-like crystal structure.

  2-Alkylimidazole, especially 2-isopropylimidazole, is a compound that is expected to be useful in various organic drug fields such as pharmaceutical intermediates or as a catalyst for various resins and dye intermediates. It is known that the 2-isopropylimidazole is usually produced by reacting ammonia, isobutyraldehyde, and glyoxal.

In the above production method, ammonia and glyoxal as raw materials are provided as an aqueous solution, while isobutyraldehyde exhibits water insolubility, resulting in a non-uniform reaction system. Therefore, it is common practice to add a water-soluble organic solvent such as methanol to make the entire system uniform (see, for example, Patent Document 1). Since 2-isopropylimidazole produced by the reaction according to this method is dissolved in the water-soluble organic solvent, it is necessary to concentrate and remove the water-soluble organic solvent during purification. And 2-isopropylimidazole is obtained by finally crystallizing and precipitating.
JP 2005-82570 A

  However, since 2-isopropylimidazole is inferior in crystallinity, it becomes oily during the concentration, and then precipitates as massive crystals (sand particles). In that case, since it crystallizes in the state which was included with the impurity which is a by-product other than 2-isopropylimidazole, the problem that the thing with low purity of 2-isopropylimidazole will be obtained will arise.

  Further, when the lump-shaped 2-isopropylimidazole is used for various purposes, it must be pulverized by using a pulverizer or the like. As a result of the pulverization, fine powder is generated and the handleability deteriorates. Arise.

  On the other hand, it may be possible to distill and purify a crystallized product having a low purity of 2-isopropylimidazole. However, since the boiling point is close to that of imidazoles contained as impurities, it is difficult to separate and remove impurities. There is.

The present invention has been made in view of such circumstances, excellent 2-alkyl imidazoles high purity at and handling, especially to provide a manufacturing how 2-isopropyl imidazole and its object.

In order to achieve the above object, the present invention provides a method for producing 2-alkylimidazole from ammonia, an alkyl aldehyde having 3 to 20 carbon atoms and glyoxal, wherein ammonia and alkyl aldehyde are in a heterogeneous state in an aqueous medium. Reacting to produce an imine compound, glyoxal is then added to the aqueous medium in which the imine compound is formed, the imine compound and glyoxal are reacted, and 2-alkylimidazole crystals are precipitated in the aqueous medium. the method for manufacturing imidazole and Abstract.

That is, the present inventor conducted research to find out a production method for obtaining a high-purity 2-alkylimidazole having a crystal structure excellent in handleability rather than a lump such as oil. As a result, instead of the homogeneous system using a conventional water-soluble organic solvent as the entire reaction system and heterogeneous in Mizunakadachi body Mizunakadachi bodies 2-alkyl imidazoles of the water-insoluble or sparingly water-soluble I recalled crystallizing inside. Based on this, first, the Mizunakadachi body now containing ammonia, after the addition of water-insoluble or sparingly water-soluble alkyl aldehydes having 3 to 20 carbon atoms and to produce a imine compound (intermediate reaction product), which When a suspension (slurry) containing 2-alkylimidazole is prepared by adding glyoxal to the reaction, separation from imidazole, which is a byproduct, is easily performed because 2-alkylimidazole is crystallized. Thus, the present inventors have found that it is possible to obtain a high-purity 2-alkylimidazole having a needle-like crystal structure instead of an oily form as in the prior art.

Thus, the production method of 2-alkyl imidazoles of the present invention, in Mizunakadachi body in, and ammonia, an alkyl aldehyde having 3 to 20 carbon atoms water insoluble or sparingly water-soluble by reaction in a heterogeneous state imine compound is generated by the imine compound is reacted adding glyoxal to Mizunakadachi body which had been produced, to crystallize the 2-alkyl imidazole in Mizunakadachi body, 2-alkyl imidazole-containing suspension (slurry-like material) Is produced. And 2-alkylimidazole of high purity can be obtained by taking out the crystallized 2-alkylimidazole from this suspension (slurry). Thus, in producing a 2-alkyl imidazoles with alkyl aldehydes of water-insoluble or sparingly water-soluble, without using the conventional water-soluble organic solvent such as, ingredients in heterogeneous reaction system in Mizunakadachi body blended, 2- by alkyl is reacted with a precipitating crystals of imidazole, 2-alkyl imidazoles are those to produce, for example, it is dried filtered Mizunakadachi body containing the reaction product obtained Thus, a 2-alkylimidazole having a needle crystal structure and having a high purity can be obtained.

  Therefore, since the boiling point is close to that of 2-alkylimidazole, it is easy to separate from imidazole, which is a by-product that has been difficult to remove by distillation purification, and has a needle-like crystal structure and has high purity. Can be obtained.

  In the method for producing 2-alkylimidazole of the present invention, ammonia, alkyl aldehyde, and glyoxal are used, and these are subjected to the reaction. The ammonia and glyoxal are usually subjected to the reaction as aqueous solutions, respectively. Specifically, an ammonia aqueous solution of 5 to 30% by weight is used as the ammonia, and an aqueous solution of about 40% by weight is used for glyoxal.

  The alkyl aldehyde is a water-insoluble or poorly water-soluble alkyl aldehyde, and may be an alkyl aldehyde having 3 to 20 carbon atoms, preferably 3 to 10 carbon atoms, more preferably 3 to 6 carbon atoms. Specific examples include propionaldehyde, isobutyraldehyde, n-butyraldehyde, valeraldehyde, isovaleraldehyde, pivaloyl aldehyde, hexanal, 2-methylpentanal, heptanal, octanal, nonanal, among others. It is effective for the production of 2-isopropylimidazole using isobutyraldehyde.

In the present invention, 2-alkylimidazole is produced as follows. First, in Mizunakadachi body in, by reacting ammonia and the alkyl aldehyde in a heterogeneous state, to produce an imine compound is an intermediate product. Then, the imine compound Mizunakadachi body which had been generated, the white suspension (like slurry) containing a crystal of 2-alkyl imidazoles by reacting while to precipitate crystals by addition of glyoxal is generated. Thus, in the present invention, performs reaction at two stages, in which the maximum of the characterized in that the whole reaction system in a heterogeneous system in Mizunakadachi body. In the present invention, the uneven state refers to a state in which ammonia is formulated in Mizunakadachi body, an alkyl aldehyde suspended not completely dissolved.

  Then, the reaction product, that is, the white suspension containing 2-alkylimidazole crystals is filtered by a centrifugal filter or the like, and the filtrate is dried to obtain 2-alkylimidazole having a needle-like crystal structure. It is done. The 2-alkylimidazole having a needle-like crystal structure thus obtained has a high purity from which impurities are removed.

  As reaction conditions in the reaction process of 2-alkylimidazole of this invention, it is preferable to set temperature conditions in the range of 5-30 degreeC.

  And as the addition method of each said compounding component, methods, such as a batch method, a division | segmentation method, a dripping method, are mention | raise | lifted, Among these, it is preferable that it is a dripping method. The dropping rate when the alkyl aldehyde is added dropwise to the aqueous ammonia solution in the addition method by the dropping method is appropriately set, but for example, within the range of the temperature conditions described above in consideration of heat generation due to the reaction. It is preferable to set the dropping speed so as to maintain the above. Therefore, specifically, it is preferable to set to 30 minutes to 2 hours.

Furthermore, the imine compound during (intermediate product) is added glyoxal aqueous solution Mizunakadachi body which had been generated imine compound resulting from the reaction of ammonia with alkyl aldehyde product ratio (intermediate product) is 10% or more In particular, it is preferable to add from the point of time of 20% or more. If the production rate is too small, the ratio of by-products tends to increase, which is not preferable.

  And also about the dripping speed | rate at the time of dripping and adding a glyoxal aqueous solution, it is preferable to set to the dripping speed | rate which can maintain the range of the above-mentioned temperature conditions in consideration of the heat_generation | fever by reaction similarly to the above. Therefore, specifically, it is preferable to set to 1 to 5 hours.

  In the method for producing 2-alkylimidazole according to the present invention, the total charge ratio of each compounding component is ammonia / alkyl aldehyde / glyoxal = 1.8 to 2.2 / 0.9 to 1.4 / 0. It is preferable to set so as to be in the range of 9 to 1.1. That is, by setting the total charge ratio of each compounding component in such a range, it is possible to suppress the reaction with only ammonia and glyoxal and to produce unsubstituted imidazole.

  In the present invention, the reaction of the second stage, that is, the reaction of the imine compound (intermediate product) and glyoxal produces 2-alkylimidazole, which is the target product, and a considerable amount of this is precipitated along with the production. Dried. What was not deposited during the reaction remains in the mother liquor during filtration, so it is concentrated, filtered, dried and taken out again. Thereby, it becomes possible to separate from the imidazole which is a by-product, and high-purity 2-alkylimidazole can be obtained. The resulting 2-alkylimidazole has a needle-like crystal structure, not a conventional lump crystal, and has a so-called long fiber shape, and an aggregate of those having such a crystal structure. As obtained.

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist.
In the examples, “parts” and “%” mean weight basis unless otherwise specified.

  In a reaction vessel charged with 150.0 g (2.2 mol) of a 25% aqueous ammonia solution, 72.1 g (1.0 mol) of isobutyraldehyde was added dropwise at 25 ° C. over about 30 minutes to cause the reaction. To the obtained reaction mixture (intermediate product), 145.0 g (1.0 mol) of 40% aqueous glyoxal solution was added dropwise at 25 ° C. over about 2 hours. After stirring for 2 hours, the obtained white suspension was filtered using a centrifugal filter and dried to obtain 88 g (yield 80%, purity 99.7%) of white crystals of 2-isopropylimidazole. It was. Further, the obtained mother liquor was concentrated to half amount, filtered and dried in the same manner as above, and 14.3 g (yield 13%, purity 99.5%) of 2-isopropylimidazole white crystals were obtained.

The obtained white crystalline 2-isopropylimidazole was an aggregate of those having an acicular crystal structure. Further, the obtained 2-isopropylimidazole having a needle-like crystal structure was confirmed with a microscope, and a micrograph thereof is shown in FIG. From the photomicrograph of FIG. 1, the obtained 2-isopropylimidazole has a needle-like crystal structure, has a so-called long fiber shape, and is obtained as an aggregate of those having such a crystal structure. I understand that.
The micrographs were taken under the condition of 50 times magnification using a Nikon microscope (model: OPTIPHOT-2). The purity and yield are measured using a gas chromatograph. In detail, column: HP-WAX 0.53 mm × 30 m × 1.0 μm manufactured by Agilent, column temperature: 220 at a temperature of 100 ° C. to 10 ° C./min. The temperature was raised to 200 ° C. and held at 220 ° C. for 8 minutes. The measurement was carried out by the internal standard method under the conditions of injection port: 250 ° C., detector (hydrogen flame ionization detector): 250 ° C., carrier gas: 20 mL / min.

  To a reaction vessel charged with 150.0 g (2.2 mol) of a 25% aqueous ammonia solution, 86.5 g (1.2 mol) of isobutyraldehyde was added dropwise at 25 ° C. over about 30 minutes to react. To the obtained reaction mixture (intermediate product), 145.0 g (1.0 mol) of 40% aqueous glyoxal solution was added dropwise at 25 ° C. over about 2 hours. After stirring for 2 hours, the obtained white suspension was filtered using a centrifugal filter and dried to obtain 79 g of 2-isopropylimidazole white crystals (yield 72%, purity 99.4%). It was. Furthermore, the obtained mother liquor was concentrated to half amount, filtered and dried in the same manner as above, and as a result, 17.6 g (yield 16%, purity 99.2%) of 2-isopropylimidazole white crystals were obtained. The purity and yield were measured according to the same measurement method as in Example 1.

[Comparative Example 1]
72.1 g (1.0 mol) of isobutyraldehyde was added dropwise to the reaction vessel charged with a solution of 120 g of methanol added to 150.0 g (2.2 mol) of 25% aqueous ammonia at 25 ° C. over about 30 minutes. I let you. To the obtained reaction mixture, 145.0 g (1.0 mol) of 40% aqueous glyoxal solution was added dropwise at 25 ° C. over about 2 hours. After stirring for 2 hours, the resulting reaction solution was quantified by gas chromatography. As a result, it contained 104.5 g (yield 95%) of 2-isopropylimidazole. The obtained reaction solution was concentrated with an evaporator to give an oily product, and this oily product was distilled under reduced pressure to give 77 g of 2-isopropylimidazole as a white solid (lump) (yield 70%, purity 98.4%). )Obtained. The obtained white solid was pulverized using a mill.

  In addition, gas chromatograph was used for the measurement of the above quantification / purity / yield, and in detail, column: HP-WAX 0.53 mm × 30 m × 1.0 μm manufactured by Agilent, column temperature: 100 ° C. to 10 ° C./min Measured at 220 ° C. for 8 minutes, inlet: 250 ° C., detector (hydrogen flame ionization detector): 250 ° C., carrier gas: 20 mL / min. did.

  The present invention is a production method for obtaining 2-alkylimidazole, especially 2-isopropylimidazole. Such 2-alkylimidazole is, for example, a pharmaceutical intermediate, a dye intermediate, and an epoxy resin or polyurethane resin. It is useful as a catalyst for various resins.

2 is a photomicrograph showing the crystal structure of 2-isopropylimidazole obtained in Example 1.

Claims (2)

  In a method for producing 2-alkylimidazole from ammonia, an alkyl aldehyde having 3 to 20 carbon atoms and glyoxal, an imine compound is formed by reacting ammonia and alkyl aldehyde in a heterogeneous state in an aqueous medium, A method for producing 2-alkylimidazole, characterized in that glyoxal is added to an aqueous medium in which an imine compound is formed, the imine compound and glyoxal are reacted, and crystals of 2-alkylimidazole are precipitated in the aqueous medium.   The method for producing a 2-alkylimidazole according to claim 1, wherein the aqueous medium on which the crystals of the 2-alkylimidazole are deposited is filtered.