JP6657975B2 - Method for producing hydroxyalkyltriethylenediamine with improved hue - Google Patents

Description

  The present invention relates to a method for producing a hydroxyalkyltriethylenediamine having an improved hue.

  Bicyclic amine compounds such as hydroxyalkyltriethylenediamines are known as compounds useful as, for example, pharmaceutical and agricultural chemical intermediates, reagents for organic synthesis, chemical adsorbents, antibacterial agents and the like (for example, Patent Documents 1 and 2). reference).

  As a method for producing hydroxyalkyltriethylenediamines, in Patent Document 1, piperazine is reacted with ethyl 2,3-dibromopropionate to give ethyl 1,4-diazabicyclo [2.2.2] octane-2-carboxylate. The resulting ester is prepared and then reduced to give 1,4-diazabicyclo [2.2.2] octane-2-methanol (hydroxymethyltriethylenediamine).

  However, this production method has disadvantages that purification is very complicated because a large amount of by-product salt is generated in the first step, and low productivity is inferior because a low substrate concentration is required. In the second step, lithium aluminum hydride, which has a high risk of ignition, is used as the reducing agent, so it is not industrially preferable. In addition, since expensive reaction substrates are used, the situation is not practical.

  For this reason, the present applicant has obtained the following formula as a simple and safe production method in which an objective product can be obtained in one step and an excessively high pressure reaction is unnecessary.

(In the formula, R represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms, and n represents an integer of 0 to 6.)
A patent application has already been filed for a method for producing a bicyclic amine compound by subjecting a dihydroxyalkylpiperazine represented by the following formula to an intramolecular dehydration condensation reaction in the presence of an acid catalyst (see Patent Document 2).

  The method described in Patent Document 2 is an excellent method that does not require a multi-step reaction and can easily and safely produce a bicyclic amine compound without using a reducing agent having a high risk of ignition. However, if the conversion is not sufficient, a step of recovering unreacted raw materials is required, and if an acid catalyst in this production method is applied to a gas phase reaction, a sufficient yield cannot be obtained, and Since organisms may be deposited in the form of tar and clog the reaction tube, there is still a problem to be improved in industrial continuous production.

  For this reason, the applicant of the present application has obtained a bicyclic amine compound in a simple and high yield, and as a production method capable of suppressing by-product tar components that hinder continuous production, the following formula:

(Wherein, R _{1 to} R ₈ each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a hydroxyl group, a hydroxymethyl group, or an alkoxy group having 1 to 4 carbon atoms. Represents an atom or a nitrogen atom, and Y represents a hydrogen atom, an alkyl group, a hydroxyl group, or a hydroxyalkyl group having 1 to 4 carbon atoms.)
Represented by the following formula as a solid catalyst

(Where A represents one or more elements selected from the group consisting of Si, Al, Mg, Ti and Zr, M represents an alkali metal element or an alkaline earth metal element, and P represents phosphorus. And O represents oxygen, subscripts a to d represent the number of moles of each element, b / a = 0.001 to 0.3 (molar ratio), c / a = 0.001 to 0.3 (mol) D) represents a value that can be arbitrarily determined depending on the bonding state of each atom, provided that when A represents two or more elements, the subscript a is the number of moles of the element having the largest number of moles. Represents.)
A patent application has already been filed for a method for producing a bicyclic amine compound by intramolecular dehydration in the gas phase in the presence of an inorganic oxide represented by the following formula (see Patent Document 3).

  Patent Document 3 discloses a production method by a gas phase reaction, and gaseous bicyclic amines generated by a gas phase reaction are usually collected by cooling once, and then, for example, re-used. It is purified by a crystallization method or a distillation method.

  In the recrystallization method, although low-color hydroxyalkyltriethylenediamines can be obtained, the amount remaining in the mother liquor is large, and multiple operations are required, and the recrystallization solvent needs to be recycled. is not. On the other hand, the distillation method is an efficient purification method with a small purification loss and a short process time, but the problem that the color of the product is deteriorated due to thermal decomposition of the hydroxyalkyltriethylenediamine itself or impurities or a side reaction during the distillation. There is. In particular, there is a problem that this hue deterioration progresses with time due to heat history.

JP 2001-504855 Gazette JP 2010-037325 A JP 2012-149048 A

  The present invention has been made in view of the background art described above, and has an object to improve a hue of a hydroxyalkyltriethylenediamine, and a production method capable of efficiently obtaining a bicyclic compound with high purity. Is provided.

  The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, completed the present invention.

  That is, the present invention is a method for producing a hydroxyalkyltriethylenediamine having an improved hue as described below.

  [1] The following general formula (1)

(In the formula, R ^{1 to} R ¹⁰ each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a hydroxyalkyl group having 1 to 4 carbon atoms.)
A crude hydroxyalkyltriethylenediamine reaction solution, which is an unpurified reaction solution, containing the hydroxyalkyltriethylenediamine represented by the formula, is brought into contact with oxygen at a temperature of 110 to 170 ° C., and then purified by distillation. A method for producing ethylenediamines.

  [2] The method for producing a hydroxyalkyltriethylenediamine according to the above [1], wherein the crude hydroxyalkyltriethylenediamine reaction liquid is brought into contact with oxygen in the air.

  [3] The hydroxyalkyltriethylenediamine according to the above [1] or [2], wherein the amount of oxygen to be brought into contact with the crude hydroxyalkyltriethylenediamine reaction liquid is 100 vol% or more based on the crude hydroxyalkyltriethylenediamine. Manufacturing method.

  [4] The method according to any one of [1] to [3], wherein the low-boiling component and water are distilled off from the crude hydroxyalkyltriethylenediamine reaction solution before contacting the crude hydroxyalkyltriethylenediamine reaction solution with oxygen. A method for producing a hydroxyalkyltriethylenediamine according to any one of the above.

[5] Any of the above-mentioned [1] to [4], wherein after contacting the crude hydroxyalkyltriethylenediamine reaction solution with oxygen, the hydroxyalkyltriethylenediamines are distilled off at a top temperature of less than 150 ° C. A method for producing a hydroxyalkyltriethylenediamine according to any one of the above.
[6] The production of hydroxyalkyltriethylenediamines according to any one of [1] to [5], wherein the Gardner color number of the distilled and purified hydroxyalkyltriethylenediamine after heating test is 7 or less. Method.

  Hereinafter, the present invention will be described in more detail.

  In the production method of the present invention, a crude hydroxyalkyltriethylenediamine reaction solution, which is an unpurified reaction solution containing the hydroxyalkyltriethylenediamine represented by the above formula (1), is brought into contact with oxygen at a temperature of 110 to 170 ° C. After that, it is characterized by distillation purification.

In the general formula (1), R ^{1 to} R ¹⁰ each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or a hydroxyalkyl group having 1 to 4 carbon atoms.

  The compound represented by the general formula (1) is not particularly limited as long as it satisfies the above definition, and examples thereof include the following compounds.

  The method for producing the hydroxyalkyltriethylenediamine represented by the general formula (1) is not particularly limited. For example, Khimiya Geterotsiklicheskikh Soedenenil, 10, 1404 (1980), and WO95 / 18104 pamphlet It can be manufactured by the method described. In addition, an ethylene oxide adduct of a hydroxyalkyl piperazine derived by a method described in Journal of Medicinal Chemistry (1993), 36 (15), 2075-2083 or JP-A-2010-120887 is intramolecularly cyclized. It can also be manufactured by this. Further, for example, it can be produced by a method described in JP-A-2010-37325, Patent Document 3, or the like, that is, an intramolecular dehydration cyclization reaction of dihydroxyalkylpiperazines by a gas phase method. Among these methods, a method of producing a dihydroxyalkylpiperazine by intramolecular dehydration cyclization is preferred from the viewpoint of the reaction step and production efficiency.

  Next, the step of contacting the crude hydroxyalkyltriethylenediamine reaction solution with oxygen in the present invention will be described.

  In the above-mentioned production method by a gas phase reaction, usually, hydroxyalkyltriethylenediamines are generated in the range of 200 to 500 ° C., and then the gaseous crude hydroxyalkyltriethylenediamine reaction liquid generated in the reaction step is subjected to the distillation step. Thus, low boiling components and high boiling components are removed. At this time, in the reaction solution, there are various components such as low boiling components derived from the decomposition of the raw materials, high boiling components due to the intermolecular reaction, and impurities in which these by-product impurities are denatured by heat or a catalyst. . The decomposition products and hydroxyalkyltriethylenediamines derived from the raw materials are colored with time due to the heat history, so that the coloring materials accompany during distillation, which may affect the quality of the product.

  In the present invention, before the distillation, the crude hydroxyalkyltriethylenediamine reaction solution is brought into contact with oxygen to promote the coloring of impurities in the reaction solution and reduce the hue deterioration due to entrainment of the coloring matter during the subsequent distillation. This improves the hue of the product.

  In the present invention, the oxygen to be brought into contact with the crude hydroxyalkyltriethylenediamine reaction solution does not need to be pure oxygen gas, and there is no problem even if it is mixed with another inert gas. Although not particularly limited, oxygen content in the air is preferable.

  The temperature of the crude hydroxyalkyltriethylenediamine reaction liquid at the time of contacting with oxygen is preferably from 110 to 170 ° C, particularly preferably from 140 to 160 ° C.

  In the present invention, since the coloring of the crude hydroxyalkyltriethylenediamine reaction solution proceeds in the presence of heat and a small amount of oxygen, a particularly high concentration of oxygen is not required, and from the viewpoint of industrial safety, the oxygen concentration to be contacted is It is preferably at least 100 vol% with respect to the crude hydroxyalkyltriethylenediamine reaction liquid.

  In the present invention, in order to minimize the coloring of the crude hydroxyalkyltriethylenediamine reaction solution, it is preferable that the contact between the reaction solution and oxygen is performed after the low-boiling components and water are distilled off.

  In the present invention, the final distillation of hydroxyalkyltriethylenediamine is preferably performed so that the tower top temperature is less than 150 ° C. in order to suppress a change in hue due to heat history.

  According to the above method, hydroxyalkyltriethylenediamines having a better hue than conventional distillation can be obtained.

  ADVANTAGE OF THE INVENTION According to the manufacturing method of this invention, since a heat history is suppressed and the hydroxyalkyl triethylene diamines with improved hue can be efficiently manufactured with high purity, it is very useful industrially.

  The present invention will be described in more detail with reference to the following Reference Examples and Examples, but the present invention should not be construed as being limited thereto.

  In addition, the hue of the compound in this example was evaluated using a color difference meter ZE6000 (manufactured by Nippon Denshoku Industries Co., Ltd.).

Reference Example 1 Preparation of 2-Hydroxymethyltriethylenediamine Reaction Solution According to the method described in Synthesis Example 2 of JP-A-2012-149225, 2-hydroxymethyltriethylenediamine was synthesized (see the following formula).

  First, 15.5 kg (180 mol) of piperazine and 15.6 L of methanol were charged into a 50 L reaction vessel, and the temperature was raised to 65 ° C. under a nitrogen atmosphere. -6.06 kg (54.8 mol) of propanediol was added dropwise over 3 hours. During the dropwise addition, the liquid temperature gradually increased, and the liquid temperature at the end was 75 ° C. Thereafter, the reaction temperature was adjusted to 70 ° C., and the mixture was aged for 3 hours. The reaction conversion was 100%. The heat source was dropped, and the mixture was allowed to stand overnight. Then, 4.6 kg (55 mol) of a 48% aqueous sodium hydroxide solution was slowly dropped into the reaction solution whose temperature had dropped to around room temperature to precipitate a by-product salt. After the reaction liquid extracted from the bottom of the kettle was desalted by filtration, methanol was distilled off using an evaporator. Furthermore, unreacted piperazine was azeotropically distilled off by simple distillation while adding water, and then the target product was isolated by distillation under reduced pressure (milky white solid, yield 8.1 kg, yield 91%). It was confirmed to be 3- (1'-piperazinyl) -1,2-propanediol (1) from GC-MS and NMR.

Next, a commercially available aluminum phosphate (Kishida Chemical Co., Ltd.) and cesium nitrate (Wako Pure Chemical Industries, Ltd.) were mixed and dehydrated in the center of a quartz glass tube having an inner diameter of 40 mm as a catalyst for a gas phase reaction, and 1% by weight of graphite After the addition, 160 mL of a molded product (diameter: 5 mm, thickness: 2 mm) obtained by tableting and baking (450 ° C., 6 hours), and the upper and lower portions thereof were filled with a Raschig ring having an outer diameter of 5 mm. The catalyst layer and the Raschig ring layer were maintained at 360 ° C. in an electric furnace, and 1.6 kg (10 mol) of 3- (1′-piperazinyl) -1,2-propanediol (1) aqueous solution (2 mol%) was added from above. , GHSV = 1,500Hr ⁻¹ . Also, a nitrogen gas was entrained as a diluent gas at GHSV = 750 Hr ⁻¹ . After 3 hours from the start of the passage, the reaction solution was collected over 1 hour and analyzed by gas chromatography. As a result, the conversion was 100%. After GC-MS analysis of the obtained component, distillation and isolation by column chromatography were performed, and analysis by NMR and elemental analysis confirmed that it was 2-hydroxymethyltriethylenediamine represented by Exemplified Compound 1 described above. did. The yield was 44%. Other products were 1,5-diazabicyclo [3.2.2] nonan-3-ol (5%), piperazine (22%) and triethylenediamine (1%) from which side chains had been eliminated. .

Example 1
After distilling off the low boiling point components and water of the crude hydroxymethyltriethylenediamine reaction solution obtained by the reaction, air was added to the reaction solution at atmospheric pressure at 150 ° C. at 9 vol% / min (1.9 vol. In terms of oxygen). % / Min) for 1 hour. The contacted oxygen amount was 113 vol%.

  After contact with air, the analysis showed that the purity of hydroxymethyltriethylenediamine did not change, but the high-boiling component of the reaction solution increased from 10.2% to 12.6%. Subsequently, distillation was performed at a pressure of 3 mmHg, a bottom temperature of 160 to 200 ° C., a top temperature of 100 to 120 ° C., and a reflux ratio of 3 to distill off a hydroxymethyltriethylenediamine fraction containing a low-boiling component. It was extracted from the bottom of the distillation column. Subsequently, the obtained hydroxymethyltriethylenediamine containing a low-boiling component is distilled at a pressure of 3 mmHg, a bottom temperature of the vessel of 140 ° C., a top temperature of 110 to 115 ° C., and a reflux ratio of 20, to remove the low-boiling component and purify the purity. 99.6% of hydroxymethyltriethylenediamine was collected from the bottom of the distillation column. Table 1 shows the Gardner color number after heating the obtained hydroxymethyltriethylenediamine at 120 ° C. for 4 hours under a nitrogen atmosphere.

Example 2
Example 1 was carried out in the same manner as in Example 1 except that the obtained hydroxymethyltriethylenediamine was heated at 160 ° C. Table 1 shows the results.

Example 3
After distilling off the low boiling point components and water of the crude hydroxymethyltriethylenediamine reaction solution obtained by the reaction, air was added to the reaction solution at atmospheric pressure at 150 ° C. at 9 vol% / min (1.9 vol. In terms of oxygen). % / Min) for 5 hours. The contacted oxygen amount was 567 vol%. Purification by distillation was performed in the same manner as in Example 1, and hydroxymethyltriethylenediamine having a purity of 99.7% was collected from the bottom of the distillation column. Table 1 shows the Gardner color number after heating the obtained hydroxymethyltriethylenediamine at 120 ° C. for 4 hours under a nitrogen atmosphere.

Example 4
Example 3 was carried out in the same manner as in Example 3, except that the obtained hydroxymethyltriethylenediamine was heated at 160 ° C. Table 1 shows the results.

Comparative Example 1
Distillation purification was performed in the same manner as in Example 1 except that the operation of bringing into contact with air was not performed, and hydroxymethyltriethylenediamine having a purity of 99.7% was collected from the bottom of the distillation column. Table 1 shows the Gardner color number after heating the obtained hydroxymethyltriethylenediamine at 120 ° C. for 4 hours under a nitrogen atmosphere.

Comparative Example 2
Comparative Example 1 was carried out in the same manner as in Comparative Example 1, except that the obtained hydroxymethyltriethylenediamine was heated at 160 ° C. Table 1 shows the results.

  From Table 1, the hydroxyalkyltriethylenediamine obtained in Examples 1 to 4 has a smaller Gardner color number than the hydroxyalkyltriethylenediamine obtained in Comparative Examples 1 and 2, the heat history is suppressed, and the hue is also reduced. It is clear that it has improved.

Claims (6)

Compounds shown below
Including hydroxyalkyltriethylenediamine represented by either, which is a crude reaction crude hydroxyalkyltriethylenediamine reaction liquid, after contacting with oxygen at a temperature of 110 to 170 ° C., and wherein the purification by distillation method for producing a hydroxyalkyl triethylene di Amin. The crude hydroxyalkyltriethylenediamine reaction solution, method for producing hydroxyalkyl triethylene di Amin of claim 1, wherein the contacting with oxygen in air. Producing a hydroxyalkyl triethylene di Amin of claim 1 or claim 2 the amount of oxygen contacting the crude hydroxyalkyltriethylenediamine reaction solution is equal to or is 100 vol% or more with respect to crude hydroxyalkyltriethylenediamine Method. The low-boiling component and water are distilled off from the crude hydroxyalkyltriethylenediamine reaction solution before the crude hydroxyalkyltriethylenediamine reaction solution is brought into contact with oxygen. the method for producing a hydroxyalkyl triethylene di Amin. After the crude hydroxyalkyltriethylenediamine reaction was allowed to contact with oxygen, to any one of claims 1 to 4, characterized in that distilling off the hydroxyalkyl triethylene di Amin at top temperature of less than 0.99 ° C. method for producing a hydroxyalkyl triethylene di Amin described. Method for producing a hydroxyalkyl triethylene di Amin according to any one of claims 1 to 5, wherein the Gardner color number after the heating test of distillation purified hydroxyalkyltriethylenediamine of 7 or less.