Method for preparing tris(hydroxymethyl)nitromethane, tris(hydroxymethyl)nitromethane prepared using method, method for preparing tris(hydroxymethyl)aminomethane, and tris(hydroxymethyl)aminomethane prepared using method

Abstract

The present invention provides a method for preparing tris(hydroxymethyl)nitromethane, tris(hydroxymethyl)nitromethane prepared using the method, a method for preparing tris(hydroxymethyl)aminomethane comprising the method; and tris(hydroxymethyl)aminomethane prepared using the method, the method for preparing tris(hydroxymethyl)nitromethane comprising the steps of: a) adding formaldehyde to a reaction vessel and dissolving the formaldehyde in a solvent; b) adding an alumina catalyst to the solution; c) adding nitromethane to the solution and reacting; and d) obtaining tris(hydroxymethyl)nitromethane through the catalytic reaction.

Description

Method for producing tris(hydroxymethyl)nitromethane, method for producing tris(hydroxymethyl)nitromethane and tris(hydroxymethyl)aminomethane produced by the method, and tris(hydroxymethyl)aminomethane produced by the method

[0001] The present invention relates to a method for producing tris(hydroxymethyl)nitromethane, a method for producing tris(hydroxymethyl)nitromethane and tris(hydroxymethyl)aminomethane produced by the method, and tris(hydroxymethyl)aminomethane produced by the method.

[0002] The Henry reaction, also known as the nitroaldol reaction, is used to synthesize β-nitroalcohols from aldehydes or ketones and nitroalkanes. The proton at the α position of the nitroalkane is readily removed by a base due to its high acidity, and the resulting anion is stabilized by the nitro group. This anion reacts with a carbonyl compound to form β-nitroalcohols. These β-nitroalcohols can be converted to nitroalkenes by dehydration, and the hydroxy and nitro groups can be converted to other functional groups, making them useful intermediates. Recently, numerous asymmetric Henry reactions using various asymmetric catalysts have been reported.

[0003] In the production of the above nitroalcohol, alkali metal hydroxides, alkaline earth metal hydroxides, basic ion exchange resins, or tertiary amines are used as basic catalysts. However, the above basic catalysts have the disadvantage of unsatisfactory conversion rates and selectivity if the exothermic reaction is not properly controlled due to the severe exothermic reaction immediately after the reaction.

[0004] In addition, the above basic catalyst has the disadvantage of being economically unfeasible and environmentally unfriendly because its reuse is limited.

[0005] In addition, the nitroalcohol is used as a useful intermediate in the synthesis of aminoalcohol, but the basic catalyst is not preferable for the reduction of the nitro group of the nitroalcohol. That is, when a basic catalyst is used, the pH of the reaction solution becomes weakly basic, and accordingly, when reducing the nitro group to an amine group under hydrogen pressure after formylation and removal of the base, it has the disadvantage of being difficult to cause a dehydration reaction. This is because the reduction reaction of the nitro group to an amine group proceeds well under conditions of low pH or in an environment in which a protonated solvent such as methanol or ethanol is present. Therefore, when producing aminoalcohol from the nitroalcohol in a subsequent process after producing the nitroalcohol, the use of a basic catalyst is not preferable.

[0006] Therefore, there is a need for the development of a method that can improve the above-mentioned shortcomings of the conventional method for producing nitroalcohol using a basic catalyst.

[0007] A prior patent related to the present invention is Japanese Patent Registration No. 5307103.

[0008] The present invention has been devised to solve the above problems of the prior art.

[0009] By using an alumina catalyst, high heat generation does not occur immediately after the reaction, high conversion and selectivity are provided, and the catalyst can be reused and regenerated, thereby providing an economical and environmentally friendly method for producing tris(hydroxymethyl)nitromethane and high-purity tris(hydroxymethyl)nitromethane produced by the method.

[0010] In addition, the present invention aims to provide a method for producing tris(hydroxymethyl)aminomethane, which improves conversion and selectivity without an additional process by forming acid conditions, which are stable reaction conditions, as a subsequent process including the process for producing the above tris(hydroxymethyl)nitromethane, and a high-purity tris(hydroxymethyl)aminomethane produced by the method.

[0011] The present invention

[0012] a) A step of placing formaldehyde in a reaction vessel and dissolving it in a solvent;

[0013] b) Step of adding an alumina catalyst to the above solution:

[0014] c) a step of adding nitromethane to the above solution and reacting it; and

[0015] d) A method for producing tris(hydroxymethyl)nitromethane is provided, including a step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction.

[0016]

[0017] In addition, the present invention

[0018] Tris(hydroxymethyl)nitromethane manufactured by the above method is provided.

[0019]

[0020] In addition, the present invention

[0021] a) A step of placing formaldehyde or paraformaldehyde in a reaction vessel and dissolving it in a solvent;

[0022] b) Step of adding an alumina catalyst to the above solution:

[0023] c) a step of adding nitromethane to the above solution and reacting it; and

[0024] d) a step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction; and

[0025] e) A method for producing tris(hydroxymethyl)aminomethane, comprising the step of reducing the above tris(hydroxymethyl)nitromethane, is provided.

[0026]

[0027] In addition, the present invention

[0028] Tris(hydroxymethyl)aminomethane manufactured by the above method is provided.

[0029] The method for producing tris(hydroxymethyl)nitromethane of the present invention uses an alumina catalyst, so that high heat generation does not occur immediately after the reaction, provides high conversion rate and selectivity, and allows reuse and regeneration of the catalyst, thereby providing improved economic efficiency and environmental friendliness.

[0030] The tris(hydroxymethyl)nitromethane of the present invention is manufactured by the above method, and thus provides an effect of high purity.

[0031] The method for producing tris(hydroxymethyl)aminomethane of the present invention is a subsequent process including the process for producing tris(hydroxymethyl)nitromethane, and forms acid conditions, which are stable reaction conditions, thereby providing the effect of improving the conversion rate and selectivity without an additional process.

[0032] In addition, the tris(hydroxymethyl)aminomethane of the present invention can be produced by the above method.

[0033] Figure 1 is a drawing illustrating the chemical formula for formaldehyde in a solution state in the present invention.

[0034] The present invention is described in detail below.

[0035] The method for producing tris(hydroxymethyl)nitromethane of the present invention has the following characteristics.

[0036] a) A step of placing formaldehyde in a reaction vessel and dissolving it in a solvent;

[0037] b) Step of adding an alumina catalyst to the above solution:

[0038] c) a step of adding nitromethane to the above solution and reacting it; and

[0039] d) A step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction.

[0040] The order of addition of the reaction components in steps a) to c) above is not limited to the above order and may be arbitrarily changed to various orders.

[0041] The above nitromethane and formaldehyde form tris(hydroxymethyl)nitromethane through the “Henry reaction” under an alumina catalyst.

[0042] In the above, formaldehyde can be added in an amount of 2 to 10 moles, preferably 3 to 5 moles, based on 1 mole of the nitromethane. As described above, formaldehyde must be added in excess so that all hydrogen groups of the methyl groups of nitromethane can be replaced with hydroxymethyl groups.

[0043]

[0044] In the above, formaldehyde may be used as a solution (containing methanol as a stabilizer) or paraformaldehyde. According to NMR analysis, formaldehyde in a solution can exist in various forms, as shown in Figure 1.

[0045] Therefore, the formaldehyde in the above solution contains about 10 to 15 wt% of methanol as a stabilizer or polymerization inhibitor. However, since the boiling point of methanol is about 65°C, if the reaction temperature exceeds 70°C, the methanol will vaporize and formaldehyde will polymerize due to the remaining water. Therefore, a large amount of unknown impurity is generated, which may increase the amount of impurities that need to be removed after the reduction reaction. Therefore, when using formaldehyde as a reactant, the reaction temperature should not exceed 70°C if possible.

[0046] However, when using a conventional basic catalyst, the reaction temperature exceeds 70°C, resulting in the generation of a large amount of impurities, and subsequent processes inevitably follow to remove these impurities. The present invention utilizes an alumina catalyst to lower the reaction temperature below the boiling point of methanol, thereby exhibiting the characteristic of being free from the aforementioned problems.

[0047]

[0048] The above alumina (Al2O3) catalyst may be added in an amount of 0.1 to 2 mol, preferably 0.1 to 1 mol, and more preferably 0.1 to 0.5 mol, based on 1 mol of nitromethane.

[0049] The reaction in step c) may be carried out at a temperature of 25 to 60°C, preferably 25 to 40°C, and more preferably 25 to 30°C. This temperature range is preferred because it provides a balance between reaction rate and impurity levels. Generally, increasing the temperature increases the reaction rate, but undesirable side reactions are promoted at higher temperatures.

[0050] In step c), the reaction may be carried out under atmospheric pressure, but is not limited thereto.

[0051] In step c), it may be preferable to add nitromethane in portions. However, this is not limited to the case, and it may be added all at once.

[0052] Additionally, when the order of addition of the reaction components in steps a) to c) above is changed, the formaldehyde component may be added in portions.

[0053] The solvent in step a) above may be at least one selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, butanol, and water, and methanol or water may be most preferably used.

[0054] After the reaction in step c), the pH of the reaction solution is advantageously 2 to 6, preferably 3 to 5, when producing tris(hydroxymethyl)aminomethane in the subsequent process.

[0055]

[0056] In addition, the present invention

[0057] Tris(hydroxymethyl)nitromethane manufactured by the above manufacturing method is provided.

[0058] The above tris(hydroxymethyl)nitromethane has the characteristic of excellent purity.

[0059]

[0060] In addition, the present invention

[0061] a) A step of placing formaldehyde in a reaction vessel and dissolving it in a solvent;

[0062] b) Step of adding an alumina catalyst to the above solution:

[0063] c) Step of adding nitromethane to the above solution and reacting;

[0064] d) a step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction; and

[0065] e) A method for producing tris(hydroxymethyl)aminomethane, comprising the step of reducing the above tris(hydroxymethyl)nitromethane, is provided.

[0066] Since steps a) to d) above are the same as those described above, their explanation is omitted.

[0067] In the above step e), reduction can be performed by supplying hydrogen gas.

[0068] In addition, in the step e), the reduction can be performed using at least one reducing agent selected from the group consisting of heterogeneous catalysts such as Ra-Ni, Pd / C, and homogeneous catalysts such as LiAlH4, NaBH4.

[0069] In addition, the present invention

[0070] Tris(hydroxymethyl)aminomethane manufactured by the above manufacturing method is provided.

[0071]

[0072] Hereinafter, the present invention will be described in more detail through examples. However, the following examples are intended to further illustrate the present invention, and the scope of the present invention is not limited by these examples. Those skilled in the art may appropriately modify or alter the following examples within the scope of the present invention.

[0073]

[0074] Example 1: Preparation of tris(hydroxymethyl)nitromethane

[0075] 1) 3 mol of a 37 wt% formaldehyde aqueous solution containing 50-55 wt% water and 10-15 wt% methanol was added to a thermocouple, reflux condenser, stirrer, and a 1-liter round-bottom flask, and 0.12 mol of an alumina catalyst (activated basic form) was added and stirred thoroughly for 10 minutes. 1 mol of nitromethane was charged to a dropping funnel at room temperature and added to the reactor at a uniform rate for 1 hour, maintaining the temperature of the reactor at 60°C. After sufficient stirring for 4 hours until the reaction was completed, the reactor was cooled to room temperature. Once the temperature dropped to room temperature, the alumina catalyst was filtered using a vacuum filter, and the composition of the remaining product was analyzed by NMR (nuclear magnetic resonance) or HPLC (high pressure liquid chromatography) to confirm whether nitromethane was consumed.

[0076] The main products of the above reaction consisted of tris(hydroxymethyl)nitromethane, water, and less than 0.5 wt% formaldehyde, and water and formaldehyde could be removed through a concentration process.

[0077]

[0078] Recycling of Alumina Catalysts

[0079] After filtering, the remaining alumina catalyst is washed cleanly using an aprotic solvent such as acetone, and the remaining catalyst is dried in an oven at 80°C for 24 hours before being reused.

[0080]

[0081] <Manufacture of tris(hydroxymethyl)aminomethane>

[0082] The reactor was charged with methanol and a Raney-Ni catalyst slurry (50 wt% Ni catalyst, 50 wt% water), and the temperature was increased to the reaction temperature, followed by supplying hydrogen to pressurize. Stirring was started, and the tris(hydroxymethyl)nitromethane solution prepared above was supplied at a uniform rate for 2.5 hr, and after the supply was completed, sufficient stirring was performed for 30 minutes. After the hydrogen was depressurized to lower the reactor pressure, the liquid product and the solid catalyst were filtered and discharged from the reactor, and the liquid phase separated through filtration was distilled to remove the solvent, and the product tris(hydroxymethyl)aminomethane was obtained.

[0083]

[0084] Example 2: Preparation of tris(hydroxymethyl)nitromethane

[0085] Tris(hydroxymethyl)nitromethane was prepared in the same manner as Example 1, except that 0.24 mol of alumina was used per 1 mol of nitromethane.

[0086]

[0087] Example 3: Preparation of tris(hydroxymethyl)nitromethane

[0088] Tris(hydroxymethyl)nitromethane was prepared in the same manner as in Example 1, except that 0.48 mol of alumina was used per 1 mol of nitromethane.

[0089]

[0090] Comparative Example 1: Preparation of tris(hydroxymethyl)nitromethane

[0091] A 37 wt% formaldehyde aqueous solution containing 50-55 wt% water and 10-15 wt% methanol was charged into a thermocouple, a reflux condenser, a stirrer, and a 1-liter round-bottom flask, and 0.01 mol of sodium hydroxide was added and stirred thoroughly for 10 minutes. 1 mol of nitromethane was charged into a dropping funnel at room temperature and fed into the reactor at a uniform rate for 2 hours. At this time, a strong exothermic reaction occurred. If the reaction temperature exceeds 70℃, the color of the reactant gradually changes to yellow and orange, and impurities are generated. Therefore, an ice bath was installed in the reactor to maintain the temperature of the reactor below 60℃, and the reactor was stirred sufficiently for 1 hour until the reaction was completed, and then the temperature of the reactor was cooled to room temperature. When the temperature was lowered to room temperature, the reaction was terminated and the product composition was analyzed using NMR (nuclear magnetic resonance) or HPLC (high pressure liquid chromatography) to confirm whether nitromethane was consumed.

[0092]

[0093] Comparative Example 2: Preparation of tris(hydroxymethyl)nitromethane

[0094] Tris(hydroxymethyl)nitromethane was prepared in the same manner as in Comparative Example 1, except that trimethylamine was used as a base catalyst.

[0095]

[0096] Comparative Example 3: Preparation of tris(hydroxymethyl)nitromethane

[0097] Tris(hydroxymethyl)nitromethane was prepared in the same manner as in Comparative Example 1, except that triethylamine was used as a base catalyst.

[0098]

[0099] Experimental Example 1: Evaluation of the Manufacturing Process for Tris(hydroxymethyl)nitromethane

[0100] The manufacturing process of tris(hydroxymethyl)nitromethane of the above examples and comparative examples was monitored and evaluated as summarized in Table 1 below.

[0101] Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 1 Example 2 Example 3 Catalyst Sodium hydroxide Trimethylamine Triethylamine Al2O3 0.12 mol Al2O3 0.24 mol Al2O3 0.48 mol Temperature change after reaction 25->75 (severely exothermic) 25->70 (severely exothermic) 25->70 (severely exothermic) 25→25 (temperature maintained) 25→26 (temperature maintained) 25→28 (temperature maintained) Color white Yellow Orange White White White Selectivity <99.5% <99.5% (TMA present) <99.5% (TEA present) >99.9% >99.9% >99.9% After reaction pH 10~11 (strong base) 9.1 (weak base) 9.2 (weak base) 3.8 (weak acid) 4.1 (weak acid) 4.2 (weak acid) Subsequent process Ion exchange resin application required for Na, K ion removal Ion exchange resin application required for amine removal Ion exchange resin application required for amine removal XXXRecyclingXXXOOO

Claims

1. a) Step of placing formaldehyde in a reaction vessel and dissolving it in a solvent; b) Step of adding alumina catalyst to the above solution: c) a step of adding nitromethane to the above solution and reacting it; and d) A method for producing tris(hydroxymethyl)nitromethane, comprising the step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction.

2. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that formaldehyde is added in an amount of 2 to 10 moles based on 1 mole of the above nitromethane.

3. In paragraph 2, A method for producing tris(hydroxymethyl)nitromethane, characterized in that formaldehyde is added in an amount of 3 to 5 mol.

4. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the alumina catalyst is added in an amount of 0.1 to 2 mol based on 1 mol of nitromethane.

5. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the reaction in step c) is performed at a temperature of 25 to 60°C.

6. In paragraph 5, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the reaction in step c) is performed at a temperature of 25 to 30°C.

7. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the reaction in step c) is performed under atmospheric pressure.

8. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that nitromethane is added in portions in the above step c).

9. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the pH of the reaction solution after the reaction in step c) is 2 to 6.

10. In paragraph 1, A method for producing tris(hydroxymethyl)nitromethane, characterized in that the solvent in step a) is at least one selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, butanol, and water.

11. Tris(hydroxymethyl)nitromethane manufactured by any one of the manufacturing methods of clauses 1 to 10. 12.a) Step of placing formaldehyde in a reaction vessel and dissolving it in a solvent; b) Step of adding alumina catalyst to the above solution: c) a step of adding nitromethane to the above solution and causing a reaction; d) a step of obtaining tris(hydroxymethyl)nitromethane by the above catalytic reaction; and e) A method for producing tris(hydroxymethyl)aminomethane, comprising the step of reducing the above tris(hydroxymethyl)nitromethane.

13. In paragraph 12, A method for producing tris(hydroxymethyl)aminomethane, characterized in that the reduction in step e) is performed by supplying hydrogen gas.

14. In paragraph 12, The reduction of step e) above is carried out by Ra-Ni, Pd / C, LiAlH 4 , and NaBH 4 A method for producing tris(hydroxymethyl)aminomethane, characterized in that it is performed using one or more reducing agents selected from the group consisting of:

15. Tris(hydroxymethyl)aminomethane manufactured by the manufacturing method of Article 12.

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