KR0163295B1 - Process for preparation of n-substituted polyhydroxy amines - Google Patents

Abstract

The present invention reacts a primary amine (R-NH ₂ ) with a reducing sugar in the presence of an antioxidant and a solvent containing at least one hydroxy group, followed by hydrogenation in the presence of a catalyst. A method for preparing amines with high productivity.

Description

Process for preparing N-substituted polyhydroxy amine

The present invention relates to a process for the preparation of N-substituted polyhydroxy amines. More specifically, the present invention reacts the primary amine (R-NH ₂ ) with reducing sugars in the presence of an antioxidant and a solvent containing at least one hydroxyl group and then hydrogenated in the presence of a catalyst to give excellent color N-substitution. To a high productivity of the prepared polyhydroxy amine.

In general, conventional surfactants have a big problem of polluting and destroying the environment and irritating to the human body, and as the amount of use thereof increases, this problem is more serious. Therefore, in order to solve these problems, there is a growing interest in natural surfactants and surfactants having hypoallergenic properties, and in the same context, intermediates of N-alkyl-N-acyl polyhydroxy amides which are natural nonionic surfactants. Attention has been directed to N-substituted polyhydroxy amines, which are widely known and are used as dyes or as intermediates for pharmaceuticals.

The process for preparing N-substituted polyhydroxy amines has been studied for a long time, and according to US Pat. No. 2,016,963, an aqueous solution of glucose and methamine are prepared by pressure reduction in the presence of a titanium catalyst. However, this method has disadvantages such as the use of a large amount of catalyst and a long reaction at a low temperature.

In general, the synthesis yield of N-methyl polyhydroxy amine (aka N-methyl glucamine) varies depending on the reaction temperature, catalyst seedling and the amount used, and the amount of methylamine used (vs. glucose). JF IIEEG et al. According to Synthesis of ¹⁴ C-labeled N-methyl glucamine, Canadian J. of pharm. SCT., 10 (1975), the reaction with low hydrogen pressure of 4 atm below 50 ° C. A good color product can be obtained, but the reaction time is long and it is unsuitable for mass production due to low yield when using aqueous ammonia solution. Therefore, in order to overcome this problem, benzyl glucamine must first be prepared and then hydrolyzed to produce N-methyl glucamine, which is complicated and expensive to manufacture.

U.S. Patent No. 2,016,926 uses a method of reacting reduced sugars with aqueous ammonia or primary and secondary amines at low temperatures, but in this case, the reaction time is long and the amount of ammonia or primary and secondary amines is required. This is a small problem.

Japanese Patent Application No. 49-27848 shows the relationship between the number of grams of nickel catalyst per gram of glucose and the hydrogen pressure for the purpose of obtaining high yield, but the product is colored by using water as a solvent. It acted as a catalyst poison, resulting in a decrease in catalyst function.

In PCT / US91 / 06978 and PCT / US91 / 06979, methanol or an amine participating in the reaction is used in an excess amount or mixed with water. However, when an excess solvent is used, a good quality object can be obtained. While the productivity is low, when a small amount of solvent is used, the productivity is improved, but problems such as color change occur. In addition, PCT / US91 / 0729 and PCT / US92 / 06022 adopt a process that does not react with oxygen, but since the color of the product changes depending on the color of glucose, the starting material, to obtain a good color product, It's cumbersome because you have to use it and you have to go through two steps.

As described above, many prior patents refer to the reaction temperature, reaction time, type of solvent and catalyst, the amount of alkylamine to glucose, the pressure of hydrogen or nitrogen used to prevent the oxidation reaction, etc. No literature suggests a fundamental way to prevent it.

Taken together, the techniques developed so far have yielded good color N-substituted polyhydroxy amines in order to react with hydrogen or nitrogen at low temperatures with as much solvent as possible or to prevent reactants from contacting oxygen. It should be reacted in the presence, and the shorter the contact time between the reducing sugar and the primary amine, the better the color. However, if the reaction at low temperature is low yield, long time reaction and use a large amount of solvent is not suitable for mass production. In addition, if the solvent is used to increase the reaction temperature to increase the reaction yield and shorten the reaction time (above 60 ° C.) or to increase the productivity, the productivity increases but the color of the product is poor, making it difficult to apply to the product without a separate decolorization process. .

The present inventors have solved the above-mentioned problems of the prior art and conducted intensive research to produce N-substituted polyhydroxy amines having excellent color with high productivity. The use of antioxidants instead of hydrogen shortens the manufacturing time, makes it easier to control the manufacturing process, and obtains high-quality products with high yields. The present invention has been completed by discovering that it can be obtained.

Hereinafter, the configuration of the present invention will be described in detail.

The present invention reacts a primary amine (R-NH ₂ ) with a reducing sugar in the presence of an antioxidant and a solvent containing at least one hydroxy group, followed by hydrogenation in the presence of a catalyst to increase the N-substituted polyhydroxy amine. It relates to a method for producing with productivity.

Primary amines used as starting materials in the present invention may include C ₁ -C ₁₈ alkyl, C ₁ -C ₁₈ hydroxyalkyl or amines substituted by benzyl, preferably C ₁ -C ₄ alkyl, Amines substituted by C ₁ -C ₄ hydroxy alkyl or benzyl, for example methyl, ethyl, propyl, butyl, hydroxyethyl, hydroxy propyl, hydroxy butyl or benzyl. They are present in anhydrous state or dissolved in a solvent, in particular water, and the concentration when present in solution is 20 to 90%, preferably 40 to 70%. The primary amine is preferably used in 1 to 20 mole times, preferably 1 to 5 mole times based on a reducing sugar such as glucose. If the amount is less than 1 mole, the amount of unreacted reducing sugar is increased, so there is a problem that the reducing sugar removal process is required, and when it is used more than 20 mole, the yield is no longer increased compared to the use of a large amount, which is undesirable.

Representatives that can be used as reducing sugar in the present invention include glucose. Glucose derived from corn syrup uses granules or powders, or those dissolved in solvents, especially water, with concentrations ranging from 40 to 90% by weight and wind to 50 to 70% by weight. It is better not to exceed the weight percentage. The color of glucose used is preferably Gardner color 1 or less, in particular 0 or white.

In the present invention, when glucose is used as the reducing sugar, the reaction process is shown in Scheme 1 below.

Wherein R represents C ₁ -C ₁₈ alkyl, C ₁ -C ₁₈ hydroxyalkyl or benzyl.

Reducing sugars usable in the present invention besides glucose include one or more selected from maltose, fructose, maltotriose, xylose, galactose, lactose and glyceraldehyde.

In the present invention, an alcohol or a polyol organic solvent containing at least one hydroxyl group is used as the solvent. In particular, when reacting in a methanol solvent, it was possible to carry out the reaction at a preferred reaction temperature. In addition, ethanol, 1-propanol, iso-propanol, butanol, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, Reaction can also be advanced preferably also in glycerol. The amount of solvent used is 50 to 100 ml, preferably 200 to 700 ml, based on 1 mole of reducing sugar (eg glucose). The use of a large amount of solvent can maintain a good color, but a suitable amount of solvent is selected in the process according to the invention because the amount of production per unit reactor volume is reduced and the use of a small amount of solvent not only results in poor color but also coloration acts as a catalyst poison. It is very important to do.

As antioxidants, organic and inorganic materials commonly used may be used.For example, sodium silicate, hydroquinone, stylenediamine tetaacetic acid (EDTA), tetraacetyl ethylenediamine (TAED), butyl hydroxytoluene (BHT), and butylated hydroxyanisol (BHA) , Organophosphates (Briquest and Dequest; Monsanto tradename) may be mentioned. Antioxidants are used in an amount of 0.1 to 30% by weight, preferably 1 to 10% by weight, based on the reducing sugar. When used at less than 0.1% by weight, the antioxidant is almost no color. This is because it does not become good and there is a problem that the reaction yield is reduced by using a large amount of antioxidant.

As a catalyst used in the process of carrying out the hydrogenation reaction, there may be mentioned conventional metals used in the hydrogenation reaction, for example nickel, platinum, platinum oxide, palladium, iron, cobalt, tungsten, or the like or alloys thereof. . Among them, as the nickel catalyst, Raney nickel, a nickel catalyst coated on silica or an alumina carrier, or the like can be used. The catalyst is used in an amount of 0.1 to 30% by weight, preferably 2 to 20% by weight, based on the reducing sugar. If the amount is less than 0.1% by weight, there is a problem that the hydrogenation reaction is not made well, and even when used in excess of 30% by weight does not improve the yield anymore.

In addition, industrial hydrogen was used in the hydrogenation reaction, and it was maintained at a hydrogen pressure of 1 to 200 atm, preferably 50 to 120 atm through a valve device that can control the hydrogen pressure.

The method according to the present invention will be described in detail as follows.

In a pressurized reactor or a four-necked flask, a primary amine and an antioxidant are added to the solvent, followed by stirring. Reducing sugar is added while increasing the reaction temperature and then reacted at 30 to 120 ° C. for 5 to 100 minutes. In this case, the amine introduced is 1 to 20 molar times based on reducing sugar, the solvent is 50 to 1000 ml per mole of reducing sugar, and an antioxidant uses 0.1 to 30% by weight based on reducing sugar.

When the reaction for reacting a primary amine with a reducing sugar is carried out in a four-necked flask, the entire reactant is transferred to an autoclave and then 0.1 to 30% by weight, preferably 2 to 20% by weight, based on the reducing sugar. The catalyst is added and hydrogenated for 3 to 10 hours under hydrogen pressure of 1 to 200 atmospheres. Since the temperature can be raised regardless of the boiling point of the solvent in the pressure reactor, when using lower alcohols such as methanol, ethanol, iso-propanol, propanol, etc., the reaction yield and reaction rate can be increased. Since the hydrogenation reaction must be performed in the second step, the reaction in the autoclave from the beginning is convenient because all the processes are completed in one reactor. When the hydrogenation reaction is complete, the solid antioxidant and catalyst are filtered off before the reactants solidify.

The method of the present invention is described in more detail by way of example.

After dissolving N-methylamine in the methanol solution, glucose and antioxidant sodium silicate are added and the temperature is increased, the reaction becomes clear. The reaction is then carried out for about 30 minutes to 1 hour. After adding Raney Nickel as a catalyst to the reaction and reacting the hydrogen at 50 to 90 atm for 3 to 5 hours at a temperature of 50 to 80 ° C., N-methyl glucamine was obtained at a yield of 95% or more and Gardner color 1 or less. A good color can be obtained. In this case, N-methylamine and methanol are used in 1 to 5 mole, 200 to 700 ml, respectively, based on 1 mol of glucose, and sodium silicate and rannickel are used in 1 to 10% by weight based on glucose.

Through the above-described configuration, the present invention achieves the effect of producing N-substituted polyhydroxy amine of good color even at a relatively high temperature with high yield.

In addition, the N-alkyl glucamine prepared according to the present invention can be used to prepare N-alkyl-N-acyl glucamide as shown in Scheme 2, in particular, to prepare N-methyl-N-acyl glucamide Used a lot for

Wherein R is as defined above and R 'represents C ₈ -C ₁₈ alkyl.

Hereinafter, the present invention will be described in more detail based on the following examples. However, this is only for better understanding of the present invention, and the scope of the present invention is not limited to these examples in any sense.

Example 1

In a autoclave equipped with a thermometer and a mechanical stirrer (1 L capacity), 155 g (2 mol) of 40 wt% N-methylamine aqueous solution was dissolved in 500 ml of methanol, followed by 30 g of 27% sodium silicate solution and 180 g of glucose (1 Mole) was added and stirred. After reacting at 50 to 60 ° C. for 1 hour to give a clear solution, 15 g of nickel nickel in 50% slurry was added thereto, and maintained for 4 hours under a hydrogen pressure of 80 kg / cm 3 and a temperature condition of 50 to 60 ° C. The reaction product was filtered to remove the nickel catalyst by cooling, and the white precipitate obtained by cooling the solution was filtered and dried to give 192 g of white solid N-methyl glucamine. The color of the obtained material was less than Gardner color 1, which was found to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 2

In the same apparatus as in Example 1, 78 g (1 mol) of 40% by weight aqueous N-methylamine solution was dissolved in 500 ml of methanol, followed by Briquest (1-hydroxyethylene-1,1-diphosphonic acid disodium salt). 4 g and 180 g (1 mol) of glucose were added and stirred. After reacting at 70 ° C. for 1 hour to give a clear solution, 20 g of nickel nickel in a slurry of 50% was added thereto and maintained for 5 hours under a hydrogen pressure of 70 kg / cm 3 and a temperature of 70 ° C. The reaction was cooled before cooling to remove the nickel catalyst, and the solution was cooled, and the white precipitate obtained was filtered and dried to yield 185 g of white solid N-methyl glucamine. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 3

In the same apparatus as in Example 1, 387 g (5 mol) of 40% by weight aqueous N-methylamine solution was dissolved in 300 ml of methanol, and 30 g of 27% sodium silicate solution and 180 g (1 mol) of glucose were added thereto and stirred. After reacting at 50 ° C. for 1 hour to give a clear solution, 20 g of nickel nickel in a slurry of 50% was added and maintained for 4 hours under a hydrogen pressure of 90 kg / cm 3 and a temperature of 50 ° C. The reaction was cooled before cooling to remove the nickel catalyst, and the solution was cooled, and the white precipitate obtained was filtered and dried to yield 185 g of white solid N-methyl glucamine. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 4

In the same apparatus as in Example 1, 155 g (2 mol) of 40% by weight aqueous solution of N-methylamine was dissolved in 500 ml of methanol, and 30 g of 27% sodium silicate solution and 342 g (1 mol) of maltose were added thereto and stirred. After reacting at 50 ° C. for 1 hour to give a clear solution, 15 g of nickel nickel in 50% slurry was added thereto, and maintained for 7 hours under a hydrogen pressure of 80 kg / cm 3 and a temperature of 60 ° C. The reactant was filtered to remove the nickel catalyst by cooling, the solution was cooled and the white precipitate obtained was filtered and dried to give 338 g of N-methyl maltamine as a white solid. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 5

In the same apparatus as in Example 1, 155 g (2 mol) of 40% by weight aqueous solution of N-methylamine was dissolved in 500 ml of methanol, followed by 25 to 25% aqueous solution of 23-27% Dequest 2066 (diethylenetri-aminepenta (methylene phosphonate) and glucose. A mixture of 144 g and 68 g of maltose (molar ratio of glucose to maltose is 8: 2, glucose + maltose = 1 mol) was added and stirred, and reacted at 50 ° C. for 1 hour to form a clear solution, followed by 50% slurry of nickel nickel 20 g was added and maintained for 7 hours under hydrogen pressure of 80 kg / cm < 3 > and temperature condition of 60 DEG C. Before the reaction was cooled, the catalyst was filtered to remove the nickel catalyst, and the solution was cooled, and the white precipitate obtained was filtered and then dried. 199 g of a white solid N-methyl polyhydroxy amine was obtained, and the color of the obtained material was Gardner color 1 or less, which was reacted with fatty acid methyl ester as it was. On polyhydroxy it was very suitable for the production of fatty acid amides.

Example 6

In the same apparatus as in Example 1, 96 g (1.5 mol) of 70% by weight aqueous N-ethylamine solution was dissolved in 500 ml of methanol, and 30 g of 27% sodium silicate solution and 180 g (1 mol) of glucose were added thereto and stirred. After reacting at 55 DEG C for 1 hour to give a clear solution, 20 g of nickel nickel in a slurry of 50% was added thereto, and maintained for 5 hours under a hydrogen pressure of 70 kg / cm < 3 > The reaction was filtered before the nickel catalyst was removed by cooling, and the white precipitate obtained by cooling the solution was filtered and dried to give 202 g of white solid N-ethyl glucamine. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 7

In a four-necked flask (1 L capacity) equipped with a thermometer and a mechanical stirrer, 70 g (1.2 mol) of propylamine was dissolved in 600 ml of methanol, followed by addition of 30 g of 27% sodium silicate solution and 180 g (1 mol) of glucose. After reacting at 60 ° C. for 1 hour to a clear solution, it was cooled to 40 ° C. and the reaction was transferred to an autoclave (1 L capacity). 15 g of Ranickel in 50% slurry was added thereto and maintained for 8 hours under a hydrogen pressure of 60 kg / cm 3 and a temperature of 60 ° C. The reaction was filtered before the nickel catalyst was removed by cooling, and the white precipitate obtained by cooling the solution was filtered and dried to give 217 g of white solid N-propyl glucamine. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Example 8

In the same apparatus as in Example 7, 128 g (1.2 mol) of benzylamine was dissolved in 700 ml of methanol, and then 4 g of buty hydroxy tolune (BHT) and 180 g (1 mol) of glucose were added and stirred. The reaction was carried out at 70 ° C. for 1 hour to give a clear solution, then cooled to 50 ° C. and the reaction was transferred to an autoclave (1 L capacity). To this was added 25 g of nickel nickel in a 50% slurry and held for 5 hours under a hydrogen pressure of 70 kg / cm 3 and a temperature of 70 ° C. The reaction product was filtered to remove the nickel catalyst by cooling, and the white precipitate obtained by cooling the solution was filtered and dried to give 262 g of white solid N-benzylglucamine. The color of the material obtained was less than Gardner color 1 and thus appeared to be very suitable for producing polyhydroxy fatty acid amide by reacting it with fatty acid methyl ester as it is.

Claims (17)

A method of preparing an N-substituted polyhydroxy amine by reacting a primary amine (R-NH ₂ ) with a reducing sugar in the presence of an antioxidant and a solvent containing at least one hydroxyl group, followed by hydrogenation in the presence of a catalyst. The method of claim 1 wherein the primary amine is C ₁ -C ₁₈ alkyl, C ₁ -C ₁₈ hydroxyalkyl or amine substituted by benzyl. The method of claim 2 wherein the primary amine is C ₁ -C ₄ alkyl, C ₁ -C ₄ hydroxy alkyl or amine substituted by benzyl. The method of claim 3 wherein the primary amine is N-methylamine. The method according to claim 1, wherein the primary amine is used in an amount of 1 to 20 mol based on the reducing sugar. The method according to claim 5, wherein the primary amine is used in an amount of 1 to 5 molar amounts based on the reducing sugar. The method of claim 1, wherein the reducing sugar is at least one selected from glucose, maltose, fructose, maltotriose, xylose, galactose, lactose, and glyceraldehyde. 8. The method of claim 7, wherein the reducing sugar is glucose. The method of claim 8, wherein the glucose is granule or powder type, or used in a vortex at a concentration of 40 to 90% by weight. The method of claim 1, wherein the antioxidant is a reducing sugar selected from sodium silicate, hydroquinone, stylenediamine tetaacetic acid (EDTA), tetraacetyl ethylenediamine (TAED), butyl hydroxytoluene (BHT), butylated hydroxyanisol (BHA), and organic phosphates. 0.1 to 30% by weight based on the method used. The method of claim 1, wherein the solvent containing at least one hydroxyl group is used in methanol, ethanol, 1-propanol, iso-propanol, butanol, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol and glycerol. A method for using at least one selected 50 to 1000ml per mole of reducing sugar. The method of claim 11, wherein the solvent is methanol. According to claim 1, wherein the hydrogenation reaction is used as a catalyst, 0.1 to 30% by weight of one paper phase selected from nickel, platinum, platinum oxide, palladium, iron, cobalt, tungsten and the like or alloys thereof based on the reducing sugar Way. The method of claim 13, wherein the nickel is coated with Raney nickel or silica or alumina carrier. The process of claim 1 wherein the reaction is carried out at a temperature of 30 to 120 ° C. The process of claim 1 wherein the hydrogenation reaction is carried out under hydrogen or nitrogen atmosphere. 17. The process of claim 16 wherein the hydrogen pressure is between 1 and 200 atmospheres.