Recycling method of by-product in preparation of 3-aminopropanol

Abstract

The invention discloses a method for recycling byproducts in preparation of 3-aminopropanol, and relates to the technical field of organic synthesis. The recycling method comprises the following steps: carrying out catalytic oxidation on amine byproducts in an anhydrous solvent to obtain imine, and then carrying out anaerobic hydrolysis to reduce the imine into the product 3-aminopropanol. According to the method, tetra-amino groups in the by-product can be converted into hydroxyl in the form of 3-aminopropanol through single treatment, the reaction yield and atom economy are improved, and the used catalytic system can be recycled.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for recycling by-products in the preparation of 3-aminopropanol. Background Art

[0002] 3-aminopropanol is an important chemical and pharmaceutical intermediate, and is particularly in wide demand in the market as a raw material for the synthesis of panthenol and its derivatives. Among the existing production methods of 3-aminopropanol, the catalytic hydrogenation of hydroxypropionitrile is the simplest route with the lowest raw material cost, and is a commonly used process in current industrial production. However, during the reaction of catalytic hydrogenation of 3-hydroxypropionitrile, side reactions such as deoxygenation hydrogenation and dehydration condensation may occur, resulting in various by-products such as n-propylamine, propanediamine, diethylenetriamine, and hydroxypropylpropanediamine; since these by-products cannot be simply converted into the target product and have no economic value for separate separation, they are all discarded, causing a certain amount of waste.

[0003] The imino group has relatively stable properties and is difficult to be directly hydrolyzed into an amino group and a hydroxyl group. It has been reported in the literature that by using a nitro radical catalyst commonly used for alcohol oxidation, the amino group and imino group can be converted into an imine (R1R2-C=N-R3) structure under oxidation conditions, and the latter is known to be easily decomposed into a primary amine and an aldehyde / ketone, realizing the cleavage of the C-N bond and the conversion of the amino group into an oxygen-containing group. However, since the hydroxyl group is more easily oxidized than the imino group, the obtained imine cannot be directly hydrolyzed and decomposed, but is further oxidized to an amide through a hemiaminal intermediate.

[0004] The prior art still lacks a method that can overcome the problem of further oxidation, reduce costs, and convert as many by-products of the hydroxypropionitrile hydrogenation process into 3-aminopropanol by using the above technology. Summary of the Invention

[0005] The present invention aims to provide a method for recycling by-products in the preparation of 3-aminopropanol, which oxidizes the by-products to imines in an anhydrous solvent, and then hydrolyzes and reduces them to the target product.

[0006] The method for recycling by-products in the preparation of 3-aminopropanol includes the following steps:

[0007] S1: The product obtained by the catalytic hydrogenation process of 3-aminopropanol hydroxypropionitrile is fractionated to remove ammonia, hydrogen, and water, and 3-aminopropanol and unreacted 3-hydroxypropionitrile are separated to obtain the remaining by-products;

[0008] S2: The by-products are subjected to oxidative imination in a copper-nitro catalytic system, then hydrolyzed, and the obtained 3-aminopropionaldehyde is separated;

[0009] S3: 3-aminopropionaldehyde is reduced to obtain the target product 3-aminopropanol.

[0010] The by-products mainly include n-propylamine, propylenediamine, dipropylenetriamine, hydroxypropylpropylenediamine, etc. In the iminoxidation, two molecules containing an amino group (-NH2) undergo oxidative coupling:

[0011]

[0012] The molecules containing an imino group (-NH-) undergo oxidative dehydrogenation:

[0013]

[0014] Then, in a non-oxidizing environment, the imine undergoes hydrolysis to form a primary amine and an aldehyde:

[0015]

[0016] The oxidation of the amino group is easier and occurs earlier than that of the imino group, and a small amount of hydroxyl groups are first oxidized to aldehydes, and the aldehyde groups are reduced to hydroxyl groups in subsequent reactions. There is no obvious regioselectivity in the position where iminoxidation occurs, but since the number of amino groups in the by-product mixture is much larger than that of hydroxyl groups, in most cases, 3-aminopropanol products will be obtained subsequently, and less malondialdehyde is formed in the middle.

[0017] Furthermore, the copper-nitro catalytic system is composed of a copper salt, a ligand, a nitro compound, a base, an oxidant, and an organic solvent.

[0018] The nitro compound in the present invention is a relatively stable N-O free radical, which plays an important role in promoting electron transfer. The combination of the nitro compound and the oxidant can promote the oxidative coupling of amino groups, but is not sufficient to oxidize secondary amines in high yield. Therefore, a copper complex is required as a co-catalyst to form a ternary transition state to improve the conversion rate of imino groups.

[0019] Preferably, the copper salt is selected from cuprous iodide (CuI), cuprous bromide-dimethyl sulfide complex (CuBr-SMe2), and cuprous trifluoromethanesulfonate-acetonitrile complex (CuOTf-MeCN), and the ligand is 2,2'-bipyridine (bpy). Further preferably, based on the molar number of amino groups in the by-products, the dosage of the copper salt is 10-20 mol%, and the dosage of the ligand is 1.0-1.2 times that of the copper salt. The "based on the molar number of amino groups" mentioned in the present invention includes the total molar number of amino groups and imino groups, and the by-products can be sampled and detected, and obtained according to the measurement methods of primary and secondary amine values.

[0020] Preferably, the nitro compound is 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO). Further preferably, based on the molar number of amino groups in the by-products, the dosage of the nitro compound is 10-15 mol%.

[0021] Preferably, the base is selected from potassium hydroxide, sodium hydroxide, triethylamine (TEA) or a combination thereof. More preferably, based on the number of moles of amino groups in the by-product, the amount of the base is 20 - 50 mol%.

[0022] Preferably, the oxidant is oxygen and the organic solvent is dimethyl sulfone. The oxygen is supplied uniformly during the reaction. Dimethyl sulfone is an aprotic solvent with a high boiling point, high polarity and does not react with strong oxidants.

[0023] Furthermore, the reaction temperature for imine oxidation is 90 - 120 °C and the time is 24 - 48 h.

[0024] Furthermore, before hydrolysis, the oxidant in the reaction mixture is removed. As mentioned above, the presence of the oxidant will oxidize the hydrolysis product of the imine to amide.

[0025] Preferably, the reduction is hydrogenation reduction catalyzed by a transition metal. Sodium borohydride method can also reduce aldehydes, but it is costly for a production process of 3 - aminopropanol.

[0026] Preferably, after separating 3 - aminopropionaldehyde from the hydrolysis reaction mixture, the remaining solution is directly used for the treatment of subsequent by-products. Besides containing a copper - nitro catalytic system, the remaining solution also contains part of propanediamine obtained by the decomposition of the imine again, which can participate in oxidative coupling in the subsequent treatment of by-products.

[0027] The beneficial effects of the technical solution of the present invention are as follows:

[0028] 1. The method for recycling by-products in the preparation of 3 - aminopropanol according to the present invention converts most of the by-products into the target product 3 - aminopropanol. The remaining part of the by-products may also be converted into products during subsequent repeated treatments, which greatly reduces the waste of by-products and improves the atom economy.

[0029] 2. The method for recycling by-products in the preparation of 3 - aminopropanol according to the present invention, except for oxygen consumed as an oxidant, the remaining raw materials can be reused. Especially for the relatively expensive copper complex and nitro compound, the treatment cost is low. Detailed Embodiments

[0030] The following further illustrates the detailed embodiments of the present invention in conjunction with examples. Obviously, the described examples are only part of the embodiments of the present invention, and should be understood as an illustration of the technical solution of the present invention rather than a limitation. The experimental methods are all conventional methods unless otherwise specified; the reagents and materials can be obtained from commercial sources unless otherwise specified.

[0031] Example 1

[0032] (1) By - products are obtained in the catalytic hydrogenation process of 3 - aminopropanol hydroxypropionitrile:

[0033] According to the technical solution of the Chinese invention with the authorization announcement number CN111195761B, 3 - aminopropanol is prepared, and the by - products described in the process S1 of the present invention are obtained. Specifically:

[0034] The hydrogenation catalyst Ni - Re - B / Al2O3 - SiO2 is placed in a fixed - bed reactor and activated in a hydrogen atmosphere at a temperature of 500 °C, a pressure of 0.1 MPa, and a space velocity of 2000 h -1 for 6 h. After the activation is completed, the temperature is adjusted to the reaction temperature of 90 °C, and hydrogen is introduced to pressurize to 10 MPa. The raw materials of 3 - hydroxypropionitrile and liquid ammonia with a molar ratio of 15:1 are pre - heated at 90 °C, and then contacted with the catalyst at a liquid hourly space velocity of 0.5 h -1 while the hydrogen volumetric space velocity is 1000 h -1 is pumped in, and a hydrogenation reaction occurs to obtain a mixture including 3 - hydroxypropionitrile, 3 - aminopropanol, liquid ammonia, hydrogen, and by - products. The by - products may be water, n - propylamine, propylenediamine, di - propylene triamine (H2N(CH2)3NH(CH2)3NH2), and hydroxypropyl propylenediamine (HO(CH2)3NH(CH2)3NH2).

[0035] The obtained reaction mixture is flash - vaporized at 80 °C in a gas - liquid separator to obtain a gas - phase mixture, while the liquid - phase mixture continues to enter a de - ammonia rectification column, and ammonia gas and hydrogen are discharged from the top of the column under a pressure of 0.5 MPa; the liquid - phase mixture at the bottom of the column enters an ammonia - stripping rectification column, and ammonia gas and water are discharged from the top of the column under a pressure of 0.3 MPa; the final bottom mixture is distilled to obtain 3 - aminopropanol, and the remaining by - products are obtained.

[0036] (2) Oxime - formation of by - products:

[0037] The amine value of the by - products is measured and the amino content therein (denoted as 1 eq.) is calculated. Then, the reactants CuI (0.18 eq.), bpy (0.2 eq.), potassium hydroxide (0.5 eq.), TEMPO (0.12 eq.), and dimethyl sulfone (5 L / mol amino) are mixed and stirred evenly to obtain a catalyst stock solution. The catalyst stock solution is mixed with the by - products, purged with pure oxygen in the headspace for 5 min, then heated to 100 °C, and stirred and reacted for 24 h in a pure - oxygen atmosphere at 1.2 atm to obtain a mixture containing imine.

[0038] (3) Hydrolysis and reduction of imine:

[0039] The imine-containing mixture was purged with nitrogen to remove oxygen, and then 10 eq. of distilled water was added. The reaction was stirred at 25 °C for 30 min. 3-Aminopropionaldehyde (atmospheric boiling point 137.9 °C) in the reaction mixture was distilled off and immediately dissolved in 5 times its mass of ethyl acetate. Under the catalysis of 2 wt% Raney nickel, hydrogenation was carried out at a hydrogen pressure of 2.5 MPa and a temperature of 70 °C for 2 h to obtain 3-aminopropanol with a yield of 39 mol% (by-product amino group).

[0040] Example 2

[0041] The only difference between this example and Example 1 is that CuI was replaced with 0.14 eq. of CuBr-SMe2, and the corresponding amount of bpy used was 0.16 eq. The yield of the obtained 3-aminopropanol was 37 mol% (by-product amino group).

[0042] Example 3

[0043] The only difference between this example and Example 1 is that the amount of TEMPO used was 0.15 eq. The yield of the obtained 3-aminopropanol was 40 mol% (by-product amino group).

[0044] Example 4

[0045] The only difference between this example and Example 1 is that potassium hydroxide was replaced with 0.35 eq. of triethylamine. The yield of the obtained 3-aminopropanol was 37 mol% (by-product amino group).

[0046] Example 5

[0047] The only difference between this example and Example 1 is that oxidation was carried out at 120 °C for 48 h. The yield of the obtained 3-aminopropanol was 42 mol% (by-product amino group).

[0048] Comparative Example 1

[0049] The difference between this example and Example 1 is that in step (2), the reaction system also included 10 eq. of water. There were no hydroxyl or aldehyde groups on the infrared spectrum of the product obtained in this step, and the formation of amide was detected.

[0050] The method for recycling the by-products in the preparation of 3-aminopropanol according to the present invention can convert part of the amino groups in the by-products into hydroxyl groups and simultaneously cleave the condensates; nearly 40% of the amino groups in the by-products can be converted into the target product in a single treatment cycle (the theoretical maximum for complete conversion is 50%), improving the yield and atom economy of 3-aminopropanol production.

[0051] Obviously, the above embodiments are merely examples for clear illustration, rather than limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description, and the obvious changes or modifications derived therefrom should still be regarded as the protection scope of the present invention.

Claims

1. A method for recycling by-products from the preparation of 3-aminopropanol, characterized in that: The following steps are involved: S1: The product obtained by the catalytic hydrogenation process of 3-aminopropanol-hydroxypropionitrile is fractionated to remove ammonia, hydrogen and water, and 3-aminopropanol and unreacted 3-hydroxypropionitrile are separated to obtain residual by-products; S2: the byproduct is subjected to oxidative imidization in a copper-nitro catalytic system, followed by hydrolysis, and the resulting 3-aminopropanal is separated; S3: 3-aminopropanal is reduced to obtain the target product 3-aminopropanol.

2. The method for recycling by-products from the preparation of 3-aminopropanol according to claim 1, characterized in that: The copper-nitro catalyst system consists of copper salt, ligand, nitro compound, base, oxidant and organic solvent.

3. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 2, characterized in that: The copper salt is selected from cuprous iodide, cuprous bromide-dimethyl sulfide complex and cuprous trifluoromethanesulfonate-acetonitrile complex, and the ligand is 2,2'-bipyridine; based on the molar number of amino groups in the by-product, the amount of copper salt is 10-20 mol%, and the amount of ligand is 1.0-1.2 times that of copper salt.

4. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 2, characterized in that: The nitro compound is 2,2,6,6-tetramethylpiperidinyl oxide; based on the molar number of amino groups in the by-product, the amount of the nitro compound is 10-15 mol%.

5. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 2, characterized in that: The base is selected from potassium hydroxide, sodium hydroxide, triethylamine or a combination thereof; the amount of the base used is 20 to 50 mol % based on the molar number of amino groups in the by-product.

6. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 2, characterized in that: The oxidant is oxygen; the organic solvent is dimethyl sulfone.

7. The method for recycling by-products from the preparation of 3-aminopropanol according to any one of claims 1 to 6, characterized in that: The reaction temperature of the oxidative imidization is 90-120° C. and the reaction time is 24-48 hours.

8. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 2, characterized in that: Prior to the hydrolysis, the oxidizing agent is removed from the reaction mixture.

9. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 1, characterized in that: The reduction is hydrogenation reduction under transition metal catalysis.

10. The method for recycling by-products produced by preparing 3-aminopropanol according to claim 1, characterized in that: After separating 3-aminopropanal from the hydrolysis reaction mixture, the remaining solution is directly used for the subsequent treatment of by-products.

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