A β-hydroxyaldehyde compound and preparation method thereof
By using specific solvent combination and purification methods in the microchannel reactor, the problem of low product yield in the synthesis of β-hydroxyaldehyde compounds is solved, and efficient and safe preparation of β-hydroxyaldehyde compounds is achieved.
Patent Information
- Application Number
- CN202310493609.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-05
- Publication Date
- 2025-08-12
- Estimated Expiration
- 2043-05-05
AI Technical Summary
The prior art is difficult to efficiently synthesize β-hydroxyaldehyde compounds, resulting in low product yield and cumbersome post-processing.
A microchannel reactor is used to carry out the addition reaction at room temperature, using a specific solvent combination (tetrahydrofuran and dichloromethane) and equimolar ratio of glyoxal is reacted with the organozinc compound. The refining process includes acid hydrolysis and extraction to improve reaction selectivity and efficiency.
A high yield of β-hydroxyaldehyde compounds (more than 90 wt%) is achieved, the post-treatment steps are simplified, and the reaction efficiency and safety are improved.
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Figure CN116768715B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of organic compound synthesis, and in particular to a beta-hydroxyaldehyde compound and a preparation method thereof. Background Art
[0002] β-Hydroxyaldehydes are novel organic compounds possessing both hydroxyl and aldehyde functional groups. Further reactions can produce a range of organic compounds. Catalytic hydrogenation of β-hydroxyaldehydes can produce high-purity α,β-diols, such as α,β-hexanediol, providing a novel preparation method. α,β-hexanediol has a wide range of applications in organic synthesis, including pesticide stabilizers and diesel engine oil antifreeze. 2-Methyl-2,4-pentanediol exhibits excellent permeability and dispersibility for inorganic substances. Besides being a solvent, it is also used in dry cleaning agents, automotive brake fluids, printing inks, pigment dispersants, and wood preservatives. The reaction of β-hydroxyaldehydes with amino compounds can produce a range of β-hydroxyα-amino compounds. Summary of the Invention
[0003] The present invention provides a beta-hydroxyaldehyde compound and a preparation method thereof. The beta-hydroxyaldehyde compound obtained by the method of the present invention has both an alpha-position aldehyde group and a beta-position hydroxyl functional group.
[0004] In order to achieve the above objectives, the present invention is implemented through the following technical solutions:
[0005] A β-hydroxyaldehyde compound having the following structure:
[0006]
[0007] Wherein R is one of a cycloalkyl group, an aryl group or a substituted aryl group, a straight-chain alkyl group having 1 to 6 carbon atoms or an isomeric alkyl group.
[0008] A method for preparing a β-hydroxyaldehyde compound comprises the following steps:
[0009]
[0010] (1) dissolving glyoxal in a first solvent to obtain a reaction solution A; dissolving an organozinc compound of formula II in a second solvent to obtain a reaction solution B;
[0011] (2) simultaneously pumping the reaction solution A, the reaction solution B, and a third solvent into a microchannel reactor for addition reaction at room temperature, collecting the reaction solution and purifying it to obtain a β-hydroxyaldehyde compound having the structure of Formula I;
[0012] Wherein R of the organic zinc compound is one of cycloalkyl, aryl or substituted aryl, linear alkyl with 1 to 6 carbon atoms or isomeric alkyl, and X is one of chlorine, bromine and iodine.
[0013] Furthermore, the first solvent is a mixture of tetrahydrofuran and dichloromethane in an equal volume ratio; the second solvent and the third solvent are both tetrahydrofuran. The dichloromethane in the solvent can increase the reactivity of the aldehyde group in glyoxal, thereby greatly improving the reaction selectivity.
[0014] Furthermore, the feeding ratio of the glyoxal and the organozinc compound is an equimolar ratio;
[0015] The ratio of the concentration of the reaction solution A to the concentration of the reaction solution B is (1-1.3):1;
[0016] The amount of the third solvent used is 30-60% of the total volume of the reaction solution A and the reaction solution B.
[0017] Furthermore, the reaction temperature of the addition reaction is 18-22°C, and the reaction time in the microchannel reactor is 0.5-5 minutes. Reaction temperatures above 22°C increase the reactivity of the organozinc, thereby generating diol byproducts and reducing the yield of the β-hydroxyaldehyde compound. Lower reaction temperatures also reduce the reactivity of the organozinc, which can lead to incomplete reactions, reduced product yields, and complicated post-processing.
[0018] Furthermore, the purification includes the following process: adding acid to the collected reaction solution for hydrolysis, separating an organic phase and an aqueous phase, extracting the aqueous phase with dichloromethane multiple times, combining the obtained organic phases, washing with water to neutrality and then drying, and then desolventizing and distilling to obtain a purified β-hydroxyaldehyde compound.
[0019] Beneficial technical effects:
[0020] The β-hydroxyaldehyde compound of the present invention is a novel compound and a novel organic synthesis building block. It possesses both an α-aldehyde group and a β-hydroxyl functional group, and has numerous advantages in organic synthesis. The present invention utilizes a microchannel reaction, enabling the addition reaction of the dialdehyde with the organozinc compound to occur within a short contact time and at an appropriately diluted concentration. This improves reaction efficiency and selectivity, and offers advantages such as high efficiency, safety, energy conservation, and ease of operation. The yield of the β-hydroxyaldehyde compound obtained by the method of the present invention reaches over 90% by weight. DETAILED DESCRIPTION
[0021] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, rather than all embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.
[0022] Unless otherwise specifically stated, the numerical value set forth in these embodiments does not limit the scope of the present invention. Technology and methods known to those of ordinary skill in the relevant art may not be discussed in detail, but in appropriate cases, the technology and methods should be considered as a part of the specification. In all examples shown and discussed here, any specific value should be interpreted as merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments can have different values.
[0023] In addition, it should be noted that the use of terms such as "first" and "second" to limit the added solvent is merely to facilitate the distinction between the solvents used in each reaction step. Unless otherwise stated, the above terms have no special meaning and therefore cannot be understood as limiting the scope of protection of the present invention.
[0024] In the following examples, experimental methods without specific conditions are generally measured according to national standards. If there are no corresponding national standards, they are measured according to the general international standards or the standards proposed by relevant companies. Unless otherwise stated, all parts are by weight and all percentages are by weight.
[0025] Hereinafter, THF stands for tetrahydrofuran and DCM stands for dichloromethane.
[0026] The organozinc compounds used in the following examples can be obtained through conventional channels or according to methods known in the art or in the literature.
[0027] Example 1
[0028] Synthesis of β-hydroxyhexanal:
[0029]
[0030] (1) Glyoxal was added to a mixture of dry THF and DCM to obtain a reaction solution A with a concentration of 0.6 mol / L, wherein THF and DCM were in an equal volume ratio;
[0031] A 0.5 mol / L THF solution of n-butylzinc chloride was used as reaction solution B;
[0032] (2) According to the feeding ratio of glyoxal and n-butylzinc chloride being an equimolar ratio, the reaction liquid A and the reaction liquid B, as well as dry THF, are simultaneously pumped into a microchannel reactor, wherein the amount of THF is 50% of the total volume of the reaction liquid A and the reaction liquid B, and the reaction liquid is retained in the microchannel reactor at 20° C. for 1 min for addition reaction, and then the reaction liquid is collected, and acid hydrolysis is added to the collected reaction liquid to separate the organic phase and the aqueous phase, and the aqueous phase is extracted with dichloromethane for multiple times, and the obtained organic phases are combined, washed with water to neutrality, and then dried, and then desolventized and rectified to obtain refined β-hydroxyhexanal with a purity of 99.7wt% and a yield of 91.3wt%.
[0033] The molecular weight M of the product of this example was identified by mass spectrometry W =116.16; the elemental content of the product was determined by elemental analyzer to be C: 61.96%, H: 10.49%, O: 27.45%, and the molecular formula of the product was determined to be C6H 12 O2.
[0034] The product was identified by H NMR spectrum: 1 HNMR (CDCl3, 400MHz): 0.93 (t, 3H, CH3); 1.32 (m, 2H, CH2); 1.29 (m, 2H, CH2); 1.77 (m, 2H, CH2); 4.08 (m, 1H, CH), 9.72 (1H, CHO); 2.0 (H, OH).
[0035] Combining the molecular formula and the hydrogen spectrum, it can be determined that the product of this example is indeed β-hydroxyhexanal.
[0036] Comparative Example 1
[0037] In this comparative example, during the preparation of β-hydroxyhexanal, DCM was not added to the reaction solution A in step (1), but was replaced entirely with THF. The β-hydroxyhexanal obtained in this comparative example had a purity of 98.4 wt % and a yield of 58.1 wt %.
[0038] Comparative Example 2
[0039] In this comparative example, a microchannel reactor was not used in the preparation of β-hydroxyhexanal. Instead, a traditional operation was adopted, in which the reagents reacted in a single reaction flask. The contact reaction time between the organozinc and glyoxal was prolonged, resulting in the generation of 5,6-dihydroxydecanediol as a by-product. The subsequent treatment was cumbersome, and the process had no practical value.
[0040] Example 2
[0041] Synthesis of β-hydroxypropionaldehyde:
[0042] (1) Glyoxal was added to a mixture of dry THF and DCM to obtain a reaction solution A with a concentration of 0.6 mol / L, wherein THF and DCM were in an equal volume ratio;
[0043] THF was added to a THF solution containing 2 mol / L methyl zinc chloride to dilute it to a methyl zinc chloride concentration of 0.5 mol / L to obtain a reaction solution B;
[0044] (2) According to the feeding ratio of glyoxal to methyl zinc chloride being an equimolar ratio, the reaction liquid A, the reaction liquid B, and dry THF are simultaneously pumped into a microchannel reactor, wherein the amount of THF is 50% of the total volume of the reaction liquid A and the reaction liquid B, and the reaction liquid is left in the microchannel reactor at 18° C. for 2 min for addition reaction, and then the reaction liquid is collected, and acid hydrolysis is added to the collected reaction liquid to separate the organic phase and the aqueous phase, and the aqueous phase is extracted with dichloromethane for multiple times. The obtained organic phases are combined, washed with water to neutrality, and then dried, and then desolventized and distilled to obtain refined β-hydroxypropionaldehyde with a purity of 99.2 wt% and a yield of 90.5 wt%.
[0045] The molecular weight M of the product of this example was identified by mass spectrometry W =74.1; the element contents of the product were determined by elemental analyzer, namely C: 48.65%, H: 8.16%, O: 43.21%, and the molecular formula of the product was determined to be C3H6O2 based on the molecular weight.
[0046] The product was identified by H NMR spectrum: 1 HNMR (CDCl3, 400MHz): 1.31 (t, 3H, CH3); 4.21 (m, 1H, CH), 9.70 (1H, CHO); 1.98 (H, OH).
[0047] Combining the molecular formula and the hydrogen spectrum, it can be determined that the product of this example is indeed β-hydroxypropionaldehyde.
[0048] Example 3
[0049] Synthesis of β-hydroxyheptanal:
[0050] (1) Glyoxal was added to a mixture of dry THF and DCM to obtain a reaction solution A with a concentration of 0.6 mol / L, wherein THF and DCM were in an equal volume ratio;
[0051] A THF solution containing 0.5 mol / L n-pentylzinc bromide was used as reaction solution B;
[0052] (2) According to the feeding ratio of glyoxal and n-pentylzinc bromide being an equimolar ratio, the reaction liquid A, the reaction liquid B, and dry THF are simultaneously pumped into a microchannel reactor, wherein the amount of THF is 50% of the total volume of the reaction liquid A and the reaction liquid B, and the reaction liquid is retained in the microchannel reactor at 22° C. for 1 min for addition reaction, and then the reaction liquid is collected, and acid hydrolysis is added to the collected reaction liquid to separate the organic phase and the aqueous phase, and the aqueous phase is extracted with dichloromethane for multiple times. The obtained organic phases are combined, washed with water to neutrality, and then dried, and then desolventized and distilled to obtain refined β-hydroxyheptanal with a purity of 99.4 wt% and a yield of 90.1 wt%.
[0053] The molecular weight M of the product of this example was identified by mass spectrometry W =130.19; the elemental content of the product was determined by elemental analyzer to be C: 64.58%, H: 10.82%, O: 24.59%, and the molecular formula of the product was determined to be C7H 14 O2.
[0054] The product was identified by nuclear magnetic hydrogen spectrum: 1 HNMR (CDCl3, 400MHz): 0.95 (t, 3H, CH3); 1.32 (m, 2H, CH2); 1.29 (m, 2H, CH2); 1.29 (m, 2H, CH2); 1.77 (m, 2H, CH2); 4.06 (m, 1H, CH), 9.71 (1H, CHO); 2.0 (H, OH).
[0055] Combining the molecular formula and the hydrogen spectrum, it can be determined that the product of this example is indeed β-hydroxyheptanal.
[0056] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solution and inventive concept of the present invention, should be covered by the scope of protection of the present invention.
Claims
1. A method for preparing a β-hydroxyaldehyde compound, characterized in that: The steps include: ， (1) dissolving glyoxal in a first solvent to obtain a reaction solution A; dissolving an organozinc compound of formula II in a second solvent to obtain a reaction solution B; The first solvent is a mixture of tetrahydrofuran and dichloromethane in an equal volume ratio; (2) Pumping the reaction solution A, the reaction solution B, and the third solvent into a microchannel reactor simultaneously for addition reaction at room temperature, collecting the reaction solution, and purifying it to obtain a β-hydroxyaldehyde compound having the structure of Formula I; The reaction temperature of the addition reaction is 18-22°C; Wherein R of the organic zinc compound is a linear alkyl group having 1 to 6 carbon atoms or one of its isomeric alkyl groups, and X is one of chlorine, bromine and iodine.
2. The method for preparing a β-hydroxyaldehyde compound according to claim 1, wherein The second solvent and the third solvent are both tetrahydrofuran.
3. The method for preparing a β-hydroxyaldehyde compound according to claim 1, wherein The feeding ratio of the glyoxal and the organozinc compound is an equimolar ratio; The ratio of the concentration of the reaction solution A to the concentration of the reaction solution B is (1.1-1.3):1; The amount of the third solvent used is 30-60% of the total volume of the reaction solution A and the reaction solution B.
4. The method for preparing a β-hydroxyaldehyde compound according to claim 1, wherein The reaction time in the microchannel reactor is 0.5-5 min.
5. The method for preparing a β-hydroxyaldehyde compound according to claim 1, wherein The purification process includes the following steps: adding acid to the collected reaction solution for hydrolysis, separating an organic phase and an aqueous phase, extracting the aqueous phase with dichloromethane for multiple times, combining the obtained organic phases, washing with water until neutral, and then drying, and then desolventizing and distilling to obtain a purified β-hydroxyaldehyde compound.