A kind of preparation method of 4-pyridinemethanol

Abstract

The invention belongs to the technical field of preparation of pyridine derivatives, and particularly relates to a method for preparing 4-pyridinemethanol, wherein an acidic aqueous solution is used as a reaction medium, ethyl isonicotinate is used as a raw material, and an electrolytic reaction is carried out at a constant current under normal temperature and pressure to prepare 4-pyridinemethanol. The preparation method of the invention can be carried out at normal temperature and pressure, while avoiding the use of a reducing agent, a transition metal catalyst and an organic solvent, the preparation process is green and environmentally friendly, the obtained 4-pyridinemethanol has a high yield, a strong atom economy, and has a strong market application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of pyridine derivatives, and particularly relates to a method for preparing 4-pyridinemethanol. Background Art

[0002] 4-Pyridinemethanol is an important fine chemical and pharmaceutical intermediate. Because it has two potential coordinating atoms with metal centers, it is widely used in the preparation of coordination compounds with antibacterial and anticancer activities. It is also used in the synthesis of phosphazene-based ionic liquids and electron transport materials in perovskite solar cells.

[0003] In the traditional method of synthesizing 4-pyridinemethanol, the reaction conditions are relatively harsh, usually using transition metal catalysts and a large amount of strong reducing agents, which leads to low cost-effectiveness of the traditional method of synthesizing 4-pyridinemethanol. Therefore, it is of great significance to develop an economical, green and safe method for producing 4-pyridinemethanol.

[0004] The electrocatalytic reduction method uses hydrogen atoms adsorbed on the electrode to hydrogenate molecules. The hydrogen atoms generally come from H + Or H2O, the reaction can generally be carried out under mild conditions and does not require additional reducing agents and expensive transition metal catalysts.

[0005] However, due to the existence of competing reactions, the electrocatalytic hydrogenation reaction has always faced the problem of low current efficiency. Hydrogen atoms adsorbed on the electrode surface can undergo hydrogen evolution reaction through Tafel or Heyrovsky mechanism, and organic matter can also undergo electroreduction reaction on the electrode surface to generate free radicals, thereby undergoing dimerization reaction. These competing reactions will greatly affect the final yield of the product and the current efficiency.

[0006] At present, there are few reports on the preparation of 4-pyridinemethanol through electrocatalytic hydrogenation reduction reaction. How to balance the reaction conditions to suppress competing reactions and achieve efficient electrocatalytic conversion to prepare 4-pyridinemethanol is still a challenging task. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a method for preparing 4-pyridinemethanol by electrocatalytic reduction. The preparation process is green and environmentally friendly, the prepared 4-pyridinemethanol has a high yield and strong atom economy, and has a strong market application prospect.

[0008] The present invention is achieved by adopting the following technical solutions:

[0009] A method for preparing 4-pyridinemethanol comprises the following steps: using an acidic aqueous solution as a reaction medium and taking ethyl isonicotinate as a raw material to carry out an electrolytic reaction at a constant current under normal temperature and pressure conditions to prepare 4-pyridinemethanol.

[0010] Reaction equation reference:

[0011]

[0012] The reaction equation only represents the preferred reaction conditions and is not a special limitation on the reaction conditions of the present invention; in the reaction equation, divided cell represents an electrolytic cell with a diaphragm; Pt(+) represents a platinum electrode as the anode of the electrolytic cell, and Pb(-) represents a lead electrode as the cathode of the electrolytic cell.

[0013] In a preferred embodiment, the acidic aqueous solution is an aqueous solution system containing a sulfuric acid solution, for example, the acidic aqueous solution is a sulfuric acid solution; or, the acidic aqueous solution is an aqueous solution system containing both a sulfuric acid solution and a protonic acid solution thereof; in a further preferred embodiment, the concentration of the sulfuric acid solution is 3 to 7 mol / L; in a particularly preferred embodiment, the concentration of the sulfuric acid solution is 5 mol / L.

[0014] In a preferred embodiment, the concentration of ethyl isonicotinate is 0.1-0.26 mol / L; in a further preferred embodiment, the concentration of ethyl isonicotinate is 0.17-0.22 mol / L; in a particularly preferred embodiment, the concentration of ethyl isonicotinate is 0.19 mol / L.

[0015] In a preferred embodiment, the normal temperature is 20-30°C, and the normal pressure is 0.95-1.05 atmospheres; in a further preferred embodiment, the normal temperature is 23-27°C, and the normal pressure is 0.98-1.02 atmospheres; in a further preferred embodiment, the normal temperature is 24.5-25.5°C, and the normal pressure is 0.99-1.01 atmospheres; in a particularly preferred embodiment, the normal temperature is 25°C, and the normal pressure is 1 atmosphere.

[0016] In a preferred embodiment, the constant current is 10-60 mA; in a further preferred embodiment, the constant current is 15-30 mA.

[0017] In a preferred embodiment, the electrolysis reaction time is 1 to 6 hours; in a further preferred embodiment, the electrolysis reaction time is 2 to 4 hours; in a particularly preferred embodiment, the electrolysis reaction time is 4 hours.

[0018] In a preferred embodiment, the anode of the electrolysis reaction is a platinum electrode, and the cathode of the electrolysis reaction is a platinum electrode, a graphite electrode or a lead electrode; in a further preferred embodiment, the anode of the electrolysis reaction is a platinum electrode, and the cathode of the electrolysis reaction is a lead electrode.

[0019] In a preferred embodiment, the separation yield of 4-pyridinemethanol prepared by the method of the present invention after separation and purification by column chromatography is not higher than 75%; the separation yield of 4-pyridinemethanol prepared by the method of the present invention after separation and purification by column chromatography is 30-75%; in a further preferred embodiment, the separation yield after separation and purification by column chromatography is 31-74%; in a particularly preferred embodiment, the separation yield after separation and purification by column chromatography is 31.3-73.8%.

[0020] The beneficial effects of the present invention are:

[0021] 1. The present invention directly uses ethyl isonicotinate as a raw material, and performs hydrogen reduction on the cathode of an electrolytic cell to obtain 4-pyridinemethanol, and the preparation steps are simple and efficient. By using a lead electrode with a high hydrogen evolution overpotential, the hydrogen evolution reaction on the cathode is effectively suppressed, thereby improving the current efficiency. Meanwhile, the present invention creatively selects special current conditions, electrolysis time, electrolysis reaction medium and other reaction conditions, and effectively improves the yield of 4-pyridinemethanol while ensuring the current efficiency. When the current efficiency is maintained at more than 95%, the yield of 4-pyridinemethanol can reach 73%, and the energy conversion rate in the preparation process is high and the atom economy is strong.

[0022] 2. The preparation method of the present invention can be carried out at room temperature and pressure without special temperature and pressure conditions; at the same time, the use of reducing agents, transition metal catalysts and organic solvents is avoided, and the preparation process is green and environmentally friendly and suitable for industrial production.

[0023] 3. The 4-pyridinemethanol prepared by the method of the present invention has low cost and has strong market application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0025] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the target product obtained in Example 1 of the present invention, and the deuterated reagent is CDCl3.

[0026] Figure 2 This is the carbon NMR spectrum of the target product obtained in Example 1 of the present invention, and the deuterated reagent is CDCl3. DETAILED DESCRIPTION

[0027] The technical scheme in the embodiment will be described clearly and completely below in conjunction with the accompanying drawings in the embodiment of the present invention. Obviously, the described embodiment is only a part of the embodiment of the present invention, not all of the embodiments. Based on the embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] Example 1

[0029] 5 mL of 5 mol / L sulfuric acid solution was added to the anode chamber and cathode chamber of the electrolytic cell respectively. The electrolytic cell used a platinum electrode as an anode, a lead electrode as a cathode and a diaphragm. 150 μL of ethyl isonicotinate was added to the cathode chamber. The electrolysis was carried out at a constant temperature of 25° C. and a constant current of 20 mA for 4 h to obtain an electrolysis product.

[0030] The electrolysis product was separated by column chromatography (dichloromethane:methanol=15:1) to obtain a light yellow solid, with a determined separation yield of 73.8% and a current efficiency of 97.0%.

[0031] The obtained light yellow solid was characterized by NMR, and its NMR hydrogen spectrum was as follows: Figure 1 Its carbon NMR spectrum is shown as Figure 2 As shown by Figure 1 and Figure 2 It can be determined that the light yellow solid is the target product 4-pyridinemethanol.

[0032] Reaction equation reference:

[0033]

[0034] The reaction equation only represents the preferred reaction conditions and is not a special limitation on the reaction conditions of the present invention; in the reaction equation, divided cell represents an electrolytic cell with a diaphragm; Pt(+) represents a platinum electrode as the anode of the electrolytic cell, and Pb(-) represents a lead electrode as the cathode of the electrolytic cell.

[0035] Example 2

[0036] The difference between this embodiment and embodiment 1 is that in this embodiment, the constant current is 10 mA, the electrolysis time is 6 h, the separation yield is 55.8%, and the current efficiency is 97.7%.

[0037] Example 3

[0038] The difference between this embodiment and embodiment 1 is that in this embodiment, the constant current is 20 mA, the electrolysis time is 3 h, the separation yield is 53.9%, and the current efficiency is 94.5%.

[0039] Example 4

[0040] The difference between this embodiment and embodiment 1 is that in this embodiment, the constant current is 40 mA, the electrolysis time is 1.5 h, the separation yield is 48.6%, and the current efficiency is 85.1%.

[0041] Example 5

[0042] The difference between this embodiment and embodiment 1 is that in this embodiment, the constant current is 60 mA, the electrolysis time is 1 hour, the separation yield is 31.6%, and the current efficiency is 55.3%.

[0043] According to the separation yields and current efficiencies of Examples 1 to 5, the optimal constant current was determined to be 20 mA in consideration of production efficiency.

[0044] The following conclusions are drawn from a comprehensive analysis of the above-mentioned Examples 1 to 5 and other examples not described in this specification: Under the conditions of ensuring that the separation yield is above 30% and the current efficiency is maintained above 50%, the greater the constant current used in the electrolysis reaction, the shorter the required electrolysis time. Considering the production efficiency factor, the preferred range of the constant current is 15 to 30 mA, and the corresponding electrolysis time is 2 to 4 h. A more preferred constant current is 20 mA.

[0045] Example 6

[0046] The difference between this embodiment and embodiment 1 is that in this embodiment, the electrolysis time is 2 hours, the separation yield is 31.3%, and the current efficiency is 82.2%.

[0047] Example 7

[0048] The difference between this embodiment and embodiment 1 is that in this embodiment, the electrolysis time is 5 hours, the separation yield is 55.1%, and the current efficiency is 57.9%.

[0049] A comprehensive analysis based on the above-mentioned Examples 1 to 7 and other examples not described in this specification leads to the following conclusions: Under the conditions of ensuring that the separation yield is above 30% and the current efficiency is maintained above 50%, the extension of the electrolysis time within a certain range can improve the separation yield. However, if the electrolysis time is too long, the target product will continue to be hydrogenated and reduced to form a by-product 4-methylpyridine, resulting in a decrease in the yield of the target product and the current efficiency. Taking into account the production efficiency factor, when the optimal constant current is 20 mA, the electrolysis time is preferably 4 h.

[0050] Example 8

[0051] The difference between this embodiment and embodiment 1 is that in this embodiment, the amount of ethyl isonicotinate added is 100 μL, the separation yield is 11.2%, and the current efficiency is 13.1%.

[0052] Example 9

[0053] The difference between this embodiment and embodiment 1 is that in this embodiment, the amount of ethyl isonicotinate added is 200 μL, the separation yield is 44.1%, and the current efficiency is 54.2%.

[0054] Combining the above-mentioned Example 1 and Examples 8-9 and other examples not described in this specification, the following conclusions were drawn through comprehensive analysis: In order to ensure a higher yield, the optimal addition amount of ethyl isonicotinate is 140-170 μL, and a more preferred addition amount is 150 μL.

[0055] Example 10

[0056] The difference between this embodiment and embodiment 1 is that in this embodiment, the concentration of the sulfuric acid solution is 3 mol / L, the separation yield is 48.7%, and the current efficiency is 64.0%.

[0057] Embodiment 11

[0058] The difference between this embodiment and embodiment 1 is that in this embodiment, the concentration of the sulfuric acid solution is 7 mol / L, the separation yield is 54.4%, and the current efficiency is 71.2%.

[0059] A comprehensive analysis based on the above-mentioned Example 1 and Examples 10 to 11 and other examples not described in this specification leads to the following conclusions: In order to ensure a higher yield and current efficiency, the electrolyte sulfuric acid concentration is preferably 4.5 to 5.8 mol / L, and the more preferred electrolyte sulfuric acid concentration is 5 mol / L.

[0060] Example 12

[0061] The difference between this embodiment and embodiment 1 is that: in this embodiment, the electrolytic cell uses a platinum electrode as a cathode, the separation yield is 0%, and the current efficiency is 0%.

[0062] Embodiment 13

[0063] The difference between this embodiment and embodiment 1 is that: in this embodiment, the electrolytic cell uses a graphite electrode as a cathode, the separation yield is 39.5%, and the current efficiency is 51.9%.

[0064] Combining the above-mentioned Example 1 and Examples 12 to 13, the following conclusion is drawn: it is better for the electrolytic cell to use a lead electrode as the cathode.

[0065] The present invention is not limited to the above examples. Within the scope defined by the claims of the present invention, various deformations or modifications that can be made by those skilled in the art without creative work are protected by this patent.

Claims

1. A method for preparing 4-pyridinemethanol, characterized in that: An acidic aqueous solution is used as a reaction medium, ethyl isonicotinate is used as a raw material, and an electrolysis reaction is carried out at a constant current under normal temperature and pressure conditions to obtain 4-pyridinemethanol, wherein the anode of the electrolysis reaction is a platinum electrode, and the cathode of the electrolysis reaction is a lead electrode; The acidic aqueous solution is an aqueous solution system containing a sulfuric acid solution, and the concentration of the sulfuric acid solution is 4.5-5.8 mol / L; The constant current is 10-40 mA; The electrolysis reaction time is 1 to 4 hours; The concentration of the ethyl isonicotinate is 0.22-0.26 mol / L.

2. The method for preparing 4-pyridinemethanol according to claim 1, characterized in that: The normal temperature is 20-30° C., and the normal pressure is 0.95-1.05 atmospheres.

3. The method for preparing 4-pyridinemethanol according to claim 1, characterized in that: The constant current is 15-30 mA.

4. The method for preparing 4-pyridinemethanol according to claim 1, characterized in that: The separation yield of the prepared 4-pyridinemethanol after separation and purification by column chromatography is no more than 75%.

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