A kind of preparation method of o-nitrobenzaldehyde

Abstract

The present invention specifically discloses a method for preparing o-nitrobenzaldehyde, comprising the following steps: S1: placing o-nitrobenzyl alcohol and an ionic liquid catalyst in a reactor and mixing them evenly; S2: adding an oxidant and a catalyst promoter and heating to react, and purifying to obtain the o-nitrobenzaldehyde after the reaction. By using an ionic liquid catalyst, the catalyst can be well dispersed in the ionic liquid, and the substrate can contact the catalyst more effectively during the reaction, thereby improving the conversion rate of the reaction; at the same time, through the synergistic effect of a metal chelating agent, a diamine compound and a metal ion, o-nitrobenzyl alcohol is oxidized, which can improve the selectivity of the oxidation reaction and avoid over-oxidation, and has broad application prospects.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing o-nitrobenzaldehyde. Background Art

[0002] o-nitrobenzaldehyde, also known as 2-nitrobenzaldehyde, has a molecular formula of C 7 H 5 NO 3 , molecular weight 151.12, is a light yellow powder crystal or bright yellow needle crystal. It can volatilize with water vapor and has the aroma of benzaldehyde. It is easily soluble in ethanol, ether, benzene, and slightly soluble in water. It is an important organic synthesis intermediate and is widely used in the pharmaceutical and dye industries. For example, it is used to synthesize drugs for the treatment of cardiovascular diseases such as nitropyridine, nisoldipine, and encainamide. At the same time, o-nitrobenzaldehyde is also a key compound for the synthesis of the expectorant drug ambroxol hydrochloride parent (3,5-dibromo-o-aminobenzaldehyde). In addition, o-nitrobenzaldehyde is also an important raw material for the synthesis of new plant growth regulators indole esters, and is used to synthesize o-nitrostyrene and o-nitrocinnamic acid series products.

[0003] The main methods for preparing o-nitrobenzaldehyde are: (1) o-nitrotoluene is directly oxidized to prepare o-nitrobenzaldehyde. The reaction product is relatively complex and contains substituted benzoic acid, benzyl acetate and a very small amount of benzaldehyde, and most of the raw materials have not yet reacted; (2) benzaldehyde is directly introduced into nitro group through nitration reaction to obtain o-nitrobenzaldehyde, but usually a mixture of o-nitrobenzaldehyde and p-nitrobenzaldehyde is obtained. The fumes cause serious pollution to the environment, the equipment is seriously corroded, and the production conditions are also relatively poor, which is no longer suitable for the needs of the current development situation; (3) o-nitrobenzoic acid or o-nitrobenzoyl chloride is directly reduced to obtain o-nitrobenzaldehyde; (4) o-nitrotoluene side chain is brominated and hydrolyzed to obtain o-nitrobenzyl alcohol, and then oxidized to obtain o-nitrobenzaldehyde. The reaction conditions are relatively mild, the selectivity is good, and the yield is high. In recent years, the literature has reported the use of clean oxidant H 2 O 2 Method for preparing benzaldehyde by catalytic oxidation of benzyl alcohol, titanium-tungsten modified HMS, iron-modified HMS, CuNiAl hydrotalcite, Keggin-type polyvalent heteropoly compounds and phosphomolybdates, etc. for catalyzing H 2 O 2 The oxidation of benzyl alcohol to synthesize benzaldehyde has achieved good results, but most of these methods require the addition of organic solvents or phase transfer catalysts to the reaction system. Although some do not use organic solvents, phase transfer catalysts and various additives, their catalytic performance is not ideal and the conversion rate of benzyl alcohol is not high; some catalysts are difficult to recycle or the reuse effect is not good. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a method for preparing o-nitrobenzaldehyde. The method provided by the present invention can prepare o-nitrobenzaldehyde with high selectivity and good conversion rate.

[0005] The technical solution of the present invention is achieved in this way:

[0006] A method for preparing o-nitrobenzaldehyde comprises the following steps:

[0007] S1: placing o-nitrobenzyl alcohol and an ionic liquid catalyst in a reactor and mixing them uniformly;

[0008] S2: adding an oxidant and a catalyst aid and heating to react, and purifying after the reaction to obtain the o-nitrobenzaldehyde.

[0009] Ionic liquids have the advantages of promoting reaction speed, improving reaction selectivity, and achieving green reaction process.

[0010] Furthermore, the preparation method of the ionic liquid catalyst is:

[0011] S1: mixing an imidazolium cation compound and toluene, adding a halogen ion compound, heating and refluxing for reaction, and separating and purifying after the reaction to obtain the ionic liquid catalyst preparation;

[0012] S2: adding a metal salt to the ionic liquid catalyst preform, and mixing them evenly to obtain the ionic liquid catalyst preform.

[0013] Furthermore, in step S1, the imidazolium cationic compound and the halogen ion compound are subjected to a quaternary amination reaction to generate an ionic liquid preparatory compound in one step, which is simple to operate and has no by-products.

[0014] Furthermore, the metal in the metal salt in step S2 is a multi-valent metal, and the metal ion is not the highest valence.

[0015] Furthermore, the metal ion is preferably a cuprous ion.

[0016] Furthermore, step S2 must be performed under the protection of an inert gas.

[0017] Since the metal ion is not of the highest valence, it has been oxidized during the addition process and needs to be carried out in an inert gas.

[0018] The metal ions in the ionic liquid can form a complex with the metal chelating agent more quickly, and then form a hydrazine metal complex with the diamine compound. During the catalytic process, the metal ions are oxidized, and then the peroxide bond breaks and intramolecular hydrogen transfer occurs to generate a copper hydroxide metal derivative and form a nitrogen-nitrogen double bond; then it is added with o-nitrobenzyl alcohol and water is removed, and intramolecular hydrogen transfer occurs again, the nitrogen-nitrogen double bond breaks and a carbon-oxygen double bond is generated, and finally o-nitrobenzaldehyde and the diamine compound are generated to form a hydrazine metal complex to complete a catalytic cycle.

[0019] Furthermore, the amount of the metal ions is 1-15% of the amount of the ionic liquid preparatory material.

[0020] When the amount of catalyst used is too small, it is not enough to completely activate molecular oxygen, and the conversion rate of o-nitrobenzyl alcohol is not high; but when the amount of catalyst used is too large, the catalytic activity is too high, which easily promotes the occurrence of side reactions such as deep oxidation.

[0021] Furthermore, the oxidant is hydrogen peroxide, and the amount used is 1-1.5 times the amount of the o-nitrobenzyl alcohol substance.

[0022] As a green oxidant, hydrogen peroxide affects the conversion rate of o-nitrobenzyl alcohol when used in insufficient amounts, but o-nitrobenzaldehyde will be further oxidized when used in excessive amounts.

[0023] Furthermore, the amount of the ionic liquid catalyst is 0.5-1.5 times the amount of the o-nitrobenzyl alcohol substance.

[0024] When the amount of ionic liquid used is small, the catalyst cannot be well dispersed in the ionic liquid, the substrate cannot effectively contact the catalyst during the reaction, and the conversion rate of o-nitrobenzyl alcohol is low.

[0025] Furthermore, the catalyst promoter includes a metal chelating agent, and the amount used is 1-2 times the amount of the metal ion substance.

[0026] Furthermore, the metal chelating agent is preferably 1,10-phenanthroline.

[0027] Furthermore, the catalyst promoter also includes a diamine compound, and the amount used is 1-2 times the amount of the metal ion substance.

[0028] Furthermore, the diamine compound is preferably hydrazine.

[0029] Excessive metal chelating agents and diamine compounds are fully combined with metal ions to ensure that the reaction proceeds fully.

[0030] Furthermore, the catalyst promoter also includes carbonate, and the amount used is 3-5% of the amount of the o-nitrobenzyl alcohol substance.

[0031] Furthermore, the heating temperature is 85-95° C., and the reaction time is 2.5-3.5 h.

[0032] Increasing the reaction temperature can fully activate the molecular oxygen, which is beneficial to the oxidation reaction and significantly increases the conversion rate of o-nitrobenzyl alcohol. However, increasing the temperature will lead to other side reactions, increase the amount of by-products, and thus reduce the selectivity of o-nitrobenzaldehyde.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] 1. Using ionic liquid catalysts, the catalyst can be better dispersed in the ionic liquid, and the substrate can contact the catalyst more effectively during the reaction, thereby improving the conversion rate of the reaction.

[0035] 2. Through the synergistic effect of metal chelators, diamine compounds and metal ions, o-nitrobenzyl alcohol can be oxidized to improve the selectivity of the oxidation reaction and avoid over-oxidation. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments 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.

[0037] Reagent Description

[0038] 1-Ethylimidazole, toluene, butyl bromide, ethyl acetate, cuprous bromide, 1,10-phenanthroline, o-nitrobenzyl alcohol, hydrogen peroxide, hydrazine, potassium carbonate, analytical grade, Sinopharm Chemical Reagent Co., Ltd.

[0039] Preparation Example 1

[0040] Preparation of ionic liquid catalysts:

[0041] S1: 0.2 mol of 1-ethylimidazole and 100 mL of toluene are placed in a container, 0.2 mol of bromobutyl is added dropwise while stirring, and the mixture is heated under reflux for 10 h. After cooling, the mixture is allowed to stand for stratification, and the lower layer is taken out and washed three times with ethyl acetate to obtain the ionic liquid catalyst preform.

[0042] S2: Under nitrogen protection, 0.1 mol of cuprous bromide is added to 1 mol of the ionic liquid catalyst preparatory body, and the mixture is stirred evenly to obtain the ionic liquid catalyst.

[0043] Example 1

[0044] S1: First, 2 mol of the ionic liquid catalyst in Preparation Example 1 and 0.3 mol of 1,10-phenanthroline were placed in a reactor and stirred for 10 minutes.

[0045] S2: Add 2 mol of o-nitrobenzyl alcohol, 2.4 mol of hydrogen peroxide, 0.3 mol of hydrazine and 0.02 mol of potassium carbonate, heat to 92°C and react for 3 hours. After the reaction is completed, stand and separate to obtain o-nitrobenzaldehyde.

[0046] Example 2

[0047] The difference between this example and Example 1 is that in the preparation example 1, the amount of cuprous bromide used is 0.01 mol, and the amount of 1,10-phenanthroline used is 0.03 mol.

[0048] The other parts are exactly the same as those in Example 1.

[0049] Example 3

[0050] The difference between this example and Example 1 is that in the preparation example 1, the amount of cuprous bromide used is 0.15 mol, and the amount of 1,10-phenanthroline used is 0.45 mol.

[0051] The other parts are exactly the same as those in Example 1.

[0052] Example 4

[0053] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid catalyst used is 1 mol, and the amount of 1,10-phenanthroline used is 0.15 mol.

[0054] The other parts are exactly the same as those in Example 1.

[0055] Example 5

[0056] The difference between this embodiment and embodiment 1 is that the amount of the ionic liquid catalyst used is 3 mol, and the amount of 1,10-phenanthroline used is 0.45 mol.

[0057] The other parts are exactly the same as those in Example 1.

[0058] Example 6

[0059] The difference between this embodiment and embodiment 1 is that the amount of hydrogen peroxide used is 2 mol.

[0060] The other parts are exactly the same as those in Example 1.

[0061] Example 7

[0062] The difference between this embodiment and embodiment 1 is that the amount of hydrogen peroxide used is 3 mol.

[0063] The other parts are exactly the same as those in Example 1.

[0064] Example 8

[0065] The difference between this embodiment and embodiment 1 is that the amount of 1,10-phenanthroline used is 0.2 mol.

[0066] The other parts are exactly the same as those in Example 1.

[0067] Example 9

[0068] The difference between this embodiment and embodiment 1 is that the amount of 1,10-phenanthroline used is 0.4 mol.

[0069] The other parts are exactly the same as those in Example 1.

[0070] Example 10

[0071] The difference between this embodiment and embodiment 1 is that the amount of hydrazine used is 0.2 mol.

[0072] The other parts are exactly the same as those in Example 1.

[0073] Embodiment 11

[0074] The difference between this embodiment and embodiment 1 is that the amount of hydrazine used is 0.4 mol.

[0075] The other parts are exactly the same as those in Example 1.

[0076] Example 12

[0077] The difference between this embodiment and embodiment 1 is that the amount of potassium carbonate used is 0.03 mol. The other parts are exactly the same as those in embodiment 1.

[0078] Embodiment 13

[0079] The difference between this embodiment and embodiment 1 is that the amount of potassium carbonate used is 0.05 mol. The other parts are exactly the same as those of embodiment 1.

[0080] Embodiment 14

[0081] The difference between this embodiment and embodiment 1 is that the heating temperature is 85°C.

[0082] The other parts are exactly the same as those in Example 1.

[0083] Embodiment 15

[0084] The difference between this embodiment and embodiment 1 is that the heating temperature is 95°C.

[0085] The other parts are exactly the same as those in Example 1.

[0086] Tests and Results

[0087] The conversion rate and selectivity of o-nitrobenzaldehyde are shown in Table 1.

[0088] Table 1

[0089]

[0090]

[0091] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for preparing o-nitrobenzaldehyde, characterized in that: The steps include: S1: First, 2 mol of ionic liquid catalyst and 0.3 mol of 1,10-phenanthroline were placed in a reactor and stirred for 10 min; S2: Add 2 mol of o-nitrobenzyl alcohol, 2.4 mol of hydrogen peroxide, 0.3 mol of hydrazine and 0.02 mol of potassium carbonate, heat to 92°C for 3 hours, and stand for separation after the reaction to obtain o-nitrobenzaldehyde; Preparation of ionic liquid catalysts: S11: 0.2 mol of 1-ethylimidazole and 100 mL of toluene are placed in a container, 0.2 mol of bromobutyl is added dropwise while stirring, and the mixture is heated under reflux for 10 h; after cooling, the mixture is allowed to stand for stratification, and the lower layer is taken out and washed three times with ethyl acetate to obtain the ionic liquid catalyst preform; S12: Under nitrogen protection, 0.1 mol of cuprous bromide is added to 1 mol of the ionic liquid catalyst preform, and the mixture is stirred evenly to obtain the ionic liquid catalyst.

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