JP4852709B2 - Method for producing aldehydes - Google Patents

Abstract

[PROBLEMS] To provide a method of stably isolating an aldehyde and a method accompanied by the generation of waste in a reduced amount in the process of producing an aldehyde by oxidizing the corresponding primary alcohol or its alkyl ether. [MEANS FOR SOLVING PROBLEMS] A method of producing an aldehyde characterized by comprising conducting a reaction by adding nitrogen dioxide or dinitrogen tetroxide together with carbon dioxide in the gaseous, liquid or supercritical state to a primary alcohol or its alkyl ester. In a preferable embodiment, nitrogen dioxide or dinitrogen tetroxide remaining after the completion of the reaction as described above and reduced compounds thereof are purged with carbon dioxide to thereby give an aldehyde at a high purity.

Description

  The present invention relates to a method for producing aldehydes, and more specifically, from the reaction of oxidizing a primary alcohol or an alkyl ether thereof to the isolation of the product, using organic solvents and water, and efficiently producing aldehydes with little waste. Regarding the method.

  In the 21st century society aiming for sustainable development, when producing useful compounds, it is required to be a comprehensive environmentally friendly manufacturing method called green chemistry (for example, non-patent literature) 1).

  Aldehydes are useful compounds as pharmaceuticals, agricultural chemicals, dyes, fragrances and other organic synthetic raw materials, but are difficult to handle because they are easily oxidized, and many synthetic methods have been proposed for aldehydes.

  Examples of the method for synthesizing corresponding aldehydes by oxidizing primary alcohol include oxidation with an oxidizing agent such as chromium and manganese, Oppenueruer oxidation, DMSO oxidation, Dess-Martin oxidation, TEMPO oxidation, oxidation with a transition metal catalyst such as ruthenium. Are known (Non-Patent Document 2).

  In addition, a method using halogen oxide as an oxidizing agent has been developed (Patent Document 1). However, these are expensive catalysts, and it is necessary to treat a harmful metal compound remaining after the reaction is completed. This is a manufacturing method with a large E-factor (ratio of waste to product: Non-Patent Document 3), which is not a preferable manufacturing method in terms of environment and economy.

  Since nitrogen dioxide is a raw material for nitric acid, it is an inexpensive oxidant after oxygen. However, since nitrogen dioxide has a strong oxidizing power, there is an economical method in which an aldehyde is obtained by diluting with an organic solvent and oxidizing a primary alcohol (for example, Patent Documents 2 and 3 and Non-Patent Document 4).

  Until now, organic solvents have been used as the reaction medium for the oxidation reaction. However, the oxidizing agent can oxidize not only the substrate but also part of the organic solvent. May run out of control. For this reason, when an oxidizing agent having a large oxidizing power such as nitrogen dioxide is used, a solvent inert to the oxidizing agent such as carbon tetrachloride, chloroform, and 1,2-dichloroethane has been used. However, such a chlorinated solvent has many problems in toxicity and disposal, and is not necessarily a preferable reaction medium.

Also, conventionally, after aldehyde synthesis reaction, work-up such as water washing, solvent concentration, aldehyde distillation, etc., aldehydes are easily oxidized, and during these treatments, some of them become carboxylic acids, and aldehydes In some cases, the yield and purity of the product decreased.
JP 2004-43317 A JP 2002-179607 A Japanese Patent No. 3371544 “Green Chemistry: Theory and Practice”, Oxford University Press, 1998 The Chemical Society of Japan, Experimental Chemistry Course, Synthesis of Organic Compounds III-Aldehyde / Ketone / Quinone, 5th Edition, Maruzen Co., Ltd., 2003, Volume 15, pages 9-44 R. A. Sheldon, Chem. Ind., 7, 903 (1992) B. 0. Field, J. Grundy, J.A. Chem. Soc. , 1955, 1110-1112.

  Therefore, the object of the present invention is to consider the safety in the oxidation reaction, and does not cause a decrease in the yield and purity of aldehydes that are easily oxidized in the isolation and purification. It is to provide an environmentally friendly aldehyde production method.

  Other problems of the present invention will become apparent from the following description.

  As a result of intensive studies on a comprehensive environmentally friendly aldehyde production method, the present inventors have completed the following inventions.

First aspect of the present invention, the primary alcohol or its alkyl ether, with carbon dioxide in a liquid-like state, a method for producing aldehydes which comprises reacting the addition of nitrogen or dinitrogen tetroxide dioxide.

According to a second aspect of the invention, after the reaction, nitrogen dioxide remaining or dinitrogen tetroxide and their changing Motokarada by removing carbon dioxide, in claim 1, characterized in that to obtain a high purity aldehyde It is a manufacturing method of described aldehydes.

  According to the present invention, safety in the oxidation reaction can be considered, and the yield and purity of aldehydes that are easily oxidized are not reduced in isolation and purification. A type aldehyde production method can be provided.

Graph showing the relationship between the mixing ratio of carbon dioxide to nitrogen dioxide and the yield of 4-methylbenzaldehyde

  Examples of the primary alcohol used in the present invention include compounds in which an alcohol residue is bonded to an aromatic ring or a heterocyclic ring as a hydroxymethyl group, and those in which an alcohol residue is bonded to an aliphatic skeleton as a hydroxyl group.

  Specific examples of the aromatic primary alcohol include compounds having one or more hydroxymethyl groups on an aromatic ring or heterocyclic ring, such as benzyl alcohol, hydroxymethylnaphthalene, furfuryl alcohol, hydroxymethylpyridine, hydroxymethylquinoline, and benzene. In dimethanol, dihydroxymethylbiphenyl, etc., the hydrogen of the aromatic ring or heterocyclic ring is alkyl group, cycloalkyl group, aryl group, alkenyl group, alkynyl group, aralkyl group, hydroxyl group, halogen, nitro group, amino group, alkoxy group, It may be substituted with an alkylamino group, formyl group, acyl group, carboxyl group, alkoxycarbonyl group or the like.

  Examples of aliphatic primary alcohols include monohydric alcohols such as ethanol, propanol, 2-methylpropanol, butanol, hexanol, heptanol, octanol, 2-ethylhexanol, decanol, dodecanol, stearyl alcohol, ethylene glycol, propylene glycol And polyhydric alcohols such as neopentyl glycol, glycerin, trimethylolpropane, trimethylolethane, pentaerythritol, dipentaerythritol, glucose, sorbitol, starch, and polyvinyl alcohol.

  The alkyl ether of the primary alcohol is obtained by replacing the hydrogen of the hydroxyl group of the primary alcohol with an alkyl group (C1-4).

  In the present invention, mainly by adjusting the mixing ratio of carbon dioxide and nitrogen dioxide and the reaction temperature, it is possible to select the reaction conditions under which the aldehyde can be obtained efficiently and selectively.

  The amount of nitrogen dioxide to be used is about 0.1 to 10 mol, preferably 0.8 to 3 mol, more preferably about 1.0 to 1.3 mol, per mol of the substrate of one alcohol residue or one alkyl ether residue thereof.

  When highly reactive nitrogen dioxide is diluted with carbon dioxide, the reaction rate can be controlled and handling becomes easier.

  Nitrogen dioxide is in equilibrium with dinitrogen tetroxide. Increasing the temperature tilts the equilibrium to the more reactive nitrogen dioxide side, but if pressure is applied, it can tilt to the milder reactive nitrous oxide side, and by controlling the pressure with carbon dioxide, the equilibrium Can control the reactivity of nitrogen dioxide.

  The mixing ratio of carbon dioxide to nitrogen dioxide can be appropriately selected according to the type of substrate, and is, for example, 1 to 1000 times, preferably 10 to 200 times, and more preferably about 30 to 100 times.

  The reaction temperature can be appropriately selected depending on the type of the substrate, and is, for example, about -50 to 150 ° C, preferably -20 to 120 ° C, and more preferably about 0 to 50 ° C. When the temperature is too high, the oxidation further proceeds and the corresponding carboxylic acid is easily generated.

Because it is gaseous at nitrogen dioxide or dinitrogen tetroxide and their place Motokarada also carbon dioxide ambient temperature and pressure, after the reaction I open the valve of the closed container, can be separated easily product.

Nitrogen dioxide dissolves very well in liquid or supercritical carbon dioxide. Therefore, such excessive nitrogen dioxide or dinitrogen tetroxide and their place Motokarada present after the reaction, can be removed together with the carbon dioxide when opening the valve of the reaction vessel. Furthermore, extraction and removal are also easy by circulating carbon dioxide in the reaction vessel.

Further, instead Motokarada such nitric oxide formed after the reaction can be readily reproduced nitrogen dioxide is oxidized with oxygen. Therefore, it can be recycled with the carbon dioxide used.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

Example 1
Weigh out 0.15 g (3.3 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 10.01 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave with a pressure gauge, weigh 4-methylbenzyl alcohol (0.37 g, 3.0 mmol), replace the autoclave with carbon dioxide, cool well, Connect with autoclave.

  Move the contents to an autoclave containing 4-methylbenzyl alcohol by operating the valve.

  When this autoclave was placed in a 40 ° C. water bath, the pressure became 5.6 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.36 g (yield 100%) of 4-methylbenzaldehyde was obtained, and the purity was 99.2%.

Example 2 <Examination of mixing ratio of carbon dioxide to nitrogen dioxide>
Weigh out 0.19 g (4.1 mol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave with a pressure gauge, weigh 4-methylbenzyl alcohol (0.37 g, 3.0 mmol), replace the autoclave with carbon dioxide, cool well, Connect with autoclave.

  Move the contents to an autoclave containing 4-methylbenzyl alcohol by operating the valve. The autoclave was placed in a 25 ° C. water bath and stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The reaction vessel was opened and the yield of 4-methylbenzaldehyde was quantified by gas chromatography.

  The relationship between the mixing ratio of carbon dioxide to nitrogen dioxide and the yield of 4-methylbenzaldehyde was examined by changing the amount of carbon dioxide to be added and performing the same operation. The results are shown in FIG.

Example 3
Weigh 0.22 g (4.8 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 9.92 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 4-methoxybenzyl alcohol (0.44 g, 3.4 mmol), replace the autoclave with carbon dioxide, cool well, and add nitrogen dioxide. Connect with autoclave.

  Move the contents to an autoclave containing 4-methoxybenzyl alcohol by operating the valve.

  When this autoclave was placed in a 25 ° C. water bath, the pressure became 5.2 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents and the reaction mixture were analyzed by ¹ H NMR using coumarin as an internal standard.

  As a result, 0.43 g (yield 100%) of 4-methoxybenzaldehyde was obtained.

Comparative Example 1
Nitrogen dioxide (0.18 g, 3.9 mmol) and 4-methoxybenzyl alcohol (0.47 g, 3.4 mmol) are weighed into a 50 ml stainless steel autoclave that has been cooled by replacing air with argon.

  The autoclave was placed in a 25 ° C. water bath and stirred for 1 hour with a magnetic stirrer.

The reaction after autoclaving was cooled with ice, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents and the reaction mixture were analyzed by ¹ H NMR using coumarin as an internal standard.

  As a result, 0.42 g (yield 91%) of 4-methoxybenzaldehyde and 0.2 g (yield 3%) of 4-methoxybenzoic acid were obtained.

Example 4
Weigh out 0.17 g (3.7 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 9.43 g at room temperature and mix well.

  Weigh benzyl alcohol (0.32 g, 3.0 mmol) into another 50 ml stainless steel autoclave equipped with a pressure gauge, replace this autoclave with carbon dioxide, cool well, and connect with the autoclave containing nitrogen dioxide. To do.

  Move the contents to an autoclave containing benzyl alcohol by operating the valve. When this autoclave was placed in a 35 ° C. water bath, the pressure became 5.2 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The reaction vessel was opened and the reaction mixture was analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.31 g (98% yield) of benzaldehyde was obtained.

Example 5
Weigh 0.12 g (3.5 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 9.87 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 3-nitrobenzyl alcohol (0.46 g, 3.0 mmol), replace the autoclave with carbon dioxide, cool well, and add nitrogen dioxide. Connect with autoclave.

  Move the contents to an autoclave containing 3-nitrobenzyl alcohol by operating the valve. When this autoclave was placed in a 40 ° C. water bath, the pressure became 5.1 MPa. The reaction was stirred with a magnetic stirrer for 2 hours.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The reaction vessel was opened and the reaction mixture was analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.45 g (99% yield) of 3-nitrobenzaldehyde was obtained.

Example 6
Weigh out 0.16 g (3.5 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add 5.50 g of liquefied carbon dioxide at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 4-chlorobenzyl alcohol (0.435 g, 3.1 mmol), replace the autoclave with carbon dioxide, cool well, and then add nitrogen dioxide. Connect with autoclave.

  Operate the valve and transfer the contents to an autoclave containing 4-chlorobenzyl alcohol. When this autoclave was placed in a 40 ° C. water bath, the pressure became 3.9 MPa. The reaction was stirred with a magnetic stirrer for 2 hours.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The reaction vessel was opened and the reaction mixture was analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.42 g (yield 98%) of 4-chlorobenzaldehyde was obtained.

Example 7
Weigh out nitrogen dioxide in a 50 ml stainless steel autoclave at 0.33 g (7.2 mmol) at room temperature, then add liquefied carbon dioxide at 10.71 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh benzyl methyl ether (0.35 g, 3.1 mmol), replace the autoclave with carbon dioxide, cool well, and reconstitute the previous autoclave containing nitrogen dioxide. Link.

  Operate the valve and transfer the contents to an autoclave containing benzyl methyl ether.

  When this autoclave was placed in a 45 ° C. water bath, the pressure became 5.9 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.32 g (98% yield) of benzaldehyde was obtained.

Example 8
Weigh 0.12 g (3.9 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 8.85 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 3-methylbenzyl alcohol (0.38 g, 3.1 mmol), replace the autoclave with carbon dioxide, cool well, and add nitrogen dioxide. Connect with autoclave.

  Operate the valve to transfer the contents to an autoclave containing 3-methylbenzyl alcohol.

  When this autoclave was placed in a 25 ° C. water bath, the pressure became 4.8 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.37 g (99% yield) of 3-methylbenzaldehyde was obtained.

Example 9
Weigh out nitrogen dioxide in a 50 ml stainless steel autoclave at 0.31 g (6.7 mmol) at room temperature, then add liquefied carbon dioxide at 10.25 g at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 2-methylbenzyl alcohol (0.37 g, 3.0 mmol), replace the autoclave with carbon dioxide, cool well, and add nitrogen dioxide. Connect with autoclave.

  Move the contents to an autoclave containing 2-methylbenzyl alcohol by operating the valve.

  When this autoclave was placed in a 25 ° C. water bath, the pressure became 5.2 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.36 g (98% yield) of 2-methylbenzaldehyde was obtained.

Example 10
Weigh 0.12 g (3.9 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add liquefied carbon dioxide at 5.62 g at room temperature and mix well.

  In another 50 ml stainless steel autoclave equipped with a pressure gauge, weigh 3-bromobenzyl alcohol (0.58 g, 3.1 mmol), replace the autoclave with carbon dioxide, cool well, and then add nitrogen dioxide. Connect with autoclave.

  Operate the valve to transfer the contents to an autoclave containing 3-bromobenzyl alcohol.

  When this autoclave was placed in a 40 ° C. water bath, the pressure became 3.8 MPa. The reaction was stirred with a magnetic stirrer for 3 hours.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed by gas chromatography using decane as an internal standard.

  As a result, 0.57 g (99% yield) of 3-bromobenzaldehyde was obtained.

Example 11
Weigh 0.15 g (3.3 mmol) of nitrogen dioxide in a 50 ml stainless steel autoclave at room temperature, then add 6.16 g of liquefied carbon dioxide at room temperature and mix well.

  In a separate 50 ml stainless steel autoclave with a pressure gauge, weigh 1,4-benzenedimethanol (0.21 g, 1.5 mmol), replace the autoclave with carbon dioxide, cool well, and contain nitrogen dioxide. Connect with the previous autoclave.

  Move the contents to an autoclave containing 1,4-benzenedimethanol by operating the valve.

  When this autoclave was placed in a 25 ° C. water bath, the pressure was 3.9 MPa. The reaction was stirred for 1 hour with a magnetic stirrer.

After the reaction, the autoclave was cooled with ice under reduced pressure, nitrogen dioxide residual or dinitrogen tetroxide and their place Motokarada removed with carbon dioxide. The contents were analyzed and quantified by ¹ H NMR using coumarin as an internal standard, and the purity was confirmed by gas chromatography.

  As a result, 0.20 g (yield 98%, purity 99.8%) of 1,4-benzenedialdehyde was obtained.

Claims (2)

A primary alcohol or its alkyl ether is selected from aromatic primary alcohols and aliphatic primary alcohols, with carbon dioxide in a liquid-like state, the aromatic primary alcohols reacted by adding nitrogen or nitrogen tetroxide dioxide is oxidized and primary alcohols or manufacturing method of aldehydes, characterized in Rukoto give the corresponding aldehyde to the alkyl ether selected from aliphatic primary alcohols. After the reaction, nitrogen dioxide remaining or dinitrogen tetroxide and their changing Motokarada by removing carbon dioxide, the production method of aldehydes according to claim 1, characterized in that to obtain a high purity aldehyde.

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