TWI408122B - A method for the production of aromatic aldehydes - Google Patents

Abstract

A preparation method for aromatic aldehyde compound includes: using an alkyl-substituted or non-substituted benzene to carry out halomethylation for forming a compound represented by general formula (I); reacting the compound having general formula (I) with an alkylaldehyde in the presence of a phase transfer catalyst (PTC) under alkaline condition and a reaction temperature to obtain an aromatic aldehyde compound. The present preparation method has the effects of low cost, high reaction yield, simple reaction steps, low pollution and not having problem of producing three wastes, thereby being suitable to industrial mass production.

Description

Method for producing aromatic aldehyde compounds

The invention relates to a method for producing an aromatic aldehyde compound, which is characterized in that the alkylbenzene is used as a raw material, does not need to pass through a reduction reaction or a high-pressure hydrogenation reaction path, and has the characteristics of low cost, high efficiency and low pollution.

Synthetic fragrances have a large demand in the perfume and fragrance industry. They are widely used in daily products such as soaps, washing powders, cosmetics, etc. Common synthetic fragrances include aromatic aldehydes such as lysmeral and floralozone. Aromatic aldehyde compound). Industrial production of aromatic aldehydes has been developed by Givaudan Corp., but its industrial production still suffers from various disadvantages.

In the preparation method of the prior art aromatic aldehyde compound, as shown in the following Reaction Scheme I, the production of 4-tert-butylbenzaldehyde is critical, and the final step of the reaction route of this method requires a high pressure hydrogenation reduction reaction. A palladium/carbon catalyst is required, which is costly, and the reaction yield of this preparation method is less than 30%. In addition, the patent WO2007045641 owned by BASF (Badische Anilin- und Soda-Fabrik Corp., BASF) is improved for the hydrogenation reduction reaction of the last step, but the reaction hydrogen pressure is as high as 30 bar (Bar), so it is still It is difficult to industrialize.

The Givaudan research team published a method for the production of aromatic aldehydes in Bull. Soc. Chem. Fr, p1194, in 1961, as shown in Reaction Scheme II below. This method uses TiCl ₄ and BF ₃ -Et ₂ O catalysts in large quantities. However, the total yield is less than 10%, in which the raw material 2-methylacrolein production is rare and difficult to obtain, TiCl _{4 is} easily hydrolyzed, so it cannot be industrially mass-produced, and three wastes, that is, waste water, are produced. ), waste gas and industrial residue, causing environmental pollution.

DE 2627112 discloses a process for producing an aromatic aldehyde compound, as shown in the following reaction scheme III, wherein the reaction yield is as high as 80%, but the raw material used for the production of 2-methylpropenol is rare and expensive, thus limiting its industrialization. development of. The paper disclosed in Journal of Molecular Catalysis A: Chemical , 231 (1-2), 61-66 (2005) is an improvement of the method of the aforementioned patent, and the theoretical yield is 95%, however, it is required to be 4- 4-butyliodobenzene is used as a raw material, and the reaction is carried out by using a rare catalyst and an ionic liquid. The reaction time is over 24 hours, and the efficiency is too low, which is disadvantageous for industrial production.

DE 285 1024 discloses a process for the preparation of aromatic aldehydes, as shown in the following Reaction Scheme IV, in which the preparation of the reaction starting materials requires a large amount of AlCl ₃ and the production process has three wastes and equipment corrosion problems. In addition, the known Vilsmeier reaction also has three waste problems with a total yield of only 35%. The paper was published in Organic Preparations and Procedures International , 14(1-2), p9-20, in 1982. However, the final step of the reaction pathway still requires high-pressure hydrogenation reduction and the use of precious metals. As a catalyst, the problem of excessive cost is caused.

In summary, in response to the current increase in demand for fragrances, there is an urgent need for a method for producing aromatic aldehyde compounds which are low in cost, high in yield, and which do not cause environmental pollution.

In view of the problems of high cost, low yield or three wastes in the production method of the aromatic aldehyde compound of the prior art, the object of the present invention is to provide a method for producing an aromatic aldehyde compound, which utilizes inexpensive raw materials and catalysts for simple reaction. Under the condition, an aromatic aldehyde compound can be synthesized to achieve the effects of low cost, high reaction yield, simple reaction step, low pollution, no three-waste problem, and is suitable for industrial mass production.

A method for producing an aromatic aldehyde compound according to the present invention, which comprises:

Halomethylation by alkyl-substituted or non-substituted benzene to form a compound of the formula I wherein R ₁ is hydrogen, methyl, or Base, isopropyl, isobutyl or tert-butyl, X is halogen;

The compound of the formula I is reacted with an alkyl aldehyde in an alkaline environment and in the presence of a phase transfer catalyst (PTC) at a reaction temperature to obtain an aromatic aldehyde compound.

According to the invention, the alkyl group in the alkyl-substituted or unsubstituted benzene may be, but not limited to, methyl, ethyl, isopropyl, isobutyl and tert-butyl.

According to the present invention, the halomethylation is carried out by a method such as, but not limited to, Youji Huaxue, 27(5), 674-677, 2007 and Synthesis, p1428, 1995. The usual reaction for the halomethylation reaction in this case is the reaction of a monoalkylbenzene in which the alkyl group is hydrogen, methyl, ethyl, isopropyl, isobutyl or t-butyl, with paraformaldehyde. The p-alkylbenzyl alcohol is formed and replaced by HBr to form a compound of formula I.

According to the invention, the alkyl aldehyde can be, but is not limited to, propionaldehyde and isobutyraldehyde.

According to the present invention, the alkaline environment can be formed by adding sodium hydroxide, potassium hydroxide or a combination thereof.

According to the invention, the interphase transfer catalyst is selected from the group consisting of: (1) having the following formula II:

Wherein R ₁ is as defined above, each of R ₄ , R ₅ , R ₆ may be an alkyl group having 1 to 6 carbon atoms, and X is as defined above; and (2) a tetraalkylammonium halide.

According to the present invention, the interphase transfer catalyst may be, but not limited to, tetrabutylammonium iodide.

Preferably, the reaction temperature is between 60 and 90 ° C; more preferably between 70 and 80 ° C.

According to the present invention, the aromatic aldehyde compound may be, but not limited to, lysmeral, that is, 2-methyl-3-(4-tert-butylphenyl)-propanal [2- Methyl-3-(4-tert-butylphenyl)-propanal], or sea breeze aldehyde, ie 3-(4-ethylphenyl)-2,2-dimethylpropanal [3-(4-ethylphenyl)- 2,2-dimethylpropanal], or 2,2-dimethyl-3-(3-methylphenyl)propanal, or rabbit ear aldehyde , 2-methyl-3-(p-isopropylphenyl)propanal, or 2,2-dimethyl-4-propanol Dimethyl-4-(1-methylethyl)benzenepropanal or 2,2-dimethyl-3-phenylpropanal.

Based on the above, the method of the present invention has the following advantages: (1) the reaction raw material and the catalyst are easily obtained, and the cost is low; (2) the reaction condition is mild, the reaction process does not corrode the equipment; no high-pressure hydrogenation reaction or other reduction reaction is required, so the reaction Easy to operate; (3) No three wastes, no environmental pollution; (4) The total yield exceeds 60%, and the target compound content of the final product exceeds 95%, so it is suitable for industrial mass production applications.

The method for producing an aromatic aldehyde compound of the present invention, as shown in the following Reaction Scheme V, includes the following steps: alkyl-substituted or non-substituted benzene for halo Homomethylation to form a compound of formula I; and reacting a compound of formula I with an alkyl aldehyde in the presence of an alkaline environment and an interphase transfer catalyst at a suitable temperature to obtain a fragrance Aldehyde compounds.

Wherein R ₁ is hydrogen, methyl, ethyl, isopropyl, isobutyl or tert-butyl, R ₂ is methyl, ethyl; R ₃ is hydrogen, methyl or ethyl; and X is halogen.

In a preferred embodiment of the invention, the temperature is between 60 and 90 °C.

In another preferred embodiment of the invention, the temperature is between 70 and 80 °C.

The invention will be further illustrated by the following examples, which are to be construed as illustrative and not restrictive.

Preparation Example 1. Preparation of Compound 1

Compound 1 was obtained by the following reaction route 1 and experimental methods.

50 g (0.37 mol) of tert-butylbenzene, 12.3 g (0.40 mol) of paraformaldehyde and 100 ml of acetic acid were placed in a reaction flask. A solution of 109.6 g of hydrogen bromide (HBr) in acetic acid was slowly added dropwise to 33% (w/w), and after 30 minutes, the temperature was raised to 120 ° C and stirred for 7.5 hours. The sample was mixed with water and mixed with methylene chloride, and the organic layer was subjected to thin-layer chromatography (TLC) to trace the reaction. After reacting to the absence of the starting material, 200 ml of water was added, and extraction was carried out three times with 200 ml of dichloromethane each time to obtain an organic layer; the organic layer was concentrated and then distilled, and collected at 165 to 170 ° C, 4.8 to 5.5 × A fraction of 10 ^-1 torr. The product of Compound 1 was 73.02 g, and the yield was 86.3%.

Preparation Example 2 Preparation of Interphase Transfer Catalyst PTC 1

The interphase transfer catalyst PTC 1 was obtained by the following reaction route 2 and experimental methods.

10 g (220.1 mmol) of Compound 1 was dissolved in 200 ml of absolute ethanol, 14.31 g of trimethylamine (242.1 mmol) was added, and the mixture was heated to reflux for 2 hours, and then the reaction solution was stood overnight. The liquid was filtered off, and the solid was washed three times with absolute ethanol, and the obtained solid was dried as an interphase transfer catalyst PTC 1 for use.

Preparation 3. Preparation of Compound 2

Compound 2 was prepared by the following reaction route 3 and experimental methods.

50 g (0.47 mol) of ethylbenzene, 15.56 g (0.52 mol) of paraformaldehyde and 100 ml of acetic acid were placed in a reaction flask. A solution of 138.6 g of hydrogen bromide in acetic acid (33% (w/w) was slowly added dropwise, and after 30 minutes, the temperature was raised to 120 ° C and stirred for 7.5 hours. The sample was mixed with water and mixed with dichloromethane, and the organic layer was taken to run the TLC sheet to track the reaction. After the reaction, 200 ml of water was added, and extraction was carried out three times with 200 ml of dichloromethane each time to obtain an organic layer; the organic layer was concentrated and then distilled, and collected at 151 to 156 ° C, 4.2 to 4.8 × 10 ^-1 torr. (torr) fraction. The compound 2 product was obtained in 81.66 g, yield 86.9%.

Preparation Example 4. Interphase Transfer Catalyst PTC 2

The interphase transfer catalyst PTC 1 was obtained by the following reaction route 4 and experimental methods.

10 g (251.2 mmol) of compound 2 was dissolved in 200 ml of absolute ethanol, 16.33 g of trimethylamine (276.3 mmol) was added, and the mixture was heated to reflux for 2 hours, and then the reaction mixture was stood overnight. The liquid was filtered off, and the solid was washed three times with absolute ethanol, and the obtained solid was dried as an interphase transfer catalyst PTC 2 for use.

Comparative example 1

In this example, the following experimental methods were used to carry out the reaction to obtain limonaldehyde.

2.3 g (57.7 mmol) of sodium hydroxide, 0.33 g (0.88 mmol) of tetrabutylammonium iodide, 7.5 ml of water, 4.2 ml of toluene, 1 ml of tetrahydrofuran were added to the reaction flask, and the temperature was raised to 70-75. °C. A mixture of 10 g (44.0 mmol) of compound 1 and 3.55 g (61.2 mmol) of propionaldehyde was slowly added dropwise over two hours using an addition funnel and stirred vigorously. After the completion of the dropwise addition, the mixture was stirred at 70 to 75 ° C for 3 hours, and the reaction was followed by gas chromatography (GC). After reacting to the absence of the starting material, the organic layer was extracted with 30 ml of water, and then the organic layer was evaporated over anhydrous sodium sulfate, filtered, and the filtrate was concentrated and evaporated to give the product 4.48 g.

Example 1

In this example, the following reaction route 5 and the experimental method were used to carry out the reaction to obtain limonaldehyde.

2.3 g (57.7 mmol) of sodium hydroxide, 0.26 g (0.88 mmol) of PTC 1, 7.5 ml of water, 4.2 ml of toluene, and 1 ml of tetrahydrofuran were added to the reaction flask, and the temperature was raised to 70 to 75 °C. A mixture of 10 g (44.0 mmol) of compound 1 and 3.55 g (61.2 mmol) of propionaldehyde was slowly added dropwise over two hours using an addition funnel and stirred vigorously. After the completion of the dropwise addition, the mixture was stirred at 70 to 75 ° C for 3 hours, and the reaction was followed by GC. After the reaction was stopped, 30 ml of water was added to extract the organic layer, and the organic layer was separated from anhydrous sodium sulfate, filtered, and the filtrate was concentrated, and then evaporated under reduced pressure to give 7.43 g of the yield of the product, the yield of 82.6%, obtained by GC analysis. The purity of the gas chromatograph was 97.27%.

The nuclear magnetic resonance analysis is as follows:

¹ H NMR (CDCl ₃ ): δ 9.73 (t, 1H, J = 6.851), 7.34 (ddd, 1H, J = 8.032, J = 3.716, J = 0.000), 7.13 (ddd, 1H, J = 8.032, J = 3.732, J = 0.000), 7.11 (ddd, 1H, J = 8.032, J = 3.716, J = 0.000), 7.32 (ddd, 1H, J = 8.032, J = 3.732, J = 0.000), 2.6 (dd , 2H, J = 6.945, J = 6.851), 3.0 (tq, 1H, J = 6.945, J = 6.911), 1.32 (m, 9H), 1.1 (d, 3H, J = 6.911).

The limonaldehyde was prepared by the method of Comparative Example 1 and the method of Example 1. The results are shown in Table 1, showing the effect of the reaction of different catalysts with temperature on the reaction yield. It is apparent from Table 1 that the self-made aromatic phase transfer catalyst PTC1 has a higher yield than that of tetrabutylammonium iodide.

Comparative Example 2:

In this example, sea air aldehyde was obtained by the following experimental methods.

2.63 g (65.8 mmol) of sodium hydroxide, 0.37 g (1.0 mmol) of tetrabutylammonium iodide, 7.5 ml of water, 4.2 ml of toluene, and 1 ml of tetrahydrofuran were added to the reaction flask, and the temperature was raised to 70-75. °C. A mixture of 10 g (50.2 mmol) of compound 2 and 5.03 g (69.8 mmol) of isobutyraldehyde was slowly added dropwise over two hours using an addition funnel and stirred vigorously. After the completion of the dropwise addition, the mixture was stirred at 70 to 75 ° C for 3 hours, and the reaction was followed by GC. After the reaction was stopped, 30 ml of water was added to extract the organic layer, and the organic layer was separated from anhydrous sodium sulfate, filtered, and the filtrate was concentrated and then evaporated under reduced pressure to yield 5.

Example 2:

In this example, sea breeze aldehyde is obtained by the following reaction route 6 and experimental methods.

2.63 g (65.8 mmol) of sodium hydroxide, 0.27 g (1.0 mmol) of PTC 2, 7.5 ml of water, 4.2 ml of toluene, and 1 ml of tetrahydrofuran were added to the reaction flask, and the temperature was raised to 70 to 75 °C. A mixture of 10 g (50.2 mmol) of compound 2 and 5.03 g (69.8 mmol) of isobutyraldehyde was slowly added dropwise over two hours using an addition funnel and stirred vigorously. After the completion of the dropwise addition, the mixture was stirred at 70 to 75 ° C for 3 hours, and the reaction was followed by GC. After the reaction was stopped, 30 ml of water was added to extract the organic layer, and the organic layer was separated from anhydrous sodium sulfate, filtered, and the filtrate was concentrated and then evaporated under reduced pressure to give a product of 7.92 g of sea bromide, yield 82.8%, obtained by GC analysis. The purity of the gas chromatograph was 95.76%.

The nuclear magnetic resonance analysis is as follows:

¹ H NMR (CDCl ₃ ): δ 9.62 (m, 1H), 7.15 (ddd, 4H, J = 8.026, J = 3.500, J = 1.319), 2.8 (m, 2H), 2.6 (q, 2H, J =7.486), 1.2 (m, 9H).

The preparation of sea breeze aldehyde by the method of Comparative Example 2 and the method of Example 2 was carried out. The results are shown in Table 2. It is shown that the influence of the reaction of different catalysts with temperature on the reaction yield can be clearly seen that the aromatic phase transfer catalyst PTC2 has a comparative effect. High yield.

Table 2

While the invention has been described with respect to the specific embodiments of the invention, it will be understood that many modifications and changes can be made without departing from the scope and spirit of the invention. The scope of the invention is therefore limited only by the scope of the appended claims.

Claims (8)

A method for producing an aromatic aldehyde compound, which comprises: halomethylation by alkyl-substituted or non-substituted benzene, having the following A compound of formula I, wherein R ₁ is hydrogen, methyl, ethyl, isopropyl, isobutyl or tert-butyl, and X is halogen; The compound of the formula I is reacted with an alkylaldehyde in an alkaline environment and in the presence of a phase transfer catalyst (PTC) at a reaction temperature to obtain an aromatic aldehyde (aromatic aldehyde). Compound). The method of claim 1, wherein the alkyl aldehyde is propionaldehyde or isobutyraldehyde. The method of claim 1 or 2, wherein the interphase transfer catalyst has the following formula II: Wherein R ₄ , R ₅ and R ₆ each may be an alkyl group having 1 to 6 carbon atoms. The method of claim 1 or 2, wherein the reaction temperature is between 60 and 90 °C. The method of claim 3, wherein the reaction temperature is between 60 and 90 °C. The method of claim 1 or 2, wherein the reaction temperature is between 70 and 80 °C. The method of claim 3, wherein the reaction temperature is between 70 and 80 °C. The method of claim 1, wherein the aromatic aldehyde compound is 2-methyl-3-(4-tert-butylphenyl)-propanal [2-Methyl-3-(4-tert-) Butylphenyl)-propanal], 3-(4-ethylphenyl)-2,2-dimethylpropanal [3-(4-ethylphenyl)-2,2-dimethylpropanal], 2,2-dimethyl- 3-(3-methylphenyl)propanal [2-, 2-dimethyl-3-(3-methylphenyl)propanal], 2-methyl-3-(p-isopropylphenyl)propanal [2- Methyl-3-(p-isopropylphenyl)propanal], 2,2-dimethyl-4-(1-methylethyl)phenylpropanal [2,2-dimethyl-4-(1-methylethyl)benzenepropanal] Or 2,2-dimethyl-3-phenylpropanal.