KR20000056308A - A process for the preparation of cinnamic acid derivatives using (S)-binaphthyl palladium complex as a catalyst - Google Patents

Abstract

PURPOSE: A process of preparing cinnamic acid derivatives using a trace amount of a palladium composite catalyst is provided which needs no complicated activation process for recovering palladium. CONSTITUTION: A cinnamic acid derivatives of formula 1 are prepared by the reaction of alkoxybenzene derivatives of formula 2 and acrylic acid derivatives of the following formula; CH2=CHCOOR2 in the presence of a (S)-binaphthyl palladium composite catalyst of formula 3 and an inorganic base. In formula, X is brome or iodine, R1 is C1-8 lower alkyl, R2 is H, C1-10 straight or branched alkyl, or hydroxyalkyl, R3 is benzene or toluene. and has high color, purity products and production yield. The process produces the title compound in high purity and yields as compared with conventional ones.

Description

A process for the preparation of cinnamic acid derivatives using (S) -binaphthyl palladium complex as a catalyst}

The present invention relates to a method for preparing the cinnamic acid derivative of the formula (1).

One

In the above formula, R ¹ is a lower alkyl group having 1 to 8 carbon atoms, R ² is hydrogen, a linear or branched alkyl group having 1 to 10 carbon atoms, or a hydroxyalkyl group.

Cinnamic acid derivatives have been used as a raw material for sunscreen cosmetics by the nature of absorbing ultraviolet rays, and various methods have been reported for preparing them.

For example, according to the method described in US Pat. No. 4,970,332, a method of preparing cinnamic acid derivatives is obtained by reacting 4-iodoanisole with alkyl acrylate under a palladium catalyst and trialkylamine bonded to a support as shown in Scheme 1 below. It has been disclosed.

In the above, R ^{2 *} is an alkyl group having 1 to 10 carbon atoms.

In addition, the preparation method of cinnamic acid derivatives described in US Pat. No. 5,457,266 is prepared by reacting an alkoxybenzene derivative of formula (2) with an alkyl acrylate under a palladium active catalyst and an alkanoic acid ammonium salt as shown in Scheme 2 to prepare a cinnamic acid derivative of formula (1). The method has been disclosed.

R ¹ is a lower alkyl group having 1 to 8 carbon atoms, and R ² is hydrogen, a straight or branched alkyl group having 1 to 10 carbon atoms, or a hydroxyalkyl group.

However, when preparing the cinnamic acid derivative of the formula (1) according to the known method described above, there are various difficulties in the manufacturing process. That is, when the palladium catalyst bonded to the support is used, there are disadvantages such as low catalyst activity, high catalyst usage, long reaction time, low reaction yield, and limited to only trialkylamine as a base, and a palladium activated carbon catalyst. Under the reaction, the reaction rate is fast, but the catalyst is used a lot, so that a demanding activation process for recovering the expensive palladium catalyst after completion of the reaction is required. In addition, in both reactions, an ammonium salt is used as a base, which does not provide satisfactory results in color and purity of the target compound.

Accordingly, the present inventors have repeatedly studied to solve the problems of the prior art as a result, by using a very small amount of a highly active palladium complex catalyst, there is no need for a demanding activation process for recovering palladium, the reaction time is short, the reaction time is short, As a base, the present invention was completed by discovering a method of preparing cinnamic acid derivative having high color, purity, and yield using an inorganic base.

Accordingly, an object of the present invention is to provide a method for producing a novel cinnamic acid derivative using a palladium complex catalyst.

The present invention relates to a process for preparing a cinnamic acid derivative of formula (1) comprising a step of reacting an alkoxybenzene derivative of formula (2) and an acrylic acid derivative of formula (4) in the presence of the (S) -binafthyl palladium complex catalyst of formula (3) and an inorganic base. It is about.

X is bromine or iodine, R ¹ is a lower alkyl group having 1 to 8 carbon atoms, R ² is hydrogen, a straight or branched alkyl group having 1 to 10 carbon atoms, or a hydroxyalkyl group, and R ³ is benzene or toluene.

The preparation method according to the present invention is represented by the following Scheme 3.

In Scheme 3, X, R ¹ and R ² are as defined above.

In the preparation method according to the present invention, the acrylic acid derivative of Formula 4 is preferably used in an amount of 0.5 to 5.0 equivalents, more preferably 2 to 4 equivalents, relative to the alkoxybenzene derivative of Formula 2. When the amount of the compound used is less than 0.5 equivalents to the alkoxybenzene derivative of Formula 2, the reactivity decreases, and when it exceeds 5 equivalents, side reactions may occur.

In the preparation method according to the present invention, the amount of the (S) -binafylpalladium complex catalyst of Formula 3 is preferably 10 to 100 ppm, more preferably 30 to 50 ppm, based on the alkoxybenzene derivative of Formula 2. When the amount of the (S) -vinaphthyl palladium complex catalyst of Formula 3 is less than 10 ppm, the reactivity may decrease, and when it exceeds 100 ppm, side reactions may occur and economic efficiency may be reduced.

In the production method according to the invention, the inorganic base is preferably selected from the group consisting of potassium carbonate, potassium hydrogen carbonate, sodium carbonate and sodium hydrogen carbonate. The amount of the inorganic base is preferably 0.5 to 5.0 equivalents, more preferably 1-3 equivalents to the alkoxybenzene derivative of the formula (2). When the amount of the inorganic base is less than 0.5 equivalents, the reactivity decreases, and when it exceeds 5 equivalents, there are difficulties in side reactions and removal.

In the production method according to the present invention, the reaction solvent is preferably selected from the group consisting of dimethylformamide, N-methylpyrrolidone and water, it is used in an amount of 1 to 10 times by mass relative to the alkoxybenzene derivative of formula (2) Preferably, it is more preferable to use 2-6 times. When the amount of the reaction solvent is less than one time compared to the alkoxybenzene derivative of Formula 2, a side reaction may occur, and when the amount of the reaction solvent exceeds 10 times, the reactivity may be deteriorated.

In the production method according to the invention, the reaction temperature is preferably 50 ~ 150 ℃, more preferably 60 ~ 120 ℃. In addition, the reaction time is preferably 0.5 to 5 hours, more preferably 1 to 2 hours. If the reaction temperature is lower than the above or the reaction time is short, the reactivity is lowered, if higher than the reaction temperature or the reaction time is long side reaction may occur.

As described above, when the reaction between the alkoxybenzene derivative of Formula 2 and the acrylic acid derivative of Formula 4 is completed, the reaction solution is extracted and concentrated, and the cinnamic acid derivative of Formula 1 produced by a purification method such as distillation under reduced pressure can be obtained in a pure state. Can be.

As described above, the method for preparing the cinnamic acid derivative of Chemical Formula 1 according to the present invention does not require an activation process for recovering an expensive palladium catalyst by using a very small amount of (S) -binafylpalladium complex catalyst and inorganic base. In addition to improving the purity, it is possible to prepare a cinnamic acid derivative of Formula 1 in high yield.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, this does not limit the scope of the invention.

Example 1

Preparation of 2-ethylhexyl 4-methoxycinnamic acid ester

300 g of water, 187.0 g of 4-bromoanisole, 138.2 g of gallium carbonate, and 276.4 g of 2-ethylhexyl acrylate were slowly added dropwise to 10 mg of (S) -vinaptyl palladium complex catalyst (R ³ = benzene). The solution was stirred at 100 ° C. for 1 hour, and then the water layer was removed by layer separation. Then, 275.9 g of the target compound was obtained by distillation under reduced pressure. The yield of the target product was 95%, the purity by GC was 99.9%. Measurement data by NMR is as follows.

¹ H-NMR (CDCl ₃ , 400 MHz, ppm): 0.86-0.98 (6H, m), 1.25-1.72 (9H, m), 3.84 (3H, s), 4.11 (2H, d), 6.85-6.95 (1H) , m), 7.44-7.54 (1H, m), 7.64 (1H, d)

Example 2

Preparation of 2-ethylhexyl 4-methoxycinnamic acid ester

276.4 g of 2-ethylhexyl acrylate was slowly added dropwise to 300 g of water, 234.0 g of 4-iodoanisole, 138.2 g of potassium carbonate, and 10 mg of (S) -binafthyl palladium complex catalyst (R ³ = benzene). The solution was stirred at 100 ° C. for 1 hour, and then the water layer was removed by layer separation. Then, 275.9 g of the target compound was obtained by distillation under reduced pressure. The yield of the target product was 95%, purity by GC was 99.9%. Measurement data by NMR is as follows.

¹ H-NMR (CDCl ₃ , 400 MHz, ppm): 0.86-0.98 (6H, m), 1.25-1.72 (9H, m), 3.84 (3H, s), 4.11 (2H, d), 6.85-6.95 (1H) , m), 7.44-7.54 (1H, m), 7.64 (1H, d)

Example 3

Preparation of 2-ethylhexyl 4-methoxycinnamic acid ester

300 g of dimethylformamide, 187.0 g of 4-bromoanisole, 138.2 g of potassium carbonate, and 276.4 g of 2-ethylhexyl acrylate were slowly added dropwise to 10 mg of the (S) -binafthyl palladium complex catalyst (R ³ = benzene). The solution was stirred at 100 ° C. for 1 hour, and then the water layer was removed by layer separation. Then, 275.9 g of the target compound was obtained by distillation under reduced pressure. The yield of the target product was 95%, the purity by GC was 99.9%. Measurement data by NMR is as follows.

¹ H-NMR (CDCl ₃ , 400 MHz, ppm): 0.86-0.98 (6H, m), 1.25-1.72 (9H, m), 3.84 (3H, s), 4.11 (2H, d), 6.85-6.95 (1H) , m), 7.44-7.54 (1H, m), 7.64 (1H, d)

Comparative example

Preparation of 2-ethylhexyl 4-methoxycinnamic acid ester

It was prepared by the method described in US Pat. No. 5,457,266. 4.68 g of 4-iodoanisole, 4.05 g of 2-ethylhexyl acetate, 2.22 g of triethylamine, 1.32 g of acetic acid and 15 mg of palladium carbon catalyst were added and stirred at 150 ° C. for 3 hours. Water and toluene were added, the layers were separated, washed with 2N hydrochloric acid solution, and distilled under reduced pressure to obtain 4.65 g of a yellow target compound with a yield of 80% and GC purity of 95%.

As confirmed in the above examples and comparative examples, the production method of the present invention was able to obtain a cinnamic acid derivative of Formula 1 with higher purity and higher yield than the conventional method.

The production method of the present invention has the advantage that it can be economically produced in high yield, high purity compared to the conventional production method of the cinnamic acid derivative of formula (1).

Claims (7)

A process for preparing a cinnamic acid derivative of formula (1) comprising the step of reacting an alkoxybenzene derivative of formula (2) and an acrylic acid derivative of formula (4) in the presence of a (S) -binafylpalladium complex catalyst of formula (3) and an inorganic base. One 2 3 4 X is bromine or iodine, R ¹ is a lower alkyl group having 1 to 8 carbon atoms, R ² is hydrogen, a straight or branched alkyl group having 1 to 10 carbon atoms, or a hydroxyalkyl group, and R ³ is benzene or toluene. The method of claim 1, wherein the amount of the acrylic acid derivative represented by the formula (4) is 0.5 to 5.0 equivalents based on the alkoxy benzene derivative represented by the formula (2). The method of claim 1, wherein the amount of the (S) -binafylpalladium complex catalyst of the formula (3) is 10 to 100 ppm with respect to the alkoxybenzene derivative of the formula (2). The method of claim 1, wherein the inorganic base is selected from the group consisting of potassium carbonate, potassium hydrogen carbonate, sodium carbonate and sodium hydrogen carbonate. The method of claim 4, wherein the amount of the inorganic base is 0.5 to 5.0 equivalents based on the alkoxybenzene derivative of the formula (2). The reaction solvent of claim 1, wherein the reaction solvent is selected from the group consisting of dimethylformamide, N-methylpyrrolidone, and water, and 1 to 10 times by mass ratio is used for the alkoxybenzene derivative of Formula 2. Method for preparing cinnamic acid derivatives. The method of claim 1, wherein the reaction temperature is 50 ~ 150 ℃, the reaction time is 0.5 to 5 hours.