LT5510B - Process for preparing of 2-(4'-phenylbenzoyl)benzoic acid - Google Patents

Abstract

Novel process for preparing 2-(4'-phenylbenzoyl)benzoic acid wherein diphenyl is acylated with phthalic anhydride under catalytic conditions is characterized by starting reaction in cooled at 0-5 oC solvent and by adding catalyst in several portions, optimally, half of the catalyst amount during the initial step and the rest amount later in several portions and heating the reaction mixture at 40-65 oC. At initial step of reaction the molar ratio of diphenyl, phthalic anhydride and Louis acidis aproximately 1:1:1. The solvent is chosen from methylene chloride, 1,2-dichloroethane or nitrobenzene. The mixture is additionaly stored at 40-65 oC, optimally, 2-4 hours. The process claimed allows to obtain 2-(4'-phenylbenzoyl)benzoic acid in almost quantitative yield (up to 95 %) and of high purity.

Description

The present invention relates to a novel process for the preparation of a known compound used in organic synthesis.

2- (4'-Phenylbenzoyl) benzoic acid is an important and only precursor for the synthesis of 2-phenylanthraquinone and 2-phenylanthracene, which have become important in organic electronics in recent years, especially for the production of OLEDs.

In all cases, 2- (4'-phenylbenzoyl) benzoic acid (I) is obtained by reacting diphenyl with phthalic anhydride, catalyzed by Lewis acid:

The known method of synthesis of this acid has remained essentially unchanged since 1930.

The main problem with this synthesis is that, unlike other aromatic monocyclic compounds, the acylation conditions of diphenyl or substituted diphenyls are much more complex - under normal acylation conditions, the benzene ring of the second diphenyl molecule is acylated in parallel with the desired monoacylation.

P.H.Groggins [P.H. Groggins. Friedel-Crafts reaction. Biphenyl series.I. Preparation of 4'phenyl-2-benzoylbenzoic acid and its derivatives.- Journal of Industrial and Engineering Chemistry (Washington, D.C.) 1930, vol. 22, p. 620-625, 626-630; Chem. Abstr. 24,3772;

Phillip H. Groggins. p-Phenyl-o-benzoylbenzoic acid. U.S. Pat. 1814145 (1931)] describes in detail the method and equipment for the synthesis of this acid: all the reactants are loaded at once in an iron drum furnace: equimolar amounts of phthalic anhydride and diphenyl, together with 2.2 mol of aluminum trichloride. The reaction mixture is heated for 8-12 hours at 60-85 ° C. After completion of the reaction, the mixture is poured into concentrated sulfuric acid, the unreacted diphenyl is distilled off with water vapor, and the hot mixture is filtered.

The precipitate is dissolved in caustic soda solution, the resulting mixture is again distilled with water vapor, it is slowly poured into acid, the precipitate is washed with water and crystallized from acetic acid.

The yield of the desired acid (I) is 68-94%.

As it can be seen, the described method is not technologically convenient (special dedicated equipment is needed, it is very energy consuming and time consuming steam distillation).

A similar method for the synthesis of acid (I) is described in the work of Russian scientists [B. A. KoBapnaKOB, M. Γ. 3onoTyxHH, C.B. Cajia3KHH, C.P.PatįmKOB.- Pi3BecTHa AKąaeMHH HayK CCCP, Ceprni XHMHHecKaa 1983 (4), 941-943; SU 1020422, C07C 50/18, 1983], only in this case is the reaction carried out in the presence of a large excess of diphenyl. The target product 2- (4'-phenylbenzoyl) benzoic acid is highly contaminated with diphenyl and, except for the product in the complex manner described above, the acid (I) is further crystallized four times from acetic acid. The product is obtained in 70-75% yield.

In later works [A.Amoldi, A. Bassoli, G. Borgonovo, L. Merlini, G. Morini.

Synthesis and structure-activity relationships of sweet 2-benzoylbenzoic acid derivatives. Journal of Agricultural and Food Chemistry, 1997, vol. 41 (4), p. 2047-2054; C.A. 127, 33088] essentially reproduces the methods previously published in the literature.

Therefore, the search for a simpler and more technological way to obtain a high purity product without reducing its yield has been a topical issue for many years.

The present invention provides a simple and efficient process for the preparation of 2- (4'-phenylbenzoyl) benzoic acid (I) by reaction in a solvent, and the sequence and proportions of the components added to the reaction mixture are determined.

Specifically, the novel process for the preparation of 2- (4'-phenylbenzoyl) benzoic acid, in which the diphenyl is acylated by phthalic anhydride under catalytic conditions, is characterized by starting the reaction in a cooled solvent and adding the catalyst in portions, optimally introducing about half the required amount of catalyst followed by addition of the remainder and heating of the reaction mixture.

The solvent is selected from methylene chloride, 1,2-dichloroethane or nitrobenzene and cooled to 05 ° C.

It uses Lewis acid as the catalyst, preferably aluminum trichloride or titanium tetrachloride.

LT 551O B

In the initial stage, the molar ratio of diphenyl: phthalic anhydride to Lewis acid is about 1: 1: 1, and the remainder of the Lewis acid is gradually added to the reaction mixture and heated to 40-65 ° C. After the addition of all the required amount of Lysic acid, the reaction mixture is additionally maintained at said temperature, preferably for 2-4 hours.

After the reaction, the product is treated and not necessarily purified by conventional means.

Specific embodiments of the present invention are described below. The following examples are provided to illustrate the invention and are not intended to limit the scope of the invention.

For the preparation of 2- (4'-phenylbenzoyl) benzoic acid, slight deviations from the following procedure are possible - a slightly different temperature or reaction solvent, product isolation technique, flushing solvent. Obviously, these deviations or the use of equivalent means do not alter the spirit of the invention.

An example

Add 4 L of 1,2-dichloroethane to a 6 L flask, cooled in an ice bath. The solvent is cooled to 0-5 [deg.] C. with stirring, and 462 g (3 mol) of diphenyl, 400.5 g (3 mol) of anhydrous aluminum chloride and 444 g (3 mol) of crushed phthalic anhydride are added. The reaction mixture is heated to 40 [deg.] C. with stirring, and a further 400.5 g (3 mol) of aluminum chloride are gradually added thereto, maintaining the temperature at 40-50 [deg.] C. Spread at such a rate that hydrogen chloride will not diffuse excessively (it is trapped in a dilute aqueous alkaline solution trap). After the addition of all the aluminum chloride, the reaction mixture was stirred at the said 40-50 ° C for a further 2 hours until the hydrogen chloride ceased. The contents of the flask are poured into 12 liters of ice-water mixture while stirring, until the aluminum salts-aromatic complex is completely decomposed, then filtered. The white amorphous precipitate was washed twice with water, once with methanol, and dried at 120 ° C.

860 g of pure (thin layer chromatography: Silufol, ethyl acetate, Rf 0.45) were obtained in 2- (4'-phenylbenzoyl) benzoic acid in 95% yield. Lyd. temp. 231-232 ° C.

1 H NMR (CDCl ₃ , □, md): 7.25 (3H, dd, J 1 = 7.7 Hz, J ₂ = 7.2 Hz), 7.39 (2H, dd, J 1 = 7.3 Hz,

J ₂ = 1.2 Hz), 7.57 (3H, d, J = 7.7 Hz), 7.93 (1H, d, J = 7.9 Hz), 8.04 (2H, d, J = 8.9 Hz), 8.19 (2H, d, J) = 8.9 Hz).

The filtrates separate the organic layer, washing and distilling off the 1,2-dichloroethane, which is suitable for reuse.

LT 551O B

An example

Place 4 L of methylene chloride in a 6 L flask, cooled in an ice bath. The solvent is cooled to 0-5 ° C with stirring, and 308 g (2 mol) of diphenyl, 267 g (2 mol) of anhydrous aluminum chloride, 296 g (2 mol) of crushed phthalic anhydride are added. The reaction mixture is heated to 40 [deg.] C. with stirring, and a further 267 g (2 mol) of aluminum chloride are gradually added thereto, maintaining the temperature at 40-43 [deg.] C. Spread at a rate such that hydrogen chloride is not released (it is trapped in a dilute aqueous alkaline solution trap). After the addition of all the aluminum chloride, the reaction mixture was stirred at the said 40-43 ° C for a further 4 hours until the hydrogen chloride ceased. The contents of the flask are poured into 12 L of ice-water mixture with stirring, stirred until the aluminum salts-aromatic complex is completely decomposed, then filtered. The white amorphous precipitate was washed twice with water, once with methanol, and dried at 120 ° C.

550 g of pure (thin layer chromatography) 2- (4'-phenylbenzoyl) benzoic acid were obtained in 91% yield.

An example

Add 4 L of 1,2-dichloroethane to a 6 L flask, cooled in an ice bath. The solvent is cooled to 0-5 [deg.] C. with stirring, 462 g (3 mol) of diphenyl, 444 g (3 mol) of crushed phthalic anhydride are added and 568 g (3 mol) of titanium tetrachloride are added dropwise. The reaction mixture was heated to 60 ° C with stirring and a further 568 g (3 mol) of titanium tetrachloride was added dropwise, maintaining the temperature at 60-65 ° C. Apply at such a rate that hydrogen chloride is not released (it is trapped in a dilute aqueous alkaline solution trap). After the addition of all the titanium tetrachloride, the reaction mixture was stirred at the said temperature of 60-65 ° C for a further 2 hours until the hydrogen chloride ceased. The contents of the flask are poured into 12 L of ice-water mixture with stirring, stirred until the titanium salt-aromatic complex is completely decomposed, then filtered. The white amorphous precipitate was washed twice with water, once with methanol, and dried at 120 ° C.

597 g of pure (thin layer chromatography) 2- (4'-phenylbenzoyl) benzoic acid were obtained in 66% yield.

An example

Add 4 L of nitrobenzene to a 6 L flask, cooled in an ice bath. Cool the solvent to 0-5 ° C with stirring and add 308 g (2 mol) diphenyl, 267 g (2 mol) anhydrous aluminum chloride,

296 g (2 mol) of crushed phthalic anhydride. The reaction mixture is heated to 40 [deg.] C. with stirring, and a further 267 g (2 mol) of aluminum chloride are gradually added thereto, maintaining the temperature at 40-43 [deg.] C. Spread at such a rate that hydrogen chloride will not diffuse excessively (it is trapped in a dilute aqueous alkaline solution trap). After the addition of all the aluminum chloride, the reaction mixture was stirred at the said 40-43 ° C for a further 4 hours until the hydrogen chloride ceased. The contents of the flask are poured into 12 liters of ice-water mixture while stirring, until the aluminum salts-aromatic complex is completely decomposed, then filtered. The white amorphous precipitate was washed twice with water, once with methanol, and dried at 120 ° C.

344 g of pure (thin layer chromatography) 2- (4'-phenylbenzoyl) benzoic acid were obtained in 57% yield.

Example (Comparative).

Add 4 L of 1,2-dichloroethane to a 6 L flask, cooled in an ice bath. The solvent is cooled to 0-5 [deg.] C. with stirring, and 801 g (6 mol) of anhydrous aluminum chloride and 444 g (3 mol) of crushed phthalic anhydride are added. The reaction mixture is heated to 40 [deg.] C. with stirring and 462 g (3 mol) of diphenyl are gradually added dropwise, maintaining the temperature at 40-50 [deg.] C. Spread at such a rate that hydrogen chloride will not diffuse excessively (it is trapped in a dilute aqueous alkaline solution trap). After the addition of all diphenyl, the reaction mixture was stirred at the said 40-50 ° C for a further 2 hours until the hydrochloride ceased to separate. The contents of the flask are poured into 12 liters of ice-water mixture, stirring, until the aluminum salts-aromatic complex is completely decomposed. A viscous colored resin is obtained which does not yield the desired 2- (4'-phenylbenzoyl) benzoic acid.

As can be seen from the examples above, the production of material (I) in the novel process of the present invention requires neither complicated equipment nor time-consuming and energy-intensive procedures. The result of the resulting process under surprisingly simple conditions is that the acid (I) is almost quantitatively obtained (yield up to 95%) and is immediately of high purity.

Claims (6)

A process for the preparation of 2- (4'-phenylbenzoyl) benzoic acid wherein the diphenyl is acylated with phthalic acid anhydride under catalytic conditions, wherein the reaction is initiated in a cooled solvent and the catalyst is added in portions, optimally adding about half the required amount of catalyst. adding the remainder of the product, both heating the reaction mixture and completing the reaction, does not necessarily purify the product by conventional means. 2. A process according to claim 1, wherein the solvent is cooled to 0-5 ° C. 3. A process according to claim 1 and / or 2, wherein the solvent is selected from the group consisting of methylene chloride, 1,2-dichloroethane and nitrobenzene. 4. A process according to any one of claims 1 to 3, wherein the catalyst is Lewis acid, preferably aluminum trichloride or titanium tetrachloride. 20th 5. A process according to any one of claims 1-4, wherein the molar ratio of diphenyl, phthalic anhydride and Lewis acid in the initial step is about 1: 1: 1. 6. A process according to any one of claims 1-5, wherein the remaining Lewis acid is added to the reaction mixture gradually and with heating to 40-65 ° C. The reaction mixture is kept at said temperature, optimally for 2 to 4 hours.