US20070010686A1

US20070010686A1 - Method of preparing phenylacetic acid

Info

Publication number: US20070010686A1
Application number: US11/325,856
Authority: US
Inventors: Elmira Ramazanova; Alimamed Shabanov
Original assignee: Property Development Corp International Ltd Inc
Current assignee: Property Development Corp International Ltd Inc
Priority date: 2005-07-08
Filing date: 2006-01-05
Publication date: 2007-01-11
Also published as: WO2007054768A2; US20070010696A1; WO2007054768A3; CA2656354A1; CA2653386A1; US7393981B2; US20080097128A1

Abstract

A method of preparing phenylacetic acid comprising phase-transfer carboxylation of benzyl sodium in the presence of a salt catalyst.

Description

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a continuation-in-part of copending and coassigned application Serial No. 11/177,893, filed Jul. 8, 2005 by Shabanov and Ramazanova.

FIELD OF INVENTION

The present invention relates to methods of preparing phenylacetic acid.

BACKGROUND OF INVENTION

Current processes for the production of phenylacetic acid using sodium-toluene, and chlorobenzene as precursors are slow and do not provide a high yield. Non-catalytic methods are not cost-effective, stable methods for the production of phenylacetic acid because of the long duration of the benzylchloride metaliation, benzylsodium production, and carboxylation stages. This makes the current processes expensive and time-consuming and therefore unsuited for continuous-process industrial production of phenylacetic acid.
Further, current processes for the production of phenylacetic acid can be used only under laboratory conditions aiming at producing small amounts of the product. Further, the purity of the product obtained is not high due to the formation of byproducts (phenylmalonic acid, etc.), which requires supplementary purification. This creation of byproducts reduces output to 65-70%. Further, current processes are environmentally unfriendly and are not capable of being carried out in a stainless steel reactor. Thus, the current processes for the production of phenylacetic acid are not economically expedient and fail to be useful as continuous methods of phenylacetic-acid industrial production.
A need exists, therefore, for a process that reduces the process time and increases the yield of phenylacetic acid, thereby providing a commercially-viable method for the production of phenylacetic acid.
All references cited herein are incorporated by reference to the maximum extent allowable by law. To the extent a reference may not be fully incorporated herein, it is incorporated by reference for background purposes and indicative of the knowledge of one of ordinary skill in the art.

SUMMARY OF INVENTION

The principles of the present invention are embodied in methods of preparing phenylacetic acid utilizing phase-transfer carboxylation of benzyl sodium in the presence of a salt catalyst.
Embodiments of the present principles realize a number of significant advantages. Among other things, application of these principles advantageously reduces process time and the formation of byproducts, and increases the phenylacetic acid yield.

BRIEF DESCRIPTION OF DRAWINGS

For a more complete understanding of the present invention, and the advantages thereof, reference is now made to the following descriptions taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a block diagram of a representative system embodying the principles of the present invention;
FIG. 2 is a schematic flow diagram illustrating an exemplary process embodying the principles of the present invention; and
FIG. 3 is a schematic flow diagram illustrating another exemplary process embodying the principles of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The principles of the present invention and their advantages are best understood by referring to the illustrated embodiment depicted in FIGS. 1-2 of the drawings, in which like numbers designate like parts.
Referring to FIG. 1, there are four basic steps to the inventive phenylacetic acid production process. Some of the basics of the process can be found in Gilman, Henry, et al, “Benzylalkali Compounds,” J. Am. Chem. Soc., Vol. 62,1514 (1940); Nobis, John, et al, “Phenylsodium Route to Phenylacetic Acid and Dimenthyl Phenylmalonate,” Indus. Eng. Chem. Vol. 46, No. 3, 539 (1954); Morton, Avery and Ingenuin Hechenbleikner “Condensations by Sodium. VII. Solvent Exchange Reactions, Preparation of Phenylmalonic Acid, and Comments on Some Mechanisms of Reactions which Employ Sodium,” J. Am. Chem. Soc., Vol. 58, 2599 (1936); Morton, Avery, et al, “Condensations by Sodium. XII. Mechanism of Formation of Phenylmalonic Acid and the Syntheses of Butyl- and Phenylmalonic Acids from Monocarboxylic Acids,” J. Am. Chem. Soc., Vol. 60,1426 (1938); R. L. Letsinger, “The Preparation of Optically Active Hydrocarbons by the Wurtz Reaction,” J. Am Chem. Soc., Vol. 70, 406 (1948); Gilman, Henry, and H. A. Pacevitz, “The Carbonation of Organoalkali Compounds,” J. Am. Chem. Soc., Vol. 62,1301 (1940); Hansley, V. L., “Sodium Reduction of Fatty Acid Esters,” Indus. Eng. Chem., Vol. 39, 55 (1947); and Pacevitz, H. A., “Lateral Organoalkali Compounds,” Chem. Abstracts, Vol. 36, 4475 (1942); incorporated herein by reference.
First, an alkali metal, a phenyl halide, a solvent, and a catalyst are combined. An example of this is combining sodium, chlorobenzene, toluene, and a catalyst. Under proper processing conditions, described herein, the sodium and chlorobenzene react to form phenylsodium. Second, this reaction mixture is boiled, which causes the phenylsodium and toluene to react and form benzylsodium. Third, the reaction mixture is carbonized, preferably over dry ice, hydrolyzed, and acidified, which leads to the formation of phenylacetic acid. Finally, the phenylacetic acid is crystallized and recovered from the reaction mixture.
In more detail, referring to FIG. 2, metallic sodium and toluene are added to a preliminary reactor 1 for sodium disintegration. A special-purpose, high-speed mixer 12, preferably capable of achieving at least 10,000 revolutions per minute, is switched on to crush the sodium and to produce a sodium-in-toluene suspension. Preferably, the mixer need only be used for around 1-1.5 minutes. The suspension is then cooled down to around 25-30° C.
A solution containing equivalent amounts of chlorobenzene and dry toluene with around 0.0005-0.001% catalyst calculated on sodium are contained in a chlorobenzene tank 11. Effective catalysts are cryptands and crown compounds, such as crown ethers. Preferably, the macrocyclic-catalyst will have a cavity size which corresponds to the ion radius of sodium. The preferred catalysts are cryptand [2,2,2] and 16-crown-5. An equivalent amount of the solution from the chlorobenzene tank 11 is added to and mixed with the preliminarily prepared suspension of metallic sodium in toluene in the preliminary reactor 1. This mixture is transferred to a phenylsodium-conversion reactor 3 with the sodium particle size not to exceed 20-25 microns.
Alternatively, the solution from the chlorobenzene tank 11 can be added directly to the phenylsodium-conversion reactor 3 without premixing the solution with the suspension in the preliminary reactor 1. Another alternative is to add the chlorobenzene and catalyst to the preliminary reaction mixture in the preliminary reactor 11 prior to initial mixing.
For a phenylsodium-conversion reactor of 2 liter volume, the feed rate of the reagents to the phenylsodium-conversion reactor should be around 4.3 mol/hr. The reactor can have an external cooling jacket.
The temperature in the phenylsodium-conversion reactor 3 is maintained in the range of around 27-40° C. by regulating the reagent feed rates and the external cooling of the phenylsodium-conversion reactor 3. The preferred amount of catalyst is 0.001% based on sodium. More than 0.001% catalyst can be used, but the economics for larger amounts of catalyst are not as good as for the preferred amount. All process steps should be carried out in an inert atmosphere such as nitrogen. Generally, any dry gas may be used in this process.
Approximately every 10 minutes the suspension accumulated in the phenylsodium-conversion reactor 3 is transferred into a reserve tank 6 where mixing is continued. The temperature of the reserve tank 6 is maintained preferably at 30-40° C. Upon reaching a desired volume, the suspension in the reserve tank 6 is transferred to a benzylsodium-conversion reactor 7. The suspension is boiled in the benzylsodium-conversion reactor 7. Boiling is maintained for approximately 0.5-1.5 hours, preferably for 1.0-1.5 hours.
After boiling in the benzylsodium-conversion reactor 7, the prepared benzylsodium suspension is transferred to a cooling tank 9 where the benzylsodium suspension is cooled to 25° C. Following cooling in the cooling tank 9, the benzylsodium suspension is discharged by jet onto disintegrated dry ice in the carbonation reactor 10 and slowly mixed. Alternatively, liquid CO₂may be used. The dry ice in the carbonation reactor 10 is in an amount of 20 fold mole excess based on benzylsodium.
After volatilization of the CO₂, the residue is hydrolyzed with water by mixing and cooling in the carbonation reactor 10. The volume of water used for hydrolysis is equal to 25-35% of the toluene volume.
The aqueous layer is then separated from the toluene layer and is acidified, preferably with hydrochloric acid. The pH is preferably lowered to a pH of approximately pH 2.
The phenylacetic acid is then crystallized and separated from the water. The phenylacetic acid prepared by the invented process has a melting temperature of 75-76° C.
1. Experiment:
4.7 g. of sodium, 30 ml of absolute toluene and 6 mg of catalyst are put into a stainless-steel preliminary reactor that has a mixer capable of mixing at 10,000 revolutions per minute, a heater, a backflow condenser, a viewing window, and a cooling jacket. All processes are carried out in a dry-nitrogen atmosphere. The reactor is heated up to the toluene boiling point. Then the high-speed mixer is switched on for 1-1.5 minutes for sodium crushing.
The suspension is then cooled down to 25-30° C. and placed in a phenylsodium-conversion reactor. 5-8ml of a chlorobenzene and toluene solution, made by mixing the 2 reagents in equal proportion with catalyst, is added to toluene-sodium suspension while mixing and cooling the reactor to 27-40° C. The reaction begins immediately and black sediments of phenylsodium are generated in the reactor. The temperature of reaction mixture is kept at 27-40° C. The chlorobenzene metallizing reaction takes approximately 1 hour.
The suspension of phenylsodium is taken from the phenylsodium-conversion reactor to a reserve tank, where reaction is completed in a nitrogen atmosphere. In order to transform phenylsodium into benzylsodium, the contents of the reserve tank are placed into a benzylsodium-conversion reactor, where the suspension boils for 1-1.5 hours. While boiling, the solution's color gets brick-red and then black again.

Upon completion of the reaction, the hot solution is removed from the benzylsodium-conversion reactor and placed into a cooling tank. Then as soon as possible, the cooled reaction mass is poured into crushed dry ice in a carbonation reactor and mixed. When vaporization of the CO₂is completed, 20 ml of water is added to the residue during cooling and mixing. The water layer is then separated and acidulated with hydrochloric acid to a pH around pH 2. The generated sediment phenylacetic acid is separated by filtration in a vacuum-filter. 12.5 g. of phenylacetic acid (92%) with melting point 77° C. is produced. The results of other experiments are given in the Table 1.

TABLE 1


Experimental results of PhAA production in the
absence and presence of catalyst respectively

	PhAA production	PhAA yields
	in the absence	in the presence
	of catalyst, %	of catalyst, %
	Rate of addition of	Rate of addition
	toluene solution of	of toluene solution
Time of	chlorobenzene and	of chlorobenzene and
boiling of	toluene suspension of	toluene suspension
phenylsodium	sodium, 4.3 mole/hr.	of sodium, 4.3 mole/hr.

in toluene, hr.	2.5	3.5	4.3	5	2.5	3.5	4.3	5

0.5	16.2	18.9	27	33	66	74	75	70
1	34.6	40.5	48	54	83.5	90	94.5	89
2	42.8	44.8	52	58	83.4	89.8	93.7	86.7
3	52.5	60.4	62.5	69	80.8	90.6	90.3	85.9
4	49.6	58.4	66.5	—	76	87	88	80.8

Table 1 shows that including a catalyst greatly increases phenylacetic-acid yield . The highest yield of the product is observed when the time of boiling in toluene equals 1 hour time. Further increase in boiling time causes a decrease in desired product field. Also, the application of a catalyst improves the stability of the results.
It was also observed that the increase in catalyst amount to 0.001% leads to a raise in yield of the desired product. Further increases in catalyst amount do not generally give an increase of the desired product.
The principles of the present invention are also embodied in methods for forming phenylacetic acid using phase transfer techniques, particularly to the phase-transfer catalytic carboxylation of benzyl-sodium in toluene/benzene in presence of a salt such as [N(C₄H₉)₄]X.
Carboxylation of benzyl-sodium in solid-liquid phase-transfer catalysis condition realizes many advantages. For example, carboxylation processes using the phase-transfer catalysis techniques of the present inventive principles consume less dry ice. Further, these phase-transfer catalysis techniques prevent minor byproduct formation reactions. Additionally, phase-transfer catalysis techniques also the simplify phenylacetic acid preparation process.
According to the principles of the present invention, a carboxylation reaction 1, 2 and 3 is carried out by mixing a toluene/benzene suspension of benzyl-sodium with a toluene solution of the tetra-ethyl-ammonium-chloride and adding the prepared mixture to crushed dry ice.
One representative carboxylation of benzyl sodium process according to the inventive principles is shown in the process diagram of FIG. 3. To 11.45 g (0.1 mol) of toluene/benzene solution of benzyl-sodium, prepared from 11.25 g (0.1 mol) of chlorobenzene, 9.4 g (0.2 mol) of sodium and 60 ml of toluene as described above and shown at Block 31 in FIG. 3, is added 1.1 g of [(C₄H₉)₄N]X(X═Cl, Br) in toluene (12 ml) under nitrogen at 25-27° C. (Block 32). The mixture is stirred 15 min and is added slowly to crushed dry ice (Block 33). The mixture is kept until removal of dry the ice (in CO₂form), and then the residue is treated with HCl (hydrochloric) acid (10%, pH=1) (Block 34) and the sediment of phenylacetic acid is separated and crystallized from water (Block 35). Yield of pure phenylacetic acid is 13.32 g (98%). Melting point of prepared product is 77° C.
The toluene/benzene solution containing the phase-transfer catalyst may be recycled many times in the carboxylation process with no loss in catalytic activity. Phenylacetic acid is thus obtained to the extent of more than 800 moles per mole of [(C₄H₉)₄N]Br taken.
Another important advantage of this system is the possibility of achieving selective carboxylation of benzyl-sodium yield of phenylacetic acid, and a carboxylation yield to 96-98%. An important practical aspect of this process is the continuous separation of the product from the catalyst, which in effect heterogenizes the homogenous catalyst. This point accounts for the high catalyst turnover, the selectivity encountered in the carboxylation of benzyl-sodium and the high activity of the catalyst.

Table 2 summarizes experimental results demonstrating carboxylation processes using the phase-transfer catalysis techniques of the present inventive principles.

TABLE 2


Mass-balance of laboratory pilot plant experiment
on preparation of phenylacetic acid

					Amount of
		Amount		Compound	formed and
	Compounds	of taken		prepared and	returned
	taken to	to reaction		returned other	compounds,
No	reaction	compounds, g	No	reaction, g	g

1	Chlorobenzene	56.3	1	Phenylacetic	66.7
				acid
2	Sodium	27.0	2	Returned	123.62
				toluene
3	Toluene	187.5	3	Formed	35.9
				benzene
4	Dry ice	440	4	Lost toluene	14.58
5	Hydrogen	214	5	Lost benzene	3.1
	chloride acid
	10%
6	Catalyst	0.27	6	Returned dry	418
				ice in from of
				CO₂
7			7	Catalyst	0.27
8			8	Water	192.6
9			9	Minor products	2.3
10			10	NaCl	68
	Sum	925.07		Sum	925.07

* Theoretical yield of phenylacetic acid on chlorobenzene is 98%

Although the invention has been described with reference to specific embodiments, these descriptions are not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternative embodiments of the invention, will become apparent to persons skilled in the art upon reference to the description of the invention. It should be appreciated by those skilled in the art that the conception and the specific embodiment disclosed might be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. It should also be realized by those skilled in the art that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the appended claims.
It is therefore contemplated that the claims will cover any such modifications or embodiments that fall within the true scope of the invention.

Claims

1. A method of preparing phenylacetic acid comprising phase-transfer carboxylation of benzyl sodium in the presence of a salt catalyst.

2. The method of method of claim 1, comprising:

combining chlorobenzene and sodium in a solution to produce a mixture;

adding the catalyst;

adding dry ice to the mixture;

maintaining the mixture until removal of the dry ice in gaseous form;

treating the remaining residue with hydrochloric acid; and

separating the phenylacetic acid from the remaining solution including the catalyst.

3. The method of claim 1, wherein the catalyst comprises a tetra-ethyl-ammonium-halide.

4. The method of claim 3, wherein the catalyst is selected from the group consisting of tetra-ethyl-ammonium-chloride and tetra-ethyl-ammonium-bromide.

5. The method of claim 2, wherein combining chlorobenzene and sodium in a solution comprises combining chlorobenzene and sodium in a solution of toluene/benzene.

6. The method of claim 2, wherein separating the phenylacetic acid from the solution including the catalyst comprises continuous separation of the phenylacetic acid and the catalyst.

7. The method of claim 2, further comprising recovering the catalyst in solution for reuse.

8. The method of claim 2, further comprising crystallizing the phenylacetic acid from water.

9. A method of preparing phenylacetic acid comprising:

combining benzyl-sodium with a tetra-ethyl-ammonium-halide catalyst;

adding dry ice to the mixture;

maintaining the mixture until removal of the dry ice in gaseous form;

treating a residue with hydrochloric acid; and

10. The method of claim 9, wherein the a tetra-ethyl-ammonium-halide catalyst is selected from the group consisting of a tetra-ethyl-ammonium-chloride and a tetra-ethyl-ammonium-bromide.

11. The method of claim 9, further comprising:

recovering the catalyst in the remaining solution; and

reusing the recovered catalyst during a subsequent combination of chlorobenzene and sodium for preparation of phenylacetic acid.

12. The method of claim 9, wherein adding dry ice to the mixture comprises adding crushed dry ice to the mixture.

13. The method of claim 9, further comprising combining chlorobenzene with sodium in a toluene solution to produce the benzyl-sodium.

14. The method of claim 9, wherein combining benzyl-sodium with a tetra-ethyl-ammonium-halide catalyst comprises adding the a tetra-ethyl-ammonium-halide catalyst with the benzyl-sodium in toluene under nitrogen at a temperature of in the range of approximately 25 to 27 degrees Celsius.

15. The method of claim 9, further comprising stirring the mixture while slowly adding the dry ice.