CA2148540A1 - Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides - Google Patents

Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides

Info

Publication number
CA2148540A1
CA2148540A1 CA 2148540 CA2148540A CA2148540A1 CA 2148540 A1 CA2148540 A1 CA 2148540A1 CA 2148540 CA2148540 CA 2148540 CA 2148540 A CA2148540 A CA 2148540A CA 2148540 A1 CA2148540 A1 CA 2148540A1
Authority
CA
Canada
Prior art keywords
alkyl
halogen
bis
catalyst
water
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA 2148540
Other languages
French (fr)
Inventor
Christian Kohlpaintner
Matthias Beller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hoechst AG
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2148540A1 publication Critical patent/CA2148540A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
    • B01J31/2208—Oxygen, e.g. acetylacetonates
    • B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
    • B01J31/2252—Sulfonate ligands
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
    • B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/10—Preparation of carboxylic acids or their salts, halides or anhydrides by reaction with carbon monoxide
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/824—Palladium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/84—Metals of the iron group
    • B01J2531/845—Cobalt
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/90—Catalytic systems characterized by the solvent or solvent system used
    • B01J2531/96—Water
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2540/00—Compositional aspects of coordination complexes or ligands in catalyst systems
    • B01J2540/30—Non-coordinating groups comprising sulfur
    • B01J2540/32—Sulfonic acid groups or their salts

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Materials Engineering (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Fats And Perfumes (AREA)

Abstract

The invention relates to a process for preparing aryl-acetic acid derivatives of the formula (I) (I) where R1 is hydrogen, halogen, , , (C1-C8)alkyl, phenyl, which can each also be substituted by hydroxy and amino groups, R2 is hydrogen, (C1-C8)-alkyl, phenyl, and Ar is phenyl, naphthyl, anthracenyl, phenanthrenyl, each of which may be unsubstituted or substituted by halogen, OH, polyfluoro-(C1-C8)-alkyl, CN, (C1-C4)-alkoxy, NO2, COO-(C1-C4)alkyl, CON[(C1-C4)alkyl]2, NH(C1-C4)alkyl, N[(C1-C4)alkyl]2, NH2, SO3H, SO3 ( C1 - C4 ) alkyl, SO2NH2, O-CO-(C1- C4 ) alkyl, CH2-halogen, which comprises carbonylating compounds of the formula (II)

Description

- 214854~
-HOECHST A~L~ SELLSCHAFT HOE 94/F 121 Dr.MU/pe Description Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides The invention relates to a process for preparing aryl-acetic acid derivatives by carbonylation of arylmethyl halides.

Arylacetic acids and their derivatives are valuable intermediates for the preparation of pharmaceuticals, scents and fragrances.

Arylacetic acids can be prepared from the correspo~; ng benzyl halides by converting these by Cl/CN eY~c-h~nge into the benzyl cyanides and saponifying the latter in a second process step to give the arylacetic acids.

The process is described, for example, in Rampp Chemie LeY;kon, 9th Edition 1991, Volume 4, page 3361 or Ullmann, 4th Edition 1976, Volume 11, page 71. Disadvan-tages are the use of NaCN for the Cl/CN ~Yrh~nge~ the formation of salt twice (lst step NaCl, 2nd step (NH4)2SO4) and the operating procedure in a two-step process.

More advantageous is the reaction of benzyl halides with carbon monoxide which enables the arylacetic acids to be obtained directly in a single-step process. This reaction is catalyzed by metals of the transition group VIII and is distinguished by the catalyst being homogeneously dissolved, together with the starting material, in an organic phase. The carboxylic acid formed as an inter-mediate during the reaction is converted into the salt by the simultaneous presence of an agueous basic solution and is also dissolved in this aqueous phase. At the end of the reaction, the aqueous phase cont~;n;ng the salt of ~1~8S4~
-carboxylic acid is separated off and the free acid is isolated by acidification with a suitable mineral acid and extraction with a suitable, water-immiscible solvent.

For example, according to FR 1 313 360, the catalyst used is the sodium salt of tetracarbonylcobaltate tNaCo(CO) 4]
together with an amine. IT 14 359 describes the procedure using Ni(CO) 4 in DMF or DMSO in the presence of iodides and alkaline earth metal oxides such as CaO and MgO. The use of 5 % palladium on activated carbon is described in JP 04 661 221. The carbonylation reaction can also be carried out, as described in DE 2 240 398, using Co2(CO)8 and metal alkoxides such as NaOMe. Here, iron pentacarb-onyl can also take the place of Co2(CO) 8 (DE 2 259 072).
Phosphane-modified palladium complexes [(PR3)2PdCl2] are likewise used according to DE 2 526 046. To accelerate the reaction, a phase transfer reagent, for example tetrabutylAmmo~;um iodide, is added. Rhodium catalysts based on RhCl3 with the presence of iodides have likewise been described for thi~ reaction (DE 2 606 655).

All these proces~es have in common the presence of the catalyst in the organic phase, while, as a result of the addition of aqueous basic solution, the product is located in the water phase. The free acid is isolated by acidification of the aqueous phase after it has been separated off.

These processes have a series of disadvantages. The base has to be added in a large excess, since the target product remainæ in the aqueous phase only in the form of its salt. The acid HX formed during the reaction gradu-ally neutralizes the base and, in the case of insuffi-cient addition of base, would liberate the phenylacetic acid whose solubility is greater in the organic medium than in the aqueous phase. A product-catalyst separation by simple phase separation would no longer be possible.
For this reason, a large excess of base has to be selected. The frequently used caustic alkalis such as 21~8~4~
the yield of phenylacetic acid when used in large excess, since the starting material benzyl halide i8 rapidly hydrolyzed in the strongly alkaline region to give the correspo~;ng benzyl alcohol. In addition, the strongly baæic conditions lead to more rapid catalyst deactivation.

The reaction in two-phase systems organic/aqueous is generally accelerated by the addition of phase-transfer reagents. Quaternary ammonium salt~ having amphiphilic properties are usually used for this purpose. To obtain satisfactory reaction rates, these reagents are addi-tionally added for the carbonylation of benzyl halides.

In the procedures prescribed, the metal catalysts are soluble to a small extent in the aqueous phase. This results in a steady metal 1088 by discharge with the product phase. This leads to a gradual reduction in the activity of the catalyst solution. Traces of metal in the product additionally cause a lowering of quality, which can only be eliminated by complicated separation processes.

In general, relatively large amounts of catalyst (from 1 to 30 mol% of metal, based on the starting material) are necessary to obtain satisfactory conversions per unit time. This has an additional adverse effect on the cost balance of such processes. The clear reactivity order I ~ Br ~ Cl for the benzyl halides restricts, in many cases, the use of the process to the usually expensive benzyl bromides and iodides. The selectivity with regard to the phenylacetic acid can be significantly reduced by the increased formation of phenylacetaldehyde (cf.
JP 60 019 734) and make these processes unfavorable in terms of costs.

The salt of the phenylacetic acid formed during the reaction has to be converted into the free carboxylic acid using a mineral acid after separation of the aqueous 21~8540 phase. For this purpo~e, a second process step is necess-ary in addition to the actual catalysis process. The formation of salts in this procedure leads to a deterio-ration of the ecological balance. To separate the acid from the salt formed in the neutralization process, a further process step is necessary, for example, extrac-tion using an organic solvent.

The carbonylation using water-soluble catalysts has hitherto been mentioned in three studies. The use of ruthenium-EDTA complexes is described in J. Mol. Catal.
1988, 44, 179 to 181. However, this case iB not concerned with a procedure in a two-phase system, since the solvent used is a water/ethanol mixture whose mixing ratio (2:8) has to be adhered to very exactly to prevent precipita-tion of the catalyst. The presence of the alcoholconsistently leads to selectivity losses, since the corresponding ester of phenylacetic acid is formed to a greater extent.

Palladium complexes modified with tppms (sodium tri-phenylphosphanemonosulfonate) are described in J. Mol.
Catal. 1989, 54, 65 to 71. These catalysts have the disadvantage of significantly lower solubility in water and correspo~;ngly increased solubility in organic solvents. This leads to incomplete product-catalyst ~eparation, to 1088 of metal and to reduction of the product quality. In addition, at the end of the reaction the product has to be extracted into an organic phase by acidification with HCl.

The use of Co2(C0) 6 (tppts) 2 catalyst~ $or the carbonyl-ation of phenylethyl bromide is disclosed in Applied Catalysis A: General 1993, 102, 53 to 67. The disadvan-tages already mentioned of cobalt catalysts also apply in this case: the use of large amounts of catalyst (8 mol%), low selectivity for the monocarbonylation product (i.e.
the result i~ mainly double carbonylation to give phenyl-pyruvic acid) and as starting material the bromide which 2i~854~
__ - 5 -is much more expensive than the correspo~; ng chloride.
In this context, reference may be made to the toxic and air-sensitive properties of the expensive Co2(CO) 8.

There was thus a great need for a process which a~oids the disadvantages described and provides arylacetic acids in high yield and purity in a manner which can be easily carried out in the industry.

This object is achieved by a process for preparing arylacetic acid deri~atives of the formula (I) ~oR2 (1) Ar o where R1 is hydrogen, halogen, -c-(cl-c8) alkyl, --C-(c1-c8~alkY
Il 11 O O

(C1-C8)alkyl, phenyl, which can each also be substi-tuted by hydroxy and amino groups, R2 i~ hydrogen, (C1-C8)-alkyl, phenyl, and Ar is phenyl, naphthyl, anthracenyl, phenanthrenyl, each of which may be unsubstituted or substituted by halogen, OH, polyfluoro-(C1-C8)-alkyl, CN, (C1-C4)-alkoxy, NO2, COO-(C1-C4)alkyl, CON~(C1-C4)alkyl] 2' NH(Cl- C4 ) alkyl, N[(C1- C4 ) alkyl~2~ NH2, SO3H, 2 0 S 03 ( Cl - C4 ) alkyl, SO2NH2, O-CO-(C1- C4 ) alkyl, CH2-halogen, which comprises carbonylating compounds of the formula (II) ( I l ) A r H a I o g e n 214~54~
_ - 6 -where Ar and R1 have the meAn;ngs given above and Halogen is I, Br, Cl, using a water-soluble metal complex as catalyst in a two-phase system.

The process has been found to be favorable for compounds where Ar is R~ R3 R

where R3 to R7 are each, independently of one another, hydrogen, halogen, (C1-C4)-alkyl, OH, CN, polyfluoro-(Cl-C4)-alkyl, O(Cl-C4)alkyl, N02, COO(Cl-C4)alkyl, CH2-halogen, CON~(C1-C4)alkyl]2 or phenyl, or R3 and R4, R4 and R5, R5 and R6 or R6 and R7 together form an aro-matic ring.

Compounds which are important here are those where R3 to R7 are each, independently of one another, hydrogen, CF3, halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, OH.

Water-soluble metal complexes which have been found to be useful are compounds which contain as central atom a metal of transition group VIII, in particular palladium, rhodium, cobalt, nickel, iron, preferably palladium and cobalt.

AB ligands, the water-soluble metal complex preferably contains hydrophilic ligands, in particular hydrophilic phosphanes and amines, preferably sulfonated monophos-phanes and bisphosphanes.

Suitable hydrophilic ligands are described, for example, in Angew. Chem. 105, 1588-1609.
Here, phosphanes in particular give good results.

_ - 7 -Hydrophilicity i8 achieved in these compounds by intro-duction of sulfonic acid groups, by hydrophilic groups on the periphery, by quaternized aminoalkyl and aminoaryl substituents, by carboxylation, by hydroxyalkyl or polyether substituents and by monoquaternization of bisphosphanes. Important representatives of these groups are, for example, phosph;nohenzoic acids, phosphino-~lk~nols, phosph;no~lkylphosphonium salts, salts of 3,3',3"-phosphanetriylbenzenesulfonic acid (tppts), salts of 3-diphenylphosrh;nohenzenesulfonic acid (tppms), 1,2-bis[bis(sulfonatophenyl)phosphino]ethane, 2,4-bis[bis-(sulfonatophenyl)phosphino]pentane, 1,2-bis[bis(sulfo-natophenyl)phosphinomethyl]cyclobutane, 3,4-dimethyl-2,5,6-tris(sulfonatophenyl)phosphanorborna-2,4-diene, diphenylphosphinoethanesulfonate, 2-diphenylphosphino-ethyltrimethylammoniumsalt,2,4-bis[bis(trimethylammino-phenyl)phosphino]pentane, 3-diphenylphosphinopropionic acid.

A compound of palladium and sodium triphenylphosphane-trisulfonate (tppts) has been found to be particularlyfavorable.

The catalyst iB used in amounts of from 0.001 to 5 mol%, in particular from 0.05 to 1.0 mol%, preferably from 0.1 to 0.5 mol%, based on arylmethyl halide used.

The catalyst is here advantageously prepared in situ from a readily available metal salt, e.g. a metal halide, sulfate, oxide, nitrate, and the ligand. It is here also possible to use mixtures of various ligands, e.g. of monophosphanes and bisphosph~ne~.
In many cases, it has here been found to be useful to use a 1 to 40-fold, in particular a 2 to 20-fold, preferably a 3 to 10-fold, molar excess of ligand.

The particular advantage of this procedure is, besides the simple manner in which it can be carried out, the fact that it iB possible to avoid the use of the 214~S4~
_ - 8 -expensive, air-sensitive and toxic metal carbonyls such as, for example, Co2(CO) 8 .

Surprisingly, arylmethyl chlorides can be carbonylated without a reduction in activity just like the corre-spo~; ng bromides and iodides. The economic balance isthereby significantly improved. Side reactions which reduce the selectivity and yield cannot be observed.

The reaction is carried out in a vigorously stirred system of two solvents which are not miscible with one another (aqueous/organic). Organic solvents which have been found to be useful are aromatic and aliphatic hydrocarbons, in particular toluene, xylene, petroleum ether, hexane, iso-hexane or heptane. The organic solvent is advantageously selected in such a way that the aryl-acetic acid formed is readily soluble therein.

The aqueous solution, which is initially alkaline, isneutralized during the course of the reaction by the liberated acid HX and, above a particular pH, liberates the phenylacetic acid from the carboxylic acid salt formed. Subsequent separation of the organic phase from the aqueous phase and crystallization of the phenylacetic acid gives the product in high purity and yield. The aqueous solution, in which the catalyst is located, can be used again for the reaction.

In many cases, it has been found to be useful to carry out the reaction at temperatures of from 20 to 110C, in particular from 50 to 90C.

Depending on the substitution pattern of the arylmethyl halides used, a CO pressure of from 1 to 70 bar has been found to be suitable.

Besides pure carbon monoxide, a CO/H2 mixture of any composition can also be used.

2148~4~

`._ For the synthesis of particular substituted phenylacetic acids it is advantageous to gradually meter in the base during the reaction or to carry out the reaction within a particular pH range under pH control.

Furthermore, the addition of phase-transfer reagents such as tetraalkylammonium salts or nucleophilic reagents such as iodides can improve the conversion and/or the selec-tivity of the process.

The advantages of this procedure compared with the classical processes are manifold. An excess of base is not necessary since the reaction also proceeds in the weakly acid region and the liberation of the arylacetic acid i8 desired. Connected therewith is reduced hydroly-sis of the starting material to the correspo~;ng aryl-methyl alcohol. The process is particularly economicalsince the mineral acid HX formed during the reaction is directly utilized for the liberation of the carboxylic acid and does not have to be externally fed in after separation of the salt. The amount of salt formed is thereby halved and leads to an improvement in the eco-logical balance of the process.

Avoidance of a large excess of base significantly increases the lifetime of the catalyst in comparison with the classical processes.

A further substantial advantage of the process of the invention is that the products contain substantially lower amounts of metal salts in comparison with the processes of the prior art (Examples 8 and 9).

The following examples illustrate the invention, without limiting it to them.

~l~s~4n ` -Examples Example 1: Carbonylation of benzyl chloride 5.06 g (40 mmol) of benzyl chloride are dissolved in 30 ml of toluene and mixed with an aqueous solution of 1.14 g (2 mmol) of tppts (= sodium triphenylphosphane-trisulfonate) and 45 mg (0.2 mmol) of Pd(OAc)2 in 18 ml of water. The two-phase system is placed in a 200 ml Hastelloy autoclave, admixed with 5.4 ml (60 mmol) of a 32 % strength NaOH solution and subsequently heated at 70C under a CO pressure of 20 bar. After a reaction time of 20 hours, the autoclave is cooled, the toluene phase is separated off and evaporated to drynes~. This gives 4.79 g of a white crystalline material which contains the product in a purity of 93 %. Recrystallization from iso-hexane gives phenylacetic acid. Yield: 4.21 g (30.9 mmol, 77 % of theory).

Example 2: Carbonylation of benzyl chloride under syn-thesis gas conditions The reaction is carried out in a similar manner to Example l, but using a mixture of CO/H2 (1:1) in place of CO. Yield: 4.33 g (31.8 mmol, 79.5 % of theory).

Example 3: Carbonylation in a two-liter autoclave 101.27 g (800 mmol) of benzyl chloride and 0.354 g - (2 mmol) of PdCl2 dissolved in 400 ml of toluene are placed in the autoclave. Subsequently, 11.43 g (20 mmol) of tppts dissolved in 350 ml of water and also 129.5 ml (1.4 mol) of a 32 % strength NaOH solution are added. The autoclave is heated to 70C and brought to a pressure of 15 bar using CO. After 6 hours, the reaction is complete, which is recognized by the end of gas absorption. The autoclave is cooled to room temperature, vented and the organic phase is separated off from the aqueous catalyst phase. The organic solution is evaporated to dryness.

214~54G

This gives 94.11 g of a white product. Yield after recrystallization from iso-hexane: 87.52 g (643 mmol, 80.4 % of theory).

Example 4: Carbonylation of 4-fluorobenzyl chloride 11.6 g (80 mmol) of 4-fluorobenzyl chloride and 45 mg (0.2 mmol) of Pd(OAc) 2 are dissolved in 50 ml of toluene and admixed with 2.29 g (4 mmol) of tppts dissolved in 25 ml of water. The two-phase mixture is transferred to a 250 ml three-necked flask and flushed repeatedly with carbon monoxide. After a reaction time of 5 hours (70C), gas absorption is complete. The toluene phase is separ-ated off and evaporated to dryness. This gives 11.54 g of crude product which after recrystallization yield 10.09 g (65.4 mmol, 81.8 % of theory) of the pure product.

Example 5: Carbonylation of 2-fluorobenzyl chloride, stepwise addition of base A solution of 8.7 g (60 mmol) of 2-fluorobenzyl chloride in 30 ml of o-xylene i8, together with a solution of 1.14 g (2 mmol) of tppts in 10 ml of water, transferred to a 250 ml three-necked flask and, after addition of 5.6 ml of a 32 % strength NaOH solution (60 mmol) and 35 mg (0.2 mmol) of PdCl2, heated to 70C under a CO
atmosphere. After 5 hours and a further 1.5 hours reac-tion time, 20 mmol of NaOH are added each time. At the end of the reaction (8 hours), the supernatant organic phase is separated off, evaporated to dryness and the residue (8.97 g) is recrystallized from iso-hexane. Pure yield: 6.69 g (72.3 % of theory).

Example 6: Carbonylation of 2-chlorobenzyl chloride The reaction is carried out in a similar manner to Example 1 using 2-chlorobenzyl chloride. PdCl2 is used in place of Pd(OAc)2. Pure yield: 4.72 g (27.6 mmol, 69.2 %
of theory).

2148~4~

Example 7: Carbonylation of 2-methylbenzyl chloride 2.81 g (20 mmol) of 2-methylbenzyl chloride and 45 mg (0.2 mmol) of Pd(OAc)2 are dissolved in 20 ml of toluene, admixed with 0.46 g (0.8 mmol) of tppts dissolved in 10 ml of water and heated to 70C in a 250 ml three-necked flask under a CO atmosphere. When the mixture has reached the temperature, 1.8 ml (20 mmol) of a 32 %
6trength solution of NaOH in water are added through a septum. After a reaction time of 5 hours, a second addition of 20 mmol of base i8 made. After the CO absorp-tion stops (8 hours), the organic phase is separated off, evaporated to dryness and the residue is recrystallized from iso-hexane. Pure yield: 2.47 g (16.4 mmol, 82.8 % of theory).

Example 8:

5.8 g (40 mmol) of 2-fluorobenzyl chloride are dis~olved in 40 ml of o-xylene and, together with a solution of 1.14 g (2 mmol) of tppts and 35 mg (0.2 mmol) of PdCl2 in 20 ml of water, are transferred to a 250 ml three-necked flask. Subsequently, 7.5 g (60 mmol) of a 32 % strength NaOH solution are added. The reaction mixture is stirred for 16 hours at T = 70C under a CO atmosphere (atmos-pheric pressure). At the end of the reaction time, the organic phase is separated off and evaporated to dryness.
Yield: 5.83 g (94.5 % of theory) of 2-fluorophenylacetic acid. The palladium content of the product is determined by atomic absorption spectroscopy (AAS). It is ~ 1 ppm of palladium.

Example 9: Comparative example according to the prior art 5.8 g (40 mmol) of 2-fluorobenzyl chloride, together with 0.53 g (2 mmol) of triphenylphosphane and 35 mg (0.2 mmol) of PdCl2, are dissolved in 40 ml of o-xylene.
7.5 g (60 mmol) of a 32 % strength NaOH solution and also 20 ml of water are added thereto. The reaction mixture i~

21~854~

subsequently stirred for 16 hours at T = 70C under a C0 atmosphers (atmospheric pressure). At the end of the reaction time, the aqueous phase is separated off (pH = 13.8). The organic phase is extracted twice with 20 ml each time of an alkaline aqueous solution. The aqueous solutions are combined and adjusted to a pH of 1 using hydrochloric acid (AR). The aqueous phase is extracted three times with 50 ml each time of ether, the ether phases are combined, filtered and evaporated to dryness. Yield: 1.05 g (17.0 % of theory) of 2-fluoro-phenylacetic acid. The palladium content of the product is determined by means of AAS. It is 110 ppm of palladium.

Claims (15)

1. A process for preparing arylacetic acid derivatives of the formula (I) (I) where R1 is hydrogen, halogen, , (C1-C8)alkyl, phenyl, which can each also be substituted by hydroxy and amino groups, R2 is hydrogen, (C1-C8)-alkyl, phenyl, and Ar is phenyl, naphthyl, anthracenyl, phenan-threnyl, each of which may be unsubstituted or substituted by halogen, OH, polyfluoro-(C1-C8)-alkyl, CN, (C1-C4)-alkoxy, NO2, COO-(C1-C4)-alkyl, CON[(C1-C4)alkyl]2, NH(C1-C4)alkyl, N[(C1-C4)alkyl]2, NH2, SO3H, SO3(C1-C4)alkyl, SO2NH2, O-CO-(C1-C4)alkyl, CH2-halogen, which comprises carbonylating compounds of the for-mula (II) where Ar and R1 have the meanings given above and Halogen is I, Br, Cl, using a water-soluble metal complex as catalyst in a two-phase system.
2. The process as claimed in claim 1, wherein Ar is where R3 to R7 are each, independently of one another, hydrogen, halogen, (C1-C4)-alkyl, OH, CN, polyfluoro-(C1-C4)-alkyl, O(C1-C4)alkyl, NO2, COO(C1-C4) alkyl, CH2-halogen, CON[(C1-C4)alkyl] 2 or phenyl, or R3 and R4, R4 and R5, R5 and R6 or R6 and R7 together form an aromatic ring.
3. The process as claimed in claim 2, wherein R3 to R7 are each, independently of one another, hydrogen, CF3, halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, OH.
4. The process as claimed in at least one of claims 1 to 3, wherein the water-soluble metal complexes used are compounds containing as cental atom a metal of transition group VIII, in particular palladium, rhodium, cobalt, nickel, iron, preferably palladium and cobalt.
5. The process as claimed in at least one of claims 1 to 4, wherein the water-soluble metal complex con-tains hydrophilic ligands.
6. The process as claimed in claim 5, wherein the hydrophilic ligands used are hydrophilic phosphanes and amines, in particular sulfonated monophosphanes and bisphosphanes.
7. The process as claimed in claim 5, wherein the ligands used are phosphinohenzoic acids, phosphino-alkanols, phosphinoalkylphosphonium salts, salts of 3,3',3"-phosphanetriylbenzenesulfonic acid (tppts), salts of 3-diphenylphosphinobenzenesulfonic acid (tppms), 1,2-bis [bis(sulfonatophenyl)-phosphino]ethane, 2,4-bis[bis(sulfonatophenyl)phosphino]pentane, 1,2-bis[bis(sulfonatophenyl)phosphinomethyl]cyclobutane, 3,4-dimethyl-2,5,6-tris(sulfonatophenyl)phosphanor-borna-2,4-diene, diphenylphosphinoethanesulfonate, 2-diphenylphosphinoethyltrimethylammonium salt,2,4-bis[bis(trimethylamminophenyl)phosphino]pentane, 3-diphenylphosphinopropionic acid.
8. The process as claimed in at least one of claims 1 to 4, wherein the catalyst used is a compound of palladium and sodium triphenylphosphanetrisulfonate (tppts).
9. The process as claimed in at least one of claims 1 to 8, wherein from 0.001 to 5.0 mol%, in particular from 0.05 to 1.0 mol%, preferably from 0.1 to 0.5 mol%, of catalyst are used, based on arylmethyl halide used.
10. The process as claimed in at least one of claims 1 to 9, wherein the water-soluble catalyst is prepared in situ from a metal salt and the ligand.
11. The process as claimed in claim 10, wherein a 1 to 40-fold, in particular a 2 to 20-fold, preferably a 3 to 10-fold, molar excess of ligand is used in the in situ preparation of the catalyst.
12. The process as claimed in at least one of claims 1 to 11, wherein halogen in the formula (II) is chlor-ide, bromide or iodide, in particular chloride.
13. The process as claimed in at least one of claims 1 to 12, wherein the carbonylation is carried out at a temperature of from 20 to 110°C, in particular from 50 to 90°C.
14. The process as claimed in at least one of claims 1 to 13, wherein the carbonylation is carried out at a Co pressure of from 1 to 70 bar.
15. The process as claimed in at least one of claims 1 to 14, wherein the two-phase system consists of water or an alcohol/water mixture and an aromatic or aliphatic hydrocarbon, in particular toluene, xylene, hexane, iso-hexane or heptane.
CA 2148540 1994-05-04 1995-05-03 Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides Abandoned CA2148540A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4415681.2 1994-05-04
DE19944415681 DE4415681A1 (en) 1994-05-04 1994-05-04 The prepn. of aryl ethanoic acid derivs

Publications (1)

Publication Number Publication Date
CA2148540A1 true CA2148540A1 (en) 1995-11-05

Family

ID=6517251

Family Applications (1)

Application Number Title Priority Date Filing Date
CA 2148540 Abandoned CA2148540A1 (en) 1994-05-04 1995-05-03 Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides

Country Status (4)

Country Link
EP (1) EP0694522A3 (en)
JP (1) JPH0859553A (en)
CA (1) CA2148540A1 (en)
DE (1) DE4415681A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9612623D0 (en) * 1996-06-17 1996-08-21 Zeneca Ltd Chemical process

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1014957B (en) * 1974-06-11 1977-04-30 Montedison Spa PROCESS FOR THE PREPARATION OF CARBOXYLIC ACIDS FROM ORGANIC HALIDE

Also Published As

Publication number Publication date
EP0694522A2 (en) 1996-01-31
DE4415681A1 (en) 1995-11-16
JPH0859553A (en) 1996-03-05
EP0694522A3 (en) 1996-09-04

Similar Documents

Publication Publication Date Title
CA1211467A (en) Catalytic hydroformylation of olefins
Das et al. Aluminium complex as an efficient catalyst for the chemo-selective reduction of amides to amines
US4201728A (en) Hydroformylation catalyst and process
CN106513048A (en) Catalyst for nonterminal olefin hydroformylation reaction and preparation method and application of catalyst
JP4210800B2 (en) Process for hydroformylation of olefinic compounds
US4745190A (en) Selective synthesis of substituted amines
EP0283586B1 (en) Homologation process
US6051743A (en) Process for the preparation of predominantly unbranched higher primary alcohols
US4239914A (en) Process for preparing 2-(6'-methoxy-2'-naphthyl)-propionic acid
US4778905A (en) Dinuclear and water-soluble rhodium complexes and hydroformylation catalysis therewith
EP0269395A2 (en) Ruthenium-phosphine complex catalysts
JP3723602B2 (en) Palladium catalyst containing sulfonated bisphosphine as ligand, process for its preparation and its use in carbonylation reactions
Aydemir et al. Synthesis and characterizations of N, N′‐bis (diphenylphosphino)‐2‐(aminomethyl) aniline derivatives: application of a palladium (II) complex as pre‐catalyst in Heck and Suzuki cross‐coupling reactions
EP0015537B1 (en) Process for the preparation of dienoic acids
EP0545997A1 (en) Carbonylation of methanol using a novel transition metal catalyst precursor.
US6323370B1 (en) Catalytic process
US5536874A (en) Process for preparing arylacetic acid and arylpropionic acid derivatives
CA2148540A1 (en) Process for preparing arylacetic acid derivatives by carbonylation of arylmethyl halides
US4289911A (en) Process for producing methylisobutylketone
JPH04226946A (en) Process for producing sec. amine
US4543411A (en) Process for selective preparation of secondary and tertiary amines
JPS6272637A (en) Manufacture of nonadecanediol
KR100311559B1 (en) Potassium para-diphenylphosphonobenzenesulfonate ligand
EP0032548A1 (en) Process for preparing aryl and heteroaryl hexadienoic acids
US20100217040A1 (en) 2, 2', 6, 6'- tetrasubstituted aminophosphine ligand and its synthesis method

Legal Events

Date Code Title Description
FZDE Dead