WO2000069866A1

WO2000069866A1 - Preparation of alkylarylphosphines or their oxides or sulfides

Info

Publication number: WO2000069866A1
Application number: PCT/US2000/010625
Authority: WO
Inventors: John H. Hillhouse; Michael Depalo
Original assignee: Cytec Technology Corp.
Priority date: 1999-05-19
Filing date: 2000-04-19
Publication date: 2000-11-23
Also published as: AU4474200A; CA2272447A1

Abstract

Arylalkylphosphines or their oxides or sulfides are prepared by reacting an alkylphosphine or its oxide or sulfide with an aryl compound bearing a leaving group attached to a carbon atom of the aromatic ring, in the presence of a Group VIII metal as heterogeneous catalyst.

Description

PREPARATION OF ALKYLARYLPHOSPHINES OR THEIR OXIDES OR

SULFIDES

The present invention relates to the preparation of arylalkylphosphines, phosphine oxides and phosphine sulphides. BACKGROUND OF THE INVENTION

Arylalkylphosphines and their oxides and sulphides, find many industrial uses, for instance as starting materials or intermediates in synthesis, or as components in catalyst for various reactions. There are known several processes for preparing these compounds, but these tend to have disadvantages. For instance, some processes involve use of Grignard reagents and phosphine halides, which is undesirable owing to the difficulty of handling such compounds. Other processes involve use of molten sodium or powdered potassium hydroxide. Clearly it is desirable to avoid use of these compounds on an industrial scale .

It is known from US Patent No. 5,550,295 to prepare arylalkylphosphines, phosphine oxides and phosphine sulphides by reacting a primary alkylphosphine or a secondary alkylphosphine, or the corresponding oxide or sulfide, with an arylhalide in the presence of a zero valence palladium catalyst and in a solvent. The catalyst is frequently prepared in situ in the reaction mixture and the catalyst is homogenous, i.e., it is soluble in the solvent. This creates difficulty in the separation of the catalyst from the desired reaction product, particularly on an industrial scale.

SUMMARY OF THE INVENTION The present invention provides a process for preparing a mixed alkylarylphosphine , phosphine oxide or phosphine sulfide, which comprises reacting a primary or secondary alkylphosphine, phosphine oxide or phosphine sulfide with an aryl compound bearing a leaving group attached to a carbon atom of the aryl ring, in the presence of a metal of Group VIII of the Periodic Table as heterogeneous catalyst. ^' DESCRIPTION OF THE PREFERRED EMBODIMENTS

In one preferred embodiment the invention provides a process for preparing a compound of formula I H (x)

(X) P 11 Λr

(y)

(z)

wherein X is oxygen or sulfur, n is 0 or l, Ar is an unsubstituted or substituted aryl group, R is an unsubstituted or substituted alkyl or cycloalkyl group, x is 0 or 1, y is 1 or 2 , z is 1 or 2 , provided that when x is 0 one of y and z is 1 and when x is 1 both of y and z are 1, which process comprises reacting a compound of formula II

wherein X, n, R and z are as defined above, with an aromatic compound bearing a leaving group attached to a carbon atom of the aromatic ring, in the presence of a metal of Group VIII of the Periodic Table as heterogeneous catalyst.

In another embodiment of the invention the primary or secondary alkylphosphine is a diphosphine compound. Examples of suitable diphosphine compounds include those of formula III RHP-Q-PHR III wherein Q is a divalent group containing 2 to 15 carbon atoms, and R is as defined above. In this embodiment, with a diphosphine of formula III there may be formed products of formulae V and VI

and

where Ar is as defined above. The oxides and sulfides of the diphosphine compounds react in similar manner to yield the corresponding oxide or sulfide products .

Q can be alkylene, cycloalkylene or an arylene group, or a combination of alkylene and arylene or of alkylene and cycloalkylene. As examples of cycloalkylene groups there are mentioned those containing 4 to 8 carbon atoms, of which cyclopentylene and cyclohexylene are preferred. As examples of arylene there are mentioned phenylene and naphthylene. For example the compound of formula III can be a diphosphine derivative of bisphenol A, so that there are formed the monoaryl product of formula

and possibly the diaryl product of formula

Of the Group VIII metals the preferred catalysts include palladium, platinum and rhodium, of which the most preferred is palladium. The metal can be unsupported, or can be supported on a solid support such as, for example, carbon, alumina, silica or an organic polymer, for example polystyrene. Mention is also made of palladium/polyethyleneimine (PEI) on silica catalysts. All these catalysts are commercially available from Aldrich Chemical Company, Wisconsin. The palladium on carbon and palladium on alumina catalyst particles are usually of a mesh size in the range of about 100 to 200. Palladium on polystyrene is usually a fibre that is about 2-5 mm in length. Palladiύm/PEI on silica particles are usually of a mesh size in the range of about 20 to 40. The catalyst is- heterogeneous so that it is readily separated from the reaction mixture by, for example, filtration or decantation, which assists in the economical work-up of the reaction products and in recycling the catalyst.

The preferred catalyst is finely divided palladium metal on a carbon support. Catalysts composed of about 5% to about 10% of palladium metal or carbon are used in organic synthesis in high pressure hydrogenation reactions, and such catalysts are suitable for the present invention. The amount of catalyst employed can range from about 0.05 mole to about 10.0 mole percent, preferably from 0.1 to about 7.5 mole percent, based on the alkylphosphine charged. When a diaryl compound is required a greater amount of catalyst is used than when a monoaryl compound is required.

An important feature of the present invention is that the catalyst does not require addition of any co-catalyst to become an active arylation catalyst. This is surprising, as many arylation reactions do require a co-catalyst such as triarylphosphine or a bidentate phosphine such as 2,2'- bis (diphenylphosphino) -1, 1 ' -binaphthyl (BINAP) or 1,2- bis (diphenylphosphino) ethane (DIPHOS). Eliminating a co- catalyst of course eliminates the cost of a co-catalyst, and this is significant as most organophosphine catalysts are expensive^', or air-sensitive, or both. It also results in a purer product, as when a co-catalyst is used some of that co- catalyst contaminates the alkylarylphosphme product, and this contaminant must be removed in a subsequent purification step. Hence the avoidance of a co-catalyst is a ma]or economic advantage of tne invention.

The heterogeneous catalyst recovered from the reaction mixture can be washed one or more times, as necessary, to remove any salts, water (derived from the work-up) unreacted starting materials and product absorbed on the catalyst. The catalyst may be washed with water-immiscible solvents, for example aromatic solvents such as toluene or xylene, water- miscible organic solvents such as acetone or alcohols and water itself, prior to drying and reuse.

The aryl compound can have only carbon atoms m the ring, or can be heterocyclic containing one or more nitrogen, oxygen or sulphur atoms. As nitrogen-containing compounds there are mentioned, e.g. pyπdine, pyrimidine, piperazine, pyrazole. As an oxygen-containmg heterocyclic compound there is mentioned furan. As a sulphur-containing heterocyclic compound there is mentioned thiophene. Heterocyclic groups can be benzo-fused. Examples of hydrocarbyl aryl compounds include phenyl, α-naphthyl, β-naphthyl, biphenyl, phenanthrenyl, anthracenyl, naphthacenyl and 2, 2 ' -bis (1, 1 ' -bmaphthyl) groups. Preferred leaving groups are the halogens, particularly chlorine, bromine and iodine. Other suitable leaving groups include, for example, tπfluoromethane- sulfonyloxy, methanesulfonyloxy, toluenesulfonyloxy and trifluoroacetate groups. The leaving group is attached to a carbon atom of the aryl ring. The aryl compound can bear one or more than one leaving group. Examples of aryl groups that bear two leaving groups, and therefore may bear two phosphorus atoms after reaction, include the 1,2-phenyl group, the 1,4- Dnenyl group, the 2, 2 ' -biphenyl group of formula

and the 2 , 2 ' -bis ( 1 , 1 ' binaphthyl) group of formula

The aryl compound is preferably an iodo- or a bromo- compound. The aryl moiety can be unsubstituted or can be substituted by groups that do not interfere with the reaction. Such substituents include hydrocarbyl groups such as alkyl, cycloalkyl and cycloalkylalkylgroups . Mention is made of alkyl groups, straight chained or branched, having up to about 8 carbon atoms, cycloalkyl groups having from 3 to 8 , preferably 5 or 6, carbon atoms, cycloalkylalkyl groups having up to 8 carbon atoms in the alkyl moiety and from 3 to 8 carbon atoms in the cycloalkyl moiety, aryl groups such as phenyl or naphthyl , aralkyl groups such as benzyl or phenethyl and alkaryl groups such as tolyl or xylyl groups . Other substituents include acyl , acyloxy, aikoxy and aryloxy groups, again having up to about 8 carbon atoms. Particular compounds include bromotoluenes , bromoxylenes , iodotoluenes and iodoxylenes . The preferred aryl halides are bromobenzene and, especially, iodobenzene .

As stated above, the aryl compound can bear substituents that do not participate in or interfere with the reaction with the alkyl phosphine. It is found that the reaction of the present invention goes better with electron- withdrawing groups, for instance trifluoromethyl , cyano , alkylcarbonyl and alkoxycarbonyl . The substituted compounds that are of greatest interest, however, are those that bear electron-donating groups, for instance lower alkyl and lower alkoxy groups. The aryl compound can bear one, two or more substituents. To avoid steric interference it is preferred that the substituents shall be in the 3-, 4-, or 5- position, relative to the leaving group. Mention is made of 3- trifluoromethylphenyl , 4 -trifluoromethylphenyl , 3 -cyanophenyl , 4-cyanophenyl, 3 -acetylphenyl , 4-acetylphenyl , 3- methoxycarbonylphenyl , 4-methoxycarbonylphenyl, 3- acetoxyphenyl, 4-acetoxyphenyl, 3-methylphenyl, 4-methylphenyl, 3 , 5-dimethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl and 3,5- dimethoxyphenyl groups, and also aryl groups other than phenyl that are correspondingly substituted. The reactant of formula II

is a monoalkyl phosphine or a dialkylphosphine , depending upon the value of z, or an oxide or sulfide thereof. The alkyl group or groups R can be the same or different when z is 2 but frequently will be the same. The number of carbon atoms in the alkyl group or groups is not critical and can range from 1 to, say, 20 or even higher, and mention is made of groups having 4 to 15 carbon atoms. The alkyl group or groups can be straight - chained or branched, and can be substituted provided that the substituents do not interfere with the course of the reaction. Suitable substituents include those mentioned above as possible substituents in the aryl group Ar. One preferred phosphine is mono ( ri-2 , 4 , 4 methylpentyl ) phosphine. If R is cycloalkyl it preferably contains 3 to 8 carbon atoms, more preferably 5 or 6 carbon atoms .

When the alkylphosphine is a primary phosphine there is the possibility of forming a monoalkylmonoarylphosphine and a monoalkyldiarylphosphine . Usually the monoalkylmonoarylphosphine product predominates with shorter reaction times of, say, less than about 30 hours, even when two or more equivalents of the aryl compound are employed. However, with a large excess of aryl compound, or with extended reaction time, say greater than about 36 hours, the amount of diarylphosphine product increases and, depending upon the molar ratio of the reactants and the length of the reaction time, the diarylphosphine becomes the major product. Significant amounts of the diarylphosphine are usually observed only when most or all of the starting monoalkylphosphine has been consumed.

The alkylphosphine and aryl compound can be used in equivalent amounts, or either reactant can be used in excess. If a primary alkylphosphine is used and a diarylphosphine is required then the aryl compound should be used in an amount equal to two equivalents or greater, say up to about five equivalents or greater.

The reaction can be carried out at ambient or elevated temperature but usually when preparing a monoarylphosphine a temperature of about 120°C is not exceeded, and a temperature in the range from about 40° to about 110°C, particularly about 70° to about 105°C, is preferred. At lower temperatures the reaction takes longer, but reaction is usually complete in a period of about 2 hours to 2 weeks, and usually within 36 hours. When preparing a diarylphosphine a higher temperature, suitably up to about 150 °C, may be used. The reaction is usually carried out at atmospheric pressure, but elevated pressure can be used if desired. Elevated pressure may be advantageous with alkylphosphine, alkylphosphine oxide or alkylphosphine sulfide reactants of low molecular weight. For instance, with methyl-, ethyl- or propylphosphine an autoclave can be used. Pressure will not normally be more than about 600 psig and will preferably be within the range of about 50 to 500 psig. The reaction is carried out under a blanket of inert gas, suitably argon or nitrogen. Efficient-stirring assists reaction and can be provided by, for instance, a magnetic stirrer or an overhead stirrer with paddle.

The reaction is preferably carried out in the presence of a solvent. Suitable solvents include gly e, acetonitrilε , diethyl ether, anisole, di-n-butyl ether, tetrahydrofuran, p-dioxane, toluene, xylene, cumene or N,N- dimethyl-formamide , a mixture of toluene and isopropanol (e.g. a 3:1 mixture) . Also suitable are aliphatic, cycloaliphatic and aromatic hydrocarbons, including hexane , heptane, octane, cyclohexane, benzene and petroleum fractions boiling at 70 140°C. Solvents that have oxidising properties, such as DMSO, should be avoided. Toluene and o-xylene are most preferred. As stated above the reaction is preferably carried out in the presence of a base promoter such as for example sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, potassium carbonate, sodium ethoxide, potassium ethoxide, ammonium carbonate, ammonium bicarbonate, calcium oxide, calcium hydroxide, magnesium oxide, magnesium hydroxide or the like. Organic bases, particularly amines, can also be used. Mention is made of pyridine and pyridine derivatives such as lower alkyl pyridines, and of tertiary amines of which triethylamine , tributylamine , and other trialkylamines are preferred. The amount of the base promoter is suitably about equal to one equivalent of the aryl compound if the aryl compound bears one leaving group, and equal to two equivalents if the aryl compound bears two leaving groups.

Preferably the alkylphosphine reactant is a phosphine rather than a phosphine oxide or phosphine sulfide, e.g., in the reactant of formula II n is 0.

The invention is further illustrated in the following examples. Example 1

Reaction of Mono 2 , 4 , 4-Trimethylpentylphosphine with lodobenzene Using 5% Palladium on Carbon Λ reac ion mixture wa:; prepared om the Hollowing components : mono (tri-2 , 4 , 4-methylpentyl) - phosphine (MTMPP) 3.3g, 0.022 mole iodobenzene 3.2g, 0.0157 mole triethylamine 1.75g, 0.0175 mole

Pd (5%) on activated carbon 0.23g, 11.5 mg Pd (purchased from

Aldrich) approx. 0.7 mole % with respect to 1 iodobenzene 3-4 ml o-xylene

The reaction mixture was allowed to stand for 24 hours, during which time no sign of reaction was observed. There was then fitted an N₂ sweep and the reaction -mixture heated in a water bath at 80°C for approximately one hour. Upon removal from the water bath a few white crystals were noticed on the walls of the vessel containing the reaction mixture. The crystals were triethylammonium iodide. After cooling overnight a large amount of solid triethylammonium iodide was observed in a dark brown/black liquid. A sample of the liquid was taken, washed with water and analyzed by gas chromatography- flame ionization detector (GC-FID) and the results showed 24.2% of mono (tri-2 , 4 , 4-methylpentyl) - monophenylphosphine and 0.5% mono (tri-2 , 4 , 4-methylpentyl) - diphenylphosphine . The product mixture was washed with water X5ml) , which dissolved the white solid which was triethylammonium iodide, but a clean separation of aqueous and organic phases was not achievable, owing to the presence of the Pd/C catalyst. The reaction mixture was then filtered through a 30 ml "Medium" pore sized glass sintered funnel and the collected catalyst was washed with a small amount of toluene.

The filtrate was transferred to a separating funnel, the aqueous layer removed and the organic layer sampled and analyzed by GC-FID and ³¹P NMR. ³¹P NMR indicated a peak at - 60ppm, which corresponds to mono (tri-2 , 4 , 4-methylphenyl) - monophenylphosphine.

The filtered catalyst was further washed with toluene, water and finally acetone, dried over N₂ and weighed, yielding 0.229 g of a fine black powder. Example 2

Reaction of Mono 2 , 4 , 4-Trimethylpentylphosphine with

Bromobenzene Using 5% Palladium on Carbon

To a mixture of mono 2 , 4 , - trimethylpentylphosphine (150 g, 1.02 moles), bromobenzene (108 g, 0.68 mole), triethylamine (66 g, 0.66 mole) in xylene (170 mL) was added 5% palladium on carbon (1.5 g, 0.1 mole % Pd) . The mixture was heated to 125°C and maintained at 125-133 °C for a total of 36 hours. Upon cooling to ambient temperature, the xylene layer was analyzed by GC/FID and found to be composed of a 20:1 mixture of mono:diaryl alkylphosphines with a total monoalkylphosphine conversion of approximately 16% at this time. The heterogeneous catalyst was isolated from the mixture by filtration and washed with water, acetone and finally toluene. Essentially all of the initial palladium on carbon catalyst was recovered by this method. Example 3

Reaction of Mono 2 , , 4 -Trimethylpentylphosphine with One Equivalent of Bromobenzene Using 5% Palladium on Alumina To a solution of mono 2 , 4 , 4-trimethylpentylphosphine

(100 g, 0.68 mole), bromobenzene (108 g, 0.68 mole), triethylamine (60 g, 0.60 mole) in xylene (250 mL) was added 5% palladium on alumina (1.4 g, 6.6 x 10 -4 mole Pd, 0.1 mole % Pd) . The mixture was heated to 130°C (reflux) under nitrogen with magnetic stirring and maintained at this temperature for 24 hours. Upon cooling to ambient temperature, the xylene layer was washed with water and analyzed by GC/FID. The GC chromatogram of this material indicated approximately 36% conversion of the mono-alkylphosphine starting material to a 98:2 mixture of 2 , 4 , 4 -trimethylpentyl (phenyl) phosphine and diphenyl (2 , , 4-trimethyl-pentyl) phosphine, respectively. The identities of these mixed alkylarylphosphines were established by GC/MS and P NMR spectroscopy . Example 4 Reaction of Mono 2 , 4 , 4 -Trimethylpentylphosphine with Two Equivalents of Bromobenzene Using 5% Palladium on Alumina

To a solution of mono 2 , 4 , 4 -trimethylpentylphosphine (100 g, 0.68 mole), bromobenzene (216 g, 1.36 moles) triethylamine (120 g, 1.2 moles) in xylene (250 mL) was added 5% palladium on alumina (1.4 g, 0.1 mole % Pd) . The mixture was heated to 132°C (reflux) under nitrogen and with magnetic stirring. The mixture was maintained at this temperature for 30 hours, then allowed to cool to ambient temperature. After a work-up procedure as described above, analysis of the xylene layer revealed an overall conversion of the monoalkylphosphine of approximately 90% (as determined by GC/FID area percent integration) , to give a 65:1 mixture of mono and diaryl alkylphosphines, respectively.

Example 5

Reaction of Mono 2 , 4 , 4 -Trimethylpentylphosphine with One Equivalent of Bromobenzene Using 10% Palladium on Polystyrene To a solution of mono 2 , , 4-trimethylpentylphosphine

(100 g, 0.68 mole), bromobenzene (108 g, 0.8 mole), triethylamine (55 g, 0.55 mole) in xylene (250 mL) was added 10% palladium on polystyrene (0.70 g, 6.6 x 10 -4 mole Pd, 0.1 mole % Pd) . This mixture was heated to 130°C under nitrogen with magnetic stirring and maintained at 130-134°C for 24 hours. After cooling to ambient temperature, analysis of the xylene layer by GC/FID revealed approximately 20% overall conversion of the monoalkylphosphine to a 98:1 mixture of mono: diaryl alkylphosphines. Example c

Reaction of Diisobutylphosphine with Bromobenzene Using 10%

Palladium on Polystyrene

To a solution of diisobutylphosphine (83 g, 0.57 mole), bromobenzene (90 g, 0.57 mole), triethylamine (56 g, 0.56 mole) in xylene (250 mL) was added 10% palladium on polystyrene (0.60 g, 5.7 x 10 -4 mole Pd, 0.1 mole % Pd) . The mixture was heated to 127°C and maintained at 127-135°C with magnetic stirring for a total of 24 hours. Analysis of the xylene layer by GC/FID at this time revealed approximately 78% conversion of the dialkylphosphine starting material to diisobutyl (phenyl) phosphine . Example 7

Reaction of Mono 2 , 4 , 4 -Trimethylpentylphosphine with One Equivalent of Iodobenzene Using 1% Palladium Polyethyleneimine on Silica To a solution of mono 2 , , -trimethylpentylphoshpine

(15 g, 0.1 mole), iodobenzene (21 g, 0.1 mole), triethylamine (10 g, 0.1 mole) in xylene (100 mL) was added 1% palladium/PEI on silica (20-40 mesh beads, 1.0 g, 0.1 mole % Pd) . The mixture was heated to 130 °C under nitrogen with magnetic stirring and maintained at this temperature for 5 hours . After cooling to ambient temperature, the xylene layer was analyzed by GC/FID and found to ^"contain a 14:1 mixture of mono: diaryl alkylphosphines, with overall conversion of the starting monoalkylphosphine at approximately 80%.

Claims

CLAIMS :

1. A process for preparing a mixed alkylarylphosphine, phosphine oxide or phosphine isulLide, which comprit-eu reacting a primary or secondary alkylphosphine, phosphine oxide or phosphine sulfide with an aryl compound bearing a leaving group attached to a carbon atom of the aryl ring, in the presence of a metal of Group VIII of the Periodic Table as heterogeneous catalys .

2. A process for preparing a compound of formula I

wherein X is oxygen or sulfur, n is 0 or 1, Ar is an unsubstituted or substituted aryl group, R is an unsubstituted or substituted alkyl or cycloalkyl group, x is 0 or 1, y is 1 or 2, z is 1 or 2 , provided that when x is 0 one of y and z is 1 and when x is 1 both of y and z are 1, which process comprises reacting an alkylphosphine, phosphine oxide or phosphine sulfide of formula II

<3-z)

3. A process according to claim 1 wherein the alkylphosphine is a compound of formula III

RHP-Q-PHR III wherein R is an unsubstituted or substituted alkyl or cycloalkyl group and Q is a divalent group containing 2 to 15 carbon atoms .

4. A process according to claim 1, 2 or 3 wherein the catalyst is palladium metal.

5. A process according to claim 4 wherein the palladium metal is on an active carbon support.

6. A process according to any one of claims 1 to 5 wherein the aromatic compound is iodobenzene.

7. A process according to any one of claims 1 to 5 wherein the aromatic compound is bromobenzene.

8. A process according to any one of claims l to 7 wherein the alkylphosphine is mono (tri-2 , 4 , 4-methylpentyl) - phosphine .

9. A process according to any one of claims 1 to 7 wherein the alkylphosphine is diisobutylphosphine.

10. A process according to any one of claims 2 and 4 to 7 wherein n is 0.

11. A process according to any one of claims 2 and 4 to 8 wherein z is 2.

12. A process according to any one of claims 1 to 11 wherein triethylamine is present as base promoter.