US3804950A - Phenylphosphonium salts for treating hyperacidity or ulceration - Google Patents

Abstract

PHENYLPHOSPHONIUM SALTS OF THIS INVENTION POSSESS USEFUL GASTRIC ANTISECRETORY, SPASMOLYTIC AND ANTIULCEROGENIC PROPERTIES. A METHOD OF TREATING GASTROINTESTINAL HYPERACIDITY AND ULCERAUON HAS ALSO BEEN DISCLOSED.

Description

United States Patent 3,804,950 PHENYLPHOSPHONIUM SALTS FOR TREATING HYPERACIDITY 0R ULCERATION Julius Diamond, Lafayette Hill, Pa., assignor to William H. Rorer, Inc., Washington, Pa.

No Drawing. Original application Jan. 22, 1972, Ser. No. 109,020, now Patent No. 3,755,459. Divided and this application Jan. 8, 1973, Ser. No. 321,509

Int. Cl. A61k 27/00 US. Cl. 424-198 8 Claims ABSTRACT OF THE DISCLOSURE Phenylphosphonium salts of this invention possess useful gastric antisecretory, spasmolytic and antiulcerogenic properties. A method of treating gastrointestinal hyperacidity and ulceration has also been disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS This is a division, of application Ser. No. 109,020, filed Jan. 22, 1972, now U.S. Pat. 3,755,459.

SUMMARY OF THE INVENTION This invention describes new phosphonium salts and processes for their preparation. This invention further provides valuable pharmaceutical preparations which contain these phosphonium salts as gastric antisecretory, spasmolytic, and antiulcerogenic agents. A method for the treatment of gastrointestinal hyperacidity and ulceration is also described.

BACKGROUND OF THE INVENTION The pharmaceutical compositions which have been used as antisecretory and spasmolytic agents have been such as atropine, homatropine, propantheline bromide, dicyclomine hydrochloride and other compounds which are structurally dissimilar to the onium salts of this invention. Due to the anticholinergic properties of these known compounds, they produce undesirable side effects such as mydriasis, xerostomia, cyclopegia, and other unwanted effects.

There have been a number of aryl phosphonium salts described in the literature. These have mainly been proposed for use as bactericidal and fungicidal agents, as well as plant growth regulators.

We have unexpectedly found novel phosphonium salts which have valuable pharmacologic properties.

We have found phosphonium salts which possess useful gastric antisecretory, spasmolytic and antiulcerogenic properties.

We have further found that the compounds of this invention are substantially void of the anticholinergic side efiects which accompany heretofore known gastric antisecretory and spasmolytic agents.

We have also found a simple and effective method for treating gastric hyperacidity and gastrointestinal ulceration such as duodenal and peptic ulcers.

DESCRIPTION AND PREFERRED EMBODIMENTS This invention provides a method of preparing novel phosphonium salts.

This invention further provides pharmacologically active chemical compounds which are useful in treating gastrointestinal hyperacidity and ulceration.

The compounds of this invention which are useful in treating gastrointestinal hyperacidity and ulceration may be described by the general Formula I:

3,804,950 Patented Apr. 16, 1974 ICC where Ar is an aryl or substituted aryl group;

R, R and R" may be the same or diiferent and are a saturated or unsaturated acylic member having up to 12 carbon atoms, or a saturated or partially unsaturated carbocyclic member having up to 12 carbon atoms; and

A* is a nontoxic inorganic or organic anion.

More specifically, the compounds of this invention may be described by the structural Formula II:

@a- Y R 11 where:

where R, is hydrogen or loweralkyl;

R R R R and R may be the same or different and are hydrogen, halo, cyano, haloloweralkyl, nitro, haloloweralkoxy, haloloweracyl, haloloweralkylsulfonyl or halodiloweralkylsulfonamido; and

A- is a pharmacetuically acceptable nontoxic inorganic or organic anion (preferably chloride, bromide, iodide, sulfate, hydrogen sulfate, nitrate, phosphate, dihydrogenphosphate, monohydrogenphosphate, acetate, maleate, citrate, benzoate, lactate, benzenesulfonate, methanesulfonate, ethanesulfonate, etc.)

The more preferred compounds of this invention are also the more preferred compounds which are useful in treating gastrointestinal disorders and diseases and are described by the structural Formula II:

where X and Y are hydrogen, halo, haloloweralkyl, nitro or haloloweralkoxy;

R, R and R" are a 5 to 12 carbon atom member which may be straight chained or branched and are alkyl or cycloalkyl;

R may also be arloweralkyl or substituted benzyl of the formula I RI! I Rt- CH- a Ra where:

R, is hydrogen or lower alkyl;

R R R R and R are hydrogen, halo, haloloweralkyl, nitro or haloloweralkoxy; and

A- is chloride, bromide, iodide, nitrate, phosphate or sulfate.

The most preferred compounds of this invention embrace those compounds of structural Formula II where X and Y are hydrogen, fluoro, chloro, bromo, trifiuoromethyl, nitro or trifluoromethoxy;

R, R and R" are amyl, hexyl, heptyl, octyl, cycloamyl,

cyclohexyl, cycloheptyl or cyclooctyl;

R may also be benzyl or substituted benzyl of the formula where R, is hydrogen or methyl; and

R ,R R R and R are hydrogen, fluoro, chloro, bromo,

trifluoromethyl, nitro or trifluoromethoxy; and

A- is chloride, bromide or iodide.

A further more preferred embodiment of this invention embraces those compounds of Formula II where:

X and Y are hydrogen, halo, haloloweralkyl, nitro or haloloweralkoxy;

R' and R" are a 5 to 12 carbon atom member which may be straight chained or branched and are: alkyl or cycloalkyl;

R is loweralkyl, loweralkenyl, loweralkynyl, cycloloweralkyl or cycloloweralkylloweralkyl;

A- is chloride, bromide, iodide, nitrate, phosphate or sulfate.

The more preferred compounds of this latter embodiment are exemplified where:

X and Y are hydrogen, fiuoro, chloro, bromo, trifluoromethyl, nitro or trifluoromethoxy;

R and R" are amyl, hexyl, heptyl, octyl, cycloamyl,

cyclohexyl, cycloheptyl or cyclooctyl;

R is loweralkyl, loweralkenyl, loweralkynyl, cycloloweralkyl or cycloloweralkylloweralkyl;

A- is chloride, bromide or iodide.

In the descriptive portions of this invention, the following definitions apply: The term lower alkyl" refers to a lower alkyl hydrocarbon group containing from 1 to 5 carbon atoms which may be straight chained or branched.

The lower alkoxy radical signifies an alkoxy group containing from 1 to 5 carbon atoms which can be straight chained or branched.

The compounds of this invention can contain an asymmetric phosphorous atom when R R' k' Ar. For this reason, they may be obtained as racemic mixtures or as dextro and levorotatory insomers. These may be separated by any of the various methods of resolution to obtain the d or 1 compound. These isomers may also be obtained via stereospecific condensation reactions. It is understood that the optical isomers of these compounds are embraced within the scope of this invention.

Representative compounds of this invention which are particularly useful are as follows:

trioctylphenylphosphonium chloride trioctyl(p-fluorophenyl)phosphonium chloride trioctyl(p-trifluoromethyl)phosphonium chloride dioctylbenzylphenylphosphonium chloride dioctyl(p-fluorobenzyl) phenylphosphonium chloride dioctyl(p-trifluoromethylbenzyl)phenylphosphonium chloride dioctylamylphenylphosphonium chloride dihexylamylphenylphosphonium chloride dioctyl(p-bromobenzyl)phenylphosphonium bromide dioctyl(2,3,4,5,6-pentafiuorobenzyl) phenylphosphonium chloride triheptylphenylphosphonium chloride trihexylphenylphosphonium chloride tricyclohexylphenylphosphonium chloride tricycloheptylphenylphosphonium chloride diheptyl(2,6-dichlorobenzyl)phenylphosphonium chloride dioctyl(2,6-dichlorobenzyl) (p-chlorophenyl)phosphonium chloride dioctyl u-methylbenzyl) (p-chlorophenyl) phosphonium chloride dihexylmethylphenylphosphonium chloride dihexylethylphenylphosphonium chloride dihexylpropylphenylphosphonium chloride dihexyl(i-propyl)phenylphosphonium chloride dihexylbutylphenylphosphonium chloride dihexyl(i-butyl)phenylphosphonium chloride dihexyl(s-butyl) phenylphosphonium chloride dihexyl(t-butyl)phenylphosphonium chloride dihexylpentylphenylphosphonium chloride dihexyloctylphenylphosphonium chloride dihexylallylphenylphosphonium chloride dihexylmethallylphenylphosphonium chloride diheXyl(2-butenyl)phenylphosphonium chloride dihexyl(3-butenyl) phenylphosphonium chloride diheXyl(4-pentenyl)phenylphosphonium chloride dihexyl(2,4-pentadienyl) phenylphosphonium chloride dihexyl(2-propynyl)phenylphosphonium chloride dihexylcyclopropylphenylphosphonium chloride dihexylcyclopropylmethylphenylphosphonium chloride dihexylcyclopropylethylphenylphosphonium chloride dihexylcyclobutylphenylphosphonium chloride dihexylcyclobutylmethylphenylphosphonium chloride dihexylcyclopentylphenylphosphonium chloride dihexyl(2-cyclopentenyl)phenylphosphonium chloride dihexylpropargylphenylphosphonium bromide dihexyl(2-cyclohexenyl)phenylphosphonium chloride dihexylperfiuorobutylphenylphosphonium chloride dipentylallylphenylphosphonium chloride diheptylallylphenylphosphonium chloride dicyclohexylallylphenylphosphonium chloride dicycloheptylallylphenylphosphonium chloride dicyclooctylallylphenylphosphonium chloride hexyloctylallylphenylphosphonium chloride heptyloctylallyphenyphosphonium choride cyclohexyloctaylallylphenylphosphonium chloride cycloheptyloctylallylphenylphosphonium chloride cyclooctyloctylallylphenylphosphonium chloride tri-octyl(o-chlorophenyl)phosphonium chloride trihexy,l(m-chlorophenyl) phosphonium chloride trihexyl(p-chlorophenyl)phosphonium chloride trihexyl(2,3-dichlorophenyl) phosphonium chloride trihexyl(2,4-dichlorophenyl)phosphonium chloride trihexyl(2,5-dichlorophenyl) phosphonium chloride trihexyl(2,6-dichlorophenyl) phosphonium chloride triheXyl 3,4-dichlorophenyl phosphonium chloride trihexyl 3,5 -dichlorophenyl phosphonium chloride trihexyl(2-bromophenyl)phosphonium chloride trihexyl(3-bromophenyl)phosphonium chloride trihexyl (4-bromophenyl) phosphonium chloride trihexyl (4-trifluoromethylphenyl) phosphonium chloride trihexyl(4-nitrophenyl) phosphonium chloride trihexyl(4-methoxyphenyl)phosphonium chloride dihexyl(o-chlorobenzyl)phenyl phosphonium chloride dihexyl(m-chlorobenzyl)phenyl phosphonium chloride dihexyl(p-chlorobenzyl)phenyl phosphonium chloride dihexyl(2,3-dichlorobenzyl)phenyl phosphonium chloride dihexyl(2,4-dichlorobenzyl)phenyl phosphonium chloride dihexyl(2,5-dichlorobenzyl)phenyl phosphonium chloride dihexyl(2,6-dichlorobenzyl)phenyl phosphonium chloride dihexyl(3,4-dichlorobenzyl)phenyl phosphonium chloride dihexyl(3,5-dichlorobenzyl)phenyl phosphonium chloride dihexyl(2,3,4-triehlorobenzyl) phenyl phosphonium chloride dihexyl(2,3,5-trichlorobenzyl) phenyl phosphonium chloride dihexyl(2,3,6-trichlorobenzyl)phenyl phosphonium chloride triisoamylphenylphosphonium chloride tricyclopentylphenylphosphonium chloride dipentylhexylphenylphosphonium chloride 7 dipentylheptylphenylphosphonium chloride dipentylcyclohexylphenylphosphonium chloride diisoa'mylhexylphenylphosphonium chloride dipentylphenylbenzylphosphonium chloride diisoamylphenylbenzylphosphonium chloride.

The compounds of this invention may be prepared by the following general procedures:

Condensation of phosphorous trichloride with a molar amount of phenyl organometallic compound results in the phenyl dichlorophosphine. Further condensation with the proper organometallic reagents resultsin the trisubstituted phosphine. Reaction of the trisubstituted phosphine with the desired alkyl or aralkyl halide results in the corresponding quatenary phosphonium halide. [Phenyldichlorophosphines may also be prepared by the Michaelis modification of the Fridel-Crafts reaction as outlined in JACS The following reaction equation illustrates thismethod of synthesis:

' Where X is chloride, bromide or iodide. When Xo'r Y is chloro,' then X is brorno or iodo'but when X or Y is br omo, then X is iodo.

' Phosphonium compounds having two similar groups are prepared by reacting 'the phenyldichlorophosphine with 1 two moles of Grignard reagent followed by condensation with the desired halide."

. kR I @"R Y i i 11" The above reactions may be carried out by the usual substitution process for reactions involving organometal- 7 lie reagents with halogen derivatives of'trivalent phosphorous compounds. g

One such method is by carrying out the reaction with one, two or three moles of the desired organorntallid reagent (preferably a Grignard reagent) in an inertlme- 'dium such as ether, tetrahydrofuran, etc., and with increased. temperatures. Isolation may be carried out either by subjecting the reaction mixture to vacuum distillation or by giving the mixture a hydrolytic treatment'with am- 75- moniac chloride solution, followed by distillation of the organic layer.

Preparation of the phosphonium salts is preferably carried out with the phenyldisubstituted phosphine and a halide of the formula RX where R and X' are as described above. The reaction is preferably carried out using a solvent and with increased temperatures. These reactions are also preferably carried out in an inert ati mosphere under nitrogen or carbon dioxide. The solvent used should be one that is miscible with the reactants and after it is convenient to use the reactant halide in excess as the solvent or alternatively a high boiling polar medium such as phenol, acetonitrile, dimethylformamide, dimethylsulfoxide, methylethylketone, etc. The reaction temperature may vary from room temperature with readily reactive reactants to about 250 C.,

although it is preferable to run the reaction at temperatures from about 50 C. to C. The isolation of the desired phosphonium halide can be carried out by distilling off the solvent in vacuo and precipitating the phosphonium halide by the addition of a hydrocarbon liquid such as n-pentane, n-hexane, cyclohexane, etc.

Other anion salts can be produced by exchange of the halide with alkali or alkaline earth salts containing the appropriate anion.

When R is substituted benzyl, it is preferable to prepare the phosphonium compound on the phenyldisubstituted phosphine with the desired benzyl halide.

R i I RI! This reaction is conveniently carried out on the benzyl peratures. This synthesis is carried out and isolated as described above.

The benzyl halide starting materials can be conveniently prepared by the following reactions.

R3 Ra Ra R:

R4- NH: R4 CN I g Ra Ra R5 Re b lrno+ Ills Illa Ra Ra n-ono R; -COOH Ra Ra Rs Ru (d) l (where Ra=loweralky1) (g) lLiAlH; R3 R: R: R2 I l m -o=o R4 CHz0H Rs a Ra Ra $41 R4 OHOH R4 CHzX' R5 Rs Ra Ra l l in -CHX 7 Diazotization of an aromatic amine in the conventional manner followed by a Sandmeyer (a) type displacement produces the nitrile, which is then hydrolyzed (b) to the carboxylic acid. Rosenmund reduction of the carboxylic acid results in the aldehyde which in turn is interacted with the desired alkyl Grignard reagent and oxidized (d) to obtain the a-alkylketone. This may then be reduced catalytically (e) to the a-alkylbenzyl alcohol. The alcohol is treated with a phosphorous trihalide, phosphorous oxyhalide, phosphorous pentahalide, thionylhalide or sulfuryl halide reagent (f) to obtain the a-alkylbenzyl halide. Lithium aluminum hydride reduction of the benzoic acid (g) results in the benzyl alcohol which is then treated as above (f) to obtain the benzyl halide.

The phenyl Grignard reagents may be prepared from the corresponding aniline by conventional diazotization followed by a Sandmeyer type reaction using cuprous bromide or cuprous iodide to obtain the desired phenyl halide which is then converted to the Grignard.

Appropriately desired end products having various X, Y, R R R R and R substituents can be prepared at various stages of the synthesis of the starting materials by using suitable reactions in order to convert one group to another. Thus, for example, using conventional methods, a halogen group can be treated under Rosenmund von Brown conditions to the nitrile compound which in turn can be hydrolyzed to a carboxy. A nitro can be reduced to an amino which can be alkylated to the dialkylamino substituent. A hydroxy compound can be prepared by demethylation of a methoxy substituent. A Sandmeyer type reaction can be carried out on an amino compound to introduce a chloro, bromo, xanthate, hydroxyl or alkoxyl group. The xanthate can then lead to the mercapto by hydrolysis, this turn can be alkylated to an alkylthio group which can be oxidized to alkylsulfinyl and alkylsulfonyl groups.

We .have found that the compounds of this invention have useful antiulcerogenic properties. Further, they have an effective degree of gastric anti-secretory activity, i.e., they reduce the volume and the acidity of the gastric fluid in humans and mammals. Still further, these compounds produce a considerable spasmolytic action on the gastrointestinal musculature, i.e., they reduce the peristaltic action of the gastrintestinal musculature which is manifested by a delay in gastric emptying time.

Until now, the known antiulcerogenic compounds which showed gastric anti-secretory and gastrintestinal spasmolytic action have included such agents as atropine, homatropine, propantheline, dicyclomine, etc. These compounds, however, cause accompanying undesirable anticholinergic properties such as mydriasis, xerostomia, cyclopegia, etc.

We have found that the phosphonium compounds of this invention are particularly useful as antisecretory, antispasmodic and antiulcerogenic agents because they are essentially devoid of these unwanted effects.

In particular, the phosphonium compounds, as herein described, are useful in the treatment of such gastrointestinal disorders and diseases as duodenal ulcer and peptic ulcer.

For all these purposes, the phosphonium compounds of this invention can be administered orally or parenterally, but they are preferably administered orally. Orally, they may be administered as tablets, aqueous or oily suspension, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs. The term parenteral,

as used herein, includes subcutaneous injection, intramuscular injection or infusion techniques.

Compositions intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions may contain one or more agents selected from the group consisting of sweetening agents, flavoring agents, coloring agents and preserving agents, in order to provide a pharmaceutically elegant and palatable preparation.

Further, these compounds may be tableted or otherwise formulated so that for every 100 parts by weight of the composition, there are present between 5 and parts by weight of the active ingredient. The dosage unit form will generally contain between about 1 mg. and about 500 mg. of the active ingredients of this invention. The preferred unit dose is between about 10 mg. and mg.

The dosage regimen in carrying out the methods of this invention is that which insures maximum therapeutic response until improvement is obtained and thereafter the minimum effective level which gives relief. Thus, in general, the dosages are those that are therapeutically effective in the treatment of ulcerogenic disease conditions or symptoms, such as duodenal and peptic ulcer. In general, the daily dose can be between about 0.1 mg./kg. and 50 mg./kg. (preferably in the range of 1-25 mg./kg./day). Bearing in mind, of course, that in selecting the appropriate dosage in any specific case, consideration must be given to the patients weight, general health, age and other factors which may influence response to the drug.

Various tests in animals have been carried out to show the ability of the compounds of this invention to exhibit reactions that can be correlated with antiulcerogenic activity in humans. These tests involve such as the effects of the phosphonium compounds on gastric secretion, gastrointestinal spasm and their effect against ulcerogenic agents. It has been found that the compounds of this invention when tested in the above variety of situations show a marked activity.

One such test is the gastric secretion test. This test is carried out as follows: Shay rats are fasted for 4-8 hours, and water is given ad lib. The rats are selected at random and separated into groups of 10. The animals are treated intraduodenally (I.D.) with the test compound or the vehicle immediately subsequent to the ligation of the stomach at the pyloric sphincter. The animals are sacrificed with chloroform at 4 hours post-drug administration, the stomach is removed and its contents are assayed for volume, pH and total acids.

A second gastric secretion test is carried out on dogs. This is outlined in the Handbook of Physiology, Section 6: Alimentary Canal, vol. II: Secretion, American Physiology Society, Washington, DC, 1967.

It has been found that the compounds of this invention when subjected to the above gastric secretion tests display a marked ability to decrease gastic volume and gastic acidity. These tests are known to correlate well with gastric activity in humans and is a standard test used to determine anti-secretory properties.

To determine the antiulcer effectiveness, the following test is employed: Male Wistar rats (-150 grams) are fasted for 24 hours, then given reserpine at 5 mg./ kg. i.p. Twenty-four hours later, the stomachs are removed and examined for ulceration. Ulcers are graded on a O-4 scale and the number of ulcers is recorded. Pretreatment with the phosphonium compounds of this invention produces a decrease in ulcer grade and the number of ulcers compared to the control reserpine-treated rats.

Determination of anti-spasmodic properties can be carried out by the procedure as outlined by D. A. Brodie and S. K. Kundrats in their article entitled Effect of Drugs on Gastric Emptying in Rats, Fed. Proc. 24:714 (1965).

Mydriasis isdetected by the procedure R. A. Turner, Screening Methods in Pharmacology, Academic Press, New York, and London, pp. 174-5, 1965. Acute toxicity 9 is calculated according to the standard Litchfield-Wilcoxon procedure.

In view of the results of these tests, the pharmacological data clearly indicates that the phosphonium compounds of this invention can be considered to be efiective antiulcerogenic, antisecretory, and antispasmodic agents which are substantially free of anticholinergic side elfects and having a low toxocity. I

The following are detailed examples which show the preparation of the compounds of this invention. They are to be construed as illustrations of said compounds and not as limitations thereof.

EXAMPLE 1 Phenyldichlorophosphine To 83 g. (0.6 mole) of phosphorus trichloride is added 27 g. (0.2 mole) of aluminum chloride and 13.8 g. (0.15 mole) of dry benzene. This reaction mixture is then gently heated for 2rhours with stirring overa blanket of nitrogen to expell the formed hydrogen chloride. The reaction mixture is then refluxed with vigorous stirring for an additional hour. The heat source is then removed and while the reaction mixture is still hot, phosphorus oxychloride 30.7 g. (0.2 mole) is gradually added. The mixture is then allowed to cool to room temperature and extracted continuously with petroleum ether for 2 hours. The petroleum ether extract is then concentrated. in vacuo and distilled to obtain phenyldichlorophosphine.

, When benzene in the above example is replaced by the compounds of Table I below and the reaction product is fractionated thenthe corresponding product of Table II below is prepared. 7

TABLE I Toluene Ethylbenzene Propylbenzene i-Propylbenzene t-Butylbenzene o-Xylene m-Xylene p-Xylene Biphenyl p-Methylbiphenyl Anisole Phenetole m-Dimethoxybenzene' Trifiuoromethoxybenzene Phenyl ether o-Diethylbenzene TABLE II p-Tolyldichlorophosphine p-Ethylphenydichlorophosphine p-Propylphenyldichlorophosphine p-i-Propylphenyldichlorophosphine p-t-Butylphenyldichlorophospine 3 ,4-dimethylphenyldichloropho sphine (2,4-dimethylphenyl)dichlorophosphine 2,5-dimethylphenyl)dichlorophosphine (p-Biphenyl)dichlorophosphine (p,p'-Methylbiphenyl)dichlorophosphine p-Methoxyphenyldichlorophosphine p-Ethoxyphenyldichlorophosphine 2,4-dimethoxyphenyldichlorophosphine p-Trifiuorornethoxyphenyldichlorophosphine p-Phe'noxyphenyldichlorophosphine 3,4-diethylphenyldichlorophosphine.

EXAMPLE 2 Dioctylphenylphosphine To a Grignard mixture of n-octylmagnesium chloride (0.53 mole) prepared from 13.8 g. of magnesium turnings and 78.4 g. of n-octyl chloride in 1300 ml. ether is added 31.2 g. (0.175 mole) of 'phenyldichlorophosphine in 100 ml. of ether with vigorous stirring and in a nitrogen atmosphere at 0 C. The reaction mixture is allowed to warm to room temperature over 2 hours. The mixture is then poured onto an ice-cold saturated solution of ammonium chloride (250 ml.) and the mixture stirred for an additional hour. The aqueous layer is extracted with 2-150 ml. portions of ether which is then combined with the ether layer, dried over sodium sulfate, evaporated to dryness and distilled to obtain dioctylphenylphosphine.

When n-octyl chloride in the above reaction is substituted with the halides of Table I below, then the corresponding product of Table 11 below is prepared.

TABLE I n-Pentyl chloride n-Hexyl chloride n-Heptyl chloride n-Nonyl chloride n-Decyl chloride n-Undecyl chloride n-Dodecyl chloride Isoamyl chloride 2-methyl-1-butenyl chloride Cyclohex-Z-enyl chloride Cyclooctyl chloride Cycloheptyl chloride Cyclopentyl chloride Cyclohexyl chloride Cyclohexylmethyl chloride 3,4,5-trimethylheptyl chloride 2-propylallyl chloride 4-methyl-3-penten-1-yl chloride 2-methylheptyl chloride 3-methylheptyl chloride 2-ethylhexyl chloride 2,2,3,3-tetramethylbutyl chloride Cyclooct-2-enyl chloride Iso-octenyl chloride.

TABLE II Dipentylphenylphosphine Dihexylphenylphosphine Diheptylphenylphosphine Dinonylphenylphosphine Didecylphenylphosphine Diundecylphenylphosphine Didodecylphenylphosphine Diisoamylphenylphosphine Di (Z-methyll-butenyl phenylphosphine Di- (cyclohex-Z-enyl phenylphosphine Dicyclooctylphenylpho sphine Dicyclohep tylphenylpho sphine Dicyclop entylphenylphosphine Dicyclohexylphenylphosphine Dicyclohexylmethylphenylphosphine Di- 3 ,4,5-trimethylheptyl )phenylphosphine Di- (2-propylallyl) phenylpho sphine Di- (4-methyl-3 -penten-1-yl) phenylphosphine I Di- (Z-methylheptyl) phenylphosphine Di- (3 -methylheptyl phenylphosphine Di- (2-ethylhexy1) phenylphosphine Di- (2,2,3, 3 -tetramethylbutyl phenylphosphine Di- (cyclooct-2-enyl) phenylphosphine Di- (iso-octenyl) phenylphosphine.

EXAMPLE 3 When phenyldichlorophosphine in Example 2, is replaced by the phosphines of Table II, Example 1, then the corresponding product of Table I below is prepared.

TABLE I Dioctyl (p-tolyl) phosphine Dioctyl (p-ethylphenyl phosphine Dioctyl p-propylphenyl )phosphine Dioctyl (p-i-propylphenyl pho sphine Dioctyl (p-t-butylphenyl) phosphine 1 1 TABLE IContinued Dioctyl (3,4-dimethylphenyl phosphine Dioctyl (2,4-dimethylphenyl) phosphine Dioctyl (2,5-dimethylphenyl) phosphine Dioctyl (p-biphenyl phosphine Dioctyl (p,p'-methylphenyl phosphine Dioctyl (p-methoxyphenyl phosphine Dioctyl (p-ethoxyphenyl phosphine Dioctyl( 2,4-dimethoxyphenyl) phosphine Dioctyl (p-trifluoromethoxyphenyl phosphine Dioctyl (phenoxyphenyl) phosphine Dioctyl 3,4-diethylphenyl phosphine.

EXAMPLE 4 When n-octylchloride in Example 2 is replaced with the halides of Table I, Example 2 and when phenyldichlorophosphine is replaced with the phosphines of Table II, Example 1, then the corresponding tertiary phosphine is prepared. A representative list of the compounds prepared is shown below in Table I.

TABLE I Dipentyl (p-tolyl phosphine Dihexyl (p-tolyl pho sphine Diheptyl (p-tolyl) phosphine dinonyl (p-tolyl) phosphine Diisoamyl (p-tolyl) phosphine Di- (cyclohex-Z-enyl) p-tolyl) pho sphine Dicyclooctyl (p-tolyl phosphine Dicycloheptyl (p-tolyl phosphine Dicyclohexyl(p-tolyl) phosphine Dicyclohexylmethyl (p-tolyl) phosphine Di- (2-propylallyl) (p-tolyl) phosphine Di- (iso-octenyl) (p-tolyl phosphine Diheptyl (p-ethylphenyl phosphine Diheptyl (p-propylphenyl phosphine Diisoamyl(p-methoxyphenyl phosphine Dicyclohex-Z-enyl) p-ethylphenyl phosphine Dicyclohexylmethyl p-t-butylphenyl pho sphine Dinonyl(p-propylphenyl) phosphine Di- (Z-ethylhexyl) (2,5-dimethylpheny1) phosphine Dicycloheptyl (p-methoxyphenyl phosphine Diisoamyl(p-methoxyphenyl phosphine Di- (2,2,3 ,3-tetramethylbutyl) (p-tolyl phosphine Di- (2-methyll-butenyl) (p-tolyl) phosphine Didecyl (p-biphenyl phosphine Dipentyl (p-tolyl phosphine Di- (cyclooct-2-enyl) (2,5-dimethylphenyl) phosphine Dicyelohex-Z-enyl) (p-tolyl) phosphine Dicyclohexylmethyl p-ethoxyphenyl) phosphine Dihexyl 3,4-diethylphenyl phosphine Dicyclohexyl (2,4-dimethylphenyl pho sphine Di-(iso-octenyl) (p-ethoxyphenyl)phosphine Di- (2-propylallyl) (p-propylphenyl phosphine Dicyclooctyl 3 ,4-dimethylphenyl phosphine Didodeeyl (p-phenoxyphenyl phosphine Dicyclopentyl p-trifiuoromethoxyphenyl) phosphine Diheptyl (p,p'-methylbiphenyl) phosphine Di- 3,5 ,5trimethylheptyl) p-ethylphenyl phosphine Di-(4-methyl-3-penten-1-yl) (p-tolyl phosphine Di- Z-methylheptyl) (p-methoxyphenyl phosphine Diundecyl (p,p'-methylbiphenyl) pho sphine Di- (3-methylhepty1) (p-tolyl) phosphine.

EXAMPLE 5 Phenyldichlorophosphine To a Grignard mixture of phenylmagnesium bromide (0.192 mole) prepared from 5 g. of magnesium turnings and 28.4 g. of bromobenzene in 600 ml. ether is added dropwise with stirring 52.8 g. (0.384 mole) of phosphorus trichloride in 120 ml. of ether, in a nitrogen atmosphere at 0 C. The reaction mixture is allowed to warm to room temperature with stirring over 2 hours. This reaction mixture is filtered and the solid washed with 2-100 m1. ether combined with the filtrate, concentrated in vacuo and distilled to obtain phenyldichlorophosphine.

When bromobenzene in the above example is replaced by the compounds of Table I below, then the corresponding phosphine of Table II below is prepared.

TABLE I l-bromo-Z-chlorobenzene 1-bromo-3-chlorobenzene 1-bromo-4-chlorobenzene 1-bromo-2,3-diehlorobenzene 1-brom0-3,S-dichlorobenzene 2-bromo-1,4-dichlorobenzene 4-bromo-1,2-dichlorobenzene 1-bromo-4-t-butylbenzene 1-bromo-2,3-dimethylbenzene 1-bromo-2,4-dimethylbenzene 4-bromo-1,2-dinitrobenzene 1-br0mo-2-ethoxybenzene 1-bromo-4-ethoxybenzene 1-bromo-4-fluorobenzene 1-bromo-2-iodobenzene 1-bromo-3-iodobenzene 1-bromo-4-iodobenzene 1-bromo-4-i-propylbenzene 2-bromo-4-i-propy1-l-methylbenzene 1-brom0-2-methoxybenzene 1-bromo-2-nitrobenzene 1-bromo-4-nitrobenzene 1-bromo-4-phenoxybenzene 1-bromo-4-trifiuoromethylbenzene 1-bromo-4-trifiuoromethoxybenzene 1-br0mo-4-biphenyl 1-bromo-4-phenoxybenzene 1-chloro-4-biphenyl 1,4'-dichlorobiphenyl 1-chloro-4-methylbenzene 1-chloro-2,4-diethylbenzene 1-iodo-2-methoxybenzene 1-iodo-3-methoxybenzene 1-iodo-4-methoxybenzene 1-iodo-4-nitrobenzene 1-iodo-2,4-dichlorobenzene 1-iodo-2,6-dichlorobenzene 1-iodo-3,4-dichlorobenzene 1-iodo-4-trifluoromethylbenzene 1-iodo-4-methylbenzene.

TABLE II (2-chlorophenyl dichloropho sphine (3 -chlorophenyl) dichlorophosphine (4-ehlorophenyl) dichlorophosphine (2, 3 -dichlorophenyl) dichloropho s phine (3,5 -dichloropheny1 dichlorophosphine (3 ,4dichlorophenyl) dichlorophosphine (4-t-butylphenyl dichlorophosphine (2,3 -dimethylphenyl dichlorophosphine (2,4-dimethylphenyl dichlo ropho sphine (3 ,4-dinitrophenyl dichlorophosphine (2-ethoxyphenyl) dichlorophosphine (4-ethoxyphenyl) dichlorophosphine (4-fluoropheny1)dichlorophosphine (2-bromophenyl dichlorophosphine (3 -bromophenyl) dichlorophosphine (4-bromophenyl dichlorophosphine 4-i-propylphenyl )dichlorophosphine (2-methyl-5-i-propylphenyl) dichloropho sphine 2-methoxyphenyl dichlorophosphine (2-nitrophenyl) dichlorophosphine (4-nitrophenyl dichlorophosphine (4-phenoxyphenyl) dichlorophosphine (4-trifiuoromethylphenyl) dichlorophosphine (4-trifiuoromethoxypheny1) dichlorophosphine (4-biphenyl) dichlorophosphine (4-phenoxyphenyl) dichloropho sphine (4,4'-chlorobiphenyl) dichlorophosphine 13 TABLE IIContinued (4-methylphenyl) dichlorophosphine 2,4-diethylpheny1) dichlorophosphine (3-methoxyphenyl) dichlorophosphine (4-methoxyphenyl dichloropho sphine (2,4-dichlorophenyl dichlorophosphine 2,6-dichlorophenyl) dichlorophosphine.

EXAMPLE 6 Dihexylphenylphosphine To a Grignard mixture of n-hexylmagnesium chloride (0.45 mole) prepared from 11.8 g. of magnesium turnings and 54 of n-hexylchloride in l l. ether is added 31.2 g. (0.175 mole) of phenyldichlorophosphine in 100 ml. of ether with vigorous stirring and in a nitrogen atmosphere at C. The reaction mixture is allowed to warm to room temperature for 3 hours. The mixture is poured onto a saturated ice-bath solution of ammonium chloride and the mixture stirred for an additional half hour. The mixture is extracted three times with 300 ml. portions of ether. The ether is dried over sodium sulfate, evaporated to dryness and fractionated to obtain dihexylphenylphosphine.

When phenyldichlorophosphine in the above example is replaced by the phenylphosphine of Table II, Example 5, then the corresponding product of Table I below is prepared.

TABLE I Dihexyl 2-chlorophenyl pho sphine Dihexyl 3-chlorophenyl) phosphine Dihexyl (4-chlorophenyl) phosphine Dihexyl (2, 3 -dichlorophenyl) pho sphine Dihexyl (3 ,5 -dichlorophenyl) pho sphine Dihexyl (3 ,4-dich1orophenyl pho sphine Dihexyl 4-t-butylphenyl) phosp hine Dihexyl 2, S-dimethylphenyl) phosphine Dihexyl (2,4-dimethylphenyl phosphine Dihexyl( 3,4-dinitrophenyl phosphine Dihexyl (2-ethoxyphenyl phosphine Dihexyl (4-ethoxyphenyl phosphine Dihexyl (4-fluorophenyl )phosphine Dihexyl (2-bromophenyl pho sphine Dihexyl 3-bromophenyl phosphine Dihexyl (4-bromophenyl)phosph1ne Dihexyl (4-i-propylphenyl) phosphine Dihexyl 2-methyl-5-i-propylphenyl )phosphine Dihexyl 2-methoxyphenyl phosphine Dihexyl (2-nitrophenyl phosphine Dihexyl 4-nitrophenyl )pho sphine Dihexyl 4-phenoxyphenyl) pho sphine Dihexyl (4-trifluororuethylphenyl phosphine Dihexyl 4-trifiuoro'methoxyphenyl )phosphine Dihexyl (4-biphenyl) phosphine Dihexyl (4-phenoxyphenyl phosphine Dihexyl (4,4-chlorobiphenyl) phosphine Dihexyl 4-methylphenyl phosphine Dihexyl 2,4-diethylphenyl) phosphine Dihexyl B-methoxyphenyl phosphine Dihexyl 4-methoxyp henyl phosphine Dihexyl 2,4-dichlorophenyl phosphine Dihexyl(2,6-dichlorophenyl phosphine.

EXAMPLE 7' Hexylphenylchlorophosphine To a Grignard mixture of hexylmagnesium chloride (0.1 mole) prepared from (2.6 g. of magnesium turnings and 16.3 g. of hexylbromide in 300 ml. of ether) is added dropwise to an inert atmosphere with stirring and at 0 C., 43 g. (0.15 mole) of phenyldichlorophosphine in 75 ml. of ether. The reaction mixture is stirred over 1% hours and allowed to gradually warm to room temperature. The reaction mixture is then filtered, residue washed with ether combined with the filtrate and concentrated in vacuo and distilled to obtain hexylphenylchlorophosphine.

When hexylbromide in the above reaction is replaced phosphine of Table I, below is prepared.

TABLE I Pentylphenylchlorophosphine Heptylphenylchlorophosphine Octylphenylchlorophosphine Nonylphenylchlorophosphine Decylp'henylchlorophosphine Undecylphenylchlorophosphine Dodecylphenylchlorophosphine Isoamylphenylchlorophosphine (2-methyl-1-butenyl) phenylchlorophosphine (Cyclohex-Z-enyl phenylchlorophosphine Cyclooctylphenylchlorophosphine Cycloheptylphenylchlorophosphine Cyclopentylphenylchlorophosphine Cyclohexylphenylchlorophosphine Cyc1ohexylrnethylphenylchlorophosphine (3 ,4,5-tri methylhepty1) phenylchlorophosphine (2-propylallyl phenylchlorophosphine (4-methyl-3-penten-1-yl)phenylchlorophosphine (Z-methylheptyl) phenylchlorophosphine 3 -methylheptyl phenylchloropho sphine (Z-ethylhexyl phenylchlorophosphine 2,2,3,3-tetramethylbutyl phenylchlorophosphine (Cyclooct-Z-enyl phenylchlorophosphine (Iso-octenyl phenylchlorophosphine.

EXAMPLE 8 When phenyldichlorophosphine of Example 7 is replaced with the phenyldichlorophosphines of Table II, Example 1 and Table II, Example 5, then the corresponding phosphines of Table I, below are prepared.

TABLE I Hexyl( 2-chlorophenyl chlorophosphine Hexyl(3-chlorophenyl) chlorophosphine Hexyl(4-chlorophenyl) chlorophosphine Hexyl 2,3-dichlorophenyl chlorophosphine Hexyl 3 ,S-dichlorophenyl chlorophosphine Hexyl 3 ,4-d ichlorophenyl chlorophosphine Hexyl (4-t-butylphenyl chlorophosphine Hexyl (2,3-dimethylphenyl chlorophosphine Hexyl 2,4-di-methylphenyl chlorophosphine Hexyl 3,4-dinitrophenyl chlorophosphine Hexyl Z-ethoxyphenyl chlorophosphine Hexyl (4-ethoxyphenyl) chlorophosphine Hexyl (4-fluorophenyl chlorophosphine Hexyl( 2-bron1ophenyl chlorophosphine Hexyl 3-bromophenyl ch10 rophosphine Hexyl (4-bromophenyl) chlorophosphine Hexyl (4-i-propylphenyl chlorophosphine Hexyl (2-methy1-S-i-propylphenyl chlorophosphine Hexyl (Z-methoxyphenyl chlorophosphine Hexyl(Z-nitrophenyl) chlorophosphine Hexyl (4-nitrophenyl chlorophosphine Hexyl 4-phenoxyphenyl chlorophosphine Hexyl 4-trifluoromethylphenyl chlorophosphine Hexyl (4-trifiuoromethoxyphenyl chlorophosphine Hexyl(4-bipheny1) chlorophosphine Hexyl (4-phenoxyphenyl chlorophosphine Hexyl (4,4-chlorobiphenyl chlorophosphine Hexyl (4-methylphenyl) chlorophosphine Hexyl 2,4-diethylphenyl chlorophosphine Hexyl (3 -rnethoxyphenyl chlorophosphine Hexyl (4-methoxyphenyl chlorophosphine Hexyl 2,4-dichlorophenyl chlorophosphine Hexyl 2,6-dichlorophenyl chlorophosphine Hexyl (p-ethylphenyl chlorophosphine Hexyl (p-propylphenyl chlorophosphine Hexyl (2,4-dimethylphenyl chloropho sphine Hexyl 2,5 -di methylphenyl chlorophosphine Hexyl 3 ,4-diethylphenyl chlorophosphine.

1 EXAMPLE 9 When phenyldichlorophosphine of Example 7 is replaced with the phenyldichlorophosphines of Table II, Example 1 and Table II, Example 5 and when hexyl chloride is replaced with the halides of Table 1. Example 2, then the corresponding disubstituted phosphine is prepared. A representative list of the compounds prepared is shown in Table I, below.

TABLE I Pentyl (2-chlorophenyl chlorophosphine Heptyl(2-nitrophenyl chlorophosphine Cyclooctyl( 2-bromophenyl chlorophosphine Cyclohexyl(2-chlorophenyl) chlorophosphine (Z-methyll-butenyl) (Z-ethoxyphenyl chlorophosphine Cyclohexyl 3 ,5 -dicl1lorophenyl) chlo rophosphine Cycloheptyl (2-methoxyphenyl chlorophosphine Decyl(3-methoxyphenyl) chlorophosphine Cyclohexyl 3 -bromophenyl) chlo ropho sphine Cyclohexyl (3 -chlorophenyl chlorophosphine Cyclohex-Z-emyl) (4 methoxyphenyl chlorophosphine (Iso-octenyl) (4-phenoxyphenyl) chlorophosphine Pentyl 4-trifiuoromethylphenyl) chlorophosphine Cyclohexylmethyl 4-bromophenyl) chlorophosphine (Z-ethylhexyl) (4-t-buty1phenyl)chlorophosphine (Cyclooct-2-enyl) (4-ethoxyphenyl chlorophosphine Cycloheptyl (4-fluorophenyl chloropho sphine onyl 4-i-propylphenyl) chlorophosphine (Z-methylheptyl) (4-nitrophenyl) chlorophosphine cyclopentyl(4-chlorophenyl chlorophosphine S-methylheptyl) (2,3-dimethylphenyl) chlorophosphine Isoamyl 2,3-dichlorophenyl chlorophosphine (4-methyl-3-pentenl-yl) (4-trifiuoromethoxyphenyl) chlorophosphine Undecy1( 4-methylphenyl chlorophosphine Isoamyl( 3,4-diethylphenyl chlorophosphine Cyclohexyl (2,4-dimethylphenyl chlorophosphine (2,2,3,B-tetramethylbutyl) (4-phenoxyphenyl) chlorophosphine (2-propylallyl) (4-biphenyl) chlorophosphine Cyclohexyl(3,4-dich1orophenyl)chlorophosphine Cyclohexylmethyl( 2,4-diethylphenyl) chlorophosphine Isoamyl 2,5-dimethylphenyl chlorophosphine Cyclopentyl( 2,4-dimethylphenyl chlorophosphine Dodecyl(2-methyl-S-i-propylphenyl) chlorophosphine Isoamyl ppropylphenyl) chlorophosphine Pentyl (2,6-dichlorophenyl) chlorophosphine Cyclohexyl (2,4-dichlorophenyl chlorophosphine (3,4,5 -trimethylheptyl) (3,4-dinitrophenyl) chloropho sphine Cyclohexyl (4,4'- chlorobiphenyl) chlorophosphine.

EXAMPLE Hexyloctylphenylphosphine To a Grignard mixture of octylmagnesium bromide (0.075 mole) in 250 ml. of ether is added dropwise with stirring 28.5 g. (0.125 mole) of hexylphenylchlorophosphine in 75 ml. of ether at 0 C. The reaction is carried out under nitrogen and vigorously stirred for 2 hours. The temperature is allowed to gradually warm up to room temperature. The reaction mixture is then poured onto an ice-cold saturated solution of ammonium chloride (300 ml.) and the mixture stirred for one hour. The aqueous layer is extracted with 200 ml. of ether combined with the ether layer, dried over sodium sulfate, evaporated to dryness and distilled to give hexyloctylphenylphosphine.

When the octylmagnesium bromide of the above reaction is replaced with the Grignard reagents of the halides of Table 1, Example 2, then the corresponding tertiary phosphine of Table I below is prepared.

Pentylhexylphenylphosphine Dihexylphenylphosphine Heptylhexylphenylphosphine Nonylhexylphenylphosphine Decylhexylphenylphosphine Undecylhexylphenylphosphine Dodecylhexylphenylphosphine Isoamylhexylphenylphosphine Z-methyll-butenyl) hexylphenylphosphine (Cyclohex-Z-enyl)hexylphenylphosphine Cyclooctylhexylphenylphosphine Cycloheptylhexylphenylphosphine Cyclopentylphenylphosphine Cyclohexylhexylphenylphosphine Cyclohexylrnethylhexylphenylphosphine (3,4,5-trimethylheptylhexylphenylphosphine (2-propylallyl)hexylphenylphosphine (4-methyl-3-penten-l-yl)hexylphenylphosphine (Z-rnethylheptyl)hexylphenylphosphine (3-methylheptyl)hexylphenylphosphine (2-ethylhexyl) hexylphenylpho sphine (2,2,3,3-tetramethylbutyl)hexylphenylphosphine (Cyclooct-2-enyl)hexylphenylphosphine Iso-octenylhexylphenylphosphine.

EXAMPLE 11 When hexylphenylchlorophosphine of Example 10 is replaced by the chlorophosphines of Table I, Example 7, then the corresponding tertiary phosphine of Table I below is prepared.

TABLE I EXAMPLE 12 When hexylphenylphosphine of Example 10 is replaced by the chlorophosphines of Table I, Example 8, then the corresponding tertiary phosphine of Table I, below is prepared.

TABLE I Octylhexyl(2-chlorophenyl phosphine Octylhexyl 3-chlorophenyl)phosphine Octylhexyl (4-chlorophenyl) phosphine Octylhexyl (2,3-dichlorophenyl phosphine Octylhexyl (3 ,5 -dichlorophenyl )phosphine Octylhexyl 3 ,4-dichlorophenyl) pho sphine Octylhexyl 4-t-butylphenyl) phosphine Octylhexy 2, 3 -dimethylphenyl phosphine Octylhexyl 2,4-dimethylphenyl phosphine Octylhexyl 3 ,4-dinitrophenyl phosphine Octylhexyl 2-ethoxyphenyl) phosphine Octylhexyl 4-ethoxyphenyl) pho sphine Octylhexyl 4-fluorophenyl phosphine Octylhexyl (2-bromophenyl phosphine Octylhexyl 3-bromophenyl phosphine Octylhexyl (4-bromophenyl phosphine Octylhexyl (4-i-propylphenyl phosphine 1 7 i TABLE I-Contin-ued Octylhexyl (Z-methyl-S-i-propylphenyl) phosphine Octylhexyl 2-methoxyphenyl phosphine Octylhexy1(2-nitrophenyl)phosphine Octylhexyl 4-nitrophenyl) phosphine Octylhexyl 4-phenoxyphenyl) phosphine Octylhexyl (4*tri-fluoromethylphenyl) phosphine Octylhexyl (4-trifluoromethoxyphenyl) pho sphine Octylhexyl 4-biphenyl) phosphine Octylhexyl (4-phenoxyphenyl phosphine Octylhexyl (4,4'-chlorophenyl phosphine Octylhexyl (4-methylphenyl phosphine Octylhexyl 2,4-diethylphenyl pho sphine Octylhexyl 3 -methxyphenyl phosphine O ctylhexyl (4-methoxyphenyl phosphine Octylhexyl (2,4-dichlorophenyl pho sphine Octylhexyl (2, 6-dichlorophenyl phosphine Octylhexy1(p-ethylphenyl)phosphine Octylhexyl p-propylphenyl )phosphine Octylhexyl (2-methy1-4-bromophenyl pho sphine Octylhexyl (2, S-dimethylphenyl) phosphine Octylhexyl (p-bromophenoxyphenyl) phosphine.

EXAMPLE 13 When octylmagnesium bromide of Example is replaced by the Grignard reagent of the halides of Table I, Example 2 and hexylphenylchlorophosphine is replaced by the chlorophosphines of Table 1, Example 9', then the corresponding representative tertiary phosphines of Table I below are prepared.

TABLE I Pentyl(Z-chlorophenyl) hexylphosphine Pentyl(3-chlorophenyl )hexylphosphine Pentyl (4-chlorophenyl) hexylphosphine Pentyl(2,3-dichlorophenyl) hexylphosphine Pentyl( 3 ,5 -dichlorophenyl hexylpho sphine Pentyl 3 ,4-dichlorophenyl hexylphosphine Pentyl(4-t-buty1phenyl) hexylphosphine Pentyl(2,3-dimethylphenyl) hexylphosphine Pentyl(2,4-dimethylphenyl hexylphosphine Pentyl (3,4-dinitrophenyl hexylphosphine Pentyl (2-ethoxyphenyl)hexylphosphine Pentyl(4-ethoxyphenyl) hexylphosphine Pentyl(4-fluoropheny1)hexylphosphine Pentyl( 2-bromophenyl)hexylphosphine Pentyl(3-bromophenyl) hexylphosphine Pentyl (4-bromophenyl)hexylphosphine Pentyl (4-i-propylphenyl) hexylphosphine Pentyl( Z-methyl-S-i-propylphenyl) hexylphosphine Pentyl( Z-methoxyphenyl hexylphosphine Pentyl(2-nitropheny1)hexylphosphine Pentyl (4-nitrophenyl hexylphosphine Pentyl (4-phenoxyphenyl) hexylphosphine Pentyl(4-trifluoromethylphenyl )vhexylphosphine Pentyl (4-trifluoromethoxy-phenyl) hexylphosphine Pentyl (4-biphenyl hexylphosphine 'Pentyl(4-phenoxyphenyl) hexylphosphine Pentyl (4,4'-chlorobiphenyl) hexylphosphine Pentyl(4-methylphenyl hexylphosphine Pentyl (2,4-diethylphenyl)hexylphosphine Pentyl(3-methoxyphenyl)hexylphosphine Pentyl(4-meth0xyphenyl) hexylphosphine Pentyl(2,4-dichlorophenyl) hexylphosphine Pentyl(2,6-dichlorophenyl) hexylphosphine Heptyl (2-nitrophenyl isoamylpho sphine Cyclooctyl (2-brornophenyl pentylphosphine Cyclohexyl(2-chlorophenyl)undecylphosphine (2-methyl-1-butenyl) (2-ethoxyphenyl) (2-ethylhexyl) phosphine Cyclohexyl(3 ,S-dichlorophenyl) hexylphosphine Cycloheptyl(Z-methoxyphenyl) (3-methylheptyl) phosphine Decyl(3-methoxyphenyl) phosphine Cyclohexyl (3-bromophenyl) pentylphosphine Cyclohexyl(3-chloropheny1) (cyclohex-z-enyl) phosphine (Cyclohex-Z-amyl) 4-methoxyphenyl )phosphine (Iso-octenyl) (4-phenoxyphenyl) cyclooctylphosphine Isoamyl (4-trifluoromethylphenyl) (2-methyl-1-butenyl) phosphine Cyclohexylmethyl(4-bromophenyl) (Lmethylheptyl) phosphine (Z-ethylhexyl) (4-t-'butylphenyl)heptylphosphine (Cyclooct-Z-enyl) (4-ethoxyphenyl) (4-methyl-3-penten- 1- yl)phosphine Cyclohetpyl (4-fluorophenyl isoamylphosphine Nonyl (4-i-propylphenyl) octylphosphine (Z-methylheptyl) (4-nitrophenyl cycloheptylphosphine Dicyclopentyl (4-chlorophenyl phosphine (3-methylhepty1) 2,3-dimethylphenyl isoamylphosphine Isoamyl 2,3 -dichlorophenyl cyclohexylphosphine (4-methyl-3 -penten-1-yl) (4-trifluoromethoxyphenyl) cyclohexylmethylphosphine Undecyl (4-methylphenyl nonylphosphine Isoamyl(4-i-propylpheny1)phosphine Cyclohexyl (2,4-dimethylphenyl decylphosphine (2,2,3,3-tetramethylbutyl) (4-phenoxyphenyl) cyclohexylphosphine (2-propylallyl) (4-biphenyl) dodecylphosphine Cyclohexyl(3,4-dichlorophenyl) (2,2,3,3-tetrarnethylbutyl)phosphine Cyclohexylmethyl(2,4-diethylphenyl)isoamylphosphine Isoamyl(2,5-dimethylphenyl) (3,4,5 -trimethylheptyl) phosphine Cyclopentyl(2,4-dimethylphenyl) (2-propylallyl) phosphine Dodecyl (2-methy1-S-i-propylphenyl cyclohexylphosphine Isoamy1(p-propylpheny1) (cyclooct-Z-enyl phosphine Cyclohexyl (2, 6-dichlorophenyl isoamylphosphine Cyclohexyl (2,4-dichlorophenyl) iso-octenyl phosphine (3,4,5-trimethylheptyl) (3,4-dinitrophenyl)pentylphosphine Cyclohexyl 4,4'-chlorobiphenyl) isoamylphosphine.

EXAMPLE 14 Hexyloctylpentylphenylphosphonium chloride To 76.5 g. (0.25 mole) of hexyloctylphenylphosphine in 500 ml. of acetonitrile is added 28.6 g. (0.27 mole) of pentyl chloride. The mixture is refluxed for 15 hours, concentrated in vacuo and the residue agitated with 3-200 ml. portions of hexane. The hexane is evaporated to give hexyloctylpentylphenylphosphonium chloride.

When the procedure is followed but pentyl chloride is substituted for the halides of Table I below, then the corresponding product is prepared.

TABLE I Methyl iodide Ethyl bromide Propyl bromide i-Propyl bromide Butyl bromide i-Butyl chloride Sec-butyl chloride t-Butyl bromide Allyl bromide Methallyl chloride 1-Bromo-2,4-pentadiene Z-Butenyl bromide 4-Pentenylbromide l-Propynyl chloride Propargyl bromide S-hexynyl chloride Cyclohex-Z-enylmethyl chloride 1-Bromo-2,4-cyclopentadiene Cyclopropyl bromide Cyclobutylbromide Z-methylcyclopropyl bromide 1 9 TABLE IContinued Cyclopropylmethyl chloride 2-ethylcyclopropylmethyl chloride Cyclobutylmethyl bromide Pentafluoroethyl chloride 5,5,5-trifluoro-l-bromopentane 3,3,3-trifluoro-l bromopropane.

EXAMPLE When the procedure of Example 14 is followed but pentyl chloride is replaced by the halides of Table I, Example 2 and Table 1, Example 14 and the hexyloctylphenylphosphine is replaced by the tertiary phosphines of Examples 2, 3, 4, 6, 10, ll, 12 and 13, then the corresponding phosphonium salt is prepared. A representative list of the phosphonium salts prepared is shown in Table 1, below.

TABLE I Dipentylcyclohexylphenylphosphonium chloride Dihexylpentylphenylphosphonium chloride Diheptyl-i-amylphenylphosphonium chloride Trinonylphenylphosphonium chloride Tridecylphenylphosphonium chloride Diisoamylhexylphenylphosphonium chloride Dicycloheptylheptylphenylphosphonium chloride Dicyclopentylcycloheptylphenylphosphonium chloride Dicyclohexyl(Z-ethylhexyl) phenylphosphonium chloride Dicyclohexylmethyl(t-butyl) phenylphosphonium bromide Di-(Z-propylallyl)methylphenylphosphonium iodide Di-( 4-methyl-3 -penten-1-yl) (4-pentenyl) phenylphosphonium bromide Di- (cyclooct-Z-enyl)methylphenylphosphonium iodide Di-(iso-octenyl)ethylphenylphosphonium bromide Trioctyl(p-tolyl) phosphonium chloride Dioctyl(i-propyl) (p-ethylphenyl) phosphonium bromide Dioctyl( 3-methylheptyl) (p-bromophenyl phosphonium chloride Dioctylallyl(p-chlorophenyl)phosphonium bromide Dioctylallyl(p-nitrophenyl) phosphonium bromide Dioctyl(2-propylallyl) (2-methyl-4- bromophenyl)phosphonium chloride Dioctylcyclopropylmethyl p-biphenyl) phosphonium chloride Dioctyl( S-hexynyl) (p-methoxyphenyl phosphonium chloride Dioctylhexyl(phenoxyphenyl)phosphonium chloride Dipentyl-t-butyl(p-chlorophenyl)phosphonium bromide Dihexylallyl(pchlorophenyl) phosphonium bromide Diheptyl-i-propyl (p-chlorophenyl phosphonium bromide Diisoamylhexyl(p-chlorophenyl)phosphonium chloride Dicycloheptyl-i-amyl (p-chlorophenyl) phosphonium chloride Dicyclohexylhexyl (p-chlorophenyl phosphonium chloride Dihexylpropargylphenylphosphonium bromide Dicyclohexylmethyl (hexyl) (p-chlorophenyl) phosphonium chloride Di-(2-propylallyl)-i-butyl(p-chlorophenyl)phosphonium chloride Diheptylhexyl(p-tolyl) phosphonium chloride Diheptylarnyl(p-nitrophenyl)phosphonium chloride Triisoamyl(p-methoxyphenyl)phosphonium chloride Tricyclohexylmethyl p-bromophenyl phosphonium chloride Tricycloheptyl(p-trifluoromethylphenyl)phosphonium chloride Diisoamylhexyl(p-rnethoxyphenyl)phosphonium chloride Tripentyl (p-tolyl) phosphonium chloride Trihexyl(p-bromophenyl)phosphonium bromide Tricyclopentyl(p-trifiuoromethoxyphenyl)phosphonium chloride Heptyl(p,p'-chlorobiphenyl)phosphonium chloride 20 Di- Z-methylheptyl hexyl p-methoxyphenyl) phosphonium chloride Dihexyloctyl(2-chlorophenyl)phosphonium chloride Dihexylpentyl(3-chlorophenyl)phosphonium chloride Dihexylpentyl(4-chlorophenyl)phosphonium chloride Dihexylpentyl (2,3-dichlorophenyl phosphonium chloride Trihexyl(3,5-dichlorophenyl) phosphonium chloride Dihexylheptyl(3,4-dichlorophenyl)phosphonium chloride Dihexylisoamyl(4-t-butylphenyl)phosphonium chloride Dihexyl pro pyl 2,4-dimethylphenyl) phosphonium bromide Dihexylmethallyl(Z-ethoxyphenyl) phosphonium chloride Trihexyl(4-ethoxyphenyl)phosphonium chloride Trihexyl(4-fluorophenyl) phosphonium chloride Dihexylcyclopropyl(2-bromophenyl)phosphonium bromide Dihexylcyclobutylmethyl 3-bromophenyl) phosphonium bromide Dihexyloctyl(4-bromophenyl)phosphonium chloride Dihexyl-i-propyl (4-ipro pylphenyl) pho sphonium bromide Trihexyl(2-methyl-5-i-propylphenyl)phosphonium chloride Dihexyl (2,4pentadienyl) 2-methoxyphenyl) phosphonium bromide Dihexylmethallylphenylphosphonium chloride Dihexylheptyl(Z-nitrophenyl) phosphonium chloride Trihexyl(4-nitrophenyl)phosphonium chloride Trihexyl(4-phenoxyphcnyl)phosphonium chloride Dihexyl(3,3,3-trifiuoropropyl) (4-trifluoromethylphenyl)phosphonium bromide Trihexyl (4-biphenyl) phosphonium chloride Dihexyl-t-butyl (4-methylphenyl) pho sphonium bromide Dihexylethyl 2,4-diethylphenyl) phosphonium bromide Dihexylcyclobutyl 3 -methoxyphenyl phosphonium bromide Trihexyl(4-methoxyphenyl) phosphonium chloride Trihexyl(2,4-dichlorophenyl)phosphonium chloride Trihexyl(2,6-dichlorophenyl)phosphonium chloride Pentylheptylhexylphenylphosphonium chloride Dihexyl-t-butylphenylphosphonium chloride Heptylhexylmethallylphenylphosphonium chloride Nonylhexylallylphenylphosphonium chloride Decylethylhexylphenylphosphonium chloride Undecylcyclopropylhexylphenylphosphonium chloride Dihexyldodecylphenylphosphonium chloride Isoamylethylhexylphenylphosphonium chloride (2-methyl-1-butenyl) -i-propylhexylphenylphosphonium bromide (Cyclohex-Z-enyl) pentylhexylphenylpho sphonium chloride Cyclooctylheptylhexylphenylphosphonium chloride Cycloheptylpentylhexylphenylphosphonium chloride Cyclopentylpentylhexylphenylphosphonium chloride Dicyclohexylhexylphenylphosphonium chloride Dicyclohexylmethylhexylphenylphosphonium chloride (3,4,5-tri-methylheptyl)methylhexylphenylphosphonium iodide (2-propylallyl)hexylmethylphenylphosphonium iodide (4-methyl-3-penten-l-yl)hexylpentylphenylphosphonium chloride Dihexyl(Z-butenyl)phenylphosphonium bromide (Z-methylheptyl)hexylisoamylphenylphosphonium chloride 3-methylheptyl )hexyl (2-propylallylphenylpho sphonium chloride (2-ethylhexylhexyl)cyclohexylphenylphosphonium chloride (2,2,3,3-tetramethylbutyl)hexylpropylphenylphosphoniurn bromide 21 ITABLE I-"Oon't'inired I (Cyclooct-Z-enyl)hexylisoamylphenylphosphonium chloride V j Iso octenylhexylcyclohexylphenylphosphonium chloride 1 Octylpentylisoamylphenylphosphoniurn chloride I Octylcyclopentylheptylphenylphosphonium chloride Dioctylmethylphenylphosphonium chloride I y Dioctylisoamylphenylphosphonium chloride Octyl(2-methyl-l-bntenyl)propylphenylphosphoninm v bromide Ovtyl (cycloheX-Z-enyl) -i-butylphenylphosphonium chloride j Octylcyclooctyl(iso-octenyl)phenylphosphonium chloride Octylcyclopentylpropargylphenylphosphonium chloride Octylmethylcycloh'exylmethylphenylphosphonium iodide ctyl(2-propylallyl)propargylphenylphosphoninm chloride Dioctyl(4-methy1-3-penten-1-yl)phenylphosphonium chloride N v octylhexylpropyl(4-chlorophenyl)phosphonium bromide Octylhexyl(2-ethylhexyl(2,3-dichlorophenyl)phospho-t. nium chloride V Octylhexyl-t-butyl(4-t-butylphenyl)phosphonium chloride Octylhexylpropynyl(2,3-dimethylphenyl)phosphonium chloride Y Octylhexylcyclobutylmethyl(2,4-dimethylphenyl)phos- I phonium chloride Octylhexylmethyl(2-ethoxyphenyl) phosphonium iodide Octylhexylpentafluoroethyl(4-fluorophenyl)phosphonium chloride Octylhexyl-i-butyl(2 bromophenyl)phosphonium chloride Dioctylhexyl(4-bromophenyl)phosphonium.chloride Octylhexyl(2,4-cyclopentadien-l-yl) (4-i-propylphenyl) phosphonium chloride Octylhexylcyclobutyl(2-methoxyphenyl) phosphonium chloride V. t t Octylhexyl(Z-methylcyclopropyl) (4-nitrophenyl)phosphonium chloride octylhexylpropyl(4-trifluoromethylphenyl)phosphonium bromide r r Dihexyl(2,4-cyclopentadien-1-yl)phenylphosphonium bromide Octylhexyl(2-ethylhexyl) (4-methoxyphenyl)rihosnhonium chloride V V Octylhexylcyclohexyl(2,4-dichloropheny1)phosphonium Y chloride r J- OctylheXyl-i-propyl(p-propylphenyl)phosphonium bromide v r 1 Pentyl-i-propyl(2-chlorophenyl)hexylphosphonium Y bromide r Pentyl-i-propyl(4-chlorophenyl)hexylphosphonium bromide Pentylisoamyl(3,5-dichlorophenyl)hexylphosphonium chloride 1 t v Pentyl-t-butyl(3,4-dichlorophenyl)hexylphosphonium bromide @V Pentyl(pentenyl) (4-t-butylphenyl)hexylphosphonium chloride I H" j I Pentyl(Z-methylcyclopropyl) (2 ,4-di methylphenyl.)hexylphosphonium chloride Dipentyl (4-ethoxyphenyl)hexylphosphonium' chloride Pentylpropyl(4-fluorophenyl)hexylphosphoniumbromide Pentyl-sec-butyl(Z-bromophenyl)hexylphosphonium. chloride I j Dipentyl(4-i-propylphenyl)hexylphosphonium chloride Pentylisoamyl(4-nitrophenyl)hexylphosphoninm chloride Pentylmethyl(4-triflnoromethylphenyl)hexylphosphonium iodide v t Pentyl(cyclohex-Z-enylmthyl) (4-methylphenyl) hexylv phosphonium chloride Penty(2-ethylcyclopropylmethyl) (4-methoxyphenyl) v hexylphosphonium chloride a -1 Dipentyl(2,4-dichl0rophenyl)hexylphosphonium' chloride Penty1(3,3,3-trifluoropropyl) 2,-6 .-dichlorophenyl)hexyl .1

phosphonium chloride Dicyclooctyl(2-bromophenylpentylphosphonium chloride (Z-methyl-l-butenyl) (Z-ethylcyclopropylmethyl) (2- ethoxyphenyl) (2-ethylhexyl)phosphonium chloride chloride Dicyclohexyl (3 -bromophenyl pentylphosphonium chloride (Cyclohex-Z-enyl ethyl (4-methoxyphenyl phosphonium bromide Diisoamyl(4-trifluoromethylphenyl) (Z-methyl-l-butenyl) phosphonium chloride I Dicyclohexylmethyl(4-bromophenyl) (2-methylheptyl) phosphonium chloride (Z-ethylhexyl) propyl (4-t-butylphenyl) heptylphosphonium bromide Dihexylcyclopropylphenylphosphonium bromide Allyl (cyclooct-2-enyl) (4-ethoxyphenyl) (4-methyl-3- penten-l-yDphosphonium bromide Cycloheptyl(4-fluorophenyl)isoamylphosphonium chloride (Z-methylheptyl) cyclopropyl (4-nitrophenyl) cycloheptyl phosphonium chloride Diisoamyl(3,4-diethylphenyl)phosphonium chloride (2,2,3,3-tetramethylbutyl)isoamyl(4-phenoxyphenyl) cyclohexylphosphonium chloride (Z-propylallyl) a1lyl(4-biphenyl) do decylphosphonium chloride Isoamyl(2,5-dimethylphenyl)pentyl(3,4,5-trimethylhepty1)phosphonium chloride Cyclopentylmcthyl(2,4-dimethylphenyl) (2-propylallyl) phosphonium chloride lsoamyl(p-propylphenyl)hexyl(cyclooct-2-enyl)phosphonium chloride Cyclohexylhexyl(2,6-dichlorophenyl)isoamylphosphonium chloride Cyclohexyl(2,4-dichlorophenyl)isoamyl(iso-octenyl) phosphonium chloride (3,4,5 -trimethylheptyl) (2-ethylhexyl) (3,4-dinitrophenyl) pentylphosphonium chloride Tripentylphenylphosphonium chloride Trihexylphenylphosphonium chloride Triheptylphenylphosphonium chloride Trioctylphenylphosphonium chloride Triisoamylphenylphosphonium chloride Tricyclopentylphenylphosphonium chloride Tricyclohexylphenylphosphonium chloride Tricycloheptylphenylphosphonium chloride Dipentylhexylphenylphosphonium chloride Dipentylheptylphenylphosphonium chloride Dipentyloctylphenylphosphonium chloride Dihexylpentylphenylphosphonium chloride Tricyclohexylmethylphenylphosphonium chloride Tri- ('3,4,S-trimethylheptylphenylphosphonium chloride w Dihexyl(4-pentenyl)phenylphosphonium bromide Tri-(2-propylallyl)phenylphosphonium chloride 'Tri-(4-methyl-3-penten-1-yl)phenylphosphonium chloride I Tri-(Z-mthylhptyl phenylphosphonium chloride Tri- 3 -methylheptyl) phenylphosphonium chloride Tri-(2-ethylhexyl)phenylphosphonium chloride Tri-(2,2,3,3-tetramethylbutyl)phenylphosphonium chloride Tri- (cyclooct-Z-enyl) phenylphosphonium chloride Tri- (iso-octenyl) phenylphosphonium chloride.

EXAMPLE l6 Dihexyl (p-trifluoromethylbenzyl)phenylphosphonium chloride Didodecylphenylbenzylphosphonium chloride to obtain dihexyl(p-trifluoromethylbenzyl)phenylphosphonium chloride. 7

When p-trifiuoromethylbenzyl chloride in the above example is substituted by the benzyl halides of Table. I below, then the corresponding product is prepared.

TABLE I Benzyl bromide Benzyl chloride Benzyl iodide p-Trifluoromethoxybenzyl chloride.

p-Trifiuorooctylbenzyl chloride o-Trifluoromethylbenzyl chloride p-Trifiuoromethylsulfonylbenzyl chloride o-Chlorobenzyl chloride m-Chlorobenzyl chloride p-Chlorobenzyl chloride 2,3-dichlorobenzyl chloride 2,4-dichlorobenzyl chloride.

2,5-dichlorobenzyl chloride 2,6-dichlorobenzyl chloride 3,4-dichloroberizyl chloride 3,5-dichlorobenzyl chloride 2,3,4-trichlorobenzyl chloride 2,3,5-trichlorobenzyl chloride 2,3,6-trichlorobenzyl chloride 3,4,5-trichlorobenzyl chloride p-Ditrifiuoromethylsulfonylbenzyl chloride p-Bromobcnzyl bromide m-Nitrobenzyl chloride pNitrobenzyl chloride p-Cyanobenzyl chloride 2,6-difluorobenzyl chloride 2,4-dibromobenzyl bromide 2,4-difiuorobcnzyl chloride 2-bromo-4-nitrobenzyl bromide 3,5-difluorobenzyl chloride o-Fluorobenzyl chloride p-Fluorobenzyl chloride 2,6-dichloro-4-fiuorobenzyl chloride I 2-fluoro-4-trifiuoromethylbenzyl chloride 4-fiuoro-3-trifluoromethylbenzyl chloride wMethylbenzyl chloride i a-Ethylbenzyl chloride V.

a-Methyl-p-chlorobenzyl chloride a-Methyl-p-fiuorobenzyl chloride a-Methyl-p-nitrobenzyl chloride u-Methyl-2,4-difiuorobenzyl chloride a-Methyl-p-trifiuoromethylbenzyl chloride J v u-Methyl-p-bromobenzyl bromide.

'EXAMPLE 17 I n When the procedure of Example 16 is followed, 'ut'ptrifiuoromethylbnzyl chloride is replacedby thefbenzyl 5 halides of Table I, Example 16 and the tertiary phosphihe is selected from Examples 2, 3, 4,5,1'0;';11, 2;gfia,;

then the corresponding phosphonium saltj is prepar d; A

representative list of the phosphonium salts prgparediis shown in 'ltableI, below.

TABLE I Diisoamylphenylbenzylphosphonium chloride K Di Z-methyll-butenyl phenylbenzylphosphonium v f chloride 7 f l Dicyclooctylphenylbenzylphosphonium chloride v i 24 Dicycloheptylphenylbenzylphosphonium chloride Dicyclopentylphenylbenzylphosphonium chloride Dicyclohe'xylphenylberizylphosphonium chloride Dicyclohexylmethylphenylbenzylphosphonium chloride Di- 3 ,4, S-trimethylheptyl phenylbenzylphosphonium chloride I Di-(Z-propylallyl) phenylbenzylphosphoniurn chloride Di- (4-methyl-3-penten-1-yl)phenylbenzylphosphonium chloride Di-(2-methylheptyl)phenylbenzylphosphonium chloride Di-(3-methylheptyl)phenylbenzylphosphonium chloride Di-(Z-ethylhexyl)phenylbenzylphosphonium chloride Di- (2,2,3 ,3-tetramethylbutyl) phenylbenzylphosphonium chloride Di-(cyclooct-Z-enyl)phenylbenzylphosphonium chloride Di-(iso-octenyl)phenylbenzylphosphonium chloride Dioctyl(p-tolyl)benzylphosphonium chloride Dioctyl (p-brornophenyl) (p-bromobenzyl) phosphonium bromide Dioctyl(p-chlorophenyl) (p-chlorobenzyl) phosphonium chloride I Dioctyl (p-nitrophenyl) (p-nitrobenzyl) phosphonium chloride Dioctyl(2,5-dimethylphenyl)benzylphosphonium chloride Dioctyl (p-methoxyphe nyl) (p-trifluorornethylbenzyl) phosphonium chloride Dio ctyl (p-trifiuoromethylphenyl benzylphosphonium chloride Dio ctyl (p-trifluoromethoxyphenyl benzylphosphonium chloride C Dipentyl(p-chlorophenyl)benzylphosphonium chloride Dihexyl(p-chlorophenyl)benzylphosphonium chloride Diheptyl(p-chlorophenyl') benzylphosphonium chloride Diisoamyl(p-chlorophenyl)benzylphosphonium chloride Di- (cyclohex-Z-enyl) (p-chlorophenyl) (p-chlorobenzyl) phosphonium chloride Dicyclooctyl(p-chlorophenyl)benzylphosphonium chloride v i Dicycloheptyl(p-chlorophenyl benzylphosphonium chloride I" 3' t- Dicyclohexyl(p-chlorophenyl) (2,4-difluorobenzyl) phosphonium chloride- Dicyclohexylmethyl (p-chlorophenyl) a-methylbenzyl) .phosphoniumchloride Diheptyl(p-tolyl)benzylphosphonium chloride Diheptyli-pmitrophenyl')benzylphosphonium chloride Diisoamyl(p-methoxyphenyl) (p-methoxybenzyl)phos-' phonium chloride y Y 1: Dicycloheptyl(p-trifluoromethylphenyl) (p-fluorobenzyl) phosphonium chl oride- Diisoamyl(p-methoxyphenyl)benzylphosphonium o id nem Didecyl(p-biplienyl')benzylphosphonium chloride 2 P p'-t ly )benzylphosphonium chloride 4 Di-(cyclooct-Z-enyl) (2,5-dimethylphenyl)benzylh sphoni m-chlori e Di-(cyclohex-Z-en l) (p-tolyl)benzylphosphonium Qfidfii F-f J: jsf'j a Y Dihexyl(p-bromophenyl)phosphonium chloride I Dic-yclohegrylQ2fmethyl-v4rbromophenyl)benzylphose phoniuin chloride 1 Y I Di;(isggctenybwdolyl)phosphonium chloride prcyelooctylprriitrophenyl)benzylphosphonium chloride D dodecylup phenoxyphenyl)benzylphosphonium chloride Dicyclopentyl(p-trifluoromethoxyphenyl)phosphonium ,p chlorobiphenyl)berizylphosphonium fl -chloride, i Di-(Z-methylheptyl) (p-methoxyphenyl)benzylphos-i nivmw hl r de r Dihexylphenyl (p-trifluoromethoxybenzyl) phosphonium chloride 1 Dihexylphenyl(o-trifiuoromethylbenzyl)phosphonium -ichlor ide Y a Dihexylphenyl(o chlorobenzyl)phosphonium chloride 27 28 TABLE I-Continued v I I therapeutically effective amount of a compound of the Cyclohexyl(3-chlorophenyl) (cyclohex-Z-enyl) formula:

benzylphosphonium chloride X I (Cyclohex-Z-enyl) (4-methoxyphenyl)benzylphosphonium L chloride I 5 I Y I Cyclohexylmethyl(4 bromophenyl)(Z-methylheptyl) benzyl phosphonium chloride I where: I I (Z-Ethylhexyl) (4-t-butylphenyl)heptylbenzylphos- I m d Y are hydrogen: HUOTQ, 1 bromo Q phonium chloride Y I filloromethyl; I I I Cycloheptyl(4-fiuorophenyl)isoamylbenzylphosphoniu and are 1 3 yl hePtYl, cycloamy Q F chlorida cyclohexyl, cycloheptyl or cyclooctyl; Nony1(4.i propy1pheny1)octylbenzylphosphonium R may also be benzyl or substitutedbenzyl of the chloride formula (2-methylheptyl) (4-nitrophenyl) cycloheptylbenzyl- I R, 4

phosphonium chloride I i 15 R1 Dicyclopentyl(4-chlorophenyl)benzylphosphonium I I Rl- 4311-, I

chloride Isoamyl(2,3-dichlorophenyl)cyclohexylbenzylphos- 7 R;

phonium chloride I I where: e I I Isoamyl(p-tolyl)benzylphosphomum chloride. I K1 is hydrogen or methyl R2, R3 R4, R5 and Ila-are hydrogen, fiuoro, chloro or bromo; a EXAMPLE 18 AfllS chloride, bromide or iodide. Dihexyloctylphenylphosphonium brromide 2. 'The method of claim 1 wherein the compound is trioctylphenylphosphonium chloride. it 26 g. of dihexyloctylphenylphosphomum chloride 1 3, The method of claim 1 wherein the compound is triadded to 200 ml. ofa saturated aqueous soduim bromide 1 h 1 h h hlo I solution. The mixture is then heated to 90, the. solid is gag g gig s 1v z the compound is UL melted ano the mixture is stirred for 'min., cooled in heptflphenylphosphonium chlorideI I II I an ice-bath and the water decanted. Another 200 ml. of 5 The methodofclaim 1 wherein the compound is saturated sodium bromide solution is added and the procyclohexylphenylphosphonium chlorida Cedure repeated The ion exchanged phosphonium 6. The method of claim 1 wherein the compound is trimide is filtered, washed with 1 liter of water followedby h l h n lphosphonium chloride. 7 2*200 Portions of hexane The Product is then heated 7 .A method of treating "gastrointestinal hyperacidity twice with 300 of distilled watel: until a melt cooled or ulceration in a human or mammal which comprises the and thefvaier decanted mturated h f dned oral or parenteral administration thereto of a therapeutit0 $12 5 tg g gsgyg fia gi i ci fig gsg g thg g fiszm cally elfective amount of a compound of the formula: plc is replaced with a solution of an appropriate salt of X Table I below, then the corresponding desired phospho- I t 1, niurn salt of Table 11 below is obtained. IY I TABLEI 1 where/f7" I I I I I I X'andIY are hydrogen, halo or haloloweralkyl; sqdPlm'lodlde potassfum R" and'R are a 5 to 12'carbon atom member which 2 39 g z g} t may be straightchained, or branchedand are: alkyl 0 rum n1 rae t I o rum p osp aer m 1 I E S -Wt t F g ll sw I R is loweralkyl, loweralkenyl, loweralkynyl or cyclo- 61 m e O 611203? I loweralkylloweralkyl', I Sodium'acetate Sodium methanesulfonate" is chlorlisleIIybl-omiIdeI iodide, lIlIitl-atev phosphatg or sulfate. LE H t 8.Themethod ofclaim7nwher'ei Dihexyloctylphenylphosphonium iodide j e X and-LY are hydrogen; fluoro, chloro, bromo 'or tri- Dihexyloctylphenylphosphonium sulfate I I I fluoromethyl; I f I II I Dihexyloctylphenylphosphonium nitrate 7 R and "R areamyl,'-hexyl"heptyl,octyl, cycloamyl, Dihexyloctylphenylphosphonium maleate I II I cyclohexyl, cycloheptyl or cyclooctyl;

R isa' 1owere1k3/ 1, loweralkenyl, lowerallcynyl, cycloloweralkyl orcycloloweralkylloweralkyl I A is .chlo t ide bromide or iodid e. I

Dihexyloctylphenylphosphonium citratev Dihexyloctylphenylphosphonium acetate Dihexyloctylphenylphosphonium oxalate Dihexyloctylphenylphosphonium bromide Dihexyloctylphenylphosphonium phosphate Dihexyloctylphenylphosphonium bromide Dihexyloctylphenylphosphonium benzoatej I' Dihexyloctylphenylphosphonium methanesulfonate. I

: -+Refer'ences'Cited-" I yNlTnn tSIATES P gaIliNTs j;

3,281,365,; 19219 6}. ,Moedritzer- 3,642,989 2/1972 Martinet a1.

When the appropriate phosphonium'saltis edfo r I I II I any of the compounds of this invention, above P i E i' procedure may be used" F. Assistant Examiner We claim: I I

1 .'A method of'treating gastrointestinal hyperacidity I or ulceration in a human or mammal which 'compr ises I the; oral or, parenteral administration *fliereto -bf f a 21 218