IE46947B1 - Phosphonium salts - Google Patents

Description

The present invention is concerned with phosphonium salts.

The phosphonium salts provided by the present invention have the following general formula wherein and R2 each represent a hydrogen or halogen atom or a lower alkoxy group, R3, R4»Rg and Kg each represent a hydrogen atom or a lower alkyl group, X represents an aryl group, Y represents the anion of an inorganic or organic acid and n stands for 1 or 2.

The phosphonium salts of formula I are useful intermediates for the manufacture of the therapeutically valuable polyene compounds which form the subject matter of latent Specification No. 46945.

A preferred class of phosphonium salts of formula I comprises those in which R3,R4,Rg and Rg each represent a hydrogen atom. Phosphonium salts of formula I in which R^ and R2 each represent a hydrogen atom or a lower alkoxy group are also preferred.

The lower alkyl groups and the lower alkyl moieties present in the lower alkoxy groups preferably contain up to 6 carbon atoms. They can be straight-chain or branched-chain such as, for example, the methyl, ethyl, isopropyl or 2-methylpropyl group.

The aryl groups denoted by X in formula I include all generally known aryl groups but especially mononuclear aryl groups such as phenyl, lower alkyl-substituted phenyl or lower alkoxy-substituted phenyl (e.g. tolyl, xylyl, mesityl and p-methoxyphenyl). Of the inorganic acid anions denoted by Y the chloride, bromide and hydrosulphate ions are preferred and, of the organic acid anions, the tosyloxy ion is preferred.

Examples of phosphonium salts of formula I hereinbefore are: 1-(1,1,3,3- Tetramethyl-5-indanyl)ethyl-triphenylphosphonium bromide, [1-(6-methoxy-l,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide, -4[1-(5,6,7,8-tetrahydro-5,5,8,8-teframethy1-2-naphthyl)ethyl]-triphenylphosphonium bromide and [1-(3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl -2-naphthyl)ethyl]-triphenylphosphonium bromide.

The phospnonium salts of formula 1 hereinbefore can he prepared, for example, as follows: A ketone of the general formula wherein anfl n have the significance given earlier, is reduced to give a corresponding alcohol at 0°C to +5°C using a complex metal hydride (e.g. sodium borohydride in an alkanol or lithium aluminium hydride in an ether, tetrahydrofuran or dioxan). The resulting alcohol is subsequently halogenated in the presence of an amine base (e.g. pyridine) using a customary halogenating agent (e.g. phosphorus oxychloride or phosphorus tribromide). The halide obtained is then reacted with a triarylphosphine in a solvent, preferably triphenylphosphine in toluene or -5xylene, to give a desired phosphonium salt of formula I. -5The following Examples illustrate the manner in which the phosphonium salts provided by the present invention can be prepared.

Example 1 2.66 g of lithium aluminium hydride are treated with 40 ml of absolute ether. While cooling to 0°-5°C there are added dropwise within 30 minutes 26 g of 1,1,3,3-tetramethyl-5-indanyl methyl ketone. After a further 30 minutes, the mixture is cautiously treated dropwise with 25 ml of a saturated sodium sulphate solution. The solution is filtered. The filtrate is washed once with a 1-N sodium hydroxide solution and twice with a saturated sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure to remove the solvent.

The residual oily a-l,l,3,3-pentamethyl-5-indanemethanol, which is uniform according to thin-layer chromatography [eluent: hexane/ether (SO:20], is immediately further processed as follows: 24.0 g of a-1,1,3,3-pentamethyl-5-indanemethanol are dissolved in 20 ml of absolute ether and 100 ml of absolute hexane. After the addition of 2 drops of pyridine, the solution is treated dropwise at 0°-5°C over a period of 30 minutes with 16.2 g of phosphorus tribromide dissolved in 80 ml of absolute hexane. After stirring for a further hour at 0°-5°C, the product is introduced into -7ice/water and exhaustively extracted with ether. The ether extract is washed twice each time with a saturated sodium bicarbonate solution and sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure to remove the solvent. The residual oily 5-(1-bromoethyl)-1,1,3,3-tetramethyl-indane, which is uniform according to thin-layer chromatography [eluent: hexane/ether (95:5)], is immediately further processed as follows: 26.3 g of triphenylphosphine are dissolved in 120 ml of xylene. The solution is treated with 30.9 g of 5-(1-bromoethyl)-1,1,3,3-tetramethyl-indane dissolved in 60 ml of xylene. The mixture is warmed to 100°C while stirring and left at this temperature for 12 hours. The thick-oily 1-(1,1,3,3-tetramethyl-5-indanyl)ethyl-triphenylphosphonium bromide which thereby separates and which crystallises after seeding melts at 151°-156°C after recrystallisation from methylene chloride/toluene (crystals contain 0.3 equivalent of toluene).

Example 2 [1-(6-Methoxy-l,1,3,3-tetramethyl-5-indanyl)ethyl]-triphenylphosphonium bromide can be prepared in a manner analogous to that described in Example 1 from (7-methoxy-l,l,3,3-tetramethyl-5-indanyl) methyl ketone via 7-methoxy-a-l,l,3,3-pentamethyl-5-indanemethanol and 5-(1-bromoethyl) -7-methoxy-l,l,3,3-tetramethyl-indane. 469 47 -8Example 3 [1-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) ethyl]-triphenylphosphonium bromide can be prepared in a manner analogous to that described in Example 1 from (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) methyl ketone via 5,6,7,8-tetrahydro-«-5,5,8,8-pentamethyl-2-naphthalenemethanol and 2-(bromoethyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene.

Example 4 [1-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide can be prepared in a manner analogous to that described in Example I from (3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) methyl ketone via 3-methoxy15 -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalene-methanol and 2-(l-bromoethyl)-3-methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-naphthalene.

Claims (5)

1. CIAIMS:1) Phosphonium salts of the general formula wherein R^ and R 2 each represent a hydrogen 5 or halogen atom or a lower alkoxy group, Rg,R 4 ,R 5 and Rg each represent a hydrogen atom or a lower alkyl group, X represents an aryl group, Y represents the anion of an inorganic or organic acid and n stands 10 for 1 or 2.

2. ) Phosphonium salts according to claim 1, wherein R^, R^/Rj and Rg each represent a hydrogen atom.

3. ) Phosphonium salts according to claim 1 or claim 2, wherein R^ and each represent a hydrogen atom or a 15 lower alkoxy group.

4. ) 1-(1,1,3,3-Tetramethyl-5-indany1)ethyl-triphenylphosphonium bromide. -105) [1-(6-Methoxy-l,1,3,3-tetramethyl-5-indanyl)ethyl]triphenylphosphonium bromide. 6) [1-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide.

5. 7) [1-(3-Methoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]-triphenylphosphonium bromide.