DE1176657B - Process for the preparation of quaternary phosphonium compounds - Google Patents

Description

Process for the preparation of quaternary phosphonium compounds Alkylations of carbon and heteroatoms with the help of quaternary ammonium salts are in known in large numbers. Experience has shown that they run smoothly under relatively mild conditions, if either the transfer of a ligand of the ammonium ion to the one to be alkylated Center favored by a mesomerism stabilization of this residue as a carbenium ion or if the ammonium salt after elimination of tertiary amine is an unsaturated System capable of forming which the condensation partner through Michael reaction added (cf. Angewandte Chemie, Brd. 65 [1953], pp.473 to 485).

On the other hand, there is an opposition to phosphorus alkylation with quaternary ammonium salts little known. Only condensations of di- and trialkyl phosphites with the methoiodides or methosulfates from Gramin (see Journal of organic Chemistry, Vol. 22 [1957], pp. 972 to 975; Recueil des Travaux chimiques des Pays-Bas, Brd. 77 [1958], p.1096 to 1106) and from the Mannich bases of acetone, acetophenone (cf. Journal of the American chemical Society, Brd. 77 [1955], pp.3101 to 3103) and ß-acetylindols (cf. Journal of the American Chemicai Society, Brd. 80 [1958], pp. 3782 to 3787; U.S. Patent 2,849,454) have been described.

It has now been found that quaternary phosphonium salts can thereby be obtained can be obtained by quaternary salts of Mannich bases of aromatic or heterocyclic Compounds in an organic solvent with tertiary phosphines under reflux heated.

The reaction is illustrated by the following equation: Suitable organic solvents are, for. B.

Methanol or dimethylformamide. The implementation is preferably under Passing through nitrogen carried out.

Of the quaternary salts of Mannich bases suitable as starting materials are especially the methoiodides and methosulfates of the dimethylaminomethyl derivatives of antipyrine, indole, N-methylindole, neroline, phthalimide and acetophenone, of the suitable tertiary phosphines especially called triethyl and triphenylphosphine.

The products of the process according to the invention are valuable intermediate products for a wide variety of syntheses. Some of them are also suitable for use as pharmaceuticals.

Example 1 3.87 g (0.01 mol) of dimethylaminomethyl antipyrine methoiodide and 3.93 g (0.15 mol) of triphenylphosphine are in 25 cc of dimethylformamide for 3 hours refluxed while bubbling with nitrogen, after which the amount of evolved Trimethylamine (identified by its mixed melting point Picrats and controlled by collecting in 1 / lo n hydrochloric acid) has reached 950/0 of theory. After evaporating the solvent in vacuo and removing the excess Triphenylphosphine by boiling the powdered, crystal clear, light yellow solid 5.6 g (96%) of a yellow product with a melting range of 180 are left behind up to 190 "C. Recrystallization from water gives 3.9 g of antipyrylmethyl-triphenyl-phosphonium iodide (67%) from m.p. 193 to 194 "C.

Example 2 2.9 g (0.0075 mol) of dimethylaminomethyl antipyrine methoiodide and 1.8 g (0.015 mol) of triethylphosphine develop on boiling in 25 cc of dimethylformamide under nitrogen within 40 minutes 900 / o of the calculated amount of Trimethylamine. After 3l / 2h boiling the solvent is evaporated in vacuo, the greasy yellow residue from an ethanol-ether mixture for crystallization brought. Man receives 3 g of antipyrylmethyl-triethyl-phosphonium iodide (88 ° / o) from m.p. 179 to 1800C.

Example 3 3.0 g (0.01 mol) of gramin methosulfate are added with 0.393 g (0.015 mol) triphenylphosphine 1 1/2 hours in 30 cc of methanol under nitrogen cooked. Working up in the manner described in Example 6 follows recrystallization from water to give 3.5 g of skatyl triphenyl phosphonium methyl sulfate (70%), a pale pink colored salt with a melting point of 185 to 186 ° C.

When heated with caustic soda, the scent odor occurs.

Example 4 N-methylskatyl-triphenyl-phosphonium iodide is obtained after Boiling 3.3 g (0.01 mol) of N-methylgramine methoiodide with 0.393 g (0.015 Mol) triphenylphosphine in 25 ccm dimethylformamide under nitrogen and work-up as in Example 1. Recrystallization from water-ethanol (2: 1) gives 3.7 g (700 / o). M.p. 218 to 219 "C.

Example 5 3.6 g (0.01 mol) of x-dimethylaminomethyl-neroline methoiodide of m.p. 148 to 149 "C and 3.4 g (0.013 mol) of triphenylphosphine develop at Boiling in 30 cc of dimethylformamide under nitrogen for 90 minutes 950/0 of the expected gaseous amine. After a reaction time of 2 hours, the solvent becomes removed in vacuo and the pale yellow residue with methanol-ether for crystallization brought.

4.5 g of [2-methoxynaphthyl- (1) -methyl] -triphenylphosphonium iodide are obtained (80 0 / o). The melting point is sharp but fluctuates with the rate of heating between 226 and 245 ° C.

Example 6 3.46 g (0.01 mole) of phthalimidomethyl trimethylammonium iodide and 3.93 g (0.015 mol) of triphenylphosphine are in 40 cc of methanol for 4 hours Passing through nitrogen (trimethylamine development after 2 hours already 80%) refluxed. When cooling down, an almost colorless precipitate separates out, the is suctioned off and washed with methanol. Crude yield: 5 g (90%) from the melting range 255 to 265 ° C. After recrystallization from water, 3.2 g (58%) of phthalimidomethyl triphenylphosphonium iodide are obtained from m.p. 264 to 267 "C (decomposition) with yellow color from 255" C.

Example 7 3.2 g (0.01 mol) of (B-benzoylethyl) trimethylammonium iodide and 3.93 g (0.015 mol) of triphenylphosphine are passed through with nitrogen Boiled in 50 cc of methanol until after 6 hours 950 / o of theory of trimethylamine have been developed.

After evaporation of the solvent in vacuo, a soon solidifying remains Smear back, which after grinding in a mortar and boiling with benzene 4 g (ß-benzoylethyl) triphenylphosphonium iodide (77 ° / 0) from m.p. 158 to 159C.

After recrystallization from water, m.p. 160 to 161 "C.

Claims (1)

Claim: Process for the production of quaternary phosphonium compounds, d u r c h e k e n n nz e i c h n e t that one can quaternary salts of Mannich bases aromatic or heterocyclic compounds in an organic solvent refluxed with tertiary phosphines. Papers considered: Journal of the American Chemical Society 70: 42334234 (1948); 71: 1058-1060 (1949); Applied Chemie, 63: 377-378 (1951)