Olefinic process for preparing aryl-substituted aliphatic carboxylic esters
AssigneeEthyl Corporation
InventorTse-Chong Wu
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Abstract
A new process for preparing aryl substituted aliphatic carboxylic acid esters is provided. A 1-aryl substituted olefinic compound is reacted with carbon monoxide in the presence of an alcohol in anhydrous conditions at a temperature between about 25.degree. C. and about 200.degree. C. An excess of several moles of anhydrous alcohol is preferred. An acid such as hydrochloric acid may also be added. As catalyst, a mixture of a palladium compound and a copper compound with at least one acid-stable ligand are present.
Claims43
A process for preparing an aryl-substituted aliphatic ester having the formula:
- ##STR4## where R.sub.1 is alkyl, R.sub.2, R.sub.3 and R.sub.4 are hydrogen, alkyl, cycloalkyl, alkyl-substituted cycloalkyl, aryl either substituted or unsubstituted, alkoxy, alkylthio, heteroaryl either substituted or unsubstituted, alkanoyl, aroyl either substituted or unsubstituted, heteroarylcarbonyl either substituted or unsubstituted, trifluoromethyl or halo and Ar is unsubstituted or substituted aryl which comprises treating a compound of the formula:
- ##STR5## where Ar, R.sub.2, R.sub.3 and R.sub.4 are as previously defined and a compound of the formula R.sub.1 OH where R.sub.1 is as previously defined with carbon monoxide at a pressure of at least about 1 atmosphere and a temperature from about 25.degree. C. to about 200.degree. C. in the absence of oxygen and water and in the presence of an effective amount of a catalyst that is i) a mixture of palladium(O) or the salts of palladium and the salts of copper and (ii) at least one acid stable ligand.
A process for preparing ibuprofen which comprises carboxylating 4-isobutylstyrene with carbon monoxide in the absence of oxygen and in an anhydrous acidic medium containing tetrahydrofuran as a solvent and about 3-24 mols of anhydrous methanol or ethanol per mol of said 4-isobutylstyrene at a temperature in the range of about 25.degree.-120.degree. C. and a carbon monoxide pressure in the range of about 400-800 psig in the presence of a catalytically effective amount of (a) a mixture of a palladium(II) compound and a copper (II) compound and (b) at least one acid-stable monodentate phosphine ligand and in the presence of an amount of hydrogen chloride such as to provide an amount up to about 10 mols of hydrogen chloride per mol of 4-isobutylstyrene.
A process for preparing ibuprofen which comprises carboxylating 4-isobutylstyrene with carbon monoxide in the absence of oxygen and in an anhydrous neutral or acidic medium containing tetrahydrofuran as a solvent and about 3-24 mols of an aliphatic alcohol per mol of said isobutylstyrene and no added acid at a temperature in the range of about 50.degree.-100.degree. C. and a carbon monoxide pressure in the range of about 400-800 psig, in the presence of (a) a mixture of palladium(II inorganic salt and a copper(II) inorganic salt, and (b) at least one acid-stable monodentate phosphine ligand.
A process for preparing ibuprofen ester which comprises carboxylating 4-isobutylstyrene with carbon monoxide in an anhydrous neutral or acidic medium containing a compound selected from the group consisting of HC(OR.sub.1).sub.3, (R).sub.2 C(OR.sub.1).sub.2, HC(O)OR.sub.1, B(OR.sub.1).sub.3, Ti(OR).sub.4 and Al(OR.sub.1).sub.3 where R is hydrogen or alkyl at a temperature from about 25.degree. to about 200.degree. C. and a carbon monoxide pressure from about 300 to about 3000 psig in the presence of (a) a mixture of a palladium(II) compound and a copper(II) compound and (b) at least one acid-stable ligand.
A process of claim 44 wherein the source of alkoxide ion is a titanium(IV) alkoxide.
A process of claim 44 wherein the source of alkoxide ion is a trialkyl orthoformate.
A process of claim 44 wherein the source of alkoxide ion is a alkyl formate.
Dependencies are inferred from the claim text.