Occidental Chemical Corporation

Neil J O'Reilly

Henry C Lin

Lawrence B Fertel

William S Derwin

Stanley A Sojka

Deanne M Nowak

3,4,6-trifluorophthalic acid is prepared in high yield by reaction of a 3,4,6-trichloro-N-substituted phthalimide with potassium fluoride at temperatures in the range of 200.degree. to 270.degree. C. in the absence of a catalyst to form the corresponding trifluoro-N-substituted phthalimide which, in turn, is hydrolyzed to form the 3,4,6-trifluorophthalic acid.

Preparation of 3,4,6-trifluorophthalic acid

3,4,6-Trifluorophthalic acid may be decarboxylated in a controlled manner to form 2,4,5-trifluorobenzoic acid by heating the phthalic acid in a dipolar aprotic solvent in the absence of any catalyst.

Preparation of 2,4,5-trifluorobenzoic acid by decarboxylation of

Plychlorophthalimides, specifically, N-substituted tetrachlorophthalimides and N-substituted trichlorophthalimides may be treated with zinc and a base in aqueous soluction to yield, after acidification, the product 3,5-dichlorophthalic acid or salts thereof.

Preparation of 3,5-dichlorophthalic acid and 3,5-dichlorophthalic

A process for the aromatization of 4-chlorotetrahydrophthalic anhydride and 4,5-dichlorotetrahydrophthalic anhydride which comprises heating a solution of either substance in the presence of activated carbon and in the partial absence of air.

Preparation of halogenated phthalic anhydrides

Disclosed is a method of selectively removing chlorine atoms in the order of fifth position first, fourth position second, and third position third from a chlorophthalic compound having at least two ring chlorine atoms such as a chlorophthalic acid or a chlorophthalic anhydride. The chlorophthalic compound is reacted in solution with a hydrodechlorinating metal in the presence of a base.

Selective removal of chlorine from chlorophthalic compounds

2-Chlorobenzylamine is prepared from 2-chlorobenzylchloride in a two-step process. In the first step, 2-chlorobenzylchloride is reacted with alkali metal phthalimide, preferably formed in situ from potassium carbonate and phthalimide, to form the novel intermediate 2-chlorobenzylphthalimide. In the second step, the phthalimide ring of the 2-chlorobenzylphthalimide is cleaved to form 2-chlorobenzylamine. The first step is preferably carried out in an unreactive solvent at 60.degree. C. to reflux temperature, for example, for 1 to 10 hours. The solvent is very preferably dimethylformamide which is advantageously recovered and used again as solvent in the conversion of 2-chlorobenzylchloride to 2-chlorobenzylphthalimide. The second step consists essentially, for example, of hydrazinolysis or hydrolysis. When the second step consists essentially of hydrazinolysis, the 2-chlorobenzylphthalimide is reacted with hydrazine to form 2-chlorobenzylamine and phthalylhydrazide, and the 2-chlorobenzylamine is separated by reacting with acid to form soluble amine salt, filtering out the phthalylhydrazide and then reacting the amine salt with base to convert it to the free amine. When the second step consists essentially of hydrolysis, the hydrolysis can be carried out in one step with alkali metal hydroxide or inorganic acid or in two steps, for example, with hydrolysis with alkali metal hydroxide followed by hydrolysis with inorganic acid. The hydrolysis is suitably carried out at temperatures of 60.degree. C. to reflux temperature utilizing base and acid strengths ranging from 5% to saturated. Preferred hyrdolyzing agents are 40-60% aqueous KOH for one step base hydrolysis, 40-60% aqueous sulfuric acid for one step acid hydrolysis and 10-30% aqueous KOH followed by a mixture of water and concentrated HCl in a volume ratio ranging from 0.5:1 to 2:1 for the two-step base/acid hydrolysis. A second step consisting essentially of hydrolysis is preferred over a second step consisting essentially of hydrazinolysis not only for safety reasons but also because phthalic acid or a mixture of this with 2-chlorobeznylphthalamic acid can be recovered as by-product or by-product derivative which, contrary to the hydrazinolysis by product, phthalylhydrazide, are readily, respectively, converted to phthalimide and 2-chlorobenzylphthalimide by reaction with concentrated aqueous ammonium hydroxide. The phthalimide is useful in the in situ reaction in the first step to form 2-chlorobenzylphthal-imide. 2-Chlorobenzylphthalimide which is introduced with phthalimide into said first step becomes part of the product of the first step.

Preparing 2-chlorobenzylamine from 2-chlorobenzylchloride via

Disclosed is a method of making ionized fluoroanthranilic acid from a fluorophthalic compound in a single pot process without isolating any intermediate product. A composition is prepared which comprises an aqueous solution of water, a fluorophthalic compound selected from the group consisting of ##STR1## and mixtures thereof, where 'n' is 1 to 4, at a concentration of about 5 to about 30 percent by weight based on the water weight, and about 1 to about 1.5 equivalents of hydroxylamine or a mineral acid salt thereof. The pH of the composition is maintained at at least about 11 and the temperature of the composition is maintained at at least about 90.degree. C. The unionized form of the acid is made by cooling below 50.degree. C. and lowering the pH to between about 4 and about 5. Also disclosed are the intermediate compounds, fluoro-N-hydroxyphthalimides, and a method of making them.

Single pot process for making a fluoroanthranilic acid

4,5-Difluorphthalic anhydride and 4,5-difluorophthalic acid may be decarboxylated in high yield to 3,4-difluorobenzoic acid by heating in N-methyl-2-pyrrolidone or dimethyl acetamide using copper, copper oxide, copper salts, or halides and salts of Zn, Cd, Ag and Ni as a catalyst.

Preparation of 3,4-difluorobenzoic acid by the decarboxylation of

It has been discovered that 3,4,6-trifluorophthalic anhydride may be decarboxylated by heating in a polar aprotic solvent to yield 2,4,5-trifluorobenzoic acid.

The instant invention relates to optically pure, L-(S)forms of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compounds and their method of preparation from optionally pure L-phenylalanine precursor compounds and their preparation utilizing novel in situ cationic catalyst systems.

Chiral 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and precursors

The present invention provides a process for the preparation of 2-(2-thienyl)-ethylamine and derivatives thereof having the general formula: ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen or taken together form a phenyl ring.

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Grand Island, NY, United States of America

Neil J O'Reilly