Method of preparing phthalide

Method for preparing phthalide by the catalytic dehalogenation of 3-chlorophthalide in the presence of hydrogenation catalyst and in the presence of an HCl acceptor. The phathalide which is produced is a valuable chemical intermediate for the manufacture of dyes, plant protecting agents and pharmaceuticals.

BACKGROUND 
The invention relates to a method of preparing phthalide by the catalytic 
dehalogenation of 3-chlorophthalide in the presence of HCl acceptors. 
Numerous processes are described in the literature for the preparation of 
phthalide by reactions of o-disubstituted benzenes, such as phthalic acid 
dichloride, o-xylyl chloride, o-tolylic acid, o-phthalic aldehyde, 
o-xylylene glycol, phthalimide and the like. Phthalide is formed from 
these starting substances only after a plurality of difficult process 
steps or in an unsatisfactory yield. Other methods of preparing phthalide 
are the reductions of phthalic acid anhydride, which are performed, for 
example, with zinc and glacial acetic acid (Ber. 17, 2178 [1884]), by 
catalytic hydrogenation with noble metal catalysts (F. Zymalkowski, 
"Katalytische Hydrierung im Organisch-Chemischen Laboratorium," Ferd. Enke 
Verlag Stuttgart, 1965, page 186), or in the presence of nickel (German 
Reich Pat. No. 368,414). 
In these reductions of phthalic acid anhydride to phthalide, reaction water 
forms, which leads to trouble in the course of the hydrogenation and 
results in contaminated products. These disadvantages are partially 
overcome in the electrochemical reduction of phthalic acid anhydride 
(Bull. Chem. Soc. Japan 7, 127 [1932], German Offenlegungsschrift No. 
2,144,419), yet the performance of electrochemical processes generally 
presents technical difficulties and involves a relatively great investment 
in apparatus. 
THE INVENTION 
It has been found that phthalide can be prepared in surprisingly good 
yields and free of by-products in a simple manner by the dehalogenation of 
3-chlorphthalide in the presence of HCl acceptors. 
The reaction takes place in accordance with the equation: 
##STR1## 
The dehydrohalogenation of 3-chlorophthalide can be performed, for example, 
by the reaction of 3-chlorophthalide, in substance or dissolved in an 
inert organic solvent, in the presence of catalysts and HCl acceptors at a 
slight hydrogen excess pressure, thus forming phthalide. 
The process of the invention is not limited to a specific type of catalyst. 
Usable are noble metal catalysts and especially hydrogenation catalysts of 
the 8th Group of the Periodic Table of the Elements. Preferred catalysts 
are palladium and nickel. The catalyst can be used plain or precipitated 
on a support. Suitable supporting substances are carbon, aluminum oxide, 
silicon dioxide, barium sulfate, bentonite, diatomaceous earth and 
kieselgur. The catalyst is used in an amount of about 0.1 to about 15%, 
preferably about 0.1 to about 8%, of the weight of the 3-chlorophthalide. 
The reaction of 3-chlorophthalide takes place at a high speed between about 
-10.degree. and about 150.degree. C., at pressures of about 0.2 to about 
100 bars. The preferred range is at temperatures of about 10.degree. to 
about 70.degree. C. and at pressures of about 1 to 20 bars. 
Aliphatic, cycloaliphatic and aromatic hydrocarbons can, for example, be 
used as solvents, but so can ethers such as diethyl ether, 
dimethoxyethane, tetrahydrofuran and dioxane, organic carboxylic acids 
such as formic acid, acetic acid, propionic acid and their esters, and 
tertiary aliphatic or aromatic amines. 
For the neutralization of the hydrochloric acid that forms in the reaction, 
HCl acceptors are used in at least stoichiometric quantity. Suitable for 
this purpose are for instance, not only tertiary amines, such as 
triethylamine and N-dimethylaniline, but also inorganic compounds such as 
sodium carbonate, sodium bicorbonate, sodium formate and sodium acetate. 
Instead of the above-named sodium compounds, the corresponding potassium 
(or other alkali metal) salts or the salts of the alkaline earth metals 
can also be used with equal success. 
The isolation of phthalide can be performed after the reaction has ended by 
separating the catalyst together with the salt that has formed. The 
catalyst can be reused for additional dehalogenations after the salt has 
been washed out of it. After distilling out the solvent, phthalide is then 
obtained by simple vacuum distillation, in purities of up to 99.35% 
(gas-chromatographic analysis). 
The phthalide prepared by the method of the invention is a valuable 
chemical intermediate for the manufacture of dyes, plant protecting agents 
and pharmaceuticals. 
The phthalide which is produced is a valuable chemical intermediate for the 
manufacture of dyes, (e.g. derivates of anthrachinone) or 3-bromo 
phthalide, which is used to introduce the phthalidyl-group in antibiotics 
(e.g. U.S. Pat. Nos. 3,860,579; 3,919,196; 3,939,180; 3,963,792 and 
3,963,704). Furthermore phthalide is used as a plasticizer for 
nitrocellulose.

EXAMPLES 
The following examples will serve to explain the invention: 
Example 1 
A 1-liter lift magnet autoclave is charged with 110 g of 3-chlorophthalide, 
10 g of nickel catalyst RCH 55/10 (commercial product of Farbwerke Hoechst 
AG) and 400 ml of tetrahydrofuran to which 66 g of triethylamine is added. 
After purging the air with nitrogen, hydrogen is pumped in to a pressure 
of 10 bars, and the temperature is raised, with stirring, to 65.degree. C. 
The hydrogen consumption is compensated by additions in the range between 
10 and 20 bars for a period of 41/2 hours. After the absorption of 
hydrogen ceases, the catalyst and precipitated salt are filtered out and 
the solvent is withdrawn. After distillation of the residue between 
88.degree. and 90.degree. C. and 0.2 Torr, 77.5 g of phthalide is 
obtained, of a melting point of 71.degree. C. (gas-chromatographic 
analysis 98.95%). 
Yield: 89% of the theory. 
Example 2 
As described in Example 1, an autoclave is charged with 110 g of 
3-chlorophthalide, 5 g of palladium-on-charcoal catalyst (metal content 
5%), 54 g of sodium acetate and 400 ml of glacial acetic acid, and treated 
for 1.5 h with hydrogen at 5 to 10 bars of pressure and 20.degree. to 
35.degree. C. After filtration and working up by distillation, 76.5 g of 
phthalide is obtained, melting point 72.degree.-73.degree. C. 
(gas-chromatographic analysis 99.35). 
Example 3 
The catalyst filtered off in Example 2 is washed three times with 20 ml of 
warm water and 10 ml of acetic acid each time. With the use of this 
catalyst and the amounts and conditions specified in Example 2, 75.9 g of 
phthalide are obtained having the same purity as in Example 2.