DE4407035A1 - Di:lactone(s) prodn. - Google Patents

Abstract

Dilactones are prepd. from alpha -hydroxycarboxylic acid esters of formula (I) in which R1 is 1-8C alkyl and R2 and R3 independently = H or 1-6CV alkyl, by reacting the ester (I) in the liq. phase with an affective amt. of a transesterification catalyst while distilling off the alcohol R1 -OH formed during the reaction, and isolating the dilactone from the reaction mixt.

Description

The present invention relates to a new method for Production of dilactones from alpha-hydroxycarboxylic acid esters general formula I.

in the R¹ for a C₁-C₈ alkyl radical and R² and R³ regardless of are hydrogen or a C₁-C₆ alkyl group.

WO 92/00292 teaches a continuous process for Production of dilactones from alpha-hydroxycarboxylic acids and their esters. According to this teaching, the starting connections evaporated, cyclized on a fixed bed catalyst to the dilactone and then isolated from the gaseous reaction mixture. In such a procedure, a back reaction of the Dilactons with water released during the reaction or Alcohol is to be expected, as these components are only processed tion are separated from the reaction mixture. Continues to come this method only for vaporizable starting compounds in Be dress.

The continuous production of dilactones from alpha-hydroxy carboxylic acids in a reactor with discharge of the process product as well as the water formed during the cyclization US Pat. No. 5,043,458 describes an inert gas stream This process can reverse react Dililone with alcohol lower the yield because these reaction products together in the Reaction discharge before isolation of the Dilactons joins.

The present invention was therefore based on the object Provide process for the preparation of dilactones that the avoids the disadvantages mentioned above.

Accordingly, the process defined at the outset was found, the is characterized in that an ester of formula I in liquid phase in the presence of effective amounts of a transesterification  converts catalyst, the formed during the reaction Alcohol R¹-OH distilled, and the dilactone from the reaction mixture isolated.

The implementation on which the method according to the invention is based can be illustrated by the following reaction equation.

C₁-C Formel alkyl esters come in as starting compounds of the formula I. Consider, of which C₄-C₈ alkyl esters are preferred. examples for such alkyl radicals are methyl, ethyl, n-propyl, n-butyl, amyl, Hexyl, heptyl and octyl, the longer chain alkyl residues ver branches or can preferably be straight-chain.

The acids on which the esters are based are in the alpha position Hydrogen or C₁-C₆ alkyl radicals. Preferred esters are derived from glycolic acid or lactic acid, the lactic acid being D-, L or mixture of D and L lactic acid may be present.

The starting compounds of the formula I are, for example, in known way by esterification of the alpha-hydroxycarbon acids with the corresponding alcohols available.

The esters of formula I are reacted in a reactor give, which is conveniently at the reaction temperature det. This temperature is generally 150 to 300 ° C, before preferably 200 to 250 ° C. The reaction is usually under a pressure of 1 to 10 bar, preferably under normal pressure, carried out.

The liquid reaction mixture contains a transesterification catalyst. These are to be understood as catalysts that Replacement of the alcohol components in catalytic carboxylic esters sieren. Such catalysts are e.g. B. in Ullmann's Encyclopedia of Ind. Chem., 5th edition, VCH 1987, volume A3, p. 575, described ben. In particular, such compounds come into consideration that the Structural elements CH₃OM, MOX, RCOOM and / or MOM have, wherein  M for the metals Mn, Zn, Sn, Sb, Pb, Ge, Co, Ni, Ca, Sr, Mg, Ca and Ba, X for chloride and sulfate and R for a C₁-C₁₀ alkyl radical stands. Catalysts are preferably used, which in Re action mixture are insoluble, because in these cases a simple Separation of the product from the catalyst is possible. you are for example by hydrolysis of hydroxides or carboxylates of the metals mentioned or by splitting off the organic radicals available by heating, forming MOM structures, that make the catalysts insoluble. You can do that Catalysts in bulk or on inert supports such as Al₂O₃, Use SiO₂, ZrO₂ or metals.

Particularly preferred catalysts are titanyl sulfate and Titanium compounds by hydrolysis of 1 mol titanium tetra alkoxide such as titanium tetrabutoxide with 1.1 to 1.5 mol of water Lich, preferably in the presence of a porous inert Carrier.

The catalyst must be present in the reaction mixture in effective amounts be there. When using heterogeneous catalysts, the Contact time expediently 0.01 to 10 minutes, preferably 0.1 to 1 minute.

The alcohol liberated is distilled off during the reaction. This is advantageously done through an outlet via a pressure holding valve. If necessary, esters removed with the alcohol of the formula I can after separation of the alcohol in the reaction to be led back. It has turned out to be for this separation Proven partially if the reactor is only two thirds maximum is filled.

The product-containing reaction mixture is ent liquid in the reactor taken and preferably worked up by distillation on the product. Separated oligomeric compounds resulting from the Output compounds have formed can be returned to the reactor to be led back.

The inventive method has the advantage that it desired process product quickly from that in the reaction put alcohol is separated, so that the back reaction strong can be reduced.

The process products, especially dilactide, serve as Starting material for the production of polymers which, for. B. as resorbable surgical sutures are used.

example Preparation of the catalyst

To 500 g 3 to 4 mm large Al₂O₃ pellets with a specific Surface area of 3.5 m² / g in 2 l of ethylene glycol dimethyl ether 170 g (0.5 mol) of titanium tetrabutylate added. With vigorous stirring 10.8 g (0.6 mol) of water and 200 ml of ethylene diglycol dimethyl ether were added. After 30 minutes the solid was decanted and dried under nitrogen.

Production of dilactide

In a vertical steel tube with an inner diameter of 30 mm, which is filled with 110 g of the catalyst described above, were 650 g / h L-lactic acid amyl ester, which was preheated to 230 ° C was promoted, the degree of filling by pumping the reaction swamp was kept constant. The reaction temperature was 230 ° C. Via a pressure control valve set to 2 bar distilled off at the top (340 g / h, thereof approx. 88% by weight amyl alcohol and 12% by weight of starting material).

The liquid discharge (307 g / h) was worked up by distillation and in addition to 76% by weight of L-lactide contained approx. 4% by weight of oligomers and 20% by weight of starting material. The turnover was 80% Selectivity 95%.

Claims (4)

1. Process for the preparation of dilactones from alpha-hydroxy carboxylic acid esters of the general formula I in which R¹ is a C₁-C₈-alkyl radical and R² and R³ independently of one another are hydrogen or a C₁-C₆-alkyl radical, characterized in that an ester of the formula I is reacted in the liquid phase in the presence of effective amounts of a transesterification catalyst, where the alcohol R¹-OH formed during the reaction is distilled off and the dilactone is isolated from the reaction mixture. 2. The method according to claim 1, characterized in that one a C₄-C₈ alkyl ester of D-lactic acid, L-lactic acid or a mixture of these acids. 3. The method according to claim 1 or 2, characterized in that the process at a temperature of 200 to 270 ° C. carries out. 4. The method according to claims 1 to 3, characterized in net that one partially hydrolyzed titanium tetraalkoxides or Tita nyl sulfate used as a transesterification catalyst.