DD261362A1 - PROCESS FOR PREPARING POLYMERIZATIONAL 1,4-DIOXANE-2,5-DIONES - Google Patents

Abstract

The invention relates to a process for the preparation of polymerizable 1,4-dioxane-diones from α-hydroxycarboxylic acids in the presence of special catalysts for the oligomerization of α-hydroxycarboxylic acids and for the subsequent thermolysis of the oligoesters formed. By separate catalysis, the cyclic monomers are obtained in high yield and purity. The polymerization-disturbing, difficult to separate impurities of the uncatalyzed very non-specific proceeding oligoester thermolysis are not formed by the proposed procedure.

Description

Features of the invention

According to the invention, this object is achieved in that oligomerization and thermolysis are catalysed separately, wherein the catalysts used specifically activate the corresponding reaction stage reaction. The oligomerization of the hydroxycarboxylic acids is carried out in the presence of known polycondensation catalysts, such as antimony oxide or titanium tetra-butoxide. According to the invention, 1CT ⁴ to 10 ^-3 MoI manganese (II) compounds, such as manganese (II) salts of organic or inorganic acids, preferably manganese (II) acetate, are used for the thermolysis of the oligomeric esters The use of a specific catalyst , which activates the dioxanedione formation, in conjunction with the use of specific polycondensation catalysts in the first reaction stage already leads to a very pure dioxan-dione in Oligoesterthermolyse, which can be used directly after one or two recrystallizations from suitable solvents for polymerization The linear di-, tri- and tetramers which can be separated only by sublimation (remain in the sublimation residue) are practically not formed by the use of a special thermolysis catalyst in the Ta bells 1 and 2 clearly visible.

Table 1: Melting points of 1,4-dioxane-2,5-diones, prepared according to the prior art (1) and according to the inventive method (2)

method

cleaning

Melting point in ⁰ C 1,4-dioxane-2,4-dione D, L-3,6-dimethyl- 1,4-dioxane-2,5-dione 70-75 50-65 80-83 85-115 81-84 118-123 83.5 to 84.5 122-125 78-82 110-115 80-84 118-122 83.5 to 84.5 126.5 to 127

without

1 χ Umkrist.

2 χ Umkrist

 Sublimation without

1 χ Umkrist.

2 χ Umkrist.

TABLE 2 Melting points and rotations of L, L-3,6-dimethyl-1,4-dioxane-2,5-dione prepared according to the prior art (1) and according to the method (2) of the invention

method

cleaning

melting point ^a D ⁰ C in Benzen 58-79 78-94 95-96 -221 75-80 90-94 96-97 -220

without

1 χ Umkrist.

2 x Umkrist. Sublimation without

1 x Umkrist.

2 χ Umkrist.

The procedure of the invention leads by the more elective Thermolysereaktion to yields that are higher by about 25% than in processes with a sublimation for the monomers formed. The polymerization of the monomers prepared according to process 1 or process 2 gave, for comparable reaction conditions (initiator, initiator concentration, temperature, polymerization time), the same conversion and the same molar mass of the polymers formed (Table 3), with 1,4-dioxane being used for these comparative polymerizations. 2,5-dione only copolymers were prepared with a content of 60 mol%.

Table 3: conversion and [n] values of polylactide and poly-glycolide-O-co-lactide ^ O])

polymer

Sales in%

[η] in ml / g

Polylactide (D, L) polylactide (L) poly (glycolide-colactide)

91.7 90.0 95.0

75 80 40

embodiments

1. D, L-3,6-dimethyl-1,4-dioxane-2,5-dione {D, L-dilactide)

300 g of a 90% strength D, L-lactic acid are heated while passing a light N ₂ -Stromesso long at 130 ⁰ C until no more water distilled off (about ₄ hours). After addition of 0.15 g of antimony (III) oxide is in vacuum at 160 ° Coliomerized. From the oligolactic acid is distilled off after addition of 100 mg of manganese (II) acetate at 160-220 ⁰ C in vacuo, the formed D, L-dilactide. The yield of the crude product is 160-17Og. For purification, it is recrystallized twice from dry ethyl acetate, the first solution being treated with activated charcoal. The purified product has the melting point of 126.5-127 ° C reported in Table 1.

2. L, L-3,6-dimethyl-1,4-dioxane-2,5-dione

300g of a 90% L-lactic acid are oligomerized and thermolyzed analogously to Example 1. The formed L, L-3,6-dimethyl-1,4-dioxane-2,5-dione has a melting point of 96-97 ° C. In benzene, a 10% solution of this L, L-dilactide shows a rotation distance of a _D = -220 °.

3. 1,4-dioxane-2,5-dione (diglycolide)

3.1. Azeotropic oligocondensation

230 g of glycolic acid are oligomerized in the presence of 0.15 g of antimony (III) oxide by means of an entraining agent for the water formed in the reaction. After complete removal of the entraining agent 100 mg of manganese (II) acetate are added in the oligomer and distilled off in vacuo at 250-300 ⁰ C about 120-13Og crude diglycolide. After two recrystallizations from dry ethyl acetate, a pure diglycolide having a melting point of 83.5-84.5 ⁰ C is obtained.

3.2. Schmelzeoligokondensation

230g glycolic acid are oligomerized as in Example 1 in bulk and then according to Example 3.1. thermolysis. The diglycolide formed has a melting point of 83.5-84.5 ⁰ C.

4. Polymerization of 1,4-dioxane-2,5-diones

The polymerization of the 1,4-dioxane-2,5-diones was carried out in bulk at 180 ⁰ C under an inert atmosphere mitZinn-ll-acetate as the initiator. Depending on the different monomer reactivity of diglycolide and dilactide, different polymerization times of 4-16 h are set. The polymers were extracted with methanol and then dried in vacuo at 50 ⁰ C. The solution viscosities were determined for polylactide in chloroform and for polylglycolide-co-lactide) in tetramethylene sulphone (sulfolane). The determination of the [r)] values took place from n _re iW.erten at 2.5 g / l <C <10.0 g / l.

Claims (2)

claims: 1. A process for the preparation of polymerizable 1,4-dioxane-2,5-diones by oligomerization of α-hydroxycarboxylic acids, catalyzed thermolysis of Oligohydroxycarbonsäuren and recrystallization of dioxane-diones; characterized in that the thermolysis of Oligohydroxycarbonsäuren in the presence of 10 ~ ⁴ to 10 " ³ MoI manganese (il) salts of organic and / or inorganic acids per mole of monomer unit is carried out as a catalyst, which is a recrystallization in ethyl acetate from 30 to 40 % solutions. 2. The method according to claim 1, characterized in that manganese acetate is used as Mangan- {ll) salt. Field of application of the invention The invention relates to a process for the preparation of polymerizable 1,4-dioxane-diones which can be used as starting monomers for high molecular weight aliphatic polyesters. Such polyesters are used as biodegradable carrier materials for active ingredients or as degradable surgical suture material. Characteristic of the known state of the art Biodegradable natural and synthetic polymers are increasingly being used for special drug formulations in long-term delivery systems and as a source material for surgical sutures. In the case of the synthetic polymers, the aliphatic polyesters and copolyesters of glycolic and lactic acids have clearly established themselves due to their ease of preparation, their excellent processing capabilities and their biocompatibility. The application of these polymers in human and veterinary medicine can be considerably extended by a specific property modification by means of copolymerization. The known technical solutions for the preparation of these aliphatic polyesters of α-hydroxycarboxylic acids are based on the cyclic 1,4-dioxane-2,5-diones, which are polymerized ionically or complex-coordinately. The simple polycondensation of hydroxycarboxylic only leads to low molecular weight products mostly sticky consistency that can not be further processed. The synthesis of the monomeric 1,4-dioxane-2,5-diones is carried out by thermolysis of the corresponding oligohydroxycarboxylic acids (cf., for example, DE-OS 1720211). The oligomer formation can be catalyzed by metal salts or metal oxides. Zinc compounds are frequently mentioned as catalysts (F. E. Kohn et al.). This reaction proceeds nonspecifically, whereby in addition to the cyclic dioxane diones also linear degradation products and higher-coupled cyclic oligomers are formed. It can be seen from the Fach (see FE Kohn et al., J. Appl. Polymer Sci. 29 [1984] 4265 and literature cited therein) and patent literature (DE-OS 2257334, DE-OS 3430852, US Pat. that these impurities, which are difficult to separate off by the usual cleaning operations, decisively influence the course of the ring-opening polymerization. In particular, the molecular weight of the polymers formed is limited by these by-products of dioxane-dione synthesis. In unfavorable cases, no initiation takes place at all, since the catalyst is blocked or inactivated by these substances. The dioxane-diones prepared according to the prior art are expensive to purify before the polymerization, with the last cleaning operation generally being a vacuum sublimation. For example, DE-OS 1643773 proposes a two-fold recrystallization from tert-amyl alcohol and washing with trichlorofluoromethane to remove the impurities for a polymerizable 2,4-dioxane-2,5-dione, followed by a sublimation of about 20 hours. Such elaborate cleaning operations burden the production of biodegradable polyester both in technological and in economic terms considerably. Object of the invention The aim of the invention is the development of a process for the preparation of polymerizable dioxan-diones in a simpler and more economical manner. Explanation of the essence of the invention
task The invention has for its object to make the synthesis of dioxane-diones so that even in the thermolysis of Oligohydroxycarbonsäuren so pure cyclic lactones formed that are obtained by simple recrystallization polymerization suitable monomers.