RU2460726C1 - Method of producing l-lactide - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: method of producing L-lactide involves a step for oligomerisation of a lactic ester in alkyl ether of lactic acid oligomers in a current of inert gas at atmospheric pressure and high temperature, and a step for depolymerisation of the alkyl ether of lactic acid oligomers at high temperature in a vacuum, carried out in the presence of the same catalyst - tin (IV) compounds, wherein the catalyst used at the oligomerisation and depolymerisation steps is tin tetrachloride.

EFFECT: high rate of oligomerisation of alkyl lactate and depolymerisation of alkyl ether of the oligomer, high output of L-lactide.

4 cl, 9 ex

Description

The invention relates to a process for producing L-lactide - a cyclic dimer (diester) of lactic acid, a monomer for the synthesis of biodegradable polymer materials used as coatings or containers for food products, as well as in the medical industry.

The currently existing industrial method for producing L-lactide is based on a two-stage process in which, at the first stage, lactic acid is oligomerized to form a linear oligomer with a molecular weight of not more than 3000, and the obtained oligomer is then subjected to depolymerization (pyrolysis) with the formation of crude lactide.

The main and main disadvantage of this method is that the resulting raw lactide contains a large range of impurities, in particular acidic impurities, water, meso-lactide, linear dimers and trimers of lactic acid. Considering the fact that the amount of acidic impurities and water in the commercial product should not exceed 30 ppm and 100 ppm, respectively, to obtain L-lactide of polymer purity in this method, a multi-stage operation of purification of raw lactide is required (US 7488783, US 5463086, US 5521278, US 5357035, WO 9302075).

Recently, there have been reports that the purification step of raw lactide can be drastically simplified by using not lactic acid as its raw material for the production of lactide, but its esters - alkyl lactates. In this case, water and free acids are not formed in the processes of oligomerization of alkyl lactates and depolymerization of the obtained ester of lactic acid oligomers, and the purification operation is simplified and includes only the steps of removing unconverted alkyl lactate, an alkyl ester of a linear dimer of a lactic acid ester and meso-lactide.

Known two-stage method for producing lactide from ethyl lactate, in which the stage of oligomerization is carried out in the presence of 0.5% wt. the catalyst is p-toluene sulfonic acid (US 7488783). The maximum temperature is 175 ° C. The reaction time is 10 hours (example d) of the patent). From 20 liters of 97% ethyl lactate (~ 20 kg of pure ethyl lactate), 7.8 kg of distillate containing 3% ethyl lactate (the rest is probably ethanol) and 12.6 kg of ethyl ester of lactic acid oligomer of molecular weight 960 were obtained.

The second depolymerization stage is carried out in the presence of a tin octoate (II) catalyst at 220-230 ° C under a vacuum of 5 and 10 mbar (4-10 mm Hg) in a thin-film evaporator with a surface of 0.2 m ² . The content of L-lactide in the obtained raw lactide was 73-78%, meso-lactide 2-5%. The rest is probably ethyl lactate and linear alkyl esters of dimers, trimers and tetramers of lactic acid. Based on 100% lactide, the meso-lactide content will obviously be higher than 2.3-6.4% wt.

Thus, from the taken 20 kg (170 mol) of ethyl lactate, 750 g of crude lactide containing 75.3% wt. L-lactide and, therefore, the yield of L-lactide at the stages of oligomerization and depolymerization, calculated on the taken ethyl lactate and pure L-lactide, amounted to 565 g (3.9 mol) or 4.6 mol%.

The disadvantages of this method are the low productivity of the process, the high content of meso-lactide, as well as the very low yield of L-lactide (even before the stage of purification). In addition, an additional disadvantage of this method is the presence of a small amount of acidic impurities in the raw lactide (83 mEq / kg). This, in our opinion, is a consequence of the use of the proton catalyst, p-toluene sulfonic acid, at the stages of oligomerization and depolymerization. Moreover, the presence of free acid in raw lactide, as noted earlier, will require additional costs in order to remove it from the lactide. This fact is also noted by the authors of US 7488783 (Column 9, paragraph 1), saying that the acidity of the resulting lactide used to produce the polymer should not exceed 10 mEq / kg, and even better - 1 mEq / kg.

Known methods for producing L-lactide from alkyl lactate, which include the stage of oligomerization of methyl ester of lactic acid with the formation of methyl ester of lactic acid oligomers with an average molecular weight of 100-5000 and cracking (depolymerization) of the obtained oligomers to obtain lactide (US 5247059, example 21; US 5274073, example 21 and US 632645 8, example 11).

The oligomerization and depolymerization stages are carried out in the presence of the same catalyst - organic tin (IV) compounds: butylstannoic (IV) acid (butyl tin acid), butyltin (IV) tris-2-ethylhexoate (butyl tris-2-ethylhexoate tin IV), taken in an amount of 0.3-1.0% per tin relative to alkyl lactate.

The first stage of oligomerization of methyl lactate is carried out in two stages. First, a mixture of methyl lactate (2.2 kg) with a catalyst (butyltin tris-2-ethylhexanoate, 0.6% wt.) Is heated from a temperature of 125 to 165 ° C at atmospheric pressure for 5 hours when an inert gas - nitrogen is introduced into the reaction mixture to facilitate removal of the forming by the reaction of alcohol. The distillate at this stage was 350 g and contained 91% methanol. The rest is probably methyl lactate.

After that, the product remaining in the cube was heated at 145 ° C under a vacuum of 50 mm Hg. within 6.8 hours The distillate at this stage (165 g) contained 83% methyl lactate and 17% methanol.

From the data given in the example, it is easy to calculate that in 11.8 hours a very low degree of oligomerization is achieved, which for this example patent is n = 2.24 (molecular weight of the obtained oligomer is 193).

Cracking (depolymerization) of the obtained lactic acid oligomer methyl ester to L-lactide is carried out by heating it at 200 ° C. under a vacuum of 10 mmHg. The depolymerization time and the amount of crude lactide obtained are not given. Only the raw lactide composition is given, which contains 3% methyl lactate, 9% linear methyl esters of dimers, trimers and tetramers of lactic acid (DP2-DP4), 76% D, L-lactide and 9% meso-lactide.

Purification of the obtained crude lactide by vacuum distillation made it possible to obtain the following quality lactide, wt.%: Methyl ester of lactic acid dimer - 0.3; meso-lactide - 9; D, L-lactide - 90.3.

The main disadvantage of this method is the very low degree of conversion of the alkyl lactate to the oligomer, the low productivity of the oligomerization and depolymerization processes (only the oligomerization time is 11.8 hours), and most importantly, the high content of meso-lactide in the commercial product.

Separately, it should be noted the method of oligomerization of esters of lactic acid and depolymerization of the obtained oligomers described in patent US 6569989 Japanese company Toyota Jidosha Kabushiki Kaisha.

At all stages of the process, a practically quantitative yield of products is achieved. The authors carry out the oligomerization of alkyl esters of lactic acid both in the presence of a catalyst (organic compounds of tin II) and without it, without giving the total process time. It also follows from the patent that when carrying out oligomerization and depolymerization processes at temperatures of 200-220 ° C both in the presence of a catalyst and in its absence, it is possible to obtain L-lactide in practically quantitative yield, i.e. from the data of the patent it follows that meso-lactide does not form at all.

However, as noted in US Pat. Nos. 5,247,059; 5274073 and 6326458, the oligomerization reaction of lactic acid esters in the absence of catalysts does not occur at all, and the raw lactide always contains meso-lactide. This is completely consistent with our experimental data. In this regard, the data of the patent US 6569989 should be treated with due care.

Thus, the disadvantage of all known methods for producing L-lactide is the long duration of the process (low productivity) and a large yield of the byproduct of meso-lactide.

The objective of this method is to increase the speed of the processes of oligomerization of alkyl lactate and depolymerization of the alkyl ether of the oligomer (decrease the process time), as well as increase the yield of L-lactide (decrease the yield of meso-lactide).

This problem is solved by a method for producing L-lactide, including the stage of oligomerization of lactic acid ester into the alkyl ether of lactic acid oligomers at atmospheric pressure and elevated temperature in an inert gas stream and the stage of depolymerization of the alkyl ester of lactic acid oligomers in vacuum at elevated temperature, carried out in the presence of one and the same catalyst, tin (IV) compounds, in which tin tetrachloride is used as a catalyst for the oligomerization and depolymerization stages.

Preferably, a mixture of lactic acid ester, ester of lactic acid oligomers and catalyst, which has previously been pressurized at a temperature above the boiling point of the lactic ester for at least 10 minutes, is fed to the oligomerization step.

Preferably, bottoms of the depolymerization step containing lactic acid oligomer ester and a catalyst are used as oligomer esters.

Preferably, the oligomerization step is carried out in a rotary film evaporator.

The following examples illustrate the method:

Stage oligomerization of alkyl lactates

Example 1

The oligomerization process was carried out in a glass flask (0.4 L volume, heated surface - 0.025 m ² ) equipped with a stirrer, reflux condenser, condenser refrigerator and bubbler for supplying an inert gas - nitrogen. 200 g of butyl lactate (1.37 mol) and 0.08 g (0.04% wt.) Of catalyst (SnCl ₄ ) were charged into the flask. The stirrer was started, nitrogen supply (1 ml / min), and then the flask was immersed in an oil bath with an oil temperature of 180 ° C. The process was carried out for 4.8 hours with a gradual increase in the temperature of the oil in the bath from 180 to 200 ° C and the flow rate of nitrogen from 1 to 20 ml / min. The butanol formed by the reaction with a part of butyl lactate with an inert gas stream from the upper part of the reflux condenser was sent to a condenser refrigerator, and the resulting liquid condensate was collected in a receiver. The viscous product of a light brown color remaining in the flask after completion of the process is butyl ether of lactic acid oligomers (BEOMK). The molecular weight of the obtained oligomers was determined by gel permeation chromatography (GPC) on a BISCHOFF instrument equipped with a UV detector (254 nm) using a 300 mm long Shode GPC K-802 polymer column with a diameter of 8.0 mm. Chloroform with a feed rate of 1 ml / min and a thermostat temperature of 300 ° C was used as an eluent. A sample of oligomers was introduced as a 3% solution in chloroform.

Total received:

110 g of the condensate composition,% wt .: butanol - 75; butyl lactate - 25.

90 g BEOMK, average molecular weight 1345.

The degree of conversion of butyl lactate is 86.3%. The productivity of the process per converted butyl lactate is 1.4 kg of butyl lactate / (m ² reactor * hour).

Example 2

The process was carried out analogously to example 2, but ethyl ester (200 g, 1.69 mol) was used as the ester. The process was carried out for 5.2 hours with a gradual increase in temperature from 150 to 200 ° C. The viscous product of a light brown color remaining in the flask after completion of the process — ethyl ester of lactic acid oligomers (EEOMC), was analyzed by determining its average molecular weight by GPC, as in Example 1.

Total received:

87 g of the condensate composition,% wt .: ethanol - 70; ethyl lactate - 30.

113 g of EEOMC, molecular weight 750.

The degree of conversion of ethyl lactate is 86.9%. The productivity of the process in the calculation of converted ethyl lactate is 1.3 kg / (m ² reactor * hour).

Example 3

The process was carried out analogously to example 2, but methyl ester (200 g, 1.92 mol) was used as an ester. The process was carried out for 5.8 hours with a gradual increase in temperature from 140 to 200 ° C. The viscous product of a light brown color remaining in the flask after completion of the process — methyl ester of lactic acid oligomers (MEOMC), was analyzed by determining its average molecular weight by GPC, as in Example 1.

Total received:

78 g of the condensate composition,% wt .: methanol - 65; methyl lactate - 35.

122 g of MEOMC, molecular weight 1581.

The conversion of methyl lactate is 86.4%. The productivity of the process in the calculation of converted methyl lactate is 1.2 kg / (m ² reactor * hour).

Example 4

The oligomerization process was carried out in a Heidolph brand rotary-film evaporator (RPI) having a rotating reactor flask (volume 1.0 l, heated surface 0.025 m ² ) equipped with an inert gas supply device to the flask space.

200 g of butyl lactate (1.37 mol) and 0.06 g (0.03% wt.) Of catalyst (SnCl ₄ ) were charged into the reactor flask, the flask rotated at 60 rpm, nitrogen was supplied at a speed of 1 ml / h and the flask was immersed -reactor in an oil bath with an oil temperature of 180 ° C.

The process is carried out for 4.3 hours with a gradual increase in the temperature of the oil in the bath from 180 to 200 ° C and the flow rate of nitrogen from 1 to 20 ml / min.

Butanol vapors formed in the reactor flask mixed with butyl lactate with an inert gas stream were removed from the reactor flask volume, butanol and butyl lactate were condensed in the refrigerator 5 and collected in receiver 6. The molecular weight of the obtained oligomers was determined analogously to Example 1.

Total received:

111 g of condensate composition,% wt .: butanol - 76; butyl lactate - 24.

89 g BEOMK, molecular weight 1867.

The degree of conversion of butyl lactate is 86.7%. The productivity of the process per converted butyl lactate is 1.6 kg of butyl lactate / (m ² reactor * hour).

Example 5

The process was carried out analogously to example 1, but 40 g of BEOMC obtained in example 1 (MM = 1345), 160 g (1.1 mol) of butyl lactate and 0.04 g of catalyst (SnCl ₄ ) were loaded into the flask. The resulting mixture with stirring was kept at a temperature of 192 ° C for 20 min and a pressure of 0.2 ati. After that, the pressure was released and nitrogen supply was started. The process was carried out for 3.1 hours with a gradual increase in temperature to 205 ° C. The molecular weight of the obtained oligomers was determined analogously to example 1.

Total received:

84 g of condensate composition,% wt .: butanol - 77; butyl lactate - 23.

116 g of oligomer, molecular weight 1022.

The degree of conversion of butyl lactate 87.9%. The productivity of the process per converted butyl lactate is 1.7 g / (m ² * hour).

Example 6

The process was carried out analogously to example 4, but 20 g of the oligomer obtained in example 3 (MM = 1581) and 0.05 g of catalyst (SnCl ₄ ) and 180 g of methyl lactate (1.73 mol) were loaded into the reactor flask. The flask was turned on at a speed of 60 rpm, and the reactor flask was immersed in an oil bath 3 with an oil temperature of 153 ° C and this mixture was kept under a pressure of 0.3 atm for 12 min. After that, the pressure was released to atmospheric pressure and nitrogen supply was started. The process was carried out for 4.8 hours with a gradual increase in temperature to 205 ° C. The molecular weight of the obtained oligomers was determined analogously to example 1.

Total received:

60 g of the condensate composition,% wt .: methanol - 80; methyl lactate - 20.

140 g MEOMC average molecular weight 1119.

The degree of conversion of butyl lactate 93.3%. The productivity of the process per converted methyl lactate is 1.4 kg / (m ² * hour).

Stage depolymerization of the alkyl ester of lactic acid oligomers in L-lactide

Example 7

The depolymerization process was carried out in a glass flask reactor (0.4 L in volume, heated surface - 0.025 m ² ), equipped with a thermometer, stirrer and refrigerator. Obtained in example 1, butyl ether of lactic acid oligomers (90 g) of molecular weight 1345, together with the catalyst (0.08 g) remaining in the oligomers after completion of the oligomerization step, were loaded into the reactor flask. The contents of the flask were heated, while simultaneously creating a vacuum, and when reaching 215 ± 5 ° C, a residual pressure of 5 mm Hg began the selection of lactide vapors. The resulting lactide vapors entering the refrigerator, in the jacket of which hot water with a temperature of 95 ° C was supplied, were condensed and collected in the receiver flask of liquid depolymerization products. To prevent lactide vapor from entering the vacuum line, the receiver flask was placed in an ice bath and equipped with a reflux condenser cooled by cold water with a temperature of 15 ± 5 ° C. The depolymerization process was carried out 1.5 hours until the lactide vapors from the reactor flask were completely stopped.

Total received:

Raw lactide (73 g) composition,% wt .: L-lactide - 82.3; meso-lactide - 2.6; butyl lactate - 4.5; butyl ether of lactic acid dimers - 10.6.

VAT residue (17 g) containing butyl esters of lactic acid oligomers with an average molecular weight of 1895 and a catalyst (0.08 g).

The degree of conversion of oligomers is 81%. The yield of pure L-lactide calculated on the oligomers taken was 66.8% wt.

Productivity of the plant for pure L-lactide: 1.6 kg of lactide / (m ² * hour).

Example 8

The depolymerization process was carried out in a rotary film evaporator (EPI) of the Heidolph brand. The oligomers obtained in Example 4 in an amount of 88 g of molecular weight 2034 together with the catalyst (0.06 g) remaining after the oligomerization step was completed were charged into a reactor flask with a heat exchange surface of 0.025 m ² . The reactor flask was immersed in an oil bath with a temperature of 220 ° C, the rotor mechanism (flask rotation) was started at a speed of 60 rpm and a vacuum of 2-4 mm Hg was created in the system. The lactide vapors formed during the course of the depolymerization reaction were sent to the refrigerator, through the jacket of which the coolant with a temperature of 95 ° C was pumped, condensed, and the condensate accumulated in the receiver flask. The process was carried out for 1.2 hours until the vapor evolution from the reactor flask was completely stopped.

Total received:

Raw lactide (73 g) composition,% wt.: L-lactide - 86.1; meso-lactide - 2.4; butyl lactate - 3.5; butyl ether of lactic acid dimers - 8.0.

VAT residue (16 g) containing butyl ether of lactic acid oligomers with an average molecular weight of 4700 and a catalyst (0.08 g).

The degree of conversion of oligomers is 83%.

The yield of pure L-lactide calculated on the oligomers taken is 71.4% wt.

Productivity of the plant for pure lactide: 2.1 kg of lactide / (m ² * hour).

Example 9

Illustrates the possibility of recycling by-products (bottoms) formed at the depolymerization stage to the oligomerization stage of the lactic acid ester.

VAT products of example 7 (17 g MM = 1895, including catalyst 0.08 g), example 8 (16 g MM = 4700, including 0.08 g of catalyst), example 9 (18 g MM = 1461, including 0.067 g of catalyst) was mixed with 183 g of butyl lactate. The resulting mixture was kept at 195 ° C and 0.3 atm for 16 min. The oligomerization of the resulting mixture was carried out for 2.9 hours in the same manner as in Example 1. 181 g of BEOMC, average molecular weight of 1243 were obtained. The productivity of the process per converted butyl lactate was 2.2 kg of butyl lactate / (m ² reactor * hour).

Carrying out the process by this method allows to reduce the time of oligomerization processes to 2.9-5.8 hours and depolymerization to 1.5-2.2 hours, as well as reduce the content of meso-lactide in raw lactide to 2.4-2.6%.

Claims (4)

1. A method for producing L-lactide, comprising the step of oligomerizing a lactic acid ester into the alkyl ester of lactic acid oligomers in an inert gas stream at atmospheric pressure and elevated temperature, and the step of depolymerizing the alkyl ester of lactic acid oligomers at elevated temperature and under vacuum, carried out in the presence of one and the same catalyst, tin (IV) compounds, in which tin tetrachloride is used as a catalyst for the oligomerization and depolymerization stages. 2. The method according to claim 1, characterized in that at the stage of oligomerization serves a mixture of lactic ester, ester of lactic acid oligomers and catalyst, previously kept under pressure at a temperature above the boiling point of the lactic ester for at least 10 min. 3. The method according to claim 2, characterized in that the cubic products of the depolymerization stage containing the ester of lactic acid oligomers and a catalyst are used as oligomer esters. 4. The method according to claim 2, characterized in that the oligomerization is carried out in a rotary film evaporator.