Lactide water removal

Another common reaction with a-hydroxy acids such as LA is the selfcondensation under water-removal circumstances, forming lactoyl lactate, oligomers, or lactide - the cyclic di-ester of LA (6) [10, 41]. These condensation reactions are dehydrations and thus retain the full functionality in the molecule, while lowering the H index see Fig. 2. Moreover, the atom economy of 80% is high with only water as side-product. Lactide is the true industrial precursor of PLA and the atom economy of 80% is equally valid for PLA [42]. 

The solution to this problem has been to isolate the lactide and to polymerize this directly using a tin(ii) 2-(ethyl)hexanoate catalyst at temperatures between 140 and 160 °C. By controlling the amounts of water and lactic acid in the polymerization reactor the molecular weight of the polymer can be controlled. Since lactic acid exists as d and L-optical isomers, three lactides are produced, d, l and meso (Scheme 6.11). The properties of the final polymer do not depend simply on the molecular weight but vary significantly with the optical ratios of the lactides used. In order to get specific polymers for medical use the crude lactide mix is extensively recrystallized, to remove the meso isomer leaving the required D, L mix. This recrystallization process results in considerable waste, with only a small fraction of the lactide produced being used in the final polymerization step. Hence PLA has been too costly to use as a commodity polymer. 

A solution of 1.0 g of thioridazine free base and 1.0 g of poly(DL-lactide) or poly(L-lactide) in 10 mL of methylene chloride was emulsified with 100 mL of an aqueous solution containing 0.4 g of sodium oleate or polyvinyl alcohol and 0-15 mL of 0.1 N NaOH (0-0.14 mole NaOH/mole lactic acid). After the emulsion was magnetically stirred for 10-15 minutes, the organic solvent was removed by rotary evaporation, 150 rpm, 375 mm Hg, at 40°C for 2 hours. The product was filtered, washed with water and vacuum dried at 30°C. 

Bacterial fermentation is used to produce lactic acid from corn starch or cane sugar which is further processed to produce lactide monomer. Because lactic acid is difficult to polymerize directly to high polymers in a single step on a commercial scale, most companies used a two-step process. Lactic acid is first oligomerized to a linear chain with a MW of less than 3,000 by removing water. 

Lactide was first synthesized by Pelouze in 1845 [7] by selfesterification of lactic acid to obtained a prepolymer and heating of the prepolymer to produce distillate crystals. Gruter and Pohl improved the process in 1914 [8]. The procedure was first polycondensation of lactic acid at 120-135°C with the aid of air flow to remove the water. Next, lactide was distilled off under vacuum at 200°C in the presence of zinc oxide. Tin (Il)-based catalysts are the most common used catalysts in the modern industry. Since the prepolymer degradation is an equilibrium reaction, lactide must be extracted from the system in order to shift the reaction... 

A crude lactide stream produced in the lactide synthesis reactors contains lactic acid, lactic acid oligomers, water, meso-lactide, and further impurities. Two main separation methods, distillation and crystallization, are currently employed for lactide purification. Crystallization may be carried out either by solvent crystallization or melt crystallization. The most used method for production of ultra-pure lactide in laboratory is by repeated recrystallization of a saturated lactide solution in mixtures of toluene and ethyl acetate [15, 23, 24]. Lactide purification using C4-12 ethers [25], and an organic solvent that is immiscible with water to extract the solution with water [26] are also reported. Melt crystallization is more practical in industry for lactide purification. Several types of equipment are described in the literature for melt crystallization [17, 27-30]. This method uses the differences in the melting points of L-, D-, and meso-lactide for separating the different lactides from each other. In a distillation process, the crude lactide is first distilled to remove the acids and water, and then meso-lactide is separated from lactide [11, 31]. Different methods are reported in the literature for distillation purification of lactide [32, 33]. In... 

The other ring-chain equilibrium constant is provided by the equilibrium monomer (r-lactide) concentration [M]e that is affected by the back-biting reaction of the hydroxyl terminal. As mentioned in the preceding section, the [M]e are lower than 1.0 wt% below 120 °C and higher than 5 wt% above 180 °C in the ROP of L-lactide. High evacuation, needed to remove condensed water, is likely to result in the removal of L-lactide from the system... 

The above thermodynamic analysis of the polycondensation reveals that PLIAs having high molecular weights may be produced when the condensed water is efficiently removed to a level of 1 ppm from the polymerization system without evaporation of the L-lactide monomer present in equilibrium. The ordinary reaction conditions that may allow the effective removal of the water may involve (1) a temperature range of 180-200 °C (2) a low pressure below 5 torr and (3) a long reaction time in the presence of an appropriate catalyst and, in some cases, azeotropic solvent for removing water efficiently. ... 

The lactic acid molecule has a hydroxyl and an acid functional group, which may result in intermolecular and intramolecular esterification reactions. The first step is the formation of a linear dimer (lactoyl lactic acid). This condensation reaction can proceed to higher oligomers and is promoted by removal of water. Also a cyclic dimer, lactide, is formed in small amounts. Lactide can be formed by intramolecular esterification of lactoyl lactic acid or by breakdown of higher oligomers. All reactions are equilibrium reactions (Figure 1.2). 

Remove uncondensed water and lactide impurity as a vapor and recede or discard... 

Remove water and lactide acid Impurities as a distillate/overhead stream, recycle or discard... 

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