Lactides synthesis

Lactide is produced by degradation reactions, mainly via intramolecular chain scission of the prepolymer. Lactide synthesis from a prepolymer with a DP in the range of 10-15 in the presence of various catalysts at 4-5 mbar and 190-245°C is reported by Noda and Okuyama [9]. The best performances were reported using 0.05-0.2 wt% tin catalysts and tin octoate (stannous 2-ethylhexanoate) in particular, which is widely available. The catalyst increases the rate of backbiting reactions from hydroxyl chain ends of prepolymers to form lactide molecules [9, 15]. The melt viscosity of the prepolymer increases because of the esterification reactions during the process, which results in decreased rate of mass transfer. 

Continuous lactide synthesis in which the prepolymer is fed continuously to a reactor is also reported in the literature [11], This procedure resulted in a product with a conversion around 70% per pass, which could be increased by recycling the residue to... 

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... 

Kang, N. and Leroux, J.C., 2004. Triblock and star-block copol3miers of iV-(2-hydroxypropyljmethacrylamide or iV-vinyl-2-pyrrolidone and D,L-lactide synthesis and self-assembling properties in water. Polymer, 45, 8967-8980. 

Ovitt, T. M. Coates, G. W. Stereoselective ring-opening polymerization of meio-lactide Synthesis of syndiotactic poly(lactic acid). J. Am. Chem. Soc. 1999,121, 4072-4073. 

L. Luo, M. Ranger, D. G. Lessard, D. L. Garrec, S. Gori, J. C. Leroux, S. Rimmer and D. Smith, Novel amphiphilic diblock copolymer of low molecular weight poly(N-vinylp5n rolidone)-J>/ocfc-poly(D,L-lactide) Synthesis, characterization and micellization. Macromolecules, 37,4008 - 4013 (2004). 

The dehydration of lactic acid to make the prepolymer should start with an —OH to —COOH ratio of 1 1. All other components with —OH and —COOH functionality disrupt the stoichiometric balance and may be incorporated as comonomers during prepolymerization, which limits the final lactide production yield from lactic acid. Little public information is available on the technical and economic relationship between lactic acid quality and lactide synthesis. Only a few patents mention the effect of metal impurities on racemization [68,69]. Stereochemical purity is one of the key parameters determining lactic acid purity. 

In the past two decades, several papers have appeared on lactide manufacture [73, 74]. A main underlying problem in understanding all information is that the reaction from oligomer to lactide is an equilibrium reaction. In order to pull the reaction toward the right, lactide must be withdrawn from the system. In reaction engineering terms, this means that the chemical kinetics of the reaction cannot be understood without consideration of the method and efficiency of lactide removal. In terms of know-how described in patents, this means that reported lactide production rates depend to a large extent on the geometry of the equipment in which lactide synthesis is performed and that provides for removal of lactide vapor from the reaction zone. 

These aspects will be relevant for both the prepolymerization and the synthesis of lactide, as these chemical systems are highly similar. In practice, however, lactide synthesis is more complex as chemistry, recovery and type of equipment are intertwined, and the viscous nature of reaction mixtures requires special attention. 

With these aspects in mind, the information on the lactide synthesis that can be found in the literature is summarized below. 

Continuous prepolymerization has also been described in a number of patents, for example, in stirred tanks in series or in evaporator-type equipment [68, 76, 77]. Usually patents describe prepolymers with a DP of 7-20 as feed to the lactide synthesis. Using modern HPLC methods, it has been shown that in oligomeric systems up to DP 10, an equilibrium is present with constant equilibrium constants between the oligomers [6, 72]. 

Because the composition of a mixture comprising lactic acid oligomers and lactide is governed by chemical equilibria, a prepolymerization exhibits relatively high concentrations of lactide (HL2-H2O-L2 equUibrium) around DP 2. Sinclair et al. distilled these fractions to recover lactide, but the crude lactide was quite impure, which may prevent economical processing [73]. In hindsight, the patent describes trials to optimize Pelouze s original lactide synthesis without catalyst [71]. 

Basic Research on Batch Lactide Synthesis and the Catalysts Used Noda and Okuyama reported on the batch synthesis of lactide from DP 15 prepolymer with various catalysts at 4—5 mbar and 190-245°C [74]. In a batch synthesis with 50 g of oligomer in a stirred flask, the evolution rate of crude lactide is rather constant and then starts to dechne and the conversion levels off at 80-90%. The tin catalyst performed best compared to other catalysts and showed the lowest levels of racemization. Tin octoate... 

Continuous Synthesis In 1992, Gruber et al. [68] described a continuous lactide synthesis in which prepolymer is fed continuously to a reactor, crude lactide is evaporated under vacuum, and residue is removed. Typical operating conditions for the reactor were residence time around 1 h, vacuum pressure 4 mbar, temperature 213°C, and catalyst amount 0.05 wt% tin(II) octoate on feed. The conversion per pass was around 70%, and the overall yield was increased by recycling the residue to the lactic acid section of the process, where the oligomers are hydrolyzed again. 

Especially in the patent literature, several different reactor types are described for continuous lactide synthesis ... 

Some metal cations such as sodium and potassium in the feed increase racemization risk, while other metals (Al, Fe) are catalytically active in transesterification, resulting in competitive polylactide formation [68,69]. Through corrosion, metals may be released in the residue and will build up there [6, 75]. Some patents discuss the presence of acid impurities in the process [6, 7, 67, 78], Mono- and dicarboxylic fermentation acids are responsible for stoichiometric imbalance in the lactic acid polycondensation reaction. Consequently, the composition of the obtained lactic acid oligomer chains can differ from pure PLA, resulting in impeded and incomplete catalytic depolymerization of the oligomers into lactide. In PLA manufacture, degradation reactions play a role, mainly via intramolecular chain scission, and this may also affect lactide synthesis. 

On the one hand, it can be concluded that the lactide synthesis is straightforward in the sense of making a prepolymer and releasing lactide by thermal catalytic depolymerization at low pressure. On the other hand, it can be concluded that the scale-up from a lab-scale process to an economical, large-scale process with high yield and no compromises on stereochemical purity is a complex multifaceted task. 

A lactide synthesis reactor invariably produces a crude lactide stream that contains lactic acid, lactic acid oligomers, water, mc50-lactide, and further impurities. The specifications for lactide are stringent mainly for free acid content, water, and stereochemical purity. Basically, two main separation methods, distillation and crystallization, are currently employed for lactide purification ... 

Metals Metal cations such as Sn, Zn, Fe, Al, and Ti not only accelerate polymerization, but can also affect hydrolysis, oxidation, racemization, or other degradation mechanisms of PLA and lactides [4, 6]. Consequently, the lactic acid used for lactide preparation should be very low (ppm) in metal cations in order to avoid considerable racemization during lactide synthesis. 

Albertsson, A-C. and Lofgren, S. (1992) Copolymers of l,5-dioxepan-2-one and L-or D,L-lactide, synthesis and characterization, Makromol. Chem., Makromol. Symp. 53, 221-231. 

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