PLA Synthesis. From the Monomer to the Polymer

KAZUNARI MASUTANI AND YOSHIHARU KIMURA

Kyoto Institute of Technology, Japan

1.1 Introduction

It is recorded that Théophile-Jules Pelouze first synthesized poly(lactic acid) (PLA) by polycondensation of lactic acid in 1845. In 1932, Wallace Hume Carothers et al. developed a method to polymerize lactide into PLA. This method was later patented by Du Pont in 1954. Until the late 1970s, PLA and its copolymers were developed as biomedical materials based on their bioabsorbable and biocompatible nature and have been utilized in many therapeutic and pharmaceutical applications such as drug delivery systems (DDS), protein encapsulation and delivery, development of microspheres and hydrogels etc. Recently, the biomedical application of PLA has been extended to tissue engineering including scaffold materials as well as to biocompatible materials for sutures and prostheses in which high- and low-molecular-weight PLAs are used, respectively. In the early 1990s, a breakthrough occurred in the production of PLA. Cargill Inc. succeeded in polymerizing high-molecular-weight poly(L-lactic acid) (PLLA) by ring-opening polymerization (ROP) of L-lactide in industrial scale and commercialized the PLLA polymer in the mid 1990s. Showing high mechanical properties in addition to a biodegradable nature, PLLA was thought to provide large opportunities to replace non-degradable oil-based polymers, such as poly(ethylene terephthalate) (PET) and polystyrene (PS). Since then, PLA has been utilized as biodegradable plastics for short-term use, such as rigid packaging containers, flexible packaging films, cold drink cups, cutlery, apparel and staple fibres, bottles, injection- and extrusion-moulds, coatings, and so on. All of them can be degraded under industrial compositing conditions. In the late 1990s, the bio-based nature of PLA was highlighted and its production as a bio-based polymer started. In this case, the newly developed polymers ought to have high-performances and long-life utilities that can compete with those of the ordinary engineering plastics. Various types of bio-based polymers are now under development, and several PLA types are also developed as promising alternatives to commercial commodities. In particular, PLLA polymers comprising high L-contents and stereo-complex PLA polymers showing high melting temperatures are now expected to be candidates for high-performance materials. The above historical view reveals the three specific features of PLA in terms of application, i.e. bio-absorbable, bio-degradable and bio-based.

Now, the synthesis of PLA polymers can be performed by direct polycondensation of lactic acid as well as by ring-opening polymerization of lactide (LA), a cyclic dimer of lactic acid. While the former method needs severe conditions to obtain a high-molecular-weight polymer (high temperature of 180–200 ?C, low pressure as low as 5 mmHg and long reaction times), the latter method can afford a high-molecular-weight PLA with narrow molecular weight distribution at relatively mild reaction conditions (low temperature of 130 ?C and short reaction times). Consequently, ROP of L-lactide is adopted in the ordinary industrial production of PLLA. On the other hand, since Ikada discovered the formation of stereo-complexes of PLLA and its enantiomer poly(D-lactic acid) (PDLA) in 1987, many trials have been done for its industrial production. Manufacturing of D-lactic acid and improvement of the stereo-complexibility of the enantiomeric segments have been the big challenges in the trials thus far. Synthesis of stereo-block polymers consisting of PLLA and PDLA macromolecular chains is a promising method for the preferential formation of stereo-complexes. This chapter deals with the whole synthetic aspects of these PLA polymers and their starting monomers.

1.2 Synthesis of Lactic Acids

1.2.1 Stereoisomers of Lactic Acid

Lactic acid (2-hydroxypropanoic acid) is the simplest 2-hydroxycarboxylic acid with a chiral carbon atom and exists in two optically active stereo-isomers, namely L and D enantiomers (S and R in absolute configuration, respectively), as shown in Scheme 1.1. These L- and D-lactic acids are generally synthesized by fermentation using suitable micro-organisms. Racemic DL-lactic acid (RS configuration) consisting of the equimolar mixture of D- and L-lactic acids shows characteristics different from those of the optically active ones. DL-lactic acid is conveniently synthesized by chemical method rather than fermentation.

1.2.2 Fermentation with Lactic Acid Bacteria

Lactic acid fermentation is one of the bacterial reactions long utilized by mankind along with alcoholic fermentation. The lactic acid bacteria are generally divided into several classes in terms of cell morphology, i.e. Lactobacillus, Streptococcus, Pediococcus, Aerococcus, Leuconostoc and Coryne species. They are also divided into various genera. Most of them produce L-lactic acid while some produce D- or DL-lactic acids. Table 1.1 compares which of D- or L-lactic acid is produced by different bacteria. The species belonging to the same Lactobacillus genus produce either L- or D-lactic acid preferentially. Lactobacillus helvetics and Sporolactobacillus produce DL- and D-lactic acids, respectively. In the lactic acid formation, therefore, stereoselectivity is much lower than in the amino acid formation where the absolute L-selectivity is shown. Table 1.2 shows the mono- and di-saccharides assimilated by the...