Polycondensation of Lactic Acids

Additional polyesters were synthesized by the polycondensation of lactic acid and castor oil (Figure 5) and examined as injectable controlled delivery carriers for cytotoxic drugs (paclitaxel, methotrexate, 5FU and cis-platin). 

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... 

The ROP route includes polycondensation of lactic acid followed by a depolymerization into the dehydrated cyclic dimer, lactide [shown in Fig. 23.3). The depolymerization is conventionally done by increasing the polycondensation temperature and lowering the pressure and distilling off the produced lactide. Due to the two stereoforms of lactic acid, the corresponding optically active lactide can be found in two different versions. In addition, lactide can be formed from one D- and one L-lactic acid molecule yielding D,L-lactide[meso-lactide) [7]. 

There are two important methods for PLA synthesis direct polycondensation of lactic acid and ROP of lactic acid cyclic dimer, known as lactide. In direct condensation, solvent is used and higher reaction times are required. The resulting polymer is a material of low to intermediate molecular weight. ROP of the lactide needs catalyst but results in PLA with controlled molecular weight. Depending on the monomer and reaction conditions, it is possible to control the ratio and sequence of d- and L-lactic add units in the final polymer [74,75],... 

PLA to certain extend without the introduction of additives or other polymers. Although two general terms of polylactic acid and polylactide used to refer to PLA, the irony is, polylactides are prepared via ROP process while polylactic acid refers to PLA produced through polycondensation of lactic acid. 

Over the past several decades, polylactide - i.e. poly(lactic acid) (PLA) - and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications as well as alternatives to petro-based polymers [1-18], Plant-derived carbohydrates such as glucose, which is derived from corn, are most frequently used as raw materials of PLA. Among their applications as alternatives to petro-based polymers, packaging applications are the primary ones. Poly(lactic acid)s can be synthesized either by direct polycondensation of lactic acid (lUPAC name 2-hydroxypropanoic acid) or by ring-opening polymerization (ROP) of lactide (LA) (lUPAC name 3,6-dimethyl-l,4-dioxane-2,5-dione). Lactic acid is optically active and has two enantiomeric forms, that is, L- and D- (S- and R-). Lactide is a cyclic dimer of lactic acid that has three possible stereoisomers (i) L-lactide (LLA), which is composed of two L-lactic acids, (ii) D-lactide (DLA), which is composed of two D-lactic acids, and (iii) meso-lactide (MLA), which is composed of an L-lactic acid and a D-lactic acid. Due to the two enantiomeric forms of lactic acids, their homopolymers are stereoisomeric and their crystallizability, physical properties, and processability depend on their tacticity, optical purity, and molecular weight the latter two are dominant factors. 

PLA can be synthesized by two routes polycondensation of lactic acid or ringopening polymerization of its cyclic dimer, lactide [12]. PLA prepared from polycondensation has low molar mass and poor mechanical properties and Is therefore not suitable for many applications [13]. High-molar-mass PLA Is most commonly made by ring-opening polymerization of lactide. In both cases, lactic acid is the feedstock for PLA production. Lactic acid has an asymmetric carbon atom, which leads to two optically active forms called L-lactic acid and D-lactic acid. When producing PLA from lactide, polymerization can start from three types of monomers LL-lactide made from two L-lactic acid molecules, DD-lactide from dimerization of D-lactic acid, and LD or wieso-lactide made from a combination of one L- and one D-lactic acid molecules [14,15]. The chemical structures of lactic acid and lactide molecules are illustrated in Figure 5.1. 

The concentration of the remaining monomer decreases to zero at 120 and 140 °C where the polymerization systems turn to solid state, whereas at 160 °C the monomer consumption reaches a plateau with the melt-state retained. The same technique is utilized to increase the molecular weight of PLA in the solid-state polycondensation of lactic acid vide infra). 

Belonging to the family of aliphatic polyesters, poly(lactic acid) or polylactide (PLA) is composed of lactic acid repetitive units, which is the simplest ot-hydro)y acid with an asymmetric carbon atom. Interestingly, the L-lactic acid monomer, and more recently the D-lactic acid monomer, can be straightforwardly obtained by bacterial fermentation from renewable resources (namely starch), making both monomers and therefore the resulting polymers environmentally friendly. Polycondensation of lactic acid and ring-opening polymerization (ROP) of lactide (LA), i.e. cyclic diesters of lactic acid, are currently used to prepare PLA polymers (Scheme 4.1). 

Aliphatic polyesters are biocompatible and biodegradable polymers that are widely used in biomedical applications. Within these, polylactides and poly(s-caprolactone) are two of the most studied ones (Fig. 2). These polyesters can be synthesized via ring-opening polymerization of the corresponding cyclic esters (s-caprolactone and lactide) and via polycondensation of lactic acid. In material science, both pure aliphatic polyesters and natural polysaccharides have limitations in some specific applications. These limitations can be overcome by the introduction of hydrophilic groups (carbohydrate compounds) into the aliphatic polyesters and modifications of natural polysaccharides with hydrophobic polyesters. 

The lactide monomer for PLA is obtained from catalytic depolymeiization of short PLA chains under reduced pressure [4]. This prepolymer is produced by dehydration and polycondensation of lactic acid under vacuum at high temperature. After purification, lactide is used for the production of PLA and lactide copolymers by ROP, which is conducted in bulk at temperatures above the melting point of the lactides and below temperatures that cause degradation of the formed PLA [4]. 

Alcohols If water is the initiator, R equals H and hydrolysis of lactide produces lactoyl lactic acid (HL2). Propagation with lactide in the presence of a polymerization catalyst produces PLA with a hydroxyl and one carboxylic acid end group, as if the PLA was obtained by polycondensation of lactic acid. 

Poly(L-lactide) (PLLA) is a biodegradable aliphatic polyester produced by ring-opening polymerization of lactide (i.e., with cyclic dimer of lactic acid) or by polycondensation of lactic acid. Although PLLA is a synthetic polymer, it is considered a renewable and bio-based plastic because its raw material lactic acid is synthesized from biomass or renewable resources such as sugars and starch. PLLA has some properties that are similar to some petroleum-based plastics, thereby making it suitable for a variety of applications in the medical, textile, and packaging industries. 

Direct polycondensation of lactic acid is usually performed in bulk by distillation of condensation water with or without a catalyst, while vacuum and temperature are progressively increased. The polymer obtained has a low molecular weight, because it is hard to remove water completely from the highly viscous reaction mixture therefore a polymer of a molecular weight of a few ten thousands is obtained. The polymer of low molecular weight is the main disadvantage of... 

Moreover, the molecular weight remained around 100 000 Da, being much lower than that of the PLLA obtained by the ring-opening polymerization of Z-lactide. Therefore, they examined the melt/solid polycondensation of lactic acid in which the melt polycondensation of Z,-lactic acid was subjected to solid-state polycondensation below Tm of PLLA [8]. In solid state, the polymerization reaction can be favored over the depolymerization or other side reactions. Particularly, in the process of crystallization of the resultant polymer, both monomer and catalyst can be segregated and concentrated in the noncrystalline part to allow the polymer formation to reach 100% [9]. Figure 3.2 shows the whole process of this melt/solid polycondensation of Z-lactic acid. In this process, a polycondensation with a molecular weight of 20 000 Da is first prepared by... 

There are a number of post-polycondensation methods and melt polycondensation of lactic acid that have for example been... 

Two routes are currently used to obtain PLA, via polycondensation of lactic acid or via lactide (a dimer of lactic acid) ring opening (see Figure 10.8). 

Lactic acid based polymer such as PLA belongs to the family of ahphatic polyesters. The PLA is formed by polycondensation of lactic acid (2-hydroxy propionic acid). It is a biodegradable polymer with a reasonable shelf life, for a wide variety of consumer products, such as paper coatings, films, moulded articles, and fiber applications (Datta et al., 1995). It degrades slowly by simple Itydrolysis of the ester bond to convert into harmless, natnral products like CO and H O (Drumright et al., 2000). 

The synthesis of high-molecular-weight PLA is generally carried out by the ring-opening polymerization of lactide or by direct polycondensation of lactic acid. Tin-based catalysts are typically used in both cases, either alone or in combination with p-toluenesulfonic acid. ° ... 

Mitsui process for the production of polylactide by polycondensation of lactic acid. 

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