Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2003-01-13
2004-10-05
Owens, Amelia A. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06800767
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a process for purifying dimeric cyclic esters (especially lactides or glycolides) of general formula:
where R
1
, R
2
, R
3
, and R
4
may alternatively be a hydrogen, an aromatic group or a substituted or unsubstituted aliphatic group having from 1 to 10 carbon atoms. These esters can be converted into polymers which are particularly useful for preparing biodegradable and bioabsorbable plastics in medicine. The polymers of lactide (where R
1
=R
3
=H and R
2
=R
4
=CH
3
) are degradable by aqueous hydrolysis under the majority of environmental conditions, giving lactic acid or oligomers.
The two optically active forms of lactic acid (L-LA) and (D-LA) may give a lactide (LD or cyclic dimer) in 3 diastereoisomeric forms: with 2 molecules of D-lactic acid (D,D-lactide or D-LD), with 2 molecules of L-lactic acid (L,L-lactide or L-LD), or with one molecule of each (meso-lactide or meso-LD). Also encountered is the racemic mixture ((D,L)-lactide) characterized by a melting point (Tf=126° C.) greater than that of L-LD or D-LD (Tf=97° C.).
Presently, the two major methods of producing lactide are distinguished essentially by the average degree of polymerization (DP) of the oligomers from the condensation step.
The first consists in extracting the water from a solution of lactic acid to obtain oligomers where 8≦DP≦25. These oligomers are subsequently depolymerized (back-biting reaction) with a Lewis acid catalyst, either under reduced pressure at a higher or lower temperature or under a stream of nitrogen. This process is realized under severe conditions which prove expensive and affect the optical purity of the lactide (high percentage of racemization).
The second method utilizes an oligomer where 1.5≦DP≦2.5 produced in vapor phase at high temperature or in liquid phase in the presence of a cosolvent which forms an azeotrope with water. The principal drawbacks are the presence of a solvent, often an aromatic solvent, with a high boiling point; a reaction temperature >180° C.; a lack of selectivity; and a not inconsiderable quantity of protic impurities.
In general, the crude lactide obtained by various synthesis routes includes a number of protic impurities (carboxylic acids, hydroxyl compounds, water, etc.) which must be extracted in order to provide a sufficient purity for the crude product to be integrated to the process of polymerization by ring opening.
PRIOR ART
Percentages will always be expressed by weight in the remainder of this text.
The skilled worker is aware of CA 2 115 472, which proposes a process for purification by dynamic crystallization in the melt state, with recovery of meso-LD in an enriched form. However, the process is applicable only to crude lactides having L-LD/D-LD ratios of at least 80/20 or at least 20/80. Where the composition of the crude product is found to correspond to a composition beyond the eutectic, there is then an enrichment which racemic mixture L-LD+D-LD, with rejection of the L-LD together with the impurities such as water, lactic acid and the oligomers. On the other hand, it is necessary to start from a crude lactide which is already rich in lactides (>90% L-LD+meso-LD).
U.S. Pat. No. 5,502,215 relates to a process for purifying crude lactide which comprises crystallizing L-LD and/or D-LD in an aqueous medium followed by centrifugal separation, gas-phase drying, and recrystallization from an organic solvent with centrifugal separation and gas-phase drying and, where appropriate, rinsing with this organic solvent. The emphasis is on the removal of the meso-LD by hydrolysis and not on the extraction of protic impurities by water. On the other hand, the aim is not to produce lactide crystals of a particular type.
The two purification methods described above, which make it possible to treat a variety of crude lactides and to obtain purities of the order of 99%, which allows polymerization to polylactide (PLA) under tolerable conditions. However, these methods involve either large yield losses due to the opening, the chemical racemization and/or the thermal racemization of the lactide ring or high investment costs and exploitation costs tied to the needs for storage and treatment which are associated with a solvent purification procedure.
The present invention overcomes these drawbacks and makes it possible to produce a lactide which is sufficiently pure for polymerization under good economic conditions.
BRIEF DESCRIPTIONS OF THE INVENTION
The present invention provides a process for purifying cyclic esters, especially the cyclic dimer of lactic acid (lactide), starting from a “crude lactide”, namely a mixture of lactic acid and/or lactic ester and their respective oligomers (L
n
A with n<5), water and/or alcohol and also various diastereoisomeric forms of lactide.
This crude product may be obtained either starting from lactic acid, and/or its salts and/or its esters originating from any synthesis known to the skilled worker, a nonexhaustive description of which has been set out above, or starting from residues from purification processes such as distillation or crystallization in a melt medium.
We will always refer below to the synthesis of lactide starting from lactic acid, although it may also be applied to the esters of lactic acid. By lactide is meant one of the two diastereoisomeric forms (L-LD or D-LD) and not meso-LD.
The purification process described in this invention is original since, starting from a crude lactide (even one poor in lactide), it provides a very high quality of lactide with a high mass yield and a minimum energy consumption. A lactide of very high quality (chemical or optical quality) may serve as a monomer for the synthesis of PLA by ring opening.
The quantitative and selective process is assured by the joint employment: (a) of controlled, extractive crystallization of the lactide in an aqueous medium, in order to promote the formation of large crystals and the transfer of the protic impurities to the liquid phase, (b) of centrifugal or other separation (with or without washing) of the lactide and of the aqueous phase, (c) of solid-phase or liquid-phase drying of the moist cake obtained, and (d) of one or more recrystallizations in a melt medium.
This sequence allows easy and quantitative recycling of the aqueous-phase impurities to the lactic acid production procedure. Optimizing the temperature and residence time conditions makes it possible, in contrast to the conventional processes, to avoid chemical and thermal deterioration of the lactide in the course of its purification. The industrial criteria of quality and of yield are attained much more readily.
The energy outlay is minimal owing to the simplicity of the technologies, to the low operating temperatures, and to the judicious juxtaposition of the steps. Recrystallization in a melt medium is known to the skilled worker, since it makes it possible to obtain a lactide of excellent quality and a selectivity which is necessary for the synthesis of PLA. However, starting from a lactide-poor crude lactide, this technology does not make it possible both to guarantee an adequate yield of lactide and to withstand an economic comparison vis-à-vis other technologies (distillation, recrystallization from solvent, etc.). On the other hand, the succession of steps (a) to (d) and the methodology recommended by the present invention compensate for handicap.
REFERENCES:
patent: 6489508 (2002-12-01), Van Gansbeghe et al.
patent: 657447 (1995-06-01), None
Bogaert Jean-Christophe
Coszach Philippe
Di Salvatore Patricia
Van Gansberghe Frédéric
Brussels Biotech
Owens Amelia A.
LandOfFree
Method for purifying cyclic esters does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for purifying cyclic esters, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for purifying cyclic esters will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3311989