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Description  |
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BACKGROUND OF THE INVENTION
The present invention relates to the catalytic production of lactide and
more particularly to its direct production from lactic acid.
For purposes of this application, the following definitions apply:
L.sub.1 A: lactic acid or 2-hydroxypropionic acid
LD: lactide or 3,6-dimethyl-1,4-dioxane-2,5-dione
L.sub.2 A: lactoyllactic acid or lactic acid dimer
L.sub.3 A: lactoyllactoyllactic acid or lactic acid trimer
L.sub.n A: n-oligomer of lactic acid.
The DP or degree of polymerization of lactic acid is "n".
Lactic acid has one asymmetric carbon atom and, thus, can be found in two
enantiomeric forms. Lactide, on the other hand, has two asymmetric carbon
atoms so that it can be found in three steroisomeric forms: L-lactide in
which both asymmetric carbon atoms possess the L (or S) configuration;
D-lactide in which both asymmetric carbon atoms possess the D (or R)
configuration; and meso-lactide in which one asymmetric atom has the L
configuration and the other has the D configuration. L-lactide and
D-lactide are enantiomers while D,L-lactide is the meso species. In the
production of lactide from lactic acid, it would be advantageous if the
absolute configuration of the lactic acid feed was maintained in its
conversion to lactide. Enantiomeric lactide, especially L-lactide, has
utility in the production of polymers, especially in the production of
environmentally degradable polymers such as proposed in commonly-assigned
U.S. applications Ser. Nos. 387,670; 387,676; 387,678; and 386,844.
Heretofore, production of lactide from lactic acid has proceeded by the
initial formation of oligomeric lactic acid, L.sub.n A, such as by
dehydration of aqueous lactic acid, followed by a catalytic
transesterification reaction known as "back-biting" as illustrated below:
##STR1##
As illustrated above, back-biting depolymerization of L.sub.n A results in
the production of lactide. Catalysts proposed for such a reaction include
tin powder, tin halides, or tin carboxylates (EP Publication 261,572); tin
alkoxides (U.K. Pat. No. 1,007,347); and zinc or tin (EP Publication
264,926).
Direct conversion of lactic acid into lactide with or without preservation
of absolute configuration of asymmetric atoms is not shown in the art.
BROAD STATEMENT OF THE INVENTION
The present invention is directed to a method for making L-lactide from
aqueous L-lactic acid. Aqueous lactic acid feed for present purposes
comprehends an aqueous mixture of one or more of L.sub.1 A, L.sub.2 A, and
L.sub.3 A, optionally with LD being present. L-lactic acid is the
preferred feed configuration for making L-lactide, and is to be understood
even though the configuration symbol is not used throughout this
application. Aqueous lactic acid feed is treated for removal of water
therefrom until a degree of polymerization (DP) not substantially above
about 2 is reached. The treatment then is ceased to produce a crude LD
product. LD then is separated from the crude LD product. A preferred
treatment involves heating the feed at elevated temperature to remove
water during which additional LD forms.
LD can be separated from the crude LD product by a variety of techniques to
produce an LD-depleted product. This LD-depleted product, optionally
augmented with additional aqueous lactic acid and/or water then can be
readmitted to the process for making additional lactide. This cyclic or
recycle process embodiment of the present invention enables very high
lactide conversions to be realized.
Advantages of the present invention include the ability to convert lactic
acid directly into lactide of high purity. Another advantage is that the
asymmetric carbon atoms in the product lactide predominate in the same
absolute configuration as the feed lactic acid from which it was made.
Another advantage is a process which is amenable to recycling unreacted
lactic acid and by-products formed during the treatment process. The
simplicity of the process is yet a further advantage. These and other
advantages will be readily apparent to those skilled in the art based upon
the disclosure contained herein.
DETAILED DESCRIPTION OF THE INVENTION
The lactic acid feed is in aqueous form for conversion to its vapor phase
as an initial step of the process of the present invention. The role
played by water in the process can be appreciated by reference to the
following equilibrium reactions:
##STR2##
or written another way:
2L.sub.1 A.revreaction.L.sub.2 A+H.sub.2 O
LA+L.sub.2 A.revreaction.L.sub.3 A+H.sub.2 O
2L.sub.2 A.revreaction.L.sub.4 A+H.sub.2 O
etc.
Thus, it will be observed that L.sub.1 A is in equilibrium with higher
oligomers of lactic acid and water. By removing water, these reactions
shift to the right. In fact, L.sub.2 A and higher lactic acid oligomers
(L.sub.n A) are made by dehydrating aqueous lactic acid. Sufficient water,
then, should be present so that the equilibrium detailed above favors the
presence of L.sub.1 A and L.sub.2 A in as the feedstock. Extra quantities
of water in the feedstock are permissible at the expense of the handling
and energy costs associated therewith.
What was unknown in the foregoing equilibrium reactions is that when water
is removed so that higher DP oligomeric lactic acid is produced, LD also
is produced. As the data will demonstrate, at a DP of about 2, the LD
content of the material is maximized. It is worth restating that removal
of water is the driving force behind this reaction. If water removal is
ceased at a DP of about 2, LD then can be separated from the reaction
mixture and recovered for use. It will be recognized that the art has
always dehydrated aqueous lactic acid to form oligomeric L.sub.n A having
a DP of 5 or above. The art then employed a catalyzed reaction known as
back-biting for production of lactide. What the art failed to grasp was
that lactide formed during the dehydration and its content was maximized
at about 2. Also, it was unrecognized that LD is sufficiently stabe in the
presence of hot L.sub.n A and water to be isolated in significant
quantities.
Since the crude LD product has a DP of around 2 and the process modality
involves removal of water, the appropriate lactic acid feed is enriched in
L.sub.1 A and L.sub.2 A, and depleted in higher oligomeric L.sub.n A
species. That is not to say that L.sub.3 A, L.sub.4 A, and some higher
olgomeric L.sub.n A species are not present in the lactic acid feed, but
their presence should be minimized in order to maximize LD production in
accordance with the precepts of the present invention. Lactic acid
feedstocks enriched in higher oligomeric L.sub.n A species preferably
should be hydrolyzed in order to take advantage of the equilibrium
equations detailed above for enriching the lactic acid feed in L.sub.1 A
and L.sub.2 A. The presence of higher oligomeric L.sub.n A species, then,
only serves to compromise yields of LD by the present process. The lactic
acid feedstock can contain LD it self, especially when employing a recycle
of the crude LD feedstock that has been treated for separating LD product
therefrom. The presence of LD in the feedstock appears to have no adverse
consequences on conversion of L.sub.1 A and L.sub.2 A to LD, i.e. LD can
be achieved by kinetic means rather than relying strictly on equilibrium
amounts.
A variety of reactors and reaction schemes can be envisioned for treating
the aqueous lactic acid feed for removal of water. A straightforward
treatment involves subjecting the aqueous lactic acid to heating at
elevated temperature (e.g. 150.degree.-225.degree. C.) to remove water
therefrom until the heated feed has a DP not substantially above about 2.
Alternative treatment schemes can be envisioned for removal of water,
however. An additional treatment may include the addition of a
water-getter which preferentially reacts with water for forming a compound
that is innocuous in the process. Such compounds include, for example,
anhydrides (e.g. acetic anhydride), acetals (e.g., the diethyl acetal of
acetaldehyde), carbodiimides, and ketals (e.g. dimethyl ketal of acetone).
Yet another technique that can be envisioned for removing water from the
aqueous lactic acid feed involves subjecting feed to an osmotic membrane
suitable for permitting water molecules to pass therethrough, yet having
the ability to exclude L.sub.1 A, L.sub.2 A, LD, and the like. So long as
water is preferentially removed from the aqueous lactic acid fee until a
DP not substantially above about 2 is reached, the equilibrium reactions
detailed above result in formation of LD product.
In a non-catalyzed process, it is believed that L.sub.2 A cyclizes (or
esterifies) to form LD. LD is in equilibrium with L.sub.2 A in the
reaction mixture, however, the crude LD product produced is not an
equilibrium reaction mixture. That is, it appears that LD is formed during
the treatment to raise the DP to a value not substantially above about 2.
The treatment then must cease and the crude LD product subjected to
processing for LD removal. If the crude LD product reaction mixture is
permitted to stand for too long, the reactants and products in the
reaction mixture will equilibrate and likely some LD values will return to
L.sub.2 A or react to form L.sub.3 A and L.sub.4 A. Extended periods of
time between generation of the crude LD product and separation of LD
therefrom is not recommended.
Conventional back-biting or depolymerization reactions of higher oligomeric
L.sub.n A species for LD production are conducted in the presence of
catalysts. Accordingly, research endeavors in connection with the present
invention also explored the effect of catalysts on the present process. As
the data in the examples will reveal, the presence of conventional
catalysts, e.g. tin compounds, had very little effect on LD production
compared to conducting the process in substantial absence of such
catalysts. These results may be explained by postulating the tin catalyst
functionality to involving cleaving higher DP oligomeric L.sub.n A species
into smaller fragments that form lactide. At a DP of around 2, the
mechanism for LD production is believed to primarily involve a rapid ring
closure that does not require the presence of a catalyst. Thus, the
presence of conventional LD-yielding catalysts are unnecessary in the
present process, though their presence is not excluded.
A variety of separation techniques also can be envisioned for separating LD
from crude LD product produced by the treatment of the aqueous lactic acid
feed. These techniques include, for example, cold water washing of the
crude LD product, fractional distillation of the crude LD product, solvent
extraction of the crude LD product, and recrystallization of the crude LD
product, for LD recovery therefrom. Combinations of these techniques may
be used additionally.
The presently preferred LD recovery processing scheme involves distillation
which preferably is conducted under vacuum and/or utilizing a
codistillation organic solvent to facilitate removal of LD from the crude
LD product. A codistillation solvent is convenient, particularly for large
stills, where heat for LD formation and distillation requires a reboiler.
The codistillation solvent provides heat to the upper part of the still
and provides heat transfer for the reaction. Additionally, a
codistillation solvent dilutes the vapor from the feed and enhances the
ring closure process. Particularly convenient is the use of a
codistillation solvent that is immiscible with LD and L.sub.n A species.
This provides additional vapor pressures of the solvent and LD, and
separation of LD from the solvent. One class of codistillation solvents
meeting the preferred requirements comprise alkyl benzenes, especially
those with a boiling point equal to or slightly higher than that of LD.
Representative preferred alkyl benzene solvents include higher alkyl
benzenes including C.sub.10 -C.sub.22 alkyl benzenes, and preferably
dodecyl benzene or tridecyl benzene. Distillation cuts that have an
average composition of dodecyl benzene also are quite appropriate for use
in the present invention. These mixed cuts supply the necessary boiling
point, are non-toxic, and are commercially available.
The crude LD product which has been treated for removal of LD contains
L.sub.n A values that can be converted into LD typically by treating the
product residue for its enrichment in L.sub.1 A and L.sub.2 A. When
distillation is the water removal treatment of choice, the still bottoms
additionally can be combined with the product residue for re-admission to
the process. Hydrolyzing this recycle stream for its enrichment in L.sub.1
A and L.sub.2 A typically is recommended most often with augmentation with
additional fresh aqueous lactic acid feed. Overall LD yields exceeding 90%
can be expected when employing such recycle techniques.
The following examples show how the present invention has been practiced,
but should not be construed as limiting. In this application, all
percentages and proportions are by weight and all units are in the metric
system, unless otherwise expressly indicated. Also, all citations referred
to herein are incorporated expressly herein by reference.
EXAMPLES
Example 1
A three-neck, one-liter round-bottom flask was fitted with a mechanical
stirrer, nitrogen sparged, and a straight distillation take-off to a
condenser, and the receiver to a vacuum take-off and manometer. The flask
was charged with 650 ml (770.4 g) of 88% L-lactic acid feed and heated at
120.degree.-130.degree. C. with stirring and nitrogen bubbling. Water was
distilled using a water aspirator at 150-200 Torr. Aliquots are removed
during the course of the heating and characterized by titration for DP
(degree of polymerization). Then, after methylation with diazomethane, the
aliquots were characterized by gas chromatography (GC) for percentages of
L.sub.2 A, L.sub.3 A, L.sub.4 A, and LD. The results recorded are set
forth below.
TABLE 1
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DP.sup.(a)
Conditions Distillation
of OLA Composition (wt %).sup.(b)
Temperature
Pressure
L.sub.1 A
L.sub.2 A
L.sub.3 A
L.sub.4 A
LD (.degree.C.)
(torr)
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1.29.sup.(c)
75.4 20.1 3.3 0.3 1.3 -- --
1.44 49.0 28.5 11.5 2.2 3.3 120-130
400-210
1.59 27.8 27.8 20.2 10.3 8.6 150 90
1.99 11.8 16.7 14.4 8.8 18.4 155 153
2.01 12.3 14.0 13.8 9.8 19.0 160 85
2.07 8.3 6.0 15.0 15.0 27.9 175 30
2.63 2.1 0.7 1.0 0.8 14.7 .sup. 185.sup.(d)
.sup. 30.sup.(d)
24.0 0.4 1.4 0.6 0.4 11.5 .sup. 185.sup.(d)
.sup. 10.sup.(d)
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.sup.(a) Titration with KOH. OLA is oligomeric lactic acid.
.sup.(b) Gas chromatography of methyl esters.
.sup.(c) Llactic acid feed.
.sup.(d) Prolonged (overnight) distillation.
As the above-tabulated data reveals, LD production surprisingly peaked at a
DP of about 2. This peak LD production was achieved under relatively mild
distillation conditions in a facile manner. If the flask contents are
further dehydrated to higher DPs, LD eventually will begin to distill.
Continued distillation to steady state results in LD in the pot being
approximately 3-6% of the oligomeric lactic acids present, i.e. in the
conventional back-biting mode.
Examples 2-11
A pot was connected to a distillation head and cooled receiver, feed
funnel, and manistat for maintaining a pressure of about 50-60 torr.
Aliquots of the various DP materials of Example 1 were incrementally
distilled by adding them dropwise from the heated funnel (145.degree. C.)
to the pot under rapid stirring. The pot temperature of the melt was
monitored by an internal thermocouple and the pot was heated by an
external oil bath. The pot temperature was varied and the distillation
rates noted. The amount of material that distills rapidly, i.e. several
drops per second, was weighed and compared to the amount remaining in the
pot. The distillations generally were marked by rapid distillations at the
beginning of each run, slowing eventually to approximately 1/5 the initial
rate, i.e. 1 drop per 2-3 seconds. The results are recorded in the
following tables.
TABLE 2
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Amount.sup.(b)
Distilled/ Distillation.sup.(c)
Not Distilled
Temperature
Distillation
Example DP.sup.(a)
(wt %) (.degree.C.)
Rate
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2 1.29 67/16 200 rapid
3 1.44 49/42 193 rapid
4 1.59 39/58 220 rapid
5 1.99 52/48 197 slow
6 1.99 54/46 225 rapid
7 1.99 43/65 215 slow
8 2.07 15/76 202 moderate
9 2.63 trace distilled
204 very slow
10 2.63 8/85 227 very slow
11 24.0 trace distilled
204 very slow
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.sup.(a) By titration.
.sup.(b) As weight percent of starting material.
.sup.(c) 50-60 torr.
TABLE 3
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L-LD.sup.(b) (wt %)
Starting
Example DP.sup.(a)
Material Distillate
Pot
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2 1.29 1.3 1.1 18.5
3 1.44 3.3 1.4 25.5
4 1.59 8.6 18.8 26.1
6 1.99 18.4 43.5 13.2
8 2.07 27.9 35.2 24.7
9 2.63 14.7 12.7 7.1
11 24 11.5 trace 5.8
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.sup.(a) Degree of polymerizat | | |
