U.S. patent application number 15/102297 was filed with the patent office on 2017-01-05 for synthesis of isohexide ethers and carbonates.
The applicant listed for this patent is ARCHER DANIELS MIDLAND COMPANY. Invention is credited to Kenneth Stensrud, Padmesh Venkitasubramanian.
Application Number | 20170002019 15/102297 |
Document ID | / |
Family ID | 53403506 |
Filed Date | 2017-01-05 |
United States Patent
Application |
20170002019 |
Kind Code |
A1 |
Stensrud; Kenneth ; et
al. |
January 5, 2017 |
SYNTHESIS OF ISOHEXIDE ETHERS AND CARBONATES
Abstract
A facile, straightforward method for alkylation of anhydrosugar
alcohols (isohexides) using a carbonate reagent is described. The
alkylation method involves: a) contacting in a solution of an
isohexide with a dialkyl, diallyl, or diaryl carbonate, and the
solution includes a Bronsted base; and b) producing either an alkyl
ether or alkyl carbonate of the isohexide compound. The alkylation
reaction is in situ, that is, performed without an extrinsic
catalyst. According to the method, one can synthesize various
ethers and carbonates.
Inventors: |
Stensrud; Kenneth; (Decatur,
IL) ; Venkitasubramanian; Padmesh; (Forsyth,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ARCHER DANIELS MIDLAND COMPANY |
Decatur |
IL |
US |
|
|
Family ID: |
53403506 |
Appl. No.: |
15/102297 |
Filed: |
December 5, 2014 |
PCT Filed: |
December 5, 2014 |
PCT NO: |
PCT/US14/68809 |
371 Date: |
June 7, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61918795 |
Dec 20, 2013 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07C 67/343 20130101;
C07C 67/08 20130101; C07D 307/12 20130101; C07D 307/42 20130101;
C07C 68/06 20130101; C07D 493/04 20130101 |
International
Class: |
C07D 493/04 20060101
C07D493/04 |
Claims
1. A method of alkylating an anhydrosugar compound comprising: a)
contacting an isohexide compound with a dialkyl, diallyl, or diaryl
carbonate and a Bronsted base; and b) producing at least an alkyl
ether or alkyl carbonate of the isohexide compound.
2. The method according to claim 1, wherein the anhydrosugar
compound is at least one of: isosorbide, isomannide, and
isoidide.
3. The method according to claim 1, wherein said dialkyl, diallyl,
or diaryl carbonate has an R-group having 1 to 20 carbon atoms.
4. The method according to claim 3, wherein when said R-group is at
least one of methyl, ethyl, propyl group, said alkyl ether is
produced predominantly.
5. The method according to claim 3, wherein when said R-group is at
least a C.sub.4-C.sub.20 group, said alkyl carbonate is produced
predominantly.
6. The method according to claim 1, wherein said alkylated ether of
said isohexide compound is at least one of: mono-ether of isoidide,
mono-ether of isomannide, mono-ether of isosorbide, di-ether of
isoidide, di-ether of isomannide, and di-ether of isosorbide.
7. The method according to claim 3, wherein said alkylated
isohexide compound is an ether having at least one of the following
alkyl groups: a mono-methyl, mono-ethyl, mono-propyl, di-methyl,
di-ethyl, or di-propyl isohexide ether.
8. The method according to claim 1, wherein said alkylated
carbonate of said isohexide compound is at least one of:
mono-carbonate of isoidide; mono-carbonate of isomannide;
mono-carbonate of isosorbide; di-carbonate of isoidide;
di-carbonate of isomannide; and di-carbonate of isosorbide.
9. The method according to claim 5, wherein said alkylated
isohexide compound is a carbonate having at least one of the
following alkyl, allyl or aryl groups: a mono-butyl, mono-pentyl,
mono-hexyl, mono-benzyl, mono-phenyl, mono-allyl, di-butyl,
di-pentyl, dihexyl, di-benzyl, di-phenyl, di-allyl, or a mono- or
di-alkyl group from C.sub.7-C.sub.20 carbon atoms.
10. The method according to claim 1, wherein said anhydrosugar
compound and said dialkyl, diallyl, or diaryl carbonate are
contacted at a temperature in a range from about 70.degree. C. to
about 200.degree. C.
11. The method according to claim 10, wherein said anhydrosugar
compound and said dialkyl, diallyl, or diaryl carbonate are
contacted at a temperature in arrange from about 80.degree. C. to
about 150.degree. C.
12. The method according to claim 1, wherein said anhydrosugar
compound and said dialkyl, diallyl, or diaryl carbonate are
contacted in a neat solution of said dialkyl, diallyl, or diaryl
carbonate.
13. The method according to claim 1, wherein said Bronsted base has
a pKa of at least 4.
14. The method according to claim 13, wherein said Bronsted base
has a pKa 7-14.
15. The method according to claim 1, wherein said Bronsted base is
at least one of the following: a carbonate; a hindered amine; a
nucleophilic base; a sodium, potassium or calcium hydride; or an
organometallic compound.
16. The method according to claim 15, wherein said organometallic
compound is an alkyl-lithium or alkyl-magnesium.
17. An ether compound prepared according to the method of claim 1,
wherein said ether compound is at least one of the following: a
monoalkyl ether or dialkyl ether.
18. The ether compound according to claim 17, wherein said ether
compound has a structure: ##STR00018## wherein for a dialkyl ether,
R is a C.sub.1-C.sub.3 alkyl group; and, for a monoalkyl ether, one
R is a C.sub.1-C.sub.3 alkyl group and another is an OH.
19. The ether compound according to claim 17, wherein said ether
compound is at least: an isoidide monoethylether, with a structure:
##STR00019## an isoidide diethylether, with a structure:
##STR00020##
20. The alkylated isohexide compound according to claim 17, wherein
said compound is an ether selected from the group consisting of:
mono-methyl ether of isoiodide; mono-ethyl ethers, of isosorbide,
isommanide, or isoiodide, respectively; diethyl ester of isoiodide;
mono-propyl ether of isomannide; dipropyl ether of isomannide;
mono-propyl ether of isoidide; dipropyl ether of isoiodide;
mono-benzyl ether of isoidide; monoallyl ethers of isosorbide,
isommanide, or isoiodide, respectively; and diallyl ethers of
isosorbide, isommanide, or isoiodide, respectively.
21. A carbonate compound prepared according to the method of claim
1, wherein said carbonate compound is at least one of the
following: a mono-alkyl carbonate, dialkyl carbonate, mono- or
di-aryl carbonate, mono- or di-allyl carbonate, or a carbonate with
an alkyl group from 4-20 carbon atoms.
22. The carbonate compound according to claim 21, wherein said
carbonate compound has a structure: ##STR00021## wherein for a
dialkyl carbonate, R is a C.sub.4 or higher carbon alkyl, phenyl,
allyl group; and, for a monoalkyl ether, one R is a C.sub.4 or
higher carbon alkyl, phenyl, allyl group and another is an OH.
23. The carbonate compound according to claim 21, wherein said
carbonate compound is: isosorbide diallyldicarbonate, with a
structure: ##STR00022##
24. The alkylated isohexide compound according to claim 21, wherein
said compound is a carbonate selected from the group consisting of:
mono-methylcarbonate of isomannide; mono-methylcarbonate of
isoidide; dimethylcarbonate of isomannide; dimethylcarbonate of
isoidide; monoethylcarbonates of isosorbide, isommanide, or
isoiodide; diethylcarbonate of isomannide; diethylcarbonate of
isoidide; mono-propyl or dipropylcarbonates of isosorbide,
isommanide, or isoiodide; mono- or dicarbonates having an alkyl
R-group of C.sub.4 to C.sub.20 of isosorbide, isommanide, or
isoiodide, respectively; mono-benzyl or dibenzyl carbonates of
isosorbide, isommanide, or isoiodide, respectively;
monophenylcarbonates of isosorbide, isommanide, or isoiodide,
respectively; and diphenylcarbonates of isomannide or isoidide.
Description
BENEFIT OF PRIORITY
[0001] The present application claims benefit of priority of U.S.
Provisional Application No. 61/918,795, filed on Dec. 20, 2013, the
contents of which are incorporated herein by reference.
FIELD OF INVENTION
[0002] The present invention is in the field of art that relates to
cyclic bi-functional materials useful as monomers in polymer
synthesis and as intermediates generally, and to the methods by
which such materials are made. In particular, the present invention
pertains to a method of preparing anhydrosugar ethers and
carbonates.
BACKGROUND
[0003] Traditionally, polymers and commodity chemicals have been
prepared from petroleum-derived feedstock. As petroleum supplies
have become increasingly costly and difficult to access, interest
and research has increased to develop renewable or "green"
alternative materials from biologically-derived sources for
chemicals that will serve as commercially acceptable alternatives
to conventional, petroleum-based or -derived counterparts, or for
producing the same materials as produced from fossil, non-renewable
sources.
[0004] One of the most abundant kinds of biologically-derived or
renewable alternative feedstock for such materials is
carbohydrates. Carbohydrates, however, are generally unsuited to
current high temperature industrial processes. Compared to
petroleum-based, hydrophobic aliphatic or aromatic feedstocks with
a low degree of functionalization, carbohydrates such as
polysaccharides are complex, multi-functionalized hydrophilic
materials. As a consequence, researchers have sought to produce
biologically-based chemicals that can be derived from
carbohydrates, but which are less highly functionalized, including
more stable bi-functional compounds. One class of such compounds
include anyhydrosugars, such as 1,4:3,6-dianhydrohexitols.
[0005] 1,4:3,6-Dianhydrohexitols (also referred to herein as
isohexides) are derived from renewable resources from cereal-based
polysaccharides. Isohexides embody a class of bicyclic furanodiols
that derive from the corresponding reduced sugar alcohols
(D-sorbitol, D-mannitol, and D-iditol respectively). Depending on
the chirality, three isomers of the isohexides exist, namely: A)
isosorbide, B) isomannide, and C) isoidide, respectively; the
structures of which are illustrated in Scheme 1.
##STR00001##
These molecular entities have received considerable interest and
are recognized as valuable, organic chemical scaffolds for a
variety of reasons. Some beneficial attributes include relative
facility of their preparation and purification, the inherent
economy of the parent feedstocks used, owing not only to their
renewable biomass origins, which affords great potential as
surrogates for non-renewable petrochemicals, but perhaps most
significantly the intrinsic chiral bi-functionalities that permit a
virtually limitless expansion of derivatives to be designed and
synthesized.
[0006] The isohexides are composed of two cis-fused tetrahydrofuran
rings, nearly planar and V-shaped with a 120.degree. angle between
rings. The hydroxyl groups are situated at carbons 2 and 5 and
positioned on either inside or outside the V-shaped molecule. They
are designated, respectively, as endo or exo. Isoidide has two exo
hydroxyl groups, while the hydroxyl groups are both endo in
isomannide, and one exo and one endo hydroxyl group in isosorbide.
The presence of the exo substituents increases the stability of the
cycle to which it is attached. Also exo and endo groups exhibit
different reactivities since they are more or less accessible
depending on the steric requirements of the derivatizing
reaction.
[0007] As interest in chemicals derived from natural resources is
increases, potential industrial applications have generated
interest in the production and use of isohexides. For instance, in
the field of polymeric materials, the industrial applications have
included use of these diols to synthesize or modify
polycondensates. Their attractive features as monomers are linked
to their rigidity, chirality, non-toxicity, and the fact that they
are not derived from petroleum. For these reasons, the synthesis of
high glass transition temperature polymers with good
thermo-mechanical resistance and/or with special optical properties
is possible. Also the innocuous character of the molecules opens
the possibility of applications in packaging or medical devices.
For instance, production of isosorbide at the industrial scale with
a purity satisfying the requirements for polymer synthesis suggests
that isosorbide can soon emerge in industrial polymer applications.
(See e.g., F. Fenouillot et al., "Polymers From Renewable
1,4:3,6-Dianhydrohexitols (Isosorbide, Isommanide and Isoidide): A
Review," PROGRESS IN POLYMER SCIENCE, vol. 35, pp. 578-622 (2010);
or X. Feng et al., "Sugar-based Chemicals for Environmentally
sustainable Applications," CONTEMPORARY SCIENCE OF POLYMERIC
MATERIALS, Am. Chem. Society, December 2010; or isosorbide-based
plasticizers, e.g., U.S. Pat. No. 6,395,810, contents of each are
incorporated herein by reference.)
[0008] A kind of derivative that can be made is ethers of
isohexides. Conventionally, ethers of dianhydrosugars are prepared
by contacting alkyl halides and dialkylsulfates with an
anhydrosugar, in the presence of a base or phase transfer catalysts
(PTC's, e.g., tetra-n-butylammonium bromide, benzyltriethyammonium
bromide or N-methyl-N,N-dioctyloctan-1-aminium chloride).
Notwithstanding the inherent costs of these exotic PTC's, these
processes generally need highly pure anhydrosugar feedstock as a
starting material, and suffer from both cumbrous and costly
downstream separation operations to effectuate propitious target
purities. These issues have complicated efforts to achieve cost
effective yields at significant quantity and quality.
[0009] To better take advantage of isohexides as a green feedstock,
a clean and simple method of preparing the isohexides as a platform
chemical or precursor that can be subsequently modified to
synthesize other compounds would be welcome by those in the green
or renewable chemicals industry. A more cost efficient process is
needed as a way to unlock the potential of anhydrosugars and their
derivative compounds, as these chemical entities have gained
attention as valuable antecedents for the preparation of polymers,
solvents, additives, lubricants, and plasticizers, etc.
Furthermore, the inherent, immutable chirality of anhydrosugars
makes these compounds useful as potential species for
pharmaceutical applications or candidates in the emerging chiral
auxiliary field of asymmetric organic synthesis. Given the
potential uses, a cost efficient and simple process that can
synthesis derivatives from anhydrosugars would be appreciated by
manufacturers of both industrial and specialty chemicals alike as a
way to better utilize biomass-derived carbon resources.
SUMMARY OF THE INVENTION
[0010] The present disclosure describes a method for alkylation of
anhydrosugar alcohols (isohexides) using a carbonate reagent. In
particular, the alkylation method involves: a) contacting an
isohexide with a dialkyl, diallyl, or diaryl carbonate, and a
Bronsted base; and b) producing at least an alkyl ether or alkyl
carbonate of the isohexide compound. The alkylation reaction is in
situ, that is, performed without an extrinsic catalyst. The
Bronsted base has a pKa of at least 4, which helps deprotonates the
isohexide compound. The isohexide is at least one of the following:
isosorbide, isomannide, and isoidide. The dialkyl, diallyl, or
diaryl carbonate has an R-group having 1 to 20 carbon atoms. When
the R-group is at least a methyl, ethyl, propyl group, an ether is
produced, and when the R-group is at least a C.sub.4-C.sub.20
group, a carbonate is generated. The resultant ether or carbonate,
respectively, can be either: a mono-alkyl ether or dialkyl ether,
or mono-alkyl, mono-allyl, mono-aryl carbonate, or dialkyl,
diallyl, or diaryl carbonate.
[0011] In another aspect, the present disclosure pertains to
certain ethers and carbonates synthesized according the foregoing
method. In general, the alkylated ether of the isohexide compound
is at least one of the following: mono-ether of isoidide;
mono-ether of isomannide; mono-ether of isosorbide; di-ether of
isoidide; di-ether of isomannide; and di-ether of isosorbide,
wherein the resultant ether has at least one of the following alkyl
groups: a mono-methyl, mono-ethyl, mono-propyl, di-methyl,
di-ethyl, or di-propyl. Generally, the alkylated carbonate of the
isohexide compound is at least one of the following: mono-carbonate
of isoidide; mono-carbonate of isomannide; mono-carbonate of
isosorbide; di-carbonate of isoidide; di-carbonate of isomannide;
and di-carbonate of isosorbide, wherein the resultant carbonate has
at least one of the following alkyl, allyl or aryl groups: a
mono-butyl, mono-pentyl, mono-hexyl, mono-benzyl, mono-phenyl,
mono-allyl, di-butyl, di-pentyl, dihexyl, di-benzyl, di-phenyl,
di-allyl, or a mono- or di-alkyl group from C.sub.7-C.sub.20 carbon
atoms.
[0012] Additional features and advantages of the present process
will be disclosed in the following detailed description. It is
understood that both the foregoing summary and the following
detailed description and examples are merely representative of the
invention, and are intended to provide an overview for
understanding the invention as claimed.
DETAILED DESCRIPTION OF THE INVENTION
Section I
Description
[0013] As biomass derived compounds that afford great potential as
surrogates for non-renewable petrochemicals,
1,4:3,6-dianhydrohexitols are a class of bicyclic furanodiols that
are valued as renewable molecular entities. (For sake of
convenience, 1,4:3,6-dianhydrohexitols will be referred to as
"isohexides" in the Description hereinafter.) As referred to above,
the isohexides are good chemical platforms that have recently
received interest because of their intrinsic chiral
bi-functionalities, which can permit a significant expansion of
both existing and new derivative compounds that can be
synthesized.
[0014] Isohexide starting materials can be obtained by known
methods of making respectively isosorbide, isomannide, or isoidide.
Isosorbide and isomannide can be derived from the dehydration of
the corresponding sugar alcohols, D-sorbitol and D mannitol
respectively. As a commercial product, isosorbide is also available
easily from a manufacturer. The third isomer, isoidide, can be
produced from L-idose, which rarely exists in nature and cannot be
extracted from vegetal biomass. For this reason, researchers have
been actively exploring different synthesis methodologies for
isoidide. For example, the isoidide starting material can be
prepared by epimerization from isosorbide. In L. W. Wright, J. D.
Brandner, J. Org. Chem., 1964, 29 (10), pp. 2979-2982,
epimerization is induced by means of Ni catalysis, using nickel
supported on diatomaceous earth. The reaction is conducted under
relatively severe conditions, such as a temperature of 220.degree.
C. to 240.degree. C. at a pressure of 150 atmospheres. The reaction
reaches a steady state after about two hours, with an equilibrium
mixture containing isoidide (57-60%), isosorbide (30-36%) and
isomannide (5-7-8%). Comparable results were obtained when starting
from isoidide or isomannide. Increasing the pH to 10-11 was found
to have an accelerating effect, as well as increasing the
temperature and nickel catalyst concentration. A similar disclosure
can be found in U.S. Pat. No. 3,023,223, which proposes to
isomerize isosorbide or isomannide. More recently, P. Fuertes
proposed a method for obtaining L-iditol (precursor for isoidide),
by chromatographic fractionation of mixtures of L-iditol and
L-sorbose (U.S. Patent Publication No. 2006/0096588; U.S. Pat. No.
7,674,381 B2). L-iditol is prepared starting from sorbitol. In a
first step sorbitol is converted by fermentation into L-sorbose,
which is subsequently hydrogenated into a mixture of D-sorbitol and
L-iditol. This mixture is then converted into a mixture of L-iditol
and L-sorbose. After separation from the L-sorbose, the L-iditol
can be converted into isoidide. Thus, sorbitol is converted into
isoidide in a four-step reaction, in a yield of about 50%. (The
contents of the cited references are incorporated herein by
reference.)
[0015] These molecular entities hold significant potential as
"green", renewable solvents derived from biomass, as well as
platform chemicals (monomethyl ethers) for the production of
surfactants, dispersants, and emollients (personal care products).
Furthermore, the reagents used in the aforementioned preparation
are non-toxic, environmentally friendly substances.
A
[0016] In the present disclosure, benign, environmentally friendly
carbonate (e.g., diethyl carbonate or potassium carbonate) are
employed to synthesize ethers and carbonates. Schemes 1 and 2 are
generalized illustrations of embodiments of the present synthesis
process. Scheme 1 depicts an embodiment in which an isohexide is
reacted with a carbonate having C.sub.1-C.sub.3 alkyl R-groups
using a Bronsted base to generate a corresponding ether. Scheme 2
shows an alternate embodiment in which an isohexide is reacted with
a carbonate having C.sub.4 and greater alkyl, phenyl, allyl
R-groups using a Bronsted base to produce a corresponding
carbonate. The base serves to deprotontate the isohexide
intermediate to generate the ether or carbonate compounds. The base
should be reasonably soluble in solution to afford satisfactory
mixing and subsequent reactivity.
##STR00002##
##STR00003##
[0017] Preferably, the reaction time for each synthesis can be
within about 24 hours. Typically, the reaction time is within about
6 hours to about 12 hours (e.g., 7 or 8 hours to about 9 or 10
hours). As the reaction proceeds for longer durations (e.g.,
.about.10-24 hours) the yields respectively of mono-ether and
di-ether products will increase to full conversion of the di-ether
species. For the carbonate products, the mono-carbonate species
quickly converts to the di-carbonate species within about 1-2
hours.
[0018] The Bronsted base should have a minimal pKa of about 4
(e.g., pyridine). Typically, the base pKa is about 7-14, usually
about 8 or 10 to about 12 or 13. In alternative embodiments, some
bases may have a greater pKa, up to about 40-55 (e.g.,
alkyl-lithium). Various kinds of Bronsted bases can be used, for
example, the base can be one of the following: a carbonate (e.g.,
sodium or potassium carbonate); a hindered amine (e.g.,
triethylamine, tributylamine, diisopropylethylamine (DIEA),
dibutylamine); a nucleophilic base (e.g., pyridine, pyrimidine,
dimethyl-aminopyridine, imidazole, pyrrolidine, morpholine); a
sodium, potassium, or calcium hydride; or an organometallic
compound (e.g., alkyl-lithium or alkyl-magnesium). The minimum
stoichiometric equivalents of base to the staring materials is
about 1 for mono-ether or mono-carbonate, and about 2 equivalents
depending on the solubility of the carbonate or miscibility of the
base (e.g., amines) in solution.
[0019] Using a non-nucleophilic amine that is sterically hindered,
such as diisopropylethylamine (DIEA), can enhance the process not
only from its solubilizing capacity and basicity, but ease of
sequestration via mild aqueous acid treatment.
[0020] The Bronsted base in some embodiments is a solid compound,
such as a mineral carbonate, which would make the removal and
purification of the final product from solution easier. In other
embodiments, hindered amines, owing to their innate liquidity and
ease of segregation by mild acid treatment comprise other salutary
bases for this process. The liquid hindered amine allows for better
mixing and miscibility but removal is more complex involving a
titration with acid and then liquid-liquid extraction.
[0021] For instance, isosorbide diallyldicarbonate separates in the
form of viscous oil, and can be stored indefinitely, with
negligible degradation, in an inert atmosphere.
[0022] According to the present invention, the alkylation reaction
can be conducted at a temperature in a range from about 70.degree.
C. or 80.degree. C. to about 180.degree. C. or 200.degree. C.,
inclusive, depending on the boiling point temperature of the
particular carbonate solvent used in the reaction (e.g., 75.degree.
C. for dimethyl carbonate, or 120.degree. C. for diethyl
carbonate). Typically, the reaction temperature is in a range from
about 85.degree. C. or 90.degree. C. or 100.degree. C. to about
160.degree. C., 170.degree. C. or 175.degree. C., inclusive of
various combinations of ranges therein. As a general consideration,
the longer or greater the number of carbons in an alkyl, allyl or
aryl group, respectively, of the dialkyl, diallyl, or diaryl
carbonate reagent, the higher the boiling point tends to be; hence,
the greater the reaction temperature. As a precaution, one risks
decarboxylation of the carbonate even though one may achieve
greater conversion of the isohexide to its corresponding ether or
carbonate at significantly higher temperatures. Particular
temperature ranges for example may be from about 110.degree. C. or
120.degree. C. to about 140.degree. C. or 150.degree. C., inclusive
of combination of ranges therein. In certain desirable iterations,
the reaction is performed at a temperature between about
115.degree. C., 117.degree. C. or 120.degree. C. to about
125.degree. C., or 130.degree. C., or 135.degree. C.
[0023] To prepare monoethers, the reaction should use at least 1 to
2 equivalents of carbonate for each equivalent of isohexide
consumed. For diethers, at least 2 equivalents are used.
[0024] We observe that carbonates with R-groups having
C.sub.1-C.sub.3 carbons tend to generate ethers, while those with
C.sub.4-C.sub.6 make predominately carbonates, and those with
C.sub.7-C.sub.20 make only carbonates. It is believed that the
possible steric interference from longer chain alkyl, allyl, or
aryl groups tends to favor the formation of the carbonate species
over the ether species.
[0025] Typically as a solvent, one may include an alcohol having
the same R-species as that which is displaced from the carbonate
molecule, such as, an ethanol when reacting with diethylcarbonate,
or an allyl alcohol when using diallylcarbonate, such in Scheme 3.
It is believed that in surplus alcohol the carbonate is
activated.
##STR00004##
[0026] In situ transesterification of the incumbent carbonate with
excess alcoholic solvent occurs readily, auspiciously permitting
alkyl etherification to occur without the need for use of
carbonates other than inexpensive dimethylcarbonate. This is shown
in Scheme 4.
##STR00005##
[0027] The reactions can be executed in a neat solution of dimethyl
or ethylcarbonate, or as previously detailed, can be generated in
situ via transesterification. The isohexide compound and the
dialkyl, diallyl, or diaryl carbonate are reacted respectively in a
neat solution of at least the dialkyl, diallyl, or diaryl
carbonate. As a cost efficient feature, one can recycle the
unconsumed dicarbonate and solvent.
[0028] Given the difference in boiling points of the carbonate
(.about.95.degree. C.) and amine (.about.120.degree. C.), the
present etherification reactions can simplify and make the
purification and recovery process relatively easy. One can distill
both the carbonate and the amine and recycle recovered carbonate
after each reaction.
[0029] An illustration of an advantage of the present synthesis
process is the employment of relatively mild conditions and safe
non-toxic reagents is, for example, the preparation of
(3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl diphenyl
dicarbonate, isosorbide diphenylcarbonate, as discussed in Example
4, below. In contrast, the conventionally way of preparing the same
compound can involve several reaction steps, and uses harsh
conditions and some reagents such as diphosgene or triphosgene,
which are toxic (see, e.g., Noordover, Bart A. J., et al.,
"Chemistry, Functionality, and Coating Performance of Biobased
Copolycarbonates from 1,4:3,6-Dianhydrohexitols," J. APPLIED
POLYMER SCIENCE, Vol. 121, 1450-1463 (2011); Sun, S. J., et al.,
"New polymers of carbonic acid. XXV. Photoreactive cholesteric
polycarbonates derived from
2,5-bis(4'-hydroxybenzylidene)cyclopentanone and isosorbide" J.
POLYMER SCIENCE: PART A: POLYM. CHEM., Vol. 37, 1125-1133 (1999);
Kricheldorf, H. R., et al., "Polymers of Carbonic Acid,"
MACROMOLECULES, Vol. 29, 8077-8082 (1996)).
B
[0030] Several plausible variations to the present synthesis
methodology can be applied to generate high yields of monoethyl or
diethyl targets. These adjustments may include, though are not
restricted to:
[0031] 1) organic bases: all linear and cyclic amines, such as
triethylamine, Hunig's base, DBU, and piperidine;
[0032] 2) inorganic bases: alkali and alkali earth metal
carbonates, such as cesium carbonate, calcium carbonate;
[0033] 3) basic resins: for continuous processes, resins with
basic-capped functionalities;
[0034] 4) other alkyl carbonates: transesterification of carbonates
that can be implimented with relatively inexpensive dimethyl or
diethyl carbonates in an excess alcohol and with a Lewis acid
catalyst. For example, isoidide mono and dibenzylethers can be
generated from the in situ production of dibenzyl carbonate
(dimethyl carbonate, a surfeit of benzyl alcohol, and catalyst)
using the present method.
[0035] The alkylated isohexide compound prepared by the present
method is either an ether or a carbonate. The isohexide ether can
be at least one of the following: a mono-alkyl ether or dialkyl
ether. The ether compound can be, for example: an isoidide
monoethylether, with a structure:
##STR00006##
or an isoidide diethylether, with a structure:
##STR00007##
In other embodiments, the alkylated isohexide ether can be one of
the following: mono-methyl ether of isoiodide; mono-ethyl ethers,
of isosorbide, isommanide, or isoiodide, respectively; diethyl
ester of isoiodide; mono-propyl ether of isomannide; dipropyl ether
of isomannide; mono-propyl ether of isoidide; dipropyl ether of
isoiodide; mono-benzyl ether of isoidide; monoallyl ethers of
isosorbide, isommanide, or isoiodide, respectively; and diallyl
ethers of isosorbide, isommanide, or isoiodide, respectively.
[0036] Isoidide monoethylether (IUPAC:
(3S,3aR,6S,6aR)-6-ethoxyhexahydrofuro[3,2-b]furan-3-ol) and
isoidide diethylether (IUPAC:
(3S,3aR,6S,6aR)-6-ethoxyhexahydrofuro[3,2-b]furan-3-ol). Examples
of the diethyl ethers of isomannide and isosorbide, as well as the
corresponding monoethyl ethers can be formed in high yields. It is
believed that the monomethyl ethers of isomannide and isosorbide
are new compositions of matter.
[0037] When a carbonate is made according to the present method,
the carbonate compound can be at least one of the following: a
mono-alkyl carbonate, dialkyl carbonate, mono- or di-aryl
carbonate, mono- or di-allyl carbonate, or a carbonate with an
alkyl group from 4-20 carbon atoms. In an example, the carbonate
compound is: isosorbide diallyldicarbonate, with a structure:
##STR00008##
[0038] In other embodiments, the isohexide carbonate can be one of
the following: mono-methylcarbonate of isomannide;
mono-methylcarbonate of isoidide; dimethylcarbonate of isomannide;
dimethylcarbonate of isoidide; monoethylcarbonates of isosorbide,
isommanide, or isoiodide, respectively; diethylcarbonate of
isomannide; diethylcarbonate of isoidide; mono-propyl or
dipropylcarbonates of isosorbide, isommanide, or isoiodide,
respectively; mono- or dicarbonates having an alkyl R-group of
C.sub.4 to C.sub.20 of isosorbide, isommanide, or isoiodide,
respectively; mono-benzyl or dibenzyl carbonates of isosorbide,
isommanide, or isoiodide, respectively; monophenylcarbonates of
isosorbide, isommanide, or isoiodide, respectively; and
diphenylcarbonates of isomannide or isoidide, respectively.
[0039] Particular illustrative examples of derivative compounds
that can be made from both FDM and THF-sulfonates are presented in
the associated examples that follow.
Section II
Examples
[0040] The following examples are provided as illustration of the
different aspects of the present disclosure, with the recognition
that altering parameters and conditions, for example by change of
temperature, time and reagent amounts, and particular starting
species and catalysts and amounts thereof, can affect and extend
the full practice of the invention beyond the limits of the
examples presented.
Example 1
Ethyl Etherification of Isoidide with Diethyl Carbonate and
Potassium Carbonate
##STR00009##
[0042] Experimental:
[0043] A 100 mL boiling flask equipped with a PTFE coated magnetic
stir bar was charged with 2 grams of isoidide (13.7 mmol), 9.45
grams of potassium carbonate (68.4 mmol), and 50 mL of diethyl
carbonate (413 mmol). While stirring, the heterogeneous mixture was
heated to 120.degree. C. for 8 hours. After this time, the residual
potassium carbonate was removed by filtration, the filtrate stored.
Three spots were identified on TLC (98% EtOAc/2% MeOH, cerium
molybdate stain), Rf.sub.1=0.76, Rf.sub.2=0.44, Rf.sub.3=0.24
(isoidide). A sample was analyzed, qualitatively, by GC/MS that
revealed a very small amount of residual isoidide, with two
preponderant signals that were congruous with the mono and diethyl
analogs of isoidide. A sample was then submitted for quantitative
analysis, which produced the following mass ratios:
Isoidide--12.5%; isoidide monoethyl ether--50.9%; isoidide diethyl
ether--33.7%.
Comparative Example 1
Failed Etherification of Isoidide with Diethyl Carbonate, Potassium
Carbonate, and Ethanol
[0044] A 100 mL boiling flask was charged with 2 grams of isoidide
(13.7 mmol), 9.45 grams of potassium carbonate (68.4 mmol), 8.30 mL
of diethyl carbonate (68.4 mmol) and 50 mL of ethanol. The
heterogeneous mixture was heated to reflux (.about.85.degree. C.
for 24 hours. Samples of the reaction mixture were removed at 2
hour increments and analyzed by GC/MS. After 24 h, no mono or
di-methyl ethers of isoidide were descried.
[0045] It is interesting that isoidide methyl etherification was
quantitative with dimethylcarbonate in methanol but completely
failed with diethyl carbonate in ethanol. An explicit
rationalization cannot be derived at this time, but could involve
either 1) steric effects of the ethyl chain and/or 2) solubility of
potassium carbonate in ethanol.
Example 2
Ethyl Etherification of Isosorbide with Diethyl Carbonate and
Potassium Carbonate
##STR00010##
[0047] Experimental:
[0048] A 100 mL boiling flask equipped with a PTFE coated magnetic
stir bar was charged with 2 grams of isosorbide (13.7 mmol), 9.45
grams of potassium carbonate (68.4 mmol), and 50 mL of diethyl
carbonate (413 mmol). While stirring, the heterogeneous mixture was
heated to 120.degree. C. for 8 hours. After this time, the residual
potassium carbonate was removed by filtration, the filtrate stored.
Four spots were identified on TLC (98% EtOAc/2% MeOH, cerium
molybdate stain), Rf.sub.1=0.76, Rf.sub.2=0.44, Rf.sub.3=0.42 and
Rf.sub.4=0.20 (isosorbide). A sample was analyzed, qualitatively,
by GC/MS that revealed a very small amount of residual isosorbide,
with three primary signals that were consistent with the mono and
diethyl analogs of isoidide. A sample was then submitted for
quantitative analysis, which produced the following mass ratios:
Isosorbide--15.2%; isosorbide monoethyl ethers--55.2%; isosorbide
diethyl ether--26.7%.
Example 3
Ethyl Etherification of Isomannide with Diethyl Carbonate and
Potassium Carbonate
##STR00011##
[0050] Experimental:
[0051] A 100 mL boiling flask equipped with a PTFE coated magnetic
stir bar was charged with 2 grams of isomannide (13.7 mmol), 9.45
grams of potassium carbonate (68.4 mmol), and 50 mL of diethyl
carbonate (413 mmol). While stirring, the heterogeneous mixture was
heated to 120.degree. C. for 8 hours. After this time, the residual
potassium carbonate was removed by filtration, the filtrate stored.
Three spots were identified on TLC (98% EtOAc/2% MeOH, cerium
molybdate stain), Rf.sub.1=0.78, Rf.sub.2=0.39, and Rf.sub.3=0.18
(isomannide). A sample was analyzed, qualitatively, by GC/MS that
revealed a very small amount of residual isomannide, with two
primary signals that were consistent with the mono and diethyl
analogs of isomannide. A sample was then submitted for quantitative
analysis, which produced the following mass ratios:
Isomannide--13.1%; isosorbide monoethyl ethers--49.4%; isosorbide
diethyl ether--30.5%.
Example 4
Synthesis of (3R,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl
diphenyl dicarbonate, Isosorbide Diphenylcarbonate, D
##STR00012##
[0053] Experimental:
[0054] A 25 mL round bottomed flask equipped with an oval PTFE
coated magnetic stir bar was charged with 1 g of isosorbide A (6.84
mmol), 3.78 g of potassium carbonate (27.36 mmol) and 10 g of
diphenylcarbonate B (46.7 mmol). While stirring, the heterogeneous
mixture was heated to 140.degree. C. overnight (a profusion of
effervescence was noted). At this time the reaction was deemed
complete by TLC (1% methanol in ethyl acetate, UV-Vis and cerium
molybdate illumination) as signified by the absence of isosorbide
and presence of only 2 spots. The heterogeneous mixture was diluted
with ethanol and filtered to remove excess salts. A white solid
appeared in the filtrate during the sequestration, which was
filtered, dried, and analyzed by .sup.1H NMR, indicating isosorbide
diphenylcarbonate D (1.55 g, 59%). No isosorbide diphenylether C
was descried by this analytical technique in the mother liquor.
.sup.1H NMR (CDCl.sub.3, 400 MHz) .delta. (ppm) 7.41-7.40 (m, 4H),
7.39-7.38 (m, 4H), 7.22-7.20 (m, 2H), 5.24-5.21 (m, 1H), 5.03 (d,
J=5.6 Hz, 1H), 4.67 (t, J=9.8 Hz, 1H), 4.33 (d, J=8.2 Hz, 1H), 4.26
(d, J=10.4 Hz, 1H), 4.23-4.22 (dd, J=9.8 Hz, J=1.4 Hz, 1H),
4.15-4.14 (dd, J=9.6 Hz, J=3.2 Hz, 1H), 4.02-4.01 (dd, J=9.2 Hz,
J=2.6 Hz, 1H); .sup.13C NMR (CDCl.sub.3, 125 MHz) .delta. (ppm)
153.32, 153.01, 151.26, 151.10, 129.88, 129.81, 121.31, 115.55,
86.04, 82.00, 81.31, 76.94, 73.44, 70.90.
Example 5
Synthesis of (3S,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl
diphenyl dicarbonate, C
##STR00013##
[0056] Experimental:
[0057] A 25 mL round bottomed flask equipped with an oval PTFE
coated magnetic stir bar was charged with 1 g of isoidide A (6.84
mmol), 3.78 g of potassium carbonate (27.36 mmol) and 10 g of
diphenylcarbonate B (46.7 mmol). While stirring, the heterogeneous
mixture was heated at 140.degree. C. overnight (significant
bubbling was observed). After this time the reaction was deemed
complete by TLC (1% methanol in ethyl acetate, UV-Vis and cerium
molybdate illumination) as signified by the absence of isoidide and
presence of only 2 spots. The heterogeneous mixture was diluted
with ethanol and filtered to remove excess salts. A white solid
appeared in the filtrate during the sequestration, which was
filtered, dried, and analyzed by .sup.1H NMR, indicating isoidide
diphenylcarbonate D (1.76 g, 66%). .sup.1H NMR (CDCl.sub.3, 400
MHz) .delta. (ppm) 7.36-7.34 (m, 4H), 7.31-7.28 (m, 4H), 7.21-7.19
(m, 2H), 4.97-4.95 (m, 2H), 4.82 (d, J=5.5 Hz, 4H), 4.37 (m, 2H),
4.32 (m, 2H); .sup.13C NMR (CDCl.sub.3, 125 MHz) .delta. (ppm)
153.67, 151.04, 129.92, 129.87, 122.07, 116.38, 89.52, 84.84,
70.48.
Example 6
Synthesis of (3R,3aR,6R,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl
diphenyl dicarbonate, C
##STR00014##
[0059] Experimental:
[0060] A 25 mL round bottomed flask equipped with an oval PTFE
coated magnetic stir bar was charged with 1 g of isomannide A (6.84
mmol), 3.78 g of potassium carbonate (27.36 mmol) and 10 g of
diphenylcarbonate B (46.7 mmol). While stirring, the heterogeneous
mixture was heated at 140.degree. C. overnight (significant
bubbling was observed). After this time the reaction was deemed
complete by TLC (1% methanol in ethyl acetate, UV-Vis and cerium
molybdate illumination) as signified by the absence of isomannide
and presence of only 2 spots. The heterogeneous mixture was diluted
with ethanol and filtered to remove excess salts. A white solid
appeared in the filtrate during the sequestration, which was
filtered, dried, and analyzed by .sup.1H NMR, indicating isoidide
diphenylcarbonate D (1.31 g, 49%). .sup.1H NMR (CDCl.sub.3, 400
MHz) .delta. (ppm) 7.41-7.40 (m, 4H), 7.39-7.38 (m, 4H), 7.22-7.20
(m, 2H), 5.12-5.09 (m, 2H), 4.97 (d, J=5.8 Hz, 4H), 4.51 (m, 2H),
4.42 (m, 2H); .sup.13C NMR (CDCl.sub.3, 125 MHz) .delta. (ppm)
153.44, 150.94, 129.81, 129.77, 122.00, 116.03, 91.37, 86.38,
70.23.
Example 7
Synthesis of diallyl((3R, 3aR, 6S,
6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)dicarbonate, isosorbide
diallyldicarbonate
##STR00015##
[0062] Experimental:
[0063] An oven dried, 25 mL round bottomed flask equipped with a
PTFE coated magnetic stir bar was charged with 100 mg of isosorbide
(A, 0.684 mmol), 1 mL of diallylcarbonate (7.03 mmol), and 477
.mu.L of diisopropylethylamine (DIEA, 2.74 mmol). A reflux
condenser capped with an argon inlet was affixed to the round
bottomed flask and the mixture heated to 120.degree. C. overnight
with vigorous stirring. After this time, an aliquot was removed,
diluted with acetone and analyzed by GC/MS. The characteristic
signal for isosorbide was absent, indicating full conversion. No
other signals were manifest, precluding the presence of
diallyisosorbide, C or monoallylisosorbide isomers. The absence of
the diallyl analog was corroborated by TLC (1:1 EtOAc:Hexanes,
cerium molybdate stain), where an authentic sample of
diallylisosorbide was loaded adjacent to the product mixture. The
signature spot was not observed in the product mixture. Product
workup entailed dilution with acetone, filtration to remove orange
solids, and concentration in vacuo, resulting in an oil with a
light-yellow color (162 mg, 75.0%). .sup.1H NMR analysis
(CDCl.sub.3, 400 MHz) .delta. (ppm) 5.97-5.91 (m, 2H), 5.39-5.38
(dd, J=13.2 Hz, J=1.2 Hz, 1H), 5.35-5.34 (dd, J=13.2 Hz, J=1.3 Hz,
1H), 5.30-5.29 (dd, J=8.6 Hz, J=1.0 Hz, 1H), 5.27-5.26 (dd, J=8.4
Hz, J=1.2 Hz, 1H), 5.11-5.09 (m, 2H), 4.90 (t, J=5.2 Hz, 1H), 4.67
(d, J=6.4 Hz, 2H), 4.64 (d, J=6.2 Hz), 4.57 (d, J=6.6 Hz, 1H),
4.07-4.03, (m, 2H), 3.91-3.90 (m, 2H). .sup.13C NMR (CDCl.sub.3,
125 MHz) .delta. (ppm) 154.56, 154.21, 131.48, 131.34, 119.62,
119.28, 86.07, 81.43, 81.10, 73.46, 70.70, 69.07, 69.04, 68.89.
Example 8
Synthesis of diallyl
((3S,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl) dicarbonate,
B
##STR00016##
[0065] Experimental:
[0066] An oven dried, 25 mL round bottomed flask equipped with a
PTFE coated magnetic stir bar was charged with 100 mg of isoidide
(A, 0.684 mmol), 1 mL of diallylcarbonate (7.03 mmol), and 477
.mu.L of diisopropylethylamine (DIEA, 2.74 mmol). A reflux
condenser capped with an argon inlet was affixed to the round
bottomed flask and the mixture heated to 120.degree. C. overnight
while vigorously stirring. After this time, an aliquot was removed,
diluted with acetone and analyzed by GC/MS. The characteristic
signal for isoidide was absent, indicating full conversion. Product
workup entailed dilution with acetone, filtration to remove brown
solids, and concentration in vacuo, resulting in an oil with a
light-yellow color (144 mg, 66.9%). .sup.1H NMR analysis
(CDCl.sub.3, 400 MHz) .delta. (ppm) 5.97-5.91 (m, 2H), 5.49-5.46
(m, 2H), 5.35-5.34 (m, 2H), 4.97-4.95 (m, 2H), 4.80 (d, J=5.5 Hz,
4H), 4.65 (d, J=7.2 Hz, 4H), 4.35 (m, 2H), 4.29 (m, 2H); .sup.13C
NMR (CDCl.sub.3, 125 MHz) .delta. (ppm) 153.33, 131.28, 117.74,
90.34, 81.63, 70.07, 62.51.
Example 9
Synthesis of diallyl
((3R,3aR,6R,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl) dicarbonate,
B
##STR00017##
[0068] Experimental:
[0069] An oven dried, 25 mL round bottomed flask equipped with a
PTFE coated magnetic stir bar was charged with 100 mg of isomannide
(A, 0.684 mmol), 1 mL of diallylcarbonate (7.03 mmol), and 477
.mu.L of diisopropylethylamine (DIEA, 2.74 mmol). A reflux
condenser capped with an argon inlet was affixed to the round
bottomed flask and the mixture heated to 120.degree. C. overnight
with vigorous stirring. After this time, an aliquot was removed,
diluted with acetone and analyzed by GC/MS. The characteristic
signal for isomannide was absent, indicating full conversion.
Product workup entailed dilution with acetone, filtration to remove
brown solids, and concentration in vacuo, resulting in an oil with
a light-yellow color (145 mg, 67.3%). .sup.1H NMR analysis
(CDCl.sub.3, 400 MHz) .delta. (ppm) 5.95-5.90 (m, 2H), 5.46-5.44
(m, 2H), 5.33-5.31 (m, 2H), 5.11-5.08 (m, 2H), 4.96 (d, J=5.8 Hz,
4H), 4.61 (d, J=7.2 Hz, 4H), 4.53 (m, 2H), 4.40 (m, 2H); .sup.13C
NMR (CDCl.sub.3, 125 MHz) .delta. (ppm) 153.72, 131.94, 117.38,
91.66, 82.07, 69.41, 60.99.
[0070] The present invention has been described in general and in
detail by way of examples. Persons of skill in the art understand
that the invention is not limited necessarily to the embodiments
specifically disclosed, but that modifications and variations may
be made without departing from the scope of the invention as
defined by the following claims or their equivalents, including
other equivalent components presently know or to be developed,
which may be used within the scope of the invention. Therefore,
unless changes otherwise depart from the scope of the invention,
the changes should be construed as being included herein.
* * * * *