Enhanced regio-selectivity in glycol acylation

Abstract

A method for acid-catalyzed acylation of an isohexide is described. The method involves a reaction of an isohexide and an excess of carboxylic acid in the presence of a Lewis acid or a Brnsted acid catalyst. One or more Lewis acid or Brnsted acid can facilitate conversion of isohexides to their corresponding mono and diesters with a pronounced greater regio-selectivity of exo-OH over endo-OH of the isohexide in the product. Particular catalytic acid species include zirconium chloride (ZrCl.sub.4) and phosphonic acid (H.sub.3PO.sub.3), which manifest a ratio of exo:endo regioselectivity of about 5.03:1 and about 4.00.3:1, respectively.

Claims

1. A method for acid-catalyzed acylation of isosorbide, comprising contacting isosorbide with an excess of carboxylic acid in the presence of a Lewis acid catalyst at a reaction temperature and for a time sufficient to produce a corresponding monoester product with a ratio of exo/endo regioselectivity of at least 3.4:1, wherein said Lewis acid catalyst is selected from the group consisting of tin (II)-2-ethylhexanoate, dibutyl-tin (II) chloride, tin (II) chloride, hafnium chloride, dibutyl-tin maleate, titanium (IV) chloride, zirconium (IV) chloride, bismuth chloride, lanthanum (III) triflate, dibutyl-tin (IV) oxide, iron (III) triflate, aluminum chloride, bismuth triflate, gallium triflate, scandium triflate, and combinations of these.

2. The method according to claim 1, wherein said reaction temperature is from 150 C. to 250 C.

3. The method according to claim 1, wherein said reaction temperature is from 170 C. to 220 C.

4. The method according to claim 1, wherein said reaction time is less than 24 hours.

5. The method according to claim 4, wherein said reaction time is 5-12 hours.

6. The method according to claim 1, wherein said carboxylic acid is selected from an alkanoic, alkenoic, alkyonoic, and aromatic acid, having a carbon chain length ranging from C.sub.2-C.sub.26.

7. The method according to claim 1, wherein said carboxylic acid is present in 2-fold to 10-fold molar excess relative to the isosorbide.

8. The method according to claim 7, wherein said carboxylic acid is present in 3-fold molar excess relative to the isosorbide.

9. The method according to claim 1, wherein the ratio of said exo/endo regioselectivity ranges from about 3.5:1 to about 3.9:1.

10. The method according to claim 1, wherein said Lewis acid is zirconium (IV) chloride.

11. The method according to claim 1, wherein said Lewis acid is present in an amount of catalyst loading that ranges from 0.0001 wt. % to 10 wt. % relative to the isosorbide content.

Description

BRIEF DESCRIPTION OF FIGURES

(1) FIG. 1, is a schematic representation of the overall synthesis of monoesters, exo and endo product.

(2) FIG. 2, shows a chromatogram of results obtained from quantitative analysis conducted by gas chromatography (GC) of isomers synthesized according to an embodiment of the present invention.

(3) FIG. 3, shows pairs of enantiomer and a table summarizing the regioselectivity of exo/endo preference in converting to monoesters that are produced with ZrCl.sub.4 as the catalyst.

(4) FIG. 4, is a graph that compares the relative regioselective preference of endo/exo-hydroxyl groups in terms of the percentage rate that each of the three isohexide species (isomannide, isosorbide, and isoidide) are converted to their corresponding esters with phosphonic acid as the catalyst.

(5) FIG. 5, is a graph that shows the relative change in regioselectivity of isohexide compounds as compared to an autocatalysis baseline. The change in regioselectivity for ZrCl.sub.4 and phosphonic acid is pronounced relative to other catalysts.

DETAILED DESCRIPTION OF THE INVENTION

Section I.Description

(6) 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.

(7) 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. 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 C. to 240 C. at a pressure of 150 atmosphere. 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.)

(8) We have found that one or more Lewis acid and/or Brnsted acid can facilitate conversion of isohexides to their corresponding mono and diesters with a pronounced greater regio-selectivity of exo-OH over endo-OH of the isohexide in the product. Particular catalytic acid species include, for example, zirconium chloride (ZrCl.sub.4), a Lewis acid, and phosphonic acid (H.sub.3PO.sub.3), a reducing Brnsted acid (also known as phosphorus acid), which manifest a ratio of exo:endo regioselectivity of about 5.00.3:1 and about 4.00.3:1, respectively.

(9) Phosphonic acid, which is a crystalline solid, commercially available, inexpensive, and possesses a strong acidity (pKa 1). This material evinces both high catalytic activity in the context of Fischer esterifications and pronounced color attenuation of the product mixture. To date, we believe that phosphonic acid has not received significant attention in this regard, either as a Brnsted acid in the catalysis of isohexide acetylation with carboxylic acids, concerning color mitigation of products or concerning high isohexide conversions. Further, at this time, phosphonic acid is one that manifests both high reactivity and concomitant color diminution.

(10) FIG. 1 shows a general schematic representation of the reaction to prepare isosorbide monoesters, which form enantiomer pairs of exo and endo species.

(11) For the acid catalysts, according to embodiments of the present reaction, the ratio of exo/endo regioselectivity is at least 3.40:1 or 3.45:1. Table 1 summarizes the relative regioselectivity of the exo/endo-hydroxyl groups in the synthesis of isohexide monoesters using examples of different kinds of acid catalysts. Table 1 lists and compares the efficacy of the different acid catalyst species in terms of their product color, catalyst load, and conversion rate relative to ZrCl.sub.4. The zirconium (IV) chloride, a preferred Lewis acid embodiment, displays a significantly augmented regioselectivity of about 4.9:1 to about 5.3:1 exo/endo monoesters (e.g., 5:0:1 to about 5:2:1) relative to other acid catalyst species. Most of the other acid catalysts exhibit 3.4:1 or 3.5:1 exo/endo regioselectivity and relatively low rates of conversion, irrespective of catalyst load. Some other catalysts have an exo/endo ratio of about 3.6:1 to about 3.8:1. Also, the zirconium (IV) chloride (5:1) exo/endo ratio is about two times greater than the ratio of the strong acid catalysts. The strong acid catalysts (i.e., sulfuric acid, p-toluenesulfonic acid) exhibited higher rates of conversion, but an even lower exo/endo ratio, respectively, 2.03:1 or 2.26:1. As a baseline, autocatalysis without using an acid catalyst results in about 3.40:1 ratio of exo/endo regioselectivity, with minimal conversion of the isohexide to its corresponding ester product.

(12) TABLE-US-00001 TABLE 1 Monoester Regioselectivity Exo/Endo Loading % (relative to (wt. % vs. Exo/ Std. Con- Auto- Catalyst isosorbide) Endo Dev. version catalysis) Autocatalysis 0.0 3.40 0.03 0.87 0 Sn(II)-2EH 5.1 3.59 0.10 2.89 0.15 (butyl).sub.2SnCl.sub.2 5.2 3.68 0.04 1.04 0.24 HaCl.sub.4 5.4 3.51 0.07 2.12 0.06 (butyl).sub.2Sn(laurate).sub.2 5.1 3.68 0.11 2.86 0.23 ZrCl.sub.4 5.4 5.02 0.07 1.38 1.57 ZrCl.sub.4 5.7 5.15 0.04 0.88 1.71 (butyl).sub.2Sn(maleate) 5.3 3.77 0.10 2.60 0.32 SnCl.sub.4 5.7 2.42 0.73 30.17 1.03 SnCl.sub.2 5.7 3.40 0.09 2.66 0.06 BiCl.sub.3 5.7 3.52 0.05 1.40 0.08 Dibutyltin(IV)oxide 5.7 3.75 0.09 2.41 0.31 Sulfuric acid 1.0 2.03 0.53 26.10 1.42 p-Toluenesulfonic 1.0 2.26 0.55 24.38 1.19 acid

(13) The ZrCl.sub.4 samples exhibit a change () in exo/endo ratio relative to autocatalysis of 1.5 to about 1.71. These results appear to be significantly higherabout at least 1.2 units greaterthan the change exhibited by the other catalyst species, which either are no greater than about 0.2 or 0.3, or have a negative value. This degree of change suggests that the ZrCl.sub.4 catalyst manifests a greater regioselectivity for exo-hydroxyl groups over endo-hydroxyl groups. These results are presented in FIG. 5, which illustrates graphically the effective regioselectivity of ZrCl.sub.4 over the other catalyst species. Phosphonic acid catalyst also shows an improved change in exo/endo ratio of about 0.75 relative to the baseline.

(14) FIG. 2, is a representative chromatogram of the results obtained from quantitative analysis conducted by gas chromatography (GC) of the two sets of four isomers synthesized according to the reaction above.

(15) FIG. 3, presents enantiomer pairs, assigned exo (A) and endo (B), of isohexide monoesters. Accompanying Table (C) presents the GC analysis of aliquots sampled over a reaction period of about 420 minutes. The reaction uses a Lewis acid, zirconium (IV) chloride, at 5 wt. % relative to the isohexide content. The results suggest that isoidide, having only exo-OH groups, is most reactive, and isomannide, having only endo-OH groups, is least reactive. The result for isosorbide, having both an exo-OH and an endo-OH, is expected to be in the middle.

(16) Similarly, FIG. 4, summaries the results from an embodiment using a Brnsted acid catalyst. The reaction is performed using about 5 wt. % phosphonic acid (H.sub.3PO.sub.3) at 175 C. for 7 hours. The percent conversion, relative to endo-OH vs. exo-OH, for the three isohexide compound species. Isomannide having only endo-hydroxyl groups showed the lowest conversion at about 75.27%, while isoidide having only exo-hydroxyl groups showed almost complete conversion at about 99.69%. Isosorbide, having both an exo and endo-hydroxyl group is in between at about 86.92% conversion. Phosphonic acid appears to contribute to a preferential regioselectivity of exo over endo of about 3.8:1 to about 4.4:1, (e.g., 4.1:1, 4.2:1, or 4.3:1).

(17) Table 2, lists the results of acylation reactions using 2-ethyl-hexanoic (2EH) acid esterification with isosorbide at 175 C., 7 h. Again, the results suggest that phosphonic acid exhibits greater regioselectivity for the exo-OH over the endo-OH of an isohexide molecule in a ratio of about 4:1. Phosphonic acid catalyzes effectively the esterification with 2EH for significant (e.g., 90%-100%) isosorbide conversion, for instance, at 205 C., 5 h.

(18) TABLE-US-00002 TABLE 2 H.sub.3PO.sub.3 Catalysis Results: 2-Ethyl-Hexanoic Acid Esterification with Isosorbide, 175 C., 7 h. % Iso- Loading sorbide Exo/ Exo/ (wt. % vs. APHA con- Endo Endo % Con- Sample isosorbide) (color) version (mean) (std. dev.) version 1. 0 96 Comp. 2. 11.6 137 93.99 4.05 0.07 1.59 3. 6.7 145 87.73 3.95 0.08 2.02 4. 4.9 151 85.92 4.09 0.08 2.02 5. 3.6 168 58.79 4.02 0.10 2.37 6. 1.3 181 44.92 3.96 0.08 2.00 N.B.: Product mixture from samples of catalysts typically used manifest APHA >275.

(19) Additionally, the phosphonic acid manifests antioxidant properties, and can greatly reduce color body development relative to the other acid catalysts described herein. A reaction using 5 wt. % H.sub.3PO.sub.3, 205 C., 7 h, generates a reaction product mixture having color with APHA value=98. A baseline color for distilled 2EH is APHA value=6. The APHA color scale, also referred to as the Hazen scale, is a color standard named for the American Public Health Association and defined by ASTM D1209. The scale for APHA color goes from 0 to 500 in units of parts per million of platinum cobalt to water. Zero on this scale represents distilled water, or what is more commonly called white water.

(20) 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 known, or to be developed, which may be used within the scope of the present invention. Therefore, unless changes otherwise depart from the scope of the invention, the changes should be construed as being included herein.