Compositions of mono-alkyl ethers of monoanhydro-hexitols, production methods thereof and use of same

Abstract

A composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) at C-3, C-5 or C-6 of the monoanhydro-hexitol, in which the alkyl group (R) is a linear or branched, cyclic or noncyclic hydrocarbon-based group comprising between 4 to 18 carbon atoms, the process for obtaining such a composition and the use thereof as a nonionic surfactant, emulsifier, lubricant, antimicrobial agent or dispersant.

Claims

1. A composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) in position C-3, C-5 or C-6 of the monoanhydro-hexitol, in which the alkyl group (R) is a linear or branched hydrocarbon-based group comprising between 4 to 18 carbon atoms.

2. The composition as claimed in claim 1, wherein the monoanhydro hexitol is chosen from monoanhydro sorbitol, monoanhydro mannitol, monoanhydro iditol and monoanhydro galactitol and mixtures thereof.

3. The composition as claimed in claim 1, comprising at least 1% (w/w) of any one monoanhydro-hexitol monoalkyl ether isomers.

4. The composition as claimed in claim 1, comprising at least 90% (w/w) of monoanhydro-hexitol monoalkyl ether isomers.

5. The composition as claimed in claim 1, wherein a ratio of [(3-alkyl monoanhydro-hexitol+5-alkyl monoanhydro-hexitol) to 6-alkyl monoanhydro-hexitol] is between 0.02 and 2.

6. The composition as claimed in claim 1, wherein the alkyl group (R) comprises between 8 and 12 carbon atoms.

7. A process for obtaining a composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) in position C-3, C-5 or C-6 of the monoanhydro-hexitol, in which the alkyl group (R) comprises between 4 to 18 carbon atoms, comprising the following steps: a) dehydration of a hexitol to obtain a monoanhydro-hexitol substrate; b) production of a hexitan alkyl acetal by acetalization or trans-acetalization of the monoanhydro-hexitol substrate obtained, with i. an aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms, by acetalization, or ii. a derivative of an aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms, by trans-acetalization, c) catalytic hydrogenolysis of the hexitan alkyl acetal without acid catalyst, and d) recovery of a composition of monoanhydro-hexitol monoalkyl ether isomers bearing an alkyl ether radical (OR) in position C-3, C-5 or C-6 of the monoanhydro-hexitol, in which the alkyl group (R) comprises 4 to 18 carbon atoms according to claim 1.

8. The process as claimed in claim 7, wherein the acetalization or trans-acetalization step b) is performed in the presence of an acid catalyst.

9. The process as claimed in claim 7, wherein the hydrogenolysis is performed in a solvent or without solvent, in the presence of a catalyst.

10. The process as claimed in claim 9, wherein the solvent is a polar solvent.

11. The process as claimed in claim 9, wherein the hydrogenolysis is performed at a temperature of between 80 and 140 C. and/or a pressure of between 15 and 40 bar.

12. The process as claimed in claim 9, wherein the hydrogenolysis is performed in the presence of a catalyst based on precious metals.

13. The process as claimed in claim 7, further comprising at least one filtration and/or purification step after any one of steps a), b) and/or d).

14. The process as claimed in claim 13, wherein the purification step is performed by chromatography or crystallization.

15. The process as claimed in claim 7, wherein the hexitol is chosen from sorbitol and mannitol.

16. The process as claimed in claim 7, wherein the aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms is acetalized in a substrate/reagent ratio of between 5/1 and 1/1.

17. The process as claimed in claim 7, wherein the derivative of an aliphatic aldehyde reagent comprising from 4 to 18 carbon atoms is trans-acetalized in a substrate/reagent ratio of between 1/1 and 1/3.

18. A product obtained by performing the process as claimed in claim 7.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

Figures

(1) FIG. 1: represents a chromatogram of the reaction mixture obtained in the course of the dehydration reaction according to Example 1.

(2) FIG. 2: represents a chromatogram of the reaction mixture obtained by trans-acetalization without solvent according to Example 8.

(3) FIG. 3: represents a chromatogram of the reaction mixture obtained by hydrogenolysis according to Example 10.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Examples

Example 1

(4) Dehydration of Sorbitol:

(5) D-sorbitol (20 g, 110 mmol) and 0.1 mol % of camphorsulfonic acid are added to a 150 mL stainless-steel autoclave. The reactor is hermetically closed, purged three times with hydrogen and hydrogen was then introduced up to a pressure of 50 bar. The system is then heated at 140 C. and stirred with a mechanical stirrer for 15 hours. After cooling to room temperature, the hydrogen pressure was released and the white foam was diluted in ethanol (200 mL) to obtain a homogeneous yellow mixture. The solvent is evaporated off under reduced pressure and the residue is then crystallized from cold methanol and filtered under vacuum. The crystalline material was washed with cold methanol to give 1,4-sorbitan (5.88 g, 35% of theoretical) in the form of a white solid. The purity is >98%, as determined by HPLC, while the crystals showed a melting point of 113-114 C. The degree of conversion of the reaction was determined as 73%, by means of which a mixture of sorbitol, 1,4-sorbitan, isosorbide and a few byproducts in vary limited amount is obtained, such that the 1,4-sorbitan/isosorbide ratio was determined as being 80/20.

Example 2

(6) Acetalization of sorbitan in DMF:

(7) 1,4-Sorbitan (X) (0.5 g, 3 mmol) was dissolved in DMF (1.4 mL) in a sealed tube. Valeraldehyde (Y) (107 L, 1 mmol) was added dropwise under argon, followed by addition of camphorsulfonic acid (10 mg, 10% w/w), followed by closing the tube. The mixture is heated to 95 C. with magnetic stirring. After 15 hours, the dark reaction mixture was cooled and the solvent evaporated off under reduced pressure. A degree of conversion of 95% was reached. The residue was diluted in ethyl acetate and the excess 1,4-sorbitan was filtered off and washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue is purified by flash chromatography (EtOAc/cyclohexane 80/20 to 100/0) to give sorbitan acetal (0.22 g, 89% isolated yield) in the form of a colorless oil. HPLC revealed a mixture of 4 isomers.

Example 3

(8) In this example, various ratios of sorbitan against the aldehyde reagent were tested. The same reaction conditions as in Example 2 were used, but the sorbitan/aldehyde ratio ranged between 1/1 and 3/1. The results are presented in Table 1 below.

(9) TABLE-US-00001 TABLE 1 Effect of the sorbitan/aldehyde ratio on the degree of conversion and the isolated yield Ratio X/Y Conversion Isolated yield (weight %) 1/1 96% 62% 2/1 81% 83% 3/1 95% 89%

(10) The above results show that excess sugar is advantageous in that it can prevent the formation of byproducts such as sugar diacetals. The unreacted sugar may be recovered at the end of the reaction.

Example 4

(11) With a sorbitan/aldehyde ratio of 3/1, various aldehyde reagents were used to give sorbitan acetal reaction products. The same reaction conditions and the same purification steps as in Example 2 were used.

(12) The results are presented in Table 2.

(13) TABLE-US-00002 TABLE 2 Aldehyde Conversion Isolated yield Hexanal 100% 98% Octanal 89% 95% Decanal 69% 85% Dodecanal 61% 80%

Example 5

(14) Besides the use of DMF as solvent, other solvents were also used to prepare the sorbitan acetal compositions. In this case also, the same reagents were used and the same procedure was followed as in Example 2, except that the reaction temperatures were about 80 C. The results are presented in Table 3.

(15) TABLE-US-00003 TABLE 3 Solvent Conversion Isolated yield Acetonitrile 100% 75% i-PrOH 97% 66% DMF 92% 92%

Example 6

(16) Sorbitan acetalization without solvent:

(17) 1,4-Sorbitan (X) (0.5 g, 3 mmol) was heated to 95 C. in a sealed tube. Valeraldehyde (Y) (107 L, 1 mmol) was added dropwise, under argon, followed by camphorsulfonic acid (10 mg, 10% w/w), before closing the tube. The mixture is heated to 95 C. with magnetic stirring. After 15 hours, the dark reaction mixture was cooled and diluted in ethyl acetate (2 mL) and the solvent is then evaporated off under reduced pressure. A degree of conversion of 80% was obtained. The residue was again diluted in ethyl acetate and the excess 1,4-sorbitan was filtered off and washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue is purified by flash chromatography (EtOAc/cyclohexane 80/20 to 100/0) to give the sorbitan acetal (0.13 g, 54% isolated yield) in the form of a colorless oil. HPLC revealed a mixture of 4 isomers.

Example 7

(18) Trans-acetalization of sorbitan in ethanol:

(19) 1,4-Sorbitan (0.5 g, 3 mmol) was dissolved in ethanol (7.5 mL) in a round-bottomed flask and 1,1-diethoxypentane (1.15 mL, 6 mmol) was added under a stream of argon, followed by camphorsulfonic acid (50 mg; 10% w/w). The mixture is heated to 80 C. with magnetic stirring. After 3 hours, the mixture was neutralized and concentrated under reduced pressure. The residue was purified by flash chromatography (ethyl acetate/cyclohexane 80/20 to 100/0) to give the sorbitan acetal (0.43 g, 66% isolated yield) in the form of a colorless oil. HPLC revealed a mixture of 4 isomers.

Example 8

(20) Trans-acetalization of sorbitan without solvent:

1,4-Sorbitan (0.5 g, 3 mmol) and 1,1-diethoxypentane (1,1-DEP) (1.15 mL, 6 mmol) (mole ratio 1/2) were placed in a round-bottomed flask under a stream of argon, followed by camphorsulfonic acid (50 mg; 10 w/w %). The mixture is heated to 80 C. with magnetic stirring. After 3 hours, the mixture was purified directly by flash chromatography (ethyl acetate/cyclohexane 80/20 to 100/0) to give the sorbitan acetal (0.517 g, 73% isolated yield) in the form of a colorless oil. HPLC revealed a mixture of 4 isomers. (FIG. 2)

Example 9

(21) The trans-acetalization reactions without solvent were performed using various mole ratios, various reagents (1,1-dimethoxypentane), various reaction temperatures and various reaction times, the catalyst being the same. Purification of the reaction mixtures was performed by flash chromatography, as in Example 8.

(22) The results are given in Table 4.

(23) TABLE-US-00004 TABLE 4 Sorbitan/ Time Temperature Isolated Reagent reagent ratio (h) yield Conversion yield 1,1-DMP 1/1 15 70 C. 99% 66% 1,1-DEP 1/1 15 70 C. 81% 66% 1,1-DEP 1/1 15 80 C. 49% 1,1-DEP 1/2 3 80 C. 80% 73%

(24) The trans-acetalization reactions starting with 1,1-DMP or 1,1-DEP are particularly pertinent in the reaction without solvent in which sorbitan and 1,1-DEP are in stoichiometric proportions.

Example 10

(25) Hydrogenolysis of sorbitan acetals:

(26) Pentylidene-(1,4)-sorbitan (51/49 mixture of regioisomers, 0.98 g, 4.22 mmol) was diluted in dry CPME (30 mL) and placed in a stainless-steel autoclave, with 5% Pd/C catalyst (0.45 g). The reactor is firmly closed and purged three times with hydrogen, and hydrogen is then introduced under pressure (30 bar). The system is heated at 120 C. and stirred for 15 hours. After cooling to room temperature, the hydrogen under pressure is released, the reaction mixture is dissolved in absolute ethanol (100 mL) and filtered (0.01 micron Millipore Durapore filter). The filtrate is evaporated under reduced pressure and the residue is purified by flash chromatography (EtOAc/cyclohexane 90/10 to 100/0, then EtOH/EtOAc 10/90). A mixture of (1,4)-sorbitan pentyl ethers (0.686 g, 69%) was thus obtained in the form of a colorless oil. Analysis by HPLC (C18 column, water/CH.sub.3CN 80/20+0.1% v/v H.sub.3PO.sub.4 eluent) showed a 27/33/40 mixture of pentyl(1,4)sorbitan regioisomers in positions 5, 3 and 6. The retention times R.sub.t are 7.20 min (27%), 9.25 min (33%) and 10.79 min (40%) (the peaks having been assigned, respectively, to the regioisomers in positions 5, 3 and 6) (FIG. 3). Spectroscopic data: .sup.1H NMR (400 MHz, d.sub.6-DMSO) .sub.H 0.85 (3H, t, J=7), 1.20-1.37 (4H, m), 1.38-1.58 (2H, m), 3.20-3.98 (10H, m, sorbitan protons+OCH.sub.2 ethers), 4.02-5.15 (3H, 7 m, OH protons); .sup.13C NMR (100 MHz, d.sub.6-DMSO) Sc for major isomer: 13.99 (CH.sub.3), 22.01 (CH.sub.2), 27.88 (CH.sub.2), 28.99 (CH.sub.2), 67.50 (CH), 70.59 (CH.sub.2), 73.36 (CH.sub.2), 73.49 (CH.sub.2), 75.66 (CH), 76.37 (CH), 80.34 (CH). .sub.C for minor isomers: 14.02 (2 CH.sub.3), 22.03 (2 CH.sub.2), 27.86 and 27.91 (2 CH.sub.2), 29.21 and 29.55 (2 CH.sub.2), 62.02 (CH.sub.2), 64.20 (CH.sub.2), 68.71 (CH), 69.51 (CH.sub.2), 69.79 (CH.sub.2), 73.15 (CH.sub.2), 73.23 (CH), 73.60 (CH.sub.2), 75.53 (CH), 76.45 (CH), 77.37 (CH), 79.28 (CH), 80.10 (CH), 83.95 (CH). HRMS (ESI.sup.+) calculated for C.sub.11H.sub.22NaO.sub.5: 257.1363 [M+Na].sup.+; found: 257.1359 (1.4 ppm).

Example 11

(27) One-pot synthesis of sorbitan ethers from 1,4-sorbitan:

(28) 1,4-Sorbitan (10 g, 62 mmol) is dissolved in dry CPME (30 mL) in a 100 mL round-bottomed flask in the presence of Na.sub.2SO.sub.4 (6.5 g, 50 mmol), under an argon atmosphere. Valeraldehyde (3.3 mL, 31 mmol) is added dropwise, followed by Amberlyst 15 (530 mg, 20 w/w % of valeraldehyde). The mixture is heated to 80 C. with magnetic stirring. After 3 hours, the hot mixture is filtered, washed with CPME (225 mL) and the filtrate is concentrated under reduced pressure. Without additional purification, the mixture is diluted in CPME (300 mL), dried over MgSO.sub.4 and filtered. The filtrate is introduced into a 500 mL stainless-steel autoclave, and 5%-Pd/C (3.3 mg) is added. The reactor is firmly closed and purged three times with hydrogen, and hydrogen is then introduced under pressure (30 bar). The system is heated at 120 C. and stirred for 15 hours. After cooling to room temperature, the hydrogen under pressure is released, the reaction mixture is dissolved in absolute ethanol (250 mL) and filtered (0.01 micron Millipore Durapore filter). The filtrate is evaporated under reduced pressure and the residue (5.8 g) is purified by flash chromatography (EtOAc/cyclohexane 90/10 to 100/0, and then EtOH/EtOAc 10/90). A mixture of (1,4)sorbitan pentyl ethers (3.97 g, 56%) was obtained in the form of a colorless oil (purity >98% by .sup.1H NMR).

Example 12

(29) Octyl-1,4-sorbitan is prepared according to the procedure described in Example 10, starting with octylidene-1,4-sorbitan (39/61 mixture of regioisomers) (5.61 g, 20.4 mmol). The residue is purified by flash chromatography (EtOAc/cyclohexane 80/20 to 100/0 and then EtOH/EtOAc 10/90) to give a mixture of octyl-1,4-sorbitan isomers as a solid white product. Analysis by HPLC (C18 column, water/CH.sub.3CN 80/20+0.1% v/v H.sub.3PO.sub.4 eluent) showed a 33/22/45 mixture of regioisomers of octyl(1,4)-sorbitan in positions 5, 3 and 6 (the peaks having been assigned, respectively, to the regioisomers in positions 5, 3 and 6).

(30) Spectroscopic data: .sup.1H NMR (300 MHz, d.sub.6-DMSO) .sub.H 0.86 (3H, t, J=7), 1.08-1.39 (10H, m), 1.39-1.58 (2H, m), 3.28-3.95 (10H, m, sorbitan protons+OCH.sub.2 ethers), 4.02-5.10 (3H, 7m, OH protons); .sup.13C NMR (75 MHz, d.sub.6-DMSO): .sub.C for major isomer: 13.98 (CH.sub.3), 22.12 (CH.sub.2), 25.69 (CH.sub.2), 28.73 (CH.sub.2), 28.92 (CH.sub.2), 29.31 (CH.sub.2), 31.29 (CH.sub.2), 67.48 (CH), 70.60 (CH.sub.2), 73.35 (CH.sub.2), 73.48 (CH.sub.2), 75.64 (CH), 76.36 (CH), 80.33 (CH) .sub.C for minor isomers: 13.98 (2 CH.sub.3), 22.12 (2 CH.sub.2), 25.69 (2 CH.sub.2), 28.88 (2 CH.sub.2), 28.92 (2 CH.sub.2), 28.98 (CH.sub.2), 29.52 (CH.sub.2), 29.88 (CH.sub.2), 31.32 (CH.sub.2), 62.00 (CH.sub.2), 64.17 (CH.sub.2), 68.69 (CH), 69.51 (CH.sub.2), 69.82 (CH.sub.2), 73.14 (CH.sub.2), 73.22 (CH), 73.59 (CH.sub.2), 75.53 (CH), 76.44 (CH), 77.37 (CH), 79.27 (CH), 80.07 (CH), 83.94 (CH) HRMS (ESI.sup.+) calculated for C.sub.14H.sub.28NaO.sub.5: 299.1829 [M+Na].sup.+; found: 299.1832 (1.2 ppm)

Example 13

(31) Decyl-1,4-sorbitan is prepared according to the procedure described in Example 10, starting with decylidene-1,4-sorbitan (36/64 mixture of regioisomers) (6.12 g, 20.2 mmol). The residue is purified by flash chromatography (EtOAc/cyclohexane 70/30 to 100/0 and then EtOH/EtOAc 10/90) to give a mixture of decyl-1,4-sorbitan isomers as a solid white product. Analysis by HPLC (C18 column, water/CH.sub.3CN 50/50+0.1% v/v H.sub.3PO.sub.4 eluent) showed a 32/16/52 mixture of regioisomers of decyl-(1,4)-sorbitan in positions 5, 3 and 6 (the peaks having been assigned, respectively, to the regioisomers in positions 5, 3 and 6).

(32) Spectroscopic data: .sup.1H NMR (300 MHz, d.sub.6-DMSO) .sub.H 0.86 (3H, t, J=7), 1.09-1.38 (14H, m), 1.38-1.58 (2H, m), 3.25-4.01 (10H, m, sorbitan protons+OCH.sub.2 ethers), 4.02-5.08 (3H, 7 m, OH protons); .sup.13C NMR (75 MHz, d.sub.6-DMSO) .sub.C for major isomer: 13.98 (CH.sub.3), 22.16 (CH.sub.2), 25.76 (CH.sub.2), 28.79 (CH.sub.2), 29.04 (CH.sub.2), 29.07 (CH.sub.2), 29.14 (CH.sub.2), 29.17 (CH.sub.2), 29.35 (CH.sub.2), 67.53 (CH), 70.63 (CH.sub.2), 73.38 (CH.sub.2), 73.50 (CH.sub.2), 75.69 (CH), 76.40 (CH), 80.35 (CH). .sub.C for minor isomers: 13.98 (2 CH.sub.3), 22.16 (2 CH.sub.2), 28.98 (2 CH.sub.2), 29.01 (2 CH.sub.2), 29.14 (2 CH.sub.2), 29.17 (2 CH.sub.2), 29.35 (2 CH.sub.2), 29.57 (2 CH.sub.2), 29.92 (2 CH.sub.2), 62.01 (CH.sub.2), 64.18 (CH.sub.2), 68.72 (CH), 69.56 (CH.sub.2), 69.84 (CH.sub.2), 73.16 (CH.sub.2), 73.27 (CH), 73.60 (CH.sub.2), 75.56 (CH), 76.48 (CH), 77.41 (CH), 79.30 (CH), 80.08 (CH), 83.96 (CH) HRMS (ESI.sup.+) calculated for C.sub.16H.sub.32NaO.sub.5: 327.2142 [M+Na].sup.+; found: 327.2135 (+2.1 ppm).