阅读说明：本技术 脂族环氧化物过水解的方法 (Process for perhydrolysis of aliphatic epoxides ) 是由 科伦丁·博迪尔 文森特·埃斯坎德 弗雷德里克·凯约 克里斯托夫·达塞尔 于 2020-02-20 设计创作，主要内容包括：本发明涉及一种在由磷钨酸组成的催化剂存在下,使用过氧化氢水性溶液通过环氧化物的过水解来合成氢过氧化醇的方法。(The invention relates to a method for the synthesis of hydroperoxyl alcohols by perhydrolysis of epoxides using an aqueous hydrogen peroxide solution in the presence of a catalyst consisting of phosphotungstic acid.)

1. A process for the synthesis of a hydroperoxy alcohol of formula (Ia) and/or (Ib):

wherein:

R¹and R²Each independently represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms or represents a group-L-A, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and A represents a hydrogen atom or a group-COXR, wherein X represents an oxygen atom or a group-NR ', and R' each independently representA group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently of the others, represents a linear or branched C group optionally substituted and/or interrupted by at least one hydroperoxy group and/or hydroxyl group₈-C₂₂An alkyl group, a carboxyl group,

or R¹And R²Together form an optionally substituted carbocyclic ring consisting of 6 to 12 ring members,

R³and R⁴Each independently represents a hydrogen atom or an optionally substituted alkyl group containing from 1 to 20 carbon atoms or represents a group-L-a, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and a represents a hydrogen atom or a group-cox R, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently of the others, represents a linear or branched C group optionally substituted and/or interrupted by at least one hydroperoxy group and/or hydroxyl group₈-C₂₂An alkyl group, a carboxyl group,

said method being characterized in that it comprises a step of perhydrolysis of an epoxide of formula (II) by reaction with an aqueous hydrogen peroxide solution in the presence of a catalyst consisting of phosphotungstic acid, said catalyst being present in a molar amount of 10 to 2000ppm moles with respect to the epoxide of formula (II),

wherein:

R¹and R²Each independently represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms or represents a group-L-A, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and A represents a hydrogen atom or a group-COXR, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently represents a linear or branched C optionally substituted and/or interrupted by at least one epoxy group₈-C₂₂An alkyl group, a carboxyl group,

or R¹And R²Together form an optionally substituted carbocyclic ring consisting of 6 to 12 ring members,

R³and R⁴Each independently represents a hydrogen atom or an optionally substituted alkyl group containing from 1 to 20 carbon atoms or represents a group-L-a, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and a represents a hydrogen atom or a group-cox R, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently represents a linear or branched C optionally substituted and/or interrupted by at least one epoxy group₈-C₂₂An alkyl group.

2. The process according to claim 1, characterized in that the catalyst is used in an amount of at least 0.01 wt.%, preferably at least 0.1 wt.%, in particular at least 0.2 wt.%, such as at least 0.4 wt.% or at least 0.5 wt.%, and for example at most 1.5 wt.%, in particular at most 1 wt.%, relative to the weight of epoxide.

3. Process according to claim 1, characterized in that the catalyst is used in an amount of at least 50ppm moles, such as at least 100ppm moles, in particular at least 200ppm moles or even at least 400ppm moles or even at least 800ppm moles, and at most 2000ppm moles, advantageously at most 1500ppm moles or even at most 1000ppm moles with respect to the molar amount of epoxide.

4. Process according to any one of claims 1 to 3, characterized in that the hydrogen peroxide is used in an amount of from 1 to 1.5 molar equivalents, preferably in a ratio of from 1.1 to 1.3 molar equivalents, with respect to the epoxide.

5. The process according to any one of claims 1 to 4, characterized in that the perhydrolysis reaction is carried out at a temperature of 5 ℃ to 60 ℃, preferably 20 ℃ to 60 ℃, more preferably 30 ℃ to 50 ℃, for a time of 10 minutes to 4 hours, such as 45 minutes to 2.5 hours.

6. Process according to any one of claims 1 to 5, characterized in that the epoxide of formula (II) is an epoxidation product of a mono-or polyunsaturated fatty acid or an ester thereof, in particular an epoxidation product of an alkyl ester or glyceride of said fatty acid.

7. The method according to claim 6, characterized in that the fatty acid is selected from palmitoleic acid, oleic acid, erucic acid, and nervonic acid, preferably the fatty acid is oleic acid.

8. A process according to claim 6 or 7, characterized in that the fatty acids or glycerides thereof are derived from vegetable oils.

9. The process according to claim 6, characterized in that the fatty acid alkyl esters are obtained by transesterification of at least one vegetable oil.

10. The process according to any one of claims 1 to 9, characterized in that the perhydrolysis reaction is carried out in the absence of an organic solvent, in particular a polar protic solvent such as an alcohol.

Technical Field

The invention relates to a method for the synthesis of hydroperoxides of the alcohol type by perhydrolysis of epoxides using an aqueous hydrogen peroxide solution in the presence of a catalyst consisting of phosphotungstic acid.

Background

The beta-hydroperoxy alcohol (HPA) unit is a particularly useful functional group in organic synthesis. It constitutes a precursor allowing the formation of protective groups for the carbonyl function, the aldehyde, or units responsible for the pharmacological activity of a large number of molecules for antimalarial use, the 1,2,4-trioxane¹。

The synthesis of said HPA units has been described by perhydrolysis of epoxides, isolated or formed in situ by epoxidation of olefins. Epoxide perhydrolysis involves the use of hydrogen peroxide (in aqueous solution or anhydrous) to act as a nucleophile on the epoxide whose electrophilic character is enhanced by activation with an acid catalyst.

Various bronsted or lewis acid catalysts have been described for this reaction: tungstic acid and derivatives thereof^2,3Molybdenum (VI) salts^4,5Perchloric acid⁶Trifluoroacetic acid (trifluoroacetic acid)⁷Tetra (oxo-tungsten dioxide) phosphate⁸Antimony (III) salt⁹Or phosphomolybdic acid¹。

Although these methods result in the formation of HPA units, they suffer from some technical limitations, which are problematic from the standpoint of industrial-scale application.

In fact, most processes utilize very high concentrations of hydrogen peroxide (a) because the production of HPA competes with the formation of the corresponding diol>90% w/v) or even anhydrous hydrogen peroxide^2,4,6,10Or even anhydrous ether extracts of hydrogen peroxide^1,5,9In order to inhibit the formation of glycols. Under these conditions, there is a considerable explosionRisks, which have been reported by the authors of these methods^1,2,9。

An alternative is to use lower concentrations of hydrogen peroxide, but in this case high levels of catalyst are required to promote HPA formation at the expense of the diol.

Where the substrate is oleic acid, catalyst loadings on the order of, for example, 10 wt% are conventionally used^3,8. Thus, patent application JP 2003/342255 describes a process for the oxidation of oleic acid to the corresponding alcohol hydroperoxide. The reaction is carried out in the presence of 1 to 20 wt%, e.g. 10 wt% of a catalyst such as H₂WO₄、H₂MoO₄、MoO₃Or H₃PMo₁₂O₄₀And 2 equivalents of 30-60% H₂O₂In the case of (2), it is carried out at 35 ℃ in a solvent such as t-butanol which dissolves both the substrate and the catalyst. However, a mixture of said hydroperoxide and the corresponding 1, 2-diol is formed and a moderate yield of hydroperoxide oxidizing alcohol of between 4 and 50% is obtained after a relatively long reaction time of the order of at least 5 hours or even 15 hours, reaching a degree of conversion of at least 75%. The low activity of the catalyst used is also reflected in a very low number of revolutions of revolution or TON (corresponding to the ratio of the molar amount of hydroperoxide alcohol produced to the molar amount of catalyst), for example 4 in the case of tungstic acid.

These various technical problems have prevented the industrial preparation of compounds incorporating HPA units by epoxide perhydrolysis.

In this context, there is still a need to develop a process for the perhydrolysis of epoxides which can meet the industrial requirements both with respect to safety and economic criteria.

More precisely, it is desirable to propose a synthesis which produces a high yield of HPA (more than 60%) in less than four hours and/or at high turnover numbers (more than 300) and which does not use hydrogen peroxide in concentrations which are dangerous for handling (up to 70% w/v).

The inventors have demonstrated that this result can be obtained by using phosphotungstic acid H as a specific catalyst₃PW₁₂O₄₀In the presence of para-epoxyThe substrate thus treated is submitted to a perhydrolysis reaction, the maximum amount of said catalyst used being 5 or even 10 times lower than the minimum recommended in document JP 2003/342255. This process can be used under simple, mild conditions, without necessarily requiring heating or the use of organic solvents, which constitutes an additional advantage of this process from an economic and environmental point of view.

Disclosure of Invention

The invention relates to a method for synthesizing hydroperoxides of the formula (Ia) and/or (Ib):

R¹-CR⁴(OOH)-CR³(OH)-R² R²-CR³(OOH)-CR⁴(OH)-R¹

(Ia) (Ib)

wherein:

R¹and R²Each independently represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms or a group-L-A, wherein L is a bond or a straight or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and A represents a hydrogen atom or a group-COXR, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently of the others, represents a linear or branched C group optionally substituted and/or interrupted by at least one hydroperoxy group and/or hydroxyl group₈-C₂₂An alkyl group, a carboxyl group,

or R¹And R²Together form an optionally substituted carbocyclic ring consisting of 6 to 12 ring members,

R³and R⁴Each independently represents a hydrogen atom or an optionally substituted alkyl group containing from 1 to 20 carbon atoms or a group-L-a, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and a represents a hydrogen atom or a group-cox R, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently of the others, represents a linear or branched C group optionally substituted and/or interrupted by at least one hydroperoxy group and/or hydroxyl group₈-C₂₂An alkyl group, a carboxyl group,

said method is characterized in that it comprises a perhydrolysis step of an epoxide of formula (II):

wherein:

R¹and R²Each independently represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms or a group-L-A, wherein L is a bond or a straight or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and A represents a hydrogen atom or a group-COXR, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently represents a linear or branched C optionally substituted and/or interrupted by at least one epoxy group₈-C₂₂An alkyl group, a carboxyl group,

or R¹And R²Together form an optionally substituted carbocyclic ring consisting of 6 to 12 ring members,

R³and R⁴Each independently represents a hydrogen atom or an optionally substituted alkyl group containing from 1 to 20 carbon atoms or a group-L-a, wherein L is a bond or a linear or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and a represents a hydrogen atom or a group-cox R, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently represents a linear or branched C optionally substituted and/or interrupted by at least one epoxy group₈-C₂₂An alkyl group, a carboxyl group,

said step being carried out by reacting with an aqueous hydrogen peroxide solution in the presence of a catalyst consisting of phosphotungstic acid, said catalyst representing from 10 to 2000ppm moles with respect to the moles of epoxide of formula (II).

Detailed Description

Defining:

"alkyl" means a saturated straight or branched chain acyclic hydrocarbon radical. Having 1 to 6 carbon atoms (or "C₁-C₆") examples of alkyl are in particular methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl or hexyl.

"alkylene" means a saturated straight or branched chain divalent acyclic hydrocarbon radical. Examples of alkylene having 1 to 12 carbon atoms are in particular methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene or dodecylene.

By "carbocyclic ring" is meant an optionally unsaturated aliphatic or aromatic, preferably aliphatic, monocyclic or polycyclic hydrocarbon group. Examples of carbocyclic rings having 6 to 12 ring members are in particular cyclohexyl, cycloheptyl, cyclooctyl or cyclododecyl.

"alkoxy" or "alkyloxy" means an alkyl group ("-O-alkyl") as defined above attached to the remainder of the molecule by an-O-bond. An example of alkoxy is in particular methoxy.

"acyloxy" means a group of formula-O-C (O) -R "wherein R" is a saturated or unsaturated, linear or branched, cyclic or acyclic, aromatic or aliphatic hydrocarbon group. Examples of acyloxy are acetoxy (-O-C (O) -CH)₃)。

The present invention relates to a process for the synthesis of hydroperoxides of the alcohol type, hereinafter referred to as "HPA", after perhydrolysis of epoxides.

Epoxides useful in the present invention have the formula:

in a first embodiment of the invention, R¹And R²Each independently represents an optionally substituted alkyl group containing from 1 to 20 carbon atoms or a group-L-A, wherein L is a bond or a straight or branched alkylene chain containing from 1 to 12 carbon atoms and optionally substituted, and A represents a hydrogen atom or a group-COXR, wherein X represents an oxygen atom or a group-NR ', and R' each independently represent a group selected from: hydrogen atom, C₁-C₆Alkyl or a radical- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶，R⁵And R⁶Each independently represents a linear or branched C optionally substituted and/or interrupted by at least one epoxy group-CH (O) CH-₈-C₂₂An alkyl group.

The alkylene chain L and R¹、R³And R⁴The alkyl groups of (a) may be substituted independently of each other by at least one group selected from: a hydroxyl group, an acyloxy group having 2 to 8 carbon atoms and an alkoxy group having 1 to 6 carbon atoms. Preferred substituents are methoxy, hydroxy and acetoxy.

Preferably, X represents an oxygen atom. Furthermore, preferably R³＝R⁴＝H。

When R is²Represents a group-L-A and wherein A is a hydrogen atom, preferably L represents an alkylene chain containing 4 to 12, more preferably 4 to 8 carbon atoms, and R¹Is represented by C₄-C₁₂An alkyl group. An example of an epoxide corresponding to this definition is the oxide of tetradec-7-ene. As a variation, L may represent a bond. An example of such an epoxide is the oxide of octadec-1-ene.

In certain embodiments, R¹Or R²is-L-A, wherein A is a hydrogen atom and L is a bond.

When R is²Represents a group-L-A and wherein A represents a group-COXR, preferably L represents an alkylene chain containing from 5 to 12, more preferably from 7 to 11, carbon atoms, and R¹Is represented by C₆-C₁₀An alkyl group. Preferably, X ═ O. Thus, the radical R advantageously represents a hydrogen atom or a methyl group. Corresponding to this definition of epoxideExamples are the methyl ester of epoxidized erucic acid (or methyl 13, 14-epoxy-docosanoate) and the methyl ester of epoxidized oleic acid (or methyl 9, 10-epoxy-octadecanoate).

As a variant, the group A may represent a group- (CH)₂)-CH(OCOR⁵)-CHOCOR⁶Wherein R is⁵And R⁶Each independently represents C optionally interrupted by at least one epoxy group-CH (O) CH-₈-C₂₂An alkyl group. Thus, the epoxide used according to the invention corresponds to a triglyceride of one or more fatty acids, which may be the same or different, preferably the same. An example of such a compound is a triglyceride of epoxidized oleic acid (or glycerol tris (9, 10-epoxyoctadecanoate)).

According to yet another possibility, R²Represents a group-L-A, wherein L is a bond and A represents a group-COXR. X is preferably an oxygen atom. Thus, in advantageous cases, the radical R represents a hydrogen atom or C₁-C₆An alkyl group. Examples of epoxides corresponding to this definition are epoxymaleic acid, epoxyfumaric acid and esters thereof.

In a second embodiment of the invention, R¹And R²Together form a carbocyclic ring consisting of 6 to 12 ring members, optionally substituted with at least one straight or branched chain C₁-C₆Alkyl substitution. Examples of epoxides corresponding to this definition are given below:

in a particular embodiment of the invention, the epoxide of formula (II) is an epoxidation product of a terpene. The terpenes include in particular monoterpenes, sesquiterpenes, diterpenes, disesquiterpenes, triterpenes, carotenoids or terpenoids. Examples of terpenes are in particular alpha-pinene, beta-pinene, carene, limonene, carotene, ocimene, myrcene, citronene, methoxycitronrene, farnesene, squalene, astaxanthin or 7-methoxy-3, 7-dimethyloct-1-ene, this list not being exhaustive.

In a preferred embodiment of the invention, the epoxide of formula (II) is an epoxidation product of a mono-or polyunsaturated fatty acid or an ester thereof, in particular an epoxidation product of an alkyl ester or glyceride of said fatty acid. Thus, the compound of formula (II) may be selected from the epoxidation products of palmitoleic acid, oleic acid, erucic acid, or nervonic acid, or esters thereof, preferably the compound of formula (II) is the epoxidation product of oleic acid, or esters thereof. The fatty acids or glycerides thereof may themselves be derived from vegetable oils. As such, the fatty acid alkyl esters may be obtained by transesterification of at least one vegetable oil.

As examples of vegetable oils we may mention in particular wheat germ oil, sunflower oil, argan oil, hibiscus oil, coriander oil, grapeseed oil, sesame oil, corn oil, apricot oil, castor oil, shea butter, avocado oil, olive oil, soybean oil, sweet almond oil, palm oil, rapeseed oil, cotton oil, hazelnut oil, macadamia nut oil, jojoba oil, alfalfa oil, poppy oil, okra oil, sesame oil, cucurbit oil, blackcurrant oil, evening primrose oil, lavender oil, borage oil, millet oil, barley oil, quinoa rye oil, safflower oil, candlenut oil, passion flower oil, musk rose oil, echium oil, wild linseed oil, or camellia oil.

The epoxidation of the vegetable oils may be carried out in a conventional manner known to the person skilled in the art, as may their optional transesterification. It is generally preferred to carry out transesterification prior to epoxidation.

In another embodiment, the substrate used in the perhydrolysis reaction is an epoxidation product of an olefin. Likewise, epoxidation may be carried out in a conventional manner known to those skilled in the art, for example using percarboxylic acids.

Whatever the epoxide type of substrate used, the process according to the invention comprises the conversion of the epoxide into HPA via perhydrolysis by adding a hydrogen peroxide solution to the epoxide in the presence of a specific catalyst consisting of phosphotungstic acid.

The concentration of the hydrogen peroxide solution is at least 30% or even at least 45% and at most 60% or even 70%, such as 30%, 45%, 60% or 70% (w/v). It was observed that higher concentrations of hydrogen peroxide caused faster reactions, which was reflected in a degree of conversion of at least 90%, preferably more than 95% or even more than 99% in less than 4 hours. The hydrogen peroxide is generally used in an amount of 1 to 1.5 molar equivalents relative to the epoxide, preferably in a ratio of 1.1 to 1.3 molar equivalents.

As such, the catalyst is generally used in an amount of from 0.01 to 2 wt.%, such as at least 0.1 wt.% or at least 0.2 wt.%, in particular at least 0.4 wt.% or at least 0.5 wt.%, and such as at most 1.5 wt.%, in particular at most 1 wt.%, relative to the weight of epoxide. Furthermore, the amount of catalyst used represents at least 10ppm moles, for example at least 50ppm moles or even at least 100ppm moles, in particular at least 200ppm moles or even at least 400ppm moles or even at least 800ppm moles, and at most 2000ppm moles, advantageously at most 1500ppm moles or even at most 1000ppm moles with respect to the molar amount of epoxide.

The perhydrolysis reaction may be carried out at a temperature of 5 ℃ to 60 ℃, preferably 20 ℃ to 60 ℃, more preferably 30 ℃ to 50 ℃ for a time of 10 minutes to 4 hours, preferably 45 minutes to 2.5 hours. It was observed that the catalyst used according to the invention in fact makes it possible to achieve a degree of conversion of the epoxide of at least 90%, preferably of at least 95% or even of at least 99% after the said time interval (e.g. by¹H NMR measured). Within the above range, the higher the temperature of the reaction, the shorter the duration.

The above reactants (epoxide, hydrogen peroxide and catalyst) may be introduced in any order into the reactor in which the reaction is carried out. Preferably, however, the perhydrolysis reaction is carried out in the absence of an organic solvent, i.e. a compound capable of dissolving the epoxide and/or the catalyst and whose structure contains one or more carbon atoms. Examples of such solvents are in particular polar protic solvents such as alcohols. In fact, these solvents have proven to slow down the perhydrolysis reaction at room temperature and generally reduce the HPA yield.

The above-described process can usually achieve the desired HPA in a yield of at least 60%, preferably at least 65% or at least 70%, usually at least 80% or even at least 85% or even at least 90%. Furthermore, the number of revolutions per revolution (TON) of the reaction is always higher than 300, typically higher than 700, and may be as high as 15000 or even as high as 20000 or even 50000. In general, a mixture of HPAs of the formulae (Ia) and (Ib) is obtained.

This process is useful for the oxidative cleavage of epoxidized vegetable oils, particularly for the formation of fatty aldehydes and/or fatty acids. The conversion of HPA obtained according to the present invention into aldehydes and/or acids can be carried out in a conventional manner known to those skilled in the art, either by acid or base catalysis or by the free-radical route.

Examples

The invention will be better understood from the following examples, which are provided purely for the purpose of illustration and are not intended to limit the scope of the invention, which is defined by the claims.

Materials and methods

The reactants were obtained from common commercial suppliers (Sigma-Aldrich-Merck, Acros, Alfa-Aesar, Fisher) and used without prior purification. Thermogravimetric analysis revealed that the commercial hydrated phosphotungstic acid contained 7.87% (w/w) water. Thus, the amounts of substances indicated hereinafter correspond to the commercial hydrated phosphotungstic acid. Methyl 9, 10-epoxystearate was prepared according to literature procedures¹¹And obtained in a purity of 82% to 99%.

NMR analysis: nuclear Magnetic Resonance (NMR) spectra of protons were recorded on an AVANCE 400 NMR spectrometer at 400.1MHz at 25 ℃ (Bruker). Chemical shifts are expressed in ppm (parts per million) of signal relative to residual non-deuterated solvent. The multiplicity of signals is described as follows: singlet(s), doublet (d), triplet (t) and multiplet (m).

TGA analysis: thermogravimetric analysis was performed using a TGA-DSC-1Mettler-Toledo apparatus under anhydrous molecular nitrogen using a heating rate of 10 ℃/min.

Example 1: perhydrolysis of methyl 9, 10-epoxystearate-Effect of temperature

In a 6-mL test tube equipped with a magnetic stirrer0.506mmol of methyl 9, 10-epoxystearate, 0.48. mu. mol of phosphotungstic acid hydrate and 0.617mmol (35. mu.L) of 60% w/v aqueous hydrogen peroxide solution were charged. The mixture was stirred at the given temperature indicated in the table below for a given time. At the end of the stirring time, 0.5mL of deuterated chloroform (CDCl)₃) Of the reaction crude product diluted in¹H NMR analysis showed complete conversion of the methyl 9, 10-epoxystearate to a mixture of 9(10) -hydroperoxy-10 (9) -methyl Hydroxystearate (HPA) and 9, 10-dihydroxystearate in the proportions given in the table below:

[ Table 1]

^[a]Degree of conversion and yield were determined by the reaction in CDCl₃Of the reaction crude product diluted in¹H NMR determination.

As this experiment shows, a temperature increase can achieve a slightly higher TON in a shorter time, but has no significant effect on the degree of conversion and the selectivity to HPA, so the reaction can be carried out at temperatures close to room temperature.

Example 2: perhydrolysis of methyl 9, 10-epoxystearate-Effect of the concentration of aqueous Hydrogen peroxide solution

In a 6-mL test tube equipped with a magnetic stirrerCharged with 0.506mmol of 9, 10-epoxymethyl stearate and 0.48 mumol of hydrated phosphotungstic acid and a known concentration of aqueous hydrogen peroxide solution (0.617 mmol). The mixture was stirred at 30 ℃ for a period of 1 hour. At the end of stirring, 0.5mL of deuterated chloroform (CDCl)₃) Of the reaction crude product diluted in¹H NMR analysis showed that methyl 9, 10-epoxystearate was converted to a mixture of methyl 9(10) -hydroperoxide-10 (9) -Hydroxystearate (HPA) and methyl 9, 10-dihydroxystearate in the proportions given in the table below:

[ Table 2]

^[a]Degree of conversion and yield were determined by the reaction in CDCl₃Of the reaction crude product diluted in¹H NMR determination.

^[b]The reaction was carried out for 2h 10min instead of 1 hour.

^[c]The reaction was carried out for 16h instead of 1 hour.

It is evident from this test that a degree of conversion of more than 99% can be achieved in only 1 hour using hydrogen peroxide at a concentration of more than 30% (w/v).

Example 3: perhydrolysis of methyl 9, 10-epoxystearate-Effect of catalyst Loading

In a 6-mL test tube equipped with a magnetic stirrer1.050mmol of methyl 9, 10-epoxystearate, a known amount of phosphotungstic acid hydrate and 1.280mmol (72.6. mu.L) of 60% w/v aqueous hydrogen peroxide were charged. The mixture was stirred at 30 ℃ for a given length of time. At the end of stirring, 0.5mL of deuterated chloroform (CDCl)₃) Of the reaction crude product diluted in¹H NMR analysis showed that methyl 9, 10-epoxystearate was converted to the ratios given in the table belowThe mixture of methyl 9(10) -hydroperoxide-10 (9) -Hydroxystearate (HPA) and methyl 9, 10-dihydroxystearate of example:

[ Table 3]

^[a]Degree of conversion and yield were determined by the reaction in CDCl₃Of the reaction crude product diluted in¹H NMR determination.

It is evident from the table that at 30 ℃, a degree of conversion higher than 99% can be obtained with a catalyst loading of less than 1 wt.%, and that the loading can even be reduced to 0.2 wt.% without substantially increasing the reaction time or affecting the yield of HPA. Furthermore, catalyst loadings on the order of 10 wt.% do not allow the desired HPA yield to be achieved and have a detrimental effect on the TON of the reaction.

Example 4: study of the perhydrolysis of methyl 9, 10-epoxystearate-reaction at 50 deg.C

In a 6-mL test tube equipped with a magnetic stirrerVariable amounts of methyl 9, 10-epoxystearate, 0.110. mu. mol of hydrated phosphotungstic acid and variable amounts of 60% w/v aqueous hydrogen peroxide solution (1.2 molar equivalents) were charged. The mixture was stirred at 50 ℃ for a given length of time. At the end of stirring, 0.5mL of deuterated chloroform (CDCl)₃) Of the reaction crude product diluted in¹H NMR analysis showed that methyl 9, 10-epoxystearate was converted to a mixture of methyl 9(10) -hydroperoxide-10 (9) -Hydroxystearate (HPA) and methyl 9, 10-dihydroxystearate in the proportions given in the table below:

[ Table 4]

^[a]Degree of conversion and yield were determined by the reaction in CDCl₃Middle thinOf the crude reaction product¹H NMR determination.

It is evident from the table that at 50 ℃, a degree of conversion of at least 90% can be obtained with a catalyst loading of less than 1 wt.%, and that the loading can even be reduced to 0.05 wt.% without any significant effect on the yield of HPA.

Example 5: perhydrolysis of methyl 9, 10-epoxystearate-Effect of solvent addition

In a 6-mL test tube equipped with a magnetic stirrer1.23mmol of methyl 9, 10-epoxystearate, 0.99. mu. mol of phosphotungstic acid hydrate, 1900. mu.L of t-butanol and 30% (w/v) of an aqueous solution of hydrogen peroxide (1.25mmol) were charged. The mixture is stirred at a temperature for a given length of time. At the end of stirring, 0.5mL of deuterated chloroform (CDCl)₃) Of the reaction crude product diluted in¹H NMR analysis showed that methyl 9, 10-epoxystearate was converted to a mixture of methyl 9(10) -hydroperoxide-10 (9) -Hydroxystearate (HPA) and methyl 9, 10-dihydroxystearate in the proportions given in the table below:

[ Table 5]

^[a]Degree of conversion and yield were determined by the reaction in CDCl₃Of the reaction crude product diluted in¹H NMR determination.

As is evident from the table, the presence of organic solvent in the reaction mixture does not always allow the highest degree of epoxide conversion and acceptable HPA yield to be achieved in up to about 2 hours. This problem can be overcome by heating the reaction mixture slightly.

However, as shown in example 2, the highest degree of conversion was obtained in up to 2h 10min with acceptable yield in the absence of solvent, even at 30 ℃. Furthermore, it was observed that at the highest hydrogen peroxide concentration, a significant increase in HPA yield can be achieved in the absence of solvent. In fact, when the perhydrolysis reaction was carried out under the conditions of example 1 but in the presence of 950. mu.L of tert-butanol, the yield of HPA was only 47% (instead of 74%) after 1 hour at 30 ℃ and only 58% (instead of 76%) after 10 minutes at 50 ℃.

Example 6: perhydrolysis of 2- (6-methoxy-6-methylhept-2-yl) oxetanes

In a 6-mL test tube equipped with a magnetic stirrer1.00mmol of 2- (6-methoxy-6-methylhept-2-yl) oxetane, 0.13. mu. mol of hydrated phosphotungstic acid and 60% (w/v) of an aqueous solution of hydrogen peroxide (1.01mmol) were charged. The mixture was stirred at 1000 rpm for 3 hours at 50 ℃. At the end of the stirring and at room temperature, 0.14mmol of hexafluorobenzene was added to the reaction mixture to serve as an internal standard for the quantification of the reaction product. In 0.5mL of deuterated dichloromethane (CD)₂Cl₂) Of the reaction crude product diluted in¹³C NMR quantitative analysis showed that 2- (6-methoxy-6-methylhept-2-yl) oxetane was converted into a mixture of 1(2) -hydroperoxy-7-methoxy-3, 7-dimethyloct-2 (1) -ol (HPA) and 7-methoxy-3, 7-dimethyloct-1, 2-diol, which were obtained in yields of 66 mol% and 34 mol%, respectively. Thus achieving a TON of 5000.

Example 7: 7-oxabicyclo [4.1.0]Perhydrolysis of heptane

In a 19-mL test tube equipped with a magnetic stirrerCharged with 5.93mmol of 7-oxabicyclo [4.1.0 ]]Heptane, 0.70 μmol of hydrated phosphotungstic acid, and 0.5mL of deuterated dichloromethane. The tube was then placed in a bath thermostatically controlled to 5 ℃ and then stirred slowly for 30 minutes. After this time, stirring was set to 1000 rpm, and then 60% (w/v) of an aqueous hydrogen peroxide solution (6.00mmol) was slowly added over a period of 30 minutes by means of a syringe pump. Finally, stirring at 5 ℃ for 30 minutes at the endThe intermediate section allows for complete conversion of the epoxide. 0.75mmol of 1, 4-dibromobenzene was then added to the reaction mixture, serving as an internal standard for the quantification of the reaction products. In 2mL deuterated dichloromethane (CD)₂Cl₂) Of the reaction crude product diluted in¹H NMR quantitative analysis showed that 7-oxabicyclo [4.1.0 ]]Heptane was converted to a mixture of 2-hydroperoxy-cyclohex-1-ol (HPA) and cyclohex-1, 2-diol, which were obtained in yields of 34 mol% and 32 mol%, respectively. Thus, TON of 2900 is achieved.

Example 8: perhydrolysis of epoxidized olive oil

In a 6-mL test tube equipped with a magnetic stirrer332.4mg of epoxidized olive oil containing 3.21mmol/g of epoxy functional groups were charged. The composition is obtained by quantifying crude olive oil¹H NMR quantitated the alkenyl functionality and then ensured complete conversion of the alkenyl functionality to the epoxide. Then 0.13. mu. mol of hydrated phosphotungstic acid and 60% (w/v) of an aqueous solution of hydrogen peroxide (1.06mmol) were added. The mixture was stirred at 1000 rpm for 4 hours at 50 ℃. At the end of the stirring and at room temperature, 1.5mL of deuteromethanol and 0.5mL of deuterochloroform were added to the crude reaction product, followed by¹Quantitative H NMR analysis showed that the epoxidized olive oil had been completely converted to a mixture of hydroperoxides and vicinal diols, which were obtained in yields of 73 mol% (as hydroperoxides functional group) and 12 mol% (vicinal diols functional group), respectively. Thus, a TON of 5600 is achieved.

Reference to the literature

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