WO2008149370A2

WO2008149370A2 - Oxidation of aldehydes and alkenes

Info

Publication number: WO2008149370A2
Application number: PCT/IL2008/000777
Authority: WO
Inventors: Arkadi Vigalok; Nelly Shapiro
Original assignee: Ramot at Tel Aviv University Ltd
Current assignee: Ramot at Tel Aviv University Ltd
Priority date: 2007-06-06
Filing date: 2008-06-05
Publication date: 2008-12-11
Anticipated expiration: 2009-12-06
Also published as: WO2008149370A3

Abstract

A general method is disclosed for the conversion of aldehydes and alkenes to the corresponding carboxylic acids and 1,2-diols. The method is carried out in a catalyst-free aqueous medium under an atmosphere of oxygen or oxygen containing gas.

Description

OXIDATION OF ALDEHYDES AND ALKENES

FIELD OF THE INVENTION

This invention relates to the oxidation of aldehydes and alkenes.

BACKGROUND OF THE INVENTION

Aldehyde oxidation to carboxylic acids is an important industrial process. It has been known for many years that pure oxygen or oxygen in air can oxidize aldehydes in a radical reaction. The reactions normally proceed in bulk liquid aldehyde, for example, as disclosed in US Patent No. 5,504,229 and in WO 01/66,505 or in an organic solvent as disclosed, for example, in US 2007/265467.

Alternatively, as disclosed in US 2007/0010688, aldehydes may be oxidized into the corresponding carboxylic acids in an ionic liquid. Because of low oxygen solubility in most liquids, organic and inorganic alike (less then 5 mM), air or oxygen stream is often passed through the liquid aldehyde or aldehyde-containing solution, which may result in a certain degree of solvent and product evaporation and thus requires additional efforts on trapping the reaction volatiles. In addition to high oxygen concentration required when organic systems are employed, which also makes such systems potentially dangerous, large amounts of by-products are typically observed under these conditions.

Several known processes for preparing carboxylic acids from the corresponding aldehydes make use of catalysts and solvents that often lead to undesired side reactions. The use of such additives also requires elaborate purification steps, to which the product of the reaction must be subjected in order to obtain the targeted carboxylic acids. To name a few, US Patent No. 7,138,544 discloses oxidation of aldehydes into carboxylic acid using alkali metal carboxylates or alkaline earth metal carboxylates or a mixture thereof as the catalyst; US Patent No. 6,800,783 discloses the oxidation of aldehydes into the corresponding carboxylic acids by gaseous oxygen or oxygen-containing gaseous mixtures in the presence of up to 5 ppm of a metal of Groups V to XI.

Non-catalytic processes known to date are frequently unsatisfactory in terms of the reaction rate and in relation to the conversion and selectivity for the required product. For example, in the process disclosed in US Patent No. 6,696,582 neat aldehyde is oxidized into the corresponding carboxylic acid in at least two stages, at two different temperatures, preferably in the absence of a catalyst. In US Patent No. 3,579,575 there is disclosed the production of carboxylic' acids by a non-catalytic oxidation reaction of lower aldehydes in a heterogeneous phase comprising an aqueous phase and an organic phase. US Patent No. 5,686,638 teaches the oxidation of aldehydes into the corresponding carboxylic acids, in the absence of a catalyst. The method disclosed involves the dissolving of the aldehyde in a carboxylic acid or a carboxylic acid/water system and using high pressure of oxygen as the oxidizing agent. US Patent No. 5,237,092 teaches the conversion of aldehydes into carboxylic acids in a volatile organic solvent in the presence of a stabilizer wherein the solvent is removed by evaporation after the completion of the oxidation process.

Since oxygen solubility in any solution is too low for practical oxidation reactions, the use of conditions where the aldehyde surface is maximized was considered in order to facilitate the aldehyde oxidation by gaseous oxygen. For example, German Patent No. DE 1154454 discloses a non-catalytic aldehyde oxidation method taking place in thin layers of aldehyde at elevated temperatures.

Similarly to organic compounds having carboxylic acid moieties, 1,2-dihydroxy alkanes (1,2-diols, vicinal diols) are highly valuable compounds also used as intermediates in the chemical industry with multi-million tons of annual production. The most commonly accepted method to manufacture the diols is a two-step process that utilizes alkenes as starting materials. In the first step, the alkene is oxidized to the corresponding epoxide with oxygen gas serving as the oxidant. A catalyst is also employed, usually a silver (I) salt. The reaction proceeds at high temperatures and pressures. In the second step, the epoxide is hydrolyzed under the acidic conditions to give the final diol. Evidently, the first step of this process causes much safety concern because hydrocarbon/oxygen mixtures are highly explosive, especially under such forcing conditions. Also, the necessity to separate the products before hydrolyzing the epoxide adds to the cost of the process and increases the time of the manufacturing cycle as a whole.

Direct dihydroxylations of carbon-carbon double bonds (C=C) are carried out in laboratory scale by using transition metal oxides in high oxidation states especially osmium, ruthenium and manganese. These dihydroxylations typically are carried out in organic media. Another common oxidizing agent is K₃[Fe(CN)₆], used in the presence of K₃CO₃ in a biphasic, heterogeneous system of water and t-butanol. However, these processes are not industrially utilized mainly due to the cost of the oxidizing agents and catalysts.

Aldehyde-alkene co-oxidation is also known. Generally, it is performed in an organic solvent, although neat aldehyde was also employed. In all instances, the product of alkene oxidation was the corresponding epoxide. Since the products of both oxidation processes are obtained in a mixture, in addition to the presence of a substantial quantity of unreacted starting materials and by-products, the separation of the target oxidized products seems to present a serious hurdle for the utilization of such methods, and as long as this problem remains, the aldehyde-alkene co-oxidation seem to be of little use for the chemical industry.

Due to the rise of environmental awareness and increasing regulations on one hand and the everlasting requirement to reduce expenses there is a growing demand for oxidation reactions of cost effective green and environmentally friendly chemistry which are energy conserving, which eliminate the need for costly and contaminating organic solvents and metallic catalysts. Therefore, there exists the necessity for the development of processes for obtaining carboxylic acids and diols as final products or as intermediates for further use.

SUMMARY OF THE INVENTION

The inventors of the present invention have surprisingly found that poorly water- soluble aldehydes, namely aldehydes having a water-solubility of up to about 1 mg/ml, and poorly water-soluble alkenes with a similar or even lower solubilities, may be converted in water, in the absence of solubilizing agents and catalysts, in a facile, environmentally safe fashion into the corresponding carboxylic acids and diols, by using pure oxygen or oxygen-containing gas mixtures (e.g. air). Against all existing chemical knowledge and expectations, the process of the invention is carried out in water— a medium which does not typically permit sufficient solubility of organic compounds so as to carry out a great majority of chemical transformations. Nonetheless, the inventors have demonstrated that such a transformation can efficiently proceed even in the absence of any amount of organic solvents.

The advantages of the method disclosed herein, reside not only in the simplistic, low cost and efficient conversion but also in the safe execution of this reaction. Since water is an excellent heat capacitor, performing radical oxidations with oxygen and/or - A - oxygen-containing gas in water rather than in neat organic substrate or its solution in an organic solvent or mixtures thereof, provides a safer process.

More specifically, the present invention provides a new method for the production of carboxylic acids from poorly water-soluble aldehydes in water in the presence of oxygen. It also provides a new method for the simultaneous production of carboxylic acids and 1,2-diols from poorly water-soluble aldehydes and poorly water- soluble alkenes, respectively, in the same pot.

The present invention provides, in one of its aspects, a method for the conversion of an aldehyde (as defined herein) into the corresponding carboxylic acid (as defined herein), said method comprising: i) obtaining a suspension of at least one aldehyde in water or a homogeneous aqueous solution, said at least one aldehyde having a water-solubility of up to about 1 mg/ml at 20⁰C; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one aldehyde to the respective carboxylic acid.

In some embodiments, the method of the invention further comprises the step of isolating the product(s).

In some further embodiments, in the method of the invention, the aqueous medium further comprises at least one poorly water-soluble alkene (having a water solubility of up to about 1 and in some embodiments up to about 0.5 mg/ml at 20°C) which also undergoes oxidation in the presence of at least one aldehyde and oxygen.

The invention, thus, provides in another aspect, a one-pot process for the conversion of aldehydes and alkenes into the corresponding carboxylic acids and 1,2- diols, respectively. This one-pot method comprises: i) obtaining a suspension of at least one aldehyde and at least one alkene in water or a homogeneous aqueous solution, wherein said at least one aldehyde having a water-solubility of up to about 1 mg/ml at 20°C and said at least one alkene having a solubility of up to about 1 mg/ml at 20⁰C; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one aldehyde to the corresponding carboxylic acid and said at least one alkene to the corresponding 1,2-diol. In a further aspect, the present invention provides a method for the conversion of at least one alkene to the corresponding 1,2-diol, said method comprising: i) obtaining a suspension of at least one alkene having a solubility of up to about 1 mg/ml at 2O⁰C and at least one aldehyde in water or a homogeneous aqueous solution; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one alkene to the corresponding 1 ,2- diol.

In the methods of the invention, the ratio of the two components aldehyde : alkene may be from 1:0 to 100:1. Non-limiting examples of such ratios are 1:0, 1:1, 2:1, 3:1, 4:1...8:1, 9:1, 10:1, 11:1....20:1, 21 :1...90:1, 91 :1, 92:2...99:1 and 100:1 aldehyde:alkene. As a person skilled in the art would appreciate, intermediate ratios are also within the scope of the present invention.

In some embodiments, the ratio is 1:0 aldehyde:alkene. In some other embodiments, the ratio is 1 :1 aldehyde:alkene. In other embodiments, the reaction is carried out with an excess of aldehyde.

Thus, the invention also provides a process comprising: i) obtaining a suspension of at least one aldehyde and at least one alkene, in water or a homogeneous aqueous solution, said at least one aldehyde and said at least one alkene having each a water-solubility of up to 1 mg/ml; and wherein the ratio between said at least one aldehyde and at least one alkene is between 1:0 and 100:1; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one aldehyde to the corresponding carboxylic acid and said at least one alkene to the corresponding 1,2-diol.

In some embodiments, the aldehyde:alkene ratio is 1 :1. In further embodiments, the ratio is 1:0. In still further embodiments, the ratio is 100:1.

Typically, the method of the invention is carried out under ambient conditions, at room temperature (the temperature of the ambient) and under atmospheric pressure. The method may also be carried out at temperatures above or below room (ambient) temperature. In some embodiments, the reaction is carried out at a temperature between 10° and 60°C, between room (ambient) temperature and 60⁰C, between 40° and 60⁰C or between 50° and 60⁰C. The methods of the invention are non-catalytic processes, which may be carried out in water, as the reaction solvent, and are typically completed within two to 24 hours when carried out at room (ambient) temperature using air as the oxygen containing gaseous mixture.

The at least one aldehyde and the at least one alkene may each be a solid, a liquid or a gas at room temperature.

The carboxylic acid obtained from the oxidation of the aldehyde is typically poorly water-soluble. The 1,2-diol obtained from the oxidation of the alkene is typically water-soluble.

The "αf least one aldehyde^"" is an organic molecule comprising of at least one functional group of the general formula R — CHO. For the sake of convenience, the term "aldehyde" is used to designate such an organic compound having one or more of said function groups, wherein R is a carbon-containing group, which may be branched or linear, preferably an alkyl (or cyclic forms thereof), alkylenyl (or cyclic forms thereof), alkenyl (or cyclic forms thereof), alkenylenyl (or cyclic forms thereof), alkynyl (or cyclic forms thereof), alkynylenyl (or cyclic forms thereof), aryl (monocyclic, polycyclic or fused aromatic systems), and arylenyl, wherein the cyclic forms are selected from monocyclic, polycyclic or fused ring systems such as cyclohexane, cycloheptane, and adamantine, which may be substituted or unsubstituted with one or more functional groups such as carbonyl-containing groups (e.g., aldehydes, esters, ketones) and triple bonds.

In some embodiments, R is of 2 or more carbon atoms. In some embodiments, R is of between 2 and 20 carbon atoms. In other embodiments, R is of between 3 to 20 carbon atoms. Still further, R is of 5 to 20 carbon atoms, or 6 to 12 carbon atoms. In some embodiments, R, as defined with respect to the number of carbon atoms, is an alkyl (being a saturated aliphatic hydrocarbon, substituted or unsubstituted, chain) or alkenyl (having at least one C-C double bond).

The aldehydes oxidized according to methods of the invention are poorly water- soluble having a water-solubility of up to about 1 mg/ml, at 20⁰C. Excluded from the scope of the invention are aldehydes having a water-solubility greater than 1 mg/ml. Particularly excluded are acetaldehyde, propanaldehyde, butyraldehyde, iso- butyraldehyde, valeraldehyde and iso-valeraldehyde, each having a water-solubility greater than 1 mg/ml. It should be noted, for the sake of clarity, that where the moiety R is defined by the number of carbon atoms, the definition does not include the carbon atom of the aldehyde moiety. For example, where R is an alkyl having 5 carbon atoms, the alkylaldehyde is hexanal. Similarly, when the aldehyde is referred to herein as having, e.g., 6 carbon atoms, this designation takes into consideration also the carbon atom of the carbonyl group.

In some embodiments, the aldehyde molecule is a mono-aldehyde (namely having a single aldehyde moiety) and in other embodiments the molecule is a poly- aldehyde (namely having two or more aldehyde moieties).

The term "at least one aldehyde" also refers to mixtures of different aldehyde molecules, being of different molecular weights, having a different number of aldehyde moieties, having different substituents, different isomers, and so on.

Non-limiting examples of aldehydes that may be used in the process of the present invention are butanal, pentanal, hexanal, heptanal, octanal, nonanal, undecanal, benzaldehyde, cyclohexane carboxaldehyde, 2-ethyl hexanal and others, and any isomers thereof.

The organic acids manufactured according to the invention are of the general formula R-COOH, wherein R is the native group of the aldehyde, as defined above. The acids may be, for example, caproic acid, capryic acid, capric acid, lauric acid, phenylacetic acid, benzoic acid, cyclohexane carboxylic acid, and 2-ethylhexane carboxylic acid.

The "alkene" molecule refers to an organic molecule having 2 or more carbon atoms and at least one carbon-carbon double bond (herein also designated as C=C), being in either the cis or trans configuration. The alkene may be substituted by one or more functional group functional groups such as carbonyl-containing groups (e.g., aldehydes, esters, ketones) and triple bonds. The alkene may also be branched or linear.

In some embodiments, the alkene is a terminal alkene, namely having the double bond at the end of the chain (-C=CH₂). In other embodiments, the double bond is not terminal.

In some embodiments, the alkene is poorly water-soluble, having water solubility of up to about 1 mg/ml. In some embodiments, the alkene has a water solubility of up to 0.5 mg/ml. Non-limiting examples of alkenes are ethylene (ethane), propene, butylenes, iso- propene, 1-pentene, 2-pentene, røeo-pentene, styrene, cyclohexene, cycloheptene, and cyclopentadiene.

In some embodiments, the alkene molecule is a mono-ene (namely having a single C=C moiety, which may be cis or trans and may or may not be terminal) and in other embodiments the term refers to a polyene (namely having two or more C=C moieties, each being cis or trans and one or more of which may or may not be a terminal double bond).

The term "alkene" also refers to mixtures of alkenes.

For the sake of clarity, it should be noted that the alkene molecule undergoing oxidation in accordance with the method of this invention, is converted into a 1,2- (vicinal) diol of the general formula:

wherein the bond between the two carbon atoms, bearing each a hydroxyl (-OH) group, is the bond having undergone conversion from a double bond to a single bond. The substituent groups R¹, R², R³ and R⁴ on the oxidized carbon atoms, now bearing each a -OH group, are the native groups originally present at these centers in the unoxidized alkene. Typically, the substituent groups are, each independently hydrogen or an alkyl.

For example, where the alkene is 1-hexene (CH₃CH₂CH₂CH₂CH=CH₂), oxidation under the conditions of the process disclosed herein leads to hexane-l,2-diol (CH₃CH₂CH₂CH₂CH(OH)CH₂OH), wherein in the above general formula each of R¹ and R² are independently a hydrogen atom, R³ or R⁴ is hydrogen and the other of R³ and R⁴ is butyl. Similarly, where the alkene is, for example, 3-hexene (CH₃CH₂CH=CHCH₂CH₃), oxidation leads to hexane-3,4-diol

(CH₃CH₂CH(OH)CH(OH)CH₂CH₃). Each of the chiral centers, if present, may be of either the R OT S configurations.

The general designation 1 ,2-diol, as used herein, does not stand to designate the position of the hydroxyl (-OH) groups along the chain in accordance with the systematic numbering used in naming the alkane product but rather stands to denote the vicinal nature of the two hydroxyl groups.

The oxidation reaction and the conversion of the two sp² carbon atoms of the double bond into sp³ centers may provide, depending on the substitution on the oxidized carbon atoms, chiral (or pro-chiral) centers of either the R or S configuration.

Thus, the present invention also encompasses products obtained by oxidation according to any method of the invention, including optical isomers and diastereomers (including racemic mixtures) prepared according to the method of the present invention.

In yet other embodiments, the molecules undergoing oxidation in accordance with the invention, are bi- or multifunctional molecules having at least one aldehyde moiety and at least one C=C double bond moiety (cis or trans). In such cases, either or both the aldehyde and/or the double bond moieties undergo oxidation to the respective carboxylic acid and/or 1,2-diol, as will be further detailed hereinbelow.

In still other embodiments, the oxidation reaction is carried out on a mixture of aldehyde molecules and alkene molecules, as defined herein.

As disclosed above, the oxidation reaction is achieved when the water suspension, of either or both components, is exposed to oxygen or "oxygen-containing gaseous mixture". Such a mixture comprise at least 5% molecular oxygen wherein the remaining gases of the mixture comprise one or more gases which are either carrier gases or impurities. The inert gases are typically unreactive under the conditions of the process employed and do not affect the oxidation of either component. The inert gases may be, for example, nitrogen (N₂), helium, argon, and others.

In some embodiments, the dioxygen molecule employed with the method of the invention, being in the form of oxygen gas or a mixture containing oxygen, may be isotopically labeled or enriched so as to provide isotopically labeled carboxylic acids or diols.

In some embodiments, the oxidation gas is oxygen, or oxygen-enriched air. In other embodiments, the gaseous mixture is air.

The process of the invention may be carried out either batch-wise or continuously. DETAILED DESCRIPTION OF EMBODIMENTS

The invention provides an approach towards carboxylic acid and 1,2-diol formations, separately or simultaneously, using water as a reaction medium and oxygen as the oxidant. It was surprisingly found that poorly water-soluble aliphatic, cycloaliphatic and aromatic aldehydes and alkenes undergo facile oxidation upon simple stirring their aqueous emulsions in air or under an oxygen atmosphere. Scheme 1 generally, and in a non-limiting fashion, depicts the oxidation of an aldehyde to the corresponding carboxylic acid. As exemplified, the oxidation occurs on the carbonyl carbon atom of the aldehyde. In Scheme 2, the two oxidation reactions that take place, i.e., oxidation of the alkene and the aldehyde, are depicted. In Scheme 2, each of the variant groups R¹, R², R³ R⁴, and R⁵ independently of each other, represent the native groups of the original unoxidized starting aldehyde or alkene (being cis or trans).

Scheme 1

The alkene of Scheme 2 may be symmetric or asymmetric, in the cis or trans configuration, or as a mixture of both, and may also have multiple functionalities. In a non-limiting example, the alkene is a symmetric diene as generally depicted in Scheme 3. In the compound of Scheme 3, A represents a spacer moiety which may be selected from alkylene, cycloalkylene, arylene moieties, a C-C bond or any other group having at least one heteroatom, and R¹ through R⁷ each independently represents a native substituent of the unoxidized alkene/aldehyde.

Scheme 2

Similar diene/polyene compounds having one or more double bonds and having a linear or cyclic form may also be oxidized. It should also be understood that the within the scope of this invention are also molecules comprising more than one carbon-carbon double bond or more than one aldehyde moiety.

Air or O₂ Water

Scheme 3

Furthermore, within the scope of this invention is the oxidation of compounds comprising both functional groups, namely which contain at least one carbon-carbon double bond and at least one aldehyde moiety in the same molecule. The reaction may also take place in the presence of an additional aldehyde, preferably with a lower solubility than the alkene-aldehyde molecule, for the purpose of co-oxidation or for its mere use as an oxidizing reagent. Such a compound ultimately mainly yields a product comprising both at least one carboxylic acid group and at least one 1,2-diol moiety. A specific, non-limiting example of an oxidizing reaction of such a compound, according to one of the embodiments of this invention, is provided in Scheme 4:

Scheme 4

The suspension comprising the material to be oxidized may be prepared by adding said at least one aldehyde or a combination of said at least one aldehyde and said at least one alkene into water or a homogeneous aqueous solution. The component(s) may be admixed or stirred in order to allow an effective contact between the molecules and the oxygen or gas to which exposure is permitted.

The progress of the oxidation reaction(s) may be monitored by employing one or more methods of analysis such as thin layer chromatography (TLC), GC-MS, NMR, IR and other spectroscopic method of analysis.

Where only the at least on aldehyde is converted into the corresponding carboxylic acid, the step taken after the oxidation is completed is the removal of solids from the aqueous phase by, for example, filtration or decantation of the aqueous solution, and further purification if desired by conventional methods such as column chromatography, recrystallization, distillation and the like. Where necessary, the carboxylic acid derivative may be treated with a base to obtain the salt thereof. Salts of the carboxylic acids, thus obtained, having an organic or inorganic counterion, are also encompassed in the scope of the present invention.

Where the at least one alkene is converted into the corresponding 1,2-diol, and the oxidation product of the aldehyde is of no particular use or is not desired, upon completion of the reaction, the starting material which remains, being the poorly water- soluble alkene, is removed from the water phase, e.g., by phase separation, and the 1,2- diol product which may be water-soluble is thereafter extracted from the aqueous phase using extraction methods known in the art.

Where the process of the invention is carried out on a mixture of at least one aldehyde and at least one alkene, in the same pot, the reaction is typically completed with high conversion rates of the starting materials into the respective carboxylic acid and 1,2-diol. Upon completion, the poorly water-soluble carboxylic acid product along with the remaining starting materials can be removed by known methods in the art for separation of liquids from solids such as filtration and decantation of the aqueous solution. In order to increase the quantity of the collectible material out of the aqueous phase known steps in the art may be implemented such as slight acidification of the aqueous phase which shifts the equilibrium between the carboxylate salt and the its more hydrophobic acidic carboxylic form to latter, or adding an inorganic salt such as NaCl to raise the dielectric constant of the aqueous phase (salting out).

After removal of the solid matter, the aqueous phase contains mainly the 1,2- diol product in high excess, which may be extracted out into an organic phase and further purified according to methods known and practiced in the art such as column chromatography, recrystallization, distillation and the like.

Where the starting materials is an aldehyde with an unsaturated moiety, as previously described, and both the aldehyde and the double carbon-carbon bond are oxidized into the corresponding carboxylic acid and 1,2-diol, respectively, the separation of the product may depend on its solubility in the aqueous medium, hi some cases, the product may be soluble in its acidic form therefore allowing the use of slightly basic conditions in order to pull as much of the product into the aqueous phase and separate it from the poorly water-soluble starting material, which may thus be removed by decantation or filtration. Upon readjustment of the pH of the aqueous phase to slightly acidic, the dihydroxy carboxylic acid may be extracted with an organic solvent.

The starting amount of water to be used as the reaction medium is at least about 40% of the total volume of the reaction volume (aqueous medium and reactants), preferably at least about 50%, most preferably 90-100% of the total volume of the reaction volume. Aqueous solutions of inorganic salts, e.g. NaCl, can also be used in place of pure water. It should be emphasized that while it is preferable to carry out the oxidation of aldehydes and/or alkenes according to the invention in a homogeneous aqueous medium (namely, containing no organic solvents as the reaction medium and therefore being a one-phase water medium or an aqueous solution comprising salts), heterogeneous systems may also be employed, wherein small amounts of organic solvents are added to the suspension constituting no more than 10% v/v of the volume of the reaction.

As analytical tools, e.g., TLC, used to follow the progression of the reactions show, most of the starting material is consumed at the beginning of the reaction, typically within the first two hours. Longer times, 8 hrs and more are typically needed to achieve high (>90%) conversions at room temperatures using air as the oxidant. Moderate heating, e.g. 4O⁰C gives slightly higher conversion rates without affecting the product distribution. Generally, less than 5% of formate by-products are observed under the conditions disclosed herein, as confirmed by the ¹H NMR spectroscopy. In comparison, bulk oxidation of liquid aldehydes under otherwise identical conditions (stirring under 1 arm of oxygen or air) gives at least 10-15% of the formate by-product. Use of pure oxygen instead of air significantly increases the oxidation rates without increasing the formation of by-products. Importantly, the oxidation process described herein does not require high pressures as, under the reaction conditions, oxygen is consumed directly from the gas phase. It also does not require gas bubbling through the liquid, which necessitates an efficient trapping of the volatiles. However, bubbling may be implemented if desired. Simple stirring (or shaking) is sufficient to achieve high reaction rates. The temperature at which the oxidation is carried out is preferably room temperature; however mild heating may be implemented to the reaction in order to increase the yield of the reaction.

In the conventional methods of the prior art, wherein organic solvents, e.g., CH₂Cl₂, are used as the reaction media, under such mild conditions no aldehyde oxidation or alkene epoxidation would take place.

Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which together with the above descriptions illustrate the invention in a non limiting fashion.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention relates. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below.

EXAMPLE 1 -Typical oxidation procedure of an aldehyde into a carboxylic acid

5 ml (4.1 g) of 2-ethylhexanal and 100 ml of de-ionized water was stirred with a magnetic stirrer in a IL flask under 1 atmosphere of oxygen for 3 hrs. The phases were separated and aqueous phase was extracted with 2x20 ml of an organic solvent such as CH₂Cl₂, diethyl ether or ethyl acetate. The combined organic fractions contained 4.5 gram of a mixture of 90% 2-ethylhexanoic acid, 5% unreacted aldehyde and 5% of formate by product, as determined by ¹H NMR spectroscopy.

Under identical conditions but without water, the ratio between the products was 84% : 1% : 15%, for the acid, aldehyde and formate, respectively.

No oxidation was observed under these conditions when CH₂Cl₂ was used as a solvent. When air was used in place of oxygen, it took about 10 hours to get the comparable yields, however, over 60% yields were observed just after 2 hrs.

The above aqueous conditions were also applied to other aldehydes: aromatic, aliphatic or cyclic aliphatic. For example, stirring 5ml of 1-octanal in air with 100 ml water for 10 hrs provided over 80% of 1-octanoic acid, the rest being unreacted aldehyde.

Similarly, 80% of benzoic acid was obtained when benzaldehyde (3 ml) that was stirred for 10 hrs in air with water (20 ml). Using oxygen instead of air gave the same yield after just 2 hrs.

Cyclohexanecarboxaldehyde was also converted to the corresponding acid in excellent yields: 95% after 10 hrs in air (90% after 2 hrs with oxygen) with no more than 1% of the formate by-product.

Since both the starting materials and product carboxylic acids, are insoluble in water, they are easily separated from the aqueous phase by filtration of the aqueous emulsion at the end of the reaction. An organic solvent may also be used to achieve a quantitative extraction of the 1,2-diol product from the aqueous filtrate upon the completion of the filtration. Aqueous solutions of inorganic salts, e.g. NaCl, were also used in place of pure water.

The reactivity of the aldehyde-alkene mixtures with water under an atmosphere of dioxygen illustrates that when cyclohexanecarboxaldehyde and styrene are used as the aldehyde (10 equiv.) and the alkene, respectively. Under these conditions, most of the styrene is converted into 1,2-styrene diol after 18 hrs at room temperature. When the reaction is performed under basic conditions, most of styrene is converted to styrene oxide rather than diol. Also, when smaller excess of the aldehyde is used (1:5 ratio or less), styrene oxide was obtained in larger quantities than the diol.

EXAMPLE 2-Typical aldehyde-alkene co-oxidation procedure

50 mg of styrene, 430 mg of cyclohexane carboxaldehyde and 2 ml of de- ionized is stirred with a magnetic stirrer in a 25 flask under 1 atmosphere of oxygen for 18 hrs. The phases are separated and aqueous phase is extracted with 2 x 20 ml of an organic solvent such as CH₂Cl₂, diethyl ether or ethyl acetate. . The combined organic fractions contained 91% styrene diol, as determined by ¹H NMR spectroscopy. Column chromatography afforded ca. 60% of pure diol and above 90% of the carboxylic acid. The above aqueous conditions can also be applied to other alkenes, internal and terminal. For example, stirring cyclohexanecarboxaldehyde with 2,3-dimethyl-2-butene under O₂ with water for 18 hrs provided pinacol as the major product, as determined by ¹H and ¹³C NMR spectroscopy. Similarly, 82% of cyclohexane diol (determined by ¹H NMR spectroscopy) and above 90% of the carboxylic acid were obtained when cyclohexane carboxaldehyde was stirred with cyclohexene for 18 hrs under O₂ with water.

Claims

CLAIMS: '

1. A method for the conversion of at least one aldehyde to at least one carboxylic acid, said method comprising exposing said at least one aldehyde in a catalyst-free water or homogeneous aqueous medium to oxygen or oxygen containing gas, said at least one aldehyde having a water-solubility of up to about 1 mg/ml at 20⁰C.

2. The method according to claim 1 , said method comprising: i) obtaining a suspension of at least one aldehyde in water or a homogeneous aqueous solution; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one aldehyde to the respective carboxylic acid.

3. The method according to claim 1, wherein said aqueous medium further comprises at least one alkene.

4. The method according to claim 3, said method comprises: i) obtaining a suspension of at least one aldehyde and at least one alkene in water or a homogeneous aqueous solution; ii) exposing said suspension to oxygen gas or a gas containing oxygen; and iii) allowing oxidation of said at least one aldehyde to the corresponding carboxylic acid and said at least one alkene to the corresponding 1,2-diol.

5. The method according to claim 4, wherein the ratio of aldehyde:alkene is between 1 :0 and 100:1.

6. The method according to claim 5, wherein the ratio is 1 :0 aldehyde:alkene.

7. The method according to claim 5, wherein the ratio is 1 : 1 aldehyde:alkene.

8. The method according to claim 5, wherein the conversion reaction is carried out with an excess of aldehyde.

9. The method according to any one of the preceding claims, wherein one or both of said at least one aldehyde and said at least one alkene is poorly water-soluble.

10. The method according to any one of the preceding claims, wherein said at least one aldehyde is of the general formula R-CHO, wherein R is a carbon-containing group of two or more carbon atoms, said group being branched or linear, and selected from an alkyl, alkylenyl, alkenyl, alkenylenyl, alkynyl, alkynylenyl, aryl, arylenyl each of said groups may be substituted or unsubstituted, and cyclic forms of any one of alkyl, alkylenyl, alkenyl, alkenylenyl, alkynyl, and alkynylenyl.'

11. The method according to claim 10, wherein R is an alkyl or alkenyl.

12. The method according to claim 11, wherein R is an alkyl or alkenyl of at least 5 carbon atoms.

13. The method according to claim 10, wherein said at least one aldehyde is at least one mono-aldehyde, at least one poly-aldehyde or mixtures thereof.

14. The method according to any one of the preceding claims, wherein said at least one alkene has two or more carbon atoms and at least one C-C double bond.

15. The method according to claim 14, wherein said at least one alkene is at least one monoene, at least one polyene or mixtures thereof.

16. The method according to any one of the preceding claims, further comprising the step of isolating the product.

17. The method according to any one of the preceding claims, wherein said conversion is carried out under atmospheric pressure.

18. The method according to any one of the preceding claims, wherein said conversion is carried out at a temperature between 10° and 60°C.

19. The method according to claim 13, wherein said temperature is between ambient temperature and 60°C.

20. The method according to claim 13, wherein said temperature is between 40° and 60°C.

21. The method according to claim 13, wherein said temperature is between 50° and 60°C.

22. The method according to any one of the preceding claims, wherein said conversion is carried out in water.

23. The method according to any one of the preceding claims, wherein said conversion is carried out in an aqueous solution.

24. A carboxylic acid obtained by the process of claim 1.

25. A l ,2-diol obtained by the process of claim 3.

26. A mixture of at least one carboxylic acid and at least one 1 ,2-diol obtained by the process of claim 4.