CATALYTIC SYNTHESIS OF ALDEHYDES BY DIRECT HYDROGENATION OF CARBOXYLIC ACIDS

Abstract: A process which makes it possible to prepare aldehydes under mild reaction conditions with a high efficiency through the reduction of carboxylic acids with molecular hydrogen. Specifically, a process of reducing an organic carboxylic acid with molecular hydrogen in the presence of a catalyst into an aldehyde corresponding to the acid, characterized by conducting the reduction in the presence of a dehydrating agent such as a carboxylic anhydride.

Description: FIELD OF THE INVENTION This invention provides a method for simple and highly efficient preparation of aldehydes in which organic carboxylic acids are reduced to corresponding organic aldehydes with molecular hydrogen in the presence of catalysts, wherein said reaction is performed in the presence of a dehydrating agent. BACKGROUND ART Aldehydes are used, not only for perfume, drugs and agricultural chemicals by themselves but also as raw materials for synthesis of fine chemicals. As the conventional procedures of aldehyde synthesis, the methods such as oxidation of hydrocarbons and reduction of acid halides are known, but these methods have problems such as poor reaction efficiency including critical oxidation conditions and stoichiometric formations of by-products such as halides, in addition to heavy environmental load. As the methods to prepare aldehydes by reducing carboxylic acids, typically multi-step reactions are used, for example, converting carboxylic acids to acid chlorides and the like followed by partial reduction thereof, or converting the acids to alcohols followed by partial oxidation thereof. An example of such a multi-step method appears in US 4,240,984 which describes the formation of aromatic aldehydes from the corresponding aromatic acid, wherein the acid is initially reacted with ethyl or isobutyl chlorocarbonate to produce the anhydride. The anhydride is then hydrogenated in the presence of a palladium/batium sulphate catalyst to produce the aldehyde. The formation of acetaldehyde from acetic anhydride has also been reported in US 4,351,964 wherein the reaction is performed in the presence of acetic acid and a palladium, platinum or rhodium catalysts which may be supported, and in US 4,329, 512 wherein the reaction is performed in the presence of a group VIII metal catalyst which can also be supported. An aldehyde synthesis reaction by catalytic hydrogenation of acid chlorides using molecular hydrogen as a hydrogen source in the presence of solid palladium catalysts is called the Rosenmund reduction, and is known to proceed almost quantitatively in various substrates by adding amines to the reaction system. This reaction has such advantages that hydrogen pressure can be the atmospheric pressure, but also disadvantages such as necessity of preparing acid chlorides and generation of acidic hydrochloric acid as a by-product. There is a report of hydrogenation in homogeneous system using palladium complexes. However, this reaction is limited to the substrates of aromatic carboxylic acid chlorides (A. Schoenberg and R.F. Heck, J. Am. Chem. Soc., 96,7761(1974)). A method developed by former Mitsubishi Chemical Ind. (presently Mitsubishi Chemical Corp.) is an example of efficient hydrogenation of carboxylic acids using molecular hydrogen. This process provides aldehydes selectively in high yield by hydrogenation in vapor phase at high temperature (330~400°C) in the presence of zirconia or chromic acid based solid catalysts (N. Ding, J. Kondo, K. Maruya, K. Domen, T. Yokoyama, N. Fujita, T. Maki, Catal., 17,309 (1993); laid-open Japanese Patent 1992-210936 (T. Yokoyama et al.); laid-open Japanese Paten 1987-108832 (T. Maki et al.); general review: T. Yokoyama, Monthly Report of Japan Chem. Ind. Association, April, 1997, p. 14). Disadvantages of this method are difficulties in applications to the substrates with poor heat stability because high temperature is required for the reaction, and to a unit reaction in small-scale synthesis due to large sized plant being required. Further examples of the production of aldehydes from carboxylic acid derivatives have also been reported. For example, US 4,613,700 relates to a process for the hydrogenation of aromatic carboxylic acids to produce aromatic aldehydes using a zirconium oxide catalyst which further contains an additional metal component, whilst US 4,328,373 describes the vapour phase production of aldehydes from the corresponding carboxylic acids and esters in the presence of a metal oxide catalyst which may be supported upon aluminium oxide. The production of aldehydes from carboxylic acids, esters or anhydrides has been described in US 5,476,827, US 5,334,769 and WO97/17135. The reactions described therein are performed in the presence of a bimetallic ruthenium-tin catalyst, wherein said catalyst may be supported upon aluminium, silicon and/or zirconium oxides. Furthermore, the formation of aromatic and aliphatic aldehydes from the corresponding aromatic or aliphatic carboxylic acids, esters, anhydrides or halides is described in US 5,059,716. The reaction described therein involves the hydrogenation of the acid derivative in the presence of a catalyst comprising titanium and/or vanadium oxides and one or more co-metals from chromium, molybdenum, cobalt, nickel, zinc, cadmium and copper. The inventors of this invention have reported a method for preparation of aldehydes by reducing carboxylic anhydrides using molecular hydrogen under mild reaction conditions in the presence of zero valent palladium complex catalysts (Chem. Lett. 1995, 365). However, this method has problems in reaction efficiency such as necessity of preparation of acid anhydrides as raw materials in advance and generation of carboxylic acids equimolar to aldehydes as by-products. BRIEF DESCRIPTION OF THE INVENTION The invention provides a method for highly efficient preparation of aldehydes under mild reaction conditions by reducing carboxylic acids using molecular hydrogen according to claim 1. The invention relates to a method for preparation of aldehydes in which organic carboxylic acids are reduced to corresponding organic aldehydes using molecular hydrogen in the presence of catalysts, wherein said reaction is performed in the presence of dehydrating agents, according to claim 1. MOST PREFERED EMBODYMENT OF THIS INVENTION In order to improve yield in the above mentioned preparation method for aldehydes using carboxylic anhydrides as raw materials (Chem. Lett. 1995, 365), the inventors have studied enthusiastically on an improvement of this reaction system. As the results, it was unexpectedly found that aldehydes was able to be obtained in high yield by converting corresponding carboxylic acids of raw materials to carboxylic anhydrides in this reaction system in the presence of dehydrating agents. The present invention relates to a process of preparing an organic aldehyde, having from 5 to 30 carbon atoms, which process comprises reducing the corresponding carboxylic acid with molecular hydrogen in the presence of a palladium complex and a dehydrating agent in a solution, wherein said dehydrating agent is a carboxylic anhydride or a dicarbonate, provided that the carboxylic anhydride is not the anhydride of the carboxylic acid from which the target aldehyde is produced, wherein said corresponding carboxylic acid is an aliphatic carboxylic acid with a primary α-position, a monocyclic cycloalkyl carboxylic acid having from 5 to 30 carbons, an unsubstituted aryl carboxylic acid, an aromatic carboxylic acid with substituents at the m- or p- position, a benzoic acid halide or a 5- to 10-membered optionally substituted heteroaryl carboxylic acid. The invention features to obtain aldehydes in high yield by hydrogenating carboxylic acids with generation of acid anhydrides in the reaction system, in coexistence of dehydrating agents such as trimethylacetic anhydride, according to claim 1. The dehydrating agents used in the invention are carboxylic anhydrides and dicarbonates, among which carboxylic anhydrides are preferred. Carboxylic anhydrides to be used as dehydrating agent include linear or branched aliphatic carboxylic anhydrides having from 1 to 20, preferably from 1 to 10 carbon atoms; aromatic carboxylic anhydrides having from 6 to 20 and preferably from 6 to 12 carbon atoms. Preferred carboxylic anhydrides include branched aliphatic carboxylic anhydrides having from 1 to 20, preferably from 1 to 10 carbon atoms. More typically, carboxylic anhydrides with sterically bulky substituents, such as trimethyl acetic anhydride, are more preferable. Organic carboxylic acid as starting material of the invention may have other groups within the molecule that do not give any adverse effect on the reaction of the invention. When the carboxylic acids have groups with adverse effects on the reaction of the invention, the acids can be provided to the reaction after protecting the said groups with suitable protection groups generally used in peptide synthesis, etc. Organic carboxylic acids as starting materials of the invention can be expressed by the following general formula (I), R-COOH (wherein, R is an organic group) and the organic group of R includes optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl. These organic carboxylic acids may be monocarboxylic acids or polybasic acids having plural carboxyl groups such as dicarboxylic acids and tricarboxylic acids. Preferred alkyl groups in the general formula (I) above include linear or branched alkyl groups having from 1 to 30, preferably from 1 to 20, and more preferably from 5 to 15 carbon atoms; preferred alkenyl groups include linear or branched alkenyl groups having from 2 to 30, preferably from 2 to 20, and more preferably from 5 to 15 carbon atoms; preferred cycloalkyl groups are monocyclic, having from 5 to 30, preferably from 5 to 20, and more preferably from 6 to 10 carbon atoms; preferred aryl groups include aryl groups of monocyclic, polycyclic or condensed ring system, having from 6 to 30, preferably from 6 to 20, and more preferably from 6 to 10 carbon atoms; and preferred heteroaryl groups include saturated or unsaturated heteroaryl groups of monocyclic, polycyclic or condensed ring system, containing at least one nitrogen, oxygen or sulfur atom, each ring having from 5 to 10, and preferably from 5 to 7 of ring members, wherein the groups may have cycloalkyl, cycloalkenyl or aryl groups in a condensed form, wherein said cycloalkyl and aryl groups are as described above and wherein preferred cycloalkenyl groups include aforementioned cycloalkyl groups having at least one unsaturated bond. Or, R groups may be so-called aralkyl groups and may include aforementioned alkyl or alkenyl groups substituted by aryl or heteroaryl groups described above. Alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl or aralkyl groups in the compounds of general formula (I) above may be substituted by substituents not adversely affecting on the reaction. If the substituents have possibilities to adversely affect the reaction, such substituents can also be protected with protecting groups. Therefore, substituents in this invention also include reactive substituents that may be protected with protection groups during the reaction. Alkyl, alkenyl, cycloalkyl, aryl, heterocyclic or aralkyl groups in the general formula (I) above may be mutually substituted by further alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic or aralkyl groups, if such mutual substitutions are possible. For example, the groups such as alkyl-substituted cycloalkyl groups, alkyl-substituted aryl groups, alkyl-substituted heteroaryl groups, alkyl-substituted aralkyl groups, cycloalkyl-substituted alkyl groups, cycloalkyl-substituted alkenyl groups and alkeny-substituted aryl groups are included. Other substituents include alkoxy groups, alkylthio groups, dialkylamino groups, alkoxy carbonyl groups consisting of alkyl groups described above; halogen atoms such as chlorine, bromine and fluorine; alkylenedioxy groups such as methylenedioxy, 2,2-dimethylmethylenedioxy groups; and cyano groups. Preferred substituents include lower alkyl groups such as methyl, ethyl, n-propyl, isopropyl and t-butyl groups; aryl groups such as phenyl and naphthyl groups; lower alkoxy groups such as methoxy, ethoxy and n-propoxy groups; lower alkylamino groups such as dimethylamino, diethylamino and dipropylamino groups; alkoxycarbonyl groups such as methoxycarbonyl and ethoxycarbonyl groups; halogen atoms such as chlorine and fluorine; alkylenedioxy groups such as methylenedioxy and 2,2-dimethylmethylenedioxy groups; and cyano groups. Typical examples of R in the general formula (I) above include, e.g., lower alkyl groups such as methyl, ethyl, n-propyl, n-butyl and hexyl groups; lower alkenyl groups such as propenyl and butenyl groups; cycloalkyl groups such as cyclohexyl and cyclopentyl groups; aryl groups such as phenyl and naphthyl groups; heterocyclic groups such as thienyl and furanyl groups; and aralkyl groups such as benzyl and phenethyl groups. Carboxylic acids as starting materials in this invention include, for example, aliphatic carboxylic acids such as caprylic acid, n-caproic acid, lauric acid and palmitic acid; aliphatic dicarboxylic acids such as adipic acid, pimelic acid, sebacic acid and dodecanoic dicarboxylic acid; esters of aliphatic polycarboxylic acids such as monomethyl adipate, monoethyl pimelate, monoethyl sebacate and monoethyl dodecanoic dicarboxylate; aliphatic unsaturated carboxylic acids such as oleic acid, erucic acid and 10-undecenoic acid; aliphatic carboxylic acids with aromatic substituents such as phenylacetic acid and 3-phenylpropionic acid; cyclic aliphatic acids such as cyclohexanecarboxylic acid; aromatic carboxylic acids such as benzoic acid, 2-naphthoic acid, 4-cyanobenzoic acid, 4-t-butylbenzoic acid, 4-methoxybenzoic acid, 3-phenoxybenzoic acid and 3,4-methylenedioxybenzoic acid; aromatic dicarboxylic acids such as terephthalic acid; aromatic tricarboxylic acids such as 1,3,5-benzenetricarboxylic acid; and heteroaryl carboxylic acids such as pyridinecarboxylic acid, furancarboxylic acid and thiophenecarboxylic acid. Amount of the dehydrating agent of the invention may be catalytic level, however, a higher level is more preferable. For example, the amount is not less than 1 equivalent, preferably, from 1 to 10 equivalent, more preferably, from 2 to 5 equivalent, still more preferably, from 3 to 5 equivalent to the carboxylic acid of raw material. As the catalyst of the invention, a palladium complex is used. The catalysts of the invention may be used as a homogeneous catalyst by making them soluble or in a heterogeneous system as solid catalysts. The catalysts may be used as the complexes having ligands such as phosphine and carbonyl, and also as the metal element itself. In using the catalyst as a complex, the complex may be formed in advance before using as a catalyst or may be formed in a reaction system by adding separately to the reaction system. Preferred catalysts include palladium complexes such as tetrakis(triphenylphosphine)palladium and palladium metal such as palladium/carbon. Particularly preferred catalysts include zero valent palladium complexes. Catalysts of the invention may be used in a supported form on a support. Supports to be used include activated carbon, and alumina. In the method of the invention, use of solvent is preferable. Preferred solvents to be used should be non-reactive and should have sufficient dissolving power for raw materials and reaction products. The solvents to be used in the method of the invention include polar solvents such as acetone and dimethylfolmamide (DMF) and ether type solvents such as tetrahydrofurane (THF) and dioxane. Pressure under which reaction of the invention is carried out may be either atmospheric or pressurized, however, the latter is preferable. Preferred reaction pressure is from 0.1 to 6.0 MPa, more preferably from 0.5 to 5.0 MPa. If carbonyl complexes are used as the catalyst, an addition of carbon monoxide is preferable, and partial pressure of the carbon monoxide is from 0.5 to 10.0 MPa, preferably from 1.0 to 6.0 MPa. Reaction temperature in the invention may be selected within a range from room temperature to boiling point of the solvent. Preferred reaction temperature is from 25 to 100 °C, more preferably from 25 to 80 °C. Target aldehydes can be isolated and purified from the reaction mixtures obtained using known methods. Methods for isolation and purification include usual processes such as distillation and chromatography Method of the invention has wider application range and is possible to make selection range for raw compounds still wider, because it enables not only to prepare target aldehydes in high yields and selectivities but also to be used both in homogeneous and heterogeneous reaction systems under mild reaction conditions, and thus it is industrially advantageous. EXAMPLES The invention is further illustrated by reference to the following examples: Example 1~9 A 100 cm 3 stainless autoclave was purged with argon gas and charged with a catalyst (0.02 mmol), solvent (5 cm 3 ), carboxylic acid (2 mmol) and dehydrating agents shown in Table 1, then pressurized at 3.0 MPa with hydrogen at room temperature. And the reaction system was stirred for 24 hr at 80 °C. The reactor was then cooled to the temperature below room temperature, hydrogen pressure was released and the reaction solution was analyzed by 1 H-NMR and gas chromatography - mass spectrometry. The reaction conditions are shown below by the following reaction formula. Results are shown in Table 1. Results in Table 1 demonstrate that various types of dehydrating agents can be used but trimethylacetic acid provides the highest yield, and aldehydes can be obtained almost quantitatively when 3 equivalents of trimethylacetic acid to each carboxylic acid is added. Examples Using carboxylic acids shown in Table 2, corresponding aldehydes were prepared by the method as described in example 1. The reactions are shown by the following general formula. Results are shown in Table 2. Results in Table 2 demonstrate the following. Aliphatic carboxylic acids of the substrates with primary α position generated aldehydes almost quantitatively. In this case, cis inner olefins of oleic acid and erucic acid were not hydrogenated, as confirmed by 1 H-NMR. In the case of trans cinnamic acid, the yield was improved by using Pd(OAc) 2 /2PPh 8 with Pd/P ratio of 1/2 as a catalyst. In 10-undecenoic acid with terminal olefin, carboxyl group was converted to formyl group in high yield. However, isomerization of the terminal olefin to inner olefin was observed, and generation of hydrogenated compound at the olefin moiety was also suggested by 1 H - NMR. Substrates with many substituents at α position showed lower yields. In the cases of 2-phenylpropionic acid and diphenyl acetic acid, a decarbonylation from acyl palladium complexes, which were regarded as reaction intermediates, occurred and generated mainly styrene and diphenylmethane respectively as by-products, thus the yields for aldehydes were significantly low. Trimethylacetic acid added as a dehydrating agent, was hardly hydrogenated under these reaction conditions. Examples 16 to 21 and Comparative Example 3 Using various aromatic carboxylic acids shown in Table 3, corresponding aldehydes were prepared by the method as described in example 1. The reactions are shown by the following general formula. Results are shown in Table 3. Results in Table 3 demonstrate that aromatic carboxylic acids with substituents at m- or p- positions were hydrogenated successfully. In naphthoic acid, it was found that decarbonylation reaction occurred also as a side reaction. Examples 22 to 25 Using various polybasic acids shown in Table 4, corresponding aldehydes were prepared by the method as described in example 1. The reactions are shown by the following general formula. Results are shown in Table 4. Results in Table 4 demonstrate that carboxyl groups were also converted efficiently to formyl groups similarly to polybasic acids. Example 26 Corresponding aldehydes were prepared as described in example 1 by the method shown by the following reaction formula. Yield was 99%. Example 27 Corresponding aldehydes were prepared as described in example 1 by the method shown by the following reaction formula. Yield was 99%. Example 28 Corresponding aldehydes were prepared as described in example 1 by the method shown by the following reaction formula. Yield was 84%. Example 29 Corresponding aldehydes were prepared from β-pyridinecarboxylic acid as described in example 1 by the method shown by the following reaction formula. Yield was 99%. Examples 30 and 31 Corresponding aldehydes were prepared from furancarboxylic acids as described in example 1 by the method shown by the following reaction formula. Yields in 3-furancarboxylic acid and 2-furancarboxylic acid were 90% and 87%, respectively Examples 32 and 33. Corresponding aldehydes were prepared from thiophenecarboxylic acids as described in example 1 by the method shown by the following reaction formula. Yields in 2-thiophenecarboxylic acid and 3-thiophenecarboxylic acid were 72% and 73%, respectively. Examples 34 to 37 Corresponding benzaldehyde halides were prepared by hydrogenation of benzoic acid halides shown by the following formula, as described in example 1. Yields were 78%, 99%, 93% and 99%, respectively. Examples 38 and 39 Corresponding aldehydes were prepared by hydrogenation of ketocarboxylic acids shown by the following formula, as described in example 1. Yields were 97% and 85%, respectively. Example 40 Corresponding aldehyde was prepared by hydrogenation of α - naphthalenecarboxylic acid shown by the following formula, as described in example 1. Yield was 50%. Example 41 In this catalytic reaction, a mixture of palladium acetate and 5 equivalents of tri(4-methylphenyl)phosphine to the palladium compound were used as a catalyst, and the reaction was carried out in acetone solvent by the following formula as described in example 1. The reaction was found to proceed fast. Example 42 Using a solid catalyst of 10% palladium supported on activated carbon as a catalyst, the reaction was carried out as described in example 1 by the following formula, and the target octanal was prepared with yield of 15 %. INDUSTRIAL APPLICABILITY According to the method of the invention, various organic carboxylic acids such as aromatic, heterocyclic or aliphatic carboxylic acids can be hydrogenated to corresponding aldehydes simply and in high yields. This method provides advantageous synthesis methods for various organic compounds because aldehydes can be converted easily to other derivatives by aldol reaction and the like.

Claims: A process of preparing an organic aldehyde, having from 5 to 30 carbon atoms, which process comprises reducing the corresponding carboxylic acid with molecular hydrogen in the presence of a palladium complex and a dehydrating agent in a solution, wherein said dehydrating agent is a carboxylic anhydride or a dicarbonate, provided that the carboxylic anhydride is not the anhydride of the carboxylic acid from which the target aldehyde is produced, wherein said corresponding carboxylic acid is an aliphatic carboxylic acid with a primary α-position, a monocyclic cycloalkyl carboxylic acid having from 5 to 30 carbons, an unsubstituted aryl carboxylic acid, an aromatic carboxylic acid with substituents at the m- or p- position, a benzoic acid halide or a 5- to 10-membered optionally substituted heteroaryl carboxylic acid. A process according to claim 1, wherein the carboxylic anhydride is aliphatic carboxylic anhydride. A process according to claim 2, wherein the carboxylic anhydride comprises a branched aliphatic group. A process according to any one of claims 1 to 3, performed in the presence of solvent. A process according to any one of claims 1 to 4, wherein the palladium complex is a zero valent palladium complex. A process according to any one of claims 1 to 5, wherein the palladium complex is a solid catalyst. A process according to any one of claims 1 to 6, performed at a temperature of from 25 to 100°C. A process according to any one of claims 1 to 7, performed under a pressure of from 0.1 to 6.0 MPa.

Inventors: NAGAYAMA KAZUHIRO, YAMAMOTO AKIO, NAGAYAMA, KAZUHIRO, YAMAMOTO, AKIO
Applicants: JAPAN SCIENCE & TECH AGENCY, JAPAN SCIENCE AND TECHNOLOGY AGENCY
Application year: 1999
Main classification: C07C45
IPC codes: C07D213, C07D307, C07D333, C07C255, C07C67, C07C45, C07C253, C07D317