Process for producing a lactone or an ester

Abstract: A process for producing a lactone or an ester represented by the following general formula (2), wherein R¹ and R², identical or different, each represents (C₁-C₂₀) alkyl group; alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy or acyloxy; phenyl group; or phenyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; phenylalkyl group; or phenylalkyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; provided that when R¹ and R², identical or different, each represents unsubstituted alkyl group or alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy, acyloxy or phenyl, the respective alkyl parts of R¹ and R² may be conjunct to each other; which comprises reacting a ketone represented by the following general formula (1), wherein R¹ and R² are as defined above, with oxygen in the presence of an aldehyde either in the absence of catalyst or in the presence of a heterogeneous iron-containing or ruthenium-containing catalyst: The above-mentioned process of this invention is an advantageous process for producing lactones or esters by the oxidation of ketones with oxygen either using no catalyst or using a readily available and recoverable catalyst.

Description: This invention relates to a process for producing a lactone or an ester by oxidation of a ketone. The above-mentioned lactone and ester are useful as synthetic intermediates in the production of various products including pharmaceuticals, pesticides, perfumes, liquid crystals, resins, pheromones, etc. Among them, ε-caprolactone is particularly important as a synthetic intermediate of the polyester used as a starting material of urethane polymers. A process for producing a lactone or an ester by the oxidation of a ketone using a peracid such as peracetic acid, m-chloroperbenzoic acid and the like is well known, as disclosed in Some Modern Methods of Organic Synthesis, 3rd ed., pp. 403-407). However, the process cannot be said to be advantageous from the industrial point of view, because peracids are high in shock sensitivity and explosive. With the aim of solving this problem, there have been developed a number of processes which comprise oxidizing a cyclic ketone in the presence of an aldehyde with various metallic catalysts (US Patent No. 3,025,306), with a soluble iron catalyst such as FeCl 3 , Fe(OAc) 3 , Fe(acac) 3 and the like (US Patent No. 3,483,222), with a soluble nickel catalyst (Japanese Patent Application KOKOKU No. 46-12456), or with soluble palladium, vanadium, molybdenum, tungsten or cerium catalyst (Japanese Patent Application KOKOKU No. 56-14095). A process for preparing lactones and carboxylic acids is also disclosed in GB-A-1009 773, NL-A-650 1334 and GB-A-1103 885. However, none of these processes can be said to be advantageous industrially because of low conversion and low selectivity. Apart from them, an improved process using a 1,3-diketonatonickel catalyst has been developed recently (Chem. Lett., 1991, 641). However, this process uses a homogeneous catalyst which makes troublesome the procedure for separating and recovering the catalyst from the objective product, i.e. lactone or ester, and therefore this process, too, cannot be said to be satisfactory from the industrial viewpoint. It is an object of the present invention to provide a process for advantageously producing a lactone or an ester by oxidizing a ketone without use of catalyst or by the use of a readily available and recoverable catalyst. With the aim of solving the problems mentioned above, the present inventors conducted various studies to attain this invention. Thus, according to the present invention, there is provided a process for producing a lactone or an ester represented by the following general formula (2): wherein R 1 and R 2 , identical or different, each represents (C 1 -C 20 ) alkyl group; alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy or acyloxy; phenyl group; or phenyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; phenylalkyl group; or phenylalkyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; provided that when R 1 and R 2 , identical or different, each represents unsubstituted alkyl group or alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy, acyloxy or phenyl, the respective alkyl parts of R 1 and R 2 may be conjunct to each other; which comprises reacting a ketone represented by the following general formula (1): wherein R 1 and R 2 are as defined above, with oxygen in the presence of an aldehyde selected from benzaldehyde, p-chlorobenzaldehyde, m-chlorobenzaldehyde, tolualdehyde and p-anisaldehyde, and, as a solvent, an aromatic hydrocarbon either in the absence of a catalyst or in the presence of ferric oxide. Alkyl groups, alkenyl groups, alkoxy groups, acyloxy groups and the alkyl moiety in substituted or unsubstituted phenylalkyl groups as used herein preferably contain not more than 20 carbon atoms. Examples of the ketone represented by formula (1) which can be used as a starting material in this invention include acetone, 2-butanone, 3-methyl-2-butanone, pinacolone, 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, 2-heptanone, 3-heptanone, 4-heptanone, 2,2-dimethyl-6-hepten-3-one, 1-chloro-3,3-dimethyl-2-butanone, 3,3-dimethyl-1-methoxy-2-butanone, 3,3-dimethyl-1-phenoxy-2-butanone, 1-acetoxy-3,3-dimethyl-2-butanone, cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclododecanone, 2-methylcyclobutanone, 2-octylcyclobutanone, 2-methylcyclopentanone, 3-methylcyclopentanone, 2-hexylcyclopentanone, 2-undecylcyclopentanone, 2,5-dimethylcyclopentanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, 4-t-butylcyclohexanone, 4-phenylcyclohexanone, 2-allylcyclohexanone, 2-chlorocyclohexanone, 4-methoxycyclohexanone, 4-phenoxycyclohexanone, 4-acetoxycyclohexanone, phenylacetone, acetophenone, 4'-methylacetophenone, 4'-chloroacetophenone, 4'-methoxyacetophenone, 3'-methoxyacetophenone, 2'-methoxyacetophenone, 4'-phenoxyacetophenone, 4'-acetoxyacetophenone, propiophenone, 4'-methoxypropiophenone, 1-(p-tolyl)-2-propanone, 1-(p-chlorophenyl)-2-propanone, 1-(p-methoxyphenyl)-2-propanone, 1-(p-phenoxyphenyl)-2-propanone, 1-(p-acetoxyphenyl)-2-propanone, benzophenone, 3α-acetoxyandrostan-17-one, 3β-acetoxyandrostan-17-one, 3α-benzoyloxyandrostan-17-one and the like. Examples of the lactone and ester represented by general formula (2) which can be obtained according to this invention include methyl acetate, ethyl acetate, isopropyl acetate, t-butyl acetate, n-propyl acetate, ethyl propionate, n-butyl acetate, n-propyl propionate, ethyl butyrate, pentyl acetate, butyl propionate, ethyl valerate, n-propyl butyrate, t-butyl 4-pentenoate, t-butyl chloroacetate, t-butyl methoxyacetate, t-butyl phenoxyacetate, t-butyl acetoxyacetate, γ-butyrolactone, δ-valerolactone, ε-caprolactone, 7-heptanolactone, 8-octanolactone, 12-dodecanolactone, 4-methyl-4-butanolactone, 4-octyl-4-butanolactone, 5-methyl-5-pentanolactone, 4-methyl-5-pentanolactone, 5-hexyl-5-pentanolactone, 5-undecyl-5-pentanolactone, 2,5-dimethyl-5-pentanolactone, 6-methyl-6-hexanolactone, 5-methyl-6-hexanolactone, 4-methyl-6-hexanolactone, 4-t-butyl-6-hexanolactone, 4-phenyl-6-hexanolactone, 6-allyl-6-hexanolactone, 6-chloro-6-hexanolactone, 4-methoxy-6-hexanolactone, 4-phenoxy-6-hexanolactone, 4-acetoxy-6-hexanolactone, benzyl acetate, phenyl acetate, p-tolyl acetate, p-chlorophenyl acetate, p-methoxyphenyl acetate, m-methoxyphenyl acetate, o-methoxyphenyl acetate, p-phenoxyphenyl acetate, p-acetoxyphenyl acetate, phenyl propionate, ethyl benzoate, p-methoxyphenyl propionate, 4'-methylbenzyl acetate, 4'-chlorobenzyl acetate, 4'-methoxybenzyl acetate, 4'-phenoxybenzyl acetate, 4'-acetoxybenzyl acetate, phenyl benzoate, 3α-acetoxy-D-homo-17a-oxaandrostan-17-one, 3β-acetoxy-D-homo-17a-oxaandrostan-17-one, 3α-benzoyloxy-D-homo-17a-oxaandrostan-17-one and the like. If the process of the present invention is carried out in the presence of a catalyst, Fe 2 O 3 is used as catalyst. The catalyst supported on heteropolyacids, silica gel, polymers and the like is also usable. Although the amount of the catalyst is not critical, it is usually used in an amount of 0.01-120% by mole, preferably 0.1-10% by mole, based on the starting ketone. The aldehydes which are used in this invention are benzaldehyde, p-chlorobenzaldehyde, m-chlorobenzaldehyde, p-tolualdehyde and p-anisaldehyde. Although the amount of the aldehyde is not critical, it is usually used in an amount of 1-30 moles, preferably 1-10 moles, per mole of the ketone. The solvents which are used are aromatic hydrocarbons such as benzene, toluene, xylene, monochlorobenzene, dichlorobenzene and the like. The oxygen used in this invention is not limited to oxygen itself, but air is also usable as an oxygen. Although the method for feeding the oxygen is not critical, a method of blowing oxygen, a method of carrying out the reaction in an atmosphere of oxygen, etc. can be referred to as examples of the method. The oxygen may be either an oxygen of ordinary pressure or an oxygen of elevated pressure. The reaction temperature is usually in the range of 0°C to the reflux temperature of reaction mixture. Preferably, it is in the range of 20°C to 80°C. The reaction time is not critical particularly, and the time when the formation of the objective lactone or ester has reached a ceiling value may be taken as an end point. It is usually in the range of one hour to one week. According to this invention, the used aldehyde is converted to the corresponding carboxylic acid which can easily be separated from the formed objective product. After completion of the reaction, the catalyst is recovered, for example, by filtration and the filtrate is washed with an aqueous solution of sodium hydrogen sulfite and an aqueous solution of sodium hydrogen carbonate and subsequently it is concentrated and, if desired, subjected to rectification or the like, whereby the objective lactone or ester can be obtained. According to this invention, a lactone or an ester can be obtained from a ketone and oxygen in the presence of an aldehyde without using catalyst or by using the readily available and recoverable Fe 3 O 3 . Thus, the process of this invention is quite excellent industrially. Next, this invention will be explained in more detail with reference to the following examples. This invention is by no means limited by these examples. Example 1 A mixture of 168 mg of cyclpentanone, 637 mg of benzaldehyde and 12 ml of benzene was vigorously stirred under an oxygen atmosphere at 25°C for 48 hours. Analysis of the reaction mixture by gas chromatography (GC) showed that δ-valerolactone had been formed in 92% yield. Example 2 A mixture of 196 mg of cyclohexanone, 637 mg of benzaldehyde and 12 ml of benzene was vigorously stirred under an oxygen atmosphere at 25°C for 48 hours. Analysis of the reaction mixture by GC showed that ε-caprolactone had been formed in 97% yield. Example 3 A mixture of 224 mg of 2-methylcyclohexanone, 637 mg of benzaldehyde and 12 ml of benzene was vigorously stirred under an oxygen atmosphere at 25°C for 48 hours. Analysis of the reaction mixture by GC showed that 6-methyl-6-hexanolactone had been formed in 95% yield. Example 4 A mixture of 300 mg of 4'-methoxyacetophenone, 637 mg of benzaldehyde and 12 ml of benzene was vigorously stirred under an oxygen atmosphere at 25°C for 48 hours. Analysis of the reaction mixture by GC showed that p-methoxyphenyl acetate had been formed in 94% yield. Reference Example 1 A mixture of 309 mg of 4-t-butylcyclohexanone, 258 mg of pivalaldehyde and 12 ml of dichloromethane was vigorously stirred under an oxygen atmosphere at 25°C for 48 hours. Analysis of the reaction mixture by GC showed that 4-t-butyl-6-hexanolactone had been formed in 90% yield. Reference Examples 2-6 Mixtures of 168 mg of cyclopentanone, 1% by mole, based on the cyclopentanone, of a catalyst (varied) shown in Table 1, 849 mg of benzaldehyde and 12 ml of dichloromethane were vigorously stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 1. the products were quantitatively analyzed by the GC-IS (internal standard) method, and their structures were identified by the GC-MS (mass pectrum) method. Example No. Catalyst Conversion (%) Yield of δ-valerolactone 2 Fe 14 9 (61) 3 FeSO 4 ·7H 2 O 77 41 (53) 4 Fe 2 O 3 76 43 (56) 5 5% Ru-C 35 26 (75) 6 RuO 2 51 33 (65) Reference Examples 7-12 Mixtures of 168 mg of cyclopentanone, 3.2 mg of Fe 2 O 3 , 4 equivalents, based on the cyclopentanone, of an aldehyde (varied) shown in Table 2 and 12 ml of dichloromethane were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 2. Reference Example No. Aldehyde Conversion (%) Yield of δ-valerolactone (%) 7 Acetaldehyde 37 9 (23) 8 Heptanal - 7 ( -) 9 2-Methylpropanal 12 4 (35) 10 Cyclohexanecarboxaldehyde 12 11 (93) 11 Isovaleraldehyde 26 20 (80) 12 m-Chlorobenzaldehyde 11 9 (81) Example 5 and Reference Examples 13-17 Mixtures of 168 mg of cyclopentanone, 3.2 mg of Fe 2 O 3 , 3 equivalents, based on the cyclopentanone, of an aldehyde (varied) shown in Table 3 and 12 ml of benzene were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 3. Example No. Aldehyde Conversion (%) Yield of δ-valerolactone (%) 5 Benzaldehyde 83 81 (98) Ref. Ex. 13 Acetaldehyde 4 4 (100) Ref. Ex. 14 Propionaldehyde 40 40 (100) Ref. Ex. 15 Heptanal 53 53 (100) Ref. Ex. 16 2-Methylpropanal 41 41 (100) Ref. Ex. 17 Pivalaldehyde 34 34 (100) Example 6 and Reference Examples 18-19 Mixtures of 168 mg of cyclopentanone, 3.2 mg of Fe 2 O 3 , 849 mg of benzaldehyde and 12 ml of a solvent (varies) shown in Table 4 were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 4. Example No. Solvent Conversion (%) Yield of δ-valerolactone (%) 6 Toluene 83 80 (96) Ref. Ex. 18 Ethyl acetate 49 47 (96) Ref. Ex. 19 Acetonitrile 25 23 (91) Examples 7-9 Mixtures of 168 mg of cyclopentanone, 3.2 mg of Fe 2 O 3 , a varied amount (shown in Table 5) of benzaldehyde and 12 ml of benzene were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 5. Example No. Amount of benzaldehyde used (equivalents based on cyclopentanone) Conversion (%) Yield of δ-valerolactone (%) 7 1 28 29 (101) 8 2 41 40 (98) 9 3 83 81 (98) Examples 10-13 Mixtures of 168 mg of cyclopentanone, a varied amount (shown in Table 6) of Fe 2 O 3 , 637 mg of benzaldehyde and 12 ml of benzene were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 6. Example No. Amount of Fe 2 O 3 (equivalent based on cyclopentanone) Conversion (%) Yield of δ-valerolactone (%) Turn-over number 10 0.001 67 64 (94) 635 11 0.005 58 54 (93) 108 12 0.05 86 80 (93) 16 13 0.10 94 85 (90) 8.5 Examples 14-25 Mixtures of 2 millimoles of a ketone (varied) shown in Table 7, 3.2 mg of Fe 2 O 3 , 637 mg of benzaldehyde and 12 ml of benzene were stirred under an oxygen atmosphere at 25°C for 17 hours. Analysis of the reaction mixtures by GC gave the results shown in Table 7. The products were quantitatively analyzed by the GC-IS method, and their structures were identified by GC-MS. In isolating the products, each of the reaction mixtures was washed with a saturated aqueous solution of sodium hydrogen carbonate and dried with sodium sulfate, the organic layer was concentrated, and the residue thus obtained was purified by silica gel column chromatography or preparative thin layer chromatography. Example No. Ketone Conversion (%) Product Yield (%) 14 Cyclobutanone 85 γ-Butyrolactone 84(99)[81] 15 Cyclohexanone 97 ε-Caprolactone 95(98)[92] 16 Cycloheptanone 11 7-Heptanolactone 11(100) 17 2-Methylcyclohexanone 83 6-Methyl-6-hexanolactone 80(97)[78] 18 4-Methylcyclohexanone 97 4-Methyl-6-hexanolactone 97(100)[93] 19 2-Heptanone 5 Pentyl acetate 5(100) 20 Pinacolone 40 t-Butyl acetate 40(100) 21 4'-Methoxyacetophenone 80 p-Methoxyphenyl acetate 80(100)[77] 22 Acetophenone 5 Phenyl acetate 5(100) 23 Propiophenone 8 Phenyl propionate 6(80) Ethyl benzoate 2(20) 2(20) 24 2-Allylcyclohexanone - 6-Allyl-6-hexanolactone [63] 25 3β-Acetoxyandrostan-17-one - 3β-Acetoxy-D-homo-17-a-oxaandrostan-17-one [56]

Claims: A process for producing a lactone or an ester represented by the following general formula (2): wherein R 1 and R 2 , identical or different, each represents (C 1 -C 20 ) alkyl group; alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy or acyloxy; phenyl group; or phenyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; phenylalkyl group; or phenylalkyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; provided that when R 1 and R 2 , identical or different, each represents unsubstituted alkyl group or alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy, acyloxy or phenyl, the respective alkyl parts of R 1 and R 2 may be conjunct to each other; which comprises reacting a ketone represented by the following general formula (1): wherein R 1 and R 2 are as defined above, with oxygen in the presence of an aldehyde selected from benzaldehyde, p-chlorobenzaldehyde, m-chlorobenzaldehyde, tolualdehyde and p-anisaldehyde and, as a solvent, an aromatic hydrocarbon. A process for producing a lactone or an ester represented by the following general formula (2): wherein R 1 and R 2 , identical or different, each represents (C 1 -C 20 ) alkyl group; alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy or acyloxy; phenyl group; or phenyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; phenylalkyl group; or phenylalkyl group substituted with alkyl, halogen, alkoxy, phenoxy or acyloxy; provided that when R 1 and R 2 , identical or different, each represents unsubstituted alkyl group or alkyl group substituted with a terminal alkenyl, halogen, alkoxy, phenoxy, acyloxy or phenyl, the respective alkyl parts of R 1 and R 2 may be conjunct to each other; which comprises reacting a ketone represented by the following general formula (1): wherein R 1 and R 2 are as defined above, with oxygen in the presence of an aldehyde selected from benzaldehyde, p-chlorobenzaldehyde, m-chlorobenzaldehyde, tolualdehyde and p-anisaldehyde, aromatic hydrocarbon as a solvent and ferric oxide. A process according to Claim 2, wherein the catalyst is used in an amount of 0.01 to 120% by mole based on the starting ketone. A process according to any of Claims 1 to 3, wherein the aldehyde is used in an amount of 1 to 30 moles per mole of the ketone. A process according to any of Claims 1 to 4, wherein the oxygen is oxygen itself or air. A process according to any of Claims 1 to 5, wherein the reaction is carried out at a temperature of 0°C to the reflux temperature of the reaction mixture. A process according to any of Claims 1 to 6, wherein the reaction is carried out for one hour to one week. A process according to any of claims 1 to 7, wherein the aromatic hydrocarbon is benzene, toluene, xylene, monochlorbenzene or dichlorbenzene. A process according to any of claims 1 to 8, wherein the aldehyde is benzaldehyde.

Inventors: MURAHASHI SHUN-ICHI, ODA YOSHIAKI, MURAHASHI, SHUN-ICHI, ODA, YOSHIAKI
Applicants: SUMITOMO CHEMICAL CO, SUMITOMO CHEMICAL COMPANY LIMITED
Application year: 1992
Main classification: C07D309
IPC codes: C07C67, C07B41, C07D315, C07J73