METHOD FOR OXIDIZING UNSATURATED AROMATIC COMPOUNDS

Abstract: This invention relates to a method for manufacturing aromatic compounds having the following formula (II) comprising the step of reacting an unsaturated aromatic compound having the following formula (I) with an aryl compound containing an iodosyl group or the salt thereof within a temperature range of from -50 to 200 o C:

Description: (1) Field of the Invention This invention relates to a novel method for oxidizing unsaturated aromatic compounds. There are many oxidized products useful as an intermediate material for various agricultural chemicals, pharmaceuticals and the like which are obtained by oxidizing unsaturated aromatic compounds. For example, an arylacetone such as 4-hydroxy-3-methoxyphenylacetone, 3, 4-dimethoxyphenylacetone, 3, 4-dihydroxyphenylacetone or the like is a compound used as an intermediate for manufacturing L-α-methyldopa which is employed as an antihypertensive agent. Furthermore, 2-(4-isobutylphenyl) propionaldehyde is utilized as an intermediate for 2-(4-isobutylphenyl) propionic acid (trade name: ibuprofen) having antiphologistic, antipyretic and lenitive activity, and (4-isobutylphenyl)acetaldehyde is an intermediate of (4-isobutylphenyl) acetic acid (trade name: ibufenac) having the same pharmacological effects as the former compound. (2) Description of the prior Art Among these useful compounds, arylacetones having high utility and for which various manufacturing methods have heretofore been proposed will be described hereinbelow as a specific example. There have been proposed the following typical methods for manufacturing arylacetones. 1) British Patent No. 1,119,612 discloses a method in which a peroxide such as peracetic acid or the like is reacted with 1-(3, 4-dimethoxyphenyl)propylene, and the resulting diol type product is treated with an acid compound such as zinc chloride to obtain 3, 4-dimethoxyphenylacetone. 2) French Patent No. 1,450,200 discloses a method in which 3, 4-dimethoxybenzaldehyde is reacted with α-chloropropionic acid ester in the presence of a strong base, and the reaction product is then treated with a strong acid to obtain 3, 4-dimethoxyphenylacetone. 3) Journal of American Chemical Society (JACS), 77, 700 (1955) describes a method in which 3, 4-dimethoxyphenylacetonitrile is reacted with sodium ethoxide in a solvent such as ethyl acetate to transform the former into an acetyl-compound, and then the acetyl-compound thus obtained is hydrolyzed to obtain 3, 4-dimethoxyphenylacetone. The above described method 1) involves such problems since the yield is low in the process of the treatment by the use of an acid compound and that special care is required for handling the the peroxide which is explosive. Furthermore, in the method 2), the raw materials 3, 4-dimethoxybenzaldehyde and α-chloropropionic acid ester are not easily available. The method 3) involves such problems that it is necessary to carry out the reaction in a system from which water has been strictly removed in case of using sodium ethoxide for preventing hydrolysis of the sodium ethoxide, that the yield is low in the hydrolysis step, and that the number of steps in the method becomes excessive as a whole if steps required for manufacturing the raw material 3, 4-dimethoxyphenylacetonitrile itself from an easily available chemical material are taken into consideration. As discussed above, it must be said that all the manufacturing methods 1), 2) and 3) are not satisfactory from industrial point of view. Fontecave, M. and Mansuy, D. J. Chem. Soc. Chem. Common. 1984, 879 and Mansuy, D. et Al. Tetrahedron 40 (1984), 2847 disclose the reaction of styrene and/or stilbene with iodosylbenzene to obtain the corresponding epoxy compounds as main products. By the reaction of styrene phenylacetaldehyde may be produced as a by-product in a yield of only up to 2 %. However, according to the methods disclosed in these references it is not possible to obtain the corresponding carbonyl compound as main product in high yields. 3. Object of the Invention An object of the present invention is to provide a method for manufacturing oxidized products of unsaturated aromatic compounds useful as intermediate materials for various agricultural chemicals, pharmaceuticals and the like from easily available and inexpensive raw materials in a high yield, further to provide also a method for manufacturing, for example, arylacetone from easily available raw materials in a high yield. 4. Summary of the Invention The present invention relates to a method for manufacturing aromatic compounds having the following formula (II) comprising the step of reacting an unsaturated aromatic compound having the following formula (I) with an aryl compound having at least one iodosyl group at a reaction temperature in the range of from -50 to 200°C wherein Ar₁ is an aryl group, each of R₁, R₂ and R₃ is a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms or an aryl group, and R₁, R₂ and R₃ may be the same or different groups, wherein the reaction is conducted with the iodosyl compound in the salt form. 5. Detailed Description of the Invention The method of the present invention is carried out by using an easily available unsaturated aromatic compound as a raw material, and reacting the same with an aryl compound having an iodosyl group in the salt form. The raw material of the present invention is an unsaturated aromatic compound having the following general formula (I) : wherein Ar₁ is an aryl group derived from an aromatic hydrocarbon such as a phenyl, naphthyl, biphenylyl group or the like and said aryl group may be substituted by one to three substituents selected from the group consisting of halogen atoms such as chlorine, fluorine, bromine, iodine, nitro group, amino group, a lower alkyl group such as methyl, ethyl group or the like, and a lower alkoxy group such as methoxy, ethoxy group or the like; and R 1, R₂ and R₃ are hydrogen atoms; lower alkyl groups each having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and the like; aryl groups such as phenyl, naphthyl, bisphenyl group and the like which may be substituted by one to three substituents selected from the group consisting of halogen atoms such as chlorine, fluorine, bromine, iodine, nitro group, amino group, and lower alkoxy groups such as methoxy, ethoxy and the like; further, R 1, R₂ or R₃ may form a ring structure with Ar 1; and R 1, R₂ and R₃ may also be identical with each other. Specific examples of the unsaturated aromatic compounds having the above described formula (I) include aryl ethylenes such as styrene, 4-methylstyrene, 3-methylstyrene, 2-methylstyrene, 4-ethylstyrene, 4-isopropylstyrene, 4-isobutylstyrene, 4-phenylstyrene, 4-chlorostyrene, 2-chlorostyrene, 3-chlorostyrene, 4-bromostyrene, 4-nitrostyrene, 4-methoxystyrene, 3-benzoylstyrene, 3-benzylstyrene, 6-methoxy-2-naphthylethylene and the like; 1-aryl propylenes such as 1-phenylpropylene, 1-(chlorophenyl)propylene, 1-(fluorophenyl)propylene, 1-(bromophenyl)propylene, 1-(nitrophenyl)propylene, 1-(dimethylaminophenyl)propylene, 1-(methylphenyl)propylene, 1-(dimethylphenyl) propylene, 1-(ethylphenyl)propylene, 1-(4-isobutylphenyl) propylene, 1-(3-trifluoromethylphenyl)propylene, 1-(methoxyphenyl)propylene, 1-(3, 4-dimethoxyphenyl)propylene, 1-(3-benzoylphenyl)propylene, 1-(6-methoxy-2-naphthyl)propylene, 1-biphenylylpropylene and the like; 2-aryl propylenes such as 2-phenylpropylene, 2-(chlorophenyl)propylene, 2-(fluorophenyl) propylene, 2-(4-bromophenyl)propylene, 2-(nitrophenyl)propylene, 2-(dimethylaminophenyl)propylene, 2-(methylphenyl)propylene, 2-(ethylphenyl)propylene, 2-(3-trifluoromethylphenyl)propylene, 2-(methoxyphenyl)propylene, 2-(3, 4-dimethoxyphenyl)propylene, 2-(ethoxyphenyl)propylene, 2-(3-phenoxyphenyl)propylene, 2-naphthylpropylene, 2-(6-methoxy-2-naphthyl)propylene, 2-benzoylphenylpropylene, 2-biphenylylpropylene and the like; 1-aryl-1-butenes such as 1-phenyl-1-butene, 1-(3-bromophenyl)-1-butene, 1-(4-chlorophenyl)-1-butene and the like; 2-aryl-1-butenes such as 2-phenyl-1-butene, 2-(4-methylphenyl)-1-butene and the like; 2-aryl-2-butenes such as 2-phenyl-2-butene, 2-(2-methylphenyl)2-butene, 2-(4-methylphenyl)-2-butene, 2-(4-isobutylphenyl)-2-butene and the like; 1-aryl-2-methylpropylenes such as 1-phenyl-2-methylpropylene, 1-(4-methylphenyl)-2-methylpropylene, 1-(4-chlorophenyl)-2-methylpropylene, 1-(3-bromophenyl)-2-methylpropylene, 1-(4-bromophenyl)-2-methylpropylene and the like; aryl pentenes; aryl hexenes; diarylethylenes such as 1, 1-diphenylethylene, 1, 1-bis(methylphenyl)ethylene, 1, 1-bis(chlorophenyl)ethylene, 1-phenyl-1-(4-methylphenyl)ethylene, 1-phenyl-1-(4-fluorophenyl)ethylene, 1-phenyl-1-(4-chlorophenyl) ethylene, 1-phenyl-1-(4-bromophenyl)ethylene, 1, 2-diphenylethylene and the like; or such compounds obtained by forming a ring structure from R 1, R₂ or R₃ in the aforesaid formula (I) with Ar₁ such as 1, 2-dihydronaphthalene, indene, and 1, 2-dihydroanthracene. According to the method of the present invention, the above-mentioned unsaturated aromatic compounds are oxidized to obtain the corresponding oxides. These products thus oxidized have the following general formula (II): wherein Ar 1, R 1, R₂ and R₃ have the same meaning as defined in the above formula (I), respectively. As is apparent from the comparison of the aforesaid formula (I) with the formula (II), according to the method of the present invention, the compounds having the formula (II) which are oxidized products are obtained seemingly in such a manner that the substituent Ar₁ in the formula (I) migrates to the carbon atom with R₂ and R 3, whilst a carbonyl group is introduced into the place Ar₁ has left. Specific examples of the oxidized products manufactured in accordance with the method of the present invention include, for example, aryl acetaldehydes, 2-aryl-propionaldehydes, aryl acetones, 2-aryl butylaldehydes, 1-aryl-2-butanones, 3-aryl-2-butanones, 2-aryl-2-methylpropionaldehydes, and diaryl ethanones which correspond to aryl ethylenes, 1-aryl propylenes, 2-aryl propylenes, 1-aryl-1-butenes, 2-aryl-1-butenes, 2-aryl-2-butenes, 1-aryl-2-methylpropylenes, and 1, 1-diaryl ethylenes, respectively. In the present invention, an aryl compound having at least one iodosyl group in the salt form is reacted with an unsaturated aromatic compound having said formula (I). The aryl compound having an iodosyl group in the salt form is represented by the following general formula (III): Ar₂ - I (X₂) (III) wherein Ar₂ is an aromatic hydrocarbon (III) residue such as phenyl, naphthyl, biphenylyl group and the like, and these aryl groups may be substituted by one or more lower alkyl groups such as methyl, ethyl, propyl and the like, lower alkoxy groups such as methoxy, ethoxy and the like, nitro group, carboxyl group and the like; and ion X is an acid residue. Said acid residue X is derived from inorganic or organic acids. Examples of the organic acid include carboxylic acids, for example, lower fatty acids such as acetic acid, propionic acid, butyric acid and the like, halogenated lower fatty acids such as chloroacetic acid, dichloroacetic acid, bromoacetic acid, trifluoroacetic acid and the like, aromatic carboxylic acids such as benzoic acid, methylbenzoic acid and the like, halogenated aromatic carboxylic acids such as bromobenzoic acid, chlorobenzoic acid and the like, nitrate aromatic carboxylic acids such as nitrobenzoic acid and the like, or the like carboxylic acids. Furthermore salts of acids such as nitric acid, sulfonic acid and the like may be used. Preferably, salts of carboxylic acids, nitric acid or sulfonic acid are employed. Specific examples of said salt of aryl compound include acetates such as iodosylbenzene diacetate, o-, m- or p-substituted iodosyltoluene diacetate, 2-iodosyl-m-xylene diacetate, 2-iodosyl-p-xylene diacetate, o-, m- or p-substituted iodosylchlorobenzene diacetate, o-, m- or p-substituted iodosylnitrobenzene diacetate, 4-iodosylethoxybenzene diacetate, 4-iodosylcyanobenzene diacetate, iodosylbiphenyl diacetate, α-iodosylnaphthalene diacetate and the like; haloacetates such as iodosylbenzene di(chloroactate), iodosylbenzene di(dichloroactate), iodosylbenzene di(trichloroactate), iodosylbenzene di(bromoactate), iodosylbenzene di(trifluoroactate) and the like; benzoates such as iodosylbenzene dibenzoate, 2-iodosyltoluene dibenzoate, 2-iodosylchlorobenzene dibenzoate, 2-iodosylnitrobenzene dibenzoate, iodosylmesitylene dibenzoate and the like; substituted benzoates such as iodosylbenzene di(4-chlorobenzoate), iodosylbenzene di(4-bromobenzoate), iodosylbenzene di(2, 4-dinitrobenzoate), iodosylbenzene di(4-methoxybenzoate), iodosylbenzene di(4-methylbenzoate) and the like; besides iodosylbenzene di(p-toluenesulfonate), iodosylbenzene dinitrate, 2-iodosylnitrobenzene dinitrate, iodosylbenzene dipropionate, iodosylbenzene dihexanoate and the like. According to the method of the present invention the salt of the aryl iodosyl compound may be also prepared from the aryl iodosyl compound, represented by the general formula IV wherein the symbols have the same meaning as aforementioned, in situ in the reaction zone: Ar₂ - I = O (IV) Furthermore, the compounds having an iodosyl group in the salt form according to the present invention may be high polymeric organic substances. More specifically, they may be a high polymeric organic substance to which has been added at least one compound containing an iodosyl group in the salt form. In a way, these substances are in such a form wherein an aryl group of the aryl compound having an iodosyl group in the salt form represented by the aforesaid formula (III) is linked with the backbone chain of a high polymeric organic substance. A specific aryl compound containing a aryl group which may be linked with a high polymeric organic backbone chain means a polymer or copolymer of styrene or a derivative monomer thereof. Into these organic high-molecular weight compounds, an iodosyl group is introduced by post-treating the polymer or copolymer of styrene or a derivative thereof, and then transforming the iodosyl group into a salt. Specifically, a method for introducing an iodosyl group by means of after-treatment can be effected in accordance with a method described, for example, in Angew. Makromol. Chem., 27 (431), 223 (1972) and a method for converting subsequently the iodosyl group introduced into a salt can be specifically effected in accordance with a method described, for example, in Die Makromolekulare Chemie, 153 - 162 (1972). It is required to use at least one equivalent of an aryl compound having an iodosyl group in the salt form with respect to the unsaturated aromatic compound used as raw material, and in general about one equivalent is sufficient for such unsaturated aromatic compound. Since there is no upper limit of the amount of aryl compound to be used, even if the amount exceeds one equivalent, no obstacle is observed. However, the use of an excessive amount of such aryl compound is merely uneconomical, so that it is not desirable. On the other hand, when the amount of aryl compound used is less than one equivalent, unreacted unsaturated aromatic compound remains in a ratio corresponding to such insufficient amount of the aryl compound so that it is undesirable. After the reaction of the present invention, the aryl compound having an iodosyl group in the salt form become aryl iodides which can be easily recovered by distillation or filtration from the reaction products. In the present invention, a catalyst may be used for the sake of accelerating the reaction, if necessary. As a reaction catalyst, a salt of transition metals such as cobalt, manganese, copper, iron and the like is used, and cobalt is preferably used. A transition metal having any oxidation number can be used in the present invention without any trouble, so far as the oxidation number of the transition metal is not zero. Said salts are, for example, salts of an organic acid such as acetic acid, butyric acid, naphthenic acid or the like; salts of an inorganic acid such as nitric acid, hydrochloric acid or the like; and complex salts such as acetylacetonato, triflate, octanoate and the like. Specific examples of such catalyst as described above include cobalt, manganese, copper, or iron acetates, nitrates, naphthenates; or complex salts such as acetylacetonato, triflate, octanoate and the like. The amount of catalyst to be used is suitable within a range of, for example, 0.01 - 20% by weight, and preferably 0.05 - 10% by weight with respect to the unsaturated aromatic compound used as raw material. In the case that the amount of the catalyst used is less than the lower limit of said range, the reaction does not proceed sufficiently, whilst even if the amount of the catalyst used is allowed to exceed the upper limit of said range, it does scarcely contribute to elevation of the rate of reaction, and the situation becomes rather worse because recovery of the catalyst comes to take much time so that it is not desirable. Furthermore, an acid may be allowed to exist in order to promote the reaction. Specifically, an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, sulfonic acid or the like is used. The reaction temperature ranges from -50 to 200°C, and preferably from 0 to 100°C. In case of a temperature of less than -50°C, since the temperature is too low, the reaction does not proceed, or the unsaturated aromatic compound used as raw material solidifies, so that it is undesirable. On the other hand, when the temperature exceeds 200°C, there is the possibility that the compound having an iodosyl group in the salt form is decomposed, and/or that by-products are produced as a result of polymerization and the like reaction of the unsaturated aromatic compound used as raw material. Thus, selectivity of the product to be manufactured decreases remarkably so that temperatures out of said range are undesirable. While the reaction time depends on the reaction condition such as the reaction temperature and the like, it is within a range of from 10 minutes to 10 hours, in usual. Since the reaction of the present invention is never affected by the pressure in the reaction system at the time of reaction, it may be suitably selected, but usually normal pressures are satisfactory. In the method of the present invention, although it is not necessarily required to use a solvent for the reaction, an inert solvent with respect to the reaction may be used in order to improve contact efficiency of the aryl compound having an iodosyl group in the salt form with an unsaturated aromatic compound. As such solvent as described above, for example, water, acetone, alcohols such as methanol, t-butyl alcohol and the like, glacial acetic acid, acetonitrile, isooctane, benzene, chloroform and the like are used, and they may be used either alone or in the form of a mixed solvent. The method of the present invention may be carried out, for example, as follows. A reaction vessel is charged with an unsaturated aromatic compound, an aryl compound having an iodosyl group in the salt form and a solvent, and the reaction is allowed to proceed under a prescribed condition, and in this case any order is not particularly determined for the addition of these components. After the reaction, the reaction mixture is extracted with an organic solvent such as benzene, ethyl acetate, chloroform or the like in accordance with a conventional procedure, and then the high-purity oxidized product of the unsaturated aromatic compound is easily obtained by either usual distillation or recrystallization of the resulting reaction mixture. As described above, when an unsaturated aromatic compound, the aromatic ring of which may have a substituent, is reacted with an aryl compound having an iodosyl group in the salt form in accordance with the present invention, an oxidized product of the unsaturated aromatic compound which is useful for an intermediate raw material of various agricultural chemicals, pharmaceuticals and the like can be manufactured in a high yield. Examples The present invention will be described further in conjunction with the following examples, but it is to be understood that the invention is not limited by only these examples in which the percentages are by weight when not otherwise specified. Example 1 A reaction vessel was charged with 2-phenylpropylene (3 mmol) as unsaturated aromatic compound being the raw material, iodosylbenzene diacetate (3 mmol) as a salt of an iodosyl compound and 30 ml of 60% aqueous acetic acid as a solvent, and the reaction was carried out under such condition of 25°C reaction temperature and 2 hour reaction time in nitrogen atmosphere. After completing the reaction, the reaction solution was poured to water, and then an oily matter was extracted with ether. After removing the ether by distillation, the degree of reaction of the raw material 2-phenylpropylene and the yield of phenylacetone being the product to be produced were 30% and 26%, respectively, as a result of a gas chromatograph analysis, and in this case iodobenzene being a by-product in the reaction was also observed. Furthermore, it was confirmed that the objective product phenylacetone obtained was identical with a standard sample as a result of NMR, IR and MASS analysis. Examples 2 - 8 Each reaction was carried out by using the starting material and the like enumerated in the following Table in accordance with the above described manner in Example 1, and the results are shown in the same Table. Example 9 A reaction was effected by employing cobalt acetate as the catalyst in glacial acetic acid in accordance with the reaction of Example 1. After the reaction, the resulting product was post-treated in accordance with the manner in Example 1. As a result of the same analysis, the degree of reaction and the yield were 100% and 44%, respectively. Examples 10 - 31 Each reaction was carried out by using the starting material and the like enumerated in the following Table in accordance with the above described manner in Example 9, and the results are shown in the same Table. Examples 32 - 40 Each reaction was carried out by using the catalyst or the reaction solvent enumerated in the following Table in accordance with the above described manner in Example 9, and the results are shown in the same Table. Example 41 A reaction vessel was charged with 2-phenylpropylene (3 mmol) as an unsaturated aromatic compound (raw material), modified polystyrene beads 15% of which having a unit having an iodosyl group (2.85 g), cobalt acetate (0.05 mmol) as a catalyst and 100 ml of glacial acetic acid as a solvent, and the reaction was carried out under such condition of 25°C reaction temperature and 2 hour reaction time in nitrogen atmosphere. After completing the reaction, the modified beads and the catalyst were filtered off, and then the filtrate was extracted with ether. After removing the ether by distillation, the degree of reaction of the raw material 2-phenylpropylene and the yield of phenylacetone being the product to be produced were 55% and 15%, respectively, as a result of a gas chromatograph analysis. Furthermore, it was confirmed that the objective product phenylacetone obtained was identical with a standard sample as a result of NMR, IR and MASS analysis. Example 42 A reaction vessel was charged with 2-(3, 4-dimethoxyphenyl)propylene (3 mmol) as an unsaturated aromatic compound (a raw material), modified polystyrene beads 25% of which having a unit in which acetic acid has been added to an iodosyl group (1.6 g) as a high-molecular weight aromatic compound, cobalt nitrate (0.05 mmol) as a catalyst and 100 ml of 60% aqueous acetic acid as a solvent, and the reaction was carried out under such condition of 25°C reaction temperature and 2 hour reaction time in nitrogen atmosphere. As a result of the post-treatment in accordance with the above described manner in Example 41, the degree of reaction and the yield were 43% and 12%, respectively.

Claims: A method for manufacturing aromatic compounds having the following formula (II) comprising the step of reacting an unsaturated aromatic compound having the following formula (I) with an aryl compound having at least one iodosyl group at a reaction temperature in the range of from -50 to 200°C wherein Ar₁ is an aryl group, each of R 1, R₂ and R₃ is a hydrogen atom, a lower alkyl group having 1 - 4 carbon atoms or an aryl group, and R 1, R₂ and R₃ may be the same or different groups, wherein the reaction is conducted with the iodozyl compound in the salt form. A method for manufacturing aromatic compounds as claimed in claim 1 wherein the aryl group Ar₁ in said unsaturated aromatic compound is an aromatic hydrocarbon residue in which 1 - 3 hydrogen atoms of the aromatic ring thereof are substituted by a substituent or substituents selected from the group consisting of halogen atom, nitro group, amino group, lower alkyl group and lower alkoxy group. A method for manufacturing aromatic compounds as claimed in claim 2 wherein said aromatic hydrocarbon residue is a phenyl group. A method for manufacturing aromatic compounds as claimed in any of the claims 1 to 3, wherein the salt of the aryl iodosyl compound is prepared from the aryl iodosyl compound in situ in the reaction zone. A method for manufacturing aromatic compounds as claimed in any of the claims 1 to 4, wherein a transition metal salt is used as a reaction catalyst. A method for manufacturing aromatic compounds as claimed in claim 5 wherein a metal of said transition metal salt is selected from the group consisting of cobalt, manganese, copper and iron. A method for manufacturing aromatic compounds as claimed in any of the claims 1 to 6, wherein said aryl compound having an iodosyl group or the salts thereof have either the following formula (III) or formula (IV), respectively; Ar₂ - I = O (IV) Ar₂ - I (X)₂ (III) in the above formulae, Ar₂ is aryl group, and ion X is acid residue. A method for manufacturing aromatic compounds as claimed in any of the claims 1 to 7, wherein said salt of an aryl compound having an iodosyl group is iodosyl benzene diacetate. A method for manufacturing aromatic compounds as claimed in any of the claims 1 to 7, wherein said aryl compound having an iodosyl group is a high molecular aromatic compound. A method for manufacturing aromatic compounds as claimed in claim 7, wherein said ion X is a carboxylic acid ion, nitric acid ion or sulfonic acid ion.

Inventors: IWAMOTO, KOUICHI, MATSUMURA, YASUO, SHIMIZU, ISOO
Applicants: NIPPON PETROCHEMICALS COMPANY, LIMITED
Application year: 1989
Main classification: C07C49
IPC codes: B01J23, C07B61, C07C45, C07C49, C07C47, C07C205, C07C57, C07C225, C07C201, C07C51, C07B41