CHLOROALKYLATION OF AROMATIC COMPOUNDS

Abstract: The co-formation of diarylalkane by-product in the chloroalkylation of an aromatic compound with an aldehyde is minimized by conducting the reaction in a continuous manner in a concentration with agitation and in the presence of both hydrogen sulfate and hydrogen chloride.

Description: CHLOROALKYLATION OF AROMATIC COMPOUNDS Field of the Invention This invention relates to a process for chloroalkylating aromatic compounds to form 1-chloro-l- arylalkanes. Background As disclosed in March, Advanced Organic Chemistry. Second Edition, McGraw-Hill, New York, 1977, pp. 501-502; Olah, Friedel-Crafts and Related Reactions. Volume 2, Interscience Publishers, New York, 1963-1964, pp. 659-784; U. S. Patent 2,516,971 (Galigzenstein et al.) ; Canadian Patent 1,135,268 (Harris); and the references cited therein, it is known that aromatic compounds can be haloalkylated by reacting them with a hydrogen halide and an appropriate aldehyde, or with an α-halo-alky1 ether or an α-haloalkyl alkyl ether, in the presence of a Lewis acid or a proton acid as a catalyst, most commonly in the presence of zinc chloride. The haloalkylations utilizing formaldehyde or a formaldehyde-derived ether have been successfully employed in providing fairly high yields of 1-halo-l-arylalkanes. Reasonably high yields of 1-halo-l-arylalkanes have sometimes also been obtained from haloalkylations utilizing higher aldehydes or ethers derived from them. However, it has frequently not been found possible to provide commercially acceptable yields of 1-halo-l-arylalkanes from higher aldehydes and ethers, especially when the aromatic compound has been one of the less reactive ones, such as a monoalkylaromatic hydrocarbon. There has been too much co- formation of diarylalkane by-product. - l - It would be desirable to find a way of increasin the 1-halo-l-arylalkane yields obtainable from such processe to provide a more economical method of preparing, the 1-halo 1- (4-alkyl-phenyl) alkanes used in known processes, such a those of U. S. Patent 4,536,595 (Gardano et al . ) , Canadia Patent 1,197,254 (Francalanci et al. ) , British Paten 1,560,082 (Dynamit Nobel) , Czechoslovakian Certificate o Authorship 219,752 (Palecek et al. ) , and Japanese Kokai 47 39050 (Miyatake et al . ) and 51-111536 (Tokutake) . Definitions As used herein, alkyl means straight or branche chain alkyl having 1 to 20 carbon atoms and includes, fo example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl secondary butyl, tertiary butyl, pentyl, isopentyl, neopentyl hexyl, heptyl, octyl, 1-ethylhexyl, 1, 1, 3, 3-tetramethylbutyl nonyl decyl, dodecyl, tetradecyl, hexadecyl, octadecyl an eicosyl; substituted phenyl and substituted naphthyl mean phenyl or naphthyl substituted by at least one substituen selected from the group consisting of halogen (chlorine bromine, fluorine or iodine), amino, nitro, hydroxy, alkyl alkoxy which means straight or branched chain alkoxy having to 10 carbon atoms, and includes, for example, methoxy ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, secondar butoxy, tertiary butoxy, pentyloxy, isopentyloxy, hexyloxy heptyloxy, octyloxy, nonyloxy and decyloxy, haloalkyl whic means straight or alkyl having 1 to 8 carbon atoms which i substituted by at least one halogen, and includes, fo example, chloromethyl, bromomethyl, fluoromethyl, iodomethyl 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 3-chloropropyl, 3 bromopropyl, 3-fluoropropyl, 4-chlorobutyl, 4-fluorobutyl dichloromethyl, dibromomethyl, difluoromethyl, diiodomethyl 2, 2-dichloroethyl, 2,2-dibromoethyl, 2,2-difluoroethyl, 3,3 dichloropropyl, 3,3-difluoropropyl, 4,4-dichlorobutyl, 4,4- difluorobutyl, trichloromethyl, trifluoro-methyl, 2,2,2- trifluoroethyl , 2 , 3 , 3-trifluoropropyl , 1,1,2,2- tetrafluoroethyl and 2,2,3,3-tetrafluoropropyl; phenylalkyl means that the alkyl moiety is straight or branched chain alkyl having 1 to 8 carbon atoms and includes, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl and 8-phenyloctyl; and substituted phenylalkyl means the above-mentioned phenylalkyl which is substituted by at least one substituent selected from the group consisting of halogen, amino, nitro, hydroxy, alkyl, alkoxy and haloalkyl on the phenyl nucleus. The Invention It has now been found that 1-chloro-l-arylalkanes can be continuously prepared with minimum co-formation of the diarylalkane by-product, even when the aromatic reactant is a monoalkyl-aromatic hydrocarbon, by adding one molar proportion of an aromatic compound having at least one free ring position to from about 0.1 to about 1.5 mol of an aldehyde with agitation at a temperature in the range of about -35°C to about 0°C and in the presence of at least one molar proportion of hydrogen chloride and about 2-15 molar proportions of hydrogen sulfate. The addition of the above-named components form a reaction mixture from which is removed a reaction effluent stream. This stream is comprised of unreacted starting materials (typically about 40% to about 60% of the starting material is not converted) , the desired aryl-substituted ethyl halide (also termed herein as a 1-halo-l-arylalkane) and higher molecular weight by-products such as dimers, trimers and the like. Typically, the by-product produced in greatest yield is the dimer, e.g., where benzene is used as the aromatic compound and acetaldehyde as the aldehyde in th presence of hydrogen chloride and hydrogen sulfate, the dime is l, 1-diphenylethane. It has been discovered that if the rate of additio of all of the components is adjusted to provide a mixture o the above-named components in the ranges indicated (and th removal of a quantity of the reaction mixture is hel substantially equal to the rate of addition of the reactants) then the amount of desired chloralkylated product is maximize while minimizing the quantity of higher molecular weight by products -- typically dimer. As such, when mixtures of th components are employed outside the ranges indicated, th yield of chloroalkylated product diminishes and the ratio o chloroalkylated product to dimer is seen to decrease. Withi the ranges noted, the yields and ratios reach a substantiall constant value. Thus, preferred ranges are about 0.1 to 1. mol of acetaldehyde per mol of the aromatic compound. Outsid of the range and preferred range disclosed, variability o yield and ratio during the course of reaction effluent strea removal occurs. Further, if the continuous removal of reactio effluent stream does not occur, i.e., a batch reaction, yield of product and ratio of product to by-product decreas dramatically. The aromatic compound employed in the practice o the invention may be a carbocyclic aromatic compound, e.g., a unsubstituted aromatic hydrocarbon, such as benzene naphthalene, anthracene, phenanthrene, etc.; polyalkylaromatic hydrocarbon such as xylene, pseudo-cumene mesitylene, etc.; and aromatic hydrocarbon bearing substituent such as halo, cyano, nitro, hydroxy, alkoxy phenoxy, alkylthio, etc. (e.g., the 2-, 3-, and 4- chloronitrobenzenes, the 2-, 3-, and 4-fluoronitrobenzenes, 4- chloronitrobiphenyl, 6-methoxynaphthalene, phenoxybenzene, etc.) ; or it may be a heterocyclic aromatic compound, such as a chlorocarbazole, 2-phenyl-l-isoindolinone, 6-fluoro-5- nitroquinoline, etc. However, because of the commercial i nterest in their haloalkylated products and the difficulty that has previously been encountered in preparing the desired 1-halo-l-arylalkanes, the preferred aromatic compounds are monoalkylaromatic hydrocarbons, such as substituted phenyl or substituted naphthyl illustrated by 1-methylnaphthalene, 2- methylnaphthalene, 2-methoxynaphthalene, and the various monoalkylbenzenes, e.g., the methyl-, ethyl, propyl-, isobutyl-, sec-butyl-, t-butyl-, isopentyl-, t-pentyl-, and hexylbenzenes. The most preferred aromatic compounds are the monoalkylbenzenes wherein the alkyl group contains 1-5 carbons. The aldehydes of use herein have the formula where R l f R 2 and R 3 are the same or different and are hydrogen, alkyl, phenylalkyl or substituted phenylalkyl. Preferably, R x is alkyl having 1 to 10 linear or branched carbon atoms and R 2 and R 3 are the same as R x or are hydrogen. Most preferably, R x has 1 to 6 carbon atoms and R 2 and R 3 are hydrogen. Particularly preferred is where R x is alkyl of 1 to 3 carbon atoms. Acetaldehyde is a very useful reactant in the process of the present invention. The amount of aldehyde employed in the chloroalkylation reaction may be the stoichiometric amount, i.e., the amount which provides one R α group per molecule o aromatic hydrocarbon. In some cases, less than this amoun may be employed. However, it is generally preferred to emplo an amount that provides at least one R x group per molecule o aromatic compounds. Most preferred is about one mole of suc aldehyde per mole of haloalkylated product. There does no appear to be any maximum to the amount of aldehyde that may b used other than the maximum that economics permit. As in known processes, the chloroalkylation i conducted in the presence of an acid catalyst, preferabl hydrogen sulfate. In order to avoid the presence of too muc water in the reaction mixture, as well as to take advantage o commercially-available materials, the hydrogen sulfate i generally introduced in the form of 88-98% sulfuric acid. Th amount employed is generally such as to provide at least abou one mol, preferably at least about 2-6 moles, per mol o aromatic compound; and it ordinarily should not exceed abou 15 moles per mol of aromatic compound. It should be note that oleum may be used and directly added to the reactio mixture. It combines with the water produced in the reactio to yield sulfuric acid at the desired concentration. The amount of hydrogen chloride used in the reactio is usually at least about one equivalent, based on the amoun of aromatic compound; and it is generally introduced b bubbling it through the reaction mixture or by pressurizin the reaction vessel with it. Since improved yields of 1-chloro-l-arylalkane ar not obtained without it, the use of the hydrogen chloride i critical. The reaction is usually conducted at a reactio temperature in the range of about -35°C to about 0°C, preferably about -35°C to about -15°C, most preferably about - 30°C to about -20°C, in order to achieve the maximum advantages of the invention. The higher temperatures generally favor higher conversions, while the lower temperatures are apt to favor higher chloroalkylation product/diarylalkane ratios. The manner of combining the ingredients does appear to be somewhat important. For example, (1) the aldehyde may be dissolved in the aromatic compound and added to the catalyst while bubbling hydrogen chloride through the reaction mixture, or (2) the pure or crude aldehyde, the aromatic compound, and the catalyst may be combined in either fashion in a reaction vessel which is pressurized with the hydrogen chloride, etc. However, the best addition method is to add all reactants to a well-mixed stream of reaction mixture. The invention is useful as an alternative method of preparing 1-chloro-l-arylalkanes from aromatic compounds that are known to be capable of providing high yields of such products by known chloroalkylation techniques. However, it is particularly advantageous as a method of preparing 1-chloro-l- arylalkanes from the less reactive aromatic hydrocarbons, such as monoalkyl-benzenes, that have not previously been found to be capable of providing high yields of such products by chloroalkylation processes other than chloromethylations. It should be noted that the process of the present invention is most preferably operated in a continuous, stirred reaction. Disadvantageously, when the process is performed in a continuous plug flow reaction rather than observing improved yields of haloalkylated product, depressed yields are obtained, closely paralleling semi-batch systems. As is known, the products obtained by the proces are useful as internal standards, intermediates for th preparation of monomers, detergents, pharmaceuticals, etc When they are used as chemical intermediates, they may b subjected to the same reactions as have previously been use to convert them to desired products. For example, the 1 chloro-1-phenylethanes can be dehydrohalogenated in any know manner to provide styrenes which can then be polymerized b known techniques. A particularly interesting application of the 1 chloro-1- (4-alkylphenyl)ethanes which are prepared in preferred embodiment of the invention is as intermediates fo the preparation of ibuprofen and related pharmaceuticals When they are used in such applications, they may be converte to the desired products in any suitable manner. For example they may be reacted with carbon monoxide in the presence of carbonylation catalyst and then acidified to the correspondin propionic acids as in Gardano et al. , Francalanci et al. , o Dynamit Nobel; or they may be cyanated and then acidified t the corresponding propionic acids as in Palecek et al. o Tokutake. Another useful synthesis involves reacting th compounds with magnesium, carbonating the resultant Grignar reagents with carbon dioxide, and acidifying the carbonate product to the propionic acid as in Miyatake et al. The following example is given to illustrate th invention and is not intended as a limitation thereof. EXAMPLE 1 (COMPARATIVE) Semi-Batch Operating Mode 1 Sulfuric acid and initial isobutylbenzene (IBB) feed, i the amounts shown in Table I, are charged to the reactor 2 These materials are circulated in the reactor pump-aroun loop until they are cooled to the appropriate temperature, while continuously being sparged with hydrogen chloride. Acetaldehyde (AA) and the rest of the isobutylbenzene feed, in the amounts shown in the Table I are charged to the reactor in the time shown in Table I as feed time. The mixture in the reactor is held at the desired temperature for the time shown in Table I to complete the reaction. Reactor pressure is held at 5 psig by venting excess HC1 and/or inerts. Periodically samples are taken from the reactor and analyzed to determine the extent of the reaction. All runs are made with sulfuric acid that had a starting concentration of 93% to 94.5%. Acetaldehyde and Sulfuric Acid mole ratios shown in Table I are based on total moles of IBB charged. Table I % Conver- Example IBB Charged (Moles! Reactant Mole Ratios Reactor Feed Total Rxn sion Yield CEBB/DB Rxn Feed Prefeed AA H2S04 Pressure Temp (C) Time (min) Time (min) IBB CEBB DBPE Ratio (psig) M 29.8 29.8 1.22 2.55 2.5 -25 to -20 60 60 26 56 25 4.5 150 38 62 25 4.9 1-2 24.2 24.2 1.22 4.00 5.0 -22 to -21 87 87 64 31 61 1.0 240 80 34 59 1.2 1-3 32.4 32.6 1.20 4.03 5.0 -26 to -13 162 158 72 20 73 0.6 205 85 20 75 0.5 265 93 17 77 0.5 1-4 28.1 29.8 1.22 2.75 5.0 -20 to -15 71 37 25 55 25 4.5 80 29 61 21 5.8 140 34 63 22 5.7 190 39 66 22 5.8 255 44 65 23 5.6 1-5 25.9 29.8 1.22 2.88 5 -25 to -14 105 65 27 56 26 4.4 110 29 59 24 5.0 170 32 61 24 5.1 240 36 62 24 5.1 290 39 62 25 4.9 1-6 29.2 29.8 1.10 2.73 5 -26 to -22 178 70 21.5 50.4 26.3 3.8 140 27.7 59.5 22.5 5.3 195 27.9 60.6 21.5 5.6 255 32.2 62.7 21.7 5.8 315 36.4 63.2 23.1 5.5 375 37.4 60.1 26.5 4.5 1-7 48.43 29.8 1.10 2.80 -25to -17 135 18 11.2 13.7 41.8 0.7 43 20.7 37.3 38.6 1.9 78 30.9 44.4 39.5 2.2 143 36.7 43.3 43.1 2.0 198 43.6 42.5 46.0 1.8 238 48.9 40.7 49.0 1.7 1-8 16.6 29.8 0.64 4.42 5 -25 to -17 108 13 8.7 9.1 33.5 0.5 28 9.7 21.5 27.1 1.6 58 11.0 33.3 21.3 3.1 108 11.3 37.2 18.6 4.0 1-9 31.3 52.2 1.10 2.50 -29 to -21 120 15 7.1 13.7 16.2 1.7 30 9.6 31.6 16.5 3.8 60 13.5 46.5 16.4 5.7 105 15.6 51.4 16.5 6.2 135 16.9 49.8 18.7 5.3 195 17.8 52.7 19.2 5.5 255 18.9 53.2 20.3 5.2 300 20.1 54.4 20.8 5.2 1-10 83.8 1.08 2.5 -27 to -22 120 15 5.3 8.0 0.0 30 8.1 31.1 7.3 8.5 60 13.1 53.4 8.4 12.7 90 17.5 60.6 10.8 11.2 130 22.0 67.3 9.9 13.6 205 27.4 69.6 12.2 11.5 245 30.0 70.9 12.4 11.4 305 34.6 71.1 14.4 9.8 1-1 1 92.8 1.25 2.5 -27 to -21 135 15 6.2 7.8 11.0 1.4 30 8.1 18.7 19.6 1.9 60 11.9 33.5 24.5 2.7 90 17.0 44.8 35.9 3.5 120 20.8 49.7 26.2 3.8 150 25.1 54.1 26.0 4.2 210 30.7 57.7 26.0 4.4 270 35.9 58.6 27.5 4.3 315 40.5 59.5 18.1 4.2 CEBB is 1 -chloro-1 -(4-isobutylphenyl)et ane DBPE is 1 ,1 -bis(4-isobιrtylphenyl)et ane All CEBB and DBPE yields are based on the amount of IBB converted. DBPE yields are adjusted to account for 2 moles of IBB per mole of DBPE. EXAMPLE 2 Continuous Operating Mode Sulfuric acid, isobutylbenzene, and acetaldehyde in the amounts shown in Table II as well as excess hydrogen chloride are continuously charged to the reactor while maintaining the reactor temperature in the desired range. Concurrently with the feed of reactants as described above, a portion of the mixture in the reactor is continuously removed from the reactor in such an amount to hold the total volume of material in the reactor constant. The feed rates and product removal rates are adjusted as required to obtain the residence times shown in Table II. Periodically samples are taken from the reactor and analyzed to determine the extent of the reaction. All runs are made with sulfuric acid that had a starting concentration of 93% to 94.5%. Acetaldehyde and Sulfuric Acid mole ratios shown in Table II are based on total moles of IBB charged. Table II Example Reactant Mole Ratios Reactor Residence Sample % Conv % Yield CEBB/DBPE IBB AA H2S04 Pressure Temp (C) Time (m ) Time (mm) IBB CEBB DBPE Ratio 2-1 1.00 1.20 2.53 5.0 -25 to -21 120 58 14.1 67.2 30.6 4.4 148 15.8 74.4 23.3 6.4 208 18.1 76.3 21.3 7.2 268 21.1 77.6 20.0 7.8 333 23.8 78.7 18.9 8.3 388 26.6 79.4 18.4 8.6 448 28.8 79.0 18.8 8.4 503 31.7 79.5 18.3 8.7 2-2 1.00 1.49 3.59 5.0 -20 to -16 120 65 14.5 68.2 29.6 4.6 120 16.3 74.3 23.5 6.3 180 21.3 77.9 19.9 7.8 240 25.9 79.1 18.6 8.5 300 32.0 80.2 17.6 9.1 360 34.0 80.3 17.6 9.2 420 37.5 80.2 17.6 9.1 465 40.8 79.7 18.0 8.8 2-3 1.00 1.57 3.26 5.0 -25 120 60 41.5 48.3 50.3 1.9 180 36.0 65.7 32.4 4.1 240 37.8 69.6 28.5 4.9 300 35.8 72.8 25.2 5.8 360 33.1 74.2 23.7 6.3 420 29.6 75.7 22.3 6.8 480 26.6 77.1 20.8 7.4 -25 240 545 24.6 77.4 20.5 7.6 600 21.6 77.4 20.4 7.6 655 30.9 80.0 17.9 9.0 725 33.4 80.8 17.0 9.5 780 35.8 81.5 16.3 10.0 835 36.4 81.3 16.5 9.9 895 37.1 81.4 16.4 10.0 950 38.1 81.1 16.7 9.7 1,010 42.6 81.2 16.6 9.8 -20 240 1,070 46.5 80.9 16.9 9.5 1,130 49.5 80.5 17.4 9.3 1.190 51.6 79.8 18.0 8.8 1,250 52.9 79.2 18.7 8.5 1,310 54.0 78.6 19.3 8.1 1,370 55.3 77.9 20.0 7.8 1,430 56.0 77.4 20.6 7.5 1,490 66.6 76.7 21.3 7.2 1,550 57.8 75.8 22.2 6.8 1,610 55.9 74.4 23.7 6.3 CEBB is 1-chloro-1-(4-isobutylphenyt)ethane DBPE is 1,1-bιs(4-isobutytphenyl)ethane All CEBB and DBPE yields are based on the amount of IBB converted. DBPE yields are adjusted to account for 2 moles of IBB per mole of DBPE. It is obvious that many variations may be made in the products and processes set forth above without departing from the spirit and scope of this invention.

Claims: WHAT IS CLAIMED IS: 1. A process for producing an aryl-substituted ethylhalide having the formula where X is halo; Ar is phenyl, substituted phenyl, naphthyl or substituted naphthyl; R lf R 2 , and R 3 are the same or different and are hydrogen, alkyl, phenylalkyl or substituted phenylalkyl, comprising a) continuously adding with agitation an aromatic compound having at least one free ring position to from about 0.1 to about 2.0 mol of an aldehyde of the formula per mol of said aromatic compound in the presence of from about 0.1 to about 2.0 moles of a halo acid per mol of said aromatic compound and about 2-15 moles of hydrogen sulfate per mol of said aromatic thereby forming a reaction mixture; b) continuously removing from said reaction mixture a reaction effluent stream at a rate substantially equal to the sum of the rates of addition of said aromatic compound; said aldehyde; said haloacid; and said hydrogen sulfate; and c) separating from said reaction effluent stream sai aryl-substituted ethyl halide, said separation bein carried out when the ratio of the concentration o said aryl-substituted ethyl halide to th concentration of the by-products of said process an the concentration of aryl-substituted ethyl halid becomes constant. 2. The process of Claim 1 wherein the aromatic compoun is monoalkylbenzene. 3. The process of Claim 2 wherein the monoalkylbenzen is one in which the alkyl substituent conta'.^s 1-5 carbons. 4. The process of Claim 3 wherein the monoalkylbenzen is isobutylbenzene. 5. The process of Claim 1 wherein the aldehyde is one i which R x is an alkyl group containing 1-10 carbons and R 2 an R 3 are the same as R x or hydrogen. 6. The process of Claim 5 wherein the aldehyde is one i which R x is an alkyl group containing 1-6 carbons and R 2 an R 3 are hydrogen. 7. The process of Claim 6 wherein the aldehyde is one i which Ri is alkyl having 1 to 3 carbons. 8. The process of Claim 7 wherein R α is methyl. 9. The process of Claim 1 wherein the amount of abou one molecule of aldehyde is employed per mole of aryl substituted ethyl halide produced. 10. The process of Claim 1 wherein the reaction temperature is in the range of about -35°C to about -15°C. 11. The process of Claim 10 wherein the reaction temperature is in the range of about -30°C to about -20°C. 12. The process of Claim 1 wherein the amount of hydrogen sulfate is about 2-6 moles per mol of aromatic compound. 13. The process of Claim 1 wherein the hydrogen sulfate is introduced into the reaction mixture in the form of 88-98% sulfuric acid or in the form of oleum. 14. The process of Claim 1 wherein the reaction is conducted in the absence of more than about 15% by weight of water, based on the weight of the hydrogen sulfate. 15. The process of Claim 1 wherein the hydrogen chloride is introduced by bubbling it through the reaction mixture. 16. The process of Claim 1 wherein the hydrogen chloride is introduced by pressurizing the reaction vessel with it. 17. The process of Claim 1 wherein the hydrogen chloride is introduced as a liquid to the reaction vessel. 18. The process of Claim 1 wherein one molar proportion of isobutylbenzene is chloroethylated by reacting it with at least about 0.1 molar proportions of acetaldehyde at a temperature in the range of about -30°C to about -20°C in the presence of about 2-6 molar proportions of hydrogen sulfate per mole of aromatic compound with less than about 15% by weight of water, based on the weight of the hydrogen sulfate, while bubbling hydrogen chloride through the reaction mixture or pressurizing the reaction vessel with hydrogen chloride the hydrogen sulfate being introduced in the form of 88-98 sulfuric acid. 19. The process of Claim 1 wherein one molar proportio of isobutylbenzene is chloroethylated by reacting it with a least about two molar proportions of acetaldehyde at temperature in the range of about -30°C to about -20°C in th presence of about 2-6 molar proportions of hydrogen sulfat per mole of aromatic compound with less than about 15% b weight of water, based on the weight of the hydrogen sulfate while adding an aqueous solution of hydrogen chloride hydrogen sulfate being introduced in the form of 88-98 sulfuric acid.

Inventors: FOCHT GARY D, HERNDON R CARL JR, JONES KARL R, FOCHT, GARY, D., HERNDON, R., CARL, JR., JONES, KARL, R.
Applicants: ALBEMARLE CORP, ALBEMARLE CORPORATION
Application year: 1995
Main classification: C07C17
IPC codes: C07C17, C07C22