DERIVATIVE OF BRENDANE AND PROCESS FOR PREPARING THE SAME

Abstract: According to the invention a derivative of brendane is provided. The derivative of brendane is represented by the general formula: wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group. The brendane derivative is prepared by reacting an alkenylnorbornene of the general formula: wherein R¹ to R³ each represent a hydrogen atom or a methyl group, with carbon monoxide and an alchol or water in the presence of a Group VIII metal compound of the periodic table as a catalyst.

Description: Field of the Invention; The present invention relates to derivatives of brendane and a process for preparing the same. More particularly, the present invention is directed to novel derivatives of brendane represented by the following general formula [I] and having utilities as medicines, perfumes and starting materials therefor. wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group. Prior Art ; Derivatives of tricyclic hydrocarbons are important as medicines, perfumes and starting materials therefor. However, they are prepared generally through extremely complicated processes from very expensive starting materials, and hence have almost no industrial value. Complicated production processes and high costs for these materials pose obstacles for development and production of novel medicines and perfumes. Under these circumstances, there is a demand for a novel derivative of tricyclic hydrocarbon which is inexpensive and can be prepared by a simple process. OBJECTS AND SUMMARY OF THE INVENTION : A primary object of this invention is to provide a novel derivative of brendane which is important as medicines, perfumes and starting materials therefor, and to provide a process for preparing the same. Another object of this invention is to provide a derivative of brendane which can be prepared from inexpensive starting materials through a simplified one-step reaction, and to provide a process for the preparation thereof. A further object of this invention is to provide a novel derivative of brendane and a process for the preparation thereof, the derivative of brendane provided by the invention having intramolecular functional groups so that it may be used as a starting material for synthesizing a variety of other tricyclic hydrocarbon derivatives. A still further object of this invention is to provide a derivative of brendane which can be subjected to a skeletal isomerization reaction, and to provide a process for the preparation thereof. The above and other objects of this invention will become apparent from the following detailed description. According to the present invention there is provided a novel derivative of brendane represented by the following general formula [I] of: wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group. Also provided in accordance with the present invention is a process for preparing a derivative of brendane represented by the following general formula [I] : wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group; comprising the step of reacting an alkenylnorbornene represented by the following general formula [II] of: wherein R¹ to R³ each represent a hydrogen atom or a methyl group; with carbon monoxide and a reactant selected from the group consisting of alcohols and water in the presence of a compound of a metal of Group VIII of the periodic table as a catalyst. BRIEF DESCRIPTION OF THE DRAWINGS : Fig. 1 is an infrared absorption spectrum chart of isopropyl 5-methylbrendane-4-one-2-carboxylate prepared by Example 1 of the invention; Fig. 2 is an H-NMR chart of the same compound; and Fig. 3 is a ¹³C-NMR chart of the same compound. DESCRIPTION OF THE INVENTION : The invention will be described in detail hereinafter. After eager pursuits for the provision of a novel tricyclic hydrocarbon derivative which can be prepared from inexpensive starting materials through a simple process, we have found that novel derivatives of brendane represented by the following general formula [I] can be prepared from alkenylnorbornenes produced by the Diels-Alder reaction between cyclopentadiene and conjugated diene compounds by reacting the alkenylnorbornenes with carbon monoxide and water or an alcohol in the presence of a catalyst made of a compound of a metal of Group VIII of the periodic table. The present invention has been accomplished on the basis of this finding. The derivatives of brendane, provided by the present invention, are represented by the general formula [I] of: wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group. R in the general formula [I] representing the compounds provided by the present invention is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, the specific examples of the hydrocarbon group being methyl, ethyl, n-propyl, isopropyl, sec-butyl, n-pentyl, n-hexyl and cyclohexyl groups. The compounds of the invention are novel derivatives of brendane each having a tricyclic hydrocarbon skeleton. Tricyclic hydrocarbon derivatives, such as patchouli alcohol and adamantane derivatives, are generally used as medicines, perfumes and starting materials therefor in a wide application range. However, in general, such tricyclic hydrocarbon derivatives are necessarily prepared from expensive starting materials through extremely complicated procedures to devaluate the industrial merits thereof. On the contrary, the compounds of the invention may be prepared from vinylnorbornenes produced by the Diels-Alder reaction between cyclopentadiene and conjugated diene compounds by reacting the vinylnorbornenes with carbon monoxide and a hydroxyl group-containing compound selected from the group consisting of water and alcohols in the presence of a catalyst made of a compound of a metal of Group VIII of the periodic table. Accordingly, the compounds of the invention can be prepared from inexpensive materials through a far simpler process. This is one of the important features of this present invention. Moreover, each molecule of the compounds of this invention has two functional groups, i.e. a ketone site and a carboxylic acid residue site. A great diversity of different tricyclic hydrocarbon derivatives may be easily synthesized from the compounds of this invention, accordingly. This is a furtherimportant merit of the present invention. Furthermore, the compounds of this invention may be subjected to skeletal isomerization reaction to prepare other tricyclic hydrocarbons having different skeletal structures. As should be appreciated from the foregoing, the compounds of this invention can be utilized as extremely valuable starting materials for a variety of novel medicines and perfumes. The process for preparing the compounds of this invention will now be described. The compound of this invention represented by the general formula [I] may be prepared by reacting an alkenylnorbornene represented by the following general formula [II] of: wherein R¹ to R³ each represent a hydrogen atom or a methyl group; with carbon monoxide and water or an alcohol in the presence of a catalyst made of a compound of a metal of Group VIII of the periodic table. The alcohols used in the process for the preparation of the compounds of this invention are alcohols having 1 to 6 carbon atoms, such as methanol, ethanol, n-propanol, isopropanol, sec-butanol, n-pentanol, n-hexanol and cyclohexanol. The catalysts used in the synthesis of the compounds of this invention are compounds of metals of Group VIII of the periodic table, and include compounds of cobalt and palladium. Examples of usable cobalt compounds are cobalt carbonyl complexes, and cobalt compounds which form cobalt carbonyl complexes during the reaction or by proper treatment can be used as effective catalysts. The reaction may be carried out at a carbon monoxide pressure of from 1 bar (kg/cm²) to 500 bar (kg/cm²), preferably from 50 to 300 bar (kg/cm²), and at a temperature of from 30 to 300°C, preferably from 100 to 200°C, while using an aromatic tertiary amine, such as pyridine or isoquinoline, as a promotor catalyst. The aromatic tertiary amine may be used in an amount of 1 to 1000 times, preferably 3 to 100 times, based on the atom equivalent of cobalt contained in the used catalyst. An example of a palladium compound catalyst is a palladium complex stabilized with an organic tertiary phosphine. The reaction may be carried out at a carbon monoxide pressure of from 1 to 500 bar (kg/cm²), preferably from 5 to 300 bar (kg/cm²), and at a temperature of from 30 to 300°C, preferably from 50 to 150°C. The organic tertiary phosphines which may be used in the process of this invention include organic tertiary phosphines providing catalysts having desirous activities under the reaction condition, the examples being triphenylphosphine (represented by PPh₃, wherein Ph is phenyl), tributylphosphine [P(C₄H₉)₃] and methyldiphenylphosphine [represented by CH₃P(Ph)₂]. It is desirable that 1 to 100 times, preferably 2 to 20 times, based on the quantity of the existing palladium, on molar base, of a phosphine is used. It is estimated that palladium is in the zero equivalency state during the reaction and forms a complex represented by PdL x (C0) 4-x (wherein L is generally an organic tertiary phosphine ligand, and x is zero or an integer of 1 to 4). However, palladium may be introduced in an initial catalyst form of other than the zero equivalency state, and it may be introduced, for example, in the forms of Pd(acetate)₂, Pd(acetylacetate)₂, PdCl₂, PdCl₂ (triphenylphosphine)₂ and Pd(triphenylphosphine)₄. An alcohol or water may be present in an amount not less than equimolecular to the alkenylnorbornene, and a large excess of an alcohol or water may be used without any problem. The reaction may proceed either in a batch process or continuous process depending on the circumstances. By the reaction described above, one molecule of an alkenylnorbornene is reacted with two molecules of carbon monoxide and one molecule of an alcohol or water to produce a compound of this invention. The reaction is a perfect single step reaction, and the compounds of this invention can be prepared extremely easily through the reaction. EXAMPLES : The present invention will be described more specifically by referring to some Examples thereof. Example 1 Into a 500 mℓ stainless steel autoclave were charged 72g (0.6 mol) of 5-vinyl-2-norbornene, 4.15g (12 millimols) of Co₂ (C0)₈, 18g (0.22 mol) of pyridine and 240 mℓ of isopropanol. 160 bar (kg/cm²) of carbon monoxide was introduced in the autoclave at the room temperature, and the temperature of the content in the autoclave was raised to 150°C. The reaction was continued at that temperature for 5 hours, and the content was allowed to stand for cooling and then discharged from the autoclave. The reaction product discharged from the autoclave was subjected to rectification to obtain 6.6g of a fraction of 119 ∼ 120°C (1.33 mbar, 1 mmHg). The chemical structure of that fraction was analyzed by the elemental analysis, infrared spectrophotometry and NMR spectrophotometry, to confirm that the fraction was isopropyl 5-methylbrendane-4-one-2-carboxylate. Fig. 1 is an infrared spectrum chart (the abscissa in the Figure is calibrated in cm⁻¹) of the thus produced isopropyl 5-methylbrendane-4-one-2-carboxylate. Fig. 2 is an H-NMR chart of the same compound (the abscissa in the Figure indicates the δ values in TMS standard), and Fig. 3 is a ¹³C-NMR chart (the abscissa in the Figure indicates the δ values in TMS standard) of the same compound. Mass Spectrum m/e (hereinafter referred to simply as MSm/e): 236 Infrared Spectrum Absorption Positions (Liquid Film Method, cm⁻¹, hereinafter referred to simply as IR): 2960, 2875, 1730, 1720, 1460, 1450, 1370, 1200, 1100 H-NMR (400 MHz, CDCl₃), δ value (ppm) 1.05 ∼ 1.25 (CH₃, 9H), 1.4 ∼ 3.0 (CH, CH₂, 10H), 4.95 (CH, 1H) ¹³C-NMR (100 MHz, CDCl₃), δ value (ppm) 222.8, 221.5 (carbonyl, ketone) 171.63, 171.56 (carbonyl, ester) 68.02 (3), 67.80 (3), 52.00 (3), 51.87 (3), 51.32 (3), 50.42 (3), 48.20 (3), 46.89 (3), 45.23 (3), 44.23 (3), 43.35 (3), 41.11 (3), 41.05 (3), 40.31 (3), 39.95 (2), 39.09 (2), 33.98 (2), 25.20 (2), 21.76 (1), 21.71 (1), 17.19 (1), 11.46 (1) The numerals in the parentheses indicate, respectively, primary, secondary and tertiary carbon. The result of the ¹³C-NMR analysis shows that the product of the invention is a mixture of two isomers. The compound was analysed in detail by the H-NMR to reveal that the product was a mixture of isopropyl endo-5-methylbrendane-4-one-2-carboxylate and isopropyl exo-5-methylbrendane-4-one-2-carboxylate mixed in a ratio of approximately 1 : 1. Example 2 A similar reaction was carried out as in Example 1, except that 240 mℓ of methanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 0.2g of a fraction of 104 ∼ 105°C (1.33 mbar, 1 mmHg). The fraction was added with 10 mℓ of isopropanol and 0.1 mℓ of BF₃·etherate and then subjected to reflux for 30 minutes for ester exchange reaction with isopropanol, whereby isopropyl 5-methylbrendane-4-one-2-carboxylate was obtained. In view of the result of ester exchange reaction, it was confirmed that the reaction product before the ester exchange reaction was methyl 5-methylbrendane-4-one-2-carboxylate. MSm/e: 208 IR: 2960, 2875, 1730, 1720, 1465, 1450, 1370, 1200, 1040 Example 3 A similar reaction was carried out as in Example 1, except that 240 mℓ of ethanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 2.8g of ethyl 5-methylbrendane-4-one-2-carboxylate (112 ∼ 114°C/1.33 mbar, 1 mmHg). MSm/e: 222 IR: 2960, 2875, 1730, 1720, 1470, 1450, 1370, 1200, 1045 Example 4 A similar reaction was carried out as in Example 1, except that 240 mℓ of n-propanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 2.2g of propyl 5-methylbrendane-4-one-2-carboxylate (123 ∼ 125°C/1.33 mbar, 1 mmHg). MSm/e: 236 IR: 2960, 2875, 1730, 1720, 1470, 1450, 1370, 1200, 1060, 1050 Example 5 A similar reaction was carried out as in Example 1, except that 240 mℓ of sec-butanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 7.1g of sec-butyl 5-methylbrendane-4-one-2-carboxylate (135 ∼ 137°C/1.33 mbar, 1 mmHg). MSm/e: 250 IR: 2960, 2875, 1730, 1720, 1460, 1450, 1370, 1200, 1120, 1100 Example 6 A similar reaction was carried out as in Example 1, except that 240 mℓ of n-pentanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 2.1g of n-pentyl 5-methylbrendane-4-one-2-carboxylate (154 ∼ 156°C/1.33 mbar, 1 mmHg). MSm/e: 264 IR: 2960, 2875, 1730, 1720, 1470, 1450, 1370, 1200, 1050 Example 7 A similar reaction was carried out as in Example 1, except that 240 mℓ of n-hexanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 1.8g of n-hexyl 5-methylbrendane-4-one-2-carboxylate (167 ∼ 169°C/1.33 mbar, 1 mmHg). MSm/e: 278 IR: 2960, 2875, 1730, 1720, 1470, 1450, 1370, 1200, 1055 Example 8 A similar reaction was carried out as in Example 1, except that 240 mℓ of cyclohexanol was used in place of isopropanol, and then the reaction product was subjected to distillation to obtain 3.5g of cyclohexyl 5-methylbrendane-4-one-2-carboxylate (160 ∼ 162°C/1.33 mbar, 1 mmHg). MSm/e: 276 IR: 2960, 2875, 1730, 1720, 1460, 1450, 1200, 1120, 1100, 1070 Example 9 A similar reaction was carried out as in Example 1, except that 120 mℓ of 1,4-dioxane and 120 mℓ of water were used in place of isopropanol. After allowing to stand the reaction mixture for cooling, the reaction mixture was discharged from the autoclave and added with 200 mℓ of diethyl ether, and then rinsed with 200 mℓ of a 10% aqueous solution of H₂S0₄ for two times to remove alcohol and pyridine. Thereafter, using 100 mℓ of a saturated aqueous solution of sodium hydrogencarbonate for each time, the carboxylic acid was extracted from the organic phase for two times. The aqueous phase was then neutralized with a 10% aqueous solution of H₂S0₄ to separate the free carboxylic acid which was extracted with 50 mℓ of diethyl ether. The organic phase was dried with sodium sulfate anhydride, and then the ether was distilled off to obtain 22g of white powders. The powders were added with 100 mℓ of isopropanol and 0.5 mℓ of concentrated sulfuric acid, followed by reflux for 3 hours, and then subjected to gas chromatography to find that 3.1g of isopropyl 5-methylbrendane-4-one-2-carboxylate was produced. Example 10 1g of the isopropyl 5-methylbrerdane-4-one-2-carboxylate prepared by Example 1 was mixed with 10 mℓ of a 10% aqueous solution of Na0H, and the mixture was boiled for 2 hours under vigorous agitation. After the completion of reaction, the reaction mixture was neutralized with a 10% aquesous solution of H₂S0₄ until the pH value of the reaction mixture reached pH 4. The separated free carboxylic acid was extracted by 20 mℓ of diethyl ether, and the organic phase was dried with sodium sulfate anhydride. Then, diethyl ether was distilled off to obtain 0.75g of 5-methylbrendane-4-one-2-carboxylic acid in the form of white powders. MSm/e: 194 Example 11 A similar reaction was carried out as in Example 1, except that 80g (0.6 mol) of 6-methyl-5-vinyl-2-norbornene was used in place of 5-vinyl-2-norbornene and then the reaction product was subjected to distillation to obtain 5.8g of isopropyl 5,9-dimethylbrendane-4-one-2-carboxylate (132 ∼ 134°C/1.33 mbar, 1 mmHg). MSm/e: 250 IR: 2960, 2875, 1730, 1720, 1460, 1450, 1370, 1200, 1100 Example 12 A similar reaction was carried out as in Example 1, except that 80g (0.6 mol) of 5-methyl-5-vinyl-2-norbornene was used in place of 5-vinyl-2-norbornene and then the reaction product was subjected to distillation to obtain 2.1g of isopropyl 5,6-dimethylbrendane-4-one-2-carboxylate (130 ∼ 132°C/1.33 mbar, 1 mmHg). MSm/e: 250 IR: 2960, 2875, 1730, 1720, 1460, 1450, 1370, 1200, 1100 Example 13 A similar reaction was carried out as in Example 1, except that 80g of propenylnorbornene was used in place of 5-vinyl-2-norbornene and then the reaction product was subjected to distillation to obtain 0.9g of isopropyl 5-ethylbrendane-4-one-2-carboxylate (130 ∼ 132°C/1.33 mbar, 1 mmHg). MSm/e: 250 IR: 2960, 2875, 1730, 1720, 1460, 1450, 1370, 1200, 1100 Example 14 Into a 500 mℓ stainless steel autoclave, charged were 72g (0.6 mol) of 5-vinyl-2-norbornene, 240 mℓ of isopropanol, 0.7g (1 millimol) of PdCl₂(PPh₃)₂ and 0.52g (2 millimols) of PPh₃, and 80 bar (kg/cm²) of C0 was introduced into the autoclave at the room temperature and then the temperature of the content in the autoclave was raised to 120°C. After reacting for 10 hours, the reaction mixture was cooled and then discharged from the autoclave and subjected to distillation to obtain 2.0g of isopropyl 5-methylbrendane -4-one-2-carboxylate.

Claims: A derivative of brendane represented by the following general formula [I] of: wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group. The derivative of brendane according to claim 1, wherein said hydrocarbon group is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, sec-butyl, n-pentyl, n-hexyl and cyclohexyl groups. A process for preparing a derivative of brendane represented by the following general formula [I] of: wherein R is a hydrogen atom or a hydrocarbon group having 1 to 6 carbon atoms, and R¹ to R³ each represent a hydrogen atom or a methyl group; comprising the step of reacting an alkenylnorbornene represented by the following general formula [II] of: wherein R¹ to R³ each represent a hydrogen atom or a methyl group; with carbon monoxide and a reactant selected from the group consisting of alcohols and water in the presence of a compound of a metal of Group VIII of the periodic table as a catalyst. The process according to claim 3, wherein said alcohols are alcohols having 1 to 6 carbon atoms. The process according to claim 4, wherein said alcohols are selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, sec-butanol, n-pentanol, n-hexanol and cyclohexanol. The process according to any of the claims 3 to 5, wherein said catalyst is selected from the group consisting of cobalt compound catalysts and palladium compound catalysts. The process according to claim 6, wherein said cobalt compound catalyst is a cobalt carbonyl complex. The process according to claim 6 or 7, wherein an aromatic tertiary amine is used, together with said cobalt compound catalyst, as a promotor catalyst in a ratio of 1 to 1000 times based on the atom equivalent of cobalt contained in said cobalt compound catalyst. The process according to claim 8, wherein said aromatic tertiary amine is selected from the group consisting of pyridine and isoquinoline. The process according to claim 6, wherein said palladium compound catalyst is a palladium complex stabilized by an organic tertiary phosphine added in a molar ratio of 1 to 100 times based on the atom equivalent of palladium contained in said palladium compound catalyst. The process according to claim 10, wherein said organic tertiary phosphine is selected from the group consisting of triphenylphosphine, tributylphosphine and methyldiphenylphosphine. The process according to any of the claims 3 to 11, wherein the pressure of said carbon monoxide ranges within 1 to 500 bar (kg/cm²) and wherein the reaction is carried out at a temperature of from 30°C to 300°C. The process according to any of the claims 3 to 12, wherein said alcohol is used in an equivalent molar ratio or more, relative to said alkenylnorbornene. The process according to any of the claims 3 to 12, wherein said water is used in an equivalent molar ratio or more, relative to said alkenylnorbornene.

Inventors: KOBORI, YOSHIHIRO, TAKEZONO, TETSUYA
Applicants: NIPPON OIL CO. LTD.
Application year: 1985
Main classification: C07C62
IPC codes: C07C51, C07C67, C07C69, C07C62, C07B61, B01J31