* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Under nitrogen protection, the addition intermediate prepared in Example 5 (85.3 g, 0.3 mol) was added to a solution with a constant pressure drop In a three-necked flask with a bucket, a thermometer, and a condenser, the oil bath was heated to 180 °C, and a mixture of deionized water and methanol (90 mL, 1/1) was slowly added dropwise with rapid stirring. The addition was completed within 4 hours. One hour after the reaction, the reaction was stopped by cooling to room temperature. Crude vacuum distillation, collecting 140-141 °C (2-3mmHg) distillate, to obtain 57.7g of methyl dihydrojasmonate, yield 85percent, purity 98percent.
283.48 g
at 215℃; for 4 h;
To a reaction apparatus equipped with a distillation distillation pipe, 283.48 g of dimethyl 2- (3-oxo-2-pentylcyclopentyl) malonate obtained in Example 1 was added, heated to 215 ° C.,Water was added dropwise. A dropwise addition reaction was carried out at 215 ° C. for 4 hours while distilling out generated carbon dioxide and methanol.After completion of the reaction, 203.27 g of crude product was obtained.Methyl (3-oxo-2-pentylcyclopentyl) acetate (148.71 g) obtained by fractionating the crude product was purified by reverse-It has fruity and jasmine-like fragrance,It was also excellent as a perfume material.
Stage #1: With sodium methylate In methanol at 0℃; for 5 h; Michael addition Stage #2: at 215℃; for 4 h;
The reaction in Example 1 was carried out twice, the product was distilled to recover cyclopentanone and water, then 0.0206 mol oxalic acid was added to 1.01 mol 2-(1-hydroxy-n-pentyl)cyclopentanone and 0.022 mol 2-pentylidene cyclopentanone from the product, and the mixture was reacted at 120°C. The reaction mixture contained 141 g (0.93 mol) 2-pentylidene cyclopentanone. Its filtered product was dissolved in 153 g n-butanol and heated at 130°C, and then a mixture of 14.5 g (0.15 mol) 3-picoline and 10.5 g (0.1 mol) 35percent hydrochloric acid was added dropwise at the same temperature over 30 minutes. Thereafter, the mixture was stirred at the same temperature for 3.5 hours. After the reaction was finished, the mixture was cooled to room temperature and neutralized with an aqueous sodium hydroxide solution, and the organic layer was analyzed. The result indicated that the reaction mixture contained 118 g 2-pentyl-2-cyclopentenone. The yield in this isomerization reaction was 83percent. From this reaction mixture, 95 g (0.6 mol) 2-pentyl-2-cyclopentenone was purified. Separately, 118 g (0.9 mol) dimethyl malonate was dissolved in 38 g anhydrous methanol in a nitrogen atmosphere and then cooled to 0°C, and 6.5 g (0.036 mol) sodium methoxide (30percent methanol) was added thereto. 95 g (0.6 mol) 2-pentyl-2-cyclopentenone obtained above was added dropwise thereto at 0°C over 2 hours. Thereafter, the mixture was stirred at the same temperature for 3 hours. Thereafter, the unreacted dimethyl malonate was distilled away under reduced pressure, whereby 160 g Michael addition product was obtained. The Michael addition product obtained above was added to a reaction device equipped with a distillation tube and then heated at 215°C, and water was added dropwise at a rate of 3.2 g/h (2percent/h). By adding water dropwise, the mixture was reacted for 4 hours at 215°C while generated carbon dioxide and methanol were distilled away. After the reaction was finished, 123 g methyl 3-oxo-2-pentylcyclopentylacetate was obtained in 126 g crude product. The yield in the whole process was 60percent. The crude product was refined by distillation to give methyl 3-oxo-2-pentylcyclopentylacetate having a fruity jasmine-like aroma, which was also excellent as a perfume material. The reaction in Comparative Example 1 was carried out 3 times, the product was distilled to recover cyclopentanone and water, then 0.0206 mol oxalic acid was added to 1.11 mol 2-(1-hydroxy-n-pentyl)cyclopentanone and 0.012 mol 2-pentylidene cyclopentanone from the product, and the mixture was reacted at 120°C. Thereafter, the reaction was carried out in the same manner as in Example 7, to give methyl 3-oxo-2-pentylcyclopentylacetate. As a result, the yield in the whole process was 28percent.
A 1 L four-neck flask equipped with a stirrer, a supply unit, a thermometer and a rectifier was charged with 600 g of raw material containing 545 g (1.92 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180°C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to 6 g/h from the start of the supply to the 2nd hour, to 3 g/h from the 2nd hour to the 8th hour and to 1.2 g/h after the 8th hour with measuring the content of water in the reaction solution by a Karl Fischer's coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) such that the content of water was limited to 0.4percent by weight or less. Then, the reaction was completed for 16 hours from the start of the supply of water. The maximum water concentration in the reaction solution was 0.21percent by weight. During the reaction, the difference (X-Y) between the integrating molar number X (excluding distilled water content) of the water to be supplied and the molar number Y of the water reacted with dimethyl 2-pentyl-3-oxo-cyclopentylmalonate was 14.8percent at a maximum based on the molar number of the charged dimethyl 2-pentyl-3-oxo-cyclopentylmalonate. It was found that the reaction product contained 423 g (1.87 mol, yield: 97.3percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 10.8 g (0.051 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.; Comparative Example 1 The same 1 L four-neck flask that was used in Example 1 was charged with 600 g of raw material containing 557 g (1.96 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180°C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to a constant rate (6 g/h) . Then, the reaction was completed for 9 hours from the start of the supply of water. During the supply of water, the content of water in the reaction solution was measured by a Karl Fischer's coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) and as a result, the maximum water concentration in the reaction solution was 0.44percent by weight. It was found that the reaction product contained 402 g (1.78 mol, yield: 90.7percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 33.5 g (0.158 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.; Example 2 The same 1 L four-neck flask that was used in Example 1 was charged with 600 g of raw material containing 550 g (1.94 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 215°C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to 18 g/h from the start of the supply to the 1st hour, to 12 g/h from the 1st hour to the 2nd hour, to 6 g/h from the 2nd hour to the 3rd hour and to 3 g/h after the 3rd hour with measuring the content of water in the reaction solution by a Karl Fischer' s coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) such that the content of water was limited to 0.4percent by weight or less. Then, the reaction was completed for 4 hours from the start of the supply of water. The maximum water concentration in the reaction solution was 0.14percent by weight. During the reaction, the difference (X-Y) between the integrating molar number X (excluding distilled water content) of the water to be supplied and the molar number Y of the water reacted with dimethyl 2-pentyl-3-oxo-cyclopentylmalonate was 10.3percent at a maximum based on the molar number of the supplied dimethyl 2-pentyl-3-oxo-cyclopentylmalonate. It was found that the reaction product contained 420 g (1.86 mol, yield: 96.0percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 5.8 g (0.027 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.
A reactor shown in Fig. 1 which was provided with a reaction vessel 1 constituted of a 1 L four-neck flask equipped with a stirrer 2, a supply unit 3, a thermometer 4 and a Packed column 5 and a cooling tube (condenser) 6 and a receiver 7 installed downstream of the Packed column 5 was used to run a reaction. The reaction vessel 1 was charged with 600 g of raw material containing 556 g (1.96 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 215°C with stirring under normal pressure. Then, water was supplied from the supply unit 3 at a rate of 12 g/h. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were condensed in the Packed column 5 and returned continuously to the reaction vessel 1. Methanol was distilled out of the system, condensed in the condenser 6 and recovered in the receiver 7. Then, the reaction was completed for 3.75 hours from the start of the supply of water. It was found that the reaction product contained 413 g (1.83 mol, yield: 93.5percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 69.8 g (2.18 mol) of methanol could be recovered from the fractions condensed outside of the system.; Example 4 A reactor shown in Fig. 2 which was provided with a reaction vessel 10 constituted of a 2L four-neck flask equipped with a stirrer 2, a supply unit 3 and a thermometer 4, a cooler provided with two cooling tubes (condensers) 8 and 9 arranged in series and a thermometer 14 arranged between the two cooling tubes and a receiver 7 was used to run a reaction. The reaction vessel 10 was charged with 1111 g of raw material containing 1068 g (3.76 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180°C with stirring under normal pressure. Then, the supply of water from supply unit 3 was started. During the supply of water, the supply rate of water was adjusted to 11.6 g/h from the start of the supply to the 2nd hour, to 5.6 g/h from the 2nd hour to the 8th hour and to 2.3 g/h after the 8th hour. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were condensed in the first cooling tube 8 with controlling the supply rate of cooling water such that the vapor temperature was 65°C at the outlet of the cooling tube 8 and returned continuously to the reaction vessel 10, and methanol was condensed in the second cooling tube 9 with supplying a 0°C cooling medium and recovered in the receiver 7. Then, the reaction was completed for 15 hours from the start of the supply of water. The reaction product contained 811 g (3.59 mol, yield: 95.5percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 132.6 g (4.14 mol) of methanol could be recovered from the fraction condensed outside of the system.; Example 5 A reactor shown in Fig. 3 which was provided with a reaction vessel 13 constituted of a 3L four-neck flask equipped with a stirrer 2, a supply unit 3, a thermometer 4 and a rectifier 11 with 15-stages, a cooling tube (condenser) 12 and a receiver 7 which were installed downstream of the rectifier 11 provided with a thermometer 15 was used to run a reaction. The reaction vessel 13 was charged with 1933 g of raw material containing 1840 g (6.48 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180°C with stirring under normal pressure. Then, the supply of water from supply unit 3 was started. During the supply of water, the supply rate of water was adjusted to 19 g/h from the start of the supply to the 2nd hour, to 9.5 g/h from the 2nd hour to the 8th hour and to 3.8 g/h after the 8th hour. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were refluxed continuously to the reaction vessel 13 at a reflux ratio of 5, while maintaining the top temperature of the rectifier at 65°C. Methanol was condensed in the condenser 12 outside of the system and recovered in the receiver 7. Then, the reaction was completed for 14 hours from the start of the supply of water. The reaction product contained 1414 g (6.26 mol, yield: 96.6percent) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 177.2 g (5.54 mol) of methanol could be recovered from the fraction condensed outside of the system.
With phosphoric acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone; In 1,4-dioxane; at 101℃; for 5h;
Add 150 mL of 1,4-dioxane, 15 g (0.066 mol) of commercially available dihydrojasmonic acid to a 500 mL three-necked flask.Methyl ester,After stirring and dissolving, DDQ 18.1 g (0.08 mol) was added, and 0.74 g (0.007 mol) of commercially available 85% phosphoric acid was added.The temperature was raised to reflux (temperature: 101 C) for 5 hours. After dropping to room temperature, the solid was removed by filtration (the main component was unreacted DDQ and DDHQ from which DDQ was reduced), and the filter cake was washed once with 1,4-dioxane 20 mL.After removing the solvent 1,4-dioxane, 150 mL of water was added to the concentrate, followed by extraction with 100 mL of cyclohexane. The cyclohexane layer was washed with a 5% aqueous solution of sodium hydrogencarbonate2 times, each time 50mL.The cyclohexane layer was concentrated and purified by silica gel column to give the final product DHH 10.7 g.The final product was a colorless oil, and the purity by gas chromatography was 95.3%.The reaction yield was 71.3%.The structure was confirmed by nuclear magnetic characterization.
With 5percent Pd/Alox; at 220℃; under 22.5023 Torr; for 24h;Dean-Stark; Inert atmosphere;
In a flask equipped with magnetic stirrer, reflux condenser and Dean Stark apparatus, under inert atmosphere, compound of formula (II) (see Table 1) was stirred vigorously at a temperature indicated in Table 1 in the presence of 5% Pd/Alox (Noblyst 1148 Evonik, dry powder, Table 1) or 5% Pd/C (Hindustan, RD343, powder, 50% moisture, Table 1) over a period indicated in Table 1. The resulting suspension was cooled to 30C and the catalyst was filtered. After rinsing by acetone and evaporation of solvent to dryness, the crude was analyzed by GC (DB-1) showing the conversions into the compound of formula (I) having the most substituted double bond. (0071) Under these conditions several compounds of formula (II) were tested. The results are reported in Table 1. (0072) Table 1: Dehydrogenation of compound of formula (II) under batch conditions (0073) such as regioisomer with an exo double bond; i.e. 6-ethylidene-2,2- dimethylcyclohexan-l-one, was not observed. b) Reaction performed under slight vacuum (3000Pa). Main product was methyl 2- (3-oxo-2-pentylcyclopent-l-en-l-yl)acetate. Only trace amount of 3-methyl-2- pentylcyclopentan-l-one (0.1%), 3-methyl-2-pentylcyclopent-2-en-l-one (0.3%), methyl 2-(2-pentylcyclopentyl)acetate (0.05%) were observed
Non-limiting examples of ketones generated from the compounds of the present invention include: ... 3-methyl-cyclopentadecanone; 4-(1,1-dimethylpropyl)pentyl-cyclohexanone*; 4-tert-pentyl-cyclohexanone*; 2-oxo-1-pentyl-cyclopentane-acetic acid methyl ester**; 3-oxo-2-pentyl-cyclopentane-acetic acid methyl ester**; 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)-ethanone*; 3-methyl-5-propyl-cyclohex-2-en-1-one*; 4-(2,6,6-trimethylcyclohex-1-en-1-yl)butan-2-one**; ...
In the following a non-limiting list of such ketones are given as examples. ... 4-(1,1-dimethylpropyl)-cyclohexanone**, 6,10-dimethyl-undeca-5,9-dien-2-one**, (3-oxo-2-pentyl-cyclopentyl)-acetic acid methyl ester**, 3-(2-Oxo-propyl)-2-pentyl-cyclopentanone**, ...
Compounds of formula I may generate the following organoleptic ketones of formula YH: ... 2-(1-methylethyl)-5-methyl-cyclohexanone* 2-(2-methylethyl)-5-methyl-cyclohexanone** 3-methyl-cyclopentadecanone 4-(1,1-dimethylpropyl)pentyl-cyclohexanone* 3-oxo-2-pentyl-cyclopentane-acetic acid methyl ester** 1-(1,2,3,4,5,6,7,8,-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl-ethanone* 3-methyl-5-propyl-cyclohex-2-en-1-one* 4(2,6,6-triethylcyclohex-1-en-1-yl)butan-2-one** ...
Compounds of formula I may generate the following ketones: ... 2-(2-methylethyl)-5-methyl-cyclohexanone* 3-methyl-cyclopentadecanone 4-dimethylpropyl)-cyclohexanone* 6,10-dimethyl-undeca-5,9-dien-2-one* 3-oxo-2-pentyl-cyclopentane-acetic acid methyl ester** 1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)-ethanone* 3-methyl-5-propyl-cyclohex-2-en-1h-one* 1-(2-cyclohexen)-2,4,4-trimethyl-but-2-enone* ...
The reaction in Example 1 was carried out twice, the product was distilled to recover cyclopentanone and water, then 0.0206 mol oxalic acid was added to 1.01 mol 2-(1-hydroxy-n-pentyl)cyclopentanone and 0.022 mol 2-pentylidene cyclopentanone from the product, and the mixture was reacted at 120C. The reaction mixture contained 141 g (0.93 mol) 2-pentylidene cyclopentanone. Its filtered product was dissolved in 153 g n-butanol and heated at 130C, and then a mixture of 14.5 g (0.15 mol) 3-picoline and 10.5 g (0.1 mol) 35% hydrochloric acid was added dropwise at the same temperature over 30 minutes. Thereafter, the mixture was stirred at the same temperature for 3.5 hours. After the reaction was finished, the mixture was cooled to room temperature and neutralized with an aqueous sodium hydroxide solution, and the organic layer was analyzed. The result indicated that the reaction mixture contained 118 g 2-pentyl-2-cyclopentenone. The yield in this isomerization reaction was 83%. From this reaction mixture, 95 g (0.6 mol) 2-pentyl-2-cyclopentenone was purified. Separately, 118 g (0.9 mol) dimethyl malonate was dissolved in 38 g anhydrous methanol in a nitrogen atmosphere and then cooled to 0C, and 6.5 g (0.036 mol) sodium methoxide (30% methanol) was added thereto. 95 g (0.6 mol) 2-pentyl-2-cyclopentenone obtained above was added dropwise thereto at 0C over 2 hours. Thereafter, the mixture was stirred at the same temperature for 3 hours. Thereafter, the unreacted dimethyl malonate was distilled away under reduced pressure, whereby 160 g Michael addition product was obtained. The Michael addition product obtained above was added to a reaction device equipped with a distillation tube and then heated at 215C, and water was added dropwise at a rate of 3.2 g/h (2%/h). By adding water dropwise, the mixture was reacted for 4 hours at 215C while generated carbon dioxide and methanol were distilled away. After the reaction was finished, 123 g methyl 3-oxo-2-pentylcyclopentylacetate was obtained in 126 g crude product. The yield in the whole process was 60%. The crude product was refined by distillation to give methyl 3-oxo-2-pentylcyclopentylacetate having a fruity jasmine-like aroma, which was also excellent as a perfume material. The reaction in Comparative Example 1 was carried out 3 times, the product was distilled to recover cyclopentanone and water, then 0.0206 mol oxalic acid was added to 1.11 mol 2-(1-hydroxy-n-pentyl)cyclopentanone and 0.012 mol 2-pentylidene cyclopentanone from the product, and the mixture was reacted at 120C. Thereafter, the reaction was carried out in the same manner as in Example 7, to give methyl 3-oxo-2-pentylcyclopentylacetate. As a result, the yield in the whole process was 28%.
The reaction finish product synthesized in the similar manner as Example 1 was rectificated, to obtain 190 g (1.2 mol) of 2-pentyl-2-cyclopentene. Then to a mixture obtained by dissolving 236 g (1.8 mol) of dimethyl malonate in 76 g of anhydrous methanol under nitrogen atmosphere, cooling to 0C, and adding 12.9 g (0.072 mmol) of sodium methoxide (30% in methanol), 190 g (1.2 mol) of 2-pentyl-2-cyclopentene obtained above was added dropwise at 0C over 2 hours. After completion of the dropping, the resultant mixture was stirred at the same temperature for 3 hours. Unreacted dimethyl malonate was distilled off under reduced pressures, to afford 320 g of a Michael addition product. A reaction apparatus equipped with a distillation outlet tube was added with the Michael addition product obtained above and heated to 215C, and then water was added dropwise at a rate of 6.4 g/h (2%/h). While distilling off the generating carbon dioxide and methanol, the dropping reaction was conducted for 4 hours at 215C. After completion of the reaction, 245 g of methyl 3-oxo-2-pentylcyclopenthyl acetate was obtained in 251 g of the crude product.
With water; at 180 - 215℃; for 4 - 16h;Product distribution / selectivity;
A 1 L four-neck flask equipped with a stirrer, a supply unit, a thermometer and a rectifier was charged with 600 g of raw material containing 545 g (1.92 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to 6 g/h from the start of the supply to the 2nd hour, to 3 g/h from the 2nd hour to the 8th hour and to 1.2 g/h after the 8th hour with measuring the content of water in the reaction solution by a Karl Fischer's coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) such that the content of water was limited to 0.4% by weight or less. Then, the reaction was completed for 16 hours from the start of the supply of water. The maximum water concentration in the reaction solution was 0.21% by weight. During the reaction, the difference (X-Y) between the integrating molar number X (excluding distilled water content) of the water to be supplied and the molar number Y of the water reacted with dimethyl 2-pentyl-3-oxo-cyclopentylmalonate was 14.8% at a maximum based on the molar number of the charged dimethyl 2-pentyl-3-oxo-cyclopentylmalonate. It was found that the reaction product contained 423 g (1.87 mol, yield: 97.3%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 10.8 g (0.051 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.; Comparative Example 1 The same 1 L four-neck flask that was used in Example 1 was charged with 600 g of raw material containing 557 g (1.96 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to a constant rate (6 g/h) . Then, the reaction was completed for 9 hours from the start of the supply of water. During the supply of water, the content of water in the reaction solution was measured by a Karl Fischer's coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) and as a result, the maximum water concentration in the reaction solution was 0.44% by weight. It was found that the reaction product contained 402 g (1.78 mol, yield: 90.7%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 33.5 g (0.158 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.; Example 2 The same 1 L four-neck flask that was used in Example 1 was charged with 600 g of raw material containing 550 g (1.94 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 215C with stirring under normal pressure. Then, the supply of water to the bottom of the reactor was started. During the supply of water, the supply rate of water was adjusted to 18 g/h from the start of the supply to the 1st hour, to 12 g/h from the 1st hour to the 2nd hour, to 6 g/h from the 2nd hour to the 3rd hour and to 3 g/h after the 3rd hour with measuring the content of water in the reaction solution by a Karl Fischer' s coulometric titration (instrument: Trace-water measuring device AQ-7, manufactured by HIRANUMA SANGYO Co. , Ltd.) such that the content of water was limited to 0.4% by weight or less. Then, the reaction was completed for 4 hours from the start of the supply of water. The maximum water concentration in the reaction solution was 0.14% by weight. During the reaction, the difference (X-Y) between the integrating molar number X (excluding distilled water content) of the water to be supplied and the molar number Y of the water reacted with dimethyl 2-pentyl-3-oxo-cyclopentylmalonate was 10.3% at a maximum based on the molar number of the supplied dimethyl 2-pentyl-3-oxo-cyclopentylmalonate. It was found that the reaction product contained 420 g (1.86 mol, yield: 96.0%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 5.8 g (0.027 mol) of 2-pentyl-3-oxo-cyclopentylacetic acid.
With water; at 180 - 215℃; for 3.75 - 15h;Product distribution / selectivity;
A reactor shown in Fig. 1 which was provided with a reaction vessel 1 constituted of a 1 L four-neck flask equipped with a stirrer 2, a supply unit 3, a thermometer 4 and a Packed column 5 and a cooling tube (condenser) 6 and a receiver 7 installed downstream of the Packed column 5 was used to run a reaction. The reaction vessel 1 was charged with 600 g of raw material containing 556 g (1.96 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 215C with stirring under normal pressure. Then, water was supplied from the supply unit 3 at a rate of 12 g/h. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were condensed in the Packed column 5 and returned continuously to the reaction vessel 1. Methanol was distilled out of the system, condensed in the condenser 6 and recovered in the receiver 7. Then, the reaction was completed for 3.75 hours from the start of the supply of water. It was found that the reaction product contained 413 g (1.83 mol, yield: 93.5%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 69.8 g (2.18 mol) of methanol could be recovered from the fractions condensed outside of the system.; Example 4 A reactor shown in Fig. 2 which was provided with a reaction vessel 10 constituted of a 2L four-neck flask equipped with a stirrer 2, a supply unit 3 and a thermometer 4, a cooler provided with two cooling tubes (condensers) 8 and 9 arranged in series and a thermometer 14 arranged between the two cooling tubes and a receiver 7 was used to run a reaction. The reaction vessel 10 was charged with 1111 g of raw material containing 1068 g (3.76 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180C with stirring under normal pressure. Then, the supply of water from supply unit 3 was started. During the supply of water, the supply rate of water was adjusted to 11.6 g/h from the start of the supply to the 2nd hour, to 5.6 g/h from the 2nd hour to the 8th hour and to 2.3 g/h after the 8th hour. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were condensed in the first cooling tube 8 with controlling the supply rate of cooling water such that the vapor temperature was 65C at the outlet of the cooling tube 8 and returned continuously to the reaction vessel 10, and methanol was condensed in the second cooling tube 9 with supplying a 0C cooling medium and recovered in the receiver 7. Then, the reaction was completed for 15 hours from the start of the supply of water. The reaction product contained 811 g (3.59 mol, yield: 95.5%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 132.6 g (4.14 mol) of methanol could be recovered from the fraction condensed outside of the system.; Example 5 A reactor shown in Fig. 3 which was provided with a reaction vessel 13 constituted of a 3L four-neck flask equipped with a stirrer 2, a supply unit 3, a thermometer 4 and a rectifier 11 with 15-stages, a cooling tube (condenser) 12 and a receiver 7 which were installed downstream of the rectifier 11 provided with a thermometer 15 was used to run a reaction. The reaction vessel 13 was charged with 1933 g of raw material containing 1840 g (6.48 mol) of dimethyl 2-pentyl-3-oxo-cyclopentylmalonate produced in the same manner as in Production Example 1 and the raw material was heated to 180C with stirring under normal pressure. Then, the supply of water from supply unit 3 was started. During the supply of water, the supply rate of water was adjusted to 19 g/h from the start of the supply to the 2nd hour, to 9.5 g/h from the 2nd hour to the 8th hour and to 3.8 g/h after the 8th hour. Among the vapor generated during the reaction, components containing methyl 2-pentyl-3-oxo-cyclopentylacetate, dimethyl 2-pentyl-3-oxo-cyclopentylmalonate and 2-pentyl-2-cyclopentenone and water were refluxed continuously to the reaction vessel 13 at a reflux ratio of 5, while maintaining the top temperature of the rectifier at 65C. Methanol was condensed in the condenser 12 outside of the system and recovered in the receiver 7. Then, the reaction was completed for 14 hours from the start of the supply of water. The reaction product contained 1414 g (6.26 mol, yield: 96.6%) of methyl 2-pentyl-3-oxo-cyclopentylacetate and 177.2 g (5.54 mol) of methanol could be recovered from the fraction condensed outside of the system.
With methanol; water; at 180℃; for 4h;Inert atmosphere;
Under nitrogen protection, the addition intermediate prepared in Example 5 (85.3 g, 0.3 mol) was added to a solution with a constant pressure drop In a three-necked flask with a bucket, a thermometer, and a condenser, the oil bath was heated to 180 C, and a mixture of deionized water and methanol (90 mL, 1/1) was slowly added dropwise with rapid stirring. The addition was completed within 4 hours. One hour after the reaction, the reaction was stopped by cooling to room temperature. Crude vacuum distillation, collecting 140-141 C (2-3mmHg) distillate, to obtain 57.7g of methyl dihydrojasmonate, yield 85%, purity 98%.
With water; at 215℃; for 4h;
A reactor equipped with a distillation effluent tube was charged with the Michael addition product obtained above and heated to 215C, and water was added dropwise at a rate of 3.2 g/h (2%/h) . While generated carbon dioxide and methanol were distilled away, the reaction was carried out at 215C for 4 hours under dropping. After the reaction was finished, 123 g of methyl 3-oxo-2-pentylcyclopentylacetate was obtained in 126 g crude product. Methyl 3-oxo-2-pentylcyclopentylacetate obtained by rectification of the crude product contained 2-(1-hydroxycyclopentyl) cyclopentanone at a very low level of 11 ppm, and had a fruity and jasmine-like fragrance, and was excellent as a perfume material.
With water; at 185℃; for 11h;
EXAMPLE 1-7 An SUS 113 L reactor was charged with 66 kg (332 mol) of 2-(1-hydroxypentyl)-cyclopentan-1-one (purity: 85%) obtained according to the method described in Synthesis Example 1, 0.52 kg of a phosphoric acid-supporting activated carbon (H3PO4/C; powder, 8.7% hydrous product; phosphorus content: 0.010 (elemental analysis)), and 4.26 kg of 5% Pd/C (available from Evonik Degussa Co., Ltd.; powder, 53.6% hydrous product). The contents of the reactor were mixed with each other under heating in an atmosphere containing hydrogen and nitrogen at a volume ratio (hydrogen: nitrogen) of 1:8 at 140C under 101 kPa. After 10 h from initiation of the reaction, 10.8 kg of a fraction was obtained. As a result of subjecting the obtained final reaction product to quantitative determination by GC, it was confirmed that 45.5 kg (299 mol) of 2-pentyl-2 -cyclopenten-1 -one were produced, and 2.0 kg (13 mol) of 2-pentylcyclopentan-1-one were by-produced. Further, it was confirmed that the yield of 2-pentyl-2-cyclopenten-1-one was 90%. In a nitrogen atmosphere, 667 g (5.1 mol) of dimethyl malonate (available from Aldrich Corp.) were dissolved in 200 g of anhydrous methanol (available from Aldrich Corp.), and the resulting solution was cooled to 10C and then mixed with 21.5 g (0.18 mol) of sodium methoxide (available from Wako Pure Chemical Industries, Ltd.; 28% methanol solution). Then, 500 g (3.1 mol) of 2-pentyl-2-cyclopenten-1-one (purity: 95%) were added dropwise to the resulting mixture at 10C, followed by stirring the mixture. After completion of the reaction, the catalyst was neutralized and removed from the reaction mixture, and then the reaction mixture was subjected to distillation under reduced pressure to distill off methanol and unreacted dimethyl malonate therefrom to obtain 871.6 g of a crude Michael addition product. The thus obtained crude Michael addition product was charged into a reactor equipped with a distilling apparatus and heated to 185C, followed by adding dropwise water thereto. While distilling off carbon dioxide and methanol generated, the contents of the reactor were subjected to the dropping reaction at 185C for 11 h. After completion of the reaction, 668.8 g of a crude reaction product was obtained. The thus obtained crude reaction product (250.0 g) was rectified to obtain methyl(3-oxo-2-pentylcyclopentyl)acetate (192.1 g; yield based on 2-pentyl-2-cydopenten-1-one: 73%). As a result, it was confirmed that the thus obtained methyl(3-oxo-2-pentylcyclopentyl)acetate had a fruity jasmine odor and was therefore an excellent perfume material.
With water; at 215℃; for 4h;
In a nitrogen atmosphere, 208 g (1.56 mol) of dimethyl malonate (available from Aldrich Corp.) were dissolved in 63 g of anhydrous methanol (available from Aldrich Corp.), and the resulting solution was cooled to 0 C. and then mixed with 6.5 g (0.035 mol) of sodium methoxide (available from Wako Pure Chemical Industries, Ltd.; 30% methanol solution). Then, 183.48 g (1.01 mol) of 2-pentyl-2-cyclopenten-1-one (purity: 84%) were added dropwise to the resulting mixture at 0 C., followed by stirring the mixture. After completion of the reaction, the catalyst was neutralized and removed from the reaction mixture, and then the reaction mixture was subjected to distillation under reduced pressure to distill off methanol and unreacted dimethyl malonate therefrom to obtain 283.48 g of a Michael addition product (1,4-addition product). The thus obtained Michael addition product (1,4-addition product) was charged into a reactor equipped with a distilling apparatus and heated to 215 C., followed by adding dropwise water thereto. While distilling off carbon dioxide and methanol generated, the contents of the reactor were subjected to the dropping reaction at 215 C. for 4 h. After completion of the reaction, 203.27 g of a crude reaction product was obtained. The thus obtained crude reaction product was rectified to obtain methyl(3-oxo-2-pentylcyclopentyl)acetate (148.71 g). As a result, it was confirmed that the thus obtained methyl(3-oxo-2-pentylcyclopentyl)acetate had a fruity jasmine odor and was therefore an excellent perfume material.
283.48 g
at 215℃; for 4h;
To a reaction apparatus equipped with a distillation distillation pipe, 283.48 g of dimethyl 2- (3-oxo-2-pentylcyclopentyl) malonate obtained in Example 1 was added, heated to 215 C.,Water was added dropwise. A dropwise addition reaction was carried out at 215 C. for 4 hours while distilling out generated carbon dioxide and methanol.After completion of the reaction, 203.27 g of crude product was obtained.Methyl (3-oxo-2-pentylcyclopentyl) acetate (148.71 g) obtained by fractionating the crude product was purified by reverse-It has fruity and jasmine-like fragrance,It was also excellent as a perfume material.
Sodium hydroxide pellets (82.6g) were dissolved in methanol (425 ml) with stirring. This solution was added to a stirred solution of methyldihydrojasmonate (425g)(obtained from F. D. Copeland) in methanol (425 ml). The reaction mixture was stirred at room temperature for 24 hours. After this time TLC analysis (10:90 ethylacetate EtOAc):Hexane) confirmed that all starting material had been consumed. Aqueous 1M hydrochloric acid solution was added slowly until the pH of the reaction mixture was ~1. The aqueous/methanol solution was extracted with ethyl acetate (4 x 150 ml) and the combined organic extracts were dried (MgS04) and evaporated under vacuum to give the dihydrojasmonic acid as a pale yellow oil (397.0g,>99%). The structure was confirmed using ¹H and ¹3C NMR.
With sodium hydroxide; In methanol; toluene; at 20℃; for 48h;
Sodium hydroxide pellets (3.53g) were dissolved in methanol (20ml) with stirring, before being added to a solution of the methyldihydrojasmonate (20g) in toluene (20ml). The reaction mixture was stirred at room temperature for 48 hours after which time TLC analysis (10:90 EtOAc:Hexane) indicated that no more starting material was present. The solvents were removed under vacuum to afford the dihydrojasmonic acid sodium salt as ayellow oil. Toluene (3 x 100 ml) was added and removed under vacuum in an attempt to azeotrope off any residue water. However, the sodium salt remained as a pale yellow oil.
With potassium hydroxide; In methanol; toluene; for 18h;Heating / reflux;Product distribution / selectivity;
Methyldihydrojasmonate (10g) was dissolved in toluene (100ml) with stirring. 2M KOH solution in methanol (22.lml) was added and the solution brought to reflux. The reaction mixture was maintained at reflux for 18 hours after which time TLC analysis (10: 90 EtOAc:hexane) indicated that no more starting material was present. The solvents were removed under vacuum to afford the dihydrojasmonic acid potassium salt as a yellow oil. Toluene (3 x 100 ml) was added and removed under vacuum in an attempt to azeotrope off any residual water. However, the potassium salt remained as a yellow oil. The structure was confirmed using ¹H and ¹3C NMR.
General procedure: For a typical 10.0 mmol scale reaction, the starting material was dissolved in isopropenyl acetate (2.2mL, 20 mmol, 2 equiv) and para-toluene sulfonic acid (0.20 g, 1 mmol, 10 mol%) was added. The resulting mixture was stirred at 90C until full conversion was achieved (TLC). Saturated aqueous NaHCO3 (15mL) and Et2O (20mL) were added and the products were extracted using further Et2O (2×20 mL). After drying over Na2SO4 and concentration in vacuo, crude products were purified using SiO2 column chromatography (hexane/EtOAc) where necessary.
98%
With toluene-4-sulfonic acid; at 90℃;
General Procedure for Acetylation of Ketones/Aldehydes (0087) For a typical 10 mmol scale reaction, the starting material was dissolved in isopropenyl acetate (2.2 mL, 2 equivalents) and para-toluene sulfonic acid (0.2 g, 10 mol %) was added. The resulting mixture was stirred at 90 C. until full conversion was achieved (TLC). Saturated aqueous NaHCO3 (15 mL) and Et2O (20 mL) were added and the products were extracted using further Et2O (2×20 mL). After drying over Na2SO4 and concentration in vacuo, crude products were purified using SiO2 column chromatography (hexane/EtOAc) where necessary. Example 1. Methyl 2-(3-acetoxy-2-pentylcyclopent-2-en-1-yl)acetate (1a) Pale brown liquid (5 mmol scale, 1.31 g, 98%). 1H NMR (400 MHz, CDCl3) delta 3.70 (s, 3H), 3.07 (m, 1H), 2.56 (dd, J=4.4, 14.8 Hz, 1H), 2.48 (m, 2H), 2.14 (s, 3H), 2.07-2.24 (m, 3H), 1.80 (m, 1H), 1.63 (m, 1H), 1.42 (m, 1H), 1.27 (m. 5H), 0.90 (t, J=7.9 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) deltaC 173.3, 168.6, 145.2, 128.3, 51.5, 39.5, 38.6, 31.7, 29.6, 27.1, 26.7, 24.4, 22.4, 20.8, 14.0 ppm; FT-IR numax 1008 (m), 1204 (s), 1368 (m), 1436 (w), 1737 (s), 2930 (w) cm-1; GC-MS Rt 4.79 min, m/z 268 [M]+, 226 [M-Ac]+.
ethyl cyano[3-(2-methoxy-2-oxoethyl)-2-pentylcyclopentylidene]ethanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With ammonium acetate; acetic acid; In toluene; for 17h;Reflux; Dean-Stark;
General procedure: The fragrance aldehyde/ketone of interest (1 eq.), ethyl cyanoacetate (1.1 eq. - 6 eq.) and ammonium acetate (0.5 eq. - 3 eq.) in a mixture of acetic acid (1 eq. - 3 eq.) and toluene (150 ml_) were refluxed with azeotropic removal of H2O in a Dean-Stark trap. The reaction mixture was cooled to room temperature (RT), washed with brine, dried over Na2SC>4 and filtered. Subsequently, the solvent was evaporated. The pure products were isolated via flash column chromatography (hexane - ethyl acetate (EtOAc) - 1 % triethylamine) unless otherwise noted. All compounds were found to be cis/trans isomers at the newly formed double bound. Depicted structures however reflect only one isomer.
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