Method for producing α-allylated cycloalkanone

Abstract

Provided is a method with which an α-allylated cycloalkanone is obtained from a macroyclic compound used as a starting material. The method is a method for producing an α-allylated cycloalkanone represented by General Formula (IV), and the method includes a step of reacting a compound represented by General Formula (I) and/or a compound represented by General Formula (II) with a compound represented by General Formula (III) in the presence of an acid catalyst to produce an α-allylated cycloalkanone represented by General Formula (IV), the acid catalyst including an acid catalyst that includes an ammonium cation and an anion. ##STR00001##
where R.sup.1, R.sup.2, and R.sup.3 are the same or different and each of them is an alky group having 1 or mom and 4 or less of carbon atoms, the group -A.sup.1- (it should be noted that the front bond refers to a bond that binds to the carbon atom C.sup.1 and the back bond refers to a bond that binds to the carbon atom C.sup.2) is an alkylene group having 4 or more and 20 or les of carbon atoms that optionally contains a hetero atom and optionally has a substituent, and R.sup.4 is a hydrogen atom or an alkyl group having 1 or more and 4 or less of carbon atoms.

Claims

1. A method for producing an α-allylated cycloalkanone represented by Formula (IV), the method comprising reacting a compound represented by Formula (I) and/or a compound represented by Formula (II) with a compound represented by Formula (III) in the presence of an acid catalyst to produce an α-allylated cycloalkanone represented by Formula (IV), wherein the acid catalyst includes an acid catalyst that consists of an ammonium cation and an anion ##STR00039## where R.sup.1, R.sup.2, and R.sup.3 are the same or different and each of them is an alkyl group having 1 or more and 4 or less of carbon atoms, the group -A.sup.1- is an alkylene group having 4 or more and 20 or less of carbon atoms that optionally contains a hetero atom and optionally has a substituent, and where the front bond of the group -A.sup.1- refers to a bond that binds to the carbon atom C.sup.1 and the back bond of the group -A.sup.1- refers to a bond that binds to the carbon atom C.sup.2 and R.sup.4 is a hydrogen atom or an alkyl group having 1 or more and 4 or less of carbon atoms, the ammonium canon is represented b Formula (X) or Formula (XI); ##STR00040## where R.sup.11, R.sup.12, R.sup.13, and R.sup.14 are the same or different and each of them is a hydrogen atom or an alkyl group having 1 or more and 5 or less of carbon atoms, the anion is a sulfonate anion represented by Formula (XII) or a halide ion: ##STR00041## where R.sup.21 is a hydrogen atom or an alkyl group having 1 or more and 5 or less of carbon atoms.

2. The method according to claim 1, wherein the group -A.sup.1- is an alkylene group having 10 or more and 14 or less of carbon atoms that optionally has a substituent.

3. The method according to claim 1, wherein the group -A.sup.1- is an alkylene group having 10 or more and 12 or less of carbon atoms.

4. The method according to claim 1, wherein an amount of the acid catalyst that is used is 10.sup.−5 equivalents or more and 1 equivalent or less relative to a total amount of the compound of Formula (I) and the compound of Formula (II).

5. The method according to claim 1, wherein the reacting a compound represented by Formula (I) and/or a compound represented by Formula (II) with a compound represented by Formula (III) in the presence of an acid catalyst is performed at a temperature of 120° C. or higher and 150° C. or lower.

6. The method according to claim 1, wherein the reacting is performed using a rectification column.

7. The method according to claim 1, further comprising reacting a compound represented by Formula (V) with an alcohol having 1 or more and 4 or less of carbon atoms in the presence of a second acid catalyst to produce the compound represented by Formula (I) and/or the compound represented by Formula (II), ##STR00042## where R.sup.1, R.sup.2, and R.sup.3 are the same or different and each of them is an alkyl group having 1 or more and 4 or less of carbon atoms, and the group -A.sup.1- is an alkylene group having 4 or more and 20 or less of carbon atoms that optionally contains a hetero atom and optionally has a substituent, and where the front bond of the group -A.sup.1- refers to a bond that binds to the carbon atom C.sup.1 and the back bond of the group -A.sup.1- refers to a bond that binds to the carbon atom C.sup.2.

8. The method according to claim 7, wherein the second acid catalyst is one or more selected from the group consisting of p-toluenesulfonic acid, montmorillonite, and pyridinium p-toluenesulfonate.

9. The method according to claim 7, wherein the second acid catalyst comprises the catalyst which is the same as the acid catalyst.

10. The method according to claim 7, wherein the group -A.sup.1- is an alkylene group having 10 or more and 14 or less of carbon atoms that optionally has a substituent.

11. The method according to claim 7, wherein the group -A.sup.1- is an alkylene group having 10 or more and 12 or less of carbon atoms.

12. The method according to claim 7, wherein the reacting of a compound represented by Formula (V) with an alcohol having 1 or more and 4 or less of carbon atoms in the presence of a second acid catalyst is performed at a temperature of 120° C. or higher and 150° C. or lower.

13. The method according to claim 1, wherein the Formula (I) is Formula (I-1) below, the Formula (II) is Formula (II-1) below, and the Formula (IV) is Formula (IV-1) below: ##STR00043##

14. A method for synthesizing muscenone, the method comprising: reacting a compound represented by Formula (I-1) and/or a compound represented by Formula (II-1) with β-methallyl alcohol in the presence of an acid catalyst to produce an α-allylated cycloalkanone represented by Formula (IV-1), wherein the acid catalyst includes an acid catalyst that consists of an ammonium cation and an anion; (i) cyclization of the α-allylated cycloalkanone represented by General Formula (IV-1); ##STR00044## (ii) hydrogenation; (iii) oxidative cleavage, (iv) reduction; and (v) ring-opening the ammonium cation is represented by General Formula (X) or Formula (XI); ##STR00045## where R.sup.11, R.sup.12, R.sup.13, and R.sup.14 are the same or different and each of them is a hydrogen atom or an alkyl group having 1 or more and 5 or less of carbon atoms, the anion is a sulfonate anion represented by General Formula (XII) or a halide ion: ##STR00046## where R.sup.21 is a hydrogen atom or an alkyl group having 1 or more and 5 or less of carbon atoms.

15. The method according to claim 14, wherein an amount of the acid catalyst that is used is 10.sup.−5 equivalents or more and 1 equivalent or less relative to a total amount of the compound of Formula (I-1) and the compound of Formula (II-1).

16. The method according to claim 14, wherein the reacting a compound represented by Formula (I-1) and/or a compound represented by Formula (II-1) in the presence of an acid catalyst is performed at a temperature of 120° C. or higher and 150° C. or lower.

17. The method according to claim 14, wherein the reacting is performed using a rectification column.

Description

EXAMPLES

(1) Gas Chromatography (GC) Apparatus and Analysis Conditions GC apparatus: Model: GC-6850, manufactured by Agilent Technologies Column: DB-1 (with an inner diameter of 0.25 mm, a length of 30 m, and a membrane thickness of 0.25 μm), manufactured by J&W Carrier gas: He, 1.5 mL/min Injection conditions: 300° C., split ratio of 100/1 Injection amount: 1 μL Detection conditions: FID method, 300° C. Column temperature conditions: 80° C..fwdarw.rising the temperature at 10° C./minute.fwdarw.keeping the temperature at 300° C. for 10 minutes

(2) Compound Identification

(3) Compounds obtained in examples, experimental examples, and the like below were each compared with a commercially available product using GC (gas chromatography) or were each separately produced and isolated through column chromatography, followed by structure confirmation through NMR, IR, and GC-MS. The followings are manufacturers of the commercially available products and documents that were helpful to identify the structures.

(4) 1,1-Dimetoxycyclododecane (I-1): Palisandal (manufactured by Symrise AG: Product No. 690230, CAS No. 950-33-4)

(5) 1,1-Diethoxycyclododecane (I-2): Synthetic Communications, 2008, 38, 2607-2618 was used as a reference.

(6) 1-Methoxy-1-cyclododecene (II-1): Cent. Europ. J. Chem. 2005, 3, 417-431 was used as a reference.

(7) 1-Ethoxy-1-cyclododecene (II-2): Tetrahedron, 1985, 41, 6051-6054 was used as a reference.

(8) 2-(2-Methylallyl)cyclododecanone (IV-1): JP 2010-95447A was used as a reference.

(9) The yield (%) was calculated using the following expression.

(10) $\begin{array}{cc}\mathrm{Yield}=\frac{\frac{\begin{array}{c}\mathrm{Weight}\mathrm{of}\mathrm{reaction}\mathrm{end}\mathrm{solution}\times \\ \mathrm{GC}\mathrm{area}\%\mathrm{of}2-\left(2-\mathrm{methylallyl}\right)\mathrm{cyclododecanone}\end{array}}{236.4}}{\frac{\begin{array}{c}\mathrm{Feed}\mathrm{amount}\mathrm{of}\mathrm{raw}\mathrm{material}\times \\ \mathrm{GC}\mathrm{area}\%\mathrm{of}1,1-\mathrm{dimethoxycyclo}\text{-}\mathrm{dodecane}\end{array}}{228.4}+\frac{\begin{array}{c}\mathrm{Feed}\mathrm{amount}\mathrm{of}\mathrm{raw}\mathrm{material}\times \\ \mathrm{GC}\mathrm{area}\%\mathrm{of}1-\mathrm{methoxy}-1-\mathrm{cyclododecene}\end{array}}{196.3}}\times 100& \left[\mathrm{Mathematical}\mathrm{Formula}1\right]\end{array}$

(11) Here, a GC area % refers to a ratio of an output chart area of the component detected using GC to the entire area.

Production Example 1

Synthesis of Mixture of 1,1-Dimetoxycyclododecane (I-1) and 1-Methoxy-1-cyclododecene (II-1)

(12) ##STR00028##

(13) Cyclododecanone (V-1) (500.0 g, 2.743 mol), trimethyl orthoformate (349.5 g, 3.292 mol), and methanol (264.3 g, 8.229 mol) were placed into a 2-L four-neck flask and stirred at room temperature into a homogeneous solution. Pyridinium p-toluenesulfonate (PPTS, 0.7 g, 2.743 mmol) was added thereto, stirred, and dissolved. A thermometer, a mechanical stirrer, and a 10-step Sulzer rectification column (manufactured by Kyowa Chemical) were installed on the 2-L four-neck flask. Under a nitrogen atmosphere, stirring of the content in the 2-L four-neck flask was started at an outside temperature of 80° C. A reactant was sampled from the 2-L four-neck flask over time and subjected to GC analysis, and thus the conversion rate of cyclododecanone (V-1) was observed. The reaction was stopped 6 hours after the start of the reaction, and the reaction mixture was cooled. As a result of gas chromatography analysis on the reaction solution at the end of the reaction, the component composition was as follows: 1,1-dimetoxycyclododecane (I-1) corresponded to 93.1 GC area %, and 1-methoxy-1-cyclododecene (II-1) corresponded to 3.6 GC area %.

(14) Next, methanol and trimethyl orthoformate contained in the product were distilled off under reduced pressure. AK-shaped pipe, a cooling pipe, and a distillate receiver were installed on the 2-L four-neck flask. Under a nitrogen atmosphere, distillation of the product under reduced pressure was started at an outside temperature of 110° C. The pressure was reduced from the ordinary pressure to 66.5 kPa one hour after the start of the distillation, and then the distillation under reduced pressure was continued. The flow of distillate into the receiver stopped in 2 hours, and the distillation under reduced pressure was finished. As a result of gas chromatography analysis on the reaction solution after the distillation, the component composition was as follows: 1,1-dimethoxycyclododecane (I-1) corresponded to 43.5 GC area %, and 1-methoxy-1-cyclododecene (II-1) corresponded to 54.5 GC area %.

Example 1

Synthesis of 2-(2-Methylallyl)cyclododecanone

(15) ##STR00029##

(16) A thermometer, a mechanical stirrer, and a 10-step Sulzer rectification column were installed on a 2-L four-neck flask containing 1,1-dimetoxycyclododecane (I-1) and 1-methoxy-1-cyclododecene (II-1) synthesized in Production Example 1. At room temperature, β-methallyl alcohol (II-1) (296.7 g, 4.115 mol) was added to the four-neck flask. The content in the flask was stirred into a homogeneous system, and then was heated in an oil bath at an outside temperature of 140° C. under nitrogen stream. The top temperature was monitored overtime and was confirmed to be 65° C. After 3.5 hours, it was confirmed if the content in the flask became free of 1,1-dimetoxycyclododecane (I-1) and 1-methoxy-1-cyclododecene (II-1), and then the reaction was stopped.

(17) Next, a K-shaped pipe, a cooling pipe, and a distillate receiver were installed on the 2-L four-neck flask containing the reaction solution (containing 2-(2-methylallyl)cyclododecanone (IV-1)), the reaction solution was heated and stirred at 18.0 kPa and 120° C. to distill off β-methallyl alcohol (III-1) (distilled-off amount: 67.1 g). After the reaction solution was heated and stirred for 2 hours, the pressure was reduced to 16 kPa, and the reaction solution was heated and stirred for another 1 hour in order to complete the distillation.

(18) After β-methallyl alcohol had been distilled off under reduced pressure, the residue was transferred to a 2-L separable reaction container with a jacket, and then alkali water obtained by dissolving K.sub.2HPO.sub.4 (0.4 g, 2.057 mmol) in 20.2 g of ion-exchange water was added thereto. A mechanical stirrer, a thermometer, a Dimroth condenser, and a nitrogen-flow device were installed on the separable reaction container. The mixture in the separable reaction container was vigorously stirred at room temperature for 1 hour. After the stirring had been finished, the mixture was heated to 80° C. using a condenser and was then left to stand till layers were separated. An aqueous layer (15.4 g) was removed from the separable reaction container, and then the pH of the residue was checked. The pH was 8.0 (pH test paper).

(19) Simple distillation was performed in order to distill off the residual β-methallyl alcohol (III-1) and water from the residue. AK-shaped pipe, a cooling pipe, and a distillate receiver were installed on the separable reaction container containing the residue, the residue was heated and stirred at 0.3 kPa and 130° C. for 2 hours to distill off β-methallyl alcohol (III-1) and water. Thus, a residue (671.2 g) was obtained. Gas chromatography analysis on the residue revealed that 2-(2-methylallyl)cyclododecanone (IV-1) corresponded to 94.7 GC area %. The yield of 2-(2-methylallyl)cyclododecanone (IV 1) calculated from the amount of 2-(2-methylallyl)cyclododecanone obtained was 99.9%.

Production Example 2

Synthesis of Mixture of 1,1-Dimetoxycyclododecane (I-1) and 1-Methoxy-1-cyclododecene (II-1)

(20) ##STR00030##

(21) After cyclododecanone (V-1) (500.0 g, 2.743 mol), trimethyl orthoformate (349.3 g, 3.292 mol), and methanol (263.7 g, 8.229 mol) were placed into a 2-L four-neck flask, and the air was purged with nitrogen, the resultant mixture was stirred at room temperature for 4 hours under a nitrogen atmosphere into a homogeneous solution. Pyridinium p-toluenesulfonate (PPTS, 0.7 g, 2.743 mmol) was added thereto, stirred, and dissolved. A Dimroth condenser was attached to the 2-L four-neck flask, and a circulator was used to flow warm water at 37° C. in the Dimroth condenser. A Dean-Stark dewatering pipe was attached to an end of the Dimroth condenser, and a 200-mL distillate receiver was attached to the lower portion of the dewatering pipe. The distillate receiver was immersed in ice water and was thus cooled with ice. Another Dimroth condenser was attached to the upper portion of the Dean-Stark dewatering pipe, and another circulator was used to flow cold water at 10° C. in the Dimroth condenser. One end of a silicone tube was attached to the top of the Dimroth condenser cooled to 10° C., and the other end was introduced to an ethanol-dry ice trap. A portion beyond the trap was sealed with nitrogen. Under a nitrogen atmosphere, the content in the 2-L four-neck flask was heated and refluxed at a bath temperature of 80° C. for 8 hours. As a result of gas chromatography analysis on the reaction end product, the component composition was as follows: 1,1-dimetoxycyclododecane (I-1) corresponded to 93.1 GC area %, 1-methoxy-1-cyclododecene (II-1) corresponded to 6.2 GC area %, and cyclododecanone (V-1) corresponded to 0.8 GC area %.

(22) A K-shaped pipe, a cooling pipe, and a distillate receiver were installed on the 2-L four-neck flask containing the reaction end product. Under a nitrogen atmosphere, the solvent was distilled off from the reaction end product at 101.3 kPa over 4.5 hours while the bath temperature was raised from 100° C. to 120° C. As a result of gas chromatography analysis on the reaction solution after the distillation, the component composition was as follows: 1,1-dimetoxycyclododecane (I-1) corresponded to 25.9 GC area %, 1-methoxy-1-cyclododecene (II-1) corresponded to 73.7 GC area %, and cyclododecanone (V-1) corresponded to 0.3 GC area %.

Example 2

Synthesis of 2-(2-Methylallyl)cyclododecanone

(23) ##STR00031##

(24) A K-shaped pipe, a cooling pipe, and a distillate receiver were installed on a 2-L four-neck flask containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V-1) synthesized in Production Example 2. β-Methallyl alcohol (III-1) (296.7 g, 4.115 mol) was dripped into the four-neck flask over 8 minutes while the reactants were heated and stirred at a bath temperature of 110° C. under a nitrogen atmosphere. Methanol was distilled off at a bath temperature of 110° C. under nitrogen stream into the four-neck flask till the content of the methallyl cyclododecanone corresponded to 40 to 50 GC area %. After 4 hours, the flow of methanol from the four-neck flask stopped (distilled-off amount: 108.9 g). The K-shaped pipe, the cooling pipe, and the distillate receiver were removed from the four-neck flask, a Dimroth condenser was attached to the four-neck flask, the bath temperature was raised to 130° C., and then the reaction mixture was heated and refluxed for 17 hours.

(25) Next, a K-shaped pipe, a cooling pipe, and a distillate receiver were installed on the 2-L four-neck flask containing the reaction solution, and the reaction solution was heated and stirred at 18.0 kPa and a bath temperature of 120° C. for 3.5 hours to distill off β-methallyl alcohol (III-1) (distilled-off amount: 79.7 g). As a result of gas chromatography analysis on the reaction solution after the distillation, the component composition was as follows: 2-(2-methylallyl)cyclododecanone corresponded to 92.5 GC area %.

(26) Alkali water obtained by dissolving K.sub.2HPO.sub.4 (0.358 g, 2.057 mmol) in 20.0 g of ion-exchange water was added to the 2-L four-neck flask containing the reaction solution after β-methallyl alcohol had been distilled under reduced pressure, and the resultant mixture was vigorously stirred at room temperature for 1 minute. Next, the viscosity of the reaction solution was reduced by raising the bath temperature to 80° C., and then the reaction solution was left to stand for 15 minutes to separate layers. The pH of the aqueous layer of the reaction solution was 8.0 (pH test paper). As a result of gas chromatography analysis on the oil layer of the reaction solution, 2-(2-methylallyl)cyclododecanone (IV-1) corresponded to 92.5 GC area %. The amount of the oil layer obtained was 644.9 g (theoretical amount: 648.5 g). The yield of 2-(2-methylallyl)cyclododecanone (IV-1) calculated from the amount of 2-(2-methylallyl)cyclododecanone obtained was 92.4%.

Production Example 3

Synthesis of Mixture of 1,1-Dimethoxycyclododecane (1-2) and 1-Ethoxy-1-cyclododecene (II-2)

(27) ##STR00032##

(28) Cyclododecanone (V-1) (4.4 g, 0.024 mol), triethyl orthoformate (8.6 g, 0.058 mol), and ethanol (6.6 g, 0.14 mol were placed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760). Pyridinium p-toluenesulfonate (PPTS, 0.035 g, 0.00014 mmol) was added thereto, stirred, and dissolved. Then, under a nitrogen atmosphere, the resultant mixture was heated and refluxed at a bath temperature of 90° C. for 36 hours.

(29) The reaction solution obtained at the end of the reaction was heated at 101.3 kPa to 165° C. by gradually raising the bath temperature from 100° C. Then, the solvent was distilled off from the four-neck flask over 7 hours. As a result of gas chromatography analysis on the reaction solution after the distillation, the component composition was as follows: 1,1-dietoxycyclododecane (I-2) corresponded to 65.7%, 1-ethoxy-1-cyclododecene (II-2) corresponded to 15.6%, and cyclododecanone (V-1) corresponded to %.

Example 3

Synthesis of 2-(2-Methylallyl)cyclododecanone

(30) ##STR00033##

(31) The reaction solution synthesized in Production Example 3 that contained 1,1-diethoxycyclododecane (1-2) in an amount of 65.7%, 1-ethoxy-1-cyclododecene (II-2) in an amount of 15.6%, and cyclododecanone (V-1) in an amount of %, and β-methallyl alcohol (III-1) (5.2 g, 0.072 mol) were placed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760). The resultant mixture was heated at 140° C. for 11 hours. A saturated aqueous solution of sodium hydrogen carbonate (10 ml) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (7.0 g). 2-(2-Methylallyl)cyclododecanone (IV-1) in the reaction end solution corresponded to 79.2 GC area %, and the yield was 92.4%.

Example 4

Synthesis of 2-(2-Methylallyl)cyclododecanone

(32) ##STR00034##

(33) A mixture (6.1 g, 27.0 mmol; manufactured by Symrise AG) containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V-1), β-methallyl alcohol (III-1) (2.6 g, 36.0 mmol), and ammonium chloride (NH.sub.4Cl, 0.7 g, 0.13 mmol) were weighed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760), and then heated at 140° C. for 3 hours using Personal Organic Synthesizer (Tokyo Rikakikai Co., Ltd., EYELA: CCX-3200). A saturated aqueous solution of sodium hydrogen carbonate (10 ml) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (6.11 g). 2-(2-Methylallyl)cyclododecanone (IV-1) in the reaction end solution corresponded to 92.3 GC area %, and the yield was 87.9%.

Examples 5 to 7

(34) 2-(2-Methylallyl)cyclododecanone (IV-1) was synthesized in the same manner as in Example 4, except that the equivalent of the catalyst (NH.sub.4Cl) in Example 4 was changed as listed in Table 3.

Examples 8 to 10

(35) 2-(2-Methylallycyclododecanone (IV-1) was synthesized in the same manner as in Example 4, except that the catalyst (NH.sub.4Cl) in Example 4 was changed to pyridinium p-toluenesulfonate (PPTS) and the equivalent thereof was changed as listed in Table 3.

Example 11

(36) ##STR00035##

(37) A mixture (3.2 g, 13.8 mmol; manufactured by Symrise AG) containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V-1), β-methallyl alcohol (III-1) (1.4 g, 19.7 mmol), and p-toluenesulfonic acid monohydrate (PTS, 0.0026 g, 0.014 mmol) were weighed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760), and then heated at 140° C. for 2 hours using Personal Organic Synthesizer (Tokyo Rikakikai Co., Ltd., EYELA: CCX-3200). A saturated aqueous solution of sodium hydrogen carbonate (10 mL) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (3.5 g). 2-(2-Methylallyl)cyclododecanone (IV-1) in the reaction end solution corresponded to 88.7 GC area %, and the yield was 92.9%.

Example 12

Synthesis of 2-(2-Methylallyl)cyclododecanone

(38) ##STR00036##

(39) A mixture (6.1 g, 27.0 mmol; manufactured by Symrise AG) containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V-1), β-methallyl alcohol (III-1) (2.6 g, 36.0 mmol), and pyridinium p-toluenesulfonate (PPTS, 0.006 g, 0.024 mmol) were weighed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760), and then heated at 140° C. for 2 hours using Personal Organic Synthesizer (Tokyo Rikakikai Co., Ltd., EYELA: CCX-3200). A saturated aqueous solution of sodium hydrogen carbonate (10 mL) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (6.7 g). 2-(2-Methylallyl)cyclododecanone (IV-1) in the reaction end solution corresponded to 92.3 GC area %, and the yield was 96.6%.

Comparative Example 1

Synthesis of 2-(2-Methylallyl)cyclododecanone

(40) ##STR00037##

(41) A mixture (6.1 g, 24.1 mmol manufactured by Symrise AG) containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V-1), β-methallyl alcohol (III-1) (3.6 g, 50.0 mmol), and malonic acid (0.003 g, 0.027 mmol, pKa1 2.65, pKa2 5.28) were weighed into a glass container with a glass side arm (Tokyo Rikakikai Co., Ltd., EYELA: Product No. 212760), and then heated at 140° C. for 2 hours using Personal Organic Synthesizer (Tokyo Rikakikai Co., Ltd., EYELA: CCX-3200). A saturated aqueous solution of sodium hydrogen carbonate (10 mL) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (5.6 g). 2-(2-Methylallyl)cyclododecanone (IV-1) in the reaction end solution corresponded to 27.6 GC area %, and the yield was 24.2%.

Comparative Example 2

Synthesis of 2-(2-Methylallyl)cyclododecanone

(42) ##STR00038##

(43) A mixture (6.1 g, 24.1 mmol; manufactured by Symrise AG) containing 1,1-dimetoxycyclododecane (I-1), 1-methoxy-1-cyclododecene (II-1), and cyclododecanone (V1), β-methallyl alcohol (III-1) (3.6 g, 50.0 mm), and propionic acid (0.004 g, 0.047 mmol, pKa 4.67) were weighed into a glass container with a glass side arm (Tokyo Rikakiikai Co., Ltd., EYELA: Product No. 212760), and then heated at 140° C. for 2 hours using Personal Organic Synthesizer (Tokyo Rikakikai Co., Ltd., EYELA: CCX-3200). A saturated aqueous solution of sodium hydrogencarbonate (10 mL) was added to the reaction solution, and the resultant mixture was stirred for 5 minutes. The oil layer of the obtained reaction end product was diluted with diethyl ether, and then the aqueous layer was removed. The solvent in the oil layer was distilled off under reduced pressure, and thus a reaction end solution was obtained (7.4 g). 2-(2-Methylallyl)cyclododecanone (I) in the reaction end solution corresponded to 0.3 GC area %, and the yield was 0.3%.

(44) Table 1 below shows the details of all of the examples and comparative examples above.

(45) TABLE-US-00001 TABLE 1 Equivalent of Yield of acid catalyst compound of Acid relative to Formula Raw material catalyst raw material.sup.*1 (IV-1)(%) Ex. 1 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.001 99.9 and 1-methoxy-1-cyclododecene (II-1) Ex. 2 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.001 92.4 and 1-methoxy-1-cyclododecene (II-1) Ex. 3 Mixture of 1,1-dietoxycyclododecane (I-1) PPTS 0.005 92.4 and 1-ethoxy-1-cyclododecene (II-1) Ex. 4 Mixture of 1,1-dimetoxycyclododecane (I-1) NH.sub.4Cl 0.005 87.9 and 1-methoxy-1-cyclododecene (II-1) Ex. 5 Mixture of 1,1-dimetoxycyclododecane (I-1) NH.sub.4Cl 0.1 93.4 and 1-methoxy-1-cyclododecenc (II-1) Ex. 6 Mixture of 1,1-dimetoxycyclododecane (I-1) NH.sub.4Cl 0.05 95.1 and 1-methoxy-1-cyclododecene (II-1) Ex. 7 Mixture of 1,1-dimetoxycyclododecane (I-1) NH.sub.4Cl 0.005 94.1 and 1-methoxy-1-cyclododecene (II-1) Ex. 8 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.005 78.0 and 1-methoxy-1-cyclododecene (II-1) Ex. 9 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.01 74.6 and 1-methoxy-1-cyclododecene (II-1) Ex. 10 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.1 44.5 and 1-methoxy-1-cyclododecene (II-1) Ex. 11 Mixture of 1,1-dimetoxycyclododecane (I-1) PTS 0.001 92.9 and 1-methoxy-1-cyclododecene (II-1) Ex. 12 Mixture of 1,1-dimetoxycyclododecane (I-1) PPTS 0.001 96.6 and 1-methoxy-1-cyclododecene (II-1) Comp. Ex. 1 Mixture of 1,1-dimetoxycyclododecane (I-1) Malonic 0.001 24.2 and 1-methoxy-1-cyclododecene (II-1) acid Comp. Ex. 2 Mixture of 1,1-dimetoxycyclododecane (I-1) Propionic 0.002 0.3 and 1-methoxy-1-cyclododecene (II-1) acid .sup.*1“Raw material” means the total of the compound of General Formula (I) and the compound of General Formula (II)

(46) As can be appreciated from Table 1 above, with the method of the present invention, it is possible to obtain a highly pure compound of Formula (IV) in increased yield from a compound of Formula (I) and/or a compound of Formula (II).

INDUSTRIAL APPLICABILITY

(47) With the production method of the present invention, it is possible to produce a highly pure compound of Formula (IV) in increased yield. Furthermore, a compound of Formula (IV) is useful to produce muscenone.