process for producing optically active 3,7-dimethyl-6-octenol

Printed by Jouve, 75001 PARIS (FR)

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(12) NEW EUROPEAN PATENT SPECIFICATIONAfter opposition procedure

(45) Date of publication and mention of the opposition decision: 28.04.2010 Bulletin 2010/17

(45) Mention of the grant of the patent: 13.12.2006 Bulletin 2006/50

(21) Application number: 01400874.2

(22) Date of filing: 05.04.2001

(51) Int Cl.:C07C 53/00 (2006.01) C07B 53/00 (2006.01)

C07C 209/00 (2006.01) C07C 209/68 (2006.01)

C07C 211/21 (2006.01) C07C 45/42 (2006.01)

C07C 47/21 (2006.01) C07C 29/141 (2006.01)

C07C 33/025 (2006.01)

(54) Process for producing optically active 3,7-dimethyl-6-octenol and process for producing intermediate therefore

Verfahren zur Herstellung von optisch aktiven 3,7-Dimethyl-6-octenol und Verfahren zur Herstellung von Zwischenprodukt dafür

Procédé de préparation de 3,7-diméthyl-6-octénol optiquement actif et procédé de préparation d’un intermédiaire pour ce procédé

(84) Designated Contracting States: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR

(30) Priority: 07.04.2000 JP 2000106649

(43) Date of publication of application: 10.10.2001 Bulletin 2001/41

(73) Proprietor: Takasago International CorporationTokyo (JP)

(72) Inventors: • Yamada, Shinya,

c/o Takasago International Corp.Hiratsuka-shi,Kanagawa (JP)

• Hori, Yoji,c/o Takasago International Corp.Hiratsuka-shi,Kanagawa (JP)

• Okeda, Yoshiki,c/o Takasago International Corp.Hiratsuka-shi,Kanagawa (JP)

• Hagiwara, Toshimitsu,c/o Takasago Int. Corp.Hiratsuka-shi,Kanagawa (JP)

(74) Representative: Uchida, Kenji et alS.A. Fedit-Loriot et Autres Conseils en Propriété Industrielle 38, avenue Hoche75008 Paris (FR)

(56) References cited: EP-A- 0 156 607 US-A- 4 029 709US-A- 4 107 219

• KUNIHIKO TAKABE ET AL.: "Telomerization of isoprene with dialkylamine: N,N-diethylnerylamine" ORGANIC SYNTHESES, [Online] vol. VIII, 1993, page 190 XP002250001 Retrieved from the Internet: <URL:http://www.orgsyn.org> [retrieved on 2003-08-01]

• KAZUHIDE TANI ET AL.: "(R)-N.N-Diethyl-(E)-citronellalenamine and (R)-(+)-citronellal via isomerization of N,N-diethylgeranylamine or N,N-diethylamine" ORGANIC SYNTHESES, [Online] vol. VIII, 1993, page 183 XP002250002 Retrieved from the Internet: <URL:http://orgsyn.org> [retrieved on 2003-08-01]

• KAZUHIDE TANI ET AL.: "Highly Enantioselective Isomerization of Prochiral Allylamines Catalysed by Chiral Diphosphine Rhodium (I) Complexes. Preparation of Optically Active Enamines" J.AM.CHEM.SOC., vol. 106, 1984, pages 5208-5217, XP002250003

• DATABASE WPI Derwent Publications Ltd., London, GB; AN 1977-56547Y XP002250004 "Citronellal prepared from geranylamine derivatives o nerylamine derivatives by isomering to enamines with catalyst containing cobalt and phosphorus, and hydrolysing the enamines." & JP 52 077005 A (TAKASAGO PERFUMERY CO LTD), 29 June 1977 (1977-06-29)

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Description

FIELD OF THE INVENTION

[0001] The present invention relates to a process for producing optically active 3,7-dimethyl-6-octenol which containsfrom 2 to 10% by weight optically active 3,7-dimethyl-7-octenol and is useful as a material for perfumes. The inventionfurther relates to a process for producing a cis-3,7-dimethyl-2,6-octadienylamine compound (hereinafter referred tosimply as "nerylamine compound") containing from 2 to 10% by weight cis-3,7-dimethyl-2,7-octadienylamine compound(hereinafter referred to simply as "α-nerylamine compound"), these amine compounds being intermediates for thoseoptically active compounds.[0002] The optically active 3,7-dimethyl-6-octenol provided by the invention, which contains from 2 to 10% by weightoptically active 3,7-dimethyl-7-octenol, has an elegant rosy fragrance and is extremely useful for fragrance impartationto aromatic articles.

BACKGROUND OF THE INVENTION

[0003] 3,7-Dimethyl-6-octenol (hereinafter referred to also as "citronellol") has conventionally been known as a materialfor rosy perfumes, and the d-, 1-, and dl-isomers have already come to be produced and practically used [Motoichi Indo,Gôsei Kôryô (Kagaku To Shôhin Chishiki), Kagaku Kogyo Nippo Sha, 1996]. Such perfume substances are not limitedto alcohols. These compounds, even when slightly different in structure, can generally have utterly different fragrancesand differ also in properties, e.g., the ability to be retained and volatility. Consequently, for obtaining a new perfume, itis highly important to synthesize many compounds and investigate their fragrances.[0004] Disclosed as processes for producing a nerylamine compound through the telomerization of isoprene with anamine compound are a method in which an n-butyllithium catalyst is used (JP-A-49-48610 (the term "JP-A" as usedherein means an "unexamined published Japanese patent application")), a method in which a catalyst prepared from asecondary amine, a conjugated olefin, and lithium metal is used (JP-A-51-4109), a method in which a catalyst preparedfrom a secondary amine, a polynuclear aromatic compound and/or a polyphenyl compound, and lithium metal is used(JP-A-53-135912), and a method in which a catalyst prepared from a secondary amine, a conjugated diene compoundand/or polycyclic aromatic compound as an unsaturated hydrocarbon, a lithium salt, and sodium metal and/or potassiummetal is used (U.S. Patent 4,186,148).[0005] However, the method disclosed in JP-A-49-48610 has the following drawbacks. The method necessitates areaction time as long as from 5.5 to 24 hours despite the use of an n-butyllithium catalyst and has low selectivity tonerylamine. Consequently, it is difficult to apply the method to an industrial process for continuously conducting thereaction and this application is costly.[0006] The method disclosed in JP-A-51-4109 has attained a yield as high as about 85% using a different lithiumcatalyst. However, a reaction time of 18 hours is necessary for attaining the yield. This method also is difficult to practiceindustrially.[0007] The method disclosed in JP-A-53-135912 has succeeded in obtaining nerylamine in a yield of 86.4% by usinga different lithium catalyst to react an amine with isoprene in a proportion of 1:5 at 80°C for 3 hours. However, since theisoprene amount is excessively large as compared with the amine amount, there have been problems concerning therecovery of isoprene and the yield of nerylamine.[0008] The method disclosed in U.S. Patent 4,186,148 has succeeded in obtaining nerylamine in a yield of 85% byreacting an amine with isoprene in a proportion of 1:5 first at 65°C for 1 hour and then at 80°C for 4 hours. However,since the isoprene amount is excessively large as compared with the amine amount, there have been problems concerningthe recovery of isoprene and the yield of nerylamine. In addition, this method is unsuitable for continuous reactionbecause preparation of the lithium catalyst necessitates use of a dangerous metal such as sodium or potassium.[0009] Furthermore, although JP-A-49-48610 discloses an N,N-dialkyl(3-methyl-2-butenyl)amine (formula 5), an N,N-dialkyl(2-methyl-2-butenyl) amine (formula 6), and an N,N-dialkyl(2-isopropenyl-5-methyl-4-hexenyl)amine (formula7), which are yielded as by-products by the method disclosed therein, there are no descriptions therein concerning theα-nerylamine represented by formula 4 in the invention. No descriptions concerning by-products are given in the spec-ification of the other references cited above.

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[0010] In a conventional method for asymmetrically isomerizing a cis-dialkyloctadienylamine obtained, the amine isisomerized in tetrahydrofuran using a rhodium-BINAP catalyst and then hydrolyzed with sulfuric acid to obtain an aldehyde(see U.S. Patent 4,604,474)Besides, Document "Bull. Soc. Chim." (No. 45, 1929, pages 809-827) discloses that citronellol has the isopropylideneform (β) and that the natural or synthetic product starting from citronellal is always a mixture of approximately 10 to 20%of the methylene isomers (α).Further, Document "Römpp Chemie Lexikon" (Vol. 1, 1996, page 759, 10th ed. and Vol. 5, 1999, page 3812, 10th ed.)discloses that α-citronellol has a rose-like perfume.Also, Document "Römpp Chemie Lexikon" (Vol. 1, 1989, page 742, 9th ed. and Vol. 5, 1992, page 3872, 9th ed.) disclosesthat citronellol of natural origin is in an optically active form and β-citronellol has a rosy perfume.[0011] The present inventors made intensive investigations on methods for synthesizing optically active 3,7-dimethyl-6-octenol (citronellol), which is useful as a material for rosy perfumes. During these investigations, they have found thatwhen the telomerization of an alkylamine with isoprene, which is known as a process for producing cis-3,7-dimethyl-2,6-octadienylamine (a nerylamine compound) serving as an intermediate for citronellol, is conducted under strictlyselected reaction conditions, then cis-3,7-dimethyl-2,7-octadienylamine (an α-nerylamine compound) serving as anintermediate for optically active 3,7-dimethyl-7-octenol, which also is useful as a material for rosy perfumes, is yieldedin a large amount.[0012] The inventors have further found that asymmetrically isomerizing the mixture of nerylamine and α-nerylaminein the same manner as in the reaction step of synthesis of citronellol from nerylamine, subsequently hydrolyzing themixture, and reducing the resultant citronellal mixture gives a mixture comprising optically active 3,7-dimethyl-7-octenoland optically active 3,7-dimethyl-6-octenol (citronellol) and this mixture is more useful as a material for rosy perfumesthan conventional ones. The invention has been completed based on this finding.

SUMMARY OF THE INVENTION

[0013] An object of the invention is to provide a process for stably producing optically active 3,7-dimethyl-6-octenolwhich contains from 2 to 10% by weight optically active 3,7-dimethyl-7-octenol and is extremely useful as a material forrosy perfumes. Another object of the invention is to provide a process for efficiently producing a cis-3,7-dimethyl-2,6-octadienylamine compound (nerylamine compound) containing from 2 to 10% by weight cis-3,7-dimethyl-2,7-octadi-enylamine compound (α-nerylamine compound), these amine compounds being useful as materials for those opticallyactive compounds.[0014] The invention, which makes it possible to stably produce the above-described optically active 3,7-dimethyl-6-octenol (citronellol) containing from 2 to 10% by weight optically active 3,7-dimethyl-7-octenol, includes the following.

(1) A process for producing optically active 3,7-dimethyl-6-octenol, a compound having an excellent fragrancerepresented by formula (1),

containing from 2 to 10% by weight optically active 3,7-dimethyl-7-octenol represented by formula (2):

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which comprises subjecting a mixture of an alkylamine and isoprene in a molar ratio in the range of from 1:4 to 1:4.5 to telomerization at a reaction temperature of from 80 to 100°C for from 2.5 to 3.5 hours in the presence of analkyllithium catalyst and/or phenyllithium catalyst to thereby prepare a nerylamine compound represented by generalformula (3):

wherein R1 and R2 each represents a hydrogen atom or an alkyl, aralkyl, or aryl group having 1 to 10 carbon atoms,containing from 2 to 10% by weight α-nerylamine compound represented by general formula (4):

wherein R1 and R2 each represents a hydrogen atom or an alkyl, aralkyl, or aryl group having 1 to 10 carbon atoms,asymmetrically isomerizing the resultant reaction product mixture, subsequently hydrolyzing the mixture to obtaina citronellal mixture, and then reducing the citronellal mixture.(2) A process for producing a nerylamine compound represented by general formula (3):

wherein R1 and R2 each represents a hydrogen atom or an alkyl, aralkyl, or aryl group having 1 to 10 carbon atoms,useful as an intermediate for 3,7-dimethyl-6-octenol, which contains from 2 to 10% by weight α-nerylamine compoundrepresented by general formula (4):

wherein R1 and R2 each represents a hydrogen atom or an alkyl, aralkyl, or aryl group having 1 to 10 carbon atoms,which comprises subjecting a mixture of an alkylamine and isoprene in a molar ratio of from 1:4 to 1:4.5 to telomerizationat a reaction temperature of from 80 to 100°C for from 2.5 to 3.5 hours in the presence of an alkyllithium catalyst and/or

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phenyllithium catalyst.

DETAILED DESCRIPTION OF THE INVENTION

[0015] The invention will be explained below in detail.[0016] Examples of the amine compound to be used in the invention include dimethylamine, diethylamine, di-n-pro-pylamine, diisopropylamine, di-n-butylamine, cyclohexylamine, piperidine, pyrrolidine, and morpholine. Of these, dimeth-ylamine, diethylamine, di-n-propylamine, and diisopropylamine are preferred.[0017] The amount of the isoprene to be added is preferably from 3 to 5 times by mole, more preferably from 4 to 4.5times by mole, the amount of the amine compound.[0018] Examples of the lithium catalyst include methyllithium, n-butyllithium, sec-butyllithium, tert-butyllithium, andphenyllithium. Of these, n-butyllithium is preferred. The amount of the lithium catalyst to be used in the telomerizationmay be from 0.5 to 5 mol% based on the amine compound to be subjected to the reaction.[0019] The telomerization reaction of the starting amine compound with isoprene for producing a nerylamine compoundcontaining from 2 to 10%, preferably from 3 to 6% α-nerylamine compound can be accomplished by introducing thelithium catalyst and the amine compound and isoprene as starting materials into the same reactor simultaneously orsuccessively.[0020] The reaction is conducted in an inert atmosphere with or without a solvent. In the case of using a solvent, thesolvent is one in which the lithium compound used as a catalyst can dissolve. Examples of solvents which can be usedinclude hydrocarbon solvents such as benzene and toluene and ether solvents such as tetrahydrofuran.[0021] The temperature for the reaction is generally from 50 to 120°C, preferably from 80 to 100°C. The reaction isconducted for generally from 2 to 6 hours, preferably from 2.5 to 3.5 hours.[0022] Subsequently, water, ethanol, CO2, or the like is added to the reaction mixture resulting from the telomerizationof the starting isoprene with the starting amine compound conducted under the reaction conditions described above,whereby the lithium compound used as a catalyst is deactivated. Thereafter, the oil layer is distilled to thereby recovera nerylamine fraction containing from 2 to 10% α-nerylamine compound.[0023] The thus-obtained nerylamine fraction containing from 2 to 10% α-nerylamine compound is subjected to anasymmetric isomerization reaction.[0024] The asymmetric isomerization reaction is conducted in a solvent in an inert atmosphere such as, e.g., nitrogenusing a known catalyst for asymmetric isomerization.[0025] As the solvent may be used an ether such as tetrahydrofuran, a ketone such as acetone, or the like.[0026] As the catalyst can be used a rhodium-phosphine complex catalyst (see JB-B-1-42959) or a catalyst such as[Rh (COD) (BINAP)]ClO4, [Rh(BINAP)2]ClO4, [Rh (BINAP)2]OTf, [Rh(COD) (t-BINAP)]ClO4, [Rh(t-BINAP)2]ClO4, or [Rh(t-BINAP)2]OTf, wherein "BINAP" means a 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl group, "t-BINAP" means a 2,2’-bis(di-p-tolylphosphino)-1,1’-binaphthyl group, and "OTf" means a triflate group.[0027] The reaction temperature is generally from 50 to 130°C, preferably from 100 to 110°C. After completion of thereaction, the reaction mixture is transferred to a distiller, where the solvent is removed by vacuum distillation to obtaina geranyl enamine compound (citronellal enamine compound) as an isomerization reaction product.[0028] The geranyl enamine compound obtained by the asymmetric isomerization reaction is subjected to a hydrolysisreaction and thereby converted to a citronellal compound.[0029] The hydrolysis reaction is an acid hydrolysis reaction. Although either an organic acid or an inorganic acid canbe used as the acid, it is preferred to use an inorganic acid such as sulfuric acid or hydrochloric acid.[0030] The hydrolysis reaction is conducted by dissolving the geranyl enamine compound in an inert solvent, e.g.,toluene, and then adding an acid, e.g., sulfuric acid, to the solution to treat the enamine compound at a temperature ofabout from 0 to 10°C in an ordinary manner.[0031] The citronellal compound obtained by the hydrolysis reaction is subjected to a catalytic hydrogenation reactionin an ordinary manner. Thus, the citronellal compound, which is an aldehyde compound, is converted to an opticallyactive citronellol compound which is an alcohol compound.[0032] This reaction is conducted with stirring using a catalyst ordinarily used for reactions for hydrogenating aldehydecompounds into alcohol compounds, such as, e.g., a copper-chromium catalyst, palladium catalyst, or Raney nickelcatalyst.[0033] Finally, the catalyst is removed from the hydrogenation reaction mixture, which is then subjected to vacuumdistillation. Thus, the target citronellol compound is obtained.

EXAMPLES

[0034] The invention will be explained below in detail by reference to Examples and Comparative Examples. However,the invention should not be construed as being limited by these Examples in any way.

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1) Reaction products were examined by gas chromatography (GLC) under the following conditions.Analytical instrument used: gas chromatograph G5000, manufactured by Hitachi Ltd.Column: TC-1 (0.25 mm x 30 m), manufactured by GL SciencesDetector: FID (Flame Ionization Detector)2) Reaction products were identified by 1H-NMR spectroscopy based on a comparison with data given in the literature.1H-NMR: DRX-500 (1H, 500 MHz), manufactured by Bruker Instruments Inc.

EXAMPLE 1

Synthesis of Cis-3,7-dimethyl-2,6-octadienyldiethylamine (Neryldiethylamine) Containing 6 wt% Cis-3,7-dimethyl-2,7-octadienyldiethylamine (α-Neryldiethylamine):

[0035] A solution prepared by mixing 2.93 g (40.0 mmol) of diethylamine with 18.0 ml (180 mmol) of isoprene wasintroduced into a 100-ml pressure tube in a nitrogen atmosphere. Thereto was gradually added dropwise at 0°C a solution(1.6 M solution) prepared by dissolving 0.064 g of n-butyllithium (1.0 mmol) in 0.63 ml of hexane. This mixture was stirredfirst at room temperature for 15 minutes and then at 90°C for 2.5 hours. To the resultant reaction mixture was added0.3 ml of water to deactivate the catalyst. After liquid separation, the organic layer was separated and distilled to recoverthe unreacted isoprene. Subsequently, the concentrate remaining after the isoprene recovery was distilled under reducedpressure to obtain 7.29 g (34.8 mmol; GC yield, 87.0%) of the target mixture comprising α-neryldiethylamine and neryl-diethylamine.Boiling point, 83-85°C/400 Pa.Neryldiethylamine1H-MMR(CDCl3) δ 1.03 (6H, T, J=7.1 Hz), 1.61 (3H, s), 1.68 (3H, s), 1.72 (3H, m), 2.07 (4H, m), 2.50 (4H, t, J=7.1 Hz),3.04 (2H, d, J=6.8 Hz), 5.11 (1H, m), 5.26 (1H, m).α-NeryldiethylamineH-NMR(CDCl3) δ 1.03 (6H, T, J=7.1 Hz), 1.61 (3H, s), 1.68 (3H, s), 1.72 (3H, m), 2.07 (4H, m), 2.50 (4H, t, J=7.1 Hz),3.04 (2H, d, J=6.8 Hz), 4.68 (1H, m), 4.71 (1H, m), 5.26 (1H, m).

EXAMPLE 2

Synthesis of Neryldiethylamine Containing 6 wt% α-Neryldiethylamine:

[0036] The same procedure as in Example 1 was conducted, except that the high-temperature stirring was conductedat 90°C for 3 hours. Thus, the target compound was obtained in an amount of 7.16 g (34.2 mmol; GC yield, 85.5%).

EXAMPLE 3


[0037] The same procedure as in Example 1 was conducted, except that the high-temperature stirring was conductedat 80°C for 3 hours. Thus, the target compound was obtained in an amount of 6.85 g (32.7 mmol; GC yield, 81.8%).

EXAMPLE 4


[0038] The same procedure as in Example 1 was conducted, except that the high-temperature stirring was conductedat 80°C for 3.5 hours. Thus, the target compound was obtained in an amount of 7.19 g (34.3 mmol; GC yield, 85.8%).

EXAMPLE 5


[0039] The same procedure as in Example 1 was conducted, except that 16.0 ml (160 mmol) of isoprene was usedin place of 18.0 ml (180 mmol) of isoprene and that the high-temperature stirring was conducted at 90°C for 3 hours.Thus, the target compound was obtained in an amount of 6.49 g (31.0 mmol; GC yield, 77.4%).

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EXAMPLE 6


[0040] Into a 5-L autoclave were introduced 365.6 g (5.0 mol) of diethylamine and 1,532 g (22.5 mol) of isoprene ina nitrogen atmosphere. Thereto was added 78.1 ml of a hexane solution (1.6 M solution) of n-butyllithium (125 mmol)with a syringe at 11°C. The resultant mixture was heated to 90°C over 35 minutes. This reaction mixture was stirred at90°C for 2.5 hours and then rapidly cooled to 15°C. Thereto was added 40 ml of water. This mixture was stirred at around10°C for 1.5 hours. After liquid separation, the organic layer was distilled to obtain 843.4 g (4.03 mol; isolation yield,80.6%) of the target compound. The still residue weighed 177.3 g.

COMPARATIVE EXAMPLE 1


[0041] The same procedure as in Example 1 was conducted, except that 14.0 ml (140 mmol) of isoprene was usedin place of 18.0 ml (180 mmol) of isoprene and that the high-temperature stirring was conducted at 90°C for 3.5 hours.Thus, the target compound was obtained in an amount of 5.75 g (27.5 mmol; GC yield, 68.7%).



[0042] The same procedure as in Example 1 was conducted, except that 12.0 ml (120 mmol) of isoprene was usedin place of 18.0 ml (180 mmol) of isoprene and that the high-temperature stirring was conducted at 70°C for 4 hours.Thus, the target compound was obtained in an amount of 2.87 g (13.7 mmol; GC yield, 34.3%).



[0043] The same procedure as in Example 1 was conducted, except that 14.0 ml (140 mmol) of isoprene was usedin place of 18.0 ml (180 mmol) of isoprene and that the high-temperature stirring was conducted at 70°C for 4 hours.Thus, the target compound was obtained in an amount of 4.19 g (20.0 mmol; GC yield, 49.9%).[0044] Reaction conditions used in each of the Examples and Comparative Examples and the yields obtained thereinare shown in Table 1.

Table 1

Example Isoprene/ diethylamine Reaction temperature (°C)

Reaction time (hr) Yield (%)

Example 1 4.5 90 2.5 87.0 (GC)

Example 2 4.5 90 3.0 85.5 (GC)

Example 3 4.5 80 3.0 81.8 (GC)

Example 4 4.5 80 3.5 85.8 (GC)

Example 5 4.0 90 3.0 77.4 (GC)

Example 6 4.5 90 2.5 80.6 (isolation)

Comparative Example 1

3.5 90 3.5 68.7 (GC)


3.0 70 4.0 34.3 (GC)


3.5 70 4.0 49.9 (GC)

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[0045] Examples 1 to 6 and Comparative Examples 1 to 3 show results of telomerization conducted with the aid of abutyllithium catalyst.[0046] Examples 1 to 6 demonstrated that the telomerization conducted for from 2.5 to 3.5 hours gives neryldiethylaminein a yield as high as from 77.4 to 87.0% when the isoprene/diethylamine ratio is in the range of from 4.0 to 4.5 and thereaction temperature is 80°C or 90°C. Even when the same butyllithium catalyst was used, a prolonged reaction timeof 5.5 hours was necessary at a reaction temperature of 75°C.[0047] Comparative Example 1 shows results of the reaction conducted at a temperature of 90°C for 3.5 hours usingan isoprene/diethylamine ratio reduced to 3.5. The yield was as low as 68.7%. Consequently, the isoprene/diethylamineratio should be 4.0 or higher.[0048] Comparative Examples 2 and 3 show results of the reaction conducted at a temperature of 70°C using isoprene/diethylamine ratios reduced to 3.0 and 3.5. The yields were as low as 34.3% and 49.9% when the reaction time was 4hours. Consequently, in order to cause the reaction to proceed in a short time period, the reaction temperature and theisoprene/diethylamine ratio should be 80°C or higher and 4.0 or higher, respectively.

EXAMPLE 7

<Asymmetric Isomerization>

[0049] Into a pressure tube in which the atmosphere had been replaced with nitrogen were introduced 297.6 g (1.424mol) of the neryldiethylamine obtained in Example 6, 377 ml of dry THF, and a THF solution of [Rh((R)-t-BINAP)2]ClO4(23.2 ml/L; S/C=7000). The THF was recovered at a temperature of 110°C and ordinary pressure. Thereafter, 337.6 gof a crude enamine was recovered under reduced pressure. The enamine obtained was distilled under reduced pressure(76°C/13.3 Pa) to obtain 294.4 g of (R)-citronellal enamine. Yield, 99.0% (of which α-citronellal enamine accounted for3.5%).

EXAMPLE 8

<Asymmetric Isomerization>

[0050] The same operation as in Example 7 was conducted except that 5.8 ml of a THF solution of [Rh((S)-t-BINAP)2]ClO4 (0.91 mol/L; S/C=7000) was used in place of [Rh ((R)-t-BINAP)2] ClO4. The THF was recovered at a temperatureof 110°C and ordinary pressure. Thereafter, 84.4 g of a crude enamine was recovered under reduced pressure. Theenamine obtained was distilled under reduced pressure (76°C/13.3 Pa) to obtain 73.6 g of (S) -citronellal enamine. Yield,99.0% (of which α-citronellal enamine accounted for 3.4%).

EXAMPLE 9

<Hydrolysis>

[0051] Into a flask were introduced 294.4 g (1.41 mol) of (R)-citronellal enamine and 300 ml of toluene. Thereto wasdropwise added 360 g (0.735 mol) of 20 wt% sulfuric acid solution over 3.5 hours at a reaction temperature of 10°C orlower. The reaction mixture was stirred for 1.5 hours. After liquid separation, the organic layer was washed with waterand 5 wt% aqueous sodium carbonate solution. The solvent was distilled off under reduced pressure and the resultantresidue was distilled under reduced pressure (93-94°C/1,870 Pa) to obtain 209.2 g of citronellal. Yield, 90%. Purity,94.6% (of which α-citronellal accounted for 3.3%).

EXAMPLE 10

<Hydrolysis>

[0052] Into a flask were introduced 73.6 g (1.40 mol) of (S)-citronellal enamine and 75 ml of toluene. Thereto wasdropwise added 90 g (0.184 mol) of 20 wt% sulfuric acid solution over 3.5 hours at a reaction temperature of 10°C orlower. The reaction mixture was stirred for 1.5 hours. After liquid separation, the organic layer was washed with waterand 5 wt% aqueous sodium carbonate solution. The solvent was distilled off under reduced pressure and the resultantresidue was distilled under vacuum (93-94°C/1,870 Pa) to obtain 52.3 g of citronellal. Yield, 90%. Purity, 94.6% (of whichα-citronellal accounted for 3.4%).

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EXAMPLE 11

<Hydrogenation Reaction>

[0053] Into a 100-ml autoclave were introduced 20.5 g (132.8 mmol) of (R)-citronellal, 1.0 g (5%, wt/wt) of a copper-chromium catalyst, and 0.04 g (0.2%, wt/wt) of sodium carbonate. After the atmosphere in the system was replaced withhydrogen, the reaction mixture was vigorously agitated in a hydrogen atmosphere (3.4 MPa) at 130°C for 4.5 hours andthen cooled. Thereafter, the catalyst was removed by filtration. The crude citronellol obtained was distilled under reducedpressure (70°C/1,870 Pa) to obtain 15.15 g of (S) -citronellol. Yield, 73%. Purity, 98.6% (of which α-citronellol accountedfor 3.4%).

<Sensory Test>

[0054] Optically active 3,7-dimethyl-7-octenol, as an impurity, has a rosy fragrance characteristic of aliphatic aldehydesand is excellent in intensity and diffusibility. Optically active 3,7-dimethyl-6-octenol ((S)-citronellol), when containing the7-octenol compound in an amount of from 2 to 10% by weight, can have a feature of rhodinol, which is an expensivesubstance isolated from geranium oil and having a mellow fragrance.[0055] According to the invention, a cis-3,7-dimethyl-2,6-octadienylamine compound (nerylamine compound) whichcontains from 2 to 10% by weight cis-3,7-dimethyl-2,7-octadienylamine compound (α-nerylaminle compound) and isuseful as a material for perfumes can be obtained in high yield in a short time period. Furthermore, (S)-citronellol, havingan excellent fragrance, can be obtained by asymmetrically isomerizing, hydrolyzing, and hydrogenating the nerylaminecompound.

Claims

1. A process for producing a mixture comprising optically active 3,7-dimethyl-6-octenol represented by formula (1):

which contains 2 to 10% by weight of optically active 3,7-dimethyl-7-octenol represented by formula (2):

said process comprising the steps of:

- subjecting a mixture of an alkylamine and isoprene in a molar ratio of from 1:4 to 1:4.5 to telomerization at areaction temperature of from 80 to 100°C for 2.5 to 3.5 hours in the presence of an alkyllithium catalyst and/orphenyllithium catalyst, to thereby obtain a cis-3,7-dimethyl-2,6-octadienylamine compound represented by gen-eral formula (3);

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wherein R1 and R2 each represent a hydrogen atom or an alkyl, aralkyl or aryl group having 1, to 10 carbon atoms;containing 2 to 10% by weight of a cis-3,7-dimethyl-2,7-octadienylamine compound represented by general formula(4):

wherein R1 and R2 are as defined above;

- asymmetrically isomerizing the resultant reaction product mixture, to thereby obtain an isomerized mixture;- hydrolyzing said isomerized mixture, to thereby obtain a citronellal mixture; and,- reducing said citronellal mixture.

2. Process according to claim 1, comprising the process for producing a cis-3,7-dimethyl-2,6-octadienylamine com-pound of the formula (3) containing from 2 to 10% by weight of a cis-3,7-dimethyl-2,7-octadienylamine compoundof the formula (4) defined in claim 1, said process comprising the steps of:

subjecting a mixture of an alkylamine and isoprene in a molar ratio of from 1:4 to 1:4.5 to telomerization at areaction temperature of from 80 to 100°C for 2.5 to 3.5 hours in the presence of an alkyllithium catalyst and/orphenyllithium catalyst.

3. Process according to claim 2, wherein said cis-3,7-dimethyl-2,6-octadienylamine compound of the formula (3) con-tains from 3 to 6% by weight of a cis-3,7-dimethyl-2,7-octadienylamine compound of the formula (4).

4. Process according to any one of claim 1, to 3, wherein said alkylamine is selected from the group consisting ofdimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, cyclohexylamine, piperidine,pyrrolidine and morpholine.

5. Process according to any one of claims 1 to 4, wherein said lithium catalyst is selected from the group consistingof methyllithium, n-butyllithium, sec-butyllithium and tert-butyllithium.

6. Process according to any one of claims 1 to 5, wherein the amount of the lithium catalyst to be used in the telom-erization is from 0.5 to 5 mol % based on the amine compound to be subjected to the reaction.

7. Process according to any one of claims 1 to 6, wherein said telomerization is conducted in an inert atmosphere witha solvent.

Patentansprüche

1. Verfahren zum Herstellen eines Gemisch, umfassend optisch aktives 3,7-Dimethyl-6-octenol, das durch Formel (1)wiedergegeben wird:

welches 2 bis 10 Gew.-% optisch aktives 3,7-Dimethyl-7-octenol enthält, das durch Formel (2) wiedergegeben wird:

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wobei das Verfahren die folgenden Schritte umfasst:

- Unterwerfen eines Gemisches aus einem Alkylamin und Isopren in einem Molverhältnis von 1:4 bis 1 :4,5einer Telomerisation bei einer Reaktionstemperatur von 80 bis 100° C während 2,5 bis 3,5 Stunden in Gegenwarteines Alkyllithiumkatalysators und/oder Phenyllithiumkatalysators, um dadurch eine cis-3,7- Dimethyl-2,6-oc-tadienylaminverbindung zu erhalten, die durch die allgemeine Formel (3) wiedergegeben wird:

worin R1 und R2 jeweils ein Wasserstoffatom oder eine Alkyl-, Aralkyl- oder Arylgruppe mit 1 bis 10 Kohlenstoffatomenbedeuten;enthaltend 2 bis 10 Gew.-% einer cis-3,7-Dimethyl-2,7-octadienylaminverbindung, die durch die allgemeine Formel(4) wiedergegeben wird:

worin R1 und R2 wie vorstehend definiert sind;

- asymmetrisches Isomerisieren des resultierenden Reaktionsproduktgemisches, um dadurch ein isomerisier-tes Gemisch zu erhalten;- Hydrolysieren des isomerisierten Gemisches, um dadurch ein Citronellalgemisch zu erhalten; und- Reduzieren des Citronellalgemisches.

2. Verfahren nach Anspruch 1, umfassend das Verfahren zum Herstellen einer cis-3,7-Dimethyl-2,6-octadienylamin-verbindung der Formel (3), enthaltend 2 bis 10 Gew.-% einer cis-3,7-Dimethyl-2,7-octadienylaminverbindung derFormel (4), die in Anspruch 1 definiert ist, wobei das Verfahren die folgenden Schritte umfasst:

- Unterwerfen eines Gemisches aus einem Alkylamin und Isopren in einem Molverhältnis von 1:4 bis 1 :4,5einer Telomerisation bei einer Reaktionstemperatur von 80 bis 100°C während 2,5 bis 3,5 Stunden in Gegenwarteines Alkyllithiumkatalysators und/oder Phenyllithiumkatalysators.

3. Verfahren nach Anspruch 2, wobei die cis-3,7-Dimethyl-2,6-octadienylaminverbindung der Formel (3) 3 bis 6 Gew.-% einer cis-3,7-Dimethyl-2,7-octadienylaminverbindung der Formel (4) enthält.

4. Verfahren nach einem der Ansprüche 1 bis 3, wobei das Alkylamin ausgewählt ist aus der Gruppe bestehend ausDimethylamin, Diethylamin, Di-n-propylamin, Diisopropylamin, Di-n-butylamin, Cyclohexylamin, Piperidin, Pyrrolidinund Morpholin.

5. Verfahren nach einem der Ansprüche 1 bis 4, wobei der Lithiumkatalysator ausgewählt ist aus der Gruppe bestehend

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aus Methyllithium, n-Butyllithium. sec-Butyllithium und tert-Butyllithium.

6. Verfahren nach einem der Ansprüche 1 bis 5, wobei die Menge des Lithiumkatalysators, der bei der Telomerisationverwendet werden soll, 0,5 bis 5 mol%, bezogen auf die Aminverbindung, die der Reaktion unterworfen werdensoll, beträgt.

7. Verfahren nach einem der Ansprüche 1 bis 6, wobei die Telomerisation in einer Inertatmosphäre mit einem Lö-sungsmittel durchgeführt wird.

Revendications

1. Procédé de préparation d’un mélange comprenant du 3,7-diméthyl-6-octénol optiquement actif représenté par laformule (1) :

qui contient de 2 à 10 % en poids de 3,7-diméthyl-7-octénol optiquement actif représenté par la formule (2) :

ledit procédé comprenant les étapes consistant à :

- soumettre un mélange d’une alkylamine et d’isoprène selon un rapport molaire de 1:4 à 1:4,5 à une télomé-risation à une température de réaction de 80 à 100°C pendant 2,5 à 3,5 heures en présence d’un catalyseur àbase d’alkyl-lithium et/ou d’un catalyseur à base de phényllithium pour obtenir ainsi un composé cis-3,7-diméthyl-2,6-octadiénylamine représenté par la formule générale (3) :

dans laquelle R1 et R2 représentent chacun un atome d’hydrogène ou un groupe alkyle, aralkyle ou aryle ayant de1 à 10 atomes de carbone ;contenant de 2 à 10 % en poids d’un composé cis-3,7-diméthyl-2,7-octadiénylamine représenté par la formulegénérale (4) :

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dans laquelle R1 et R2 sont tels que définis ci-dessus ;

- effectuer une isomérisation asymétrique du mélange de produits de réaction résultant pour obtenir ainsi unmélange isomérisé ;- hydrolyser ledit mélange isomérisé pour obtenir ainsi un mélange contenant du citronellal ; et- réduire ledit mélange contenant du citronellal.

2. Procédé selon la revendication 1, comprenant le procédé de préparation d’un composé cis-3,7-diméthyl-2,6-octa-diénylamine de formule (3), contenant de 2 à 10 % en poids d’un composé cis-3,7-diméthyl-2,7-octadiénylaminede formule (4) défini dans la revendication 1, ledit procédé comprenant les étapes consistant à :

- soumettre un mélange d’une alkylamine et d’isoprène selon un rapport molaire de 1:4 à 1:4,5 à une télomé-risation à une température de réaction de 80 à 100°C pendant 2,5 à 3,5 heures en présence d’un catalyseur àbase d’alkyl-lithium et/ou d’un catalyseur à base de phényllithium.

3. Procédé selon la revendication 2, dans lequel ledit composé cis-3,7-diméthyl-2,6-octadiénylamine de formule (3)contient de 3 à 6 % en poids d’un composé cis-3,7-diméthyl-2,7-octadiénylamine de formule (4).

4. Procédé selon l’une quelconque des revendications 1 à 3, dans lequel ladite alkylamine est choisie dans l’ensembleconstitué des diméthylamine, diéthylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, cyclohexylamine,pipéridine, pyrrolidine et morpholine.

5. Procédé selon l’une quelconque des revendications 1 à 4, dans lequel ledit catalyseur au lithium est choisi dansl’ensemble constitué des méthyl-lithium, n-butyl-lithium, sec-butyl-lithium et tert-butyl-lithium.

6. Procédé selon l’une quelconque des revendications 1 à 5, dans lequel la quantité du catalyseur au lithium à utiliserdans la télomérisation est de 0,5 à 5 % en moles par rapport au composé d’amine à soumettre à la réaction.

7. Procédé selon l’une quelconque des revendications 1 à 6, dans lequel ladite télomérisation est effectuée dans uneatmosphère inerte avec un solvant.

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REFERENCES CITED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader’s convenience only. It does not form part of the Europeanpatent document. Even though great care has been taken in compiling the references, errors or omissions cannot beexcluded and the EPO disclaims all liability in this regard.

Patent documents cited in the description

• JP 49048610 A [0004] [0005] [0009]• JP 51004109 A [0004] [0006]• JP 53135912 A [0004] [0007]

• US 4186148 A [0004] [0008]• US 4604474 A [0010]

Non-patent literature cited in the description

• Bull. Soc. Chim., 1929, (45), 809-827 [0010]• Römpp Chemie Lexikon. vol. 1, 759 [0010]• ROMPP CHEMIE LEXIKON. 1999, vol. 5, 3812

[0010]

• Römpp Chemie Lexikon. 1989, vol. 1, 742 [0010]• ROMPP CHEMIE LEXIKON. 1992, vol. 5, 3872

[0010]

process for producing optically active 3,7-dimethyl-6-octenol

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