WO2008074653A1 - Procédé de préparation de dérivés de menthyle - Google Patents

Procédé de préparation de dérivés de menthyle Download PDF

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Publication number
WO2008074653A1
WO2008074653A1 PCT/EP2007/063473 EP2007063473W WO2008074653A1 WO 2008074653 A1 WO2008074653 A1 WO 2008074653A1 EP 2007063473 W EP2007063473 W EP 2007063473W WO 2008074653 A1 WO2008074653 A1 WO 2008074653A1
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general formula
radical
alkyl
meanings
acyloxyalkyl
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PCT/EP2007/063473
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German (de)
English (en)
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Andreas Job
Uwe Westeppe
Lars Rodefeld
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Saltigo Gmbh
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Publication of WO2008074653A1 publication Critical patent/WO2008074653A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
    • C07B37/04—Substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B49/00—Grignard reactions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the present invention relates to an improved process for the preparation of Menthy 1 derivatives.
  • Menthol is known for its physiological cooling effect on the skin and mucous membrane of the mouth and is widely used as a flavor in foods, drinks, toothpaste, mouthwash, as well as a component in a variety of toiletries, ointments and lotions for topical application.
  • the Ktihl bin is a physiological effect due to the direct effect of menthol on the nerve endings of the human body, which are responsible for the perception of heat or cold, and is not based on the latent heat of vaporization. It is believed that menthol has a direct stimulating effect on the cold receptors on the nerve endings, which in turn stimulate the central nervous system.
  • menthol is limited because of its strong peppermint odor and its relatively high volatility.
  • the proportion of the menthyl epimer is 57-80 wt.% Based on the sum of menthyl and Neomenthyl epimer. Since the menthyl epimer has a greater physiological cooling effect than the neomenthyl epimer, US Pat. No. 4,366,317 seeks to provide an improved process in which the product obtained contains at least 90% by weight of the menthyl epimer and at most 10% by weight. % consists of the neomenthyl epimer.
  • the invention relates to a process for the preparation of compounds of the general formula (1)
  • R 1 Ci-C 30 alkyl, C 2 -C 20 alkenyl, C 2 -C 2fl alkynyl, C 7 -C 2 o-alkylaryl, C 6 -C 0 -AIyI, Cs-C
  • R ! and R 2 together form an alkylene chain optionally interrupted by one or more heteroatoms, preferably oxygen or sulfur, taken together with the nitrogen atom to which R 1 and R 2 are bonded, forming a maximum 10-membered ring, or ZC (OH) R 4 R 5 means in which
  • R 4 and R 3 are the same or different and those previously indicated for R 1
  • R ⁇ has the meanings given for R 1 , or Z is CR 7 R 8 R 9 , in which
  • R 7 has the meanings given for R 1 and
  • R 8 and R 9 are the same or different and are 0-Ci-C 3 o-alkyl, or wherein alternatively
  • R 7 and R 8 are the same or different and have the meanings given for R 1 and
  • R 9 is 0-Ci-C 3 o-alkyl, or Z is CHR 10 CHR "OH, wherein
  • R 10 and R 11 are the same or different and those previously indicated for R 1
  • R 12 is an optionally substituted C ⁇ -Cis-aryl radical.
  • Hal is chlorine, bromine or iodine, reacted with magnesium and optionally elemental iodine or an alkyl halide, and then in the presence of an additive with an electrophile, which is selected from the group consisting of
  • R 1 and R 2 have the meanings given for the general formula (I) and R 13 is a C 1 -C 20 -alkyl radical
  • R 7 and R 8 are the same or different and have the meanings given for R 1 in the general formula (I) and R 9 and R 14 are identical or different and represent O-Ci- C 3 o-alkyl,
  • R 7 has the meanings given for R 1 in the general formula (I)
  • R 8 , R 9 and R 14 are identical or different and represent 0-C 1 -C 30 -alkyl
  • Epoxides of the general formula (XB) wherein R 10 and R 11 have the meanings given for the general formula (1)
  • radicals mentioned in the context of this application which may be in branched or unbranched form, such as. Alkyl, alkoxy, alkenyl and alkynyl radicals, the mention of these radicals includes both the unbranched and the branched forms.
  • a Cjj-Cio-heteroaryl radical is an aromatic radical in which at least one skeletal carbon atom in the rest is replaced by a heteroatom selected from the group of nitrogen, sulfur or oxygen.
  • a heteroatom selected from the group of nitrogen, sulfur or oxygen Preferably, one, two, three or four skeletal carbon atoms in the entire radical are replaced by heteroatoms selected from the group of nitrogen, sulfur or oxygen.
  • additives are LiCl, LiBr, ZnCl 2 , ZnBr 2 , SnCl 2 , SnCU, MgCl 2 , MgBr 2 , AlCl 3 , TiCl 4 , Al (OiPr) 3 , Ti (OiPr) 4 , CeCl 3 , ZnEt, CuBr, LiClO 4 , BCl 3 , BF 3 and their etherate, boric acid, unsubstituted and substituted phenylboronic acids and other Lewis acids used.
  • the additive may be added at all times in the course of the process, i. before, during or after addition of the electrophile of the general formulas (III) to (XIII).
  • the addition of the additive is carried out before the addition of the electrophile, wherein the addition can be done either to the finished Grignard compound or before the preparation of the Grignard compound to magnesium.
  • the additive is introduced together with magnesium under inert gas, mixed with the solvent and then optionally elemental iodine or the alkyl halide is added.
  • the additive is added to the solution containing the Grignard compound simultaneously, before or after the electrophile.
  • the additive in an amount of 1-100 mol%, preferably 10-50 mol%, based on the forming Grignard compound.
  • the reaction of the starting materials of the general formula (II) with the Grignard compound can be carried out in various solvents (see, for example, J. Org. Chem. 2000, 65, 2337 with regard to possible solvents for the preparation of the Grignard compound).
  • Suitable solvents are THF, dioxane, methyl THF, cyclopentyl methyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether or mixtures of the abovementioned solvents with aromatic solvents such as toluene or xylene.
  • R 1 is CpCso-alkyl, C 2 -C 2 -o [kenyl, C 2 -C 20 -alkyl, C r C 20 -alkylaryl, C 6 -C 10 -aryl, C 5 -C 10 -heteroaryl or by Cs-Cio heteroaryl substituted phenyl], C 3 -C 2 o-cycloalkyl, C 3 - C 2 o-cycloalkenyl, C 3 -C 20 cycloalkynyl, C r C 20 hydroxyalkyl, C 3 -C 2 o-acyloxyalkyl, C 1 -C 20 -alkoxy, C 2 -C 20 alkoxyalkyl, C 2 -C 2 o-alkylthioalkyl, C 2 -C 2 o-aminoalkyl, C 3 - C 2 o-acylaminoalkyl, C 2 -C 2 o-carboxy
  • R 1 in the general formula (III) is
  • R 1 in the general formula (III) is a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert.
  • heterocycles of the general formula (IV) can also be used in the reaction according to the invention.
  • R 1 can assume all general, preferred or particularly preferred meanings which R 1 has in the general formula (III), and
  • X is a straight or branched C
  • carbamoyl chlorides of the general formula (V) can also be used in the reaction according to the invention.
  • R 1 and R 2 are the same or different and may have all the general, preferred and particularly preferred meanings given above for the general formula (III).
  • Z is a radical C (K)) NR 1 R 2 , in which R 1 and R 2 are identical or different and have all the general meanings given above for the general formula (HI), have preferred and particularly preferred meanings.
  • aminoethers of the general formula (VI) can also be used in the reaction according to the invention.
  • R 1 Ci-Cao-alkyl, C 2 -C rAlkenyl 2t, C 2 -C 20 alkynyl, C 7 -C 2O -AUCyIaIyI, C 6 -C 0 aryl, C 5 -C 0 - heteroaryl, by C 5 -Cio-heteroaryl-substituted phenyl, C 3 -C 2 o-cycloalkyl, Cs-C 20 - cycloalkenyl, C 3 -C 2 o-cycloalkynyl, C 1 -C 20 -hydroxyalkyl, C 3 -C 2 o-acyloxyalkyl, C 1 - C 20 alkoxy, C 2 -C 20 alkoxyalkyl, C 2 -C 2 o-alkylrhioalkyl, C 2 -C 20 -AmInOaIkVl, Cj-C 20 - acylamino
  • R 2 has the same meaning as R ', further hydrogen or a radical -X-OH, wherein X represents a straight-chain or branched Ci-Cjn-alkylene group, which is optionally interrupted by one or more heteroatoms, or wherein
  • R 1 and R 2 together form an alkylene chain optionally interrupted by one or more heteroatoms, taken together with the nitrogen atom to which R 1 and R 2 are bonded, forming a maximum 10-membered ring, and
  • R 13 is a C 1 -C 20 -alkyl radical.
  • Amino ethers of the general formula (VI) are preferably used, wherein R 1 is C 1 -C] 4 -alkyl, C 2 -C 0 alkenyl, C 2 -C 0 alkynyl, Cj-Cjo-cycloalkyl, C5 -C 0 -Cycloalkenyl, C 5 -Cin .
  • R 2 has the same meanings as R 1 , may mean fine hydrogen or a radical -X-OH, wherein X represents a straight-chain or branched Ci-C ⁇ -alkylene group, which is optionally interrupted by one or more heteroatoms, or wherein R 1 and R 2 together represent an optionally interrupted by one or more heteroatoms
  • R 2 are bonded, forms a maximum 8-membered ring, and R 13 is a Ci-Ci 4 -alkyl radical.
  • R 1 is a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2 Methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl.
  • R 2 has the same meanings as R 1 , furthermore hydrogen or a radical -X-OH, where X represents a straight-chain or branched Ci-Cn-alkylene group, which is optionally interrupted by one or more sulfur or oxygen atoms, or wherein
  • R 1 and R 2 together form an alkylene chain optionally interrupted by one or more sulfur or oxygen atoms, taken together with the nitrogen atom to which R 1 and R 2 are bonded, forming a maximum 8-membered ring, and
  • R 13 is a Ci-Cio-alkyl radical, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-Metliylbutyl , 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl , 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-di-, methylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbuty
  • aldehydes of the general formula (VII) can also be used in the reaction according to the invention, wherein
  • R 4 Ci-C30 alkyl, C2-C2o-alkenyl, CrQo alkynyl, C 7 -C 20 - alkylaryl, C 6 -C 0 -ATyI, C 5 -C 0 - heteroaryl, by Cs-CIO Heteroaryl-substituted phenyl, C 5 -C 2 o-cycloalkyl, C 3 -C 2O -cycloalkenyl, C 3 -C 20 -cycloalkynyl, C 1 -C 20 -hydroxyalkyl, C 3 -C 2 o-acyloxyalkyl, Q-C 20 - alkoxy, C 2 -C 2ß alkoxyalkyl, C 2 -C 2 o-alkylthioalkyl, C 2 -C 20 aminoalkyl, C 3 -C 20 - acylaminoalkyl, C 2 -C 20 carboxyalkyl, a radical -
  • R 4 Ci-Cw-alkyl, C 2 -C 0 -Aikenyl, C 2 -C 0 alkynyl, C 5 -C -Cyc1oalkyl 0, Cj-C 10 cycloalkenyl, C 5 -Cio-cycloalkynyl, CRDO hydroxyalkyl, C 3 -C
  • R 4 a straight-chain or branched Ci-Cjo-alkyl radical, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1 -Methylb ⁇ tyl, 2 Methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4 Methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbuty
  • ketones of the general formula (VIII) can also be used in the reaction according to the invention, wherein
  • R 4 and R 5 are identical or different and are Ci-Cjo alkyl, C 2 -C 2 -alkenyl, C 2 -C 2 o-alkynyl, Cv-C 2 o-alkylaryl, Ce-Cio-aryl, Cs Cio-heteroaryl, substituted by Cs-Cio-heteroaryl, phenyl, C 3 -C 2O -Cy cloalkyl, C 3 -C 2 o-cycloalkenyl, C 3 -C 2 o-cycloalkynyl, Ci-Cio-hydroxyalkyl, C 3 -C2o -Acyloxyalkyl ) Ci-C 20 -alkoxy, C 2 -C 2 o-Alkoxyalkyl, C 2 - C 2 o-Alkylthioalkyl, C 2 -C 20 -Ammoalkyl, C3-C 2 o-Acyla
  • ketones of the general formula (VIII) in which R 4 and R 5 are the same or different and Ci-Cw-alkyl, C 2 -C
  • R 4 and R 5 are identical or different and are a straight-chain or branched C I -C JO - alkyl radical, especially methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl , n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-diniethylpropyl, 1,2-dimethylpropyl, I- Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl
  • nitriles of the general formula (IX) can also be used in the reaction according to the invention.
  • R 6 can assume all general, preferred or particularly preferred meanings which R 1 has in the general formula (III).
  • R 7 and R 8 are identical or different and are Ci-C 30 - alkyl, C 2 -C 2 -alkenyl, C 2 -C 20 -AIkJ nyl, C 7 - C 20 alkylaryl, C 6 -C 0 -aryl , C 5 -Cio-heteroaryl, substituted by Cs-Cio-heteroaryl, phenyl, C 3 -C 2 o-cycloalkyl, C 3 -C 20 cycloalkenyl, C 3 -C 20 cycloalkynyl, C 1 -C 20 - hydroxyalkyl, C 3 -C 20 -Acyloxyalkyl, C 20 alkoxy, C 2 -C 20 -AIkOXyBIlCyI, C 2 -C 20 - alkylthioalkyl, C 2 -C 20 aminoalkyl, CrC ⁇ o-Acylarninoalkyl, C
  • R 9 and R 14 are the same or different and are -O-Ci-C 3 ⁇ -alkyl.
  • R 7 and R 8 are identical or different and d-C ⁇ alkyl, C 2 -C ⁇ o alkenyl, C 2 -C 0 alkynyl, C 5 - Cio-cycloalkyl, C 5 -Cio-cycloalkenyl, Cs-q O- cycloalkynyl, Ci-Cio-hydroxyalkyl, C 3 - Cio-Acyloxyalky-, Ci-Cio-alkoxy, C 2 -Cio-AIkoxyalkyl, C 2 -C 10 - Al kylthioalkyl, C 2 -C 0 - aminoalkyl, C 3 -C 10 -Acylaminoalkyl, C 2 -Ci 0 -Carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or an oxazolyl, triazolyl, morpholinyl or pyrazoly
  • R 9 and R 14 are the same or different and are -OC
  • R 7 and R 8 are the same or different and a straight-chain or branched C r C
  • 0 -alkyl radical especially methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo Pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1, 2-dimethylpropyl, 1, 2-dimethylpropyl, 1 Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbuty
  • R 7 C-Cso alkyl, C ⁇ -C ⁇ o alkenyl, -C 2 o-alkynyl, C 7 -C 20 -A] kylary1, C 6 -C 0 -ATyI, C 3 -C 0 - heteroaryl, by Cs-Cio-heteroaryl substituted phenyl, C3-C2o-cycloalkyl, C 3 -C 20 - cycloalkenyl, C 3 -C 2 o-cycloalkynyl, -C 2 o-hydroxyalkyl, Cs-Cao-Acyioxyalkyl, Ci- C2o Alkoxy, C 2 -C 2 o -alkoxyalkyl, C 2 -C 20 -alkylthioalkyl, C 2 -C 2 t> -aminoalkyl, Cj-C 2O - acylaminoalkyl, C 2
  • R 8 , R 9 and R 14 are the same or different and are -O-C 1 -C 30 -alkyl.
  • Orthoester of the general formula (XI) are preferably employed, wherein, R 7 CRCI 4 alkyl, C 2 -C, o-alkenyl, C 2 -Cio-alkynyl, C 5 -C 0 cycloalkyl, C 5 -C
  • Orthoesters of the general formula (XI) are particularly preferably used in the reaction according to the invention, in which
  • R 7 denotes a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl], tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyi, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethyli
  • R 8, R 9 and R 14 are identical or different and are -O-C
  • R 10 and R are the same or different and are -C 30 -AUCyI, C r C 20 alkenyl, C 2 -C 2 o-alkynyl, C 7 -C 2 o-Alkylaiyl, C ⁇ -Cio-aryl, Cs-CIO heteroaryl, by CrCio-heteroaryl substituted phenyl, C 3 -C 2 o-cycloalkyl, C 3 -C 2 o-cycloalkenyl, C 3 -C 2 o-cycloalkynyl, Ci-C 2 o-hydroxyalkyl, C 3 -C 20 - acyloxyalkyl, C 20 alkoxy, C 2 -C 20 - alkoxyalkyl, C 2 - C 20 alkylthioalkyl, C 2 -C 20 aminoalkyl, C 3 -C 20 -Acylaminoalkyl, C 2 -C 2 o-carboxy
  • Epoxides of the general formula (XII) are preferably used, wherein R 10 and R 1 1 are the same or different and are Ci-C 4 alkyl (C 2 -Cio-alkenyl, C 2 -C 0 alkynyl, C 5 -C 0 cycloalkyl, C 5 -C 0 cycloalkenyl; C 5 -C
  • epoxides of the general formula (XII) in which R 10 and R 11 are identical or different and represent a straight-chain or branched C 1 -C 20 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n- Butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2- Dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbenzyl, 2,2-dimethylbutyl, 2, 3-dimethylbutyl
  • R 12 represents an optionally substituted C ⁇ -Cu-aryl radical.
  • the molar ratio of magnesium to the compound of the general formula (II) is (0.9-1.6): 1, preferably (1.0-1.4): 1.
  • the addition is made in such a manner that the Temperature of the reaction mixture in a range of 2O 0 C to 8O 0 C moves. Again, an adaptation to the solvent used can be done. Subsequently, will Usually stirred for a while, the reaction mixture was cooled to a temperature of 20 0 C to 5O 0 C and filtered off or decanted.
  • the addition of the additive is then usually followed by the reaction with the electrophile in the form of the isocyanate of the general formula (III), the heterocycle of the general formula (IV), the carbamoyl chloride of the general formula (V), of the amino ether of the general formula ( VI), the aldehyde of the general formula (VII), the ketone of the general formula (VIH), the nitrile of the general formula (IX), the acetal of the general formula (X), the orthoester of the general formula (XI), the epoxide the general formula (XII) or the sulfonyl chloride of the general formula (XIII).
  • These compounds may be either as such, i. be used in substance or diluted in an organic solvent.
  • a variant of the procedure is to add the electrophile to the reaction mixture, which is obtained in the reaction of the compound of general formula (II) with magnesium. It is also possible, however, to reverse the order of addition, i. the reaction mixture from the reaction of the compound of the general formula (II) with magnesium is added to the respective electrophiles of the formulas (III) to (XIII).
  • the molar ratio of the compound of the general formulas (III) to (XIII) to the compound of the general formula (II) is (0.95-1.4): 1, preferably (1.0-1.2): 1. It is also possible to partially distill off the solvent used for the reaction with magnesium before adding these reagents. In this case, the reagent to be added is then advantageously used dissolved in an organic solvent, for example toluene or xylene. After the reaction, the still present, originally used for the reaction with magnesium and lower boiling solvent can be further distilled off and optionally recycled.
  • reaction mixture is treated with aqueous acid and the mixture is worked up, for example by phase separation or extraction with an organic solvent.
  • the desired compound of general formula (I) is removed via the organic phases, dried and isolated.

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  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un procédé amélioré de préparation de dérivés de menthyle par conversion d'halogénures de menthyle à l'aide de magnésium et conversion ultérieure avec des électrophiles en présence d'additifs.
PCT/EP2007/063473 2006-12-20 2007-12-06 Procédé de préparation de dérivés de menthyle WO2008074653A1 (fr)

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DE102006060949.2 2006-12-20
DE102006060949A DE102006060949A1 (de) 2006-12-20 2006-12-20 Verfahren zur Herstellung von Menthylderivaten

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109851522A (zh) * 2018-12-10 2019-06-07 万华化学集团股份有限公司 N-乙基-新-薄荷基甲酰胺构型翻转制备n-乙基-l-薄荷基甲酰胺的方法

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US4350832A (en) * 1981-04-27 1982-09-21 Philip Morris, Incorporated Synthesis of N-t-butyl-p-menthane-3-carboxamide
US4366317A (en) * 1981-06-22 1982-12-28 Philip Morris Incorporated Process for synthesis of N-(hydrocarbyl)substituted-p-menthane-3-carboxamide
WO2004020390A1 (fr) * 2002-08-09 2004-03-11 Grünenthal GmbH Procede pour produire du 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol
WO2007096074A1 (fr) * 2006-02-21 2007-08-30 Saltigo Gmbh Procede de fabrication d'amide de menthyle

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4350832A (en) * 1981-04-27 1982-09-21 Philip Morris, Incorporated Synthesis of N-t-butyl-p-menthane-3-carboxamide
US4366317A (en) * 1981-06-22 1982-12-28 Philip Morris Incorporated Process for synthesis of N-(hydrocarbyl)substituted-p-menthane-3-carboxamide
WO2004020390A1 (fr) * 2002-08-09 2004-03-11 Grünenthal GmbH Procede pour produire du 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol
WO2007096074A1 (fr) * 2006-02-21 2007-08-30 Saltigo Gmbh Procede de fabrication d'amide de menthyle

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Title
ARKADY KRASOVSKIY ET AL: "Eine LiCl-vermittelte Br/Mg-Austauschreaktion zur Herstellung funktionalisierter Aryl- und Hetreoarylmagnesium-Verbindungen ausgehend von organischen Bromiden", ANGEW. CHEM., vol. 116, no. 25, 2004, pages 3396 - 3399, XP002476337 *
JENS BECKMANN ET AL: "New Insights into the Classic Chiral Grignard Reagent (1R,2S,5R)-Menthylmagnesium Chloride", ANGEW. CHEM. INT. ED, vol. 45, no. 39, 2006, pages 6509 - 6512, XP002476338 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109851522A (zh) * 2018-12-10 2019-06-07 万华化学集团股份有限公司 N-乙基-新-薄荷基甲酰胺构型翻转制备n-乙基-l-薄荷基甲酰胺的方法

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