Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
  • C07C29/32—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions without formation of -OH groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
  • C07C29/56—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by isomerisation
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
  • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups

Definitions

• the present invention is a process for the preparation of m- or p-alkyl-substituted phenylalkanols by Friedel-Crafts alkylation of Phenylalka- nolen and subsequent isomerization of the unwanted byproducts to the desired m- or p-alkyl-substituted phenylalkanol.
• the m- or p-alkyl-substituted phenylalkanols and the m- or p-alkyl-substituted phenylalkanals prepared therefrom, for example derivatives of the odorant 3-phenyl-1-propanol, are of interest as aroma chemicals.
• Various syntheses are known for the preparation of alkyl-substituted phenylalkanols and their derivatives.
• WO 2008/053148 describes a 3-stage synthesis for preparing 3- (3-tert-butylphenyl) propanal starting from 1-tert-butyl-3-ethylbenzene.
• the starting compound is first brominated to 1-tert-butyl-3- (1-bromo-ethyl) benzene and then eliminated to the corresponding substituted styrene.
• hydroformylation the 3- (3-tert-butylphenyl) propanal is subsequently obtained.
• this synthesis seems less suitable due to low yields.
• EP 0 045 571 discloses the Friedel-Crafts alkylation of 2-methyl-3-phenylpropanol to 2-methyl-3- (3-tert-butylphenyl) propanol and 2-methyl-3- (4-tert-butylphenyl) propanol described.
• the alkylating reagents used are isobutylene, diisobutylene and tert-butyl chloride.
• the catalysts used are iron chloride and phosphoric acid and as solvent methylene chloride or phosphoric acid. Depending on the reaction conditions and the catalyst, m / p ratios of 1/13 to 1/5 are obtained. Total yields (m-isomer and p-isomer) are up to 52%.
• the process according to the invention makes it possible to obtain the m-substituted phenylalkanols or the p-substituted phenylalkanols, which serve as precursors for the very interesting correspondingly substituted phenylalkanols (phenylalkylaldehydes), inexpensively and in good yield and with a - makes the simplest way.
• the present invention relates to a process for the preparation of m- or p-substituted phenylalkanols, which can be obtained by Friedel-Crafts alkylation of unsubstituted phenylalkanols together with alkyl halides. The alkylation takes place on certain Friedel-Crafts catalysts.
• the invention thus provides a process for preparing m- or p-alkyl-substituted phenylalkanols of the formula (I)
• Ri is bonded in the m- or p-position to the phenyl ring and d-Cs-alkyl and R2, R3, 4 and R5 independently of one another are hydrogen or methyl, which is characterized in that an unsubstituted phenylalkanol of the formula (II )
• R 2 , R 3 , R 4 and R 5 have the meanings given under formula (I) together with a C 1 -C 5 -alkyl halide of the formula (III)
• R1 has the meaning given under formula (I) and Hal is halogen, alkylated in the presence of a Friedel-Crafts catalyst to a mixture of m- and p-alkyl-substituted phenylalkanols of formula (I) and then the reaction mixture, preferably in the presence of water at alkaline pH, worked up and the desired m-alkyl-substituted phenylalkanol of the formula (I) or the desired p-alkyl-substituted phenylalkanol of the formula (I) separated, preferably separated by distillation, and the remaining by-products formed in the reaction mixture and this isomerized in the presence of a Friedel-Crafts catalyst to the desired m- or p-alkyl-substituted phenylalkanol.
• a work-up preferably aqueous workup, preferably at alkaline pH, most preferably is an aqueous work-up in the presence of alkali, such as sodium hydroxide and / or potassium hydroxide
• alkali such as sodium hydroxide and / or potassium hydroxide
• the isomerization step can be carried out virtually continuously, by carrying out an aqueous workup after each isomerization step, preferably under alkaline conditions as indicated above, with subsequent separation, preferably by distillation, in order to increase the yield of the desired product.
• the aqueous working up of the reaction mass according to the present process takes place after the alkylation and also after the isomerization step by adding the reaction mass at room temperature with water, preferably at alkaline pH, more preferably in the presence of alkali, in particular caustic soda or potassium hydroxide solution. Subsequently, the desired reaction product is separated, preferably by distillation. It has been found that in the alkylation of unsubstituted phenylalkanols to give alkyl-substituted phenylalkanols, m / p isomer ratios of> 1.5 / 1 can be obtained under certain conditions.
• Examples of suitable C 1 -C 5 -alkyl halides in the process according to the invention are: methyl bromide, methyl iodide, ethyl bromide, ethyl iodide, n-propyl chloride, n-propyl bromide, n-propyl iodide, isopropyl chloride, isopropyl bromide, isopropyl iodide, n-butyl chloride, n-butyl bromide, isobutyl chloride , Isobutyl bromide, sec-butyl chloride, sec-butyl bromide, tert-butyl chloride, tert-butyl bromide, n-pentyl chloride, n-pentyl bromide.
• Preferred d-Cs-alkyl halides of the formula (III) are ethyl halide, in particular ethyl bromide and ethyl iodide, isopropyl halide, in particular isopropyl chloride and isopropyl bromide, isobutyl halide, in particular isobutyl chloride and isobutyl bromide, tert-butyl halide, in particular tert-butyl chloride.
• Ri, R.2, R3, R 4 and R5 have the meanings given under formula (I), which is characterized in that an unsubstituted phenylpropanol of the formula
• R 2 , R 3 , R 4 and R 5 have the meanings given under formula (IV) together with a C 1 -C 5 -alkyl halide of the formula (III)
• R1 and Hai have the meanings given under formula (III), alkylated in the presence of a Friedel-Crafts catalyst to a mixture of m- and p-alkyl-substituted phenylpropanol of the formula (IV), then the reaction mixture, preferably in the presence of water at alkaline pH Value, worked up and the desired m- or p-alkyl-substituted phenylpropanol of the formula (IV) separated, preferably separated by distillation, the remaining by-products formed in the reaction mixture and these in the presence of a Friedel-Crafts catalyst to the desired m- or p- alkyl-substituted phenylpropanol isomerized.
• reaction mixture preferably in the presence of water at alkaline pH, worked up and the desired m- or p-alkyl-substituted phenylpropanol of the formula (VII) separated , preferably separated by distillation, the remaining by-products formed in the reaction mixture and this isomerized in the presence of a Friedel-Crafts catalyst to the desired m- or p-substituted phenylpropanol.
• a very particularly preferred process is characterized in that, as starting compound, 2-methyl-3-phenylpropanol together with tert-butyl halide, in particular tert-butyl chloride, in the presence of aluminum trichloride (AICI3) to form 2-methyl-3- (3- or 4-methylphenyl) tert-butylphenyl) propanol, then the reaction mixture, preferably in the presence of water at alkaline pH, worked up and the desired 3-methyl-3- (3- or 4-tert-butylphenyl) -propanol separated, preferably separated by distillation , and the remaining by-products formed in the reaction mixture and this isomerized in the presence of the Friedel-Crafts catalyst to the desired 3-methyl-3- (3- or 4-tert-butylphenyl) propanol.
• AICI3 aluminum trichloride
• a likewise particularly preferred process is characterized in that the starting compound used is 2-methyl-3-phenylpropanol, 3-phenylpropanol, 3-phenyl-2,2-dimethylpropanol or 3-phenylbutanol and the alkylation in the presence of an isobutyl halide, preferably isobutyl chloride, tert-butyl halide, preferably tert-butyl chloride, isopropyl halide, preferably isopropyl chloride, ethyl halide, preferably ethyl bromide, and in the presence of a Friedel-Crafts catalyst to the compounds 2-methyl-3- (3- or 4-isobutylphenyl) - propanol, 3- (3- or 4-tert-butylphenyl) propanol, 2-methyl-3- (3- or 4-isopropylphenyl) propanol, 3- (3- or 4-ethylphenyl) -2,2-di
• a further preferred embodiment is characterized in that after working up of the reaction mixture, preferably aqueous workup at alkaline pH value, the desired m-substituted reaction product is separated, i. that is preferably the m-alkyl-substituted phenylalkanol of the formula (I), or the m-alkyl-substituted phenylpropanol of the formula (IV), or the m-alkyl-substituted phenylpropanol of the formula (VII), or the 3-methyl-3 - (3-tert-butylphenyl) -propanol, or the compounds 2-methyl-3- (3-iso-butylphenyl) -propanol, 3- (3-tert-butylphenyl) propanol, 2-methyl-3- ( 3-isopropylphenyl) propanol, 3- (3-ethylphenyl) -2,2-dimethylpropanol or 3- (3-
• Friedel-Crafts catalysts can be used. Examples include AlC, AIBr3, TiCu, ZrCu, VC, ZnC, FeBrs and FeC.
• the Friedel-Crafts catalysts AICI3 or AIBr3 are preferably used.
• amounts of catalyst of from 1 to 200 mol%, based on the molar amount of the phenylalkanol compound used are used.
• the alkylation and the isomerization are carried out at temperatures between 0 ° C and 100 ° C. Particularly preferred are temperatures between 10 ° C and 50 ° C.
• the reaction times are 30 minutes to 24 hours. Reaction times between 1 hour and 6 hours are particularly preferred.
• the alkylation reaction as well as the isomerization reaction can be carried out solvent-free or in a solvent.
• Suitable solvents are: cyclohexane, toluene, p-tert-butyltoluene, dichloromethane, 1,2-dichloroethane, chlorobenzene, dichlorobenzene. Particularly preferred are dichloromethane and chlorobenzene.
• Preferred starting materials for the alkylation are the following substrates: 2-methyl-3-phenylpropanol, 2-methyl-3-phenylpropanol, 3-phenylpropanol, 2-methyl-3-phenylpropanol, 3-phenyl-2,2-dimethylpropanol, 3 phenylbutanol.
• Preferred alkylating agents are: isobutyl chloride, tert-butyl chloride, isopropyl chloride, ethyl bromide.
• the reaction also gives rise to the following p-isomers as products of the reaction: 2-methyl-3- (4-tert-butylphenyl) propanol, 2-methyl-3- (4-isobutylphenyl) propanol, 3- (4 tert-butylphenyl) propanol, 2-methyl-3- (4-isopropylphenyl) propanol, 3- (4-ethylphenyl) -2,2-dimethylpropanol, 3- (4-isopropylphenyl) butanol.
• the substrates are particularly preferably 2-methyl-3- (3- or 4-tert-butylphenyl) propanol.
• the reaction is generally carried out in such a way that the catalyst is introduced together with the alkyl halide of the formula (III) into the phenylalkanol dissolved in the solvent.
• the workup is carried out by working up with water and, if necessary, sodium hydroxide solution, and by distillation of the solvent.
• the purification of the crude product and the isolation of the desired m- or p-substituted phenylalkanol is generally carried out by distillation.
• the reaction mass to preferably aqueous workup are preferably recycled to at alkaline pH, and preferably distillative separation.
• the equilibrium between the p-substituted and the m-substituted component and the mono- and tri-substituted phenylalkanols is constantly readjusted, which results in an increased proportion of the desired m- or p- Substituted product is obtained, since this desired product of the reaction mass before each recycling (after work-up and distillation) is removed.
• the reaction is advantageously carried out as a one-pot reaction in which the alkylation is carried out in a first step, the reaction products, together with unreacted starting material, after aqueous work-up, are preferably removed by distillation, the fraction of the desired ten m- or p-substituted phenylalkanols is collected and the by-products of the formulas (A), (B) and (C) are recycled to the reaction vessel and in a second step again in the presence of a Friedel-Crafts catalyst, optionally in a solvent the indicated conditions are isomerized to the desired m- or p-substituted phenylalkanol compound.
• the isomerization with subsequent aqueous workup and distillative removal of the desired component and the recycling of the remaining components of the formulas (A), (B) and (C) for re-isomerization can be carried out repeatedly or quasi-continuously to the proportion of the desired component, m - or p-alkyl-substituted phenylalkanol to obtain in high yield.
• alkanols of the formula (I) prepared according to the invention can be converted into the corresponding aldehydes, based on known dehydrogenation or oxidation methods (cf., for example: Houben-Weyl "Methods of Organic Chemistry", Volume 7/1, p 160ff, p. 171f).
• Particularly interesting compounds of this class of substances are 2-methyl-3- (3- or 4-tert-butylphenyl) propanal, 2-methyl-3- (3- or 4-isobutylphenyl) propanal, 3- (3- or 4- tert-butylphenyl) propanal, 2-methyl-3- (3- or 4-isopropylphenyl) -propanal, 3- (3- or 4-ethylphenyl) -2,2-dimethylpropanal and 3- (3- or 4-isopropylphenyl) butanal.
• phenylpropanols can be converted by oxidation or dehydrogenation into the corresponding phenylpropanals. This reaction is achieved, for example, by copper chromite-catalyzed liquid phase dehydrogenation.
• Preferred starting materials for the reaction to the aldehyde are 2-methyl-3- (3- or 4-tert-butylphenyl) propanol, 2-methyl-3- (3- or 4-iso-butylphenyl) propanol, 3- (3- or 4-tert-butylphenyl) propanol, 2-methyl-3- (3- or 4-isopropylphenyl) propanol, 3- (3- or 4-ethylphenyl) -2,2-dimethylpropanol, 3- (3- or 4-isopropylphenyl ) butanol.
• Another object of the invention is thus the preparation of the obtainable from the m- or substituted phenylalkanols of the formula (I) by oxidation or dehydrogenation value products of the formula (VIII), which play an interesting role as fragrances and Aromachemikalien,
• Ri is bonded in m- or p-position to the phenyl and Ci-Cs-alkyl importance tet and R2, R3, R 4 and R 5 are independently hydrogen or methyl, is characterized in that an unsubstituted phenylalkanol of formula (Ii)
• R 2 , R 3 , R 4 and R 5 have the meanings given under formula (VIII) together with a C 1 -C 5 -alkyl halide of the formula (III)

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• 2010
  • 2010-10-14 US US13/503,515 patent/US8692025B2/en not_active Expired - Fee Related
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