Process for preparation of ether, thioether or secondary amine derivatives in presence of heterogeneous acidic catalyst

Abstract

The present invention relates to the field of organic synthesis, more particularly to a process for the preparation of an ether, thioether or secondary amine of formula (I), comprising reacting an alcohol, thiol or amine of formula (II) with an epoxide of formula (III) in the presence of a heterogeneous acidic catalyst.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and more specifically, to a method for preparing an ether, a thioether or a secondary amine of formula (I), comprising reacting an alcohol, a thiol or an amine of formula (II) with an epoxide of formula (III) in the presence of a heterogeneous acidic catalyst. Background Art

[0002] Ether, thioether or secondary amine derivatives represent highly desirable backbones that can be used alone or as key intermediates for the preparation of more complex compounds in different fields such as fragrances, cosmetics, pharmaceuticals or agrochemistry. Related ether derivatives such as 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol, which is used in the synthesis of (trademark of Firmenich SA of Switzerland), is one of the most sought after ingredients in the fragrance industry.

[0003] The synthetic reaction pathways are limited in possibilities and require 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol as a key intermediate. Traditionally, α-3,3-trimethylcyclohexane methanol is reacted with 1,2-epoxy-2-methylpropane in the presence of a homogeneous acidic catalyst (e.g., a soluble Lewis acid). Unfortunately, the selectivity and conversion efficiency (yield) of this reaction are low. The low efficiency mainly stems from unwanted side reactions, including the ring opening reaction of α-3,3-trimethylcyclohexane methanol and the formation of heavier products from the reaction of 1,2-epoxy-2-methylpropane with the in situ generated 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol. In addition, the homogeneous catalysts suitable for this reaction can also corrode the equipment used to carry out the reaction. Furthermore, the use of homogeneous catalysts which require substantial post-reaction wash steps appears to be particularly problematic due to the nature of 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol, ie, its surfactant action.

[0004] Therefore, it is necessary to develop a reaction process with higher conversion efficiency and selectivity, thereby improving the yield and simplifying the post-processing procedures.

[0005] The present invention solves the above problems by using a heterogeneous acidic catalyst to prepare the ether, thioether or secondary amine of formula (I). To the best of our knowledge, the conditions of the present invention have never been reported in the prior art. Summary of the invention

[0006] Surprisingly, it has now been found that the preparation of compounds of formula (I) by reaction of compounds of formula (II) with epoxides of formula (III) in the presence of heterogeneous acidic catalysts allows the preparation of compounds of formula (I) in high yields and with high selectivity.

[0007] Therefore, a first object of the present invention is a process for preparing a compound of formula (I),

[0008]

[0009] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0010] Y is a sulfur atom, an oxygen atom or an NH group,

[0011] R 1 Represents C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 Alkyl; and

[0012] R 2 , R 3 , R 4 Each independently represents a hydrogen atom or a C 1-4 alkyl;

[0013] The method comprises reacting a compound of formula (II) with an epoxide of formula (III) in the presence of a heterogeneous acidic catalyst.

[0014]

[0015] wherein X is a thiol group, an alcohol group or a primary amine group, and

[0016] Where R 1 and R 2 has the same meaning as defined above;

[0017]

[0018] Where R 3 and R 4 has the same meaning as defined above.

[0019] For the sake of clarity, by expressing "any stereoisomer thereof or a mixture thereof" or similar expressions, it is intended to mean the normal meaning understood by those skilled in the art, that is, the compounds cited in the present invention may be pure enantiomers, or mixtures of multiple enantiomers. In other words, the compounds cited in the present invention may have at least one stereocenter, and the stereocenter may have two different stereochemistries (e.g., R or S), for example, R 1The group may contain at least one stereocenter. The compound may even be in the form of a pure enantiomer, or in the form of a mixture of multiple enantiomers. When the compound has more than one stereocenter, the compound cited in the present invention may even be in the form of a pure diastereomer, or in the form of a mixture of multiple diastereomers. The compound may be in racemic form or in non-racemic (scalemic, ratio optical) form. Therefore, the compound may be a stereoisomer, or in the form of a material composition comprising or consisting of various stereoisomers.

[0020] It will be appreciated that if Y is a sulfur atom, the compound comprises a thiol ether group.

[0021] It will be appreciated that if Y is an oxygen atom, the compound comprises an ether group.

[0022] It will be appreciated that if Y is an NH group, the compound comprises a secondary amine group.

[0023] The term "optionally" is to be understood as meaning that a group may or may not contain a certain functional group or substituent.

[0024] The term "alkyl" is understood to include straight-chain or branched-chain alkyl groups.

[0025] The term "alkenyl" is understood to include straight-chain or branched alkenyl groups.

[0026] Expression "C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 "Alkyl" is understood to mean a cycloalkyl or cycloalkenyl group optionally substituted with 1 to 3 C 1-4 alkyl.

[0027] According to a particular embodiment, X is an alcohol group and Y is an oxygen atom.

[0028] According to a particular embodiment, R 1 C 1-10 Alkyl, C 2-10 Alkenyl, C 5-10 Cycloalkyl or C 5-10 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 In particular, R 1 C 1-8 Alkyl, C 2-8 Alkenyl, C 5-10 Cycloalkyl or C 5-10Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 In particular, R 1 C 1-6 Alkyl, C 2-6 Alkenyl, C 5-10 Cycloalkyl or C 5-10 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 In particular, R 1 C 5-10 Cycloalkyl or C 5-10 Cycloalkenyl, preferably C 5-8 Cycloalkyl or C 5-8 Cycloalkenyl, preferably C 5-7 Cycloalkyl or C 5-7 Cycloalkenyl, preferably C 5-6 Cycloalkyl or C 5-6 Cycloalkenyl, more preferably C 6 Cycloalkyl, each optionally substituted with 1 to 3 C 1-4 Alkyl, preferably substituted with 1 to 2 C 1-3 Alkyl, even more preferably substituted with 1 to 2 C 1-2 Alkyl. Even more particularly, R 1 It is 3,3-dimethyl-1-cyclohexyl.

[0029] According to a particular embodiment, R 2 Represents hydrogen atom or C 1-3 In particular, R 2 represents methyl or ethyl, more preferably methyl.

[0030] According to a particular embodiment, R 3 Represents hydrogen atom or C 1-3 In particular, R 3 represents methyl or ethyl, more preferably methyl.

[0031] According to a particular embodiment, R 4 Represents hydrogen atom or C 1-3 In particular, R 4 represents methyl or ethyl, more preferably methyl.

[0032] According to a more specific embodiment, R 3 and R 4 Each represents a methyl group.

[0033] According to a particular embodiment, the invention relates to a process, wherein the compound of formula (II) corresponds to formula (IIa),

[0034]

[0035] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0036] in

[0037] One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and

[0038] X is a thiol group, an alcohol group or a primary amine group, and

[0039] Each R 2 , R 5 , R 6 , R 7 and R 8 Each independently represents a hydrogen atom or a C 1-4 Alkyl; or

[0040] R 7 and R 8 Connect to form C 5-7 cycloalkyl or cycloalkenyl; and

[0041] The compound of formula (I) conforms to formula (Ia),

[0042]

[0043] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0044] Wherein, Y is a sulfur atom, an oxygen atom or an NH group,

[0045] Dashed line, R 2 , R 5 , R 6 , R 7 and R 8 has the same meaning as defined above; and

[0046] R 3 and R 4 Each independently represents a hydrogen atom or a C 1-4 alkyl.

[0047] For the sake of clarity, the statement “one dashed line is a carbon-carbon single bond or double bond, and the other dashed line is a carbon-carbon single bond” refers to the normal meaning understood by those skilled in the art, that is, the entire bond (solid line and dashed line) between the carbon atoms connected by the dashed lines is a carbon-carbon single bond or double bond.

[0048] Those skilled in the art will appreciate that when R 8 When R represents a hydrogen atom, 8 The dashed lines between adjacent carbon atoms represent hydrogen-carbon single bonds.

[0049] For the sake of clarity, the statement “If R 7 and R8 interconnected, they form C 5-7 Cycloalkyl or cycloalkenyl" refers to R 7 and R 8 Can be chemically connected through carbon-carbon single or double bonds to form a C that includes other carbon atoms in the structure. 5-7 Cycloalkyl or cycloalkenyl.

[0050] According to a specific embodiment, R 2 To R 8 has the same meaning as defined above.

[0051] According to a particular embodiment, the compound of formula (IIa) conforms to formula (IIa,i)

[0052]

[0053] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0054] wherein X is a thiol group, an alcohol group or a primary amine group, and

[0055] R 2 A hydrogen atom or C 1-4 Alkyl; and

[0056] The compound of formula (Ia) conforms to formula (Ia,i)

[0057]

[0058] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0059] wherein Y is a sulfur atom, an oxygen atom or an NH group, and

[0060] R 2 , R 3 , R 4 Each independently represents a hydrogen atom or a C 1-4 alkyl.

[0061] According to a particular embodiment, the invention relates to a process, wherein the compound of formula (II) corresponds to formula (IIb),

[0062]

[0063] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0064] Where n is 0 or 1;

[0065] X is a thiol group, an alcohol group or a primary amine group, and

[0066] One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and

[0067] R 2 , R 5 and R 6 Each independently represents a hydrogen atom or a C 1-4 Alkyl; and

[0068] The compound of formula (I) conforms to formula (Ib),

[0069]

[0070] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0071] Wherein, Y is a sulfur atom, an oxygen atom or an NH group,

[0072] Dashed line, n, R 2 , R 5 and R 6 has the same meaning as defined above; and

[0073] R 3 and R 4 Each independently represents a hydrogen atom or a C 1-4 alkyl.

[0074] According to a particular embodiment, n is 1.

[0075] According to a specific embodiment, R 2 To R 6 has the same meaning as defined above.

[0076] According to a particular embodiment, the invention relates to a process, wherein the compound of formula (II) corresponds to formula (IIc),

[0077]

[0078] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0079] wherein X is a thiol group, an alcohol group or a primary amine group, and

[0080] R 2 Hydrogen atom or C 1-4 Alkyl; and

[0081] The compound of formula (I) conforms to formula (Ic),

[0082]

[0083] The compound is in the form of any one of its stereoisomers or a mixture thereof,

[0084] Wherein, Y is a sulfur atom, an oxygen atom or an NH group,

[0085] R 2 , R 3 , R 4 Each independently represents a hydrogen atom or a C 1-4 alkyl.

[0086] According to a specific embodiment, R 2 To R 4 has the same meaning as defined above.

[0087] According to a more specific embodiment, the compound of formula (I) conforms to formula (Id),

[0088]

[0089] The compound is in the form of any stereoisomer or a mixture thereof; and the compound of formula (II) conforms to formula (IId),

[0090]

[0091] The compound is in the form of any stereoisomer or a mixture thereof, and the epoxide of formula (III) conforms to formula (IIId),

[0092]

[0093] Heterogeneous acid catalyst

[0094] According to any embodiment of the present invention, the heterogeneous acidic catalyst may be amorphous or crystalline, in particular crystalline.

[0095] According to any embodiment of the present invention, the heterogeneous acidic catalyst may include at least one metal selected from silicon, tin, zirconium, hafnium or titanium or a mixture thereof, and optionally at least one metal selected from aluminum, boron, iron or a mixture thereof. Preferably, the heterogeneous acidic catalyst includes at least one metal selected from silicon or tin or a mixture thereof, and optionally at least one metal selected from aluminum, boron, iron or a mixture thereof.

[0096] According to any embodiment of the present invention, the heterogeneous acidic catalyst may be a Lewis acid supported on a solid support.

[0097] Those skilled in the art will be able to select a suitable Lewis acid. A suitable Lewis acid may be HClO 4 , BF 3 、AlCl 3 、FeCl 3 , CuCl 2、ZnCl 2 , ZnBR 2 、ZrCl 4 、TiCl 4 or TiCl 4-x (OR) x , where R represents C 1-12 Other suitable Lewis acids may be metal trifluoromethanesulfonates, wherein the metal may be a metal selected from the lanthanide series, preferably lanthanum. Other suitable Lewis acids may be heteropoly acids (also known as heteropolymetallates). A person skilled in the art will be able to select a suitable heteropoly acid based on their general knowledge in the art. A preferred heteropoly acid is silicotungstic acid (H 4 S W 12 O 40 ·nH 2 O), phosphomolybdic acid (H 3 Mo 12 PO 40 ·nH 2 O) or phosphotungstic acid (H 3 W 12 PO 40 ·nH 2 O).

[0098] According to one embodiment, the supported Lewis acid may be a mixture of two or more Lewis acids.

[0099] A solid support is understood to be one that remains solid under the selected reaction conditions. According to a particular embodiment, the solid support may be an organic or inorganic polymer. According to a particular embodiment, the solid support may be an inorganic support material. According to a particular embodiment, the inorganic support material may be a metal oxide. According to a particular embodiment, the inorganic support material may include a metal selected from silicon, tin, aluminum, zirconium, titanium, iron, boron or a mixture thereof, preferably silicon. According to a particular embodiment, the inorganic support material may be silicon dioxide. According to a particular embodiment, the supported Lewis acid is BF 3 / SiO 2 or HClO 4 / SiO 2 .

[0100] According to any embodiment of the present invention, the heterogeneous acidic catalyst is an aluminosilicate catalyst.

[0101] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a zeolite or a clay.

[0102] According to any embodiment of the present invention, the heterogeneous acidic catalyst is clay.

[0103] The clay may be commercially available clay. According to any embodiment of the present invention, the commercially available clay may contain water. The water may be partially or completely removed before use. Methods for removing water are well known to those skilled in the art, such as azeotropic distillation, vacuum stripping or heating under a nitrogen stream.

[0104] According to any embodiment of the present invention, the clay may be naturally occurring. According to any embodiment of the present invention, the heterogeneous acidic catalyst is an acid-treated clay. Acid-treated clay is understood herein as clay that has been acid-treated according to the methods described in patents US2470872A, US2671058A, US2981697A or US1926148A before being used as a heterogeneous acidic catalyst. The technician can select the most suitable conditions for acid-treating the clay based on his general knowledge in the art and the teachings of these patent applications.

[0105] Non-limiting examples of suitable clays can include K-type clays, such as K-5, K10-S300, K-20, K-30, K-41, or K-306 (currently sold by Clariant), former Filtrol-type clays, such as F-20X, F20-XLM, F-21X, F-24X, F-25X, F-31X, F-54X, F-22, or F-118FF (currently sold by EP Minerals), Fulcat-22F, Fulcat-22B, or Fulcat 435 (currently sold by Byk), EXBC 0001 (currently sold by Clariant). In one embodiment, the clay is K10-S300.

[0106] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a zeolite.

[0107] According to any embodiment of the invention, the zeolite is used in its proton form. The latter can be provided directly by the manufacturer and used directly, or obtained by thermal decomposition in an ammonium exchanged form. In a specific embodiment, the zeolite is a preactivated zeolite. The preactivation can be carried out by removing the previously described trapped water in the clay or by heating the zeolite to a temperature of 300° C. to 600° C. for at least 1 hour under air or an inert gas.

[0108] The heterogeneous acidic catalyst is a commercially available compound or can be prepared by various methods, such as those reported in US20040141911, US6054113, US4840930, US2470872 and EP0398636.

[0109] Non-limiting examples of suitable zeolites may include CBV780, CBV901 currently sold by Zeolyst, or HSZ-385HUA or HSZ-390HUA currently sold by Tosoh.

[0110] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a large pore zeolite.

[0111] The term "large pore zeolite" has the usual meaning in the art, ie, a 12-membered ring zeolite having a pore size ranging from 6.0 angstroms to 7.5 angstroms. Non-limiting examples of suitable large pore zeolites may include FAU, BEA, MOR.

[0112] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a zeolite having a FAU topology.

[0113] The term "FAU topology" is understood as commonly used in the zeolite field and is well known to those skilled in the art. Framework topology is usually defined by a three-letter code, following the rules established by the IUPAC Zeolite Nomenclature Committee in 1978 (RM Barrer, Pure Appl. Chem. 51, 1091 (1979)).

[0114] Zeolites with FAU topology are understood to be zeolites with the faujasite crystal structure. The person skilled in the art is aware of the definition of the faujasite crystal structure, which is described, for example, in Chemie Lexikon, Georg Thieme Verlag, 9. Edition, 1990, page 1311.

[0115] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a Y-type zeolite.

[0116] The term Y-zeolite is to be understood as the commonly used meaning in the field of zeolites and is well known to those skilled in the art. Y-zeolite is to be understood as a zeolite with a FAU topology. Typical features of Y-zeolites are spherical internal cavities (so-called "super cages"), which are connected in a tetrahedral form by pore openings of about 8 angstroms and contain rings formed by twelve oxygen atoms.

[0117] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a dealuminated zeolite.

[0118] Dealumination is generally understood to be the removal of aluminum atoms from the zeolite structure. Dealumination results in an increase in the silicon: aluminum ratio of the zeolite. Non-limiting examples of suitable dealumination methods known in the art are hydrothermal treatment, acid treatment, treatment with gaseous halides or halogens, or complexation with chelating agents. Those skilled in the art are aware of these methods and how they are performed.

[0119] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a dealuminated ultrastable Y (USY) zeolite.

[0120] USY zeolite is usually prepared from Y-type zeolite, and aluminum in the framework is removed by ion exchange, steam treatment, acid leaching and calcination to improve its stability and catalytic activity. For example, such treatment methods are described in patents US5601798A and US4477336A and are well known to those skilled in the art.

[0121] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a hydrophobic zeolite.

[0122] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a hydrophobic dealuminated USY zeolite.

[0123] The hydrophobicity of zeolites is usually defined by the hydrophobicity index (HI). According to I. Halasz et al. in Molecular Physics, 2002, 100, 3232-3232, the hydrophobicity index is defined as the amount of cyclohexane (usually in grams) adsorbed per unit weight (usually in grams) of water adsorbed on the zeolite when the vapor pressures of cyclohexane and water are 933 Pa (7 Torr) and 666 Pa (5 Torr), respectively.

[0124] According to any embodiment of the present invention, the hydrophobicity index is 5 to 100, preferably 10 to 75, and more preferably 20 to 50.

[0125] According to any embodiment of the present invention, the silicon:aluminum ratio is in the range of 5:1 to 350:1.

[0126] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 10:1 to 325:1.

[0127] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 15:1 to 300:1.

[0128] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 22:1 to 275:1.

[0129] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 30:1 to 250:1.

[0130] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 40:1 to 250:1.

[0131] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 50:1 to 250:1.

[0132] In a particular embodiment, the heterogeneous acidic catalyst is selected from the group consisting of clay, zeolite and supported Lewis acid. Clay, zeolite and supported Lewis acid may be as defined above, respectively.

[0133] A heterogeneous acidic catalyst may be added to the reaction medium of the process of the present invention to form the compound of formula (I) over a wide range of concentrations.

[0134] According to any embodiment of the present invention, the heterogeneous acidic catalyst is used in an amount of 2 to 50 wt %, preferably 3 to 30 wt %, more preferably 4 to 15 wt %, even more preferably 5 to 10 wt % relative to the amount of epoxide of formula (III).

[0135] According to any embodiment of the present invention, the compound of formula (II) or formula (IIa) is used in an amount of 1.0 to 10 equivalents, preferably 1.4 to 7 equivalents, more preferably 1.8 to 4.2 equivalents relative to the amount of the epoxide of formula (III).

[0136] According to any embodiment of the present invention, the process temperature is maintained in the range of 0 to 50° C., preferably 25 to 48° C., more preferably 43 to 47° C. A person skilled in the art can select the preferred temperature according to the melting and boiling points of the starting and final products and the desired time, conversion or selectivity of the reaction.

[0137] The process of the present invention for preparing the compound of formula (I) can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, then any solvent of the type of reaction at the time may be used for the purposes of the present invention. Non-limiting examples include C 6-12 Aromatic solvents such as xylene, toluene, 1,3-diisopropylbenzene, cumene, pseudocumene, anisole or chlorobenzene or mixtures thereof, hydrocarbon solvents such as cyclohexane, heptane or mixtures thereof, nitrile solvents such as acetonitrile, or ether solvents such as tetrahydrofuran, diethyl ether, methyltetrahydrofuran or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or catalyst, and a person skilled in the art is fully capable of selecting the most suitable solvent in each case to optimize the reaction.

[0138] The process of the present invention for preparing the compound of formula (I) can be carried out under batch and / or continuous conditions.

[0139] The process according to any embodiment of the present invention can be used to prepare a compound of formula (IV),

[0140]

[0141] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0142] Y is a sulfur atom, an oxygen atom or an NH group,

[0143] R 1 Represents C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 Alkyl; and

[0144] R 2 , R 3 , R 4 Each independently represents a hydrogen atom or a C 1-4 Alkyl; and

[0145] R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 Cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl;

[0146] The method comprises reacting a compound of formula (I) with a compound of formula ZC(O)-R 10 The compound reaction proceeds, wherein Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

[0147] According to any embodiment of the present invention, the compound of formula (IV) conforms to formula (IVa),

[0148]

[0149] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0150] One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and

[0151] Y is a sulfur atom, an oxygen atom or an NH group,

[0152] R 2 , R 3 , R 4 , R 5 , R 6 and R 7 Each independently represents a hydrogen atom or a C 1-4 alkyl; and

[0153] R 8 Represents C 1-4 Alkyl; or

[0154] R 7 and R 8 Connect to form C 5-7 cycloalkyl or cycloalkenyl; and

[0155] R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl; and

[0156] The compound of formula (Iva) is prepared by reacting a compound of formula (Ia) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

[0157] According to any embodiment of the present invention, the compound of formula (IV) conforms to formula (IVa,i),

[0158]

[0159] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0160] One dashed line is a carbon-carbon single bond or double bond, and the other dashed line is a carbon-carbon single bond; and

[0161] Y is a sulfur atom, an oxygen atom or an NH group, and

[0162] R 2 , R 3 and R 4 Each independently represents a hydrogen atom or a C 1-4 Alkyl; and

[0163] R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl; and

[0164] The compound of formula (IVa) is prepared by reacting a compound of formula (Ia) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

[0165] According to any embodiment of the present invention, the compound of formula (IV) conforms to formula (IVb),

[0166]

[0167] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0168] n is 0 or 1; and

[0169] One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and

[0170] Y is a sulfur atom, an oxygen atom or an NH group,

[0171] R 2 , R 3 , R 4 , R 5 and R 6 Each independently represents a hydrogen atom or a C 1-4 Alkyl; and

[0172] R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl; and

[0173] The compound of formula (IVb) is prepared by reacting a compound of formula (Ib) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

[0174] According to any embodiment of the present invention, the compound of formula (IV) conforms to formula (IVc),

[0175]

[0176] The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein

[0177] Y is a sulfur atom, an oxygen atom or an NH group,

[0178] R 2 , R 3 and R 4 Each independently represents a hydrogen atom or a C 1-4 Alkyl; and

[0179] R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably ethyl, ethylene, cyclopropane or cyclopentane, more preferably ethyl; and

[0180] The compound of formula (IVc) is prepared by reacting a compound of formula (Ic) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

[0181] According to a particular embodiment, R 1 represents optionally substituted with 1 to 2 C 1-3 Alkyl C 5-8 Cycloalkyl, preferably substituted with 1 to 2 C 1-2 Alkyl C 5-8 Cycloalkyl, more preferably C substituted with 2 methyl groups 6 Cycloalkyl.

[0182] According to a particular embodiment, R 2 represents methyl or ethyl, more preferably methyl.

[0183] According to a particular embodiment, R 3 represents methyl or ethyl, more preferably methyl.

[0184] According to a particular embodiment, R 4 represents methyl or ethyl, more preferably methyl.

[0185] According to a more specific embodiment, R 3 and R 4 Each represents a methyl group.

[0186] According to a particular embodiment, R 5 represents methyl or ethyl, more preferably methyl.

[0187] According to a particular embodiment, R 6 represents methyl or ethyl, more preferably methyl.

[0188] According to a more specific embodiment, R 5 and R 6 Each represents a methyl group.

[0189] According to a particular embodiment, R 7 Represents a hydrogen atom.

[0190] According to a specific embodiment, R 8 represents methyl or ethyl, more preferably methyl.

[0191] According to any embodiment of the present invention, the compound of formula (IV) conforms to formula (IVd),

[0192]

[0193] The compound is in the form of any one of its stereoisomers or a mixture thereof.

[0194] Typical modes for implementing the method of the present invention will be reported in the following examples, but should not be considered as limiting the present invention. In the examples, unless otherwise indicated, abbreviations have the usual meanings in the art, temperatures are expressed in degrees Celsius (° C.), and percentages are expressed in weight percentage (wt %). DETAILED DESCRIPTION

[0195] Example

[0196] Example 1: General Catalyst Screening Procedure

[0197] In a 0.5 L double-jacketed glass reactor equipped with a mechanical stirrer, 130 g (0.832 mol) of (R)-1-((S)-3,3-dimethylcyclohexyl)ethan-1-ol (referred to herein as Cyclademol) was stirred vigorously at 45°C in the presence of 2.08 g of catalyst (10 wt% relative to isobutylene oxide (IBO)). TM , source DRT). 20.8 g (0.288 mol) of isobutylene oxide (IBO, source BASF) was slowly added to the solution over two hours, and the reaction was continued with stirring for two hours. After filtering the catalyst, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol relative to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0198] Example 2: Zeolite Catalyst

[0199] Several zeolites listed in Table 1 were used as catalysts in the step of Example 1. The results of the screening are shown in Table 1. Each zeolite in Table 1 was calcined before use.

[0200] Table 1: Freshly calcined zeolites

[0201]

[0202] Example 3: As-received USY zeolite with low catalyst loading

[0203] In a 1 L double-jacketed glass reactor equipped with a mechanical stirrer, 400 g (2.56 mol) of (R)-1-((S)-3,3-dimethylcyclohexyl)ethan-1-ol (hereinafter referred to as Cyclademol) was stirred vigorously at 45°C in the presence of 3.2 g of the original catalyst (5 wt% relative to isobutylene oxide (IBO)). TM , source DRT). 64 g (0.887 mol) of isobutylene oxide (IBO, source BASF) was slowly added to the solution over two hours, and the reaction was continued with stirring for two hours. After filtering the catalyst, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol relative to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0204] Table 2: As-received USY zeolite

[0205]

[0206] Example 4: Comparison of homogeneous catalysts

[0207] In a 0.5 L double-jacketed glass reactor equipped with a mechanical stirrer, 130 g (0.832 mol) of (R)-1-((S)-3,3-dimethylcyclohexyl)ethan-1-ol (referred to herein as Cyclademol) was stirred vigorously at 30°C in the presence of 16.8 mmol of the homogeneous catalyst defined in Table 3 below. TM , source DRT). 20.8 g (0.288 mol) of isobutylene oxide (IBO, source BASF) was slowly added to the solution over two hours, and the reaction was stirred for one hour. After the solution was quenched with sodium citrate aqueous solution, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol relative to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0208] Table 3: Homogeneous Catalysts

[0209]

[0210] Example 5: Preparation of 2-((3,5-dimethylhex-3-en-2-yl)oxy)-2-methylpropan-1-ol

[0211] 14 g (0.109 mol) of 3,5-dimethylhex-3-en-2-ol (prepared according to the method described in WO2004 / 050595A1 - Example 1) was vigorously stirred at 45°C in the presence of 0.274 g of HSZ-390HUA (Tosoh). 2.74 g (0.038 mol) of isobutylene oxide (IBO, source BASF) was slowly added to the solution, and the reaction was continued for 1 hour under stirring. After filtering the solid catalyst, the yield of 2-((3,5-dimethylhex-3-en-2-yl)oxy)-2-methylpropan-1-ol relative to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard, and the result reached 42.3 mol%.

Claims

1. A method for preparing a compound of formula (I), The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein Y is a sulfur atom, an oxygen atom or an NH group, R1 represents C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 Alkyl; and R2, R3, and R4 each independently represent a hydrogen atom or a C 1-4 alkyl; The method comprises reacting a compound of formula (II) with an epoxide of formula (III) in the presence of a heterogeneous acidic catalyst. wherein X is a thiol group, an alcohol group or a primary amine group, and wherein R1 and R2 have the same meanings as defined above; wherein R3 and R4 have the same meanings as defined above.

2. The method according to claim 1, wherein the compound of formula (II) conforms to formula (IIa), The compound is in the form of any one of its stereoisomers or a mixture thereof, in One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and X is a thiol group, an alcohol group or a primary amine group, and Each of R2, R5, R6, R7 and R8 independently represents a hydrogen atom or a C 1-4 Alkyl; or R7 and R8 are connected to form C 5-7 Cycloalkyl or cycloalkenyl; and The compound of formula (I) conforms to formula (Ia), The compound is in the form of any one of its stereoisomers or a mixture thereof, in Y is a sulfur atom, an oxygen atom or an NH group, and The dashed line, R2, R5, R6, R7 and R8 have the same meanings as defined above; and R3 and R4 each independently represent a hydrogen atom or a C 1-4 alkyl.

3. A method according to any one of the preceding claims, wherein the compound of formula (II) conforms to formula (IIc), The compound is in the form of any one of its stereoisomers or a mixture thereof, in X is a thiol group, an alcohol group or a primary amine group, and R2 is a hydrogen atom or C 1-4 alkyl; and The compound of formula (I) conforms to formula (Ic), The compound is in the form of any one of its stereoisomers or a mixture thereof, in Y is a sulfur atom, an oxygen atom or an NH group, and R2, R3, and R4 each independently represent a hydrogen atom or a C 1-4 alkyl.

4. A process according to any one of the preceding claims, wherein X is an alcohol group and Y is an oxygen atom.

5. A process according to any one of the preceding claims, wherein R2 represents a methyl group.

6. A process according to any one of the preceding claims, wherein each of R3 and R4 represents a methyl group.

7. The process according to any one of the preceding claims, wherein the heterogeneous acidic catalyst is an aluminosilicate catalyst.

8. The process according to any one of the preceding claims, wherein the heterogeneous acidic catalyst is a zeolite or a clay.

9. A process according to any one of the preceding claims, wherein the zeolite is a large pore zeolite.

10. The process according to any one of the preceding claims, wherein the heterogeneous acidic catalyst is a hydrophobic zeolite.

11. The process according to any one of the preceding claims, wherein the heterogeneous acidic catalyst is a zeolite having a FAU topology.

12. The process according to any one of the preceding claims, wherein the heterogeneous acidic catalyst is a dealuminated ultrastable Y (USY) zeolite.

13. A method according to any one of the preceding claims, wherein the silicon:aluminium ratio is in the range of 5:1 to 350:1, preferably 15:1 to 300:1, more preferably 30:1 to 250:

1.

14. A process according to any one of the preceding claims for preparing a compound of formula (IV), The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein Y is a sulfur atom, an oxygen atom or an NH group, R1 represents C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 Cycloalkenyl, each optionally substituted with 1 to 3 C 1-4 Alkyl; and R2, R3, and R4 each independently represent a hydrogen atom or a C 1-4 Alkyl; and R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl; and The compound of formula (IV) is prepared by reacting a compound of formula (I) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

15. The method according to claim 14, wherein the compound of formula (IV) conforms to formula (IVa), The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein One dashed line is a carbon-carbon single or double bond and the other dashed line is a carbon-carbon single bond; and Y is a sulfur atom, an oxygen atom or an NH group, R2, R3, R4, R5, R6 and R7 each independently represent a hydrogen atom or a C 1-4 Alkyl; and R8 represents C 1-4 Alkyl; or R7 and R8 are connected to each other to form C 5-7 cycloalkyl or cycloalkenyl; and R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl, and The compound of formula (IVa) is prepared by reacting a compound of formula (Ia) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

16. The method according to any one of claims 14 to 15, wherein the compound of formula (IV) conforms to formula (IVc), The compound is in the form of any one of its stereoisomers or a mixture thereof; wherein Y is a sulfur atom, an oxygen atom or an NH group, R2, R3 and R4 each independently represent a hydrogen atom or a C 1-4 Alkyl; and R 10 Represents C 1-6 Alkyl, C 2-6 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-4 Alkyl, C 2-4 Alkenyl, C 3-6 Cycloalkyl; preferably C 1-3 Alkyl, C 2-3 Alkenyl, C 3-5 cycloalkyl; preferably ethyl, vinyl, cyclopropyl or cyclopentyl, more preferably ethyl, and The compound of formula (IVc) is prepared by reacting a compound of formula (Ic) with a compound of formula ZC(O)-R 10 Compounds react to form, where Z is R 10 -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group.

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