Process for producing an ether, thioether or secondary amine derivative in the presence of a heterogeneous acidic catalyst

Abstract

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

[0002] Background Art Ether, thioether or secondary amine derivatives represent very desirable skeletons that can be used as such or as important intermediates, especially for the preparation of more complex compounds in different fields such as cosmetics, toiletries, pharmaceuticals and agrochemicals. Related ether derivatives are, for example, 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol, which is used in the synthesis of Helvetide® (trademark of Firmenich SA, Suisse) and represents one of the most sought-after ingredients in the cosmetics industry.

[0003] However, the possible reaction pathways for the synthesis of Helvetid® are limited and pass through 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol as an important intermediate. Conventionally, α-3,3-trimethylcyclohexanemethanol reacts with 1,2-epoxy-2-methylpropane in the presence of a homogeneous acidic catalyst, such as a soluble Lewis acid. Unfortunately, the selectivity of this reaction, and thus the conversion efficiency (yield), is low. This lack of efficiency is mainly due to unwanted side reactions, including ring-opening reactions of α-3,3-trimethylcyclohexanemethanol and the formation of heavier products resulting from the in-situ reaction of 1,2-epoxy-2-methylpropane with 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol formed. Furthermore, homogeneous catalysts suitable for this reaction can also be corrosive to the equipment used to carry out the reaction. Additionally, the use of homogeneous catalysts that require a basic post-reaction washing step has been particularly problematic due to the nature of 2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol, which behaves as a surfactant.

[0004] As a result, there is a need to develop a reaction process with improved conversion efficiency and selectivity, and thus improved yield and simplified post-treatment procedures.

[0005] The present invention makes it possible to solve the above problems by using a heterogeneous acidic catalyst for the preparation of ethers, thioethers or secondary amines of formula (I). To the best of the inventors' knowledge, the state of the present invention has not been reported in the prior art.

[0006] DETAILED DESCRIPTION OF THE INVENTION Surprisingly, it has now been discovered that the production of a compound of formula (I) by the reaction of a compound of formula (II) with an epoxide of formula (III) in the presence of a heterogeneous acidic catalyst makes it possible to produce the compound of formula (I) in high yield and high selectivity.

[0007] Accordingly, a first object of the present invention is a compound of formula (I) [Chemical formula] A process for producing 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, Each R1 is a C 1-4 alkyl group optionally substituted with 1 to 3 C 1-12 alkyl, C 2-12 alkenyl, C 5-12 cycloalkyl or C 5-12 cycloalkenyl group; and Each R2, R3, R4 is, separately and independently of one another, a hydrogen atom or a C 1-4 alkyl group; The compound of formula (II) [Chemical formula] [wherein X is a thiol group, an alcohol group or a primary amine group, wherein R1 and R2 have the same meanings as defined above]; and The epoxide of formula (III) [Chemical formula] [wherein R3 and R4 have the same meanings as defined above]; and A method comprising a reaction in the presence of a heterogeneous acid catalyst.

[0008] For the sake of clarity, the expression "any one of its stereoisomers or a mixture thereof" or a similar expression means the ordinary meaning understood by those skilled in the art, i.e., the compound cited in the present invention can be a pure enantiomer or a mixture of enantiomers. In other words, the compound cited in the present invention may have at least one stereocenter that can have two different stereochemistries (e.g., R or S), e.g., R 1The base may contain at least one stereocenter. The compound may be in the form of a pure enantiomer or a mixture of enantiomers. When the compound cited in the present invention has two or more stereocenters, the compound may be in the form of a pure diastereoisomer or a mixture of diastereoisomers. The compound may be a racemate or a scalemic form. Thus, the compound may be one stereoisomer or may be in the form of a composition of matter containing or consisting of various stereoisomers.

[0009] When Y is a sulfur atom, it is understood that the compound contains a thioether group.

[0010] When Y is an oxygen atom, it is understood that the compound contains an ether group.

[0011] When Y is an NH group, it is understood that the compound contains a secondary amine group.

[0012] The term "optionally" is understood to mean that a group can or cannot contain a particular functional group or substituent.

[0013] The term "alkyl group" is understood to include straight-chain or branched alkyl groups.

[0014] The term "alkenyl group" is understood to include straight-chain or branched alkenyl groups.

[0015] "Each 1 to 3 C 1-4 Optionally substituted with an alkyl group C 1-12 Alkyl, C 2-12 Alkenyl, C 5-12 Cycloalkyl or C 5-12 The expression "cycloalkenyl group" means 1 to 3 C 1-4 Optionally substituted with an alkyl group, cycloalkyl or cycloalkenyl is understood.

[0016] According to a specific embodiment, X is an alcohol group and Y is an oxygen atom.

[0017] According to a specific embodiment, R1 is a C 1-10 alkyl, C 2-10 alkenyl, C 5-10 cycloalkyl or C 5-10 cycloalkenyl group, each optionally substituted with 1 to 3 C 1-4 alkyl groups. In particular, R1 is a C 1-8 alkyl, C 2-8 alkenyl, C 5-10 cycloalkyl or C 5-10 cycloalkenyl group, each optionally substituted with 1 to 3 C 1-4 alkyl groups. In particular, R1 is a C 1-6 alkyl, C 2-6 alkenyl, C 5-10 cycloalkyl or C 5-10 cycloalkenyl group, each optionally substituted with 1 to 3 C 1-4 alkyl groups. In particular, R1 is a C 5-10 cycloalkyl or C 5-10 cycloalkenyl group, preferably a C 5-8 cycloalkyl or C 5-8 cycloalkenyl group, preferably a C 5-7 cycloalkyl or C 5-7 cycloalkenyl group, preferably a C 5-6 cycloalkyl or C 5-6 cycloalkenyl group, more preferably a C6 cycloalkyl group, each optionally substituted with 1 to 3 C 1-4 alkyl groups, preferably 1 to 2 C 1-3 alkyl groups, even more preferably 1 to 2 C 1-2 alkyl groups. Even more specifically, R1 is a 3,3-dimethyl-1-cyclohexyl group.

[0018] According to a specific embodiment, R 2 represents a hydrogen atom or a C 1-3 alkyl group. In particular, R 2represents a methyl group or an ethyl group, more preferably a methyl group.

[0019] According to a particular embodiment, R 3 represents a hydrogen atom or a C 1-3 alkyl group. In particular, R 3 represents a methyl group or an ethyl group, more preferably a methyl group.

[0020] According to a particular embodiment, R 4 represents a hydrogen atom or a C 1-3 alkyl group. In particular, R 4 represents a methyl group or an ethyl group, more preferably a methyl group.

[0021] According to a more particular embodiment, each R 3 and R 4 represents a methyl group.

[0022] According to a particular embodiment, the present invention provides that the compound of formula (II) is in the form of any of its stereoisomers or a mixture thereof of formula (IIa)

Chemical formula

Chemical formula

[0023] For the sake of clarity, the expression "one of the dotted lines is a carbon-carbon single bond or double bond and the other is a carbon-carbon single bond" has the ordinary meaning understood by those skilled in the art, i.e., the entire bond (solid and dotted lines) between the carbon atoms connected by said dotted line is a carbon-carbon single bond or double bond.

[0024] When R8 represents a hydrogen atom, it is understood by those skilled in the art that the dotted line between the carbon atom adjacent to R8 and R8 represents a hydrogen-carbon single bond.

[0025] For the sake of clarity, the expression "when R7 and R8 are linked to each other, they form a C 5-7 cycloalkyl or cycloalkenyl group" means that R7 and R8 can be chemically bonded via a carbon-carbon single bond or double bond forming a cycloalkyl or cycloalkenyl group containing other carbon atoms of the structure. 5-7

[0026] According to a particular embodiment, R 2 ~R 8 has the same meaning as defined above herein.

[0027] According to a particular embodiment, the compound of formula (IIa) is in the form of any of its stereoisomers or a mixture thereof of formula (IIa,i)

Chemical formula

Chemical formula

[0028] According to a particular embodiment, the present invention relates to a compound of formula (II) being in the form of any of its stereoisomers or a mixture thereof of formula (IIb)

Chemical formula

Chemical formula

[0029] According to a particular embodiment, n is 1.

[0030] According to a particular embodiment, R 2 ~R 6 has the same meaning as defined above herein.

[0031] According to a particular embodiment, the present invention provides that the compound of formula (II) is in the form of any of its stereoisomers or a mixture thereof of formula (IIc)

Chemical formula

Chemical formula

[0032] According to a particular embodiment, R 2 ~R 4 has the same meaning as defined above herein.

[0033] According to a more particular embodiment, the compound of formula (I) is of formula (Id)

Chemical formula

[0034] Heterogeneous acid catalyst According to any embodiment of the present invention, the heterogeneous acid catalyst can be amorphous or crystalline, particularly crystalline.

[0035] According to any embodiment of the present invention, the heterogeneous acid catalyst can comprise at least one metal selected from the group consisting of silicon, tin, zirconium, hafnium or titanium or mixtures thereof, and optionally at least one metal selected from the group consisting of aluminum, boron, iron or mixtures thereof. Preferably, the heterogeneous acid catalyst comprises at least one metal selected from the group consisting of silicon or tin or mixtures thereof, and optionally at least one metal selected from the group consisting of aluminum, boron, iron or mixtures thereof.

[0036] According to any embodiment of the present invention, the heterogeneous acid catalyst can be a Lewis acid supported on a solid support.

[0037] One skilled in the art can select a suitable Lewis acid. Suitable Lewis acids are HClO4, BF3, AlCl3, FeCl3.CuCl2, ZnCl2, ZnBr2, ZrCl4, TiCl4 or TiCl 4-x (OR) x (wherein R is C 1-12(which may represent an alkyl or alkenyl group). Other suitable Lewis acids may be metal trifluoromethanesulfonates, and the metal may be a metal selected from a series of lanthanides, preferably lanthanum. Other suitable Lewis acids may be heteropolyacids (also called heteropolymetalates). One skilled in the art can select appropriate heteropolyacids based on general knowledge in the art. Preferred heteropolyacids are silicotungstic acid (H4SiW 12 O 40 ·nH2O), phosphomolybdic acid (H3Mo 12 PO 40 ·nH2O) or phosphotungstic acid (H3W 12 PO 40 ·nH2O).

[0038] According to one embodiment, the supported Lewis acid can be a mixture of two or more Lewis acids.

[0039] The solid support is understood to remain solid under the selected reaction conditions. According to certain embodiments, the solid support can be an organic or inorganic polymer. According to certain embodiments, the solid support can be an inorganic support material. According to certain embodiments, the inorganic support material can be a metal oxide. According to certain embodiments, the inorganic support material can contain a metal selected from the group consisting of silicon, tin, aluminum, zirconium, titanium, iron, boron or mixtures thereof, preferably silicon. According to certain embodiments, the inorganic support material can be silicon dioxide. According to certain embodiments, the supported Lewis acid is BF3 / SiO2 or HClO4 / SiO2.

[0040] According to any embodiment of the present invention, the heterogeneous acidic catalyst is an aluminosilicate catalyst.

[0041] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a zeolite or a clay.

[0042] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a clay.

[0043] The clay can be commercially available clay. According to any embodiment of the present invention, the commercially available clay can contain water. The water can be partially or entirely removed before use. Those skilled in the art are well aware of methods for removing water, such as azeotropic distillation, vacuum stripping, or heating under a nitrogen stream.

[0044] According to any embodiment of the present invention, the clay can be naturally occurring. According to any embodiment of the present invention, the heterogeneous acid catalyst is acid-treated clay. The acid-treated clay is understood herein to be clay that is subjected to acid treatment before being used as a heterogeneous acid catalyst according to the methods described in U.S. Pat. Nos. 2,470,872A, 2,671,058A, 2,981,697A, or 1,926,148A. Those skilled in the art can select the most appropriate conditions for the acid treatment of the clay based on general knowledge in the art and the teachings of these patent applications.

[0045] 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), 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), and old Filtrol-type clays such as EXBC 0001 (currently sold by Clariant). In one embodiment, the clay is K10-S300.

[0046] According to a preferred embodiment of the present invention, the heterogeneous acid catalyst is zeolite.

[0047] According to any embodiment of the present invention, the zeolite is used in its proton form. The latter can be provided directly by the manufacturer and used as such, or can be obtained by thermal decomposition of the ammonium-exchanged form. In certain embodiments, the zeolite is a pre-activated zeolite. The pre-activation can be carried out by removing the water of capture as described above in the case of clay, or by heating the zeolite at a temperature comprised between 300 °C and 600 °C for at least 1 hour under air or an inert gas.

[0048] The heterogeneous acid catalyst can be a commercially available compound or can be prepared by several methods such as those reported in US20040141911, US6054113, US4840930, US2470872 and EP0398636.

[0049] Non-limiting examples of suitable zeolites include CBV780, CBV901 currently sold by Zeolyst, or HSZ-385HUA or HSZ-390HUA currently sold by Tosoh.

[0050] According to any embodiment of the present invention, the heterogeneous acid catalyst is a macroporous zeolite.

[0051] The term "macroporous zeolite" has its ordinary meaning in the art. That is, a 12-membered ring zeolite having a pore diameter comprised within the range of 6.0 angstroms to 7.5 angstroms. Non-limiting examples of suitable macroporous zeolites can include FAU, BEA, MOR.

[0052] According to any embodiment of the present invention, the heterogeneous acid catalyst is a zeolite having a FAU topology.

[0053] The term "FAU topology" is understood to have the meaning conventionally used in the field of zeolites and is well known to those skilled in the art. The framework topology is usually defined by a three-letter code following the rules set by the IUPAC Commission on Zeolite Nomenclature in 1978 (R.M. Barrer, Pure Appl. Chem. 51, 1091 (1979)).

[0054] Zeolites having the FAU topology are understood as zeolites having a faujasite crystal structure. Those skilled in the art are aware of the definition of the faujasite crystal structure described, for example, in Rompp Chemie Lexikon, Georg Thieme Verlag, 9. Edition, 1990, page 1311.

[0055] According to any embodiment of the present invention, the heterogeneous acid catalyst is a Y-type zeolite.

[0056] The term "Y-type zeolite" is understood to have the meaning conventionally used in the field of zeolites and is well known to those skilled in the art. Y-type zeolites are understood to be zeolites having the FAU topology. Y-type zeolites are typically characterized by spherical internal cavities (so-called "supercages") containing rings of 12 oxygen atoms, which are tetrahedrally connected through pore openings of about 8 angstroms.

[0057] According to any embodiment of the present invention, the heterogeneous acid catalyst is a dealuminated zeolite.

[0058] Dealumination has conventionally been understood as 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 methods suitable for dealumination known in the art are hydrothermal treatment, acid treatment, treatment with gaseous halogen or halogen, or complex formation with a chelating agent. Those skilled in the art know these methods and how to carry them out.

[0059] According to any embodiment of the present invention, the heterogeneous acidic catalyst is dealuminated ultrastable Y (USY) zeolite.

[0060] USY zeolites are typically prepared from Y zeolites to enhance their stability and improve their catalytic activity by removing framework aluminum using a combination of treatments including ion exchange, steaming, acid leaching, and calcination. Such treatments are described, for example, in U.S. Patents US5601798A and US4477336A and are well known to those skilled in the art.

[0061] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a hydrophobic zeolite.

[0062] According to any embodiment of the present invention, the heterogeneous acidic catalyst is a hydrophobic dealuminated USY zeolite.

[0063] The hydrophobicity of zeolites has conventionally been defined by the hydrophobicity index (HI). The hydrophobicity index is defined as the amount of cyclohexane adsorbed (usually in grams) per unit weight of water adsorbed (usually in grams) by the zeolite when the vapor pressures of cyclohexane and water are 933 Pa (7 Torr) and 666 Pa (5 Torr), respectively, according to I. Halasz et al., Molecular Physics, 2002, 100, 3232 - 3232.

[0064] According to any embodiment of the present invention, the hydrophobicity index is from 5 to 100, preferably from 10 to 75, more preferably from 20 to 50.

[0065] According to any embodiment of the present invention, the silicon:aluminum ratio is in the range of 5:1 to 350:1.

[0066] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 10:1 to 325:1.

[0067] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 15:1 to 300:1.

[0068] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 22:1 to 275:1.

[0069] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 30:1 to 250:1.

[0070] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 40:1 to 250:1.

[0071] According to a preferred embodiment, the silicon:aluminum ratio is in the range of 50:1 to 250:1.

[0072] In certain embodiments, the heterogeneous acid catalyst is selected from the group consisting of clays, zeolites, and supported Lewis acids. The clays, zeolites, and supported Lewis acids can each be as defined above.

[0073] The heterogeneous acid catalyst can be added to the reaction medium of the process of the invention to form the compound of formula (I) at a wide range of concentrations.

[0074] According to any embodiment of the invention, the heterogeneous acid 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% based on the amount of the epoxide of formula (III).

[0075] According to any embodiment of the invention, the compound of formula (II) or (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 based on the amount of the epoxide of formula (III).

[0076] According to any embodiment of the present invention, the process temperature is maintained within 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 a preferred temperature as a function of the melting and boiling points of the starting and final products and the desired reaction time, conversion or selectivity.

[0077] 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. If a solvent is required or used for practical reasons, current solvents in such reaction types can 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, cymenes, 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 is a function of the nature of the substrate and / or catalyst, and a person skilled in the art can adequately select the most suitable solvent for each case in order to optimize the reaction.

[0078] The method of the present invention for producing the compound of formula (I) can be carried out under batch and / or continuous conditions.

[0079] The method according to any embodiment of the present invention is for the compound of formula (IV)

Chemical formula

[0080] According to any embodiment of the present invention, the compound of formula (IV) is in the form of any of its stereoisomers or a mixture thereof of formula (IVa)

Chemical formula

[0081] According to any embodiment of the present invention, the compound of formula (IV) is in the form of any of its stereoisomers or a mixture thereof of formula (IVa,i)

Chemical formula

[0082] According to any embodiment of the present invention, the compound of formula (IV) is in the form of any of its stereoisomers or a mixture thereof of formula (IVb)

Chemical formula

[0083] According to any embodiment of the present invention, the compound of formula (IV) is in the form of formula (IVc) [Chemical formula] 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; each R2, R3 and R4 is, separately and independently of one another, a hydrogen atom or a C 1-4 alkyl group; and R 10 is a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 3-6 cycloalkyl group; preferably an ethyl group, an ethylene group, a cyclopropane group or a cyclopentane group, more preferably an ethyl group; and The compound of formula (IVc) is formed by reacting the compound of formula (Ic) with a compound of Z-C(O)-R 10 [wherein Z is an R 10 -C(O)-O group, a thiol group, a chlorine atom, an alcohol group or an amine group].

[0084] According to a particular embodiment, R 1 is 1 to 2 C 1-3 alkyl groups, even more preferably C 1-2 cycloalkyl optionally substituted with 1 to 2 C 5-8 alkyl groups, more preferably C6 cycloalkyl substituted with 2 methyl groups.

[0085] According to a particular embodiment, R 2 represents a methyl group or an ethyl group, more preferably a methyl group.

[0086] According to a particular embodiment, R 3 represents a methyl group or an ethyl group, more preferably a methyl group.

[0087] According to a particular embodiment, R 4 represents a methyl group or an ethyl group, more preferably a methyl group.

[0088] According to a more specific embodiment, each R 3 and R 4 represents a methyl group.

[0089] According to a specific embodiment, R 5 represents a methyl group or an ethyl group, more preferably a methyl group.

[0090] According to a specific embodiment, R 6 represents a methyl group or an ethyl group, more preferably a methyl group.

[0091] According to a more specific embodiment, each R 5 and R 6 represents a methyl group.

[0092] According to a specific embodiment, R 7 represents a hydrogen atom.

[0093] According to a specific embodiment, R 8 represents a methyl group or an ethyl group, more preferably a methyl group.

[0094] According to any embodiment of the present invention, the compound of formula (IV) is in the form of any of its stereoisomers or a mixture thereof of formula (IVd)

Chemical formula

[0095] A typical manner for carrying out the process of the present invention is reported below in the examples, which should not be regarded as limiting the present invention. In the examples, unless otherwise specified, abbreviations have their usual meanings in the art, temperatures are indicated in degrees Celsius (°C), and percentages are indicated by weight percent (wt%).

[0096] Examples Example 1: General Catalyst Screening Procedure In a 0.5 L glass reactor with a double jacket 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™, supplied by DRT) was vigorously stirred at 45 °C in the presence of 2.08 g of a catalyst (10 wt% with respect to isobutylene oxide (IBO)). To this solution, 20.8 g (0.288 mol) of isobutylene oxide ((IBO), supplied by BASF) was slowly added over 2 hours, and the reaction mixture was left to stand for a further 2 hours while stirring was continued. After filtration of the catalyst, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol with respect to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0097] Example 2: Zeolite catalyst Several zeolites listed in Table 1 were used as the catalyst in the procedure of Example 1. The results of this screening are shown in Table 1. Each zeolite in Table 1 was calcined before use.

[0098] [Table 1]

[0099] Example 3: Crude (as-received) USY zeolite with a lower catalyst loading In a 1 L glass reactor with a double jacket equipped with a mechanical stirrer, 400 g (2.56 mol) of (R)-1-((S)-3,3-dimethylcyclohexyl)ethan-1-ol (referred to herein as Cyclademol™, supplied by DRT) was vigorously stirred at 45 °C in the presence of 3.2 g of a crude catalyst (5 wt% with respect to isobutylene oxide (IBO)). To this solution, 64 g (0.887 mol) of isobutylene oxide ((IBO), supplied by BASF) was slowly added over 2 hours, and the reaction mixture was left to stand for a further 2 hours while stirring was continued. After filtration of the catalyst, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol with respect to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0100]

Table 2

[0101] Example 4: Comparative homogeneous catalyst In a 0.5 L glass reactor with a double jacket 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™, supplied by DRT) was vigorously stirred at 30 °C in the presence of 16.8 mmol of a homogeneous catalyst as defined in Table 3 below. To this solution, 20.8 g (0.288 mol) of isobutylene oxide ((IBO), supplied by BASF) was slowly added over 2 hours, and the reaction mixture was left to stand for a further 1 hour while stirring was continued. After quenching the solution with an aqueous sodium citrate solution, the yield of (S)-2-((3,3-dimethylcyclohexyl)methoxy)-2-methylpropan-1-ol with respect to IBO in the crude sample was evaluated by gas chromatography using n-decane as an internal standard.

[0102]

Table 3

[0103] Example 5: Preparation of 2-((3,5-dimethylhex-3-en-2-yl)oxy)-2-methylpropan-1-ol 14 g (0.109 mol) of 3,5-dimethylhex-3-en-2-ol (prepared according to the procedure described in Example 1 of WO2004 / 050595 A1) was vigorously stirred at 45 °C in the presence of 0.274 g of HSZ-390 HUA (Tosoh). To this solution, 2.74 g (0.038 mol) of isobutylene oxide ((IBO), supplier BASF) was slowly added over 2 hours, and the reaction mixture was left further with stirring for 1 hour. After filtration of 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 reached 42.3 mol.%.

Claims

1. A compound of formula (I) 【Chemical Formula 1】 [wherein,[[]]END] Y is a sulfur atom, an oxygen atom or an NH group, R １ represents a C having 1 to 3 C's each １－４ alkyl group optionally substituted with an alkyl group, C １－１２ alkyl group, C ２－１２ alkenyl group, C ５－１２ cycloalkyl group or C ５－１２ cycloalkenyl group; and Each R ２ , R ３ , R ４ represents, separately and independently of one another, a hydrogen atom or a C １－４ alkyl group], and is a method for producing in the form of any of its stereoisomers or a mixture thereof, A compound of formula (II) [Chemical Formula 2] [wherein, X is a thiol group, an alcohol group or a primary amine group, wherein, R １ and R ２ have the same meaning as defined above]; An epoxide of formula (III) [Chemical Formula 3] [wherein, R ３ and R ４ have the same meanings as defined above]; and A process comprising a reaction in the presence of a heterogeneous acidic catalyst.

2. The compound of formula (II) is of formula (IIa) 【Chemical Formula 4】 [wherein,[[]]END] One of the dotted lines is a carbon-carbon single bond or a double bond, and the other is a carbon-carbon single bond; and X is a thiol group, an alcohol group or a primary amine group, Each R ２ , R ５ , R ６ , R ７ and R ８ represents, separately and independently of one another, a hydrogen atom or a C １－４ alkyl group; or R ７ and R ８ are linked to each other, C ５－７ forms a cycloalkyl or cycloalkenyl group], in the form of any of its stereoisomers or a mixture thereof, The compound of formula (I) is of formula (Ia) 【Chemical Formula 5】 [wherein,[[]]END] Y is a sulfur atom, an oxygen atom or an NH group, The dotted line, R ２ , R ５ , R ６ , R ７ and R ８ have the same meaning as defined above; and Each R ３ and R ４ each, independently of one another, represents a hydrogen atom or a C １－４ alkyl group], in the form of any of its stereoisomers or a mixture thereof, the method according to claim 1.

3. The compound of formula (II) is of formula (IIc) 【Chemical Formula 6】 [wherein,[[]]END] X is a thiol group, an alcohol group or a primary amine group, R ２ is in the form of any of its stereoisomers or a mixture thereof, which is a hydrogen atom or a C １－４ alkyl group] The compound of formula (I) is of formula (Ic) 【Chemical Formula 7】 [wherein,[[]]END] Y is a sulfur atom, an oxygen atom or an NH group, Each R ２ , R ３ , R ４ is, separately and independently of one another, in the form of any of its stereoisomers or a mixture thereof, representing a hydrogen atom or a C １－４ alkyl group], the method according to any one of claims 1 to 2.

4. The process according to any one of claims 1 to 3, wherein X is an alcohol group and Y is an oxygen atom.

5. R ２ The method according to any one of claims 1 to 4, wherein R represents a methyl group.

6. Each R ３ and R ４ which represents a methyl group, the method according to any one of claims 1 to 5.

7. The process according to any one of claims 1 to 6, wherein the heterogeneous acidic catalyst is an aluminosilicate catalyst.

8. The process according to any one of claims 1 to 7, wherein the heterogeneous acidic catalyst is a zeolite or a clay.

9. The process according to any one of claims 1 to 8, wherein the zeolite is a macroporous zeolite.

10. The process according to any one of claims 1 to 9, wherein the heterogeneous acidic catalyst is a hydrophobic zeolite.

11. The process according to any one of claims 1 to 10, wherein the heterogeneous acidic catalyst is a zeolite having a FAU topology.

12. The process according to any one of claims 1 to 11, wherein the heterogeneous acidic catalyst is dealuminated ultrastable Y-type (USY) zeolite.

13. The process according to any one of claims 1 to 12, wherein the silicon:aluminum 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 compound of formula (IV) 【Chemical 8】 [wherein,[[]]END] Y is a sulfur atom, an oxygen atom or an NH group, R １ represents a C that is optionally substituted with one to three C １－４ alkyl groups; and １－１２ alkyl, C ２－１２ alkenyl, C ５－１２ cycloalkyl or C ５－１２ cycloalkenyl group; and Each R ２ , R ３ , R ４ represents, separately and independently of one another, a hydrogen atom or a C １－４ alkyl group; and R １０ is a C １－６ alkyl group, a C ２－６ alkenyl group, a C ３－６ cycloalkyl group; preferably, a C １－４ alkyl group, a C ２－４ alkenyl group, a C ３－６ cycloalkyl group; preferably, a C １－３ alkyl group, a C ２－３ alkenyl group, a C ３－５ cycloalkyl group; preferably represents an ethyl group, a vinyl group, a cyclopropyl group or a cyclopentyl group, more preferably an ethyl group]; is used for the production in the form of any of its stereoisomers or a mixture thereof, and The compound of formula (IV) is obtained by reacting the compound of formula (I) with a compound of Z-C(O)-R １０ wherein Z is R １０ -C(O)-O group, thiol group, chlorine atom, alcohol group or amine group], according to any one of claims 1 to 13.

15. Said compound of formula (IV) is of formula (IVa) 【Chemical Formula 9】 [wherein,[[]]END] One of the dotted lines is a carbon-carbon single bond or a double bond, and the other is a carbon-carbon single bond; and Y is a sulfur atom, an oxygen atom or an NH group, Each R ２ ,R ３ ,R ４ ,R ５ ,R ６ and R ７ represents, separately and independently of one another, a hydrogen atom or a C １－４ alkyl group; and R ８ represents a C １－４ alkyl group; or R ７ and R ８ are linked to each other to form a C ５－７ cycloalkyl or cycloalkenyl group; and R １０ is a C １－６ alkyl group, C ２－６ alkenyl group, C ３－６ cycloalkyl group; preferably, a C １－４ alkyl group, C ２－４ alkenyl group, C ３－６ cycloalkyl group; preferably, a C １－３ alkyl group, C ２－３ alkenyl group, C ３－５ cycloalkyl group; preferably an ethyl group, vinyl group, cyclopropyl group or cyclopentyl group, more preferably an ethyl group] in the form of any of its stereoisomers or a mixture thereof, and Said compound of formula (IVa) is formed by reacting a compound of formula (Ia) with a compound of Z-C(O)-R １０ wherein Z is １０ a -C(O)-O group, a thiol group, a chlorine atom, an alcohol group or an amine group], the method according to claim 14.

16. The compound of formula (IV) is of formula (IVc) 【Chemical 10】 [wherein Y is a sulfur atom, an oxygen atom or an NH group Each R ２ , R ３ and R ４ each, independently of one another, represents a hydrogen atom or a C １－４ alkyl group; and R １０ is a C １－６ alkyl group, C ２－６ alkenyl group, C ３－６ cycloalkyl group; preferably, a C １－４ alkyl group, C ２－４ alkenyl group, C ３－６ cycloalkyl group; preferably, a C １－３ alkyl group, C ２－３ alkenyl group, C ３－５ cycloalkyl group; preferably an ethyl group, vinyl group, cyclopropyl group or cyclopentyl group, more preferably an ethyl group], in the form of any of its stereoisomers or a mixture thereof, and The compound of formula (IVc) is obtained by reacting the compound of formula (Ic) with a compound of １０ wherein Z is １０ a -C(O)-O group, a thiol group, a chlorine atom, an alcohol group or an amine group], according to any one of claims 14 to 15.

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