Process for the preparation of phenylpropionaldehyde derivatives

Abstract

The present invention relates to the field of organic synthesis, and more particularly, to a process for the preparation of a compound of formula (I). More particularly, to a valuable novel chemical intermediate useful for the production of perfuming ingredients. Furthermore, the present invention also encompasses a process for the production of a compound of formula (I).

Description

Technical Field

[0001] This invention relates to the field of fragrance industry (commodity fragrance). More particularly, this invention relates to valuable novel chemical intermediates for the production of flavoring ingredients. Furthermore, this invention includes a method for preparing compounds of formula (I). Background Technology

[0002] In the fragrance industry, there has always been a need for compounds that can impart entirely new sensory notes. In particular, there is great interest in ingredients that can impart the scent of lily of the valley, or at least one of the key sensory facets of lily of the valley. Therefore, there is a particular need for compounds that impart this note to reproduce the subtle floral scent of muguet, which cannot be preserved even by the gentlest extraction methods, thus making it impossible to extract the essential oil. To achieve this, compounds of formula (I), such as 1H-indene-ar-propanal, 2,3-dihydro-1,1-dimethyl (also known as Hivernal), are used. ® Compounds such as 3-(4-isopropyl-2-methylphenyl)propanal, 3-(4-isopropylphenyl)-2-methylpropanal, and 3-(4-(tert-butyl)phenyl)-2-methylpropanal have previously been reported in various existing technologies as components that impart a lily-of-the-valley fragrance. Compounds of formula (I) can be prepared via various routes, such as hydroformylation, palladium-catalyzed coupling, and hydrogenation following the Müller-Cunradi-Pieroh reaction. However, the reported routes for preparing compounds of formula (I) suffer from the need to use expensive precious metals (such as rhodium, palladium, or ruthenium) and the generation of complex mixtures of isomers. Furthermore, these products have significant industrial applications, thus there is always a need to develop new processes with improved yields and increased conversion rates.

[0003] Therefore, there is a need to develop a more sustainable synthetic method for compounds of formula (I) to avoid waste generation, use abundant and inexpensive reagents, limit the formation of isomers, and use readily available starting materials.

[0004] This invention provides a method for obtaining compound (I) from compound (II) via a novel route and a previously undisclosed novel intermediate, while also controlling the generated isomers. In particular, most of the compounds of formula (II) for which this invention is aimed have never been reported or proposed before in the context of preparing compounds of formula (I). Summary of the Invention

[0005] Surprisingly, it has now been found that compounds of formula (I) can be prepared from compounds of formula (II), thereby reducing preparation steps and costs while avoiding the generation of other isomers. The method of this invention opens up a new avenue for obtaining compounds of formula (I) with fewer steps and higher overall yield compared to methods known in the prior art.

[0006] Therefore, the first object of the present invention is a method for preparing compound (I).

[0007]

[0008] The compound is in the form of any one of its isomers or mixtures thereof; wherein

[0009] R and R 1 Each can independently represent a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl; and the condition is R and R 1 At least one group in it is not a hydrogen atom;

[0010] R 2 Represents a hydrogen atom or a methyl group;

[0011] R' is a hydrogen atom; or

[0012] R and R' together represent C 3-8 Alkyl or -O-(CH2) m -O-, where m is 1 or 2;

[0013] This method includes the oxidative cleavage of the compound of formula (II),

[0014]

[0015] The compound is in the form of any one of its isomers or mixtures thereof; wherein R 1 R 2 R 3 R and R' have the same meaning as defined above; R a and R b C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms 1-16 Hydrocarbon group or group of formula (a),

[0016]

[0017] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above.

[0018] For clarity, the phrase "any of its stereoisomers or mixtures thereof" or similar expressions refer to the common meaning understood by those skilled in the art, namely that compounds of formula (I) and (II) can be pure enantiomers or diastereomers. In other words, compounds of formula (I) and (II) can have multiple stereocenters, and each stereocenter can have two different stereochemical configurations (e.g., R or S). Compounds of formula (I) and (II) can be in the form of pure enantiomers or mixtures of multiple enantiomers or diastereomers. Compounds of formula (I) and (II) can be in racemic or scalemic (proportional optical rotation) forms. Therefore, compounds of formula (I) and (II) can be a single stereoisomer or a composition of substances comprising or composed of various stereoisomers.

[0019] According to any embodiment of the invention, the compound of formula (II) may be in the form of its E or Z isomer or a mixture thereof. For example, the invention comprises a composition of substances consisting of one or more compounds of formula (II) having the same chemical structure but different double bond configurations. Specifically, compound (II) may be in the form of a mixture of isomers E and Z, wherein isomer E accounts for at least 50% to at least 75% of the total mixture (i.e., the E / Z ratio of the mixture is between 75 / 25 and 100 / 0).

[0020] The terms “alkyl,” “alkoxy,” and “alkadiyl” should be understood to include alkyl and alkadiyl groups that contain both branched and straight chains.

[0021] It should be understood that by “...alkyl group…”, the term refers to a group consisting of hydrogen and carbon atoms, and may be in the form of an aliphatic hydrocarbon, i.e., a straight-chain or branched saturated hydrocarbon (e.g., alkyl), a straight-chain or branched unsaturated hydrocarbon (e.g., alkenyl or ynyl), a saturated cyclic hydrocarbon (e.g., cycloalkyl), or an unsaturated cyclic hydrocarbon (e.g., cycloalkenyl or cycloynyl), or may be in the form of an aromatic hydrocarbon, i.e., an aryl, or may be in the form of a mixture of groups of the aforementioned types. For example, unless specifically limited to only one type mentioned, a particular group may comprise a straight-chain alkyl, a branched alkenyl (e.g., having one or more carbon-carbon double bonds), a (poly)cycloalkyl, and an aryl moiety. Similarly, in all embodiments of the invention, when a group is mentioned as being in more than one type of topological (e.g., straight-chain, cyclic, or branched) and / or saturated or unsaturated (e.g., alkyl, aromatic, or alkenyl) form, it also means that it may comprise a group having any of the aforementioned topological or saturated or unsaturated moieties as explained above. Similarly, in all embodiments of the invention, when a group is referred to as being in a saturated or unsaturated form (e.g., alkyl), it means that the group can be of any type of topology (e.g., straight-chain, cyclic, or branched) or have several parts with various topological structures. Preferably, the hydrocarbon group does not have any carbon-carbon double bonds.

[0022] Therefore, the term “any one of its isomers or mixtures thereof” used for compounds of formula (I) means “any one of its stereoisomers or mixtures thereof” as described above.

[0023] However, the term “any of its isomers or mixtures thereof” used for compounds of formula (II) is used both as “any of its stereoisomers or mixtures thereof” as described above, and as “its E or Z isomers or mixtures thereof” as described above.

[0024] It should be understood that the term "...hydrocarbon group, optionally containing one or more oxygen atoms..." means that the hydrocarbon group optionally contains one, two, three or more oxygen atoms, which are present in the form of alcohol, ketone, aldehyde, ether, ester, carboxylic acid, or carbonate groups. These groups may replace the hydrogen atom of the hydrocarbon group and thus side-attach to the hydrocarbon, or replace the carbon atom of the hydrocarbon group (if chemically possible) and thus insert into the hydrocarbon chain. For example, the -CH2-CH2-CHOH-CH2- group represents a C4 hydrocarbon group containing an alcohol group (substitution of hydrogen atoms), i.e., a C4 hydrocarbon group containing oxygen atoms; the -CH2-CH2-COO-CH2-CH2CH2-CH2- group represents a C7 hydrocarbon group containing one ester group (substitution / insertion into the hydrocarbon chain of carbon atoms), i.e., a C7 hydrocarbon group containing two oxygen atoms; and similarly, the -CH2-CH2-O-CH2-CH2-O-CH2-CH2- group represents a C6 hydrocarbon group containing two ether groups, i.e., a C6 hydrocarbon group containing two oxygen atoms.

[0025] The term "optionally" should be understood as meaning that the specific group that is optionally substituted may or may not be substituted by a specific functional group.

[0026] The term "oxidative cleavage" or similar terms refers in the conventional sense to a reaction in which a carbon-carbon double bond breaks and is oxidized to produce two compounds with carbon-oxygen double bonds, such as aldehydes, ketones, acids, and esters. Under specific conditions, the resulting aldehyde or ketone can be converted in situ to the corresponding acetal.

[0027] According to any embodiment of the invention, R 2 It is a hydrogen atom.

[0028] According to any embodiment of the invention, R and R' together represent C. 4-8 Alkyl or -O-(CH2) m -O-, where m is 1 or 2. Specifically, R and R' together represent C. 4-6 Alkyl or -O-(CH2) m -O-, where m is 1 or 2. Specifically, R and R' together represent C. 5-6 Alkyl or -O-(CH2) m -O-, where m is 1 or 2. More specifically, R and R' together represent -C(CH3)2-(CH2)2- or -O-(CH2)-O- groups.

[0029] According to any embodiment of the invention, R a It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-14 Hydrocarbon group, or group of formula (a),

[0030]

[0031] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... a It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-12 Hydrocarbon group, or group of formula (a),

[0032]

[0033] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... a It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-10Hydrocarbon group, or group of formula (a),

[0034]

[0035] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... a It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-8 Hydrocarbon group, or group of formula (a),

[0036]

[0037] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... a It can be a hydrogen atom, or optionally a carbon atom containing one or two oxygen atoms. 1-6 Hydrocarbon group, or a group of formula (a),

[0038]

[0039] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... a It can be a hydrogen atom, or optionally a carbon atom containing one or two oxygen atoms. 1-6 Hydrocarbon group, or a group of formula (a'),

[0040]

[0041] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R has the same meaning as defined above. Specifically, R a It can be a hydrogen atom, C 1-6 Alkyl, C6 aryl, or groups of formula (a')

[0042]

[0043] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R has the same meaning as defined above. Specifically, R a It can be a hydrogen atom, C 1-6 Alkyl or C6 aryl. Specifically, R a It can be a hydrogen atom, C 1-6Alkyl or phenyl. Specifically, R a It can be a hydrogen atom, C 1-4 Alkyl or phenyl. Specifically, R a It can be a hydrogen atom, C 1-3 Alkyl or phenyl. Specifically, R a It can be a hydrogen atom, C 1-2 Alkyl group. Specifically, R a It can be a hydrogen atom or a methyl group. Specifically, R a It can be a hydrogen atom.

[0044] According to any embodiment of the invention, R b It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-14 Hydrocarbon group, or group of formula (a),

[0045]

[0046] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... b It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-12 Hydrocarbon group, or group of formula (a),

[0047]

[0048] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... b It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-10 Hydrocarbon group, or group of formula (a),

[0049]

[0050] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... b It can be a hydrogen atom, or optionally a carbon atom containing one to three oxygen atoms. 1-8 Hydrocarbon group, or group of formula (a),

[0051]

[0052] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R2 R and R' have the same meaning as defined above. Specifically, R... b It can be a hydrogen atom, or optionally a carbon atom containing one or two oxygen atoms. 1-6 Hydrocarbon group, or a group of formula (a),

[0053]

[0054] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above. Specifically, R... b It can be a hydrogen atom, or optionally a carbon atom containing one or two oxygen atoms. 1-6 Hydrocarbon group, or a group of formula (a'),

[0055]

[0056] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R has the same meaning as defined above. Specifically, R b It can be a hydrogen atom, a C1-C6 alkyl group, a C6 aryl group, or a group of formula (a').

[0057]

[0058] The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R has the same meaning as defined above. Specifically, R b It can be a hydrogen atom, C 1-6 Alkyl or C6 aryl. Specifically, R b It can be a hydrogen atom, C 1-6 Alkyl or phenyl. Specifically, R b It can be a hydrogen atom, C 1-4 Alkyl or phenyl. Specifically, R b It can be a hydrogen atom, C 1-3 Alkyl or phenyl. Specifically, R a It can be a hydrogen atom or a carbon atom. 1-2 Alkyl group. Specifically, R b It can be a hydrogen atom or a methyl group. Specifically, R b It can be a hydrogen atom.

[0059] R is particularly preferred. a and R b None of them contain any CC double bonds.

[0060] Furthermore, it is preferred that the substituents R, R', and R are present. 1 R 2R a and R b None of them contain any carbon-carbon double bonds.

[0061] According to any embodiment of the invention, the compound of formula (I) conforms to formula (III).

[0062]

[0063] The compound is in the form of any one of its isomers or mixtures thereof; wherein R and R 1 It has the same meaning as the definition above.

[0064] According to any embodiment of the invention, the compound of formula (II) conforms to formula (IV).

[0065]

[0066] The compound is in the form of any one of its isomers or mixtures thereof; wherein R and R 1 It has the same meaning as the definition above.

[0067] According to any embodiment of the invention, R 1 It can be a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl group. Specifically, R 1 It can be a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-2 Alkyl group. Specifically, R 1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a methyl group. Specifically, R 1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 One or both of the alkoxy or OC(O)H groups. In particular, R1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-4 One or both of the alkoxy or OC(O)H groups. In particular, R 1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-3 One or both of alkoxy or OC(O)H. Specifically, R 1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-2 One or both of alkoxy or OC(O)H. Specifically, R 1 It can be a hydrogen atom, C 1-6 Alkoxy or C 1-6 Alkyl group, optionally substituted with one or both of a hydroxyl group, a methoxy group, or an OC(O)H group. In particular, R 1 It can be a hydrogen atom, C 1-4 Alkoxy or C 1-4 Alkyl group, optionally substituted with one or both of a hydroxyl group, a methoxy group, or an OC(O)H group. In particular, R 1 It can be a hydrogen atom or a carbon atom. 1-3 Alkoxy or C 1-3 Alkyl group, optionally substituted with one or both of a hydroxyl group, a methoxy group, or an OC(O)H group. In particular, R 1 It can be a hydrogen atom or a carbon atom. 1-2 Alkoxy or C 1-2 Alkyl group. Specifically, R 1 It can be a hydrogen atom, a methyl group, or a methoxy group. Specifically, R... 1 It can be a hydrogen atom or a methyl group. Even more specifically, R... 1 It can be a hydrogen atom.

[0068] According to any embodiment of the invention, R can be a hydrogen atom or C. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl group. Specifically, R can be a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-2 Alkyl group. Specifically, R can be a hydrogen atom, C... 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It can be a hydrogen atom or a methyl group. Specifically, R can be a hydrogen atom, C can be a methyl group, or C can be a hydrogen atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 One or both of the alkoxy or OC(O)H groups. Specifically, R can be a hydrogen atom, C... 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-4 One or both of the alkoxy or OC(O)H groups. Specifically, R can be a hydrogen atom, C... 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-3 One or both of alkoxy or OC(O)H. Specifically, R can be a hydrogen atom, C... 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-2 One or both of alkoxy or OC(O)H. Specifically, R can be a hydrogen atom, C... 1-6 Alkoxy or C 1-6 Alkyl group, optionally substituted with one or both of a hydroxyl group, a methoxy group, or an OC(O)H atom. In particular, R can be a hydrogen atom, C... 1-4 Alkoxy or C 1-4 Alkyl group, optionally substituted with one or both of a hydroxyl group, a methoxy group, or an OC(O)H atom. In particular, R can be a hydrogen atom, C... 1-3 Alkoxy or C 1-4 Alkyl group. Specifically, R can be a hydrogen atom, C... 1-2 Alkoxy or C 1-4 Alkyl group. Specifically, R can be a hydrogen atom, a methoxy group, or a C atom. 1-4 Alkyl group. Specifically, R can be C10. 1-4 Alkyl group. More specifically, R can be propyl, isopropyl, butyl, isobutyl, or tert-butyl.

[0069] According to any embodiment of the invention, R is not a group of the formula -CH2-C(Me)2OH.

[0070] Preferably, the compound of formula (II) is a compound selected from the compounds of formulas (IIa), (IIb), (IIc), (IId) and (IIe), especially a compound selected from formulas (IIa), (IIc) or (IId).

[0071]

[0072]

[0073] Especially when R a =R b =H or CH3.

[0074] According to any embodiment of the invention, oxidative pyrolysis can be carried out under conventional conditions known to those skilled in the art, i.e., in the presence of an oxidant, such as ozone (the reaction is also called ozonolysis), OsO4 / NaIO4, KMnO4 / NaIO4, RuCl3 / NaIO4, RuCl3 / NaOCl, H2O2 / NaIO4, or an organic peroxide / NaIO4. In particular, oxidative pyrolysis can be ozonolysis, i.e., the reaction of the compound of formula (II) with ozone. Even more particularly, oxidative pyrolysis can be ozonolysis followed by a reduction step.

[0075] It should be emphasized that, due to the high toxicity of pyridine chlorochromate (PCC), PCC is excluded from the reagents used in the oxidative pyrolysis of this invention.

[0076] For clarity, by using the term "reduction step" or similar expressions, those skilled in the art will understand that the resulting intermediate (in order to obtain the compound of formula (I)) is treated with at least one reducing agent well known to those skilled in the art. This treatment with a reducing agent can be carried out in a post-processing step (work-up). Non-limiting examples of such reducing agents include: amines, particularly tertiary amines or pyridines; sulfites, such as basic sulfites (e.g., sodium sulfite or potassium sulfite, sodium bisulfite); C 2-6 Dialkyl sulfides, such as dimethyl sulfide or methyl phenyl sulfide; sodium salts of 3,3'-thiodipropionic acid; triphenylphosphine; Zn / AcOH; Zn / AcOH / water; Na2S; thiourea; thiodiethylene glycol; 3,3'-thiodipropanol; 3,3'-thiodipropionitrile; H2; Pd / C or Raney / Ni; P(OMe)3; P(OEt)3; P(OPh)3, MeO(SO)OMe, MeSSMe, etc. Sulfites, such as basic sulfites (e.g., sodium sulfite or potassium sulfite, sodium bisulfite), can be listed in particular, optionally with sodium salts of 3,3'-thiodipropionic acid or C... 2-6Combinations of dialkyl sulfides (e.g., dimethyl sulfide).

[0077] Ozone decomposition can be carried out with or without a solvent. Any solvent currently used in ozone decomposition reactions may be used for the purposes of this invention when a solvent is required or used for practical reasons. Non-limiting examples include: water, C... 5-10 Saturated hydrocarbon solvents (e.g., hexane or cyclohexane), saturated C 4-10 Ethers or esters (e.g., AcOEt, tetrahydrofuran, dioxane, or MTBE), saturated carboxylic acids (e.g., acetic acid or propionic acid), saturated polar solvents (e.g., acetonitrile), alcohols (e.g., isopropanol, methanol, butanol, or ethanol), saturated ketones (e.g., butanone or isobutyl methyl ketone), chloroalkanes (e.g., chloroform or dichloromethane), or mixtures thereof. The specific choice of solvent depends on the nature of the compound of formula (II) and the desired reaction rate. Those skilled in the art can select the most suitable solvent to optimize the ozone decomposition reaction based on the specific circumstances. Specifically, the solvent used in the ozone decomposition reaction contains water; that is, it contains only water, or at least one of an organic solvent and water. Surfactants may also be added to the reaction medium, especially when the solvent used in the ozone decomposition reaction contains water. Water can be added to the reaction medium in a wide range of concentrations. As a non-limiting example, a concentration of water ranging from 0.5% by weight to 5% by weight relative to the amount of the compound of formula (II) can be cited. Examples of suitable surfactants include sodium dodecyl sulfate, bis[4-({2-(methoxycarbonyl)phenyl}amino)-4-oxobutyric acid]-polyethylene glycol 1000, Triton X-100, and TPGS-750-M.

[0078] The preferred temperature for the oxidation reaction is in the range of -100°C to 40°C, particularly, in the range of -80°C to 20°C, particularly, in the range of -40°C to 10°C, particularly, in the range of -20°C to 10°C, particularly, in the range of -10°C to 10°C, and even more particularly, in the range of 0°C to 10°C. Of course, those skilled in the art can select the preferred temperature based on the melting and boiling points of the starting materials and the final product, as well as the desired reaction or conversion time.

[0079] Ozone can be added to the reaction medium in a wide range of concentrations. As a non-limiting example, concentrations ranging from 0.5% to 20% by weight in oxygen or air can be cited. Needless to say, those skilled in the art will understand that the optimal concentration of ozone depends on the nature of the compound of formula (II), whether the reaction is batch or continuous, the desired conversion rate, and the required reaction time. Of course, those skilled in the art can certainly adjust the pressure or flow rate of ozone (e.g., in continuous reactions) to obtain the desired concentration range depending on whether the reaction is batch or continuous.

[0080] The reducing agent can be added to the reaction medium in a wide range of concentrations. As a non-limiting example, a concentration range of 0.5 to 10 molar equivalents relative to the amount of compound (II) can be cited as a value for the reducing agent concentration. Preferably, the concentration of the reducing agent is 0.8 to 10 molar equivalents. Even more preferably, the concentration of the reducing agent is 1 to 5 molar equivalents. Needless to say, those skilled in the art will understand that the optimal concentration of the reducing agent depends on the properties of the reducing agent, the properties of compound (II), the desired conversion rate, and the required reaction time.

[0081] The method of the present invention can be carried out under intermittent or continuous conditions. According to a specific embodiment of the present invention, the method is a continuous method.

[0082] According to any embodiment of the invention, the compound of formula (II) can be prepared by a Grignard reaction; that is, the compound of formula (II) can be prepared by making (R... a ')(R b ')C=CH-CHR 2 -X is prepared by reacting with a compound of formula (V).

[0083]

[0084] Among them, R, R', R 1 and R 2 It has the same meaning as defined above; R a 'and R b 'C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms' 1-16 hydrocarbon group;

[0085] Y represents a halogen atom;

[0086] Z is either MgY or a halogen atom.

[0087] The condition is

[0088] If Z is MgY, then X is a halogen atom;

[0089] or

[0090] If Z is a halogen atom, then X is MgY;

[0091] Compound of formula (II) was obtained.

[0092] According to any embodiment of the present invention, the method for preparing compound (I) preferably includes the following steps:

[0093] a) Make (R) a ')(R b ')C=CH-CHR 2-X reacts with the compound of formula (V),

[0094]

[0095] Where R, R', R 1 and R 2 It has the same meaning as defined above; R a 'and R b 'C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms' 1-16 hydrocarbon group;

[0096] Y represents a halogen atom;

[0097] Z is either MgY or a halogen atom.

[0098] The condition is

[0099] If Z is MgY, then X is a halogen atom;

[0100] or

[0101] If Z is a halogen atom, then X is MgY;

[0102] The compound of formula (II) as defined above was obtained;

[0103] b) Oxidatively cleave the compound of formula (II) to obtain the compound of formula (I).

[0104] According to any embodiment of the invention, R a 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-14 Hydrocarbon group. Specifically, R a 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-12 Hydrocarbon group. Specifically, R a 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-10 Hydrocarbon group. Specifically, R a 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-8 Hydrocarbon group. Specifically, R a 'Can be a hydrogen atom or optionally a C atom containing one or two oxygen atoms.' 1-6 Hydrocarbon group. Specifically, R a 'It can be a hydrogen atom, C 1-6 Alkyl or C6 aryl. Specifically, R a 'It can be a hydrogen atom, C 1-6 Alkyl or phenyl. Specifically, R a 'It can be a hydrogen atom, C 1-4 Alkyl or phenyl. Specifically, R a 'It can be a hydrogen atom, C1-3 Alkyl or phenyl. Specifically, R a 'Can be a hydrogen atom or a C atom' 1-2 Alkyl group. Specifically, R a 'It can be a hydrogen atom or a methyl group.' Specifically, R a It could be a hydrogen atom.

[0105] According to any embodiment of the invention, R b 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-14 Hydrocarbon group. Specifically, R b 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-12 Hydrocarbon group. Specifically, R b 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-10 Hydrocarbon group. Specifically, R b 'Can be a hydrogen atom or optionally a C atom containing one to three oxygen atoms.' 1-8 Hydrocarbon group. Specifically, R b 'Can be a hydrogen atom or optionally a C atom containing one or two oxygen atoms.' 1-6 Hydrocarbon group. Specifically, R b 'It can be a hydrogen atom, C 1-6 Alkyl or C6 aryl. Specifically, R b 'It can be a hydrogen atom, C 1-6 Alkyl or C6 aryl. Specifically, R b 'It can be a hydrogen atom, C 1-6 Alkyl or phenyl. Specifically, R b 'It can be a hydrogen atom, C 1-4 Alkyl or phenyl. Specifically, R b 'It can be a hydrogen atom, C 1-3 Alkyl or phenyl. Specifically, R b 'It can be a hydrogen atom, C 1-2 Alkyl group. Specifically, R b 'It can be a hydrogen atom or a methyl group.' Specifically, R b It could be a hydrogen atom.

[0106] According to a specific embodiment of the present invention, a method for preparing compound (I) includes the following steps:

[0107] a) React CH2=CH-CHR2-X with the compound of formula (V),

[0108]

[0109] Where R, R', R 1 and R 2 It has the same meaning as the text above;

[0110] Y represents a halogen atom;

[0111] Z is either MgY or a halogen atom.

[0112] The condition is

[0113] If Z is MgY, then X is a halogen atom;

[0114] or

[0115] If Z is a halogen atom, then X is MgY;

[0116] Compound of formula (VI) is obtained.

[0117]

[0118] Among them, R, R', R 1 and R 2 It has the same meaning as the definition above;

[0119] b) Perform oxidative cleavage on compound (VI) as defined above to obtain compound (I).

[0120] According to any preferred embodiment of the invention; Z is MgCl and X is a Cl atom, or Z is a Cl atom and X is MgCl. In particular, Z is a Cl atom and X is MgCl.

[0121] (R a ')(R b ')C=CH-CHR 2 -X can be added to the reaction medium in a wide range of concentrations. As a non-limiting example, a range of 1 to 2 equivalents relative to the amount of compound of formula (V) can be cited as (R). a ')(R b ')C=CH-CHR 2 -X concentration value. Preferably, (R a ')(R b ')C=CH-CHR 2 The concentration of -X is 1.1 to 1.5 equivalents relative to the amount of compound (IV). Needless to say, those skilled in the art will know that (R a ')(R b ')C=CH-CHR 2 The optimal concentration of -X depends on the properties of the compound of formula (V), the required conversion rate, and the required reaction time.

[0122] The preparation of compounds of formula (II) or (VI) can be carried out with or without a solvent. When a solvent is required or used for practical reasons, compounds of formula (V) can be dissolved, and any solvent currently used in such reactions is suitable for the purposes of this invention. Non-limiting examples include: C 5-10 Saturated hydrocarbon solvents (e.g., hexane or cyclohexane), aromatic solvents (e.g., toluene), saturated C 4-10 Ethers (e.g., tetrahydrofuran, methyltetrahydrofuran, 4-methyltetrahydropyran, dioxane, or MTBE), or mixtures thereof. The specific choice of solvent depends on the nature of the compound of formula (II) or (VI) and the desired reaction rate. Those skilled in the art can select the most suitable solvent to optimize the reaction based on the specific circumstances.

[0123] The temperature range in which compounds of formula (II) or (VI) can be prepared is -100°C to 100°C, particularly, in the range of -80°C to 100°C, particularly, in the range of -40°C to 80°C, particularly, in the range of -20°C to 80°C, particularly, in the range of -10°C to 80°C, and even more particularly, in the range of 0°C to 80°C. Of course, those skilled in the art can select the preferred temperature based on the melting and boiling points of the starting materials and the final product, as well as the desired reaction or conversion time.

[0124] Another object of the present invention is the compound of formula (I) obtained by the above method.

[0125] Compound (II) is generally a novel compound and has many advantages as described above and in the examples. Therefore, another object of the present invention is to provide a compound of formula (II).

[0126]

[0127] The compound is in the form of any one of its isomers or mixtures thereof; wherein

[0128] R and R 1 Each can independently represent a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl; and the condition is R and R 1 At least one group in it is not a hydrogen atom; and the condition is that when R is C 3-4 When alkyl, R 1 It is not a hydrogen atom;

[0129] R2 Represents a hydrogen atom or a methyl group;

[0130] R' is a hydrogen atom; or

[0131] R and R' together represent C 3-8 Alkyl;

[0132] R a and R b C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms 1-16 Hydrocarbon group or group of formula (a),

[0133]

[0134] This group is in the form of any of its isomers or mixtures thereof; R 1 R 2 R and R' have the same meaning as defined above.

[0135] R is particularly preferred. a and R b None of them contain any CC double bonds.

[0136] Furthermore, it is preferred that the substituents R, R', and R are present. 1 R 2 R a and R b None of them contain any carbon-carbon double bonds.

[0137] A further preferred embodiment is that when R is H, R 1 It is neither methyl nor methoxy.

[0138] Preferably, when R 1 When H is present, R is not methyl, ethyl, n-propyl, or C. 1-3 Alkyl group.

[0139] Particularly preferred is that the compound of formula (II) is not selected from the following compounds:

[0140]

[0141]

[0142] Preferably, the compound of formula (II) is selected from compounds of formulas (IIa), (IIb), (IIc) and (IId), especially the compound of formula (IIa).

[0143] Particularly preferred is that the compound of formula (I) is a compound selected from the compounds of formulas (Ia), (Ib), (Ic) and (Id), especially the compounds of formulas (Ia), (Ic) or (Id).

[0144]

[0145] .

[0146] Typical methods for implementing the method of the present invention are reported in the embodiments below. Detailed Implementation

[0147] Example

[0148] The invention will now be described in further detail through the following embodiments, wherein abbreviations have their usual meanings in the art, and temperature is expressed in degrees Celsius (°C). Using 400MHz ( 1 H) and 100MHz ( 13 Bruker Avance II Ultrashield 400 plus operating at C) or 500MHz ( 1 H) and 125MHz ( 13 Bruker Avance III 500 operating at C), or at 600MHz ( 1 H) and 150MHz ( 13 NMR spectra were obtained using a Bruker Avance III 600 cryoprobe operated under C) conditions. Spectra were used as an internal reference relative to 0.0 ppm tetramethylsilane. 1 The H NMR signal shift is expressed in δ ppm, and the coupling constant (J) is expressed in Hz. It exhibits the following multiplicity: s, singlet; d, doublet; t, triplet; q, quartet; m, multiply; b, broad peak (indicating unresolved coupling), and is interpreted using Bruker Topspin software. 13 C10 NMR data are expressed as chemical shift δ ppm and hybridization from DEPT 90 and DEPT 135 experiments: C, quaternary; CH, methine; CH2, methylene; CH3, methyl.

[0149] Example 1

[0150] Preparation of compound of formula (I) according to the method of the present invention

[0151] a) Preparation of 1-(4-(but-3-en-1-yl)phenyl)-2-methylprop-2-ol:

[0152] 1-(3-Buten-1-yl)-4-chlorobenzene:

[0153] Allyl magnesium chloride (52.3 g, 2 M tetrahydrofuran solution, 105 mmol) was added to a 250 mL round-bottom flask. The solution was stirred at 25 °C. 4-Chlorobenzyl chloride (15.4 g, 91 mmol) in tetrahydrofuran solution (30.4 g) was added dropwise over 2 hours. The reaction mixture was stirred for another hour, followed by the addition of toluene (30 g). The reaction mixture was quenched at 15 °C with acetic acid (31 g, 20% aqueous solution). The phases were separated by decantation. The organic phase was washed twice with water and 5% NaHCO3 solution, and evaporated to give crude product 1-(3-buten-1-yl)-4-chlorobenzene (15.7 g), which was purified by distillation (12.7 g, 84% yield).

[0154] δH (500 MHz; CDCl3; Me4Si) Unit ppm: 7.26-7.21 (m, 2H), 7.13-7.08 (m, 2H), 5.87-5.76 (m, 1H), 5.05-4.95 (m, 2H), 2.67 (t, 2H), 2.38-2.31 (m, 2H) ppm.

[0155] δ C (125 MHz; CDCl3; Me4Si) Unit ppm: 140.2 (C), 137.6 (CH), 131.5 (C), 129.8 (CH), 128.4 (CH), 115.3 (CH2), 35.3 (CH2), 34.7 (CH2).

[0156] 1-(4-(3-Buten-1-yl)phenyl)-2-methylprop-2-ol:

[0157] Magnesium (2.97 g, 122 mmol) and tetrahydrofuran (80 g) were added to a 500 mL round-bottom flask. The reaction mixture was stirred and heated at 60 °C. 1-(3-buten-1-yl)-4-chlorobenzene (20 g, 120 mmol) was added dropwise over 2 hours, followed by the addition of tetrahydrofuran (70 g) over 1 hour. The reaction mixture was then stirred at 60 °C for 20 hours. The reaction mixture was then cooled to 15 °C, and cuprous chloride (0.12 g, 1.2 mmol) was added, followed by the addition of isobutylene oxide (8.65 g, 120 mmol) over 1 hour. The reaction mixture was quenched at 15 °C with citric acid (57.6 g, 20% aqueous solution) in the presence of 60% H₂O₂ (0.14 g, 2.4 mmol). Toluene (80 g) was added, and the reaction mixture was stirred for 1 hour. The phases were separated by decantation. The organic phase was washed successively with 10% potassium citrate solution and 5% NaHCO3 solution, and evaporated to obtain crude product 1-(4-(3-buten-1-yl)phenyl)-2-methylprop-2-ol (22.6 g), which was purified by column distillation (16.2 g, yield 66%).

[0158] δ H (500 MHz; CDCl3; Me4Si) Unit ppm: 7.16-7.10 (m, 4H), 5.90-5.82(m, 1H), 5.07-4.96 (m, 2H), 2.73 (s, 2H), 2.69 (t, 2H), 2.40-2.33 (m, 2H)1.49 (br, 1H), 1.22 (s, 6H) ppm.

[0159] δ C (125 MHz; CDCl3; Me4Si) Unit ppm: 140 (C), 138.1 (CH), 135.1 (C), 130.4 (CH), 128.3 (CH), 114.9 (CH2), 70.7 (C), 49.3 (CH2), 35.5 (CH2), 35.0 (CH2), 29.1 (CH3).

[0160] b) Ozone decomposition of 1-(4-(but-3-en-1-yl)phenyl)-2-methylprop-2-ol in an acetonitrile / water mixture.

[0161] 1-(4-(but-3-en-1-yl)phenyl)-2-methylprop-2-ol (20 g, 96 mmol) was added to a 1.5 L glass reactor equipped with a magnetic stirrer in air, followed by acetonitrile (800 g) and water (80 g). The reaction mixture was cooled to 1 °C in an ice-water bath after stirring. Then, a mixture of 0.55 wt% ozone (O3 / O2) was bubbled into the reaction mixture at a flow rate of 40 L / h for 8 hours. A small sample (MTBE / PPh3) was analyzed by GC, indicating that the reaction was complete, producing the aldehyde 3-(4-(2-hydroxy-2-methylpropyl)phenyl)propanal in 92% yield, and the acid 3-(4-(2-hydroxy-2-methylpropyl)phenyl)propionic acid in 7% yield. The reaction mixture was poured into a separatory funnel, diluted with toluene (800 mL), and the aqueous phase (42.5 g, pH 3–4) was separated. The organic phase was washed successively with 10% Na₂SO₃ solution (2 × 250 mL and 3 × 125 mL) and water (2 × 250 mL). The organic phase was dried over anhydrous Na₂SO₄ and filtered. The peroxidation index (IP < 10) was determined, and the reaction mixture was then concentrated under reduced pressure to give the target crude aldehyde (17.8 g, GC 99%, 84.6 mmol, yield 88%). Distillation under reduced pressure (bp: 96 °C / 0.001 mbar) gave 3-(4-(2-hydroxy-2-methylpropyl)phenyl)propanal (14.4 g, GC 99%, 69 mmol, yield 72%) as a colorless oil.

[0162] δ H (500 MHz; CD2Cl2; Me4Si) in ppm: 1.17 (6H, s, Me), 1.43 (1H, brs, OH), 2.70 (2H, s), 2.75 (2H, t, J = 7.4 Hz, CH2), 2.92 (2H, t, J = 7.5 Hz,CH2), 7.13 (4H, s, CH arom.), 9.78 (1H, br s, CHO).

[0163] δ C (125 MHz; CD2Cl2; Me4Si) Unit ppm: 28.06 (CH2), 29.39 (CH3), 45.63 (CH2), 49.61 (CH2), 70.89 (C), 128.36 (CH arom.), 131.03 (CH arom.), 136.35 (Carom.), 139.01 (Carom.), 201.98 (CHO).

[0164] Example 2

[0165] a) Preparation of 2-methyl-1-(4-(4-methylpent-3-en-1-yl)phenyl)prop-2-ol

[0166] 1-Chloro-4-(4-methylpent-3-en-1-yl)benzene

[0167] Magnesium (15.1 g, 0.621 mol) and methyltetrahydrofuran (300 g) were added to a 2 L round-bottom flask. The suspension was stirred at 20 °C. A solution of 4-chlorobenzyl chloride (100 g, 0.621 mol) in methyltetrahydrofuran (300 g) was added dropwise over 2 hours. The reaction mixture was stirred for another hour. Isopreneyl chloride (74 g, 0.621 mol) was added dropwise over 2 hours at 20 °C. After 1 hour, the reaction was quenched with acetic acid (187 g, 20% aqueous solution) at 15 °C. The phases were separated by decantation. The organic phase was washed twice with water and twice with 5% NaHCO3 solution. Evaporation yielded crude 1-chloro-4-(4-methylpent-3-en-1-yl)benzene (116.8 g), which was purified by distillation (88.3 g, yield 73%, still containing 8% 1-chloro-4-(2,2-dimethylbut-3-en-1-yl)benzene). The desired major isomer was separated from the minor isomer by fractional distillation.

[0168] 1 ¹H NMR (500 MHz, CDCl₃): 1-(3-buten-1-yl)-4-chlorobenzene; δ = 7.25–7.22 (m, 2H), 7.12–7.08 (m, 2H), 5.15–5.10 (m, 1H), 2.59 (t, 2H), 2.29–2.23 (m, 2H), 1.68 (s, 3H) 1.54 (s, 3H) ppm. 13 C NMR (125 MHz, CDCl3): δ = 140.8 (s), 132.5(s), 131.4 (s), 129.8 (d), 128.3 (d), 123.2 (d), 35.4 (t), 29.9 (t), 25.7(q), 17.7 (q) ppm.

[0169] 2-Methyl-1-(4-(4-methylpent-3-en-1-yl)phenyl)prop-2-ol

[0170] Magnesium (10.15 g, 0.418 mol) and methyltetrahydrofuran (50 g) were added to a 1 L round-bottom flask. The reaction mixture was stirred and heated to 65 °C. 1-Chloro-4-(4-methylpent-3-en-1-yl)benzene (80 g, 0.41 mol) was added dropwise over 2 hours, followed by the addition of more methyltetrahydrofuran (270 g) over 1 hour. The reaction mixture was then stirred at 65 °C for 44 hours. The reaction mixture was then cooled to 15 °C, and cuprous chloride (0.41 g, 4.1 mmol) was added, followed by the addition of isobutylene oxide (29.5 g, 0.41 mol) over 2 hours. The reaction mixture was quenched at 15 °C with citric acid (200 g, 20% aqueous solution) in the presence of 60% H₂O₂ (0.46 g, 8.2 mmol). The reaction mixture was stirred for 1 hour. The phases were separated by decantation. The organic phase was washed successively with 10% potassium citrate solution and 5% NaHCO3 solution, and evaporated to obtain crude product 2-methyl-1-(4-(4-methylpent-3-en-1-yl)phenyl)prop-2-ol (108.6 g), which was purified by column distillation (63.7 g, yield 67%).

[0171] 1 ¹H NMR (500 MHz, CDCl₃): 1-(4-(3-buten-1-yl)phenyl)-2-methylprop-2-ol; δ = 7.15–7.10 (m, 4H), 5.20–5.15 (m, 1H), 2.73 (s, 2H), 2.63–2.58 (m, 2H), 2.25–2.31 (m, 2H), 1.68 (s, 3H), 1.56 (s, 3H), 1.22 (s, 6H) ppm. 13 C NMR (125 MHz, CDCl3): δ = 140.6 (s), 134.9 (s), 132.1 (s), 130.3 (d), 128.3 (d), 123.8 (d), 70.7 (s), 49.3 (t), 35.7 (t), 30.1 (t), 29.1 (q), 5.7 (q), 17.7 (q) ppm.

[0172] b) Ozone decomposition of 2-methyl-1-(4-(4-methylpent-3-en-1-yl)phenyl)prop-2-ol

[0173] 2-Methyl-1-(4-(4-methylpent-3-en-1-yl)phenyl)prop-2-ol (5 g, 21 mmol) was added to a 150 mL glass reactor equipped with a magnetic stirrer in air, followed by dichloromethane (100 mL). The reaction mixture was stirred and cooled to -75 °C. Then, a mixture of 2.5 wt% ozone (O3 / O2) was bubbled into the reaction mixture at a flow rate of 30 L / h for 1 hour. A small sample (MTBE / PPh3) was analyzed by GC, indicating that the reaction was complete, producing the aldehyde 3-(4-(2-hydroxy-2-methylpropyl)phenyl)propanal. The reaction mixture was then quenched with dimethyl sulfide (3.1 mL, 42 mmol, 2 equivalents) at -60 °C and stirred overnight. The aqueous layer was removed, and the organic phase was extracted with toluene (150 mL). The peroxide content in the reaction mixture was determined, and the solvent was removed by rotary evaporation to give 6.3 g of crude product. Purified by ball-to-ball distillation, the target aldehyde 3-(4-(2-hydroxy-2-methylpropyl)phenyl)propanal (3 g, 14.5 mmol, yield 70%) was obtained as a pale yellow oil.

[0174] δ H (500 MHz; CD2Cl2; Me4Si) in ppm: 1.17 (6H, s, Me), 1.43 (1H, brs, OH), 2.70 (2H, s), 2.75 (2H, t, J = 7.4 Hz, CH2), 2.92 (2H, t, J = 7.5 Hz,CH2), 7.13 (4H, s, CH arom.), 9.78 (1H, br s, CHO).

[0175] δ C (125 MHz; CD2Cl2; Me4Si) Unit ppm: 28.06 (CH2), 29.39 (CH3), 45.63 (CH2), 49.61 (CH2), 70.89 (C), 128.36 (CH arom.), 131.03 (CH arom.), 136.35 (Carom.), 139.01 (Carom.), 201.98 (CHO).

[0176] Example 3

[0177] Ozone decomposition of 5-(2-methylbut-3-enyl)-1,3-benzodioxane in dichloromethane.

[0178] 5-(2-methyl-3-butenyl)-1,3-benzodioxane (1.4 g, 7.4 mmol) was added to a 0.05 L glass reactor equipped with a magnetic stirrer in air, followed by dichloromethane (26.5 g). The reaction mixture was stirred in a dry ice / acetone bath and cooled to -75 °C. Then, an O3 / O2 mixture of 1 wt% ozone was bubbled into the reaction mixture at a flow rate of 40 L / h for 1 h. A small sample (MTBE / PPh3) was taken for GC analysis, which showed that the reaction was complete, producing 90% of the aldehyde 3-(1,3-benzodioxane-5-yl)-2-methylpropanal. Triphenylphosphine (3.9 g, 14.7 mmol) was added to the cooled solution. The reaction mixture was slowly heated to room temperature over 1 h. Then, the mixture was poured into a separatory funnel, diluted with toluene (800 mL), and the aqueous phase (42.5 g, pH 3–4) was separated. The organic phase was washed successively with 10% Na₂SO₃ solution (2 × 250 mL and 3 × 125 mL), followed by washing with water (2 × 250 mL). The organic phase was dried over anhydrous Na₂SO₄ and filtered. The peroxidation index (IP < 10) was determined, and the reaction mixture was then concentrated under reduced pressure to give the target crude aldehyde (17.8 g, GC 99%, 84.6 mmol, yield 88%). Distillation under reduced pressure (bp: 96 °C / 0.001 mbar) yielded 3-(1,3-benzodioxane-5-yl)-2-methylpropanal (0.57 g, GC 98%, 3 mmol, yield 40%) as a colorless oil.

[0179] δ 1 H (500 MHz; CDCl3; Me4Si) Unit ppm: 9.69 (d, 1H, J=1.5 Hz), 6.78-6.58 (m, 3H), 5.93 (s, 2H), 2.99 (dd, 1H, J=5.4, 13.2 Hz), 2.57 (m, 2H), 1.08 (d, 3H, J=6.9 Hz).

[0180] δ 13 C (125 MHz; CDCl3; Me4Si) Unit ppm: 204.3, 147.7, 146.1, 132.5, 121.9, 109.3, 108.2, 100.9, 48.2, 36.4, 13.2.

[0181] Example 4

[0182] Ozone decomposition of 1H-indene-ar-(but-3-enyl)-2,3-dihydro-1,1-dimethyl in dichloromethane.

[0183] In a 0.15 L glass reactor equipped with a magnetic stirrer, 1H-indene-ar-(3-butenyl)-2,3-dihydro-1,1-dimethyl (5.0 g, 24.96 mmol) was added to air, followed by dichloromethane (132.5 g). The reaction mixture was stirred in a dry ice / acetone bath and cooled to -75 °C. Then, a mixture of O3 / O2 gas containing 2 wt% ozone was bubbled into the reaction mixture at a flow rate of 30 L / h for 1 hour. A small sample (MTBE / PPh3) was subjected to GC analysis, which indicated that the reaction was complete, producing 90% of the aldehyde 1H-indene-ar-propanal, 2,3-dihydro-1,1-dimethyl. Dimethyl sulfide (4.8 g, 76.89 mmol) was added to the cooled solution. The reaction mixture was slowly heated to room temperature and stirred at room temperature for 17 hours. The peroxidation index (IP < 10) was determined. The crude reaction mixture was purified by silica gel column chromatography to give 1H-indene-ar-propanal, 2,3-dihydro-1,1-dimethyl (4.4 g, GC 90%, 21.75 mmol, yield 44%), as a colorless oil.

[0184] δ 1 H (500 MHz, CDCl3; Me4Si) Unit ppm: 9.82-9.80 (m, 1H), 7.12-6.94 (m, 3H), 2.93 (q, J 7.8, 2H), 2.87-20 2.82 (m, 2H), 2.78-2.73 (m, 2H), 1.91 (t, J 7.2, 2H), 1.24 (s, 3H), 1.23 (s, 3H).

[0185] δ 13 C (125 MHz; CD2Cl2; Me4Si) Unit ppm: 201.9, 201.9 (d), 153.1, 150.7(s), 143.3, 140.9 (s), 138.4, 138.2 (s), 126.4, 126.2 (d), 124.5, 124.4 (d),122.0, 121.9 (d), 45.7, 45.5 (t), 43.9, 43.6 (s), 41.6, 41.5 (t), 29.9, 29.6(t), 28.6, 28.5 (q), 28.6 (q), 28.2, 28.0(t).

Claims

1. A method for preparing a compound of formula (I), The compound is in the form of any one of its isomers or mixtures thereof; wherein R and R 1 Each can independently represent a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl; and the condition is R and R 1 At least one group in it is not a hydrogen atom; R 2 Represents a hydrogen atom or a methyl group; R' is a hydrogen atom; or R and R' together represent C 3-8 Alkyl or -O-(CH2) m -O-, where m is 1 or 2; This method includes the oxidative cleavage of the compound of formula (II), The compound is in the form of any one of its isomers or mixtures thereof; wherein R 1 R 2 R 3 R and R' have the same meaning as defined above; R a and R b C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms 1-16 Hydrocarbon group or group of formula (a), The group is in the form of any of its isomers or mixtures thereof; wherein R 1 R 2 R and R' have the same meaning as defined above.

2. The method according to claim 1, wherein R 2 It is a hydrogen atom.

3. The method according to any one of claims 1 to 2, wherein R a It is a hydrogen atom or a carbon atom. 1-6 Alkyl or C6 aryl; preferably, R a It is a hydrogen atom.

4. The method according to any one of claims 1 to 3, wherein R b It is a hydrogen atom or a carbon atom. 1-6 Alkyl, C6 aryl; preferably, R b It is a hydrogen atom.

5. The method according to any one of claims 1 to 4, wherein the oxidative pyrolysis is ozone decomposition.

6. The method according to claim 5, wherein a reduction step is performed after the ozone decomposition.

7. The method according to claim 6, wherein the reduction step is carried out using a reducing agent selected from the group consisting of: amines, particularly tertiary amines or pyridines, supported amines, sulfites, sulfides, sodium salts of 3,3'-thiodipropionic acid, triphenylphosphine, Zn / AcOH, Zn / AcOH / water, Na2S, thiourea, thiodiethylene glycol, 3,3'-thiodipropanol, thioethylene glycol, 3,3'-thiodipropionitrile, H2, and Pd / C or Raney / Ni, P(OMe)3, P(OEt)3, P(Oct)3, P(Ph)3, P(OPh)3, MeO(SO)OMe, MeSSMe.

8. The method according to any one of claims 1 to 7, wherein the ozone decomposition is carried out in the presence of water.

9. The method according to any one of claims 1 to 8, wherein the compound of formula (I) conforms to formula (III), Where R and R 1 It has the same meaning as defined in claims 1 to 8; Furthermore, compound (II) conforms to formula (IV). Where R and R 1 It has the same meaning as defined in claims 1 to 8.

10. The method according to any one of claims 1 to 9, wherein R 1 It is a hydrogen atom or a carbon atom. 1-4 Alkoxy or C 1-4 Alkyl group, optionally substituted with one or more of hydroxyl, methoxy or OC(O)H.

11. The method according to any one of claims 1 to 10, wherein R 1 It can be a hydrogen atom or a methyl group.

12. The method according to any one of claims 1 to 11, wherein R is a hydrogen atom or C 1-4 Alkoxy or C 1-4 Alkyl group, optionally substituted with one or more of hydroxyl, methoxy or OC(O)H.

13. The method according to any one of claims 1 to 12, wherein the method for preparing the compound of formula (I) comprises the following steps: a) React CH2=CH-CHR2-X with the compound of formula (V), Where R, R', R 1 and R 2 It has the same meaning as defined in claims 1 to 12; Where Y is a halogen atom; Z is either MgY or a halogen atom. The condition is If Z is MgY, then X is a halogen atom; or If Z is a halogen atom, then X is MgY; Compound of formula (VI) is obtained. Among them, R, R', R 1 and R 2 It has the same meaning as defined in claims 1 to 12; b) subjecting the compound of formula (VI) to oxidative cleavage as defined in claims 1 to 12.

14. A compound of formula (II), The compound is in the form of any one of its isomers or mixtures thereof; wherein R and R 1 Each can independently represent a hydrogen atom or a carbon atom. 1-6 Alkoxy or C 1-6 Alkyl groups, optionally substituted with hydroxyl groups, C... 1-6 Alkyl or OC(O)R 3 One or two of the groups, wherein R 3 It is a hydrogen atom or a carbon atom. 1-3 Alkyl; and the condition is R and R 1 At least one group in it is not a hydrogen atom; and the condition is that when R is C 3-4 When alkyl, R 1 It is not a hydrogen atom; R 2 Represents a hydrogen atom or a methyl group; R' is a hydrogen atom; or R and R' together represent C 3-8 Alkyl; R a and R b C atoms that are independently hydrogen atoms or optionally contain one to three oxygen atoms 1-16 Hydrocarbon group or group of formula (a), This group is in the form of any of its isomers or mixtures thereof; R 1 R 2 R and R' have the same meaning as defined above.

15. The compound according to claim 14, wherein the compound of formula (II) conforms to formula (IV), Where R and R 1 It has the same meaning as defined in claim 14.

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