Alkylation of alcohols with dialkoxyethane derivatives

Abstract

The present invention relates to a process for obtaining a compound of formula (I), as well as a composition of matter comprising a compound of formula (IV) obtained by the process disclosed herein.

Description

[0001] Alkylation of Alcohols with Dialkoxyethane Derivatives

[0002] Technical Field

[0003] The present invention relates to a process for obtaining a compound of formula (I), as well as a composition of matter comprising a compound of formula (IV) obtained by the process disclosed herein.

[0004] Backaround of the invention

[0005] The development of efficient synthetic methodologies for functionalized organic compounds remains a critical area of research in organic and pharmaceutical chemistry.

[0006] The alkylation of alcohols with acetals is a valuable transformation in organic synthesis, particularly in the production of ethers and functionalized molecules. This reaction is widely applied in the pharmaceutical, agrochemical, and fine chemical industries due to its efficiency in introducing alkyl groups under mild conditions.

[0007] In this reaction, an alcohol reacts with an acetal that possesses a leaving group, facilitating a substitution process in which the alcohol replaces the leaving group.

[0008] Conventional methods often rely on Bransted or Lewis acid catalysts to promote acetal activation. However, these approaches may suffer from limitations such as harsh reaction conditions, low selectivity, and undesired side reactions, including hydrolysis or polymerization. Efforts to improve this transformation have focused on developing more selective catalysts, optimizing reaction conditions, and minimizing unwanted byproducts.

[0009] Despite these advancements, there remains a need for improved methodologies that enhance yield, selectivity, and process efficiency while being compatible with a broad range of substrates. This invention provides a novel and efficient approach to the alkylation of alcohols with acetals, addressing the challenges of conventional processes and offering superior performance in terms of selectivity and scalability.

[0010] The present invention specifically focuses on the alkylation of alcohols with dialkoxy ethane derivatives bearing a nucleofuge utilizing a lithium compound. This approach provides a controlled and efficient method for synthesizing alpha alkoxy acetals, enhancingregioselectivity and minimizing unwanted side reactions. By leveraging this novel substitution strategy, the invention aims to offer improved efficiency, selectivity, and environmental sustainability while maintaining cost-effectiveness. This method facilitates broader commercial and industrial applications of alpha alkoxy acetals.

[0011] of the Invention

[0012] In a first aspect, the invention relates to a process for obtaining a compound of formula (I)

[0013]

[0014] (I),

[0015] wherein

[0016] R1 is a linear or branched C2-18 alkyl or alkenyl group,

[0017] Ra and Rb, each independently, are C1-4 alkyl groups or

[0018] Ra and Rb, when combined, form a 5- or 6-membered heterocyclic ring, optionally substituted with one or more C1-4 alkyl groups

[0019] comprising the step of bringing a compound of formula (II)

[0020]

[0021] OH

[0022] (II),

[0023] wherein R1 has the same meaning as defined above,

[0024] to reaction in the presence of a compound of formula (III)

[0025]

[0026] (HI)

[0027] wherein Ra and Rb have the same meaning as defined above and X is a nucleofuge, and a lithium species.In a second aspect, the invention relates to a composition of matter comprising a compound of formula (IV)

[0028]

[0029] obtained by the process according to the first aspect of the invention.

[0030] Detailed description of the invention

[0031] A first aspect of the invention is a process for obtaining a compound of formula (I)

[0032]

[0033] (I),

[0034] wherein

[0035] R1 is a linear or branched C2-18 alkyl or alkenyl group,

[0036] Ra and Rb, each independently, are Ci.4alkyl groups or

[0037] Ra and Rb, when combined, form a 5- or 6-membered heterocyclic ring, optionally substituted with one or more Ci.4alkyl groups

[0038] comprising the step of bringing a compound of formula (II)

[0039]

[0040] (II),

[0041] wherein R1 has the same meaning as defined above,

[0042] to reaction in the presence of a compound of formula (III)

[0043]

[0044] (HI)

[0045] wherein Ra and Rb have the same meaning as defined above and X is a nucleofuge, and a lithium species.

[0046] The compound of formula (I) can be obtained in the form of any of its stereoisomers or as a mixture thereof.

[0047] For the sake of clarity, by the expression “any one of its stereoisomers or a mixture thereof’, or the similar, it is meant the normal meaning understood by a person skilled in the art, i.e. that the compound of formula (I) can be a pure enantiomer or diastereomer. In other words, the compound of formula (I) may possess several stereocenters and each of said stereocenter can have two different stereochemistries (e.g. R or S). The compound of formula (I) may even be in the form of a pure enantiomer or in the form of a mixture of enantiomers or diastereoisomers. The compound of formula (I) can be in a racemic form or scalemic form. Therefore, the compound of formula (I) can be one stereoisomer or in the form of a composition of matter comprising, or consisting of, various stereoisomers.

[0048] The term “alkyl group” refers to a linear or branched hydrocarbon chain comprising carbon and hydrogen atoms and having the general formula CnH2n+i, where n is an integer.

[0049] The term “alkenyl” is understood as an alkyl group that comprises at least one 1 olefinic double bond.

[0050] According to an embodiment, the term “alkenyl” refers to an alkyl group that contains 1 olefinic double bond.

[0051] The term “heterocyclic ring” refers to a cyclic molecular structure that contains at least one atom other than carbon (such as nitrogen, oxygen, or sulfur) within the ring framework.

[0052] According to an embodiment, the heterocyclic ring comprises at least two oxygen atoms within the ring framework.

[0053] According to a preferred embodiment, the heterocyclic ring contains two oxygen atoms within the ring framework.According to an embodiment, R1 is a linear or branched C3-14 alkyl or alkenyl group, preferably a linear or branched C5-12 alkyl or alkenyl group, more preferably a branched C7-10 alkyl or alkenyl group, most preferably a branched C8-9 alkyl or alkenyl group.

[0054] According to an embodiment, Ra and Rb, each independently, are Ci.2alkyl groups or Ra and Rb, when combined, form a 5- or 6-membered heterocyclic ring.

[0055] According to a preferred embodiment, Ra and Rb, each independently are Ci.2alkyl groups, preferably Ci alkyl groups.

[0056] The term "nucleofuge" refers to a leaving group that, upon reaction, departs from a molecular structure with the pair of bonding electrons, thereby facilitating a nucleophilic substitution reaction.

[0057] According to an embodiment, X is Cl, Br or sulfonate group, such as a mesylate group, tosylate group or the like.

[0058] According to a preferred embodiment, X is a Cl group.

[0059] According to an embodiment, the reaction of the first aspect of the invention comprises at least 1.0 molar equivalent, preferably at least 1.1 molar equivalent of the nucleofuge, based on the molar ratio of the compound of formula (II).

[0060] According to an embodiment, the compound of formula (I) is a compound of formula (la)

[0061]

[0062] (la)

[0063] wherein R2 is a linear or branched C2.9alkyl or alkenyl group, preferably a linear or branched C4-8 alkyl or alkenyl group, more preferably a branched C5-7 alkyl or alkenyl group and R3 is a C1-3 alkyl group, preferably a Ci alkyl group.According to an embodiment, the compound of formula (I) or of formula (la) is 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene.

[0064] According to an embodiment, the compound of formula (II) is a compound of formula (Ila)

[0065] R3

[0066]

[0067] (Ha),

[0068] wherein R2 is a linear or branched C2-9 alkyl or alkenyl group, preferably a linear or branched C4-8 alkyl or alkenyl group, more preferably a branched C5-7 alkyl or alkenyl group and R3 is a C1-3 alkyl group, preferably a Ci alkyl group.

[0069] According to an embodiment, the compound of formula (II) or of formula (Ila) is citronellol.

[0070] The term “lithium species” refers to any chemical entity containing lithium, including but not limited to lithium, lithium salts, lithium organometallic compounds, lithium complexes, and lithium-containing reagents. Such species may function as bases, nucleophiles, counterions, or catalysts.

[0071] According to an embodiment, the lithium species is selected from the group consisting of lithium, lithium halide, lithium hydroxide, lithium carbonate, lithium alkoxide, lithium amide and mixtures thereof.

[0072] According to an embodiment, the lithium species is selected from the group consisting of lithium, lithium hydroxide, lithium carbonate, lithium alkoxide, lithium amide and mixtures thereof.

[0073] According to a preferred embodiment, the lithium species is a basic lithium species, preferably lithium hydroxide, lithium carbonate, lithium alkoxide, lithium amide or mixtures thereof, more preferably lithium hydroxide or lithium methoxide, even more preferably lithium hydroxide. According to an embodiment, the lithium species is a combination of 2 or more different lithium species, for example, 2, 3, or 4 different lithium species, preferably 2 different lithium species. More particularly, the 2 or more lithium species are selected from the group consisting of lithium, lithium halide, lithium hydroxide, lithium carbonate, lithium alkoxide, and lithium amide. In a particular embodiment, the lithium species is a combination of 2 different lithium specieswherein one of the lithium species is a basic lithium species In a particular embodiment, the lithium species is a combination of 2 different lithium species wherein one of the lithium species is lithium hydroxide. In an embodiment, the lithium species is a combination of lithium hydroxide and lithium halide.

[0074] The lithium halide may be any suitable lithium halide, for example, LiBr, or Lil, preferably, the lithium halide is be Lil.

[0075] According to an embodiment, the reaction of the first aspect of the invention comprises at least 0.5 molar equivalent, preferably at least 0.9 molar equivalent of the lithium species, based on the molar ratio of the compound of formula (II).

[0076] According to an embodiment, the reaction of the first aspect of the invention is less than or equal to 2 molar equivalent, preferably less than or equal to 1.2 molar equivalent of the lithium species, based on the molar ratio of the compound of formula (II).

[0077] According to an embodiment, the reaction of the first aspect of the invention comprises at least 0.5 molar equivalent and less than or equal to 2 molar equivalent, preferably at least 0.9 molar equivalent and less than or equal to 1.2 molar equivalent of the lithium species, based on the molar ratio of the compound of formula (II).

[0078] According to an embodiment, the reaction of the first aspect of the invention is carried out in a solvent or a mixture of solvent.

[0079] According to an embodiment, the reaction of the first aspect of the invention is carried out in the presence of an inert solvent.

[0080] According to a preferred embodiment, the reaction of the first aspect of the invention is carried out in the exclusive presence of an inert solvent.

[0081] According to an embodiment, the inert solvent is not miscible with water and has a boiling point of more than 100 °C, preferable of at least 110 °C.

[0082] According to an embodiment, the inert solvent forms an azeotrope with water.For the sake of clarity, the expression “not miscible with water” refers to a substance that under standard conditions, exhibits limited or negligible solubility in water, such that it forms a separate phase when combined with water.

[0083] According to an embodiment, the inert solvent is selected from the group consisting of aprotic arenes, alkanes with a carbon number of at least 8, ethers with a boiling point of at least 120 °C, and mixtures thereof.

[0084] For the sake of clarity, the term “aprotic arene” refers to a monocyclic or polycyclic aromatic hydrocarbon containing one or more benzene rings which do not contain any hydrogen atoms, capable of participating in hydrogen bonding.

[0085] According to an embodiment, the inert solvent is selected from the group consisting of toluene, xylene, n-octane, n-nonane, n-decane, diglyme, mesitylene, pseudocumene, and mixtures thereof, preferably wherein the inert solvent is xylene.

[0086] According to an embodiment, the reaction of the first aspect of the invention comprises at least 25 wt% of the inert solvent, preferably at least 40 wt% of the inert solvent, and even more preferably at least 50 wt% of the invert solvent, based on the total weight of the compound of formula (II).

[0087] According to an embodiment, the reaction of the first aspect of the invention comprises less than or equal to 500 wt% of the inert solvent, preferably less than or equal to 400 wt% of the inert solvent and even more preferably less than or equal to 300 wt% of the inert solvent, based on the total weight of the compound of formula (II).

[0088] According to an embodiment, the reaction of the first aspect of the invention comprises at least 25 wt% and less than or equal to 500 wt% of the inert solvent, preferably at least 40 wt% less than or equal to 400 wt% of the inert solvent, and even more preferably at least 50 wt% less than or equal to 300 wt% of the invert solvent, based on the total weight of the compound of formula (II).

[0089] According to an embodiment, the reaction of the first aspect of the invention is carried out in the presence of a polar aprotic solvent.For the sake of clarity, the term “polar aprotic solvent” refers to a solvent that possesses a significant dipole moment and dielectric constant, thereby enabling the dissolution of ionic and polar compounds, while lacking hydrogen atoms capable of forming hydrogen bonds.

[0090] According to an embodiment, the polar aprotic solvent is selected from the group consisting of substituted polyglycol ethers, substituted acetamides, substituted formamides, substituted cyclic amides, dimethylsulfoxide, sulfolane and mixtures thereof, preferably wherein the substitution of the amides occurs at the N-atom.

[0091] For the sake of clarity, the term “cyclic amide” refers to a compound containing an amide functional group (-C(=O)-NR-) as part of a ring structure. The term encompasses both unsubstituted and substituted cyclic amides, including those where the nitrogen bears one or more alkyl groups.

[0092] According to an embodiment, the cyclic amide is substituted with a Ci to C6alkyl group, preferably wherein the substitution occurs at the N-atom.

[0093] According to a preferred embodiment the polar aprotic solvent is N-methyl-2-pyrrolidone.

[0094] According to an embodiment, the polar aprotic solvent is selected from the group consisting of polyglycol dimethyl ether, dimethylacetamide, dimethylformamide, N-methyl-2-pyrrolidone, and mixtures thereof.

[0095] According to an embodiment, the reaction of the first aspect of the invention comprises at least 0.1 molar equivalents of the polar aprotic solvent, preferably at least 0.3 molar equivalents of the polar aprotic solvent, and even more preferably at least 0.5 molar equivalents of the polar aprotic solvent based on the molar ratio of the compound of formula (II).

[0096] According to an embodiment, the reaction of the first aspect of the invention comprises less than or equal to 5 molar equivalents of the polar aprotic solvent, preferably less than or equal to 3 molar equivalents of the polar aprotic solvent and even more preferably less than or equal to 1.5 molar equivalents of the polar aprotic solvent based on the molar ratio of the compound of formula (II).

[0097] According to an embodiment, the reaction of the first aspect of the invention comprises at least 0.1 molar equivalents and less than or equal to 5 molar equivalents of the polar aprotic solvent,preferably at least 0.3 molar equivalents and less than or equal to 3 molar equivalents of the polar aprotic solvent, and even more preferably at least 0.5 molar equivalents and less than or equal to 1.5 molar equivalents of the polar aprotic solvent based on the molar ratio of the compound of formula (II).

[0098] According to an embodiment, the reaction of the first aspect of the invention is carried out in an inert solvent and in the presence of a polar aprotic solvent.

[0099] All definitions and embodiments related to the inert solvent and the polar aprotic solvent also apply mutatis mutandis for the reaction of the first aspect of the invention that is carried out in an inert solvent and in the presence of a polar aprotic solvent,

[0100] According to an embodiment, the compound of formula (I) is further reacted to a compound of formula (IV)

[0101]

[0102] (IV),

[0103] wherein R1 as the same meaning as R1 for the compound of formula (I).

[0104] All definitions and embodiments, relating to the compound of formula (I) apply mutatis mutandis for the compound of formula (IV). This applies in particular for R1.

[0105] According to an embodiment, the reaction of the compound of formula (I) to the compound of formula (IV) comprises water.

[0106] According to a preferred embodiment, the reaction of the compound of formula (I) to the compound of formula (IV) comprises water and an acidic environment, such as using formic acid, sulfuric acid, citric acid, oxalic acid, acetic acid, a cationic exchange resin or mixtures thereof, preferably acetic acid.

[0107] According to an embodiment, the compound of formula (IV) is a compound of formula (IVa)

[0108] R3

[0109]

[0110] (IVa),

[0111] wherein R2 and R3 have the same meaning as R2 and R3 for the compound of formula (la).

[0112] All definitions and embodiments, relating to the compound of formula (I) apply mutatis mutandis for the compound of formula (IV). This applies in particular for R2 and R3.

[0113] According to an embodiment, the compound of formula (IV) or (IVa) is 2-[(3,7-dimethyloct-6-en-1-yl)oxy]acetaldehyde.

[0114] Another aspect of the invention is a composition of matter comprising a compound of formula (IV) obtained by the process according to the first aspect of the invention.

[0115] All definitions and embodiments, relating to the compound of formula (IV) according to the first aspect of the invention apply mutatis mutandis for the compound of formula (IV) this aspect of the invention.

[0116] According to an embodiment, the composition of matter comprising a compound of formula (IV) obtained by the process according to the first aspect of the invention comprises the purified or the crude mixture of the compound of formula (IV).

[0117] According to an embodiment, the composition of matter comprises the acid adduct of the compound of formula (IV).

[0118] According to an embodiment, the composition of matter comprises the formate, citrate, oxalate, sulfate or acetate of the compound of formula (IV), preferably the acetate of the compound of formula (IV).

[0119] According to an embodiment, the composition of matter comprising a compound of formula (IV) obtained by the process according to the first aspect of the invention comprises the compound of formula (IV) and the formate, citrate, oxalate, sulfate or acetate of the compound of formula (IV), preferably the acetate of the compound of formula (IV).

[0120] According to an embodiment, the composition of matter comprises at least 0.01 wt.%, preferably at least 0.1 wt% of the formate, citrate, oxalate, sulfate or acetate, preferably the acetate of the compound of formula (IV).According to an embodiment, the composition of matter comprises less than or equal to 2.0 wt.%, preferably less than or equal to 1.5 wt% of the formate, citrate, oxalate, sulfate or acetate, preferably the acetate of the compound of formula (IV).

[0121] According to an embodiment, the composition of matter comprises at least 0.01 wt.%, preferably 0.1 wt% and comprises less than or equal to 2.0 wt%, preferably less than or equal to 1.5 wt% of the formate, citrate, oxalate, sulfate or acetate, preferably the acetate of the compound of formula (IV).

[0122] According to an embodiment, the composition of matter comprises 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl formate and / or 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate and / or 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene and / or [(7-hydroxy-3,7-dimethyloctyl)oxy]acetaldehyde, preferably 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate.

[0123] According to an embodiment, the composition of matter comprises at least 0.01 wt.%, preferably at least 0.1 wt% of 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate.

[0124] According to an embodiment, the composition of matter comprises less than or equal to 2.0 wt.%, preferably less than or equal to 1.5 wt% of 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate.

[0125] According to an embodiment, the composition of matter comprises at least 0.01 wt.%, preferably 0.1 wt% and comprises less than or equal to 2.0 wt%, preferably less than or equal to 1.5 wt% of 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate.

[0126] According to an embodiment, the composition of matter comprises at least 1.5 wt%, preferably at least 2.0 wt% of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene.

[0127] According to an embodiment, the composition of matter comprises less than or equal to 15 wt%, preferably less than or equal to 12 wt% of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene.

[0128] According to an embodiment, the composition of matter comprises at least 1.5 wt%, preferably at least 2 wt% and less than or equal to 15 wt%, preferably less than or equal to 12 wt% of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene.According to an embodiment, the composition of matter comprises at least 0.01 wt%, preferably at least 0.1 wt % of [(7-hydroxy-3,7-dimethyloctyl)oxy]acetaldehyde.

[0129] According to an embodiment, the composition of matter comprises less than or equal to 3.0, preferably less than or equal to 2.0 wt% of [(7-hydroxy-3,7-dimethyloctyl)oxy]acetaldehyde.

[0130] According to an embodiment, the composition of matter comprises at least 0.01 wt%, preferably at least 0.1 wt % and less than or equal to 3 wt%, preferably less than or equal to 2.0 wt% of [(7-hydroxy-3,7-dimethyloctyl)oxy]acetaldehyde.

[0131] According to an embodiment, the composition of matter comprises at least 0.01 wt.%, preferably at least 0.1 wt% and comprises less than or equal to 2 wt%, preferably less than or equal to 1.5 wt% of 2,6-dimethyl-8-(2-oxoethoxy)octan-2-yl acetate and / or at least 1.5 wt%, preferably at least 2 wt% and less than or equal to 15 wt%, preferably less than or equal to 12 wt% of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene and / or at least 0.01 wt%, preferably at least 0.1 wt % and less than or equal to 3 wt%, preferably less than or equal to 2.0 wt% of [(7-hydroxy-3,7-dimethyloctyl)oxy]acetaldehyde.

[0132] The expression “purified” refers to the state of a compound after it has been separated from the mixture in which it was synthesized, such that the compound is not in the same composition as the original reaction mixture. This implies that the compound has undergone a purification process to remove the majority of other reactants, solvents, catalysts, and any remaining starting materials, to a level where these components are present in amounts less than 0.1 wt%. The purity of the compound can be determined by common methods known to the person skilled in the art such as high performance liquid chromatography (HPLC) and gas chromatography - mass spectrometry (GC-MS).

[0133] The expression “crude mixture” refers to the state of a compound that has not been separated from the mixture in which it was synthesized. The implies that the composition of matter still comprises reactants, solvents, catalysts and remaining starting materials. The components of the compositions of matter can be determined by common methods known to the person skilled in the art such as HPLC and GC-MS.

[0134] The following Examples illustrate the invention without limiting its scope.Example 1 (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene)

[0135] Citronellol (500.0 g, 3.20 mol), o-xylene (500.0 g) and lithium hydroxide hydrate (147.7 g, 3.52 mol.) were charged in a reactor. The mixture was stirred and heated up to reflux removing water via the separator for 10 hours. The mixture was cooled to 110°C, distilled water was discarded and N-methyl-2-pyrrolidinone (317.2 g, 3.20 mol.) was charged. The suspension turned from white to beige. The mixture was heated up to reflux via the separator and chloroacetaldehyde dimethyl acetal (478.3 g, 3.84 mol) was added in 8 hours removing formed water in the separator. The mixture was heated up to reflux for 10 hours after the end of the addition and cooled to 50°C. Distilled water was discarded. Water (850.0 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed with water. The mixture was dried azeotropically under reduced pressure. The solvent was distilled under reduced pressure. The crude product was purified by distillation under reduced pressure through a column packed with glass rings giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (96.3% purity, 87% yield).

[0136] 1H-NMR (500 MHz, CDCI3) 55.09 (t, J = 7.0 Hz, 1 H), 4.50 (t, J = 5.2 Hz, 1 H), 3.55 - 3.45 (m, 4H), 3.40 (s, 6H), 2.04-1.91 (m, 2H), 1.67 (s, 3H), 1.66-1.61 (m, 1H), 1.60 (s, 3H), 1.58-1.50 (m, 1H), 1.46-1.37 (m, 1H), 1.37-1.29 (m, 1H), 1.24-1.10 (m, 1H), 0.89 (d, J = 6.8 Hz, 3H).

[0137] 13C-NMR (125 MHz, CDCI3) 5 131.2 (s), 124.8 (d), 102.8 (d), 70.5 (t), 70.1 (t), 53.9 (q), 53.9 (q), 37.2 (t), 36.5 (d), 29.5 (d), 25.7 (q), 25.5 (t), 19.6 (q), 17.6 (q).

[0138] Example 2 (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene) Citronellol (200.0 g, 1.24 mol), o-xylene (200.0 g) and lithium hydroxide hydrate (57.1 g, 1.36 mol) were charged in a reactor. The mixture was stirred and heated up to reflux removing water via the separator for 10 hours. The mixture was cooled to 110°C, distilled water was discarded and N-methyl-2-pyrrolidinone (122.7 g, 1.24 mol.) was charged. The suspension turned from white to beige. The mixture was heated up to reflux via the separator and bromoacetaldehyde dimethyl acetal (251.1 g, 1.49 mol) was added in 8 hours removing formed water in the separator. The mixture was heated up to reflux for 10 hours after the end of the addition and cooled to 50°C. Distilled water was discarded. Water (347.2 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed with water. The mixture was dried azeotropically under reduced pressure. The solvent was distilled under reduced pressure. The crude product was purified by distillation under reduced pressurethrough a column packed with glass rings giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (96.5% purity, 77% yield).

[0139] Example 3 (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene)

[0140] o-Xylene (200.0 g) and metallic lithium (9.8 g, 1.41 mol.) were charged in a reactor. The mixture was stirred and heated up to 120°C. Citronellol (200.0 g, 1.28 mol) was added in 2 hours. After the end of the addition, the mixture was heated up to reflux during 1 hour. The mixture was cooled to 110°C, N-methyl-2-pyrrolidinone (63.4 g, 0.64 mol.) was charged. The suspension turned from white to light green. Chloroacetaldehyde dimethyl acetal (175.4 g, 1.41 mol) was charged and the mixture was heated up to reflux for 8 hours. The mixture was cooled to 50°C and water (250.0 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed twice with water. The mixture was dried azeotropically under reduced pressure. The solvent was distilled under reduced pressure. The crude product was purified by distillation under reduced pressure through a column packed with glass rings giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (96.6% purity, 91% yield).

[0141] Example 4 (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene)

[0142] Citronellol (300 g, 1.92 mol), o-xylene (300 g) and lithium hydroxide hydrate (88.6 g, 2.11 mol) were charged in a reactor. The mixture was stirred and heated up to reflux removing water via the separator for 10 hours. The mixture was cooled to 110°C, distilled water was discarded. N-methyl-2-pyrrolidinone (190.3 g, 1.92 mol.) and lithium iodide (12.8 g, 0.10 mol) was charged. The suspension turned from white to beige. The mixture was heated up to reflux via the separator and chloroacetaldehyde dimethyl acetal (287.0 g, 2.30 mol) was added in 8 hours removing formed water in the separator. The mixture was heated up to reflux for 10 hours after the end of the addition and cooled to 60°C. Distilled water was discarded. Water (500.0 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed with water. The mixture was dried azeotropically under reduced pressure. The solvent was distilled under reduced pressure. The crude product was purified by distillation under reduced pressure through a column packed with glass rings giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (96.1% purity, 79% yield).Comparative Example 1a (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene using sodium hydroxide instead of Lithium hydroxide)

[0143] Sodium hydroxide (81.91 g, 2.05 mol, 1.6 eq.), tricaprylylmethylammonium chloride (5.53 g, 0.01 mol, 0.01 eq.) and citronellol (200 g, 1.28 mol, 1 eq.) were charged under nitrogen and the resulting mixture was heated up to 140 °C. Then, chloroacetaldehyde dimethyl acetal (164.35 g, 1.28 mol, 1 eq.) was added to the mixture over a period of 45 min. After 4 h, additional sodium hydroxide (30.7 g, 0.77 mol, 0.6 eq.) and tricaprylylmethylammonium chloride (5.53 g, 0.01 mol, 0.01 eq.) were added to the mixture.

[0144] After 7 h, the reaction mixture was cooled to 50 °C and water (350 g) was added. Then, the aqueous phase was decanted and the organic phase was washed with water (100 g). The remaining organic phase was concentrated under reduced pressure and distilled under reduced pressure giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (purity 41.3%, yield 33%).

[0145] Comparative Example 1b (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene using sodium methoxide instead of Lithium hydroxide)

[0146] Citronellol (50.0 g, 0.32 mol), o-xylene (100 g) and sodium methoxide 30% in methanol (63.4 g, 0.35 mol) were charged in a reactor. Methanol was distilled out of the mixture until the vapour temperature reached 135°C. The mixture was cooled to 80°C, distilled methanol was discarded and N-methyl-2-pyrrolidinone (31.7 g, 0.32 mol) was charged. The suspension turned from white to brown. Chloroacetaldehyde dimethyl acetal (47.8 g, 0.38 mol) was added. The mixture was heated up to 130°C for 3 hours and cooled down to 60°C. Water (70.0 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed twice with water. The solvent was distilled under reduced pressure. The crude product was purified by flash distillation giving 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (39.7% purity, 32% yield).

[0147] Comparative Example 1c (preparation of 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene using potassium methoxide instead of Lithium hydroxide) Citronellol (200.0 g, 1.28 mol), o-xylene (300 g) and potassium methoxide 32% in methanol (308.5 g, 1.41 mol) were charged in a reactor. Methanol was distilled out of the mixture until the vapour temperature reached 135°C. The mixture was cooled to 75°C, distilled methanol was discarded and N-methyl-2-pyrrolidinone (31.7 g, 0.32 mol) was charged. The suspensionturned from white to yellow. The mixture was heated up to 110°C and chloroacetaldehyde dimethyl acetal (175.4 g, 1.41 mol) was added in 1 hour. The mixture was stirred at 110°C for 4 hours after the end of the addition and cooled down to 60°C. Water (300.0 g) was charged and the mixture was stirred until complete dissolution of the solid (5 minutes). The mixture was allowed to settle. The aqueous phase was decanted and discarded. The organic phase was washed with water. The mixture was dried azeotropically under reduced pressure. The solvent was distilled under reduced pressure. A very low conversion of citronellol is obtained (17%). The product is not purified.

[0148] Example 2 (preparation of 2-[(3,7-dimethyloct-6-en-1-yl)oxy1acetaldehyde)

[0149] 8-(2,2-dimethoxyethoxy)-2,6-dimethyloct-2-ene (400.0 g, 1.58 mol.), acetic acid (1060 g) and water (217.6 g) were charged in a reactor. The mixture was stirred and heated up to 80°C for 4 hours. The mixture was cooled to 60°C and lights and aqueous acetic acid were distilled under reduced pressure. The mixture was cooled to 25°C and water (200.0 g) and heptane FC (300.0 g) were charged. The mixture was allowed to settle. The aqueous phase was decanted and discarded. The mixture was washed with water (200.0 g). The solvent was distilled under reduced pressure. Crude product was distilled with a thin film evaporator giving 2-[(3,7-dimethyloct-6-en-1-yl)oxy]acetaldehyde (86.4% purity, 83% yield).

[0150] 1H-NMR (500 MHz, CDCI3) 5 9.75 (s, 1H), 5.12 - 5.08 (m, 1H), 4.07 (s, 2H), 3.61-3.54 (m, 1H), 3.51-3.43 (m, 1H), 2.06-1.93 (m, 2H), 1.69 (s, 3H), 1.69 (s, 3H), 1.74-1.15 (m, 4H), 0.93 (d, J = 6.7 Hz, 3H), 0.91 - 0.86 (m, 1 H).

[0151] 13C-NMR (125 MHz, CDCI3) 5201.2 (d), 131.3 (s), 124.7 (d), 76.4 (t), 70.5 (t), 37.2 (t), 36.5 (t), 29.4 (d), 25.7 (q), 25.4 (t), 19.5 (q), 17.7 (q).

Claims

WHAT IS CLAIMED IS1. A process for obtaining a compound of formula (I)(I)whereinR1 is a linear or branched C2-18 alkyl or alkenyl group,Ra and Rb, each independently, are C1-4 alkyl groups orRa and Rb, when combined, form a 5- or 6-membered heterocyclic ring, optionally substituted with one or more C1-4 alkyl groupscomprising the step of bringing a compound of formula (II)(II),wherein R1 has the same meaning as defined above,to reaction in the presence of a compound of formula (III)(HI)wherein Ra and Rb have the same meaning as defined above and X is a nucleofuge, anda lithium species.

2. The process according to claim 1, wherein the lithium species is lithium, lithium hydroxide, lithium halide, lithium carbonate, lithium alkoxide or lithium amide, or a mixture thereof, preferably lithium hydroxide.

3. The process according to any of the preceding claims, wherein the reaction is carried out in the presence of an inert solvent, preferably wherein the reaction is carried out in the exclusive presence of an inert solvent, more preferably wherein the inert solvent is xylene, toluene, , n-octane, n-nonane, n-decane, diglyme, mesitylene, pseudocumene, and mixtures thereof.

4. The process according to any of the preceding claims, wherein the reaction is carried out in the presence of a polar aprotic solvent, more preferably wherein the polar aprotic solvent is N-methyl-2-pyrrolidone, polyglycol dimethyl ether, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, sulfolane and mixtures thereof.

5. The process according to any of the preceding claims, wherein the compound of formula (I) is reacted further to a compound of formula (IV)(IV)wherein R1 has the same meaning as defined in the preceding claims.

6. The process according to any of the preceding claims, wherein R1 is a linear or branched C3-14 alkyl or alkenyl group, preferably a linear or branched C5-12 alkyl or alkenyl group, more preferably a branched C7-10 alkyl or alkenyl group, most preferably a branched C8-9 alkyl or alkenyl group.

7. The process according to any of the preceding claims, wherein Ra and Rb, each independently, are C1-2 alkyl groups or Ra and Rb, when combined, form a 5- or 6- membered heterocyclic ring.

8. The process according to any of the preceding claims, wherein X is Cl, Br, or sulfonate nucleofuge, preferably Cl.

9. The process according to any of the preceding claims, wherein the compound of formula (I) is a compound of formula (la)(la)whereinR2 is a linear or branched C2-9 alkyl or alkenyl group, preferably a linear or branched C4-8 alkyl or alkenyl group, more preferably a branched C5-7 alkyl or alkenyl group and R3 is a C1-3 alkyl group, preferably a Ci alkyl group,and the compound of formula (II) is a compound of formula (Ila)R3R2'^ / ^OH(Ha)wherein R2 and R3 have the same meaning as defined above.

10. The process according to claim 5, wherein the compound of formula (IV) is a compound of formula (IVa)(IVa)wherein R2 and R3 have the same meaning as defined in the preceding claims.

11. A composition of matter comprising a compound of formula (IV) obtained by the process according to any of the previous claims.

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