Squalane preparation method

Abstract

The present invention relates to the field of organic synthesis, and specifically relates to a squalane preparation method. The preparation method comprises the following steps: in a solvent, effecting a dimerization reaction of beta-farnesene in the presence of a palladium catalyst and a basic medium to obtain a mixture; and in the presence of a second catalyst, subjecting the resulting mixture to hydrogenative reduction to obtain a resulting product. The chemical formula of the squalane is as shown in formula (1). The squalane product resulting from the preparation method is significantly improved in terms of purity and yield, with a large reduction in the proportion of isomers, significantly lower reagent costs, and less waste generated, thereby reducing production costs and making the preparation method suitable for the industrial production of squalane.

Description

A method for preparing squalane Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for preparing squalane. Background Technology

[0002] Squalane was originally produced by hydrogenating and reducing squalene extracted from deep-sea shark liver, resulting in a saturated alkane oil, hence its alternative name, deep-sea shark liver oil. Studies have shown that squalane is one of the few animal oils with high chemical stability and an excellent user experience. It has good skin affinity, very low polarity, and good spreadability. Pure squalane is a colorless, odorless, shiny, and transparent liquid. Due to its sensory characteristics, biocompatibility, and consistently robust composition, squalane is one of the highest quality and most widely used emollients on the market. It is a non-polar, fully saturated, and very stable hydrocarbon, which happens to be naturally present on the skin. Therefore, it can act as a special moisturizer, preventing moisture loss and giving the skin softness and elasticity. Squalane provides a silky, smooth, and luxurious feel without leaving a greasy or heavy feeling after use, making it a long-time favorite in cosmetic formulations. Squalane has the following characteristics and benefits: 1. It does not contain acne-causing ingredients; 2. It promotes cell metabolism; 3. It provides moisture and prevents moisture loss; 4. It improves skin elasticity; 5. It reduces the appearance of wrinkles and fine lines; 6. It enhances the integrity of the skin barrier; 7. It improves radiance. Its main applications are in skin care and hair care.

[0003] Squalane is a natural product belonging to the triterpenoid class of compounds, widely found in plants, marine organisms, etc., and possesses various biological activities and applications. The synthesis of squalane involves several technical challenges: (1) Complex structure and stereochemistry: Squalane has a complex molecular structure, containing multiple stereocenters and different functional groups. Precise control of chemical reactions is required during synthesis to ensure correct stereochemistry and molecular structure. (2) Multi-step reaction sequence: Squalane synthesis typically requires a multi-step chemical reaction sequence, each step requiring high selectivity and yield to avoid unnecessary side reactions and losses. The reaction conditions and reagent selection for each step need careful design and optimization. (3) Low-yield intermediate synthesis: Due to the complexity of squalane, the synthesis of intermediates may face low yield problems. This may require finding new reaction routes, catalysts, or reaction conditions to improve the yield and stability of intermediates. (4) Selection of synthetic route: Choosing a suitable synthetic route is crucial. The synthetic route for squalane can include the chemical synthesis of precursor molecules from natural sources or a completely artificial synthesis route. Selecting a suitable synthetic route requires consideration of factors such as economy, feasibility, and yield. (5) Catalyst Development: During the synthesis process, new catalysts may need to be developed to facilitate specific chemical transformations. Finding efficient and selective catalysts is crucial for synthesizing complex molecules such as squalane. (6) Separation and Purification: After the synthesis of squalane, effective separation and purification processes are required to remove residual reagents, intermediates, and impurities. This is essential for obtaining a high-purity product. (7) Challenges of Scale-Up Production: After successfully synthesizing squalane in the laboratory, scaling up the process to industrial production is a significant challenge. Ensuring high yield, high selectivity, and consistent product quality in large-scale production is a complex issue.

[0004] Traditional methods for preparing squalane involve the cationic polymerization of isobutylene to obtain saturated linear polyisobutylene, but these methods suffer from drawbacks such as cumbersome separation and purification processes and low yields of the target product. For example, Chinese patent application CN108017742A discloses a method for preparing oligomeric isobutylene for squalane synthesis. This method uses a novel lanthanide trifluoromethanesulfonate and a co-catalyst to catalyze isobutylene polymerization. During polymerization, an auxiliary agent is added to prepare oligomeric isobutylene with a molecular weight of 295-350 suitable for squalane synthesis. After polymerization, the reaction is quenched with water, and the product separates into layers. The oil phase is separated to obtain polyisobutylene, which is then hydrogenated to obtain the synthesized squalane product.

[0005] Therefore, it is particularly important to select a suitable monomer and develop a catalytic system for the directed polymerization of that monomer into squalane.

[0006] Summary of the Invention

[0007] The purpose of this invention is to provide an efficient method for synthesizing squalane, which improves product purity, reduces the proportion of isomers, lowers reagent costs, and reduces waste generation, thereby reducing production costs.

[0008] In order to achieve the above-mentioned technical objectives, the present invention hereby proposes the following technical solution:

[0009] One objective of this invention is to provide a method for preparing squalane, the method comprising the following steps:

[0010] (1) In a solvent, β-farnesene undergoes a dimerization reaction in the presence of a palladium catalyst and an alkaline medium to obtain a mixture;

[0011] (2) In the presence of a second catalyst, the mixture obtained in step (1) is hydrogenated and reduced to obtain the prepared product;

[0012] or

[0013] (I) β-farnesene reacts with diethylamine under alkaline conditions to yield farnesyldiethylamine;

[0014] (II) In the presence of chloroformate, the farnesyl diethylamine reacts to generate farnesyl chloride;

[0015] (III) In an organic solvent, in the presence of an initiator, the farnesyl chloride reacts with metallic magnesium to generate squalene;

[0016] (IV) The squalene is hydrogenated and reduced to squalane by a catalyst;

[0017] or

[0018] (i) All-trans farnesol reacts with a halogenating agent to form farnesyl halides;

[0019] (ii) In an organic solvent, in the presence of an initiator, the farnesyl halide reacts with metallic magnesium to generate squalene;

[0020] (iii) The squalene is hydrogenated and reduced to squalane by a catalyst;

[0021] The chemical formula of the squalane is shown below:

[0022] The chemical formula of the all-trans farnesol is shown below:

[0023] The chemical formula of the farnesyl halide is shown below:

[0024] Where X is a halogen, preferably Br or Cl.

[0025] In a preferred embodiment, based on the total weight of the product prepared in step (2), the product includes squalane: more than 92.0 wt%, and isosqualane and neosqualane: less than 4.5 wt%;

[0026] The chemical formula of the isosqualane is shown below:

[0027] The chemical formula of the new squalane is shown below:

[0028] In one embodiment, the purity of the squalane is greater than 90%.

[0029] In a preferred embodiment, the squalane has a purity of 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.91%, 99.92%, 99.93%, 99.94%, 99.95%, 99.96%, 99.97%, 99.98%, or 99.99%.

[0030] In one embodiment, β-farnesene is β-farnesene obtained through bio-fermentation.

[0031] In one embodiment, the palladium catalyst in step (1) is selected from one or more of the following:

[0032] XPhos Pd G4, BrettPhos Pd G4, RuPhos Pd G4, G2, tBuBrettPhos-Pd-G3, Ephos Pd G4, AdBrettPhos Pd G3, RockPhos Pd G3, Pd-PEPPSI-IHept Cl, Pd-PEPPSI-IPentC, Pd-PEPPSI-IPr Cl, PEPPSI-IPENT, Pd(dppf)Cl2, RuPhos Pd G1, Pd(CF3CO2)2, PdCl2(Amphos)2, (DPPF)PdCl2·CH2Cl2, Pd(t-Bu3P)2, XPhos Pd G3 or PdCl2(dtbpf).

[0033] In a preferred embodiment, the palladium catalyst in step (1) is selected from XPhos Pd G4 and / or Ad2nBuP Pd G3.

[0034] In a preferred embodiment, the palladium catalyst in step (1) is Ad2nBuP Pd G3.

[0035] In one embodiment, the solvent in step (1) includes a protic solvent.

[0036] In one embodiment, the solvent in step (1) includes, but is not limited to, isopropanol, ethanol, tert-butanol or tert-amyl alcohol.

[0037] In a preferred embodiment, the solvent in step (1) is isopropanol.

[0038] In one embodiment, the alkaline medium in step (1) includes, but is not limited to, sodium formate, potassium formate, sodium acetate and / or potassium acetate.

[0039] In a preferred embodiment, the alkaline medium in step (1) is sodium formate.

[0040] In one embodiment, the second catalyst in step (2) is a hydrogenation reduction catalyst.

[0041] In a preferred embodiment, the second catalyst in step (2) includes, but is not limited to: palladium catalyst, nickel catalyst, platinum catalyst, Raney nickel, Wilkinson catalyst, copper chromite, rhodium catalyst and / or ruthenium catalyst.

[0042] In a preferred embodiment, in step (2), the second catalyst is a palladium catalyst, preferably palladium on carbon, more preferably wet palladium on carbon.

[0043] In one embodiment, the reactions in steps (1) and (2) are carried out in an inert gas atmosphere.

[0044] In a preferred embodiment, the inert gas includes, but is not limited to, argon, nitrogen, helium, and / or neon.

[0045] In a preferred embodiment, the inert gas is nitrogen.

[0046] In one embodiment, the molar equivalent ratio of the palladium catalyst and β-farnesene in step (1) is (0.001-0.05):1.

[0047] In a preferred embodiment, the molar equivalent ratio of the palladium catalyst and β-farnesene in step (1) is 0.001:1, 0.002:1, 0.003:1, 0.004:1, 0.005:1, 0.006:1, 0.007:1, 0.008:1, 0.009:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, or 0.05:1.

[0048] In a preferred embodiment, the molar equivalent ratio of the palladium catalyst and β-farnesene in step (1) is 0.005:1.

[0049] In one embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene in step (1) is (0.1-0.5):1.

[0050] In a preferred embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene in step (1) is 0.1:1, 0.2:1, 0.3:1, 0.4:1, or 0.5:1.

[0051] In a preferred embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene in step (1) is 0.3:1.

[0052] In one embodiment, the mass-to-volume ratio of the solvent to β-farnesene in step (1) is (1.5-10):1, where the mass is in g and the volume is in mL.

[0053] In one implementation, the reaction temperature of step (1) is 80-85°C.

[0054] In a preferred embodiment, the reaction temperature of step (1) is 80, 81, 82, 83, 84, or 85 °C.

[0055] In one implementation, the reaction time for step (1) is 1-10 hours.

[0056] In a preferred embodiment, the reaction time of step (1) is 6-10 hours, for example, 6, 7, 8, 9, or 10 hours.

[0057] In a preferred embodiment, the reaction time for step (1) is 8 hours.

[0058] In one embodiment, step (1) further includes activated carbon adsorption.

[0059] In one embodiment, the activated carbon is 1%-15% by mass, based on the mass of β-farnesene described in step (1).

[0060] In one embodiment, the initiator in step (III) includes at least one of elemental iodine and 1,2-dibromoethane.

[0061] In one embodiment, the organic solvent in step (III) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether.

[0062] In one embodiment, the metallic magnesium in step (III) includes at least one of magnesium powder, magnesium shavings, or magnesium strips.

[0063] In one embodiment, the temperature of the reaction in step (III) is -5℃ to 80℃.

[0064] In one embodiment, the initiator in step (III) is elemental iodine, and its molar amount ranges from 0 to 0.01, based on the molar equivalent of farnesyl chloride described in step (III).

[0065] In one embodiment, the initiator in step (III) is 1,2-dibromoethane, with a molar amount ranging from 0.001 to 0.1, based on the molar equivalent of farnesyl chloride described in step (III).

[0066] In one embodiment, the molar amount of metallic magnesium in step (III) ranges from 1.0 to 3.0, based on the molar equivalent of farnesyl chloride described in step (III).

[0067] In one embodiment, the ratio of the volume of the organic solvent to the mass of the farnesyl chloride, based on the mass of the farnesyl chloride in step (III), is 3-20:1.

[0068] In one embodiment, the halogenated reagent in step (i) is at least one of phosphorus trichloride and phosphorus tribromide.

[0069] In one implementation, the temperature of the reaction in step (i) is -10°C to 30°C.

[0070] In one embodiment, the organic solvent in step (ii) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether.

[0071] In one embodiment, the initiator in step (ii) includes at least one of elemental iodine and 1,2-dibromoethane.

[0072] In one embodiment, the metallic magnesium in step (ii) includes at least one of magnesium powder, magnesium shavings, or magnesium strips.

[0073] In one implementation, the temperature of the reaction in step (ii) is -5°C to 40°C.

[0074] In one embodiment, the initiator in step (ii) is elemental iodine, and its molar amount ranges from 0 to 0.01, based on the molar equivalent of the farnesyl halide described in step (ii).

[0075] In one embodiment, the initiator in step (ii) is 1,2-dibromoethane, with a molar amount ranging from 0 to 0.1, based on the molar equivalent of the farnesyl halide described in step (ii).

[0076] In one embodiment, the ratio of the volume of the organic solvent in step (ii) to the mass of the farnesyl halide is 3-20:1, based on the mass of the farnesyl halide.

[0077] The second objective of this invention is to provide the use of squalane obtained by any of the aforementioned methods in the preparation of cosmetics or cosmetic raw materials.

[0078] The third objective of this invention is to provide a method for preparing isosqualene, the method comprising the following steps:

[0079] In a solvent, β-farnesene undergoes a dimerization reaction in the presence of a palladium catalyst and an alkaline medium to yield isosqualene;

[0080] The chemical formula of the isosqualene is shown below:

[0081] In one embodiment, β-farnesene is β-farnesene obtained through bio-fermentation.

[0082] In one embodiment, the palladium catalyst is selected from one or more of the following:

[0083] XPhos Pd G4, BrettPhos Pd G4, RuPhos Pd G4, G2, tBuBrettPhos-Pd-G3, Ephos Pd G4, AdBrettPhos Pd G3, RockPhos Pd G3, Pd-PEPPSI-IHept Cl, Pd-PEPPSI-IPentC, Pd-PEPPSI-IPr Cl, PEPPSI-IPENT, Pd(dppf)Cl2, RuPhos Pd G1, Pd(CF3CO2)2, PdCl2(Amphos)2, (DPPF)PdCl2·CH2Cl2, Pd(t-Bu3P)2, XPhos Pd G3 or PdCl2(dtbpf).

[0084] In a preferred embodiment, the palladium catalyst is selected from XPhos Pd G4 and / or Ad2nBuP Pd G3.

[0085] In a preferred embodiment, the palladium catalyst is Ad2nBuP Pd G3.

[0086] In one embodiment, the solvent includes a protic solvent.

[0087] In one embodiment, the solvent includes, but is not limited to, isopropanol, ethanol, tert-butanol, or tert-amyl alcohol.

[0088] In a preferred embodiment, the solvent is isopropanol.

[0089] In one embodiment, the alkaline medium includes, but is not limited to, sodium formate, potassium formate, sodium acetate, and / or potassium acetate.

[0090] In a preferred embodiment, the alkaline medium is sodium formate.

[0091] In one embodiment, the reaction is carried out in an inert gas atmosphere.

[0092] In a preferred embodiment, the inert gas includes, but is not limited to, argon, nitrogen, helium, and / or neon.

[0093] In a preferred embodiment, the inert gas is nitrogen.

[0094] In one embodiment, the molar equivalent ratio of the catalyst to β-farnesene is (0.001-0.05):1.

[0095] In a preferred embodiment, the molar equivalent ratio of the catalyst to β-farnesene is 0.001:1, 0.002:1, 0.003:1, 0.004:1, 0.005:1, 0.006:1, 0.007:1, 0.008:1, 0.009:1, 0.01:1, 0.02:1, 0.03:1, 0.04:1, or 0.05:1.

[0096] In a preferred embodiment, the molar equivalent ratio of the palladium catalyst to β-farnesene is 0.005:1.

[0097] In one embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene is (0.1-0.5):1.

[0098] In a preferred embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene is 0.1:1, 0.2:1, 0.3:1, 0.4:1, or 0.5:1.

[0099] In a preferred embodiment, the molar equivalent ratio of the alkaline medium to β-farnesene is 0.3:1.

[0100] In one embodiment, the mass-to-volume ratio of the solvent to β-farnesene is (1.5-10):1, wherein the mass is in g and the volume is in units of g.

[0101] In one implementation, the reaction temperature is 80-85°C.

[0102] In a preferred embodiment, the reaction temperature is 80, 81, 82, 83, 84, or 85°C.

[0103] In one implementation scheme, the reaction time is 1-10 hours.

[0104] In a preferred embodiment, the reaction time is 6-10 hours, for example, 6, 7, 8, 9, or 10 hours.

[0105] In a preferred embodiment, the reaction time is 8 hours.

[0106] In one embodiment, the preparation method further includes activated carbon adsorption.

[0107] In one embodiment, the activated carbon comprises 1%-15% by mass, based on the mass of β-farnesene.

[0108] The fourth objective of this invention is to provide the use of isosqualene obtained by the aforementioned preparation method in the preparation of squalane.

[0109] In one embodiment, the purpose is to hydrogenate and reduce isosqualene to obtain squalane.

[0110] Fifthly, this invention provides a method for preparing squalene, the method comprising the following steps:

[0111] I) β-Farnese reacts with diethylamine under alkaline conditions to yield farnesyldiethylamine;

[0112] II) In the presence of chloroformate, the farnesyl diethylamine reacts to generate farnesyl chloride;

[0113] Ⅲ) In an organic solvent, in the presence of an initiator, the farnesyl chloride reacts with metallic magnesium to generate squalene;

[0114] or

[0115] i) All-trans farnesol reacts with a halogenating agent to form farnesyl halides;

[0116] ii) In an organic solvent, in the presence of an initiator, the farnesyl halide reacts with metallic magnesium to generate squalene.

[0117] In one embodiment, the initiator in step III) includes at least one of elemental iodine and 1,2-dibromoethane.

[0118] In one embodiment, the organic solvent in step III) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether.

[0119] In one embodiment, the metallic magnesium in step III) includes at least one of magnesium powder, magnesium shavings, or magnesium strips.

[0120] In one embodiment, the temperature of the reaction in step III) is -5℃ to 80℃.

[0121] In one embodiment, the initiator in step III) is elemental iodine, and its molar amount ranges from 0 to 0.01, based on the molar equivalent of farnesyl chloride described in step III).

[0122] In one embodiment, the initiator in step III) is 1,2-dibromoethane, and its molar amount ranges from 0.001 to 0.1.

[0123] In one embodiment, the molar amount of metallic magnesium in step III) ranges from 1.0 to 3.0, based on the molar equivalent of farnesyl chloride described in step III).

[0124] In one embodiment, the ratio of the volume of the organic solvent to the mass of the farnesyl chloride, based on the mass of the farnesyl chloride in step III), is 3-20:1.

[0125] In one embodiment, the halogenated reagent in step i) is at least one of phosphorus trichloride and phosphorus tribromide.

[0126] In one implementation, the temperature of the reaction in step i) is -10℃ to 30℃.

[0127] In one embodiment, the organic solvent in step ii) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether.

[0128] In one embodiment, the initiator in step ii) includes at least one of elemental iodine and 1,2-dibromoethane.

[0129] In one embodiment, the metallic magnesium in step ii) includes at least one of magnesium powder, magnesium shavings, or magnesium strips.

[0130] In one implementation, the temperature of the reaction in step ii) is -5°C to 40°C.

[0131] In one embodiment, the initiator in step ii) is elemental iodine, and its molar amount ranges from 0 to 0.01, based on the molar equivalent of the farnesyl halide described in step ii).

[0132] In one embodiment, the initiator in step ii) is 1,2-dibromoethane, and its molar amount ranges from 0 to 0.1.

[0133] In one embodiment, the ratio of the volume of the organic solvent in step ii) to the mass of the farnesyl halide is 3-20:1, based on the mass of the farnesyl halide.

[0134] The method for preparing squalane provided by this invention has at least the following advantages compared with the prior art:

[0135] (1) The β-farnesene prepared by microbial fermentation in this invention has a single configuration. Compared with the β-farnesene with a mixed cis-trans configuration obtained by other methods, it produces fewer impurities and has higher product purity.

[0136] (2) The palladium catalyst preferred in this invention has high catalytic efficiency and good selectivity, and produces fewer types and lower contents of isosqualene isomers.

[0137] (3) The raw materials used in the synthesis method of the present invention are readily available, low in cost, controllable in process conditions, simple in reaction feeding, post-processing and purification, with little waste and high product purity;

[0138] (4) The squalane product prepared by this invention is colorless, odorless, bright and transparent, with very low polarity and good spreadability, and has an excellent user experience. Attached Figure Description

[0139] Figure 1 illustrates the chemical synthesis route for preparing squalane from naturally extracted β-farnesene via a two-step conventional conversion, including impurities generated in each step of the reaction. Detailed Implementation

[0140] To make the objectives, technical solutions, and advantages of the embodiments of this disclosure clearer, the technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this disclosure. All other embodiments obtained by those skilled in the art based on the described embodiments of this disclosure without creative effort are within the scope of protection of this invention.

[0141] This disclosure may be implemented in other specific forms without departing from the essential attributes of the invention. It should be understood that, without conflict, any and all embodiments of the invention may be combined with technical features of any or more other embodiments to obtain further embodiments. The invention includes further embodiments obtained through such combinations.

[0142] All publications and patents mentioned in this disclosure are incorporated herein by reference in their entirety. In the event of any conflict between the use or terminology used in any publications and patents incorporated by reference and the use or terminology used in this disclosure, the use and terminology of this disclosure shall prevail.

[0143] The chapter titles used in this article are for organizational purposes only and should not be construed as limiting the subject matter.

[0144] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly used in the field to which this invention pertains. For the purposes of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural forms, and vice versa.

[0145] Unless the context clearly indicates otherwise, the terms “a” and “an” as used herein include plural references. For example, reference to “a cell” includes multiple such cells and equivalents known to those skilled in the art, etc.

[0146] As disclosed herein, the term "about" indicates a range of ±20% of the following value. In some embodiments, the term "about" indicates a range of ±10% of the following value. In some embodiments, the term "about" indicates a range of ±5% of the following value.

[0147] The range of numbers used in this disclosure should be understood as including all numbers within that range. For example, the range 1 to 20 should be understood to include any number, combination of numbers, or subrange from the following group: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

[0148] As disclosed herein, the terms “comprises” or “comprising” mean “including, but not limited to”. This term is intended to be open-ended to specify the presence of any of the stated features, elements, integers, steps, or components, but does not exclude the presence or addition of one or more other features, elements, integers, steps, components, or groups thereof. Therefore, the term “comprising” includes the more restrictive terms “consisting of” and “substantially consisting of”. In one embodiment, the term “comprising” as used throughout the application, particularly in the claims, may be replaced by the term “consisting of”.

[0149] As indicated in this disclosure, the terms “optional,” “any,” “arbitrary,” or “any one” mean that the event or situation described below may, but does not necessarily, occur, including the circumstances in which the event or situation occurs or does not occur. As used herein, “an” and “a” refer to one or more grammatical objects.

[0150] As this disclosure illustrates, “and / or” should be understood to mean any one of the options or a combination of any two or more of the options.

[0151] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. Unless otherwise specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments without specified manufacturers are commercially available conventional products. Numerous specific details are provided in the following detailed embodiments to better illustrate the invention. The specific embodiments described herein are for illustrative purposes only and are not intended to constitute any limitation on the invention. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concept of the invention. Such structures and techniques have also been described in numerous publications.

[0152] The synthetic route for squalane disclosed herein is as follows:

[0153] or

[0154] or

[0155] The Ad2nBuP Pd G3 (cataCXiumAPdG3) disclosed herein was purchased from Jiangsu Xinnoco Catalyst Co., Ltd., product number: 1651823-59-4.

[0156] Example 1: Synthesis of isosqualene

[0157] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (35.6 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.92 g of a light yellow liquid product with a purity of 97.2% (85.1% isosqualene + 12.1% squalene) and a yield of 93.2%.

[0158] Example 2: Synthesis of isosqualene

[0159] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add BrettPhos Pd G4 (45.0 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.70 g of a light yellow liquid product with a purity of 33.9% (isosqualene 20.7% + squalene 13.2%), yield 28.8%.

[0160] Example 3: Synthesis of isosqualene

[0161] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add RuPhos Pd G4 (41.6 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.81 g of a light yellow liquid product with a purity of 66.0% (51.4% isosqualene + 14.6% squalene) and a yield of 59.7%.

[0162] Example 4: Synthesis of isosqualene

[0163] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add XantPhos Pd G4 (79.2 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.83 g of a light yellow liquid product with a purity of 60.7% (44.2% isosqualene + 16.5% squalene) and a yield of 55.5%.

[0164] Example 5: Synthesis of isosqualene

[0165] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add tBuXPhos Pd G3 (38.8 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.56 g of a light yellow liquid product with a purity of 27.0% (isosqualene 13.0% + squalene 14.0%) and a yield of 21.1%.

[0166] Example 6: Synthesis of isosqualene

[0167] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add CPos Pd G3 (39.4 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.76 g of a light yellow liquid product with a purity of 70.3% (55.6% isosqualene + 14.7% squalene) and a yield of 61.8%.

[0168] Example 7: Synthesis of isosqualene

[0169] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add SPhos Pd G3 (38.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.43 g of a light yellow liquid product with a purity of 31.6% (isosqualene 19.3% + squalene 12.3%), yield 22.6%.

[0170] Example 8: Synthesis of isosqualene

[0171] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add DavePhos Pd G3 (37.3 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.39 g of a light yellow liquid product with a purity of 29.5% (isosqualene 18.1% + squalene 11.4%) and a yield of 20.5%.

[0172] Example 9: Synthesis of isosqualene

[0173] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add XPhos Pd G4 (42.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.73 g of a light yellow liquid product with a purity of 88.9% (73.3% isosqualene + 15.4% squalene) and a yield of 76.9%.

[0174] Example 10: Synthesis of isosqualene

[0175] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add APhos Pd G3 (31.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.77 g of a light yellow liquid product with a purity of 84.9% (70.2% isosqualene + 14.7% squalene) and a yield of 75.1%.

[0176] Example 11: Synthesis of isosqualene

[0177] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Cy3P Pd G3 (31.8 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.74 g of a light yellow liquid product with a purity of 78.1% (62.1% isosqualene + 16.0% squalene) and a yield of 67.9%.

[0178] Example 12: Synthesis of isosqualene

[0179] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen for protection, and stir for 5 minutes. Then add tBu3P Pd G2 (25.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.41 g of a light yellow liquid product with a purity of 30.8% (isosqualene 17.9% + squalene 12.9%), yield 21.7%.

[0180] Example 13: Synthesis of isosqualene

[0181] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add tBuBrettPhos-Pd-G3 (41.8 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.39 g of a light yellow liquid product with a purity of 30.3% (isosqualene 15.8% + squalene 14.5%), yield 21.0%.

[0182] Example 14: Synthesis of isosqualene

[0183] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ephos Pd G4 (44.9 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.33 g of a light yellow liquid product with a purity of 24.3% (isosqualene 12.4% + squalene 11.9%), yield 16.1%.

[0184] Example 15: Synthesis of isosqualene

[0185] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add AdBrettPhos Pd G3 (49.4 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.34 g of a light yellow liquid product with a purity of 23.4% (isosqualene 11.7% + squalene 11.7%), yield 15.6%.

[0186] Example 16: Synthesis of isosqualene

[0187] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add RockPhos Pd G3 (41.0 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.44 g of a light yellow liquid product with a purity of 27.8% (isosqualene 14.7% + squalene 13.1%), yield 20.0%.

[0188] Example 17: Synthesis of isosqualene

[0189] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd-PEPPSI-IHept Cl (47.59 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.54 g of a light yellow liquid product with a purity of 43.8% (32.9% isosqualene + 10.9% squalene) and a yield of 33.7%.

[0190] Example 18: Synthesis of isosqualene

[0191] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd-PEPPSI-IPentC (42.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.60 g of a light yellow liquid product with a purity of 41.5% (30.4% isosqualene + 11.1% squalene) and a yield of 33.2%.

[0192] Example 19: Synthesis of isosqualene

[0193] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd-PEPPSI-IPrCl (36.6 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.58 g of a light yellow liquid product with a purity of 30.9% (20.2% isosqualene + 10.7% squalene) and a yield of 24.4%.

[0194] Example 20: Synthesis of isosqualene

[0195] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen for protection, and stir for 5 minutes. Then add PEPPSI-IPENT (38.7 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.40 g of a light yellow liquid product with a purity of 24.2% (isosqualene 13.7% + squalene 10.5%) and a yield of 16.9%.

[0196] Example 21: Synthesis of isosqualene

[0197] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd(dppf)Cl2 (35.8 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.80 g of a light yellow liquid product with a purity of 84.1% (67.6% isosqualene + 16.5% squalene) and a yield of 75.7%.

[0198] Example 22: Synthesis of isosqualene

[0199] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add RuPhos Pd G1 (39.9 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.61 g of a light yellow liquid product with a purity of 48.6% (34.7% isosqualene + 13.9% squalene) and a yield of 39.1%.

[0200] Example 23: Synthesis of isosqualene

[0201] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd(CF3CO2)2 (16.2 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.81 g of a light yellow liquid product with a purity of 82.4% (65.2% isosqualene + 17.2% squalene) and a yield of 74.5%.

[0202] Example 24: Synthesis of isosqualene

[0203] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add PdCl2(Amphos)2 (34.7 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.72 g of a light yellow liquid product with a purity of 66.4% (54.3% isosqualene + 12.1% squalene) and a yield of 57.1%.

[0204] Example 25: Synthesis of isosqualene

[0205] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add (DPPF)PdCl2·CH2Cl2 (39.9 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.79 g of a light yellow liquid product with a purity of 79.8% (63.4% isosqualene + 16.4% squalene) and a yield of 71.4%.

[0206] Example 26: Synthesis of isosqualene

[0207] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Pd(t-Bu3P)2 (25.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating and add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 1 hour, allow to cool naturally to room temperature, filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.43 g of a light yellow liquid product with a purity of 25.0% (isosqualene 14.2% + squalene 10.8%) and a yield of 17.8%.

[0208] Example 27: Synthesis of isosqualene

[0209] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add XPhos Pd G3 (41.1 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.73 g of a light yellow liquid product with a purity of 79.8% (67.3% isosqualene + 12.5% ​​squalene) and a yield of 69.0%.

[0210] Example 28: Synthesis of isosqualene

[0211] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add PdCl2 (dtbpf) (31.5 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.65 g of a light yellow liquid product with a purity of 53.3% (isosqualene 40.3% + squalene 13.0%), yield 43.9%.

[0212] Example 29: Synthesis of isosqualene

[0213] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (7.1 mg, 0.001 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.90 g of a light yellow liquid product with a purity of 69.8% (65.4% isosqualene + 4.4% squalene) and a yield of 66.3%.

[0214] Example 30: Synthesis of isosqualene

[0215] Add β-farnesene (2.0 g, 1 eq) and ethanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (7.1 mg, 0.001 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.93 g of a light yellow liquid product with a purity of 35.4% (31.2% isosqualene + 4.2% squalene) and a yield of 34.1%.

[0216] Example 31: Synthesis of isosqualene

[0217] Add β-farnesene (2.0 g, 1 eq) and tert-butanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (7.1 mg, 0.001 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.89 g of a light yellow liquid product with a purity of 74.4% (71.5% isosqualene + 2.9% squalene) and a yield of 70.3%.

[0218] Example 32: Synthesis of isosqualene

[0219] Add β-farnesene (2.0 g, 1 eq) and tert-amyl alcohol (6 mL, 3V) to a reaction flask, purge with nitrogen for protection, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (7.1 mg, 0.001 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.87 g of a light yellow liquid product with a purity of 66.4% (65.1% isosqualene + 1.3% squalene) and a yield of 62.0%.

[0220] Example 33: Synthesis of isosqualene

[0221] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (0.35 g, 0.05 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.88 g of a light yellow liquid product with a purity of 72.2% (65.1% isosqualene + 7.1% squalene) and a yield of 67.8%.

[0222] Example 34: Synthesis of isosqualene

[0223] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (0.35 g, 0.05 eq) and potassium formate (0.25 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.91 g of a light yellow liquid product with a purity of 77.1% (67.7% isosqualene + 9.4% squalene) and a yield of 73.6%.

[0224] Example 35: Synthesis of isosqualene

[0225] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (0.35 g, 0.05 eq) and sodium acetate (0.24 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.61 g of a light yellow liquid product with a purity of 21.2% (isosqualene 10.0% + squalene 11.2%), yield 17.0%.

[0226] Example 36: Synthesis of isosqualene

[0227] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (0.35 g, 0.05 eq) and potassium acetate (0.29 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.53 g of a light yellow liquid product with a purity of 19.9% ​​(8.2% isosqualene + 11.7% squalene) and a yield of 15.2%.

[0228] Example 37: Synthesis of isosqualene

[0229] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (35.6 mg, 0.005 eq) and sodium formate (0.07 g, 0.1 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.72 g of a light yellow liquid product with a purity of 55.3% (49.1% isosqualene + 6.2% squalene) and a yield of 47.5%.

[0230] Example 38: Synthesis of isosqualene

[0231] Add β-farnesene (2.0 g, 1 eq) and isopropanol (6 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (35.6 mg, 0.005 eq) and sodium formate (0.33 g, 0.5 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.81 g of a light yellow liquid product with a purity of 79.1% (69.7% isosqualene + 9.4% squalene) and a yield of 71.5%.

[0232] Example 39: Synthesis of isosqualene

[0233] Add β-farnesene (2.0 g, 1 eq) and isopropanol (4 mL, 2 V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (35.6 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.94 g of a light yellow liquid product with a purity of 86.1% (77.1% isosqualene + 9.0% squalene) and a yield of 83.5%.

[0234] Example 40: Synthesis of isosqualene

[0235] Add β-farnesene (2.0 g, 1 eq) and isopropanol (10 mL, 5V) to a reaction flask, purge with nitrogen, and stir for 5 minutes. Then add Ad2nBuP Pd G3 (35.6 mg, 0.005 eq) and sodium formate (0.2 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating, add activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption, stir for 1 hour, and allow to cool naturally to room temperature. Filter with diatomaceous earth, wash the filter cake with a small amount of isopropanol, and concentrate the filtrate to obtain 1.89 g of a light yellow liquid product with a purity of 75.1% (68.4% isosqualene + 6.7% squalene) and a yield of 70.9%.

[0236] Example 41: Synthesis of Squalane

[0237] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to the reaction flask, purge with nitrogen, and stir for 30 minutes. Then add Ad2nBuP Pd G3 (3.56 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >93.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Westergren rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 185.3g of a clear, transparent, colorless liquid was collected, with a purity of 99.2% and a yield of 89.2%.

[0238] Example 42: Synthesis of Squalane

[0239] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add CPhos Pd G3 (3.9 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for approximately 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >70.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 128.3g of a clear, transparent, colorless liquid was collected, with a purity of 96.4% and a yield of 60.1%.

[0240] Example 43: Synthesis of Squalane

[0241] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add XPhos Pd G4 (4.21 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >85.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 151.4g of a clear, transparent, colorless liquid was collected, with a purity of 97.6% and a yield of 71.8%.

[0242] Example 44: Synthesis of Squalane

[0243] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add APhos Pd G3 (3.1 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for approximately 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >83.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 148.4g of a clear, transparent, colorless liquid was collected, with a purity of 97.9% and a yield of 70.6%.

[0244] Example 45: Synthesis of Squalane

[0245] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add Cy3P Pd G3 (3.1 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for approximately 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >75.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 136.8g of a clear, transparent, colorless liquid was collected, with a purity of 95.1% and a yield of 63.2%.

[0246] Example 46: Synthesis of Squalane

[0247] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add Pd(dppf)Cl2 (3.6 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for approximately 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >83.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 148.8g of a clear, transparent, colorless liquid was collected, with a purity of 97.7% and a yield of 70.6%.

[0248] Example 47: Synthesis of Squalane

[0249] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add Pd(CF3CO2)2 (1.6 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for about 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >82.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 153.9g of a clear, transparent, colorless liquid was collected, with a purity of 95.9% and a yield of 71.7%.

[0250] Example 48: Synthesis of Squalane

[0251] Add β-farnesene (200.0 g, 1 eq) and isopropanol (600 mL, 3V) to a reaction flask, purge with nitrogen, and stir for 30 minutes. Then add XPhos Pd G3 (4.1 g, 0.005 eq) and sodium formate (20 g, 0.3 eq) sequentially, and stir. Under nitrogen protection, heat to 80-85℃ and stir for approximately 8 hours until the reaction is complete. Stop heating and add 8 g of activated carbon (4% of the mass of β-farnesene) to the reaction solution containing isosqualene and squalene for adsorption. Stir for 5 hours and allow to cool naturally to room temperature. After the activated carbon adsorption time is complete, filter the decolorized reaction solution by pressure. Wash the filter cake with a small amount of isopropanol. Transfer the filtrate to a flask, add isopropanol, stir for 10 minutes, and let stand for 10 minutes. Separate the lower brown layer (0.36% of the total volume) and transfer the upper layer to a clean stainless steel hydrogenation reactor. Nitrogen gas (0.3 bar) was introduced into the reactor, and the pressure was released to atmospheric pressure. This nitrogen purging was repeated three times. Then, hydrogen gas (3.0 bar) was introduced into the stainless steel reactor. The reactor was sealed, and the pressure was maintained at a constant level for 30 minutes, indicating good sealing. The stainless steel reactor lid was opened, and under nitrogen protection, 14 g of 5% wet palladium on carbon was added, along with isosqualene and the squalene organic phase. The reactor lid was closed, and nitrogen gas (0.3 bar) was introduced into the reactor for purging three times. Hydrogen gas was then introduced for purging three times (3.0 bar). Hydrogen gas was then introduced again, and the pressure was maintained at 3.0 bar for 30 minutes. The pressure remained constant, indicating good sealing. After hydrogen purging, the pressure was increased to 16-20 bar, and the power switch was turned on to heat the reactor to 75°C. Once the temperature stabilized at 75°C, the reaction was continued under pressure. The hydrogenation reaction lasted approximately 24 hours. Heating was then stopped, and the reactor temperature was cooled from 75°C to 45°C. The pressure relief valve was opened to release pressure, and once the pressure dropped to atmospheric pressure, the reactor lid was opened. A sample was taken for GC analysis; the squalane purity was >78.0%. The hydrogenation reaction solution was filtered, washed with a small amount of solvent, and the filter cake was reused with activated carbon. The filtrate was concentrated under reduced pressure, and the solvent was recovered. The concentrate was then used for distillation of squalane in a column. The concentrate was transferred to a single-necked flask, a small amount of boiling chips was added to prevent bumping, and a distillation column (12cm stainless steel Western column rings) was added. The oil pump maintained a vacuum of 250-350 Pa, and the heating mantle was used to heat the flask at 230-300°C (outer wall of the flask). When the temperature at the top of the distillation column reached 200-230°C, the distillate was the squalane fraction. 144.3g of a clear, transparent, colorless liquid was collected, with a purity of 96.3% and a yield of 67.5%.

[0252] The products prepared in Examples 1-48 were tested, and the results are shown in Tables 1 and 2.

[0253] Table 1

[0254] Table 2

[0255] The mono-configuration β-farnesene prepared by microbial fermentation primarily produces isosqualene, followed by squalene, under palladium catalysis. Impurities generated in the reaction only require small-scale adsorption with activated carbon, filtration, and liquid-liquid separation before being used in the next reaction step. In the next step, isosqualene and squalene can be converted to squalane. In this step, several isomers of isosqualene are converted into corresponding isosqualane and neosqualane. These impurities can be controlled to a low level through distillation. Under optimized experimental conditions, high-purity (>99%) squalane can be obtained in high yield.

[0256] Example 49: Preparation of squalane

[0257] (1) Preparation of diethylfarnesine

[0258] Add 86.4 g of diethylamine to a three-necked flask under nitrogen protection. Add 20.5 mL of n-butyllithium (2.5 M) dropwise under an ice-water bath. Heat to 55-60 °C, add 105 g of β-farnesene, and react at 75 °C for 2 h. Stop heating, cool to room temperature, add 600 mL of water to quench the reaction, and add 600 mL of petroleum ether. Stir for 10 min, extract three times, and evaporate the organic phase to dryness to obtain the crude product. Add 150 mL of petroleum ether and 75 mL of water to the crude product, add 15 mL of acetic acid, stir thoroughly, adjust the pH of the aqueous phase to 5-6, separate the layers, adjust the pH of the aqueous phase to >12 with 50% NaOH solution, extract three times with petroleum ether, and evaporate the organic phase to dryness to obtain a total of 123 g of product (GC purity 92%, yield 79%).

[0259] (2) Preparation of farnesyl chloride

[0260] 90 g of isopropyl chloroformate and 360 mL of toluene were added to a three-necked flask. Under nitrogen protection, the product from the first step (123 g) was slowly added dropwise in an ice bath (0 °C). The mixture was then heated to room temperature and reacted for 5 h. The reaction was quenched with 60 mL of methanol. After rotary evaporation, the product was extracted with petroleum ether, methanol, and water. The liquid phase was separated, and the organic phase was collected. Then, a water / methanol solution of 30 / 300 mL was added, followed by petroleum ether extraction. The liquid phase was separated, and the organic phase was collected and rotary evaporated to obtain 100 g of the product (GC purity 90%, yield 92%).

[0261] (3) Preparation of squalene

[0262] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0263] Reactant preparation: Magnesium shavings (2.5 g, 100 mmol) and elemental iodine (51 mg, 0.2 mmol) were added sequentially to a 250 mL three-necked flask, and nitrogen was used for protection. Farnesyl chloride (10 g, 41 mmol) was dissolved in 100 mL of tetrahydrofuran solution, and stirring was started. 10 mL of the tetrahydrofuran solution of farnesyl chloride was added dropwise to the above reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (0.3 mL, 0.65 g, 3.46 mmol). The reaction was successfully initiated. Finally, the remaining tetrahydrofuran solution of farnesyl chloride was added dropwise, and the temperature was controlled at 25 °C. The reaction solution was stirred at 25 °C under nitrogen protection for 3 hours until the reaction was complete.

[0264] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 200mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (100mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 8g of squalene (purity 92%, yield 86%).

[0265] (4) Preparation of squalane

[0266] Reactor feed: Squalene (8g, 17.91mmol), isopropanol (40mL), and 5% wet palladium on carbon (0.4g) obtained in the previous step were added sequentially to a 250mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then with hydrogen three times, and then with hydrogen (pressure 2.5-3.0bar). The reaction was stirred at 75℃ for 12h until the reaction was complete.

[0267] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 7.8 g of squalane (purity 93%, yield 95%).

[0268] Example 50: Preparation of squalane

[0269] (1) Preparation of farnesyl chloride

[0270] In a round-bottom flask, 210 g of all-trans farnesol obtained from microbial fermentation and 2 L of methyl tert-butyl ether were added. The reaction mixture was cooled to 0 °C. Then, 0.42 L of phosphorus trichloride was added dropwise. The reaction mixture was stirred at room temperature for 2 hours. After the farnesol was completely consumed, methanol was added to quench the reaction, and the mixture was evaporated to dryness, extracted, separated, and evaporated to dryness again. The resulting product (225 g) had a purity of 93% and a yield of 92%, and could be used directly in the next step without further purification.

[0271] (2) Preparation of squalene

[0272] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0273] Reactant preparation: Magnesium shavings (2.0 g, 82 mmol) and elemental iodine (102 mg, 0.4 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl chloride (10 g, 41 mmol) was dissolved in 100 mL of 2-methyltetrahydrofuran solution, and stirring was started. 10 mL of the farnesyl chloride in 2-methyltetrahydrofuran solution was added dropwise to the reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (0.15 mL, 0.32 g, 1.73 mmol). The reaction was successfully initiated. Finally, the remaining farnesyl chloride in 2-methyltetrahydrofuran solution was added dropwise. The temperature was maintained at 40 °C, and the reaction mixture was stirred for 5 hours under nitrogen protection at 40 °C until the reaction was complete.

[0274] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 200mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (100mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 7.2g of squalene (purity 90%, yield 76%).

[0275] (3) Preparation of squalane

[0276] Reactor feed: Squalene (7.2 g, 15.77 mmol), isopropanol (35 mL), and 5% wet palladium on carbon (0.36 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was complete.

[0277] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 7.0 g of squalane (purity 90%, yield 94%).

[0278] Example 51: Preparation of squalane

[0279] (1) Preparation of squalene

[0280] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0281] The preparation of farnesyl chloride is the same as in Example 49.

[0282] Reactant preparation: Magnesium shavings (0.8 g, 31 mmol) and elemental iodine (25 mg, 0.1 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl chloride (5 g, 21 mmol) was dissolved in 30 mL of diethyl ether solution, and stirring was started. 5 mL of the farnesyl chloride diethyl ether solution was added dropwise to the reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (18 μL, 39 mg, 0.21 mmol). The reaction was successfully initiated. Finally, the remaining farnesyl chloride diethyl ether solution was added dropwise. The temperature was maintained at 20 °C, and the reaction mixture was stirred for 2 hours under nitrogen protection at 20 °C until the reaction was complete.

[0283] Post-processing: Dilute hydrochloric acid aqueous solution (1N, 100mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with ether (50mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 4.1g of squalene (purity 95%, yield 91%).

[0284] (2) Preparation of squalane

[0285] Reactor feed: Squalene (4.1 g, 9.48 mmol), isopropanol (25 mL), and 5% wet palladium on carbon (0.2 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was completed.

[0286] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 4.1 g of squalane (purity 96%, yield 98%).

[0287] Example 52: Preparation of squalane

[0288] (1) Preparation of squalene

[0289] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0290] The preparation of farnesyl chloride is the same as in Example 49.

[0291] Reactant preparation: Magnesium shavings (1.0 g, 38 mmol) and elemental iodine (38 mg, 0.15 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl chloride (5 g, 21 mmol) was dissolved in 60 mL of methyl tert-butyl ether solution, and stirring was started. 8 mL of the farnesyl chloride methyl tert-butyl ether solution was added dropwise to the above reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (0.18 mL, 394 mg, 2.1 mmol). The reaction was successfully initiated. Finally, the remaining farnesyl chloride methyl tert-butyl ether solution was added dropwise. The temperature was controlled at 30 °C, and the reaction mixture was stirred at 35 °C under nitrogen protection for 2 hours until the reaction was complete.

[0292] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 100mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (50mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 3.3g of squalene (purity 87%, yield 67%).

[0293] (2) Preparation of squalane

[0294] Reactor feed: Squalene (3.3 g, 7.0 mmol), isopropanol (25 mL), and 5% wet palladium on carbon (0.2 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was complete.

[0295] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 3.1g of squalane (purity 86%, yield 90%).

[0296] Example 53: Preparation of squalane

[0297] (1) Preparation of bromine derivatives

[0298] Farnesol (50 g, 0.22 mol) was dissolved in MTBE (500 mL) at 0 °C. Phosphorus tribromide (30.4 g, 0.11 mol) was added dropwise to the mixture under N2 conditions at 0 °C. The mixture was stirred at 0 °C for 1 hour until the reaction was complete. The reaction mixture was slowly poured into 1250 mL of ice water, and 500 mL of MTBE was added. The MTBE phase was washed successively with water (500 mL x 3) and brine (250 mL), then dried over Na2SO4. The product, farnesyl bromide, was concentrated to obtain 64 g (purity 96%, yield 96%). No further purification was required; the product was used directly in the next step.

[0299] (2) Preparation of squalene

[0300] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0301] Reactant preparation: Magnesium shavings (1.2 g, 50 mmol) and elemental iodine (76 mg, 0.3 mmol) were added sequentially to a 250 mL three-necked flask, and nitrogen was used for protection. Farnesyl bromide (10 g, 35 mmol) was dissolved in 100 mL of tetrahydrofuran solution, and stirring was started. 10 mL of the tetrahydrofuran solution of farnesyl bromide was added dropwise to the reaction flask at room temperature, successfully initiating the reaction. Finally, the remaining tetrahydrofuran solution of farnesyl bromide was added dropwise, and the temperature was controlled at 25℃-40℃. The reaction solution was stirred at 40℃ under nitrogen protection for 2 hours until the reaction was complete.

[0302] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 200mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (100mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 7.0g of squalene (purity 95%, yield 92%).

[0303] (3) Preparation of squalane

[0304] Reactor feed: Squalene (7.0 g, 16.2 mmol), isopropanol (35 mL), and 5% wet palladium on carbon (0.35 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was complete.

[0305] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 7.1 g of squalane (purity 96%, yield 99%).

[0306] Example 54: Preparation of squalane

[0307] The preparation of farnesyl bromide is the same as in Example 53.

[0308] (1) Preparation of squalene

[0309] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0310] Reactant preparation: Magnesium shavings (1.7 g, 70 mmol) and elemental iodine (127 mg, 0.5 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl bromide (10 g, 35 mmol) was dissolved in 100 mL of 2-methyltetrahydrofuran solution. Stirring was started, and 15 mL of the farnesyl bromide-2-methyltetrahydrofuran solution was added dropwise to the reaction flask at room temperature. The reaction was successfully initiated. Finally, the remaining farnesyl bromide-2-methyltetrahydrofuran solution was added dropwise. The temperature was maintained at 40 °C, and the reaction mixture was stirred for 3 hours under nitrogen protection at 40 °C until the reaction was complete.

[0311] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 200mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (100mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 6.5g of squalene (purity 91%, yield 82%).

[0312] (2) Preparation of squalane

[0313] Reactor feed: Squalene (6.5 g, 14.4 mmol), isopropanol (35 mL), and 5% wet palladium on carbon (0.32 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was complete.

[0314] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 6.3g of squalane (purity 90%, yield 93%).

[0315] Example 55: Preparation of squalane

[0316] (1) Preparation of chlorinated products

[0317] Farnesol (50 g, 0.22 mol) was dissolved in MTBE (500 mL) at 0 °C. Phosphorus trichloride (15.1 g, 0.11 mol) was added dropwise to the mixture under N2 conditions at 0 °C. The reaction mixture was slowly heated to 20 °C and stirred at 20 °C for 1 hour until the reaction was complete. The reaction mixture was slowly poured into 1250 mL of ice water, and 500 mL of MTBE was added. The MTBE phase was washed successively with water (500 mL x 3) and brine (250 mL), then dried over Na2SO4. The product, farnesyl chloride (95% purity, 93% yield), was concentrated to obtain 53 g (95% purity, 93% yield). The product required no further purification and was used directly in the next step.

[0318] (2) Preparation of squalene

[0319] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0320] Reactant preparation: Magnesium shavings (1.9 g, 74 mmol) and elemental iodine (30 mg, 0.24 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl chloride (10 g, 42 mmol) was dissolved in 80 mL of diethyl ether solution, and stirring was started. 10 mL of the farnesyl chloride diethyl ether solution was added dropwise to the reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (43 μL, 94 mg, 0.50 mmol). The reaction was successfully initiated. Finally, the remaining farnesyl chloride diethyl ether solution was added dropwise. The temperature was maintained at 20 °C, and the reaction mixture was stirred for 2 hours under nitrogen protection at 20 °C until the reaction was complete.

[0321] Post-treatment: Dilute hydrochloric acid aqueous solution (1N, 100mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with ether (50mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 8.3g of squalene (purity 94%, yield 92%).

[0322] (3) Preparation of squalane

[0323] Reactor feed: Squalene (8.3 g, 14.4 mmol), isopropanol (42 mL), and 5% wet palladium on carbon (0.41 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was complete.

[0324] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 8g of squalane (purity 95%, yield 95%).

[0325] Example 56: Preparation of squalane

[0326] The preparation of farnesyl chloride is the same as in Example 55.

[0327] (1) Preparation of squalene

[0328] Pretreatment before reaction feeding: 1. Take an appropriate amount of magnesium shavings and use sandpaper to simply polish the surface until it is shiny; 2. Use an oil pump to evacuate the reaction flask and keep it under high temperature baking gun for ten minutes, then fill it with nitrogen. Repeat this evacuation and filling process three times to achieve anhydrous and oxygen-free conditions.

[0329] Reactant preparation: Magnesium shavings (2.2 g, 83.6 mmol) and elemental iodine (83.6 mg, 0.33 mmol) were added sequentially to a 250 mL three-necked flask, and the mixture was purged with nitrogen for protection. Farnesyl chloride (10 g, 42 mmol) was dissolved in 120 mL of methyl tert-butyl ether solution, and stirring was started. 12 mL of the farnesyl chloride methyl tert-butyl ether solution was added dropwise to the above reaction flask at room temperature, followed by the addition of 1,2-dibromoethane (0.40 mL, 867 mg, 4.6 mmol). The reaction was successfully initiated. Finally, the remaining farnesyl chloride methyl tert-butyl ether solution was added dropwise. The temperature was controlled at 30 °C, and the reaction mixture was stirred at 35 °C under nitrogen protection for 2 hours until the reaction was complete.

[0330] Post-processing: Dilute hydrochloric acid aqueous solution (1N, 150mL) was added dropwise to the reaction solution at room temperature. The mixture was extracted three times with methyl tert-butyl ether (100mL each time). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 6.5g of squalene (purity 86%, yield 66%).

[0331] (2) Preparation of squalane

[0332] Reactor feed: Squalene (6.5 g, 13.6 mmol), isopropanol (42 mL), and 5% wet palladium on carbon (0.41 g) obtained in the previous step were added sequentially to a 250 mL stainless steel hydrogenation reactor. The reactor lid was closed, and the reactor was purged with nitrogen three times, then purged with hydrogen three times, and then hydrogen was introduced again (pressure 2.5-3.0 bar). The reaction was stirred at 75 °C for 12 h until the reaction was completed.

[0333] Post-processing: Cool the reaction solution to room temperature, filter the reaction solution with diatomaceous earth, and concentrate the filtrate to obtain 6.2 g of squalane (purity 85%, yield 92%).

[0334] Example 57: Structural Characterization of Squalane

[0335] The squalane product of this invention was structurally characterized by proton NMR spectroscopy, carbon NMR spectroscopy, and infrared spectroscopy.

[0336] 1 H NMR(400MHz, CDCl3)δ:0.84-0.88(24H,m),1.05-1.29(36H,m),1.53-1.55-1.06(2H,m).

[0337] 13C NMR(75MHz, CDCl3)δ:19.71,19.73,19.77,19.79,22.64,22.73,24.49,24.65,24.83,27.46,27.84,27.99, 28.16,29.73,32.60,32.78,32.81,37.13,37.23,37.13,37.23,37.31,37.41,37.42,37.44,37.47,39.39.

[0338] IR(KBr)v: 6000-4500cm -1 .

[0339] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing squalane, characterized in that, The preparation method includes the following steps: (1) In a solvent, β-farnesene undergoes a dimerization reaction in the presence of a palladium catalyst and an alkaline medium to obtain a mixture; (2) In the presence of a second catalyst, the mixture obtained in step (1) is hydrogenated and reduced to obtain the prepared product; or (I) β-farnesene reacts with diethylamine under alkaline conditions to yield farnesyldiethylamine; (II) In the presence of chloroformate, the farnesyl diethylamine reacts to generate farnesyl chloride; (III) In an organic solvent, in the presence of an initiator, the farnesyl chloride reacts with metallic magnesium to generate squalene; (IV) The squalene is hydrogenated and reduced to squalane by a catalyst; or (i) All-trans farnesol reacts with a halogenating agent to form farnesyl halides; (ii) In an organic solvent, in the presence of an initiator, the farnesyl halide reacts with metallic magnesium to generate squalene; (iii) The squalene is hydrogenated and reduced to squalane by a catalyst; The chemical formula of the squalane is shown below: The chemical formula of the all-trans farnesol is shown below: The chemical formula of the farnesyl halide is shown below: Where X is a halogen, preferably Br or Cl.

2. The preparation method according to claim 1, characterized in that, Based on the total weight of the product prepared in step (2), the product includes: squalane ≥ 92.0 wt%, isosqualane and neosqualane ≤ 4.5 wt%; The chemical formula of the isosqualane is shown below: The chemical formula of the new squalane is shown below:

3. The preparation method according to claim 1, characterized in that, The initiator in step (III) includes at least one of elemental iodine and 1,2-dibromoethane; and / or The organic solvent in step (III) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether; and / or The metallic magnesium in step (III) includes at least one of magnesium powder, magnesium shavings, or magnesium strips; and / or The reaction temperature in step (III) is -5℃ to 80℃.

4. The preparation method according to claim 3, characterized in that, Based on the molar equivalent of farnesyl chloride described in step (III), the initiator described in step (III) is elemental iodine, with a molar amount ranging from 0 to 0.01; and / or Based on the molar equivalent of farnesyl chloride described in step (III), the initiator described in step (III) is 1,2-dibromoethane, with a molar amount of 0.001-0.1; and / or Based on the molar equivalent of farnesyl chloride described in step (III), the molar amount of metallic magnesium described in step (III) ranges from 1.0 to 3.0; and / or Based on the mass of farnesyl chloride described in step (III), the ratio of the volume of the organic solvent to the mass of farnesyl chloride is 3-20:

1.

5. The preparation method according to claim 1, characterized in that, The halogenated reagent in step (i) is at least one of phosphorus trichloride and phosphorus tribromide; and / or The reaction temperature in step (i) is -10℃ to 30℃; and / or The organic solvent in step (ii) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether; and / or The initiator in step (ii) includes at least one of elemental iodine and 1,2-dibromoethane; and / or The metallic magnesium in step (ii) includes at least one of magnesium powder, magnesium shavings, or magnesium strips; and / or The reaction temperature in step (ii) is -5℃ to 40℃.

6. The preparation method according to claim 5, characterized in that, Based on the molar equivalent of the farnesyl halide described in step (ii), the initiator described in step (ii) is elemental iodine, with a molar amount ranging from 0 to 0.01; and / or Based on the molar equivalent of the farnesyl halide described in step (ii), the initiator described in step (ii) is 1,2-dibromoethane, with a molar amount ranging from 0 to 0.1; and / or Based on the mass of the farnesyl halide described in step (ii), the volume of the organic solvent described in step (ii) and the volume of the farnesyl halide... The mass ratio of the objects is 3-20:

1.

7. The preparation method according to any one of claims 1-2, characterized in that, The palladium catalyst in step (1) is selected from one or more of the following: XPhos Pd G4, BrettPhos Pd G4, RuPhos Pd G4, G2, tBuBrettPhos-Pd-G3, Ephos Pd G4, AdBrettPhos Pd G3, RockPhos Pd G3, Pd-PEPPSI-IHept Cl, Pd-PEPPSI-IPentC, Pd-PEPPSI-IPr Cl, PEPPSI-IPENT, Pd(dppf)Cl2, RuPhos Pd G1, Pd(CF3CO2)2, PdCl2(Amphos)2, (DPPF)PdCl2·CH2Cl2, Pd(t-Bu3P)2, XPhos Pd G3 or PdCl2(dtbpf).

8. The preparation method according to claim 7, characterized in that, The palladium catalyst in step (1) is selected from XPhos Pd G4 and / or Ad2nBuP Pd G3, preferably Ad2nBuP Pd G3.

9. The preparation method according to claim 1, characterized in that, The solvent includes a protic solvent, preferably at least one of isopropanol, ethanol, tert-butanol or tert-amyl alcohol, more preferably isopropanol.

10. The preparation method according to claim 1, characterized in that, The alkaline medium in step (1) includes sodium formate, potassium formate, sodium acetate and / or potassium acetate, preferably sodium formate.

11. The preparation method according to claim 1, characterized in that, The second catalyst is a hydrogenation reduction catalyst, preferably at least one of palladium catalyst, nickel catalyst, platinum catalyst, Raney nickel, Wilkinson catalyst, copper chromite, rhodium catalyst or ruthenium catalyst, more preferably palladium catalyst.

12. The preparation method according to claim 1, characterized in that, The reactions in steps (1) and (2) are carried out in an inert gas atmosphere; And / or, the reaction temperature in step (1) is 80-85℃; And / or, the reaction time for step (1) is 1-10 hours; And / or, step (1) may further include activated carbon adsorption.

13. The preparation method according to claim 12, characterized in that, The inert gas includes argon, nitrogen, helium and / or neon, with nitrogen being preferred; And / or, the reaction time for step (1) is 8 hours; And / or, based on the mass of β-farnesene, the activated carbon comprises 1%-15% by mass.

14. The preparation method according to claim 1, characterized in that, The molar equivalent ratio of the palladium catalyst and β-farnesene in step (1) is (0.001-0.05):1, preferably 0.005:

1.

15. The preparation method according to claim 1, characterized in that, The molar equivalent ratio of the alkaline medium to β-farnesene in step (1) is (0.1-0.5):1, preferably 0.3:

1.

16. Use of squalane obtained by any of the preparation methods according to claims 1-15 in the preparation of cosmetics or cosmetic ingredients.

17. A method for preparing isosqualene, characterized in that, The preparation method includes the following steps: In a solvent, β-farnesene undergoes a dimerization reaction in the presence of a palladium catalyst and an alkaline medium to yield isosqualene; The chemical formula of the isosqualene is shown below:

18. The preparation method according to claim 17, characterized in that, The palladium catalyst is selected from one or more of the following: XPhos Pd G4, BrettPhos Pd G4, RuPhos Pd G4, G2, tBuBrettPhos-Pd-G3, Ephos Pd G4, AdBrettPhos Pd G3, RockPhos Pd G3, Pd-PEPPSI-IHept Cl, Pd-PEPPSI-IPentC, Pd-PEPPSI-IPr Cl, PEPPSI-IPENT, Pd(dppf)Cl2, RuPhos Pd G1, Pd(CF3CO2)2, PdCl2(Amphos)2, (DPPF)PdCl2·CH2Cl2, Pd(t-Bu3P)2, XPhos Pd G3 or PdCl2(dtbpf), preferably XPhos Pd G4 and / or Ad2nBuP Pd G3, more preferably Ad2nBuP Pd G3.

19. The preparation method according to claim 18, characterized in that, The solvent includes a protic solvent, preferably at least one of isopropanol, ethanol, tert-butanol or tert-amyl alcohol, more preferably isopropanol.

20. The preparation method according to any one of claims 17-19, characterized in that, The alkaline medium includes at least one of sodium formate, potassium formate, sodium acetate, or potassium acetate, preferably sodium formate.

21. The preparation method according to claim 17, characterized in that, The reaction is carried out in an inert gas atmosphere; And / or, the reaction temperature is 80-85℃; And / or, the reaction time is 1-10 hours; And / or, the preparation method further includes activated carbon adsorption.

22. The preparation method according to claim 17, characterized in that, The molar equivalent ratio of the catalyst to β-farnesene is (0.001-0.05):1, preferably 0.005:

1.

23. The preparation method according to claim 17, characterized in that, The molar equivalent ratio of the alkaline medium to β-farnesene is (0.1-0.5):1, preferably 0.3:

1.

24. Use of isosqualene obtained by any of the preparation methods according to claims 17-23 in the preparation of squalane.

25. A method for preparing squalene, characterized in that, The preparation method includes the following steps: I) β-Farnese reacts with diethylamine under alkaline conditions to yield farnesyldiethylamine; II) In the presence of chloroformate, the farnesyl diethylamine reacts to generate farnesyl chloride; Ⅲ) In an organic solvent, in the presence of an initiator, the farnesyl chloride reacts with metallic magnesium to generate squalene; or i) All-trans farnesol reacts with a halogenating agent to form farnesyl halides; ii) In an organic solvent, in the presence of an initiator, the farnesyl halide reacts with metallic magnesium to generate squalene.

26. The preparation method according to claim 25, characterized in that, Step III) The initiator includes at least one of elemental iodine and 1,2-dibromoethane; and / or Step III) The organic solvent includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether; and / or Step III) The metallic magnesium includes at least one of magnesium powder, magnesium shavings, or magnesium strips; and / or The reaction temperature in step III) is -5℃ to 80℃.

27. The preparation method according to claim 26, characterized in that, Based on the molar equivalent of farnesyl chloride described in step III), the initiator described in step III) is elemental iodine, with a molar amount ranging from 0 to 0.01; and / or Based on the molar equivalent of farnesyl chloride described in step III), the initiator described in step III) is 1,2-dibromoethane, with a molar amount ranging from 0.001 to 0.1; and / or Based on the molar equivalent of farnesyl chloride described in step III), the molar amount of metallic magnesium described in step III) ranges from 1.0 to 3.0; and / or Based on the mass of farnesyl chloride described in step III), the ratio of the volume of the organic solvent to the mass of farnesyl chloride is 3-20:

1.

28. The preparation method according to claim 25, characterized in that, The halogenated reagent in step i) is at least one of phosphorus trichloride and phosphorus tribromide; and / or The reaction temperature in step i) is -10℃ to 30℃; and / or The organic solvent in step ii) includes at least one of diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, and methyl tert-butyl ether; and / or The initiator in step ii) includes at least one of elemental iodine and 1,2-dibromoethane; and / or Step ii) The metallic magnesium includes at least one of magnesium powder, magnesium shavings, or magnesium strips; and / or The reaction temperature in step ii) is -5℃ to 40℃.

29. The preparation method according to claim 28, characterized in that, Based on the molar equivalent of the farnesyl halide described in step ii), the initiator described in step ii) is elemental iodine, with a molar amount ranging from 0 to 0.01; and / or Based on the molar equivalent of the farnesyl halide described in step ii), the initiator described in step ii) is 1,2-dibromoethane, with a molar amount ranging from 0 to 0.1; and / or Based on the mass of the farnesyl halide described in step ii), the ratio of the volume of the organic solvent in step ii) to the mass of the farnesyl halide is 3-20:1.

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