Biphenyl pyrogallol compounds, their preparation methods and uses

Abstract

This invention discloses a biphenyl pyrogallol compound having the structure shown in formula (I). The biphenyl pyrogallol compound provided by this invention is an important intermediate for the synthesis of tripentate phosphite ligands of the biphenyl skeleton, playing a crucial role in hydroformylation reactions and their industrial applications. This invention also provides various methods for preparing biphenyl pyrogallol compounds, including an oxidative coupling method. The oxidative coupling method provided by this invention allows for the one-step synthesis of biphenyl pyrogallol compounds, offering advantages such as readily available and inexpensive catalysts, simple operation, good yield, low cost, and the ability to produce on a large scale.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, specifically the design of biphenyl pyrogallol compounds, their preparation methods, and applications. Background Technology

[0002] Biphephosphonates are widely used as ligands in metal-catalyzed organic reactions and chemical applications. For example, bidentate phosphite ligands derived from biphenyl compounds have been widely reported and commercialized by major international chemical companies such as BASF, Dow, Shell, and Eastman, as well as by research groups, in hydroformylation reactions. Using olefins such as propylene as raw materials, and carbon monoxide and hydrogen as feedstocks, hydroformylation reactions in the presence of metal catalyst precursors and ligands can convert to butyraldehyde or other aldehydes. Aldehydes can be readily converted into corresponding alcohols, carboxylic acids, esters, imines, and other compounds with important applications in organic synthesis. Aldehydes synthesized via hydroformylation are now produced on a large scale in industrial production, with annual production reaching 10 million tons. The type of catalyst or ligand significantly affects the substrate suitability, reaction conditions, and results of the hydroformylation reaction. Therefore, developing novel biphenyl-based phosphite ligands, developing efficient preparation methods, and providing inexpensive and readily available ligand raw materials are of great importance.

[0003] Biphenyl compounds are important intermediates in the preparation of phosphite ligands for the biphenyl skeleton, and are usually obtained by coupling reactions of phenolic compounds. A coupling reaction is a process in which two organic chemical units undergo a chemical reaction to yield an organic molecule, including radical coupling reactions and transition metal-catalyzed coupling reactions. Classical coupling reactions such as Suzuki, Heck, Sonogashira, Stille, Kumada, Negishi, and Hiyama are coupling reactions between organometallic reagents and pre-activated haloalkanes. While haloalkanes require pre-preparation, increasing the reaction steps and experimental procedures, this method is applicable to couplings between homo- and hetero-aryl groups. Furthermore, the coordination compound of the noble metal palladium, Pd(PPh3)4, is the most commonly used catalyst for this type of reaction; other catalysts include PdCl2(PPh3)2 and PdCl2(MeCN)2.

[0004] Oxidative coupling reactions are a class of oxidation reactions in which a low-valence carbon atom in a reactant is converted into a high-valence carbon atom compound. This reaction requires the presence of an oxidizing agent to directly couple two nucleophiles, enabling the direct activation and functionalization of the CH bonds in alkenes, alkynes, and aromatics. Oxidative coupling reactions play an increasingly important role in the synthesis of organic intermediates in pharmaceuticals, pesticides, chemicals, and materials. However, coupling reactions between different aryl groups are challenging due to low selectivity.

[0005] Oxidative coupling reactions catalyzed by inexpensive metals can be traced back to 1869, when Glaser reported the preparation of conjugated diyne via the self-oxidative coupling of terminal alkynes: using CuCl as a catalyst, 1,3-diyne was obtained from phenylacetylene in air in a mixed solvent of ammonia and ethanol. In 1953, Albert studied the oxidative self-coupling reactions of various 3,4,5-trialkylphenols under K₂Cr₂O₇ / H₂SO₄ catalysis, obtaining different types of biphenylhydrazine with yields ranging from 23% to 76%. Under different oxidants (K₂Cr₂O₇, benzoyl peroxide, MCPBA / FeCl₃) and reaction conditions, Researchers reported the self-oxidative coupling of a series of commercially available compounds, including p-hydroxyphenylpropionate and 3-tert-butyl-4-hydroxyphenylpropionate, with yields reaching 22-32%. In 1962, Hay used O2 as an oxidant and catalytic amounts of TMEDA and CuCl to catalyze the self-coupling of terminal alkynes. Noji used CuCl(OH)TMEDA as a catalyst to oxidize 2-naphthol in air in dichloromethane solution to obtain binaphthol, with a chemical yield of 90-96%; Deuβen refluxed 2-naphthol and FeCl3 in tetrahydrofuran, achieving a yield of 54%. In addition, numerous patent documents, such as US3210384, US481589, WO99 / 46227A1, WO9946227, JP2002069022, US4101561, US4070383, J.Chem.Soc.C 1971,2967, J.Org.Chem.1983,48,4948, have reported the self-coupling of various alkyl-substituted phenols catalyzed by Cu / O2 complexes to prepare biphenyl hydrochloride, with yields ranging from approximately 35% to 95%.

[0006] The core of oxidative coupling is the catalytic metal source and oxidant. Compared with traditional coupling reactions, oxidative coupling does not require the prior preparation of halogenated raw materials and has advantages such as shortening reaction steps and atom economy. However, for coupling between different aryl or phenolic compounds, this method currently has low selectivity and unsatisfactory yield, and there are few reports on it. Summary of the Invention

[0007] definition

[0008] For ease of understanding of the present invention, unless otherwise stated, some terms, abbreviations or other acronyms used herein are defined as follows.

[0009] "alkyl", when used alone or in combination with other groups, represents a saturated straight-chain or branched group containing 1 to 8 carbon atoms, such as: methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, n-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, and n-decyl, etc.

[0010] "Alkenyl", used alone or in combination with other groups, represents a straight-chain or branched group containing 1 to 8 carbon atoms and unsaturated double bonds, including straight-chain or branched dienes, such as: vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1,3-butadiene, 1,3-pentadiene, 2-methyl-1,3-butadiene, etc.

[0011] "Cycloalkyl" refers to a 3-7 membered carbon ring group, whether used alone or in combination with other groups, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0012] "Aryl" or "aromatic" refers to an aromatic carbocyclic group containing one, two, or three rings, optionally substituted, which are linked by bonds or fusion, such as phenyl, biphenyl, naphthyl, tetrahydronaphthalene, and dihydroindene, which may be further substituted by other aryl or aryl-containing substituents.

[0013] "Heteroaryl" or "heteroaromatic" refers to an aromatic heterocyclic group containing one or two optionally substituted rings, whether used alone or in combination with other groups. The heterocycle has one to three heteroatoms, which may be the same or different and are selected from O, N, and S, such as phenyl, biphenyl, naphthyl, tetrahydronaphthalene, and dihydroindene. It may be further substituted by other aryl groups or aryl-containing substituents.

[0014] As used herein, the term "substituted" in describing a compound or chemical moiety means that at least one hydrogen atom of the compound or chemical moiety is replaced by a second chemical moiety. Non-limiting examples of substituents include those present in the exemplary compounds and embodiments disclosed herein, as well as fluorine, chlorine, bromine, iodine; oxo; imine, nitro; cyano, isocyano, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, cycloalkenyl, alkynyl; lower alkoxy, aryloxy; acyl, thiocarbonyl, sulfonyl; amide, sulfonamide; ketone; aldehyde; ester, sulfonate; haloalkyl (e.g., difluoromethyl, trifluoroalkyl ... Fluoromethyl); can be a monocyclic, fused, or unfused polycyclic carbocycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl); or can be a monocyclic, fused, or unfused polycyclic heterocyclic alkyl group (e.g., pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiazinyl); or can be a monocyclic or fused aryl group (e.g., phenyl, naphthyl, thiazolyl, oxazolyl, imidazolel, isoxazolyl, pyrrolidinyl, pyrazolyl, triazolyl, tetrazolyl, thiopheneyl, ... Furanyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazoloneyl, benzimidazolyl, benzofuranyl, benzothiophenylyl, benzothiazolyl, benzoxazoleyl, benzoisoxazoleyl); or may also be: aryl-lower alkyl; -CHO; -CO (alkyl); -CO (aryl); -CO2 (alkyl); -CO2 (aryl); -CONH2; -SO2NH 2; -OCH2CONH2; -OCHF2; -OCF3; -CF3; -N(alkyl)(aryl); -N(aryl)2; Furthermore, when the substituent is oxygen, it means that two hydrogen atoms on the same or different carbons are replaced by the same oxygen atom to form a carbonyl or cyclic ether, such as ketone carbonyl, aldehyde carbonyl, ester carbonyl, amide carbonyl, ethylene oxide, etc.; In addition, these moieties may also be optionally replaced by fused ring structures or bridges (e.g., -OCH2O-). In this invention, it is preferred that one, two, or three substituents independently selected from halogen, nitro, cyano, alkyl, alkoxy or perhalogen substitution are used, such as trifluoromethyl, pentafluoroethyl, and when the substituent contains hydrogen, the above-mentioned substituents may be optionally further substituted by substituents selected from such groups.

[0015] When used herein to describe a compound or chemical part as “independently being”, it should be understood that the plurality of compounds or chemical parts specified before the term should enjoy the range of choices provided thereafter without interference with each other, and should not be understood as a limitation on any spatial connection between the individual groups; spatial connection is expressed herein by terms such as “independently” and “connected”; these should be distinguished; and in this invention, “independently being” has substantially the same meaning as “each independently being” and “each independently selected”. Invention Details

[0017] To address the shortcomings of existing technologies, the present invention aims to provide a novel biphenyl pyrogallol compound, its preparation method, and its applications. The biphenyl pyrogallol compound provided by this invention can be prepared by various methods. The oxidative coupling method provided by this invention allows for the one-step synthesis of the biphenyl pyrogallol compound, offering advantages such as readily available and inexpensive catalysts, simple operation, good yield, low cost, and the ability to be prepared on a large scale. Furthermore, the biphenyl pyrogallol compound provided by this invention is an important intermediate in the synthesis of tridentate phosphite ligands of the biphenyl skeleton, playing a crucial role in hydroformylation reactions and their industrial applications.

[0018] To achieve the objectives of this invention, one aspect of this invention provides a biphenyl pyrogallol compound having the structure shown in formula (I).

[0019]

[0020] in,

[0021] R 1 ~R 7 Each group is independently H, D, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 alkylthio.

[0022] In some embodiments, R 1 ~R 7 Each group is independently H, D, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, or methylthio.

[0023] In some embodiments, R 1 ~R 3 All are H;

[0024] In some embodiments, R 1 R 3 They are, independently, methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethylthio, isopropoxy, and tert-butylthio;

[0025] In some embodiments, R 2 It is isopropyl, tert-butyl, isopropoxy, or tert-butoxy;

[0026] In some embodiments, R 4 ~R 7 All are H;

[0027] In some embodiments, R 5 and R 7 At least one of them is independently methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethio, isopropylthio, or tert-butylthio.

[0028] In some embodiments, R 6 It is isopropyl, isopropoxy, tert-butyl, and tert-butoxy;

[0029] In some embodiments, R 4 For H;

[0030] In some embodiments, R 4 It is methyl or methoxy, and R 6 and R 7 At least one of them is a non-hydrogen substituent;

[0031] In some embodiments, R 1 With R 3 The same, preferably, R 1 With R 3 Both are methyl and tert-butyl;

[0032] In some embodiments, R 5 With R 7 The same, preferably, R 5 With R 7 Both are methyl and tert-butyl.

[0033] In some embodiments, the biphenyl pyrogallol compound is selected from one of the following structures:

[0034]

[0035]

[0036] To achieve the objectives of this invention, a second aspect of this invention provides a method for preparing the aforementioned biphenyl pyrogallol compound, wherein compound (I) is prepared by oxidative coupling of compound (II) and compound (III) in a solvent in the presence of a catalyst and an oxidant.

[0037]

[0038] in,

[0039] R 1 ~R 7 The definitions of each group are as described above.

[0040] The catalyst is a mixture of an acid, a metal complex, or a metal salt that can form a metal complex with an organic base.

[0041] In some embodiments, the acid is selected from one or more of H2SO4, HPF6, HCl, and HNO3.

[0042] In some embodiments, the metal complex is a Cu complex, and the metal salt is a Cu salt.

[0043] In some embodiments, the Cu complex is one or a mixture of [Cu(MeCN)4][PF6], CuCl(OH)(TMEDA), CuBr(OH)(TMEDA), Cu(TMEDA)Cl2, and Cu(Et3N)Cl.

[0044] In some embodiments, the Cu salt is one or a mixture of CuCl, CuCl2, Cu(OTf)2, CuI, and CuSO4.

[0045] In some embodiments, the organic base is one or more of TMEDA, DTEDA, TMPDA, DMAEA, and TEEDA.

[0046] In some embodiments, the oxidant is one or a combination of H2O2, O2, O3, tBuOOH, K2Cr2O7, CrO3, KMnO4, MnO2, KClO4, KHSO5, and FeCl3.

[0047] In some embodiments, the solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane, acetic acid, acetic anhydride, THF, diethyl ether, 2-methyltetrahydrofuran, dioxane, water, or a combination thereof.

[0048] In some embodiments, the catalyst is an acid, the oxidant is K2Cr2O7, CrO3, KMnO4, MnO2, KClO4, KHSO5, FeCl3, and / or the solvent is an aqueous solution of acetic acid.

[0049] In some embodiments, a combination of acid HNO3 and oxidant FeCl3 or a combination of acid HCl and oxidant KClO4 is preferred.

[0050] In some embodiments, the catalyst is an acid, and the molar percentage of the oxidant to the compound of formula (III) is 30–80 mol%.

[0051] In some embodiments, the catalyst is an acid, and the molar percentage of the acid to the compound of formula (III) is 0.5–10 mol%, preferably 2–8 mol%.

[0052] In some embodiments, the catalyst is an acid, and the method for preparing the biphenyl pyrogallol compound includes the following process steps to achieve kilogram-scale preparation:

[0053] (a) The oxidizing agent dissolves in water to form a first solution;

[0054] (b) Dissolve the compound of formula (II), the compound of formula (III), and the acid in a solvent to form a second solution;

[0055] (c) The second solution formed in step (b) is added dropwise to the first solution in step (a) at 40–50 °C to obtain a mixture containing compound (I).

[0056] In some embodiments, the catalyst is a metal complex or a mixture of a metal salt that can form a metal complex and an organic base, the oxidant is H2O2, tBuOOH, KHSO5, O2 or O3, and / or the solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane, or a mixture thereof with water.

[0057] In some embodiments, a combination of a metal salt, CuCl, CuCl2, or Cu(OTf)2, and an organic base, TMEDA or TMPDA, is preferred.

[0058] In some embodiments, the preferred metal complex is [Cu(MeCN)4][PF6].

[0059] In some embodiments, the molar percentage of the metal complex relative to the compound of formula (III) is 0.5% to 10%, preferably 2% to 4%.

[0060] In some embodiments, the molar percentage of the metal salt relative to the compound of formula (III) is 0.5% to 10%, preferably 2% to 4%, and the molar ratio of the metal salt to the organic base is 1:1 to 10:1, preferably 2:1 to 5:1.

[0061] In some embodiments, the catalyst is a metal complex or a mixture of a metal salt capable of forming a metal complex and an organic base, and the method for preparing the biphenyl pyrogallol compound includes the following process steps to achieve kilogram-scale preparation:

[0062] (a) The metal salt and organic base dissolve in the solvent to form the first solution;

[0063] (b) Dissolve the compound of formula (II) and the compound of formula (III) in a solvent to form a second solution;

[0064] (c) Make the first solution formed in step (a) come into full contact with the oxidant, and add the second solution formed in step (b) dropwise into the first solution in step (a) at 30-60°C to obtain a mixture containing compound (I);

[0065] In some embodiments, the process of bringing the first solution formed in step (a) into full contact with the oxidant can be achieved by introducing a gaseous oxidant into the first solution formed in step (a), or by exposing the first solution formed in step (a) directly to air until the catalyst color changes from light to dark, indicating that the solution is saturated with oxygen, or by adding an oxidant to the first solution formed in step (a).

[0066] In some embodiments, the method for preparing biphenyl pyrogallol compounds at the kilogram-scale further includes the following process steps:

[0067] (d) When the mixture in step (c) contains a large amount of precipitated solids, the solids are separated by filtration or centrifugation; otherwise, the solvent in the mixture in step (c) is evaporated to obtain a crude product, and then the solids are precipitated by a methanol / water mixed solvent with a volume ratio of 2:1 to 4:1; preferably, the ratio of the methanol / water mixed solvent is 2:1 to 3:1.

[0068] In some embodiments, the ratio of compound (II) to compound (III) is 5:1 to 1:5, preferably 3:1 to 1:3.

[0069] In some embodiments, the reaction temperature of the oxidative coupling is -10 to 60°C; when an acid is used as a catalyst, the preferred reaction temperature is 40 to 50°C; when a metal complex or a mixture of a metal salt that can form a metal complex and an organic base is used as a catalyst, the preferred reaction temperature is 30 to 60°C.

[0070] To achieve the objectives of this invention, a third aspect of this invention also provides one of the following methods for preparing the aforementioned biphenyl pyrogallol compound.

[0071] Method (1)

[0072]

[0073] Method (2)

[0074]

[0075] Method (3)

[0076]

[0077] in,

[0078] R 1 ~R 7 The definitions of each group are as described above.

[0079] R 8 ~R 10 At least one of the groups is methyl.

[0080] Compound (IV) can be demethylated to obtain compound (I) under the following conditions: the demethylation reaction conditions are conventional methyl ether demethylation reaction conditions in the art, including but not limited to BBr3 / DCM, AlCl3 / DCM, 48% HBr aqueous solution, pyridine hydrochloride, AlBr3 / EtSH, and AlCl3 / EtSH.

[0081] In some embodiments, the catalytic precursor in method (2) is Pd(OAc)2;

[0082] In some embodiments, the ligand in method (2) is XPhos or BI-DIME;

[0083]

[0084] In some embodiments, the alkali metal salt in method (2) is one or a mixture of K2CO3, Na2CO3, K3PO4 or Na3PO4.

[0085] In some embodiments, the catalyst, oxidant, and solvent in method (3) are defined in the same way as in the preparation method of the biphenyl pyrogallol compound described in the second aspect above.

[0086] To achieve the objectives of this invention, a fourth aspect of this invention also provides the use of the aforementioned pyrogallol compounds in the preparation of tripenteric phosphite ligand compounds having a pyrogallol skeleton.

[0087] In some embodiments, the tripentate phosphite ligand compound is composed of the aforementioned biphenyl pyrogallol compound and Cl-PR. 11 R 12 It is prepared in an organic solvent under the action of an alkali, wherein...

[0088] R 11 R 12 Each is independently alkyl, aryl, heteroaryl, or OR 13 C(=O)OR 14 OC(=O)R 15 R 11 R 12 It can be directly bonded or bridged by 1 to 3 atoms to form a 5 to 10-membered cyclic group of phosphorus heterogeneity, which is a monocyclic ring or participates in the formation of a fused ring, wherein the 1 to 3 atoms can be substituted or are part of an aromatic ring;

[0089] Among them, R 13 R 14 R 15 Each is independently alkyl, aryl, or when R 11 R 12 When connected, R 13 R 14 R 15 It may not exist;

[0090] R 11 R 12In this compound, each aryl group is optionally substituted with one or more groups independently selected from F, Cl, Br, I, CF3, NO2, C1-C4 alkyl, phenyl C1-C4 alkyl, and C1-C4 alkoxy groups, and each alkyl group is optionally substituted with one or more groups independently selected from F, Cl, Br, I, CF3, phenyl, phenoxy, and C1-C4 alkoxy groups.

[0091] In some embodiments, the base is n-butyllithium, diisopropylethylamine, ethylenediamine, diethylamine, triethylamine, or tri-n-butylamine.

[0092] In some embodiments, the organic solvent is tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, methyl tert-butyl ether, or dioxane.

[0093] In some embodiments, R 11 R 12 Each of the following is independently: O, C(=O)O, OC(=O), C1-C6 alkoxy, phenyl, phenoxy, naphthyl, naphthoxy, tetrahydronaphthyl, tetrahydronaphthoxy, wherein each of the phenyl, phenoxy, naphthyl, naphthoxy, tetrahydronaphthyl, and tetrahydronaphthoxy groups is optionally substituted by one or more groups independently selected from F, Cl, Br, I, CF3, NO2, methyl, isopropyl, tert-butyl, 2-phenylprop-2-yl, diphenylmethyl, diphenylethyl, methoxy, isopropoxy, and tert-butoxy, and the C1-C6 alkyl group is optionally substituted by one or more groups independently selected from F, Cl, Br, I, CF3, phenyl, phenoxy, methoxy, ethoxy, and isopropoxy; when R 11 R 12 When at least one of them is O, C (=O), O, or OC (=O), R 11 With R 12 Intuitive connection or bridge.

[0094] In some embodiments, R 11 With R 12 same.

[0095] In some embodiments, R 11 R 12 Directly connected or via O, S, CH2, CHCH3, CH2CH2, CH=CH, Bridge connecting.

[0096] In some embodiments, R 11 The following groups, whether substituted or unsubstituted: C1–C6 alkoxy, phenyl, phenoxy, naphthyl, naphthoxy, tetrahydronaphthyl, tetrahydronaphthoxy, R 12 is O, C(=O)O, OC(=O), and R 11 With R 12 Direct key connection.

[0097] In some embodiments, PR 11 R 12 It has one of the following structures:

[0098]

[0099] In some embodiments, the tripentate phosphite ligand compound has the structure shown in formula (X):

[0100]

[0101] in,

[0102] R 1 ~R 7 and R 11 R 12 The definitions of each group are as described above.

[0103] Beneficial effects:

[0104] The novel biphenyl pyrogallol compound provided by this invention can be prepared by various methods. Among them, the oxidative coupling method provided by this invention can synthesize biphenyl pyrogallol compound in one step with a yield of up to 60%, which is significantly higher or basically equivalent to the total yield of other multi-step preparation methods (about 10% for method (1) and about 48% for method (2)). However, even with comparable or slightly better yields, the oxidative coupling preparation method provided by this invention has a significantly shorter reaction step, the catalyst is inexpensive and readily available, the operation is simple, and there is no need for halogenation or preparation of boric acid intermediates, which has the advantages of higher atom economy and lower cost. In addition, it can be prepared on a large scale. Furthermore, the biphenyl pyrogallol compound provided by this invention is an important intermediate for the synthesis of tridentate phosphite ligands of the biphenyl skeleton, and has important value in hydroformylation reaction and its industrial applications. Attached Figure Description

[0105] Figure 1 This is a schematic diagram of the batch-type small-scale hydroformylation reaction equipment involved in Example 8 of the present invention. Detailed Implementation

[0106] The above-described approach of the present invention will be specifically described below through embodiments. It should be noted that these embodiments are only used to further illustrate the present invention and do not constitute any limitation on the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the content of the present invention.

[0107] Example 1 Preparation of 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa)

[0108] Step 1.1 Preparation of 4,6-di-tert-butyl-1,3-dihydroxybenzene (compound 12a)

[0109]

[0110] Compound 11a (55 g), tert-butanol (92.5 g), and concentrated sulfuric acid (70 g) were added sequentially to a 2 L three-necked flask. After the addition was complete, the reaction flask was purged under a nitrogen atmosphere and heated to reflux for 24 hours. The solvent was evaporated to dryness under reduced pressure, and 400 mL of water was added. The mixture was extracted three times with ethyl acetate (500 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue was subjected to rapid column chromatography to obtain 88 g of the target product 12a, with a yield of 80%.

[0111] 1 H NMR (400MHz, CDCl3): δ = 7.13 (s, 1H), 6.09 (s, 1H), 4.83 (s, 2H), 1.38 (s, 18H).

[0112] Step 1.2 Preparation of 4,6-di-tert-butyl-1,3-dimethoxybenzene (compound 13a)

[0113]

[0114] In a 2L four-necked round-bottom flask, 12a (31.5g), methyl iodide (101g), potassium carbonate (98.2g), and 0.5L acetone were added sequentially. The resulting reaction mixture was heated to 30°C and reacted for 4 hours. After concentration, 400mL of water was added, and the mixture was extracted three times with 600mL of ethyl acetate each time. The residue was subjected to column chromatography to give 30.5g of the target product 13a, with a yield of 86%.

[0115] 1 H NMR (400MHz, CDCl3): δ = 7.17 (s, 1H), 6.47 (s, 1H), 3.83 (s, 6H), 1.35 (s, 18H).

[0116] Step 1.3 Preparation of 1-bromo-3,5-di-tert-butylphenol (compound 22a)

[0117]

[0118] In a 2L four-necked round-bottom flask, 41.2g of 21a, 37.4g of NBS, and 0.3L of acetonitrile were added sequentially. The resulting reaction mixture was reacted at room temperature for 70 minutes. After concentration, 14g of potassium carbonate and 200mL of water were added, and the mixture was extracted three times with 600mL of ethyl acetate each time. The residue was subjected to column chromatography to give 42.7g of the target product 22a, with a yield of 75%.

[0119] 1H NMR (400MHz, CDCl3): δ = 9.67 (s, 1H), 7.24 (s, 1H), 7.11 (s, 1H), 3.83 (s, 6H), 1.41 (s, 9H), 1.28 (s, 9H).

[0120] Step 1.4 Preparation of 1-bromo-3,5-di-tert-butylmethoxybenzene (compound 23a)

[0121]

[0122] In a 2L four-necked round-bottom flask, 22a (62.0 g), DDMS (37.8 g), potassium carbonate (40.6 g), and 0.5 L of acetone were added sequentially. The resulting reaction mixture was stirred overnight at room temperature. The resulting reaction mixture was concentrated and extracted three times with ethyl acetate (500 mL each time). The residue was subjected to column chromatography to give 58.5 g of the target product 23a, in 90% yield.

[0123] 1 H NMR (400MHz, CDCl3): δ = 7.42 (s, 1H), 7.27 (s, 1H), 3.83 (s, 3H), 1.40 (s, 9H), 1.27 (s, 9H).

[0124] Step 1.5 Preparation of 2,2',6-trimethoxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 31aa) Preparation

[0125]

[0126] 5.5 g of 4,6-di-tert-butyl-1,3-dimethoxybenzene 13a was added to a dry Schlenk flask (1 L). The flask was then purged with nitrogen, and 100 mL of tetrahydrofuran and TMEDA (8.0 g) were added at room temperature. 10 mL of 2.5 M n-butyllithium solution was added dropwise, followed by 50 mL of a tetrahydrofuran solution of 1-bromo-3,5-di-tert-butylmethoxybenzene 23a (3.0 g) to the lithiumized solution of 13a. The resulting mixture was reacted overnight at 60 °C. After quenching with water, 300 mL of water was added, and the mixture was extracted three times with ethyl acetate (80 mL each time). The resulting organic phase was dried over anhydrous sodium sulfate and then evaporated under reduced pressure to obtain a brown oil. Column chromatography yielded 1.1 g of the target product 31aa, in 15% yield.

[0127] 1 H NMR (400MHz, CDCl3): δ = 7.73 (s, 1H), 7.56 (d, 2H), 3.83 (s, 9H), 1.39 (s, 36H).

[0128] Step 1.6 Preparation of 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa)

[0129]

[0130] In a 1L Schlenk flask under nitrogen protection, 2,2',6-trimethoxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl 4 (31aa, 5g), 100mL of anhydrous dichloromethane, and 17g of boron tribromide were added dropwise. The resulting reaction mixture was allowed to react at room temperature for 48 hours. Then, 200mL of water was added, followed by extraction three times with 200mL of ethyl acetate. The resulting organic phase was dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. Column chromatography yielded 4.3g of the target product 32aa, with a yield of 95%.

[0131] 1 H NMR (600MHz, CDCl3): δ = 9.60 (s, 3H), 7.56 (s, 1H), 7.40 (s, 2H), 1.40 (s, 36H).

[0132] The above-mentioned method for demethylating methoxy ethers on biphenyl compounds is a relatively mature method. It can also be replaced by reaction conditions such as AlCl3 / DCM, 48% HBr aqueous solution, pyridine hydrochloride, AlBr3 / EtSH or AlCl3 / EtSH, which can also obtain similar reaction results with yields between 95% and 99%.

[0133] Example 2 Preparation of 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa)

[0134] Step 2.1 Preparation of 1-bromo-3,5-di-tert-butyl-2,6-dimethoxybenzene (compound 14a)

[0135]

[0136] In a 2L four-necked round-bottom flask, 90.2g of 13a, 85.0g of NBS, and 1.2L of acetonitrile were added sequentially. The resulting reaction mixture was reacted at room temperature for 3 hours. After concentration, 60g of potassium carbonate and 200mL of water were added, and the mixture was extracted three times with 600mL of ethyl acetate each time. The residue was subjected to column chromatography to give 102.0g of the target product 14a, with a yield of 86%.

[0137] 1 H NMR (400MHz, CDCl3): δ=7.30 (s, 1H), 3.83 (s, 6H), 1.41 (s, 18H).

[0138] Step 2.2 Preparation of 2,4-di-tert-butylmethoxybenzene (compound 1c)

[0139]

[0140] In a 2L four-necked round-bottom flask, 21a (80.0 g), DMS (45.2 g), potassium carbonate (63.2 g), and 1.5 L of acetone were added sequentially. The resulting reaction mixture was stirred overnight at room temperature. After concentration, 800 mL of water was added, and the mixture was extracted three times with 600 mL of ethyl acetate each time. The residue was subjected to column chromatography to give 78.6 g of the target product 24a, with a yield of 92%.

[0141] 1 H NMR (400MHz, CDCl3): δ = 7.48 (s, 1H), 6.68 (s, 2H), 3.74 (s, 3H), 1.40 (s, 9H), 1.28 (s, 9H).

[0142] Step 2.3 Preparation of 3,5-di-tert-butyl-1-methoxyphenylboronic acid (compound 25a)

[0143]

[0144] 10.5 g of 2,4-di-tert-butylmethoxybenzene 24a was added to a dry 0.5 L Schlenk flask. The flask was then purged with nitrogen, and 110 mL of tetrahydrofuran was added at room temperature. 20 mL of 2.5 M n-butyllithium solution was added dropwise, followed by the slow addition of methyl borate (10.0 g) under nitrogen protection. After the addition was complete, the mixture was stirred overnight at room temperature. The reaction solution was quenched with water, then 400 mL of water was added, and the mixture was extracted three times with 150 mL of ethyl acetate each time. The resulting organic phase was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. Column chromatography yielded 8.8 g of the target product 25a, with a yield of 70%.

[0145] 1 H NMR (400MHz, CDCl3): δ = 7.73 (s, 1H), 7.56 (d, 2H), 3.83 (s, 9H), 1.39 (s, 36H).

[0146] Step 2.4 Preparation of 2,2',6-trimethoxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 31aa) Preparation

[0147]

[0148] Under a nitrogen atmosphere, 1-bromo-3,5-di-tert-butyl-2,6-dimethoxybenzene 14a (5.0 g), 3,5-di-tert-butyl-1-methoxyphenylboronic acid 25a (2.0 g), palladium acetate (45 mg), BI-DIME (350 mg), anhydrous potassium phosphate (10.2 g), and anhydrous tetrahydrofuran (150 mL) were added to a dry Schlenk flask (0.5 L). The resulting reaction system was heated to 60 °C and stirred overnight. The reaction system was cooled to room temperature and quenched with water (200 mL). Subsequently, the organic phase was separated, and the aqueous phase was extracted twice with dichloromethane (50 mL each time). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under reduced pressure. The residue was subjected to silica gel column chromatography to obtain the target product 31aa 5.7 g, yield 80%.

[0149] Step 2.5 Preparation of 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa)

[0150] Compound 32aa can be prepared according to the method described in step 1.6 of Example 1.

[0151] Example 3 Preparation of 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa)

[0152]

[0153] Under a nitrogen atmosphere, 50.0 g of 4,6-di-tert-butyl-1,3-dihydroxybenzene 12a, 4.95 g of cuprous chloride, 52.3 g of TMEDA, 500 ml of methanol, and 250 ml of water were added sequentially to a 2 L three-necked flask. Then, 20.0 g of 2,4-di-tert-butylphenol 21a was added dropwise to the flask while oxygen was bubbled into the solution. After the addition was complete, oxygen or compressed air was continuously bubbled below the surface of the reaction liquid (identified by bubbling), and the reaction was carried out at 60 °C for 48 hours. The solvent was evaporated under reduced pressure, and a certain proportion of n-hexane was added to the crude product. The mixture was stirred and slurried until solid particles precipitated. After filtration, 43 g of the target product 32aa was obtained, with a yield of 45%.

[0154] Example 4 - Optimization of kilogram-scale preparation process and screening of conditions 1

[0155] The formula for 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa) in an alkaline system Preparation method of kilogram

[0156]

[0157] In a kilogram-scale synthesis ventilation chamber, solvent (3L), organic base (0.055–0.12mol), and metal compound (0.025–0.6mol) are sequentially added to a 20L double-glass jacketed reactor equipped with an explosion-proof mechanical stirrer, a dropping funnel, an explosion-proof high and low temperature cycle, a temperature probe, a gas conduit, a reflux condenser, and a bottom discharge valve. The mixture is stirred uniformly at room temperature for about 0.5 hours. During stirring, an oxidant is added to the reaction system or oxygen or compressed air is continuously introduced below the surface of the reaction liquid (which can be determined by bubbling) until the catalyst color changes from light to dark, indicating that the solution is saturated with oxygen. After the metal-organic base complex is formed, a mixed solution of 4,6-di-tert-butylresorcinol (compound 12a, 4.5 mol, 3.0 L) and 2,4-di-tert-butylphenol (compound 21a, 1.5 mol, 1.8 L), pre-dissolved in solvent, is slowly added dropwise to the reaction vessel using a dropping funnel, while oxygen or air is continuously purged. After the addition is complete, the reaction solution is stirred at the rated temperature for 24–72 hours. During this period, solvent loss due to gas removal is compensated by replenishing the solvent. After the reaction was completed, when a large number of solid particles precipitated in the reactor, the filter cake obtained by batch filtration using a Buchner funnel or centrifuge was the oxidative coupling product 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa). When no solid precipitated, the solvent was evaporated to obtain a viscous crude product. The crude product was crystallized using methanol / water (2:1 to 3:1), and the mixture was stirred with a mechanical stirrer until solid particles precipitated. After filtration, product 32aa was obtained. The results are shown in Table 1 below.

[0158] Table 1

[0159]

[0160] a: Mole percentage of the metal compound relative to compound 21a

[0161] b: Molar percentage of the basic compound relative to metal compound 21a

[0162] As can be seen from Table 1, yields of over 30% can be achieved under most reaction conditions. The yields of reactions numbered 1, 3, 5, and 8 can all reach over 40%, with the highest yield reaching 60%.

[0163] Example 5 - Optimization of kilogram-scale preparation process and screening of conditions 2

[0164] The formula for 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa) in an acidic system Kilogram-level preparation

[0165]

[0166] In a kilogram-scale synthesis ventilation chamber, a clear aqueous solution (2 L) of oxidant (0.45–1.2 mol) is added to a 20 L double-glass jacketed reactor equipped with an explosion-proof mechanical stirrer, dropping funnel, explosion-proof high and low temperature circulation system, temperature probe, reflux condenser, and bottom discharge valve. Subsequently, in a 10 L extraction vessel, 4,6-di-tert-butylresorcinol (compound 12a, 4.5 mol), 2,4-di-tert-butylphenol (compound 21a, 1.5 mol), acid (2–8%), and a 1:1 acid-water mixture (4.8 L) are added and stirred until dissolved. The solution is then slowly added dropwise to the previous reactor. During the dropwise addition, localized heat release occurs in the reactor; the temperature inside the reactor must be controlled to approximately 40–50 °C using an explosion-proof high and low temperature circulation system. After the addition was complete, the reaction was stirred at the rated temperature and monitored until the conversion was complete. When a large number of solid particles precipitated in the reactor, the filter cake obtained by batch filtration using a Buchner funnel or centrifuge was the oxidative coupling product 2,2',6-trihydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl (compound 32aa). When no solid precipitated, the solvent was evaporated using an explosion-proof rotary evaporator to obtain a viscous crude product. The crude product was then crystallized using methanol / water (2:1 to 3:1) with a mechanical stirrer until solid particles precipitated. After filtration, product 32aa was obtained. The results are shown in Table 2 below.

[0167] Table 2:

[0168]

[0169] a: Molar percentage of oxidant relative to compound 21a

[0170] b: Mole percentage of acid added relative to compound 21a

[0171] As can be seen from Table 2, the reaction conditions used in serial numbers 5 and 7 can achieve yields of over 40%, and the reaction temperature is low, with the reaction completed in 12 hours. Therefore, they have the characteristics of mild conditions, high reaction efficiency, and good yield.

[0172] Example 6

[0173]

[0174] In a kilogram-scale synthesis ventilation chamber, methanol (3 L), TMEDA (180 mmol), and CuCl (90 mol) were sequentially added to a 20 L double-glass jacketed reactor equipped with an explosion-proof mechanical stirrer, a dropping funnel, an explosion-proof high and low temperature cycle, a temperature probe, a gas conduit, a reflux condenser, and a bottom discharge valve. The mixture was stirred uniformly at room temperature for approximately 0.5 hours. During stirring, oxygen was continuously introduced below the surface of the reaction liquid. After the Cu-TMEDA complex was formed, a mixed solution of resorcinol compound 12x (4.5 mol, 3.0 L) and phenol compound (compound 21y, 1.5 mol, 1.8 L), pre-dissolved in methanol, was slowly added dropwise to the reactor using a dropping funnel, while maintaining continuous oxygen supply. After the addition was complete, the reaction solution was stirred for 72 hours. After the reaction was completed, the oxidative coupling product 32xy was obtained by solid filtration or rotary evaporation and recrystallization. The results are shown in Table 3 below.

[0175] Table 3

[0176]

[0177] Example 7 2,2',6-Tris[(1,1'-biphenyl-2,2'-diyl)phosphonite]-3,3',5,5'-tetratert-butyl- Preparation of 1,1'-biphenyl (ligand L1)

[0178] Step 7.1 Preparation of 1,1'-biphenyl-2,2'-dioxyphosphine (compound 7)

[0179]

[0180] 2,2'-Biphenyl (30g) was added to excess PCl3, heated under reflux for 6 hours, and then the excess PCl3 was removed by vacuum distillation to obtain a yellow oily product (34g, yield 90%).

[0181] 1 H NMR (400MHz, CDCl3): δ=7.41 (dd, J=7.5, 1.9Hz, 2H), 7.36–7.25 (m, 4H), 7.15 (dt, J=7.9, 1.2Hz, 2H);

[0182] 31 P NMR (162MHz, CDCl3): δ=179.54.

[0183] Step 7.2 2,2',6-Tris[(1,1'-biphenyl-2,2'-diyl)phosphonite]-3,3',5,5'-tetratert-butyl- Preparation of 1,1'-biphenyl (ligand L1)

[0184]

[0185] Under nitrogen protection, 6.2 g of 2,2',6-tetrahydroxy-3,3',5,5'-tetratert-butyl-1,1'-biphenyl and 100 mL of anhydrous tetrahydrofuran were added sequentially to a 0.5 L Schlenk flask. Then, 15 mL of 2.5 M n-butyllithium was added dropwise at -78 °C. The reaction mixture was brought to room temperature and refluxed for 1 hour. The reaction solution was then added dropwise to 100 mL of anhydrous tetrahydrofuran solution of 1,1′-dioxyphosphine chloride (13 g) at -78 °C. After the addition was complete, the mixture was reacted at room temperature for 24 hours. The reaction solution was concentrated under nitrogen atmosphere, and the residue was purified by column chromatography to obtain 8.7 g of the target product, with a yield of 50%.

[0186] 1 H NMR (600MHz, CDCl3): δ=7.32–7.84(m,16H),7.56(s,1H),7.02(d,8H),7.41(d,2H),1.32–1.39(m,36H).

[0187] 31 P NMR (243MHz, CDCl3): δ=144.35, δ=142.31.

[0188] APCI-TOF / MS: Calculated for C 64 H 63 O9P3[M+H] + :1069.1239; Found:1069.1239.

[0189] Example 8: Application of biphenyl tripentient phosphite ligand in hydroformylation reaction

[0190] The hydroformylation reaction in this embodiment adopts... Figure 1 The batch-type pilot-scale reaction equipment shown can simulate the hydroformylation reaction of mixed C4 in industry; the hydroformylation reaction in this embodiment uses mixed C4 as reactants, which, by mass percentage, consists of 25 wt% 1-butene, 40 wt% cis-2-butene and 35 wt% trans-2-butene.

[0191] To ensure ligand activity and prevent aldehyde product oxidation, the reactants undergo a pretreatment process. This process removes water, oxygen, sulfur (sulfides), chlorine (halides), and nitrogen-containing compounds (such as HCN). Additionally, it removes carboxylic acids, butadiene, propylene, and alkynes from the C4 feedstock that inhibit rhodium catalyst activity. To test the reactivity of the biphenyl tridentate phosphite ligand in the mixed / etherified C4, we compared ligand L1 prepared in Example 7 with other commercially available and literature-reported ligands under nearly identical reaction conditions. The specific structures are shown below:

[0192]

[0193] Under an argon atmosphere, a certain amount of Rh(acac)(CO)₂ (0.01 mmol, 2.6 mg) and a certain amount of the ligand Ligand 1-12 (0.02–0.06 mmol) were added to a 200 ml stainless steel high-pressure reactor equipped with a pressure sensor, temperature probe, online sampling port, and safety relief valve. A certain volume of n-pentanal and the internal standard n-decane were also added. The mixture was stirred magnetically for 30 minutes to form a rhodium-ligand catalytic complex. Subsequently, after connecting the gas pipeline and fully purging it, a certain proportion of liquid mixed C₄ was added to the reactor using a metering plunger pump with a two-position four-way valve, controlling the concentration of the rhodium catalyst in the total solution to approximately 159 ppm. The mixture was then stirred uniformly at room temperature for 5–10 minutes. After homogenization, a 1:1 mixture of carbon monoxide and hydrogen was introduced into the reaction apparatus until the total pressure reached 1.0 MPa. The reactor was heated to the required temperature (80–110°C) using a magnetic stirrer (heating the bottom of the reactor) and an electric heating mantle (heating the reactor body). Gas was continuously added during the reaction to maintain a constant total pressure of 1.0 MPa. After 2–4 hours of reaction, the reactor was connected to a -40°C cooling mantle for cooling. Once the reactor temperature had dropped to room temperature, the online sampling port was opened to take a sample without opening the reactor. The sample was diluted with chromatographic grade ethyl acetate and the n-to-iso ratio (ratio of n-pentanal / 2-methylbutanal: 1:b) was determined by gas chromatography (GC). After opening the reactor, the gas inside the high-pressure reactor was completely released in a fume hood, and the sample was weighed. The results are shown in Table 4.

[0194]

[0195] Table 4: Results of hydroformylation reactions with different ligands

[0196]

[0197] a The reaction temperature of 40℃-75℃ refers to the following: 1-Butene begins to react at around 40℃, while cis-2-butene and trans-2-butene react at...

[0198] The reaction begins at around 75℃.

[0199] b The reaction temperature of 40℃-75℃ refers to the following: 1-Butene begins to react at around 40℃, while cis-2-butene and trans-2-butene react at...

[0200] The reaction begins at around 75℃.

[0201] As can be seen from Table 4, in terms of conversion rate, L1 and the comparative ligands 1, 10 and 11 are significantly better than the other comparative ligands, all exceeding 90%; while in terms of the positive-to-negative ratio, L1 is significantly higher than the comparative ligands 1, 10 and 11; considering the reaction temperature and reaction time, the biphenyl tridentate phosphite ligand L1 provided by this invention has a significant advantage in the hydroformylation reaction.

Claims

1. A method for preparing a biphenyl pyrogallol compound, characterized in that, Compound (I) is prepared by oxidative coupling of compound (II) and compound (III) in a solvent in the presence of a catalyst and an oxidant. ， in, R 2 R 6 R 4 Each group is independently H; R 1 R 3 R 5 R 7 Each group is independently tert-butyl; The catalyst is a Cu complex, and the Cu complex is [Cu(MeCN)4][PF6]; the oxidant is O2, and the compounds of formula (II) and (III) are added after the Cu complex is formed. The biphenyl pyrogallol compound is: .

2. The method for preparing the biphenyl pyrogallol compound according to claim 1, characterized in that, The solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane, or a mixture thereof with water; The Cu complex has a molar percentage of 0.5% to 10% relative to the compound of formula (III); The reaction temperature for the oxidative coupling is 30~60℃. o C.

3. The method for preparing the biphenyl pyrogallol compound according to claim 1, characterized in that, The ratio of compound (II) to compound (III) is 5:1 to 1:

5.

4. The method for preparing the biphenyl pyrogallol compound according to any one of claims 1 to 3, characterized in that, The process includes the following steps: (a) Cu salt and organic base dissolve in solvent to form the first solution; (b) Dissolve the compound of formula (II) and the compound of formula (III) in a solvent to form a second solution. (c) Ensure the first solution formed in step (a) is in full contact with the oxidant, and maintain a temperature of 30–60 °C. o C. The second solution formed in step (b) is added dropwise to the first solution in step (a) to obtain a mixture containing compound (I).

5. The method for preparing the biphenyl pyrogallol compound according to claim 4, characterized in that, It also includes process steps: (d) If the mixture in step (c) contains a large amount of precipitated solids, the solids shall be separated by filtration or centrifugation; otherwise, the solvent in the mixture in step (c) shall be evaporated to obtain a crude product, and then the solids shall be precipitated by a methanol / water mixed solvent with a volume ratio of 1:1 to 4:

1.

6. Tridentate phosphorous ligand compounds having the structure shown in formula L1: 。 7. A method for preparing the tripentate phosphite ligand compound shown in Formula L1, characterized in that... include: The pyrogallol compound represented by formula 32aa is reacted with Cl-PR 11 R 12 L1 was prepared in an organic solvent under the action of an alkali, wherein Cl-PR 11 R 12 -PR in 11 R 12 for ， ， ； in, The base is n-butyllithium, diisopropylethylamine, ethylenediamine, diethylamine, triethylamine, or tri-n-butylamine; And / or, the organic solvent is tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, methyl tert-butyl ether, or dioxane.

8. The method for preparing the tridentate phosphite ligand compound according to claim 7, characterized in that, Also includes: The method for preparing the biphenyl pyrogallol compound according to any one of claims 1-5 shall be used to prepare the biphenyl pyrogallol compound.

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