阅读说明：本技术 联苯三酚化合物及其制备方法和用途 (Biphenyl triphenol compound and preparation method and application thereof ) 是由 张润通 闫鑫 丁岸 张绪穆 于 2020-07-16 设计创作，主要内容包括：本发明公开了一种联苯三酚化合物,其具有如有下式(I)所示的结构,本发明提供的联苯三酚化合物是合成联苯骨架的三齿亚磷酸酯配体的重要中间体,在氢甲酰化反应及其工业应用中具有重要的作用。本发明还提供多种联苯三酚化合物的制备方法,包括氧化偶联方法,应用本发明提供的氧化偶联方法合成联苯三酚化合物,能够一步到位,具有催化剂廉价易得、操作简单、收率良好、成本低、能够大规模制备的优点,<Image he="483" wi="547" file="DDA0002587090250000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(The invention discloses a biphenyl triphenol compound which has a structure shown as a formula (I) below, is an important intermediate for synthesizing tridentate phosphite ligands with biphenyl skeletons, and plays an important role in hydroformylation reaction and industrial application thereof. The invention also provides a preparation method of various biphenyltriphenol compounds, which comprises oxidative couplingThe method for synthesizing the biphenyltriphenol compound by applying the oxidative coupling method provided by the invention can be used in one step, has the advantages of cheap and easily obtained catalyst, simple operation, good yield, low cost and large-scale preparation,)

1. A biphenyltriol compound characterized by having a structure represented by the following formula (I),

wherein the content of the first and second substances,

R¹～R⁷each group is independently H, D, C₁-C₄Alkyl radical, C₁-C₄Alkoxy radical, C₁-C₄An alkylthio group.

2. The biphenyltriphenol compound according to claim 1,

R¹～R⁷each group is H, D, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio;

and/or, R¹～R³Are all H; or, R¹、R³Each independently is methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethylthio, isopropylthio, tert-butylthio, and/or, R²Is isopropyl, tert-butyl, isopropoxy or tert-butoxy;

and/or, R⁴～R⁷Are all H; or, R⁵And R⁷Is independently at least one of methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethylthio, isopropylthio, tert-butylthio, and/or, R⁶Is isopropyl, isopropoxy, tert-butyl, tert-butoxy;

and/or, R⁴Is H; or, R⁴Is methyl or methoxy, and R³And R⁷At least one of which is a non-hydrogen substituent;

and/or, R¹And R³Same, preferably R¹And R³Methyl and tert-butyl;

and/or, R⁵And R⁷Same, preferably R⁵And R⁷Methyl and tert-butyl;

alternatively, the first and second electrodes may be,

the biphenyltriphenol compound is selected from the following structures:

3. a process for producing a biphenyltriphenol compound, which comprises reacting a biphenyltriphenol compound,

the compound of formula (I) is prepared by oxidative coupling of a compound of formula (II) and a compound of formula (III) in a solvent in the presence of a catalyst and an oxidant,

wherein the content of the first and second substances,

R¹～R⁷the groups are as defined in any one of claims 1 to 2,

the catalyst is a mixture of an acid, a metal complex or a metal salt capable of forming the metal complex and an organic base;

alternatively, the first and second electrodes may be,

which is prepared by one of the following methods,

method (1)

Method (2)

Method (3)

Wherein the content of the first and second substances,

R¹～R⁷the groups are as defined in any one of claims 1 to 2,

R⁸～R¹⁰at least one of the radicals being a methyl radical,

the compound of the formula (IV) is subjected to demethylation reaction conditions to obtain the compound of the formula (I).

4. The method for producing a biphenyltriphenol compound according to claim 3,

in the oxidative coupling reaction:

the acid is selected from H₂SO₄、HPF₆HCl and HNO₃One or more of;

and/or the metal complex is a Cu complex, and the metal salt is a Cu salt;

and/or the organic base is one or a mixture of TMEDA, DTEDA, TMPDA, DMAEA and TEEDA;

and/or the oxidant is H₂O₂、O₂、O₃、tBuOOH、K₂Cr₂O₇、CrO₃、KMnO₄、MnO₂、KClO₄、KHSO₅、FeCl₃One or a combination thereof;

and/or the solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane, acetic acid, acetic anhydride, THF, diethyl ether, 2-methyltetrahydrofuran, dioxane, water or combination thereof;

and/or the feeding ratio of the compound of the formula (II) to the compound of the formula (III) is 5: 1-1: 5, preferably 3: 1-1: 3;

and/or, when the catalyst is an acid, at least one of the following characteristics:

the oxidant is K₂Cr₂O₇、CrO₃、KMnO₄、MnO₂、KClO₄、KHSO₅、FeCl₃；

The solvent is acetic acid aqueous solution;

the acid is HNO₃And the oxidant is FeCl₃Or, the acid is HCl and the oxidant is KClO₄；

The molar percentage of the oxidant to the compound of the formula (III) is 30-80 mol%;

the molar percentage of the acid to the compound of formula (III) is 0.5-10 mol%, preferably 2-8 mol%;

the reaction temperature of the oxidative coupling is 40-50 ℃;

when the catalyst is a metal complex or a metal salt capable of forming a metal complex in combination with an organic base, the catalyst also has at least one of the following characteristics:

the oxidant is H₂O₂、tBuOOH、KHSO₅、O₂Or O₃；

The solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane or a mixed solvent of the methanol, the ethanol, the isopropanol, the acetone, the ethyl acetate and the dichloromethane;

the metal salt is CuCl or CuCl₂、Cu(OTf)₂、CuI、CuSO₄One or more of the following;

the metal salt is CuCl or CuCl₂Or Cu (OTf)₂And the organic base is TMEDA or TMPDA;

the metal complex is [ Cu (MeCN) ]₄][PF6]、CuCl(OH)(TMEDA)、CuBr(OH)(TMEDA)、Cu(TMEDA)Cl₂、Cu(Et₃N) Cl, preferably [ Cu (MeCN) ]₄][PF₆]One or more of the following;

the molar percentage of the metal complex relative to the compound of formula (III) is between 0.5% and 10%, preferably between 2% and 4%; or the molar percentage of the metal salt relative to the compound of the formula (III) is 0.5-10%, preferably 2-4%, and the feeding molar ratio of the metal salt to the organic base is 1: 1-10: 1, preferably 2: 1-5: 1;

the reaction temperature of the oxidative coupling is 30-60 ℃;

in the method (2):

the catalytic precursor is Pd (OAc)₂，

And/or the ligand is XPhos or BI-DIME,

and/or the alkali metal salt is K₂CO₃、Na₂CO₃、K₃PO₄、Na₃PO₄A mixture of one or more of;

in the method (3):

the catalyst, oxidant and solvent are defined as described in the oxidative coupling reaction.

5. Process for the preparation of biphenyltriphenol compounds according to claim 3 or 4, characterized in that the oxidative coupling preparation comprises the process steps of:

when the catalyst is an acid, the acid is,

(a) the oxidant is dissolved in water to form a first solution,

(b) dissolving the compound of formula (II), the compound of formula (III) and an acid in a solvent to form a second solution,

(c) dripping the second solution formed in the step (b) into the first solution in the step (a) at 40-50 ℃ to obtain a mixture containing a compound in a formula (I);

when the catalyst is a metal complex or a metal salt capable of forming a metal complex is mixed with an organic base,

(a) dissolving a metal salt and an organic base in a solvent to form a first solution;

(b) dissolving the compound of formula (II) and the compound of formula (III) in a solvent to form a second solution;

(c) fully contacting the first solution formed in the step (a) with an oxidant, and dripping the second solution formed in the step (b) into the first solution formed in the step (a) at the temperature of 30-60 ℃ to obtain a mixture containing the compound of the formula (I).

6. The method for preparing biphenyltriphenol compounds according to claim 5, wherein the oxidative coupling preparation method further comprises the process steps of:

(d) when the mixture of step (c) contains a substantial amount of precipitated solids, separating the solids by filtration or centrifugation; otherwise, spin-drying the solvent in the mixture in the step (c) to obtain a crude product, and then separating out a solid by adopting a methanol/water mixed solvent with the volume ratio of 1: 1-4: 1.

7. Use of the biphenyltriphenol compound according to claims 1-2 or the biphenyltriphenol compound obtained by the preparation method according to any one of claims 3-6 in the preparation of tridentate phosphite ligand compounds.

8. The use of the biphenyltriphenol compound of claim 7 in the preparation of a tridentate phosphite ligand compound, wherein the tridentate phosphite ligand compound is prepared from the biphenyltriphenol compound and Cl-PR¹¹R¹²Prepared in an organic solvent under the action of alkali, wherein,

R¹¹、R¹²each independently is alkyl, aryl, OR¹³、C(＝O)OR¹⁴、OC(＝O)R¹⁵，R¹¹、R¹²The phosphorus-doped 5-10-membered cyclic group can be directly bonded or bridged by 1-3 atoms to form a phosphorus-doped 5-10-membered cyclic group which is a monocyclic ring or participates in forming a condensed ring, wherein the 1-3 atoms can be substituted or part of an aromatic ring;

wherein R is¹³、R¹⁴、R¹⁵Each independently is alkyl, aryl or when R¹¹、R¹²When they are linked, R¹³、R¹⁴、R¹⁵May be absent;

R¹¹、R¹²wherein each aryl group is optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CF₃、NO₂、C₁～C₄Alkyl, phenyl C₁～C₄Alkyl radical, C₁～C₄Alkoxy, each alkyl being optionally substituted with one or more groups independently selected from F, Cl, Br, I, CF₃Phenyl, phenoxy, C₁～C₄Alkoxy groups.

9. The use of the biphenyltriphenol compound according to claim 8 for preparing a tridentate phosphite ligand compound,

the base is n-butyl lithium, 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;

and/or the presence of a gas in the atmosphere,

R¹¹、R¹²each independently O, C (═ O) O, OC (═ O), C₁～C₆Alkoxy, phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy, wherein each phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy is optionally substituted by one or more groups independently selected from F、Cl、Br、I、CF₃、NO₂Methyl, isopropyl, tert-butyl, 2-phenylprop-2-yl, benzhydryl, diphenylethyl, methoxy, isopropoxy, tert-butoxy, C₁～C₆Alkyl is optionally substituted by one or more groups independently selected from F, Cl, Br, I, CF₃Phenyl, phenoxy, methoxy, ethoxy, isopropoxy, when R is¹¹、R¹²Is O, C (═ O) O, OC (═ O), R is¹¹And R¹²Are connected or bridged intuitively;

and/or, R¹¹And R¹²The same;

and/or, R¹¹、R¹²Directly connected or through O, S, CH₂、CHCH₃、CH₂CH₂、CH＝CH、

and/or, R¹²Is C₁～C₆Alkoxy, phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy, and R¹¹And R¹²Direct bonding;

and/or, PR¹¹R¹²Is one of the following structures:

10. the use of the biphenyltrisphenol compound according to claim 7 for preparing a tridentate phosphite ligand compound, wherein the tridentate phosphite ligand compound has a structure represented by the following formula (X):

wherein the content of the first and second substances,

to R¹～R⁷Is as defined in any one of claims 1 to 2.

Technical Field

The invention belongs to the technical field of chemical synthesis, and particularly relates to a biphenyltriphenol compound and a preparation method and application thereof.

Background

Phosphonite (Biphephos) compounds as ligands are widely applied to metal-catalyzed organic reactions and chemical applications, for example, Bidentate phosphite ligands derived from Biphenyldiphenol compounds have been widely reported and commercialized by large chemical companies such as BASF, Dow, Shell and Eastman and some research groups abroad for use in hydroformylation reactions, using olefin compounds such as propylene as a raw material, carbon monoxide and hydrogen as a raw material, in the presence of metal catalyst precursor and ligand, the hydroformylation reaction can convert butyraldehyde or other aldehydes which can be easily converted into corresponding alcohol, carboxylic acid, ester, imine and other compounds with important application in organic synthesis, aldehydes synthesized by hydroformylation are synthesized on a large scale in industrial production, and the amount of aldehydes produced by reaction per year is currently up to 1000 ten thousand tons. And the difference of the catalyst or the ligand has important influence on the applicability of a substrate of the hydroformylation reaction, reaction conditions and results, so that the development of a novel biphenyl skeleton phosphite ligand, the development of an efficient preparation method and the provision of cheap and easily available ligand raw materials have important significance.

Biphenol compounds are important intermediates for preparing phosphite ligands of biphenyl frameworks and are generally obtained by coupling reaction of phenol compounds. The coupling reaction is a process of obtaining an organic molecule by carrying out a certain chemical reaction by two organic chemical units, wherein the process comprises a free radical coupling reaction and a transition metal catalytic coupling reaction. Classical coupling reactions such as Suzuki, Heck, Sonogashira, Stille, Kumada, Negishi and Hiyama are coupling reactions between organometallic reagents and preactivated halogenated hydrocarbons. The halogenated hydrocarbon needs to be prepared in advance, so that the reaction steps and the experimental flow are increased, but the method is suitable for coupling between the same aryl and different aryls. Furthermore, a complex compound of a noble metal palladiumPd(PPh₃)₄Is the most commonly used catalyst for such reactions, other catalysts include PdCl₂(PPh₃)₂、PdCl₂(MeCN)₂And the like.

The oxidative coupling reaction refers to a type of oxidation reaction for converting a carbon atom with a lower valence state in a reactant into a carbon atom compound with a higher valence state, and the reaction needs to directly couple two nucleophiles (nucleophiles) in the presence of an oxidant, so that C-H bonds of alkene, alkyne, aromatic hydrocarbon and the like can be directly activated and functionalized. Oxidative coupling reactions play an increasingly important role in the synthesis of organic intermediates such as medicines, pesticides, chemical engineering, materials and the like, but for coupling reactions between different aryl groups, the selectivity is low, and the difficulty is high.

The oxidation coupling reaction catalyzed by cheap metal can be traced back to 1869, Glaser reports that conjugated diyne can be prepared by terminal alkyne self-oxidation coupling: CuCl is used as a catalyst, and phenylacetylene is used as a raw material in a mixed solvent of ammonia water and ethanol to obtain 1, 3-diyne. Albert studied in 1953 at K₂Cr₂O₇/H₂SO₄Under the catalysis, different types of diphenols are obtained through the oxidation self-coupling reaction of various 3, 4, 5-trialkyl phenols, and the yield is 23-76%. In different oxidizing agents (K)₂Cr₂O₇Benzoyl peroxide, MCPBA/FeCl₃) Under the reaction conditions of the raw materials and the reaction,the autoxidative coupling of a series of commercially available compounds such as p-hydroxyphenylpropionate and 3-tert-butyl-4-hydroxyphenylpropionate is reported to achieve a yield of 22-32%. Hay expressed as O in 1962₂Noji uses CuCl (OH) TMEDA as catalyst, air oxidizes 2-naphthol in dichloromethane solution to obtain dinaphthalene diphenol with chemical yield of 90-96%, Deu β en uses 2-naphthol and FeCl₃Reflux in tetrahydrofuran gave a yield of 54%. Further, there are numerous patent documents such as US3210384, US481589, WO99/46227A1,Cu/O is reported in WO9946227, JP2002069022, US4101561, US4070383, J.chem.Soc.C 1971, 2967, J.org.chem.1983, 48, 4948 and the like₂The yield of the reaction for preparing the diphenol by oxidizing and self-coupling various alkyl substituted phenols under the catalysis of the complex is about 35-95%.

Compared with the traditional coupling reaction, the oxidative coupling reaction does not need to prepare a halogenated raw material in advance, and has the advantages of shortening reaction steps, being atom economical and the like.

Disclosure of Invention

Definition of

To facilitate an understanding of the invention, some terms, abbreviations or other acronyms used herein are defined as follows, unless otherwise indicated.

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

"alkenyl", alone or in combination with other groups, represents a straight or branched chain group containing 1 to 8 carbon atoms and containing unsaturated double bonds, including straight or branched chain 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 and the like.

"cycloalkyl", alone or in combination with other groups, represents a 3-7 membered carbocyclic group, for example: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

"aryl" or "aromatic", alone or in combination with other groups, refers to an optionally substituted aromatic carbocyclic group containing 1, 2 or 3 rings linked by bonds or by fusion, such as: phenyl, biphenyl, naphthyl, tetralin, indane, which may be further substituted with other aryl or aryl-containing substituents.

"heteroaryl" or' "heteroaromatic", alone or in combination with other groups, means an optionally substituted heteroaromatic group containing 1 or 2 rings, said heterocyclic ring having 1 to 3 heteroatoms, which may be the same or different, selected from O, N, S, for example: phenyl, biphenyl, naphthyl, tetralin, indane, which may be further substituted with other aryl or aryl-containing substituents.

As used herein to describe a compound or chemical moiety being "substituted" means that at least one hydrogen atom of the compound or chemical moiety is replaced with a second chemical moiety. Non-limiting examples of substituents are those present in the exemplary compounds and embodiments disclosed herein, as well as fluorine, chlorine, bromine, iodine; oxo; imino and nitro; cyano, isocyano, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkenyl, cycloalkenyl, alkynyl; lower alkoxy, aryloxy; acyl, thiocarbonyl, sulfonyl; amides, sulfonamides; a ketone; an aldehyde; esters, sulfonates; haloalkyl (e.g., difluoromethyl, trifluoromethyl); a carbocyclic alkyl group which may be monocyclic or fused or non-fused polycyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl); or a heterocycloalkyl group which may be a single ring or fused or non-fused polycyclic (e.g., pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiazinyl); or may be a monocyclic or fused aryl group (e.g., phenyl, naphthyl, thiazolyl, oxazolyl, imidazolyl, isoxazolyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, thienyl, furyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, indolyl, quinolyl, isoquinolyl, quinoxalyl, quinazolinonyl, benzimidazolyl, benzofuryl, benzothienyl, benzothiazolyl, benzoxazolyl, benzisoxazolyl); or can also be: aryl-lower alkyl; -CHO; -CO (alkyl); -CO (aryl); -CO₂(alkyl); -CO₂(aryl); -CONH₂；-SO₂NH₂； -OCH₂CONH₂；-OCHF₂；-OCF₃；-CF₃(ii) a -N (alkyl) (aryl); -N (aryl)₂(ii) a Further, when the substituent is oxygen, it means that two hydrogen atoms on the same or different carbons are substituted with the same oxygen atom to form a carbonyl group or a cyclic ether, such as a ketocarbonyl group, an aldehyde carbonyl group, an ester carbonyl group, an amide carbonyl group, ethylene oxide, etc.; in addition, these moieties may also optionally be substituted with fused ring structures or bridges (e.g., -OCH₂O-) is substituted. In the present invention, it is preferred that one, two, three substituents independently selected from halogen, nitro, cyano, alkyl, alkoxy or perhalo are substituted, such as trifluoromethyl, pentafluoroethyl, and, when the substituents contain hydrogen, these substituents may optionally be further substituted with a substituent selected from such groups.

As used herein, describing a compound or chemical moiety as being "independently" should be understood as meaning that the plurality of compounds or chemical moieties defined before the term should each enjoy the selection ranges provided thereafter equally, without interfering with each other, and should not be understood as defining any spatial connection relationship between the various groups; spatially connected relationships are referred to herein by the terms "independently of one another," "connected," and the like; should be distinguished; in the present invention, "independently" and "independently each other" and "independently selected from" have substantially the same meaning.

Detailed Description

Aiming at the defects of the prior art, the invention aims to provide a novel biphenyltriphenol compound and a preparation method and application thereof. The biphenyltriphenol compound provided by the invention can be prepared by various methods, can be synthesized by one step by applying the oxidative coupling method provided by the invention, and has the advantages of cheap and easily-obtained catalyst, simple operation, good yield, low cost and large-scale preparation.

In order to achieve the object of the present invention, in one aspect, the present invention provides a biphenyltriol compound having a structure represented by the following formula (I),

wherein the content of the first and second substances,

R¹～R⁷each group is independently H, D, C₁-C₄Alkyl radical, C₁-C₄Alkoxy radical, C₁-C₄An alkylthio group.

In some embodiments, R¹～R⁷Each group is H, D, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio;

in some embodiments, R¹～R³Are all H;

in some embodiments, R¹、R³Each independently is methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethylthio, isopropylthio, tert-butylthio;

in some embodiments, R²Is isopropyl, tert-butyl, isopropoxy or tert-butoxy;

in some embodiments, R⁴～R⁷Are all H;

in some embodiments, R⁵And R⁷Each independently is methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, methylthio, ethylthio, isopropylthio, tert-butylthio;

in some embodiments, R⁶Is isopropyl, isopropoxy, tert-butyl, tert-butoxy;

in some embodiments, R⁴Is H;

in some embodiments, R⁴Is methyl or methoxy, and R⁶And R⁷At least one of which is a non-hydrogen substituent;

in some embodiments, R¹And R³Same, preferably, R¹And R³Methyl and tert-butyl;

in some embodiments, R⁵And R⁷Same, preferably, R⁵And R⁷The same is methyl and tertiary butyl.

In some embodiments, the biphenyltriphenol compound is selected from the structures of one of:

in order to achieve the object of the present invention, the second aspect of the present invention provides a process for producing the aforementioned biphenyltriphenol compound, the compound of formula (I) being produced by oxidative coupling of the compound of formula (II) with the compound of formula (III) in a solvent in the presence of a catalyst and an oxidizing agent,

wherein the content of the first and second substances,

R¹～R⁷the definition of each group is as described above,

the catalyst is a mixture of an acid, a metal complex or a metal salt capable of forming a metal complex and an organic base.

In some embodiments, the acid is selected from H₂SO₄、HPF₆HCl and HNO₃One or more of (a).

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

In some embodiments, the Cu complex is [ Cu (MeCN) ]₄][PF6]、CuCl(OH)(TMEDA)、 CuBr(OH)(TMEDA)、Cu(TMEDA)Cl₂、Cu(Et₃N) Cl.

In some implementationsIn the examples, the Cu salt is CuCl or CuCl₂、Cu(OTf)₂、CuI、CuSO₄One or more of them.

In some embodiments, the organic base is a mixture of one or more of TMEDA, DTEDA, TMPDA, DMAEA, TEEDA.

In some embodiments, the oxidizing agent is H₂O₂、O₂、O₃、tBuOOH、K₂Cr₂O₇、CrO₃、KMnO₄、 MnO₂、KClO₄、KHSO₅、FeCl₃One or a combination thereof.

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.

In some embodiments, the catalyst is an acid and the oxidant is K₂Cr₂O₇、CrO₃、KMnO₄、MnO₂、KClO₄、KHSO₅、FeCl₃And/or the solvent is acetic acid aqueous solution.

In some embodiments, the acid HNO is preferred₃With an oxidant FeCl₃Combination of acid HCl and oxidizing agent KClO₄Combinations of (a) and (b).

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

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

In some embodiments, the catalyst is an acid and the method of preparing the biphenyltriphenol compound comprises the following process steps to achieve kilogram scale preparation:

(a) dissolving an oxidant in water to form a first solution;

(b) dissolving a compound of formula (II), a compound of formula (III), and an acid in a solvent to form a second solution;

(c) and (c) dripping the second solution formed in the step (b) into the first solution in the step (a) at 40-50 ℃ to obtain a mixture containing the compound in the formula (I).

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, and the oxidizing agent is H₂O₂、tBuOOH、KHSO₅、O₂Or O₃And/or the solvent is methanol, ethanol, isopropanol, acetone, ethyl acetate, dichloromethane or a mixed solvent of the methanol, the ethanol, the isopropanol, the acetone, the ethyl acetate and the dichloromethane or water.

In some embodiments, the preferred metal salt is CuCl, CuCl₂Or Cu (OTf)₂And the organic base is TMEDA or TMPDA.

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

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%.

In some embodiments, the mole 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.

In some embodiments, the catalyst is a metal complex or a metal salt that can form a metal complex in combination with an organic base, and the method for preparing the biphenyltriphenol compound includes the following process steps to achieve kilogram-scale preparation:

(a) dissolving a metal salt and an organic base in a solvent to form a first solution;

(b) dissolving the compound of formula (II) and the compound of formula (III) in a solvent to form a second solution;

(c) fully contacting the first solution formed in the step (a) with an oxidant, and dripping the second solution formed in the step (b) into the first solution formed in the step (a) at the temperature of 30-60 ℃ to obtain a mixture containing a compound shown in a formula (I);

in some embodiments, the step of sufficiently contacting the first solution formed in step (a) with the oxidant may be to introduce a gaseous oxidant into the first solution formed in step (a), or to directly expose the first solution formed in step (a) to air until the color of the catalyst changes from light to dark, indicating that the solution is saturated with oxygen, or to add an oxidant into the first solution formed in step (a).

In some embodiments, the method for preparing a biphenyltriphenol compound that enables kilogram-scale preparation further comprises the process steps of:

(d) when the mixture of step (c) contains a substantial amount of precipitated solids, separating the solids by filtration or centrifugation; otherwise, spin-drying the solvent in the mixture in the step (c) to obtain a crude product, and then separating out a solid by adopting a methanol/water mixed solvent with the volume ratio of 2: 1-4: 1; preferably, the ratio of the methanol/water mixed solvent is 2: 1-3: 1.

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

In some embodiments, the reaction temperature of the oxidative coupling is-10 to 60 ℃; when an acid is used as the catalyst, the reaction temperature is preferably 40 to 50 ℃, and when a metal complex or a mixture of a metal salt capable of forming a metal complex and an organic base is used as the catalyst, the reaction temperature is preferably 30 to 60 ℃.

In order to achieve the object of the present invention, the third aspect of the present invention also provides a method for producing one of the aforementioned biphenyltriphenol compounds,

method (1)

Method (2)

Method (3)

Wherein the content of the first and second substances,

R¹～R⁷the definition of each group is as described above,

R⁸～R¹⁰at least one of the radicals being a methyl radical,

the compound of formula (IV) is subjected to demethylation conditions conventional in the art, including but not limited to BBr, to provide the compound of formula (I)₃/DCM、AlCl₃/DCM, 48% aqueous HBr, pyridine hydrochloride, AlBr₃/EtSH、AlCl₃/EtSH。

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

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

in some embodiments, the alkali metal salt in method (2) is K₂CO₃、Na₂CO₃、K₃PO₄Or Na₃PO₄A mixture of one or more of them.

In some embodiments, in the process (3), the definition of the catalyst, the oxidizing agent and the solvent is the same as that of the method for producing the biphenyltriphenol compound described in the second aspect above.

In order to achieve the object of the present invention, the fourth aspect of the present invention also provides use of the aforementioned biphenyltriphenol compound for preparing a tridentate phosphite ligand compound having a biphenyltriphenol skeleton.

In some embodiments, the tridentate phosphite ligand compound is formed from a biphenyltriphenol compound as described above and Cl-PR¹¹R¹²Prepared in an organic solvent under the action of alkali, wherein,

R¹¹、R¹²each independently is alkyl, aryl, heteroaryl, OR¹³、C(＝O)OR¹⁴、OC(＝O)R¹⁵，R¹¹、 R¹²The phosphorus-doped 5-10-membered cyclic group can be directly bonded or bridged by 1-3 atoms to form a phosphorus-doped 5-10-membered cyclic group which is a monocyclic ring or participates in forming a condensed ring, wherein the 1-3 atoms can be substituted or part of an aromatic ring;

wherein R is¹³、R¹⁴、R¹⁵Each independently is alkyl, aryl or when R¹¹、R¹²When they are linked, R¹³、R¹⁴、R¹⁵May be absent;

R¹¹、R¹²wherein each aryl group is optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CF₃、NO₂、C₁～C₄Alkyl, phenyl C₁～C₄Alkyl radical, C₁～C₄Alkoxy, each alkyl being optionally substituted with one or more groups independently selected from F, Cl, Br, I, CF₃Phenyl, phenoxy, C₁～C₄Alkoxy groups.

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

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

In some embodiments, R¹¹、R¹²Independently from each other: o, C (═ O) O, OC (═ O), C₁～C₆Alkoxy, phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy, wherein each phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy is optionally substituted by one or more groups independently selected from F, Cl, Br, I, CF₃、NO₂Methyl, isopropyl, tert-butyl, 2-phenylprop-2-yl, benzhydryl, methoxy, isopropoxy, tert-butoxy, C₁～C₆Alkyl is optionally substituted by one or more groups independently selected from F, Cl, Br, I, CF₃Phenyl, phenoxy, methoxy, ethoxy, isopropoxy; when R is¹¹、R¹²ToWhen one of the radicals is O, C (═ O) O, OC (═ O), R¹¹And R¹²Are connected or bridged intuitively.

In some embodiments, R¹¹And R¹²The same is true.

In some embodiments, R¹¹、R¹²Directly connected or through O, S, CH₂、CHCH₃、CH₂CH₂、CH＝CH、Bridging.

In some embodiments, R¹¹The following groups substituted or unsubstituted: c₁～C₆Alkoxy, phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy, R¹²Is O, C (═ O) O, OC (═ O), and R¹¹And R¹²Directly linked.

In some embodiments, PR¹¹R¹²Is one of the following structures:

in some embodiments, the tridentate phosphite ligand compound has a structure as shown in formula (X) below:

wherein the content of the first and second substances,

R¹～R⁷and R¹¹、R¹²The definition of each group is as described above.

Has the advantages that:

the novel biphenyltriphenol compound provided by the invention can be prepared by a plurality of methods, wherein the biphenyltriphenol compound synthesized by the oxidative coupling method provided by the invention can be obtained in one step with a yield as high as 60%, and the total yield is obviously improved or basically equivalent to that of other multistep preparation methods (about 10% in the method (1) and about 48% in the method (2), but even if the yield is equivalent or slightly good, the reaction steps of the oxidative coupling preparation method provided by the invention are greatly shortened, the catalyst is cheap and easy to obtain, the operation is simple, and no halogenated or boric acid intermediate reagent is needed, so that the novel biphenyltriphenol compound has the advantages of higher atom economy and lower cost, and can be prepared in a large scale, and in addition, the biphenyltriphenol compound provided by the invention is an important intermediate for synthesizing tridentate phosphite ligands of a biphenyl skeleton, has important value in hydroformylation reactions and industrial applications thereof.

Drawings

FIG. 1 is a schematic view of a batch type pilot plant for hydroformylation according to example 8 of the present invention.

Detailed Description

The above route of the present invention is described in detail by the following examples, which should be noted that the present invention is only for further illustration and not limited to the present invention. Those skilled in the art may make insubstantial modifications and adaptations to the present invention.