CN111747827A - Biphenyl triphenol compound and preparation method and application thereof - Google Patents

Biphenyl triphenol compound and preparation method and application thereof Download PDF

Info

Publication number
CN111747827A
CN111747827A CN202010684768.0A CN202010684768A CN111747827A CN 111747827 A CN111747827 A CN 111747827A CN 202010684768 A CN202010684768 A CN 202010684768A CN 111747827 A CN111747827 A CN 111747827A
Authority
CN
China
Prior art keywords
compound
tert
formula
biphenyltriphenol
solvent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202010684768.0A
Other languages
Chinese (zh)
Inventor
张润通
闫鑫
丁岸
张绪穆
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Southwest University of Science and Technology
Southern University of Science and Technology
Original Assignee
Southwest University of Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Southwest University of Science and Technology filed Critical Southwest University of Science and Technology
Priority to CN202010684768.0A priority Critical patent/CN111747827A/en
Publication of CN111747827A publication Critical patent/CN111747827A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
    • C07C39/15—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings with all hydroxy groups on non-condensed rings, e.g. phenylphenol
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1845—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing phosphorus
    • B01J31/185—Phosphites ((RO)3P), their isomeric phosphonates (R(RO)2P=O) and RO-substitution derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/49—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide
    • C07C45/50—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with carbon monoxide by oxo-reactions
    • C07C45/505—Asymmetric hydroformylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
    • B01J2231/321—Hydroformylation, metalformylation, carbonylation or hydroaminomethylation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/822—Rhodium

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

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,
Figure DDA0002587090250000011

Description

Biphenyl triphenol compound and preparation method and application thereof
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,
Figure BDA0002587090230000021
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),
Figure BDA0002587090230000041
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:
Figure BDA0002587090230000042
Figure BDA0002587090230000051
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,
Figure BDA0002587090230000052
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)
Figure BDA0002587090230000071
Method (2)
Figure BDA0002587090230000081
Method (3)
Figure BDA0002587090230000082
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;
Figure BDA0002587090230000083
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、
Figure BDA0002587090230000091
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:
Figure BDA0002587090230000101
in some embodiments, the tridentate phosphite ligand compound has a structure as shown in formula (X) below:
Figure BDA0002587090230000102
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.
Example 12 preparation of each of 2, 2 ', 6-trihydroxy-33', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (chemical compound 32aa)
Step 1.14 preparation of, 6-di-tert-butyl-1, 3-dihydroxybenzene (Compound 12a)
Figure BDA0002587090230000111
Compound 11a (55g), t-butanol (92.5g), and concentrated sulfuric acid (70g) were sequentially added to a 2L three-necked flask. After the addition, the reaction flask was replaced with nitrogen atmosphere and heated to reflux for 24 hours. The solvent was spin dried under reduced pressure, 400mL of water was added, and the mixture was extracted three times with ethyl acetate (500mL each). The obtained organic phase is dried by anhydrous sodium sulfate, then is decompressed and dried by spinning, and 88g of the target product 12a is obtained by flash column chromatography of the residue, with the yield of 80%.
1H NMR(400MHz，CDCl3)：＝7.13(s，1H)，6.09(s，1H)，4.83(s，2H)，1.38(s，18H)。
Step 1.24 preparation of, 6-di-tert-butyl-1, 3-dimethoxybenzene (Compound 13a)
Figure BDA0002587090230000121
In a 2L four necked round bottom flask, 12a (31.5g), methyl iodide (101g), potassium carbonate (98.2g) and 0.5L acetone were added in this order. The resulting reaction was raised to 30 ℃ for 4 hours. The resulting reaction mixture was concentrated, 400mL of water was added, and the mixture was extracted three times with ethyl acetate (600 mL each). The residue was subjected to column chromatography to obtain 30.5g of the target product 13a with a yield of 86%.
1H NMR(400MHz，CDCl3)：＝7.17(s，1H)，6.47(s，1H)，3.83(s，6H)，1.35(s，18H)。
Step 1.31 preparation of bromo-3, 5-di-tert-butylphenol (Compound 22a)
Figure BDA0002587090230000122
In a 2L four necked round bottom flask, 21a (41.2g), NBS (37.4g) and 0.3L acetonitrile were added sequentially. The resulting reaction system was reacted at room temperature for 70 minutes. The resulting reaction mixture was concentrated, 14g of potassium carbonate and 200mL of water were added, and the mixture was extracted three times with ethyl acetate (600 mL each). And carrying out column chromatography on the residue to obtain 42.7g of the target product 22a with the yield of 75%.
1H NMR(400MHz，CDCl3)：＝9.67(s，1H)，7.24(s，1H)，7.11(s，1H)，3.83(s，6H)，1.41 (s，9H)，1.28(s，9H)。
Step 1.41 preparation of bromo-3, 5-di-tert-butylmethoxybenzene (Compound 23a)
Figure BDA0002587090230000123
In a 2L four necked round bottom flask, 22a (62.0g), DMS (37.8g), potassium carbonate (40.6 g) and 0.5L acetone were added sequentially. The resulting reaction was stirred at room temperature overnight. The resulting reaction mixture was concentrated and extracted three times with ethyl acetate (500mL each). The residue was subjected to column chromatography to obtain 58.5g of the target product 23a with a yield of 90%.
1H NMR(400MHz，CDCl3)：＝7.42(s，1H)，7.27(s，1H)，3.83(s，3H)，1.40(s，9H)，1.27 (s，9H)。
Step 1.52 preparation of 2 ', 6-trimethoxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (Compound 31aa) Prepare for
Figure BDA0002587090230000131
To a dry Schlenk bottle (1L) was added 4, 6-di-tert-butyl-1, 3-dimethoxybenzene 13a (5.5g), the reaction flask was replaced with a nitrogen atmosphere, and 100mL of tetrahydrofuran and TMEDA (8.0g) were added at room temperature. A2.5M n-butyllithium solution (10mL) was added dropwise thereto, followed by slowly adding 1-bromo-3, 5-di-t-butylmethoxybenzene 23a (3.0g) in tetrahydrofuran to a lithiated solution of 50mL to 13a dropwise. The resulting mixture was reacted at 60 ℃ overnight, and after the reaction solution was quenched with water, 300mL of water was added and extracted three times with ethyl acetate (80 mL each). The organic phase was dried over anhydrous sodium sulfate and then dried under reduced pressure to give a brown oil, which was subjected to column chromatography to give the desired product 31aa, 1.1g, 15% yield.
1H NMR(400MHz，CDCl3)：＝7.73(s，1H)，7.56(d，2H)，3.83(s，9H)，1.39(s，36H)。
Step 1.62 preparation of 2 ', 6-Trihydroxyl-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -Biphenyl (Compound 32aa)
Figure BDA0002587090230000132
2, 2 ', 6-trimethoxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl 4(31aa, 5g) and 100mL of anhydrous dichloromethane were sequentially added to a 1L Schlenk flask under nitrogen protection, and 17g of boron tribromide was added dropwise at-78 ℃. The resulting reaction mixture was warmed to room temperature and reacted for 48 hours. Then, 200mL of water was added thereto, and 200mL of ethyl acetate was added thereto and extracted three times. The organic phase is dried by anhydrous sodium sulfate, decompressed, steamed and removed with solvent, and the target product 32aa 4.3 g is obtained by column chromatography with 95% yield.
1H NMR(600MHz，CDCl3)：＝9.60(s，3H)，7.56(s，1H)，7.40(s，2H)，1.40(s，36H)。
The demethylating method of the methoxy ether on the biphenyl compound is a mature method, and AlCl can also be adopted3/DCM, 48% aqueous HBr, pyridine hydrochloride, AlBr3EtSH or AlCl3The reaction conditions of/EtSH and the like are replaced, similar reaction results can be obtained, and the yield is between 95 and 99 percent.
Example 22 preparation of 2, 2 ', 6-Trihydroxyl-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -Biphenyl (Compound 32aa)
Step 2.11 preparation of bromo-3, 5-di-tert-butyl-2, 6-dimethoxybenzene (Compound 14a)
Figure BDA0002587090230000141
In a 2L four necked round bottom flask, 13a (90.2g), NBS (85.0g) and 1.2L acetonitrile were added sequentially. The resulting reaction system was reacted at room temperature for 3 hours. The resulting reaction mixture was concentrated, 60g of potassium carbonate and 200mL of water were added, and the mixture was extracted three times with ethyl acetate (600 mL each). And performing column chromatography on the residue to obtain 102.0g of the target product 14a with the yield of 86%.
1H NMR(400MHz，CDCl3)：＝7.30(s，1H)，3.83(s，6H)，1.41(s，18H)。
Step 2.22 preparation of, 4-di-tert-butylmethoxybenzene (Compound 1c)
Figure BDA0002587090230000142
In a 2L four necked round bottom flask, 21a (80.0g), DMS (45.2g), potassium carbonate (63.2 g) and 1.5L acetone were added sequentially. The resulting reaction was stirred at room temperature overnight. The resulting reaction mixture was concentrated, 800mL of water was added, and the mixture was extracted three times with ethyl acetate (600 mL each). And performing column chromatography on the residue to obtain 78.6g of the target product 24a with the yield of 92 percent.
1H NMR(400MHz，CDCl3)：＝7.48(s，1H)，6.68(s，2H)，3.74(s，3H)，1.40(s，9H)，1.28 (s，9H)。
Step 2.3 preparation of di-t-butyl-1-methoxyphenylboronic acid (Compound 25a)
Figure BDA0002587090230000143
2, 4-di-tert-butylmethoxybenzene 24a (10.5g) was charged into a dry Schlenk flask (0.5L), the reaction flask was replaced with a nitrogen atmosphere, and 110mL of tetrahydrofuran was added at room temperature. A2.5M n-butyllithium solution (20mL) was added dropwise thereto, followed by slowly adding methyl borate (10.0g) dropwise to the bottle under a nitrogen atmosphere. After the addition was complete, the mixture solution was stirred at room temperature overnight. After the reaction solution was quenched with water, 400mL of water was added and extracted three times with ethyl acetate (150mL each). The obtained organic phase is dried by anhydrous sodium sulfate, then is decompressed and dried by spinning, and the target product 25a 8.8g is obtained by column chromatography, and the yield is 70%.
1H NMR(400MHz，CDCl3)：＝7.73(s，1H)，7.56(d，2H)，3.83(s，9H)，1.39(s，36H)。
Step 2.42 preparation of, 2 ', 6-trimethoxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (Compound 31aa) Prepare for
Figure BDA0002587090230000151
To a dried Schlenk bottle (0.5L) were added, under a nitrogen atmosphere, 1-bromo-3, 5-di-tert-butyl-2, 6-dimethoxybenzene 14a (5.0g), 3, 5-di-tert-butyl-1-methoxyphenylboronic acid 25a (2.0g), palladium acetate (45mg) and BI-DIME (350mg), anhydrous potassium phosphate (10.2g) and anhydrous tetrahydrofuran (150 mL). The resulting reaction was heated to 60 ℃ and stirred for reaction overnight. The reaction was cooled to room temperature and quenched by the addition of water (200 mL). Subsequently, the organic phase was separated and the aqueous phase was extracted twice with dichloromethane (50 mL each). And combining organic phases, drying the organic phases by using anhydrous sodium sulfate, filtering the organic phases, carrying out reduced pressure rotary evaporation to remove the solvent, and carrying out silica gel column chromatography on the residues to obtain the target product 31aa 5.7g with the yield of 80%.
Step 2.52 preparation of 2, 2 ', 6-Trihydroxyl-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -Biphenyl (Compound 32aa)
Compound 32aa can be prepared as described in step 1.6 of example 1.
Example preparation of 32, 2 ', 6-Trihydroxyl-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -Biphenyl (Compound 32aa)
Figure BDA0002587090230000152
To a 2L three-necked flask, 4, 6-di-tert-butyl-1, 3-dihydroxybenzene 12a (50.0g), cuprous chloride (4.95g), TMEDA (52.3g), methanol (500ml) and water (250ml) were added in this order under a nitrogen atmosphere. Subsequently, 2, 4-di-tert-butylphenol 21a (20.0g) was added dropwise to the three-necked flask while introducing oxygen into the solution. After the completion of the dropwise addition, oxygen or compressed air (which can be distinguished by bubbling) was continuously introduced below the surface of the reaction solution, and the reaction was carried out at 60 ℃ for 48 hours. And (3) carrying out reduced pressure spin drying on the solvent, adding a certain proportion of normal hexane into the crude product, continuously stirring and pulping until solid particles are separated out, and filtering to obtain a target product 32aa 43g with a yield of 45%.
Example 4-kilogram-level optimization of the preparation Process and Condition screening 1
Preparation of 2, 2 ', 6-trihydroxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (compound 32aa) in alkaline system Jin-class preparation method
Figure BDA0002587090230000161
In a kilogram-level synthesis ventilation room, sequentially adding a solvent (3L), organic base (0.055-0.12mol) and metal compound (0.025-0.6mol) into a 20L double-layer glass jacket reaction kettle provided with an explosion-proof mechanical stirring paddle, a dropping funnel, an explosion-proof high-low temperature circulation device, a temperature probe, a gas conduit, a reflux condenser, a discharge valve and other devices, and uniformly stirring for about 0.5 hour at room temperature; during the stirring period, oxidant is added into the reaction system or oxygen or compressed air (which can be distinguished by bubbling) is continuously introduced below the reaction liquid level until the color of the catalyst changes from light to dark, which indicates that the oxygen in the solution is saturated. After the metal-organic base complex is formed, a mixed solution of 4, 6-di-tert-butylresorcinol (compound 12a, 4.5mol, 3.0L) and 2, 4-di-tert-butylphenol (compound 21a, 1.5mol, 1.8L), which have been dissolved in a solvent in advance, is slowly dropped into the reaction kettle by using a dropping funnel, and oxygen or air is kept being introduced all the time. After the dropwise addition, the reaction solution is stirred and reacts for 24-72 hours at a rated temperature. During this time, the loss of solvent carried over by the gas is compensated by replenishing the solvent. After the reaction is finished, when a large amount of solid particles are separated out in the kettle, a filter cake obtained by batch filtration by using a Buchner funnel or a centrifugal machine is the oxidative coupling product 2, 2 ', 6-trihydroxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (compound 32 aa); when no solid is separated out, the solvent is dried in a rotating mode to obtain a viscous crude product, the crude product is crystallized by adopting methanol/water (2: 1-3: 1), a mechanical stirring paddle is used for pulping until solid particles are separated out, and the product 32aa is obtained after filtration; the results are shown in table 1 below.
TABLE 1
Figure BDA0002587090230000162
a: mole percent of metal compound relative to compound 21a
b: molar percentage of basic compound relative to metal compound 21a
As can be seen from Table 1, yields of 30% or more were obtained under most of the reaction conditions, and the reaction yields of Nos. 1, 3, 5 and 8 were 40% or more, and the yield was 60% at the highest.
Example 5-kilogram-level preparation Process optimization and Condition SieveOption 2
Preparation of 2, 2 ', 6-trihydroxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (compound 32aa) in acidic system Preparation of jin grade
Figure BDA0002587090230000171
In a kilogram-level synthesis ventilation room, a 20L double-layer glass jacket reaction kettle provided with an explosion-proof mechanical stirring paddle, a dropping funnel, an explosion-proof high-low temperature circulation device, a temperature probe, a reflux condenser, a discharge valve and other devices is added with 2L of clarified aqueous solution (0.45-1.2mol) of an oxidant. Subsequently, a 10L extraction vessel was charged with a mixed solvent of 4, 6-di-t-butylresorcinol (compound 12a, 4.5mol), 2, 4-di-t-butylphenol (compound 21a, 1.5mol), acid (2-8%) and acid water (4.8L) in a volume ratio of 1: 1, and after stirring until dissolved, the solution was slowly dropped into the previous reaction vessel. During the dripping period, the reaction kettle has local heat release phenomenon, and the temperature in the kettle needs to be controlled to be about 40-50 ℃ by explosion-proof high-low temperature circulation. After the dropwise addition is finished, stirring the mixture for reaction at a rated temperature, monitoring until the reaction conversion is finished, and when a large amount of solid particles are separated out in the kettle, filtering the mixture in batches by using a Buchner funnel or a centrifugal machine to obtain a filter cake, namely the oxidative coupling product 2, 2 ', 6-trihydroxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl (compound 32 aa); and when no solid is separated out, the solvent is dried in a rotating manner by using an explosion-proof type evaporator to obtain a viscous crude product, the crude product is crystallized by using methanol/water (2: 1-3: 1), pulping is carried out by using a mechanical stirring paddle until solid particles are separated out, and the product 32aa is obtained after filtration. The results are shown in table 2 below:
table 2:
Figure BDA0002587090230000172
a: mole percent of oxidizing agent relative to Compound 21a
b: acid addition in mol percent relative to Compound 21a
As can be seen from Table 2, the reaction conditions adopted in the serial numbers 5 and 7 can achieve a yield of more than 40%, and the reaction temperature is low, and the reaction can be completed in 12 hours, so that the method has the characteristics of mild conditions, high reaction efficiency and good yield.
Example 6
Figure BDA0002587090230000181
In a kilogram-level synthesis ventilation room, sequentially adding methanol (3L), TMEDA (180mmol) and CuCl (90mol) into a 20L double-layer glass jacket reaction kettle provided with an explosion-proof mechanical stirring paddle, a dropping funnel, an explosion-proof high-low temperature circulation device, a temperature probe, a gas conduit, a reflux condenser, a discharge valve and other devices, and uniformly stirring for about 0.5 hour at room temperature; during the stirring, oxygen was continuously introduced below the reaction liquid level. After the formation of the Cu-TMEDA complex, a mixed solution of resorcinol compound 12x, (4.5mol, 3.0L) and phenol compound (compound 21y, 1.5mol, 1.8L), which had been dissolved in methanol in advance, was slowly dropped into the reaction vessel using a dropping funnel while keeping the oxygen gas introduced. After the dropwise addition was completed, the reaction solution was stirred under stirring for reaction for 72 hours. After the reaction is completed, the oxidation coupling product 32xy is obtained by solid filtration or dry weight rotation crystallization, and the results are shown in the following table 3:
TABLE 3
Figure BDA0002587090230000182
Example 72, 2 ', 6-Tris [ (1, 1 ' -biphenyl-2, 2 ' -diyl) phosphonite]-3, 3 ', 5, 5' -tetra-tert-butyl- Preparation of 1, 1' -biphenyl (ligand L1)
Step 7.11 preparation of, 1 '-Biphenyl-2, 2' -dioxychlorophosphine (Compound 7)
Figure BDA0002587090230000183
2, 2' -biphenol (30g) was added to an excess of PCI3Heating and refluxing for 6 hr, and steaming under reduced pressureDistillation to remove excess PCl3The product was obtained as a yellow oil (34g, yield 90%).
1H NMR(400MHz，CDCl3)：＝7.41(dd，J＝7.5，1.9Hz，2H)，7.36-7.25(m，4H)，7.15(dt，J＝7.9，1.2Hz，2H)；
31P NMR(162MHz，CDCl3)：＝179.54。
Step 7.22, 2 ', 6-Tris [ (1, 1 ' -biphenyl-2, 2 ' -diyl) phosphonite]-3, 3 ', 5, 5' -tetra-tert-butyl- Preparation of 1, 1' -biphenyl (ligand L1)
Figure BDA0002587090230000191
Under nitrogen protection, 6.2g of 2, 2 ', 6-tetrahydroxy-3, 3', 5, 5 '-tetra-tert-butyl-1, 1' -biphenyl and 100mL of anhydrous tetrahydrofuran were sequentially added to a 0.5L Schlenk flask, and 15mL of 2.5M n-butyllithium was added dropwise at-78 ℃. The reaction mixture was warmed to room temperature and refluxed for 1 hour. Then, the reaction solution was dropped into 100mL of an anhydrous tetrahydrofuran solution of 1, 1' -dioxyphosphorochloridite (13g) at-78 ℃ and reacted at room temperature for 24 hours after the dropping, the reaction solution was concentrated under a nitrogen atmosphere, and the residue was subjected to column chromatography to obtain 8.7g of the objective product with a yield of 50%.
1H NMR(600MHz，CDCl3)：＝7.32-7.84(m，16H)，7.56(s，1H)，7.02(d，8H)，7.41(d，2H)，1.32-1.39(m，36H)。
31P NMR(243MHz，CDCl3)：＝144.35，＝142.31。
APCI-TOF/MS：Calculated for C64H63O9P3[M+H]+：1069.1239；Found：1069.1239。
Example 8 use of Biphenyl tridentate phosphite ligands in hydroformylation reactions
The hydroformylation reaction of this example employs a batch type pilot plant reaction apparatus shown in FIG. 1, which can simulate an industrial hydroformylation reaction of mixed C4; the hydroformylation reaction of this example employed mixed C.sub.four as the reactant material, which consisted of 25 wt% 1-butene, 40 wt% cis-2-butene and 35 wt% trans-2-butene, in mass percent.
In order to ensure the activity of the ligand and the aldehyde product not to be oxidized, the reaction materials pass through a raw material pretreatment device, and besides water removal, oxygen removal, sulfur (sulfide), chlorine (halide), nitrogen-containing compounds (such as HCN) and the like, substances such as carboxylic acid, butadiene, allene, alkyne and the like which have an inhibiting effect on a rhodium catalyst in the raw materials of carbon and carbon are also removed. To test the reactivity of the biphenyl tridentate phosphite ligand at mixed/ethereal carbon four, we tested ligand L1 prepared in example 7 in comparison with other commercial and literature reported ligands under nearly identical reaction conditions, with the specific structure shown below:
Figure BDA0002587090230000201
adding a certain amount of Rh (acac) (CO) into a 200ml stainless steel high-pressure reaction kettle provided with a pressure sensor, a temperature probe, an online sampling port, a safety relief valve and the like under the argon atmosphere2(0.01mmol, 2.6mg) and a certain amount of Ligand 1-12(0.02-0.06mmol), adding a certain volume of n-valeraldehyde and internal standard substance n-decane, and stirring and complexing for 30 minutes by using a magneton to generate a catalytic complex of rhodium and Ligand. And then, connecting a gas line, fully replacing, adding a certain proportion of liquefied mixed C4 into the reaction kettle by using a plunger pump with a metering function under the switching of a two-position four-way valve, controlling the concentration of the rhodium catalyst in the total solution to be about 159ppm, and uniformly stirring at room temperature for 5-10 minutes. After stirring evenly, the reaction device is filled with the mixed gas (1: 1) of carbon monoxide and hydrogen to the total pressure of 1.0 MPa. And (3) raising the temperature of the reaction kettle to the required temperature (80-110 ℃) by using a magnetic stirrer (the bottom of the heating kettle) and an electric heating sleeve (a heating kettle body), and continuously supplementing gas in the reaction to keep the total pressure constant at 1.0 MPa. After reacting for 2-4 hours, connecting the reaction kettle into a-40 ℃ cold sleeve for cooling, opening an online sampling port for sampling when the temperature of the kettle is reduced to normal temperature without opening the kettle, diluting with chromatographic grade ethyl acetate, and performing gas chromatographyThe ratio of normal to iso (ratio of n-valeraldehyde to 2-methylbutyraldehyde: l: b) was determined by means of a Gas Chromatograph (GC). And after the kettle is opened, completely releasing the gas in the high-pressure reaction kettle in a fume hood, and sampling and weighing. The results are shown in Table 4.
Figure BDA0002587090230000211
Table 4: hydroformylation reaction results of different ligands
Figure BDA0002587090230000212
aThe reaction temperature is 40-75 ℃ and means that: 1-butene begins to react at about 40 ℃ and cis-2-butene and trans-2-butene begin to react at about 75 ℃
bThe reaction temperature is 40-75 ℃ and means that: 1-butene begins to react at about 40 ℃ and cis-2-butene and trans-2-butene begin to react at about 75 ℃
It can be seen from table 4 that L1 and comparative ligands 1, 10 and 11 are clearly superior to the other comparative ligands in terms of conversion, both above 90%; while in the positive-to-hetero ratio, L1 was significantly higher than the control ligands 1, 10 and 11; considering the combination of reaction temperature and reaction time, the biphenyl tridentate phosphite ligand L1 provided by the invention has obvious advantages in hydroformylation reaction.

Claims (10)

1. A biphenyltriol compound characterized by having a structure represented by the following formula (I),
Figure FDA0002587090220000011
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:
Figure FDA0002587090220000012
Figure FDA0002587090220000021
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,
Figure FDA0002587090220000022
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)
Figure FDA0002587090220000023
Method (2)
Figure FDA0002587090220000031
Method (3)
Figure FDA0002587090220000032
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、
Figure FDA0002587090220000061
Figure FDA0002587090220000062
Bridging;
and/or, R12Is C1～C6Alkoxy, phenyl, phenoxy, naphthyl, naphthyloxy, tetrahydronaphthyl, tetrahydronaphthyloxy, and R11And R12Direct bonding;
and/or, PR11R12Is one of the following structures:
Figure FDA0002587090220000063
Figure FDA0002587090220000071
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):
Figure FDA0002587090220000072
wherein the content of the first and second substances,
to R1～R7Is as defined in any one of claims 1 to 2.
CN202010684768.0A 2020-07-16 2020-07-16 Biphenyl triphenol compound and preparation method and application thereof Pending CN111747827A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010684768.0A CN111747827A (en) 2020-07-16 2020-07-16 Biphenyl triphenol compound and preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010684768.0A CN111747827A (en) 2020-07-16 2020-07-16 Biphenyl triphenol compound and preparation method and application thereof

Publications (1)

Publication Number Publication Date
CN111747827A true CN111747827A (en) 2020-10-09

Family

ID=72711203

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010684768.0A Pending CN111747827A (en) 2020-07-16 2020-07-16 Biphenyl triphenol compound and preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN111747827A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111909003A (en) * 2020-02-10 2020-11-10 惠州凯特立斯科技有限公司 Oxidative coupling method for preparing kilogram-grade novel biphenyltetraphenol and catalyst thereof
CN112159313A (en) * 2020-10-30 2021-01-01 惠州凯特立斯科技有限公司 Preparation method of big steric-hindrance bi-phenol skeleton and phosphonite ligand thereof
CN115536498A (en) * 2022-10-24 2022-12-30 遵义医科大学 Method for oxidative coupling of substituted phenol catalyzed by butanedione

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102875599A (en) * 2012-09-29 2013-01-16 武汉大学 Novel tridentate phosphine ligand and application of same to linear hydroformylation and similar reactions
CN106349024A (en) * 2015-07-14 2017-01-25 彤程化学（中国）有限公司 Synthesis method and application of hindered phenol antioxidant
CN111253222A (en) * 2020-03-02 2020-06-09 福建省中科生物股份有限公司 Phenolic compound ZKYY-037 and preparation method and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102875599A (en) * 2012-09-29 2013-01-16 武汉大学 Novel tridentate phosphine ligand and application of same to linear hydroformylation and similar reactions
CN106349024A (en) * 2015-07-14 2017-01-25 彤程化学（中国）有限公司 Synthesis method and application of hindered phenol antioxidant
CN111253222A (en) * 2020-03-02 2020-06-09 福建省中科生物股份有限公司 Phenolic compound ZKYY-037 and preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CAELAN RANDOLPH ET AL.: "Biobased Chemicals: 1,2,4-Benzenetriol, Selective Deuteration and Dimerization to Bifunctional Aromatic Compounds"", 《ORG. PROCESS RES. DEV.》 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111909003A (en) * 2020-02-10 2020-11-10 惠州凯特立斯科技有限公司 Oxidative coupling method for preparing kilogram-grade novel biphenyltetraphenol and catalyst thereof
CN111909003B (en) * 2020-02-10 2023-05-30 广东欧凯新材料有限公司 Oxidative coupling method for preparing kilogram-level novel biphenyl tetraphenol and catalyst thereof
CN112159313A (en) * 2020-10-30 2021-01-01 惠州凯特立斯科技有限公司 Preparation method of big steric-hindrance bi-phenol skeleton and phosphonite ligand thereof
CN112159313B (en) * 2020-10-30 2024-02-09 广东欧凯新材料有限公司 Preparation method of large-steric-hindrance biphenol skeleton and phosphonite ligand thereof
CN115536498A (en) * 2022-10-24 2022-12-30 遵义医科大学 Method for oxidative coupling of substituted phenol catalyzed by butanedione
CN115536498B (en) * 2022-10-24 2023-10-20 遵义医科大学 Butanedione catalyzed substituted phenol oxidative coupling method

Similar Documents

Publication Publication Date Title
CN111747827A (en) Biphenyl triphenol compound and preparation method and application thereof
Vabre et al. Direct, one-pot synthesis of POCOP-type pincer complexes from metallic nickel
CN101990543B (en) Method for manufacturing ruthenium carbene complexes
CN103804413B (en) Three Phosphine ligands preparation method of biphenyl and progressively replace PPh in hydroformylation3Application
CN106146454B (en) The method that Negishi couplings prepare polyfluoro biaryl hydrocarbon compound
Osińska et al. Suzuki–Miyaura and Hiyama coupling catalyzed by PEPPSI-type complexes with non-bulky NHC ligand
Miyaura et al. Cross-coupling reactions of 1-alkenylboranes with 3, 4-epoxy-1-butene catalyzed by palladium or nickel complexes
CN111848683A (en) Biphenyl tridentate phosphite ligand and preparation method and application thereof
CN108380245A (en) A kind of novel bidentate phosphorus-azepine Cabbeen p-cymene type catalyzed by ruthenium complexes agent and preparation method thereof and synthesis application
CN107629093A (en) Double (phosphino-) ferrocene ligands of 1,1` for alkoxycarbonylation
CN110590658B (en) Method for catalytic hydrogenation of nitrogen-containing unsaturated heterocyclic compound
Elvers et al. Photochemical Unmasking of 1, 3‐Dithiol‐2‐ones: An Alternative Route to Heteroleptic Dithiolene Complexes from Low‐Valent Molybdenum and Tungsten Precursors
TWI659038B (en) Process for the preparation of esters by means of carbonylation of ethers
TWI668208B (en) Process for the alkoxycarbonylation of ethers
TWI668225B (en) Process for the alkoxycarbonylation of alcohols
CN113620990A (en) Thiourea type nitrogen phosphine ligand and preparation method and application thereof
CN102977040B (en) Method for synthesizing 2-quinoxalinyl dimethylacetal and 2-quinoxalinyl formaldehyde
WO2022155936A1 (en) Method for synthesizing aryl benzyl ether compound
US7271276B2 (en) Metal complexes for catalytic carbon-carbon bond formation
CN105801578B (en) A kind of synthetic method of semi-saturation pyrazines derivatives and application
EP2842959A1 (en) Phosphorous compound and transition metal complex thereof
WO2008059960A1 (en) Method for producing quarter-pyridine derivative and intermediate of quarter-pyridine derivative
CN115041236A (en) Supported Au-Ag nanocluster catalyst and application thereof in ketoethynylation reaction
CN106661063B (en) Pyridylium base phosphine, their preparation method and the purposes that N- replaces
KR810000579B1 (en) Process for preparation of catalyst

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination