CN113735694A - Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone - Google Patents
Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone Download PDFInfo
- Publication number
- CN113735694A CN113735694A CN202111072888.6A CN202111072888A CN113735694A CN 113735694 A CN113735694 A CN 113735694A CN 202111072888 A CN202111072888 A CN 202111072888A CN 113735694 A CN113735694 A CN 113735694A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- solvent
- synthesizing
- carrying
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 128
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 17
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 238000006069 Suzuki reaction reaction Methods 0.000 claims abstract description 5
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 51
- 239000002904 solvent Substances 0.000 claims description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 230000020477 pH reduction Effects 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- DAUCSGSCDZOKLE-UHFFFAOYSA-N methyl 1-bromonaphthalene-2-carboxylate Chemical compound C1=CC=CC2=C(Br)C(C(=O)OC)=CC=C21 DAUCSGSCDZOKLE-UHFFFAOYSA-N 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 229910002666 PdCl2 Inorganic materials 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- 230000009471 action Effects 0.000 claims description 2
- HMIBDRSTVGFJPB-UHFFFAOYSA-N methyl 1-hydroxynaphthalene-2-carboxylate Chemical compound C1=CC=CC2=C(O)C(C(=O)OC)=CC=C21 HMIBDRSTVGFJPB-UHFFFAOYSA-N 0.000 claims description 2
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 abstract description 4
- 239000002351 wastewater Substances 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 abstract description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 230000007935 neutral effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- ICPSWZFVWAPUKF-UHFFFAOYSA-N 1,1'-spirobi[fluorene] Chemical compound C1=CC=C2C=C3C4(C=5C(C6=CC=CC=C6C=5)=CC=C4)C=CC=C3C2=C1 ICPSWZFVWAPUKF-UHFFFAOYSA-N 0.000 description 4
- 238000009776 industrial production Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 150000001733 carboxylic acid esters Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- VUVIRKAVBZITDO-UHFFFAOYSA-N 1-bromonaphthalene-2-carboxylic acid Chemical compound C1=CC=CC2=C(Br)C(C(=O)O)=CC=C21 VUVIRKAVBZITDO-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- MEGKIGMEJZZEOX-UHFFFAOYSA-N 9-chlorobenzo[c]fluoren-7-one Chemical compound C1=CC=CC2=C3C4=CC=C(Cl)C=C4C(=O)C3=CC=C21 MEGKIGMEJZZEOX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 238000004770 highest occupied molecular orbital Methods 0.000 description 2
- 238000004768 lowest unoccupied molecular orbital Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000007039 two-step reaction Methods 0.000 description 2
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 238000005401 electroluminescence Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/24—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfuric acids
-
- 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
- C07C45/41—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Abstract
The invention discloses a method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone (a compound shown in a formula I), wherein X is one of Cl and Br. The method comprises the following steps: 1-hydroxy-2-methyl naphthoate is used as a raw material, and is etherified by trifluoromethanesulfonate to obtain a compound shown in a formula A; carrying out Suzuki reaction on the compound of the formula A and 4-halogenated phenylboronic acid to obtain a compound of a formula B; carrying out alkaline hydrolysis on the compound of the formula B to obtain a compound of a formula C; and (3) carrying out ring closure on the compound of the formula C under an acidic condition to obtain the compound of the formula I. The method solves the problems of large dosage of ring closing reagents, large tar amount, difficult purification, low yield and large wastewater amount in the prior method, and is more beneficial to the subsequent amplified production process by improving the reaction method of intermediate compounds and final products.
Description
Technical Field
The invention belongs to the technical field of organic electroluminescence (OLED), and particularly relates to a synthesis method of 9-halogen-7H-benzo [ c ] fluorene-7-ketone. The invention also provides a synthetic intermediate compound of the compound shown in the formula I and a preparation method thereof.
Background
Currently, fluorene compounds are widely used in organic optoelectronic molecular devices, electrophotographic materials, solar cell materials, color liquid crystal materials, organic optical information recording materials, and the like. The spirobifluorene molecule has the characteristics of a non-planar space structure, higher glass transition temperature, proper HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels and higher Eg orbitals due to unique structural characteristics, can be sublimated under the conditions of no decomposition and no residue, can effectively improve the luminous performance and the service life of an OLED device, and is suitable for the OLED devices of phosphorescence and fluorescence (including TADF). The compound of the formula I is an essential intermediate in the preparation process of spirobifluorene molecules, and is generally applied to terminal compounds containing spirobifluorene structures.
Wherein, X is one of Cl and Br.
The synthetic routes for compounds of formula i disclosed in KR2014128879, KR2014128878, KR2015095545 and KR2016113488 preset the ketocarbonyl function on the benzene ring before the ring closure reaction, resulting in the synthetic results of this synthetic route yielding a large amount (20% to 50%) of the isomeric product. The synthetic routes of the compounds of formula I disclosed in CN11592464 and CN105418357 use 1-bromo-2-naphthoate as a starting material, and the price of 1-bromo-2-naphthoate is high, so that the cost problem exists in large-scale industrial production by adopting the synthetic routes. The synthetic route for the compound of formula I disclosed in JP5320722B2 solves the problem of high product cost by replacing expensive methyl 1-bromo-2-naphthoate with inexpensive methyl 1-hydroxy-2-naphthoate, but the last step of the patent is actually a two-step reaction, i.e., hydrolysis of carboxylic acid ester under acidic conditions and carboxylic acid ring-closing reaction. Those skilled in the art will readily appreciate that acidic hydrolysis of carboxylic acid esters is a reversible reaction with limited yields. The two-step reaction is combined into one step, so that the dosage of a ring closing reagent is large, the tar content of a system is large, and the yield of the last step is only 57%. Meanwhile, a large amount of ring closing reagents are used, so that the amount of waste water is increased, and the environmental protection pressure is increased.
Although the above patents all suggest synthetic routes to the compounds of formula I, the existence of these problems limits the subsequent commercial production of the compounds of formula I as an essential intermediate for the compounds containing spirobifluorene structure. Therefore, it is necessary to research the optimization of the synthesis process of the compound of formula I and provide guarantee for the industrial production of the compound of formula I.
Disclosure of Invention
The invention aims to solve the problems of large dosage of a ring closing reagent, large tar amount, difficult purification, low yield and large wastewater amount in the JP5320722B2 patent, and provides a synthetic method for the compound shown in the formula I, which is suitable for industrial production.
Based on the purposes, the invention prepares the compound shown in the formula I by ring closure under acidic conditions, has high synthesis result yield, and improves the reaction method of intermediate compounds and final products, so that the method is more favorable for subsequent scale-up production process.
In one aspect, the invention relates to compounds of formula I:
wherein, X is one of Cl and Br.
In another aspect, the present invention relates to a method of synthesizing a compound of formula i, comprising the steps of:
and (3) ring closing the compound of the formula C under an acidic condition to obtain a compound of the formula I:
wherein, X is one of Cl and Br.
In another aspect, the invention relates to a method of synthesizing a compound of formula C, comprising the steps of:
and (3) carrying out alkaline hydrolysis on the compound of the formula B to obtain a compound of a formula C:
wherein, X is one of Cl and Br.
In another aspect, the present invention relates to a method of synthesizing a compound of formula B, comprising the steps of:
the compound of the formula A and 4-halogenated phenylboronic acid are subjected to Suzuki reaction to obtain a compound of a formula B:
wherein, X is one of Cl and Br.
In another aspect, the present invention relates to a method of synthesizing a compound of formula a, comprising the steps of:
1-hydroxy-2-methyl naphthoate is used as a raw material, and is etherified by trifluoromethanesulfonate to obtain a compound shown as a formula A:
in another aspect, the present invention provides the following reaction scheme for compounds of formula i:
specifically, the compound of the formula A is prepared by the following steps:
dissolving a raw material 1-hydroxy-2-methyl naphthoate in a solvent I, wherein the volume mass ratio of the solvent to the raw material 1-bromo-2-methyl naphthoate is 2: 1-10: 1, adding an acid-binding agent, the molar ratio of the acid-binding agent to the raw material 1-bromo-2-methyl naphthoate is 1: 1-3: 1, dropping trifluoromethanesulfonic anhydride at-20-40 ℃, adding trifluoromethanesulfonic anhydride and the raw material 1-hydroxy-2-methyl naphthoate at a molar ratio of 0.9: 1-1.5: 1, reacting at-20-40 ℃ for 1-6 h after dropping, and carrying out acidification, extraction, water washing and concentration to obtain the compound shown in the formula A.
In some embodiments, wherein the process is carried out in the presence of a solvent; preferably, the solvent I is selected from dichloromethane, dichloroethane, chloroform, toluene, methylcyclohexane; preferably, the reaction solvent I is one of dichloromethane and toluene.
In some embodiments, wherein the method is performed in the presence of an acid scavenger; preferably, the acid-binding agent is selected from triethylamine, pyridine, dimethylethylenediamine or 4-dimethylaminopyridine; preferably, the acid-binding agent is one of triethylamine and pyridine.
Specifically, the compound of formula B is prepared by the following steps:
under the action of a catalyst, the molar ratio of the catalyst to a compound of a formula A is 0.0001: 1-0.01: 1, the compound of the formula A, 4-halogenated phenylboronic acid and alkali are uniformly mixed in a solvent II, the molar ratio of the compound of the formula A to the 4-halogenated phenylboronic acid is 1: 0.9-1: 1.5, the volume mass ratio of the solvent II to the compound of the formula A is 5: 1-15: 1, the mol ratio of the alkali to the compound of the formula A is 0.5: 1-3: 1, Suzuki reaction is carried out at the temperature of 60-120 ℃ for 2-25 h, and the compound of the formula B is prepared by extraction, water washing and concentration.
In some embodiments, wherein the process is carried out in the presence of a catalyst; preferably, the catalyst used is selected from Pd (Pph)3)4、PdCl2(Pph3)2、Pd-132。
In some embodiments, wherein the process is carried out in the presence of a solvent; preferably, the solvent II is one, two or three of ethanol, toluene, dioxane, tetrahydrofuran and water; preferably, the solvent II is a mixed solvent of toluene and water; preferably, the solvent II is toluene.
In some embodiments, wherein the process is carried out in an alkaline environment; preferably, the base for the reaction is selected from K2CO3、Na2CO3、KHCO3、NaHCO3、CH3COOK、CH3COONa; preferably, the reaction is carried outThe base is selected from K2CO3、Na2CO3、KHCO3。
Specifically, the compound of formula C is prepared by the following steps:
mixing a compound shown in the formula B with an alkaline hydrolysis reagent, carrying out reflux reaction on the mixture and a solvent III for 1-10 hours at 70-100 ℃, wherein the molar ratio of the alkaline hydrolysis reagent to the compound shown in the formula B is 1.5: 1-5: 1, and the volume mass ratio of the solvent III to the compound shown in the formula B is 3: 1-10: 1, and carrying out acidification, extraction, water washing and drying on the mixture to obtain a compound shown in the formula C;
in some embodiments, wherein the process is carried out in the presence of an alkaline hydrolyzing reagent; preferably, the alkaline hydrolysis agent used is selected from potassium hydroxide, sodium hydroxide.
In some embodiments, wherein the process is carried out in the presence of a solvent; preferably, the solvent III is one or a mixture of methanol, ethanol and water.
Specifically, the compound of the formula I is prepared by the following steps:
dissolving a compound shown in the formula C in a solvent IV, wherein the volume mass ratio of the solvent IV to the compound shown in the formula C is 4: 1-10: 1, adding a ring closing reagent, the mass ratio of the ring closing reagent to the compound shown in the formula C is 5: 1-10: 1, the reaction temperature is 40-140 ℃, the reaction time is 4-15 h, and extracting, washing, concentrating and recrystallizing to obtain a compound shown in the formula I;
in some embodiments, wherein the method is performed in the presence of a ring closing agent; preferably, the ring closing reagent used is selected from PPA, methanesulfonic acid.
In some embodiments, wherein the process is carried out in the presence of a solvent; preferably, the solvent used is selected from dichloromethane, dichloroethane, toluene or xylene.
Compared with the prior art, the invention has the following beneficial effects or advantages:
(1) the ring closing reaction of the compound of the formula I is decomposed into two steps of alkaline hydrolysis and ring closing reaction, the classical alkaline hydrolysis of carboxylic ester replaces acidolysis, the occurrence of reversible reaction is avoided, the yield of the two steps of reaction is more than 90%, and the large-scale industrial production is facilitated;
(2) the compound of the formula C is selected as a precursor for synthesizing the compound of the formula I, and the carboxyl in the compound of the formula C is easy to generate substitution reaction to prepare the compound of the formula I, so that the yield of the step is ensured;
(3) the invention has low dosage of ring closing reagent, avoids the generation of tar in a reaction system, simplifies the purification of a final product and reduces the dosage of waste water.
Detailed Description
The methods of the present invention may be carried out using the methods disclosed herein and conventional modifications thereof, which will be apparent from the disclosure herein and methods well known in the art. Conventional and well-known synthetic methods may be used in addition to those taught herein. The synthesis of typical compounds described herein (e.g., compounds of formula i) can be accomplished as described in the examples below.
Example 1
This example provides the preparation and synthesis of compounds of formula A, B, C, and I.
(1) Preparation of Compounds of formula A
Under the protection of nitrogen, 600ml of toluene, 202.2g of 1-hydroxy-2-methyl naphthoate and 101.2g of triethylamine are sequentially added into a 3L three-necked bottle, the temperature of the system is reduced to-20 ℃, 253.9g of trifluoromethanesulfonic anhydride is added dropwise, the temperature is controlled to be-20 ℃ to-10 ℃, the reaction is carried out for 6 hours after the addition is finished, and the reaction is stopped. And pouring the reaction system into 2000ml of 7% diluted hydrochloric acid, stirring, adding 2000ml of toluene for extraction, combining organic phases, washing to be neutral, and concentrating under reduced pressure until no solvent flows out to obtain 300.0g of the compound of the formula A.
Wherein GC (gas phase purity) > 96% and Y (yield) ═ 90%.
(2) Preparation of Compounds of formula B
300.0g of the compound of the formula A, 1500ml of toluene, 126.3g of 4-chlorophenylboronic acid, 61.9g of potassium carbonate and 0.06g of the catalyst Pd-132 are added in succession to a 5L three-necked flask under nitrogen protection. Heating, refluxing and reacting at 114-118 ℃ for 1h, cooling to room temperature, extracting the reaction system of 2000ml of water with 500ml of toluene once, combining organic phases, washing to be neutral, and concentrating under reduced pressure until no solvent flows out to obtain 240.0g of the compound of the formula B in a reddish brown viscous concentrated product.
Wherein, LC (liquid phase purity) > 98% and Y is 90%.
(3) Preparation of Compounds of formula C
Adding 240.0g of the compound of the formula B obtained in the step (2), 67.9g of potassium hydroxide and 720g of water into a 5L three-necked bottle, heating to 100 ℃, stirring for reaction until the system is clear (about 4h), cooling the reaction liquid to room temperature, adjusting the pH of the system to be less than 4 by using concentrated hydrochloric acid, filtering, leaching the obtained white solid to be neutral by using water, and drying at 100 ℃ to constant weight to obtain 228.6g of the compound of the formula C.
Wherein LC is more than 99%, and Y is 100%.
(4) Preparation of the target product Compound of formula I
2280ml of xylene, 228.6g of the compound of the formula C and 1143g of PPA were sequentially added to a dry 3L three-necked flask, heated to 140 ℃ and reacted under reflux for 15 hours. The reaction system is cooled to room temperature, poured into 3000ml of water, extracted by 2280ml of toluene, the organic phases are combined, washed to be neutral by water, concentrated under reduced pressure until no solvent flows out, the obtained orange solid is recrystallized by dichloroethane, and dried at 100 ℃ to obtain 193.0g of the compound (9-chloro-7H-benzo [ c ] fluorene-7-one) in the formula I.
Wherein LC is more than 99.9%, and Y is 90%.
Example 2
(1) Preparation of Compounds of formula A
Under the protection of nitrogen, 2000ml of dichloromethane, 202.2g of 1-hydroxy-2-methyl naphthoate and 237.0g of pyridine are sequentially added into a 3L three-necked bottle, the system is cooled to 10 ℃, 564.3g of trifluoromethanesulfonic anhydride is added dropwise, the temperature is controlled to be 10-20 ℃, the reaction is stopped after the addition of materials is finished for 1 h. The reaction system is poured into 2000ml of 7% diluted hydrochloric acid, stirred, added with 2000ml of toluene for extraction, the organic phases are combined, washed to be neutral, and concentrated under reduced pressure until no solvent flows out, thus obtaining 327.6g of the compound of the formula A.
Wherein GC > 96%, Y98%.
(2) Preparation of Compounds of formula B
To a 10L three-necked flask were added 327.6g of the compound of formula A, 3270ml of toluene, 655ml of ethanol, 295.23g of 4-bromophenylboronic acid, 246.97g of sodium bicarbonate, 655ml of water, and 6.87g of bis (triphenylphosphine) palladium dichloride in this order under nitrogen protection. And after mixing, heating to the reaction temperature of 70-74 ℃, carrying out reflux reaction for 25h, cooling to room temperature, adding 2000ml of water into the reaction system, separating, extracting once with 500ml of toluene, combining organic phases, washing with water to be neutral, and concentrating under reduced pressure until no solvent flows out to obtain 282.1g of the compound of formula B as a reddish brown viscous concentrated product.
Wherein LC is more than 98%, and Y is 97%.
(3) Preparation of Compounds of formula C
282.1g of the compound of the formula B obtained in example 2, 190.1g of sodium hydroxide, 1400ml of water and 1400ml of methanol are added into a 5L three-necked bottle, the mixture is heated to 70-75 ℃, stirred and reacted until the system is clear (about 10h), the reaction liquid is cooled to room temperature, concentrated hydrochloric acid is used for adjusting the pH of the system to be less than 4, filtration is carried out, the obtained white solid is rinsed to be neutral by water, and the mixture is dried to constant weight at 100 ℃ to obtain 268.76g of the compound of the formula C.
Wherein LC is more than 99%, and Y is 100%.
(4) Preparation of the target product Compound of formula I
920ml of methylene chloride, 228.6g of the compound of the formula C and 2286g of methanesulfonic acid were sequentially added to a dry 3L three-necked flask, and the mixture was heated to 40 ℃ to reflux and reacted for 4 hours. The reaction system is cooled to room temperature, poured into 3000ml of water, extracted by 920ml of dichloromethane, the combined organic phases are washed to be neutral by water, concentrated under reduced pressure until no solvent flows out, the obtained orange solid is recrystallized by dichloroethane, and dried at 100 ℃ to obtain 200.0g of the compound (9-chloro-7H-benzo [ c ] fluorene-7-ketone) in the formula I.
Wherein LC is more than 99.9%, and Y is 93.5%.
(5) Pattern detection of Compounds of formula I
The compound of formula I (9-chloro-7H-benzo [ c ] fluoren-7-one) obtained was analyzed using a gas chromatography-mass spectrometry (GC-MS) spectrometer with the following profile data:
mass spectrum of target compound (GC-MS): m264.
1H-NMR (500MHz, CDCl3) of the target compound: δ 8.40 (1H); δ is 7.85 to 7.95 (1H); δ 7.60 (1H); δ 7.60 to 7.65 (3H); δ 7.48(1H), thus demonstrating the successful synthesis of the compound.
As described above, the present invention can be preferably implemented, and the above-mentioned embodiments only describe the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various changes and modifications of the technical solution of the present invention made by those skilled in the art without departing from the design spirit of the present invention shall fall within the protection scope defined by the present invention.
Claims (10)
1. A method of synthesizing a compound of formula i:
wherein
X is one of Cl and Br;
the method comprises the following steps:
etherifying 1-hydroxy-2-methyl naphthoate to form a compound of formula a; carrying out Suzuki reaction on the compound of the formula A to form a compound of a formula B; carrying out alkaline hydrolysis on the compound of the formula B to obtain a compound of a formula C; and converting the compound of formula C to a compound of formula I,
the compound of formula a is:
the compounds of formula B are:
the compound of formula C is:
2. the method for synthesizing the compound of formula I according to claim 1, wherein the step of preparing the compound of formula A comprises the steps of dissolving the raw material methyl 1-hydroxy-2-naphthoate in the solvent I, adding an acid-binding agent, dropwise adding trifluoromethanesulfonic anhydride at the reaction temperature of-20 to 40 ℃, reacting for 1 to 6 hours at-20 to 40 ℃ after completing dropwise addition, and obtaining the compound of formula A through acidification, extraction, water washing and concentration.
3. The method for synthesizing the compound of formula I according to claim 2, wherein the molar ratio of the trifluoromethanesulfonic anhydride to the methyl 1-bromo-2-naphthoate is 0.9:1 to 1.5:1, and the volume-to-mass ratio of the solvent I to the methyl 1-bromo-2-naphthoate is 2:1 to 10: 1; the solvent I is one of dichloromethane, dichloroethane, chloroform, toluene and methylcyclohexane; the acid-binding agent is one of triethylamine and pyridine.
4. The method for synthesizing the compound of formula I according to claim 1, wherein the step of preparing the compound of formula B comprises the steps of uniformly mixing the compound of formula A, the 4-halogenated phenylboronic acid and the base in a solvent II under the action of a catalyst, carrying out a Suzuki reaction at 60-120 ℃ for 2-25 h, extracting, washing with water, and concentrating to obtain the compound of formula B.
5. The method for synthesizing the compound of formula I according to claim 4, wherein the molar ratio of the compound of formula A to the 4-halophenylboronic acid is 1:0.9 to 1:1.5, and the molar ratio of the catalyst to the compound of formula A is 0.0001:1 to 0.01: 1; the catalyst is Pd (Pph)3)4、PdCl2(Pph3)2And Pd-132; the solvent II is one, two or three of ethanol, toluene, dioxane, tetrahydrofuran and water; the base is K2CO3、Na2CO3、KHCO3、NaHCO3、CH3COOK、CH3COONa.
6. The method for synthesizing the compound of formula I according to claim 1, wherein the step of preparing the compound of formula C comprises the steps of mixing the compound of formula B with an alkaline hydrolysis reagent, carrying out reflux reaction on the mixture and a solvent III at 70-100 ℃ for 1-10 h, and carrying out acidification, extraction, water washing and material drying to obtain the compound of formula C.
7. The method for synthesizing the compound of formula I according to claim 6, wherein the molar ratio of the alkaline hydrolysis reagent to the compound of formula B is 1.5:1 to 5: 1; the mass ratio of the solvent III to the compound of the formula B is 3: 1-10: 1; the alkaline hydrolysis reagent is one of potassium hydroxide and sodium hydroxide; the solvent III is one or a mixture of methanol, ethanol and water.
8. The method for synthesizing the compound of formula I according to claim 1, wherein the step of converting the compound of formula C into the compound of formula I comprises the steps of dissolving the compound of formula C in a solvent IV, adding a ring closing reagent, reacting for 4-15 h at a reaction temperature of 40-140 ℃, extracting, washing with water, concentrating, and recrystallizing to obtain the compound of formula I.
9. The method for synthesizing the compound shown in the formula I according to claim 8, wherein the mass ratio of the ring closing reagent to the compound shown in the formula C is 5: 1-20: 1, and the mass ratio of the solvent IV to the compound shown in the formula C is 4: 1-10: 1; the ring closing reagent is one of PPA and methanesulfonic acid; and the solvent IV is one of dichloromethane, dichloroethane, toluene and xylene.
10. Use of a process according to any one of claims 1 to 9 for the synthesis of 9-halo-7H-benzo [ c ] fluoren-7-one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111072888.6A CN113735694A (en) | 2021-09-14 | 2021-09-14 | Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111072888.6A CN113735694A (en) | 2021-09-14 | 2021-09-14 | Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113735694A true CN113735694A (en) | 2021-12-03 |
Family
ID=78738606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111072888.6A Pending CN113735694A (en) | 2021-09-14 | 2021-09-14 | Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113735694A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040185255A1 (en) * | 2003-03-20 | 2004-09-23 | Walters Robert W | Indeno-fused photochromic naphthopyrans, naphthols and photochromic articles |
| JP2009114114A (en) * | 2007-11-06 | 2009-05-28 | Tosoh Corp | Benzofluorenone derivative and method for producing the same |
| CN106458953A (en) * | 2014-05-13 | 2017-02-22 | Sfc株式会社 | Heterocyclic compound containing aromatic amine group, and organic light-emitting device comprising same |
| CN109863153A (en) * | 2017-02-28 | 2019-06-07 | 株式会社Lg化学 | Heterocyclic compound and organic luminescent device comprising it |
| CN110832657A (en) * | 2017-07-11 | 2020-02-21 | Sfc株式会社 | Organic light emitting element with high efficiency |
| CN111592464A (en) * | 2019-02-20 | 2020-08-28 | 常州强力电子新材料股份有限公司 | Organic compound containing spirobifluorene structure and application thereof |
-
2021
- 2021-09-14 CN CN202111072888.6A patent/CN113735694A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040185255A1 (en) * | 2003-03-20 | 2004-09-23 | Walters Robert W | Indeno-fused photochromic naphthopyrans, naphthols and photochromic articles |
| CN102532088A (en) * | 2003-03-20 | 2012-07-04 | 光学转变公司 | Indeno-fused photochromic naphthopyrans, naphthols and photochromic articles |
| JP2009114114A (en) * | 2007-11-06 | 2009-05-28 | Tosoh Corp | Benzofluorenone derivative and method for producing the same |
| CN106458953A (en) * | 2014-05-13 | 2017-02-22 | Sfc株式会社 | Heterocyclic compound containing aromatic amine group, and organic light-emitting device comprising same |
| CN109863153A (en) * | 2017-02-28 | 2019-06-07 | 株式会社Lg化学 | Heterocyclic compound and organic luminescent device comprising it |
| CN110832657A (en) * | 2017-07-11 | 2020-02-21 | Sfc株式会社 | Organic light emitting element with high efficiency |
| CN111592464A (en) * | 2019-02-20 | 2020-08-28 | 常州强力电子新材料股份有限公司 | Organic compound containing spirobifluorene structure and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| JUN-TAO HU等: "Expedient synthesis of 9,10-phenanthrenes via LiOPiv-promoted and palladium-catalysed aryne annulation by vinyl triflates", 《ORGANIC CHEMISTRY FRONTIERS》, vol. 5, pages 2045 - 2050 * |
| 曹正白等: "《有机反应中的酸碱催化》", vol. 1, 31 July 1995, 高等教育出版社, pages: 68 * |
| 荣国斌等: "《大学有机化学基础》", vol. 1, 31 July 2001, 华东理工大学出版社, pages: 410 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107141207B (en) | Synthetic method of 3 '-acyl-2, 4' -dihydroxy benzophenone compound | |
| CN108774129A (en) | The method that visible light catalytic organic boronic prepares esters of alpha, beta, unsaturated carboxylic acids derivative | |
| CN108610278B (en) | Synthetic method of 6-amino-5-acyl benzo [ a ] carbazole compound | |
| CN112979402A (en) | Industrial production method of benzo [ a ] anthracene | |
| CN113735694A (en) | Method for synthesizing 9-halogen-7H-benzo [ c ] fluorene-7-ketone | |
| CN102942444B (en) | Synthesis method of 2,2'-dibromo-9,9'-spirobifluorene | |
| CN110922373A (en) | Synthesis method of methyl platinolate | |
| CN111362795B (en) | Preparation method of substituted butyrate derivatives | |
| CN108299466B (en) | Improved dolutegravir synthesis method | |
| CN113698375A (en) | Synthesis method of 4-cyclohexylimine methyl substituted benzofuran derivative | |
| CN113651788A (en) | 3-amine alkyl chromone compound and preparation method thereof | |
| CN103965041A (en) | Method for preparing 2-(4-benzyloxy phenyl)ethanol fatty acid ester | |
| CN108976198B (en) | Synthetic method of 3- (4-pyridine) indole compound | |
| CN106749315B (en) | 8- hexyl-thieno [3 ', 2 ':3,4] benzo [1,2-c] carbazole compound and its synthetic method | |
| CN110078746B (en) | 2-carbonyl thiazolothiophene compound with luminescent property and preparation method and application thereof | |
| CN115215778B (en) | Alpha-difluoro selenomethyl ketone derivative and preparation method thereof | |
| CN116574049A (en) | Synthesis method for efficiently coupling electron-rich iodo benzene with carbazole | |
| CN108358826B (en) | Synthesis method of tetrahydroindole | |
| CN103936753B (en) | Natural products Daldinin and the like total synthesis method | |
| CN111116513B (en) | Fixed-point bromination method of 2,1, 3-benzothiadiazole derivative | |
| TWI466861B (en) | Synthesis method of oligo-anthracene and oligo-anthracene thereof | |
| CN115260057B (en) | Improved method for preparing functionalized cis-trans dicyanoethylene compound through desulfurization of 2, 5-dinitrothiophene | |
| CN114249679B (en) | Method for preparing alpha, alpha-gem difluoro carbonyl compound | |
| CN112159347B (en) | Preparation method of picolitamide | |
| CN110452097B (en) | Preparation method of 1-hydroxypyrene |
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 |