CN116768756A - Novel 2-hydroxy diaryl methane compound and efficient synthesis method thereof - Google Patents
Novel 2-hydroxy diaryl methane compound and efficient synthesis method thereof Download PDFInfo
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- CN116768756A CN116768756A CN202310622194.8A CN202310622194A CN116768756A CN 116768756 A CN116768756 A CN 116768756A CN 202310622194 A CN202310622194 A CN 202310622194A CN 116768756 A CN116768756 A CN 116768756A
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 88
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 87
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 32
- RKHXQBLJXBGEKF-UHFFFAOYSA-M tetrabutylphosphanium;bromide Chemical compound [Br-].CCCC[P+](CCCC)(CCCC)CCCC RKHXQBLJXBGEKF-UHFFFAOYSA-M 0.000 claims abstract description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 30
- MXSVEBOOHMKMQG-UHFFFAOYSA-N 3-bromo-3h-1-benzofuran-2-one Chemical compound C1=CC=C2C(Br)C(=O)OC2=C1 MXSVEBOOHMKMQG-UHFFFAOYSA-N 0.000 claims abstract description 29
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims abstract description 29
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- BWHDROKFUHTORW-UHFFFAOYSA-N tri-tert-butylphosphine Substances CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000654 additive Substances 0.000 claims abstract description 5
- 230000000996 additive effect Effects 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 84
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 24
- 239000000758 substrate Substances 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 10
- 239000000843 powder Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- -1 2,4-bis (4-hydroxybenzyl) phenol (2, 4-bis (4-hydroxybenzyl) phenol) Chemical compound 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ACZGCWSMSTYWDQ-UHFFFAOYSA-N 3h-1-benzofuran-2-one Chemical compound C1=CC=C2OC(=O)CC2=C1 ACZGCWSMSTYWDQ-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 2
- 229960004045 tolterodine Drugs 0.000 description 2
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 2
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical class OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- RZCPLOMUUCFPQA-UHFFFAOYSA-N (4-ethylphenyl)boronic acid Chemical class CCC1=CC=C(B(O)O)C=C1 RZCPLOMUUCFPQA-UHFFFAOYSA-N 0.000 description 1
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical class OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 1
- NSFJAFZHYOAMHL-UHFFFAOYSA-N (4-nitrophenyl)boronic acid Chemical class OB(O)C1=CC=C([N+]([O-])=O)C=C1 NSFJAFZHYOAMHL-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical class OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- 206010005052 Bladder irritation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 241000305491 Gastrodia elata Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010027566 Micturition urgency Diseases 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 208000022934 urinary frequency Diseases 0.000 description 1
- 230000036318 urination frequency Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/53—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a novel 2-hydroxy diaryl methane compound and a high-efficiency synthesis method thereof, wherein bromobenzofuranone and phenylboronic acid derivatives are used as raw materials, di-tri-tert-butyl phosphine palladium is used as a catalyst, potassium hydroxide is used as alkali, tetrabutyl phosphonium bromide is used as an additive, toluene and water are used as solvents, and the 2-hydroxy diaryl methane compound is obtained in high yield. The method has the advantages of low cost, high yield, simple operation, no pollution and the like, and has potential industrial application prospect. The method provides a cheap and green way for preparing the 2-hydroxy diaryl methane compounds.
Description
[ field of technology ]
The invention relates to a novel 2-hydroxy diaryl methane compound and a high-efficiency synthesis method thereof, belonging to the field of organic synthesis. The reaction yield is excellent, the substrate is widely applicable, and the benzofuranone is coupled and decarbonylated to be converted into the 2-hydroxy diaryl methane compound by using a palladium catalyst.
[ background Art ]
The 2-hydroxy diaryl methane compound is an important fine chemical intermediate and can be widely applied to the fields of pesticides, organic functional materials, medicines and the like. Such as Tolterodine (Tolterodine), which is a competitive muscarinic receptor antagonist, is used to treat urinary incontinence, urinary frequency, and urgency symptoms caused by bladder irritation. 2,4-bis (4-hydroxybenzyl) phenol (2, 4-bis (4-hydroxybenzyl) phenol) is a natural product present at the root of gastrodia elata and was first extracted for the treatment of headache, dizziness, rheumatism, convulsions and epilepsy. The synthesis method of the aryl methane derivative is mainly synthesized by methods such as Friedel-Crafts benzylation promoted by Lewis acid or cross dehydrogenation benzyl arylation catalyzed by transition metal. These strategies typically require the substrate to have an activating group in the benzyl position or the use of an excess of base, oxidizing agent or free radical initiator. Substituents on aromatic hydrocarbons generally have a great influence on the reaction regioselectivity. Benzofuranone is a drug molecular skeleton and has wide application in the field of organic synthesis. The 2-hydroxy diaryl methane compound is synthesized by using bromobenzofuranone and phenylboric acid as initial raw materials, using ditri-butyl phosphine palladium as a catalyst, using potassium hydroxide as alkali, using tetrabutyl phosphonium bromide as an additive, using toluene and water as solvents and using a nitrogen next-pot method, and the method has the advantages of easily available raw materials, simple operation, mild reaction conditions, high product yield and purity and less synthesis process reports. The synthesized novel 2-hydroxy diaryl methane derivative has better bioactivity and physicochemical properties and has greater pharmaceutical value.
[ invention ]
The invention aims to provide a novel method for efficiently and selectively synthesizing 2-hydroxy diaryl methane compounds by taking benzofuranone and phenylboronic acid as raw materials by taking di-tri-tert-butylphosphine palladium as a catalyst and a preparation method thereof, and the method has the advantages of low cost, high yield, simplicity and convenience in operation, no pollution and the like, and has a certain feasibility for realizing industrial production. The method is characterized in that: di-tri-tert-butylphosphine palladium is used as a catalyst, potassium hydroxide is used as alkali, tetrabutyl phosphonium bromide is used as an additive, bromobenzofuranone substrate I and phenylboronic acid substrate II are used as reaction raw materials, and the 2-hydroxy diaryl methane compound III can be obtained in the period of 6-18h by effectively reacting at 120-160 ℃ under the condition that toluene and water are used as solvents.
Wherein said R is 1 Is a functional group such as hydrogen, methyl, ethyl, dimethyl, fluorine, etc., R 2 Is a functional group such as hydrogen, methyl, fluorine, chlorine, bromine, trifluoromethyl, tert-butyl, tert-butoxycarbonyl, etc.
In the synthesis method, the dosage of the catalyst of the di-tri-tert-butylphosphine palladium is 0.1-1 equivalent, the dosage of the base is 0.5-2 equivalent, the solvent is toluene, 1, 4-dioxane, water and other solvents, preferably toluene and water; the reaction time is 6-18h, preferably 12h, and the reaction temperature is 80-160 ℃, preferably 160 ℃.
The synthesis method of the novel 2-hydroxy diaryl methane compound catalyzed by the di-tri-tert-butyl phosphine palladium opens up a new low-cost simple way, and has the advantages that: the yield of the target product is high, the reaction condition is simple, and the reaction operation is simple.
Principle of reaction
[ description of the drawings ]
FIG. 1 shows a scheme for preparing novel 2-hydroxy diaryl methane compounds
[ detailed description ] of the invention
The invention provides a novel efficient catalytic synthesis method of 2-hydroxy diaryl methane compounds, which is shown in the accompanying drawings: and (3) placing bromobenzofuranone, phenylboronic acid, potassium hydroxide and tetrabutyl phosphonium bromide into a reaction vessel, reacting for 12 hours in a nitrogen environment at 160 ℃, and separating by a column after the reaction is finished to obtain a target product. The invention is further illustrated below in connection with specific preparations:
condition screening
Example 1:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium carbonate 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.5mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-cyano), white powder, yield 51%. Characterization data: 1 H NMR(400MHz,DMSO)δ9.23(s,1H),7.85(d,J＝8.2Hz,2H),7.78(d,J＝8.3Hz,2H),7.59(d,J＝8.0Hz,2H),7.34(d,J＝8.0Hz,2H),6.90(s,1H),6.84(d,J＝8.3Hz,1H),6.76(d,J＝8.1Hz,1H),3.90(s,2H),2.15(s,3H). 13 C{ 1 H}NMR(101MHz,DMSO)δ153.2,145.1,142.9,136.1,133.2,131.4,129.9,128.2,127.9,127.8,127.4,127.2,119.5,115.5,110.2,35.6,20.7.HRMS(EI)m/z:[M]Calcd for C 21 H 17 NO 299.1310,Found 299.1312.
example 2:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction is finished, no target product exists. Example 3:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction is finished, no target product exists. Example 4:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, di-tri-tert-butyl0.02mmol of palladium (II) alkylphosphine, 0.4mmol of potassium hydroxide, 0.4mmol of tetrabutylphosphonium bromide, 1mL of toluene and 0.4mL of water, and the reaction was stirred at 160℃for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-cyano), white powder with 92% yield.
Example 5:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-ethyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-ethyl, R 2 =4-cyano), white powder, yield 87%.
Example 6:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-isopropyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-isopropyl, R 2 =4-cyano), white powder with a yield of 83%.
Example 7:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =3, 5-dimethyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =3, 5-dimethyl, R 2 =4-cyano), white powder with a yield of 80%. Example 8:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 Beta-naphthyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 Beta-naphthyl, R 2 =4-cyano), white powder with a yield of 85%.
Example 9:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =2-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =2-methyl, R 2 =4-cyano), white powder with 99% yield.
Example 10:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methoxy, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methoxy, R 2 =4-cyano), white powder with 99% yield.
Example 11:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-phenyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-phenyl, R 2 =4-cyano), white powder, yield 74%.
Example 12:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-hydroxy, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-hydroxy, R 2 =4-cyano), white powder with a yield of 32%.
Example 13:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-trifluoromethyl, phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-trifluoromethyl), white powder with a yield of 89%. Example 14:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-methyl), white powder, yield 80%.
Example 15:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-t-butoxycarbonyl group, phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-t-butoxycarbonyl), white powder, yield 66%. Example 16:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-nitro, phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-nitro), white powder with a yield of 61%.
Example 17:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-ethyl phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-ethyl), white powder with a yield of 72%.
Example 18:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-methoxy), white powder with a yield of 75%. Example 19:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction is finished, separating by column chromatographyIsolating to obtain the target compound III (R) 1 =4-methyl, R 2 =4-H), white powder, yield 74%.
Example 20:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of =2, 4-difluoro), phenylboronic acid derivative II (R 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =2, 4-difluoro), white powder with a yield of 34%. Example 21:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-fluoro phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-fluoro), white powder with a yield of 51%.
Example 22:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-ethynyl group, phenylboronic acid derivative II (R 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-ethynyl), white powder, yield 75%. Example 23:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-hydroxy, phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, reactionThe reaction was stirred at 160℃for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-hydroxy), white powder with a yield of 94%.
Example 24:
into a 10mL reaction tube was charged bromobenzofuranone derivative I (R 1 =4-methyl, R 2 0.2mmol of 4-chloro phenylboronic acid derivative II (R) 2 =4-cyano) 0.4mmol, ditri-butyl phosphine palladium 0.02mmol, potassium hydroxide 0.4mmol, tetrabutyl phosphonium bromide 0.4mmol, toluene 1mL, water 0.4mL, and the reaction was stirred at 160 ℃ for 12h. After the reaction, the target compound III (R 1 =4-methyl, R 2 =4-chloro), white powder with a yield of 68%.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present patent is to be determined by the appended claims.
Claims (2)
1. A novel 2-hydroxy diaryl methane compound and a high-efficiency synthesis method thereof are characterized in that di-tri-tert-butyl phosphine palladium is adopted as a catalyst, potassium hydroxide is adopted as alkali, tetrabutyl phosphonium bromide is adopted as an additive, bromobenzofuranone substrate I and phenylboronic acid substrate II are adopted as reaction raw materials, and are effectively reacted at 140-160 ℃ under the condition of toluene and water as solvents, 2-hydroxy diaryl methane compound III can be obtained within 6-18h, wherein R is as follows 1 Is a functional group such as hydrogen, methyl, ethyl, dimethyl, fluorine, etc., R 2 Is a functional group such as hydrogen, methyl, fluorine, chlorine, bromine, trifluoromethyl, tert-butyl, tert-butoxycarbonyl, etc.
2. The synthesis method according to claim 1, wherein the catalyst is 0.05-0.1 equivalent of di-tert-butylphosphine palladium, 1-2 equivalents of alkali potassium hydroxide, 1-2 equivalents of additive tetrabutyl phosphonium bromide, and the solvent is toluene and water; the reaction time is 6-18h, preferably 12h, and the reaction temperature is 140-160 ℃, preferably 160 ℃.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003011880A1 (en) * | 2001-07-31 | 2003-02-13 | Kissei Pharmaceutical Co., Ltd. | Glucopyrano syloxybenzyl benzene derivative, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof |
| CN114835664A (en) * | 2022-03-25 | 2022-08-02 | 湖南大学 | Novel trans-styryl benzofuranone compound and efficient synthesis method thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003011880A1 (en) * | 2001-07-31 | 2003-02-13 | Kissei Pharmaceutical Co., Ltd. | Glucopyrano syloxybenzyl benzene derivative, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof |
| CN114835664A (en) * | 2022-03-25 | 2022-08-02 | 湖南大学 | Novel trans-styryl benzofuranone compound and efficient synthesis method thereof |
Non-Patent Citations (3)
| Title |
|---|
| LUIS BERING，等: "Metal-Free C−O Bond Functionalization: Catalytic Intramolecular and Intermolecular Benzylation of Arenes", ORG. LETT., vol. 20, 14 June 2018 (2018-06-14) * |
| ZHOU TONG, 等: "Cu(I)-Catalyzed C−H Alkenylation of Tertiary C(sp3)−H Bonds of 3‑Aryl Benzofuran-2(3H)‑ones to Give Z- and E‑Styrene Containing Quaternary Carbon Centers with 99/1 Regioselectivity", J. ORG. CHEM., vol. 87, 12 April 2022 (2022-04-12) * |
| ZHOU TONG, 等: "Nickel-Catalyzed Decarbonyloxidation of 3‑Aryl Benzofuran- 2(3H)‑ones to 2‑Hydroxybenzophenones", J. ORG. CHEM., vol. 85, 2 June 2020 (2020-06-02) * |
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