CN108440251B - Method for photo/nickel concerted catalysis of monoarylation diol - Google Patents

Method for photo/nickel concerted catalysis of monoarylation diol Download PDF

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CN108440251B
CN108440251B CN201810129076.2A CN201810129076A CN108440251B CN 108440251 B CN108440251 B CN 108440251B CN 201810129076 A CN201810129076 A CN 201810129076A CN 108440251 B CN108440251 B CN 108440251B
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黄治炎
孟鸽
解昆
马俊杰
薛东
杨俊�
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Shaanxi Normal University
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Abstract

The invention discloses a method for photo/nickel concerted catalysis of monoarylation diol, which directly takes simple and easily obtained brominated aromatic hydrocarbon and diol as raw materials, adopts BODIPY organic photosensitizer and cheap nickel source to concertedly catalyze the cross coupling between the diol and the brominated aromatic hydrocarbon under the condition of no external ligand, and realizes the selective monoarylation diol compound, wherein the monoarylation/biarylation ratio is as high as 18: 1. The method has good functional group tolerance, and is suitable for various diol compounds with different structures, such as vicinal diol, 1, 3-diol, 1, 4-diol, monodisperse polyethylene glycol, etc. More importantly, the method has the advantages of low dosage of the photosensitizer, reaction temperature close to room temperature, greenness, economy and high efficiency. The advantages enable the invention to have higher scale synthesis value and can serve the development of social economy.

Description

Method for photo/nickel concerted catalysis of monoarylation diol
Technical Field
The invention belongs to the technical field of selective monoarylation diol, and particularly relates to a method for selective monoarylation diol through photo/nickel concerted catalysis.
Background
Aryl alkyl ethers are important in the preparation of natural products, pharmaceuticals and polymer material molecules. The aromatic glycol ether series has no toxicity, high miscibility, moderate volatilization rate, excellent coalescence and coupling capacity and low surface tension, and thus is widely used in automobile and automobile repairing paint, electrophoretic paint, industrial stoving varnish, ship, container and woodenware paint. Glycol aromatic ethers are also good solvents for polymers such as fats and oils, natural resins, cellulose fibers, alkyd resins, etc., and are widely used as solvents and in personal care products such as soaps, detergents, perfumes, cosmetics, toilet products and pharmaceuticals.
The polyethylene glycol in the diol is a linear polymer and is polymerized by ethylene oxide. In the field of drug modification and drug carrier research, polyethylene glycol (PEG) and its derivatives are of great interest because of their amphiphilicity, biocompatibility, non-immunogenicity, non-toxic side effects, and the like. Experiments prove that after PEG modification, the immunogenicity of some proteins and enzymes in animal bodies is greatly reduced, and the half-life period of the proteins and the enzymes in the bodies is prolonged. Unlike polysaccharides, only the terminal hydroxyl groups of PEG can be activated and react with proteins, avoiding the complexity of the reaction and the complexity of the product. However, PEG has two hydroxyl groups, and if reacting with protein, it may form "PEG-protein-PEG-protein" conjugates with different degrees of cross-linking, and even precipitation may occur. Therefore, the selective unilateral derivatization of polyethylene glycol, especially monodisperse polyethylene glycol, is very important.
The current methods for synthesizing such products mainly comprise:
(1) in 1983, it was reported that ethylene glycol phenyl ether was obtained by refluxing triphenylbismuth diacetate in an excess of ethylene glycol in methylene chloride. However, bismuth triphenyl diacetate is expensive and not suitable for large-scale preparation (J.org.chem.1983,48, 441-.
Figure BDA0001574321160000011
(2) In 1995, the synthesis of monoarylated products was reported in the literature using iron-benzene complexes as starting materials and reacting them with diethylene glycol. This method requires two steps and yields are moderate, but the aryl reagent is complex and not suitable for large scale preparation (J.org.chem.1995,60, 281-284.).
Figure BDA0001574321160000021
(3) In 2006, the literature reported the preparation of ethylene glycol phenyl ether using aniline as the arylating agent and ethylene glycol as the solvent. The method has the advantages of simple and easily obtained raw materials, but needs glycol as a solvent, and the yield is only 9% (J.chem.Res.2006,12, 800-803).
Figure BDA0001574321160000022
(4) In 2010, the literature reports that phenol is used as an arylating reagent, ethylene glycol is in four-fold excess, and a product can be obtained under a high-temperature condition by adding reagents such as urea, sodium carbonate and zinc oxide into a reaction system. The method is harsh in reaction conditions and not suitable for scale-up production (j.chi.chem.soc., 2010,57, 2.).
Figure BDA0001574321160000023
(5) In 2012, the literature reports that the phenyl glycol ether is synthesized by using glycol as a raw material through a two-step method of selective activation and nucleophilic attack. The selective conversion of hydroxyl groups to easily leaving groups such as halogens, sulfonates, and the like is critical to the process and often requires a large excess of starting material to avoid the formation of the bishydroxy derivatized intermediate followed by nucleophilic substitution. This results in a large number of process steps, high waste, and a significant increase in cost (j.med.chem.2012,55, 6898-.
Figure BDA0001574321160000024
(6) 2012's patent (CN 102617257a) also reported the preparation of phenyl glycol ether using iodobenzene reacted with 8 times the amount of ethylene glycol under copper catalysis. However, this method requires iodobenzene having high activity, and the diol can be a simple diol having a small carbon number, and the yield is low.
Figure BDA0001574321160000031
(7) The reaction of various substituted bromobenzenes with ethylene glycol was reported in 2014 with good yields. However, this reaction must be carried out under high temperature conditions with ethylene glycol as a solvent, and is only applicable to inexpensive ethylene glycol (org. biomol. chem,2014,12, 4747-4753).
Figure BDA0001574321160000032
(8) In 2017, the preparation of phenyl glycol ether by directly coupling ethylene glycol and benzene under the synergetic catalysis of light/metal cobalt is reported. This method has atomic economy but very low yields (org. Lett.2017,19, 2206-.
Figure BDA0001574321160000033
The coupling reaction is the most direct, economical and efficient method for synthesizing the aryl glycol ether. The method needs to solve the biggest problems of inhibiting the generation of bi-arylation products and improving the mono-arylation selectivity. The bi-arylation product is a by-product, which on the one hand reduces the yield of the mono-arylation product and on the other hand makes it difficult to separate and purify the desired product. The relevant chemical reaction equation is as follows:
Figure BDA0001574321160000034
disclosure of Invention
The technical problem to be solved by the invention is to provide a method for selectively and directly mono-arylating diol by taking simple and easily obtained brominated aromatic hydrocarbon and diol as coupling raw materials through light/nickel concerted catalysis.
The technical scheme for solving the technical problems is as follows: adding bromoarene shown as a formula I, a diol compound shown as II-1, II-2 or II-3, a nickel source, a BODIPY organic photosensitizer and alkali into an organic solvent, carrying out cross coupling reaction under the conditions of no water and no oxygen, illumination and stirring at 40-60 ℃, after the reaction is completed, carrying out quenching reaction by using water, and separating and purifying to obtain diol monoaryl ether shown as III-1, III-2 or III-3;
Figure BDA0001574321160000041
in the formula, R1、R2Each independent representative H, C1～C4Any one of alkyl and phenyl, and X represents CH2O or N-Ts (Ts represents p-toluenesulfonyl), Y represents CH2Or N-Boc (Boc represents tert-butyloxycarbonyl), m is an integer of 0-11, and N is an integer of 0-2; ar represents phenyl, cyano-substituted phenyl, C1～C4Alkyl acyl substituted phenyl, aldehyde substituted phenyl, halogenated phenyl, C1～C4Any one of alkoxy acyl substituted phenyl, trifluoromethyl substituted phenyl and naphthyl.
In the preparation method, the molar ratio of the brominated aromatic hydrocarbon, the diol compound, the nickel source, the BODIPY organic photosensitizer and the alkali is 1: 1.3-1.5: 0.02-0.20: 0.0001-0.01: 1.5-2.0.
The nickel source is any one of bis (1, 5-cyclooctadiene) nickel, nickel chloride, nickel bromide, nickel iodide, nickel acetate and nickel trifluoromethanesulfonate.
The BODIPY organic photosensitizer is any one of the following 1 a-1 c:
Figure BDA0001574321160000042
wherein the synthesis method of BODIPY 1b and BODIPY 1c is the same as that of BODIPY 1a (Journal of Organic Chemistry,2014,79(22),10981-10987.), only the phenyl Grignard reagent used in the synthesis of BODIPY 1a needs to be replaced by the corresponding 3, 5-di-tert-butylphenyl Grignard reagent and 2-naphthyl Grignard reagent.
The base is any one of N, N-dicyclohexylmethylamine, N-dimethylcyclohexylamine, N-diethylcyclohexylamine, N-dimethylisopropylamine and 1-azabicyclo [2.2.2] octane.
The light source adopted for the illumination is white light, blue light or green light.
The organic solvent is any one of N, N-dimethylformamide, N-diethylformamide, N-dimethylacetamide and acetonitrile.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention adopts BODIPY organic photosensitizer as photocatalyst, adopts cheap nickel salt as metal catalyst, does not need additional ligand, and forms carbon-oxygen bond under the condition of near room temperature under the irradiation of visible light, and simultaneously inhibits the occurrence of secondary arylation.
2. The method solves the problem of monoarylation of nearly equivalent diol and brominated aromatic hydrocarbon for the first time, and controls the selectivity of monoarylation/diarylation to be 18: 1.
3. The method has the advantages of mild reaction conditions, simple and convenient operation, low photocatalyst consumption, no ligand participation, reaction basically performed at room temperature, lower cost, higher activity, better substrate applicability and extremely high industrial production prospect compared with the traditional coupling.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1
Synthesis of 4- (2- (2-hydroxyethoxy) ethoxy) benzonitrile
Figure BDA0001574321160000051
Under anhydrous and oxygen-free conditions, 91mg (0.5mmol) of p-bromobenzonitrile and 8.7mg (0.04mmol) of NiBr20.16mg (0.00025mmol) BODIPY 1b, 80mg (0.75mmol) diethylene glycol, 176mg (0.9mmol) N, N-dicyclohexylmethylamine are added into 1.5mL N, N-dimethylformamide, the mixture is heated to 40 ℃, the mixture is stirred and reacted for 12 hours under 2W white light illumination, after the reaction is completed, water is added for quenching reaction, the reaction solution is washed by saturated saline solution and extracted by dichloromethane, the dichloromethane extract is dried by anhydrous sodium sulfate, reduced pressure evaporation is carried out, silica gel column chromatography is used for separation, a developing agent is petroleum ether/ethyl acetate (3:1), and pure 4- (2- (2-hydroxyethoxy) ethoxy) benzonitrile is obtained, the yield is 82%, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.55(d,J＝8.8Hz,2H),6.95(d,J＝8.8Hz,2H),4.16(t,J＝4.4Hz,2H),3.86(t,J＝4.6Hz,2H),3.73(br,2H),3.64(t,J＝4.8Hz,2H),2.33(br,1H)；13C NMR(100MHz,CDCl3):161.9,133.9,119.0,115.2,104.1,72.6,69.2,67.6,61.6.
example 2
Synthesizing 4- (2- (2-hydroxyethoxy) ethoxy) acetophenone
Figure BDA0001574321160000061
In this example, the p-bromobenzonitrile from example 1 was replaced with equimolar amounts of 4-bromoacetophenone, the reaction temperature was raised to 60 ℃, the reaction time was extended to 24 hours, and other steps were followedThe same as in example 1 gave pure 4- (2- (2-hydroxyethoxy) ethoxy) acetophenone in 83% yield and the structural characterization data as:1H NMR(600MHz,CDCl3):7.93(d,J＝8.9Hz,2H),6.95(d,J＝8.9Hz,2H),4.21(t,J＝4.5Hz,2H),3.90(t,J＝4.7Hz,2H),3.79-3.76(m,2H),3.68(t,J＝4.8Hz,2H),2.56(s,3H),2.06(t,J＝6.0Hz,1H)；13C NMR(100MHz,CDCl3):196.7,162.4,130.4,130.3,114.1,72.6,69.2,67.4,61.5,26.2.
example 3
Synthesis of 4- (2- (2-hydroxyethoxy) ethoxy) benzaldehyde
Figure BDA0001574321160000062
In this example, the p-bromobenzonitrile of example 1 was replaced by equimolar 4-bromobenzaldehyde, the reaction temperature was raised to 60 ℃ and the reaction time was prolonged to 24 hours, and the other steps were the same as in example 1, to obtain pure 4- (2- (2-hydroxyethoxy) ethoxy) benzaldehyde in 81% yield and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):9.89(s,1H),7.84(d,J＝8.7Hz,2H),7.03(d,J＝8.6Hz,2H),4.23(t,J＝4.5Hz,2H),3.91(t,J＝4.7Hz,2H),3.79-3.77(m,2H),3.69(t,J＝4.7Hz,2H),2.03(br,1H)；13C NMR(100MHz,CDCl3):190.7,163.6,131.9,130.0,114.7,72.6,69.2,67.6,61.6.
example 4
Synthesis of 2- (2- (naphthyl-2-oxy) ethoxy) ethanol
Figure BDA0001574321160000063
In this example, the p-bromobenzonitrile in example 1 was replaced by equimolar 2-bromonaphthalene, the reaction temperature was raised to 60 ℃, the reaction time was prolonged to 24 hours, the developing solvent was petroleum ether/ethyl acetate (4:1), and other steps were the same as in example 1, to obtain pure 2- (2- (naphthyl-2-oxy) ethoxy) ethanol in 78% yield and the structural characterization data as follows:1H NMR(400MHz,CDCl3):7.75(q,J＝11.9Hz,3H),7.46-7.42(m,1H),7.36-7.32(m,1H),7.20-7.15(m,2H),4.27(t,J＝4.6Hz,2H),3.95(t,J＝4.8Hz,2H),3.81-3.77(m,2H),3.71(t,J＝4.7Hz,2H),2.13(t,J＝5.9Hz,1H)；13C NMR(100MHz,CDCl3):156.5,134.4,129.4,129.0,127.6,126.7,126.3,123.7,118.8,106.8,72.6,69.6,67.3,61.7.
example 5
Synthesizing 2- (2- (4-fluorophenoxy) ethoxy) ethanol with the structural formula
Figure BDA0001574321160000071
In this example, the p-bromobenzonitrile in example 1 was replaced by equimolar 4-fluorobromobenzene, the reaction temperature was raised to 60 ℃, the reaction time was prolonged to 24 hours, and other steps were the same as in example 1, to obtain pure 2- (2- (4-fluorophenoxy) ethoxy) ethanol with a yield of 61%, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):6.99-6.95(m,2H),6.87-6.84(m,2H),4.10(t,J＝4.4Hz,2H),3.85(t,J＝5.0Hz,2H),3.78-3.75(m,2H),3.67(t,J＝4.8Hz,2H),2.21(t,J＝6.0Hz,1H)；13C NMR(100MHz,CDCl3):158.6,155.5(d,J＝145.0Hz),115.8(d,J＝23.0Hz),115.7(d,J＝8.0Hz),72.6,69.7,68.1,61.8；19F NMR(376MHz,CDCl3):-123.5(s,1F).
example 6
Synthesizing 2- (2- (4-chlorophenoxy) ethoxy) ethanol with the structural formula
Figure BDA0001574321160000072
In this example, the bromobenzonitrile in example 1 was replaced by equimolar 4-chlorobromobenzene, the reaction temperature was raised to 60 ℃ and the reaction time was prolonged to 24 hours, and other steps were the same as in example 1, to obtain pure 2- (2- (4-chlorophenoxy) ethoxy) ethanol in a yield of 70%, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.22(d,J＝9.3Hz,2H),6.84(d,J＝8.7Hz,2H),4.10(t,J＝4.5Hz,2H),3.85(t,J＝5.6Hz,2H),3.75(br,2H),3.66(t,J＝5.1Hz,2H),2.16(br,1H)；13C NMR(100MHz,CDCl3):157.3,129.3,125.9,115.9,72.6,69.6,67.7,61.8.
example 7
Synthesis of methyl 4- (2- (2-hydroxyethoxy) ethoxy) benzoate
Figure BDA0001574321160000073
In this example, the p-bromobenzonitrile of example 1 was replaced by equimolar amounts of methyl 4-bromobenzoate and the other steps were the same as in example 1 to give pure methyl 4- (2- (2-hydroxyethoxy) ethoxy) benzoate in 80% yield and the structural characterization data are as follows:1H NMR(600MHz,CDCl3):7.98(d,J＝8.8Hz,2H),6.92(d,J＝8.8Hz,2H),4.18(t,J＝4.5Hz,2H),3.87(t,J＝5.2Hz,2H),3.87(s,3H),3.76(br,2H),3.66(t,J＝4.8Hz,2H),2.22(br,1H)；13C NMR(100MHz,CDCl3):166.7,162.4,131.6,122.9,114.1,72.6,69.4,67.5,61.7,51.8.
example 8
Synthesizing 2- (2- (4- (trifluoromethyl) phenoxy) ethoxy) ethanol with the structural formula
Figure BDA0001574321160000081
In this example, the p-bromobenzonitrile of example 1 was replaced by equimolar 4-trifluoromethylbromobenzene, the reaction temperature was raised to 60 ℃ and the reaction time was prolonged to 24 hours, and other steps were the same as in example 1, to obtain pure 2- (2- (4- (trifluoromethyl) phenoxy) ethoxy) ethanol in 81% yield and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.54(d,J＝8.5Hz,2H),6.98(d,J＝8.5Hz,2H),4.18(t,J＝4.5Hz,2H),3.88(t,J＝4.9Hz,2H),3.77(br,2H),3.68(t,J＝4.8Hz,2H),2.13(br,1H)；13C NMR(100MHz,CDCl3):161.1,126.9(q,J＝3.8Hz),124.4(q,J＝269.4Hz),123.2(q,J＝32.8Hz),114.6,72.6,69.5,67.6,61.8；19F NMR(376MHz,CDCl3):-61.4(s,3F).
example 9
Synthesizing 2- (2-phenoxyethoxy) ethanol with the structural formula as follows
Figure BDA0001574321160000082
In this example, the bromobenzene in example 1 was replaced by equimolar bromobenzene, the reaction temperature was raised to 60 ℃ and the reaction time was prolonged to 24 hours, and the other steps were the same as in example 1, to obtain pure 2- (2-phenoxyethoxy) ethanol with a yield of 65%, and the structural characterization data is as follows:1H NMR(600MHz,CDCl3):7.28(d,J＝8.2Hz,2H),6.96(d,J＝7.3Hz,1H),6.92(d,J＝8.0Hz,2H),4.14(t,J＝4.6Hz,2H),3.87(t,J＝4.7Hz,2H),3.76(td,J＝7.4,3.9Hz,2H),3.68(t,J＝4.8Hz,2H),2.24(t,J＝6.1Hz,1H).13C NMR(100MHz,CDCl3):158.6,129.5,121.0,114.6,72.6,69.7,67.3,61.8.
example 10
Synthesis of 4- (2-hydroxyethoxy) benzonitrile of the formula
Figure BDA0001574321160000091
In this example, the diethylene glycol of example 1 was replaced by an equimolar amount of ethylene glycol, and the procedure was otherwise the same as in example 1, to obtain pure 4- (2-hydroxyethoxy) benzonitrile in 86% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.60(d,J＝8.8Hz,2H),6.98(d,J＝8.8Hz,2H),4.14(t,J＝4.2Hz,2H),4.00(t,J＝4.7Hz,2H)；13C NMR(100MHz,CDCl3):161.9,134.0,119.0,115.2,104.2,69.5,60.9.
example 11
Synthesis of 4- ((8-hydroxy-3, 6-dioxaocta) oxy) benzonitrile of the formula
Figure BDA0001574321160000092
In this example, replacing diethylene glycol in example 1 with equimolar triethylene glycol and petroleum ether/ethyl acetate (1:1) as the developing solvent, the other steps were the same as in example 1 to obtain pure 4- ((8-hydroxy-3, 6-dioxaocta) oxy) benzonitrile in 94% yield, and the structural characterization data are as follows: 1H NMR (400MHz, CDCl3):7.55(d, J ═ 8.9Hz,2H),6.95(d, J ═ 8.8Hz,2H),4.15(t, J ═ 4.6Hz,2H),3.85(t, J ═ 4.9Hz,2H),3.72-3.66(m,6H),3.58(t, J ═ 4.9Hz,2H),2.54(br, 1H);13C NMR(100MHz,CDCl3):161.9,133.9,119.0,115.2,104.1,72.4,70.8,70.2,69.3,67.6,61.6.
example 12
Synthesis of 4- ((11-hydroxy-3, 6, 9-trioxaundecyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000093
In this example, diethylene glycol of example 1 was replaced by equimolar tetraethylene glycol, the reaction time was extended to 24 hours, the developing solvent was methylene chloride/methanol (40:1), and the other steps were the same as in example 1, to obtain pure 4- ((11-hydroxy-3, 6, 9-trioxaundecyl) oxy) benzonitrile in 92% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.56(d,J＝9.2Hz,2H),6.96(d,J＝9.2Hz,2H),4.17(t,J＝3.2Hz,2H),3.86(t,J＝4.0Hz,2H),3.72-3.65(m,10H),3.59(dd,J＝7.6,4.4Hz,2H),2.62(br,1H)；13C NMR(100MHz,CDCl3):162.0,133.9,119.1,115.3,104.1,72.5,70.8,70.6,70.5,70.2,69.3,67.7,61.7.
example 13
Synthesis of 4- ((14-hydroxy-3, 6,9, 12-tetraoxatetradecyloxy) benzonitrile of the formula
Figure BDA0001574321160000101
In this example, diethylene glycol of example 1 was replaced with an equimolar amount of pentaethylene glycol, and the reaction time was extended to 24 hoursThe developing solvent is dichloromethane/methanol (30:1), other steps are the same as example 1, and pure 4- ((14-hydroxy-3, 6,9, 12-tetraoxatetradecyloxy) benzonitrile is obtained, the yield is 80%, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.57(d,J＝8.0Hz,2H),6.96(d,J＝9.0Hz,2H),4.17(t,J＝4.6Hz,2H),3.87(t,J＝9.5Hz,2H),3.73-3.71(m,4H),3.68-3.66(m,10H),3.61-3.60(m,2H),2.64(t,J＝6.2Hz,1H)；13C NMR(100MHz,CDCl3):162.1,133.9,119.2,115.3,104.1,72.5,70.9,70.6-70.5(4C),70.3,69.4,67.7,61.7.
example 14
Synthesis of 4- ((17-hydroxy-3, 6,9,12, 15-pentaoxaheptadecyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000102
In this example, the diethylene glycol of example 1 was replaced by an equimolar amount of hexaethylene glycol, the reaction time was extended to 24 hours, the developing solvent was methylene chloride/methanol (30:1), and the other steps were the same as in example 1, to obtain pure 4- ((17-hydroxy-3, 6,9,12, 15-pentaoxaheptadecaoxy) benzonitrile in 85% yield, and the structural characterization data are as follows:1HNMR(400MHz,CDCl3):7.55(d,J＝8.3Hz,2H),6.95(d,J＝8.3Hz,2H),4.15(t,J＝4.6Hz,2H),3.84(t,J＝4.7Hz,2H),3.90-3.56(m,20H),2.70(br,1H)；13C NMR(100MHz,CDCl3):162.1,133.9,119.2,115.4,104.1,72.6,70.8,70.6-70.5(5C),70.3,69.4,67.8,61.7.
example 15
Synthesis of 4- ((23-hydroxy-3, 6,9,12,15,18, 21-heptaoxatrico) oxy) benzonitrile of the formula
Figure BDA0001574321160000103
In this example, the diethylene glycol of example 1 was replaced with an equimolar amount of octaethylene glycol, the reaction time was extended to 24 hours, and the procedure was the same as in example 1 except that the developing solvent was methylene chloride/methanol (20:1), to obtain 4-The pure product of ((23-hydroxy-3, 6,9,12,15,18, 21-heptaoxaditridecyl) oxy) benzonitrile has the yield of 81 percent, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.57(d,J＝8.9Hz,2H),6.96(d,J＝8.8Hz,2H),4.16(t,J＝4.7Hz,2H),3.86(t,J＝4.8Hz,2H),3.72-3.59(m,28H),2.64(t,J＝6.2Hz,1H)；13C NMR(100MHz,CDCl3):162.1,133.9,119.2,115.3,104.1,72.5,70.9,70.6-70.5(10C),70.3,69.4,67.8,61.7.
example 16
Synthesis of 4- ((35-hydroxy-3, 6,9,12,15,18,21,24,27,30, 33-undecoxytriapentadecyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000111
In this example, the diethylene glycol of example 1 was replaced by an equimolar amount of dodecaethylene glycol, the reaction time was extended to 24 hours, the developing solvent was methylene chloride/methanol (5:1), and the other steps were the same as in example 1, to obtain pure 4- ((35-hydroxy-3, 6,9,12,15,18,21,24,27,30, 33-undecaoxatripentadecyl) oxy) benzonitrile in 53% yield, and the structural characterization data was:1H NMR(400MHz,CDCl3):7.57(d,J＝8.7Hz,2H),6.96(d,J＝8.7Hz,2H),4.16(t,J＝4.7Hz,2H),3.86(t,J＝4.9Hz,2H),3.72-3.59(m,44H),2.80(br,1H)；13C NMR(100MHz,CDCl3):162.1,133.9,119.1,115.3,104.1,72.5,70.9,70.6-70.5(18C),70.3,69.4,67.8,61.7.
example 17
Synthesis of 4- ((3-hydroxybutoxy-2-yl) oxy) benzonitrile of the formula
Figure BDA0001574321160000112
In this example, the reaction time was extended to 24 hours by replacing diethylene glycol in example 1 with equimolar 2, 3-butanediol, and the other steps were the same as in example 1 to obtain pure 4- ((3-hydroxybutoxy-2-yl) oxy) benzonitrile in 90% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.59(dd,J＝9.0,2.7Hz,2H),6.96(dd,J＝8.9,6.12Hz,2H),4.44-4.38(m,0.5H),4.28-4.21(m,0.5H),4.07-3.99(m,0.5H),3.92-3.86(m,0.5H),2.33(d,J＝3.7Hz,0.5H),1.94(d,J＝5.0Hz,0.5H),1.29(dd,J＝7.4,6.3Hz,3H),1.26(d,J＝6.5Hz,3H)；13C NMR(100MHz,CDCl3):161.1,134.1,119.1,116.3,104.0,79.0,77.6,70.6,69.4,18.5,17.9,15.4,13.5.
example 18
Synthesis of 4- ((1R,2R) -2-hydroxy-1, 2-diphenylethoxy) benzonitrile of the formula
Figure BDA0001574321160000121
In this example, replacing diethylene glycol in example 1 with equimolar (R, R) -hydrobenzoin, the reaction time was extended to 24 hours, the developing solvent was petroleum ether/ethyl acetate (4:1), and the other steps were the same as in example 1, to obtain pure 4- ((1R,2R) -2-hydroxy-1, 2-diphenylethoxy) benzonitrile in 91% yield, and the structural characterization data were:1H NMR(400MHz,CDCl3):7.48(d,J＝8.9Hz,2H),7.25-7.19(m,6H),7.10(dd,J＝7.1,1.8Hz,2H),7.01(dd,J＝7.2,1.7Hz,2H),6.93(d,J＝8.8Hz,2H),5.17(t,J＝7.6Hz,1H),4.97(dd,J＝7.5,2.2Hz,1H),3.05(d,J＝2.2Hz,1H)；13C NMR(100MHz,CDCl3):160.8,138.2,135.9,133.8,128.41,128.38,128.1,128.0,127.2,127.0,118.9,116.6,104.5,85.6,78.2.
example 19
Synthesis of 4- (((3R,4S) -4-hydroxytetrahydrofuran-3-yl) oxy) benzonitrile of the formula
Figure BDA0001574321160000122
In this example, diethylene glycol of example 1 was replaced with equimolar 1, 4-anhydroerythritol, and the procedure was otherwise the same as in example 1 except that petroleum ether/ethyl acetate (4:1) was used as a developing solvent, to obtain pure 4- (((3R,4S) -4-hydroxytetrahydrofuran-3-yl) oxy) benzonitrile at a yield of 91%, and the structural characteristics were such thatThe data are as follows:1H NMR(400MHz,CDCl3):7.62(d,J＝8.8Hz,2H),6.70(d,J＝8.8Hz,2H),4.81(q,J＝5.5Hz,1H),4.55-4.52(m,1H),4.16(dd,J＝10.2,5.6Hz,1H),4.05(dd,J＝9.5,5.6Hz,1H),3.93(dd,J＝10.2,4.1Hz,1H),3.81(dd,J＝9.5,5.3Hz,1H),2.37(d,J＝7.4Hz,1H)；13C NMR(100MHz,CDCl3):160.4,134.2,118.7,116.1,105.4,77.1,72.8,71.1,70.4.
example 20
Synthesis of 4- ((2-hydroxycyclopentyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000123
In this example, diethylene glycol of example 1 was replaced by equimolar 1, 2-cyclopentanediol, the reaction time was extended to 24 hours, and the other steps were the same as in example 1, to obtain pure 4- ((2-hydroxycyclopentyl) oxy) benzonitrile in 53% yield, and the structural characterization data are:1H NMR(400MHz,CDCl3):7.56(d,J＝7.9Hz,2H),6.96(d,J＝8.6Hz,2H),4.58-4.55(m,1H),4.31(br,1H),2.24-2.18(m,1H),2.11-2.05(m,1H),1.87-1.62(m,5H)；13C NMR(100MHz,CDCl3):161.3,134.0,119.2,116.0,103.7,84.9,77.2,33.1,29.9,21.4.
example 21
Synthesis of 4- (((1S,2S) -2-hydroxycyclohexyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000131
In this example, the reaction time was extended to 24 hours by replacing diethylene glycol in example 1 with equimolar (1S) -trans-1, 2-cyclohexanediol, and the other steps were the same as in example 1 to obtain pure 4- (((1S,2S) -2-hydroxycyclohexyl) oxy) benzonitrile in 93% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.57(d,J＝8.8Hz,2H),6.99(d,J＝8.8Hz,2H),4.12-4.07(m,1H),3.77-3.73(m,1H),2.38(d,J＝2.3Hz,1H),2.14-2.09(m,2H),1.79-1.77(m,2H),1.44-1.31(m,4H)；13C NMR(100MHz,CDCl3):161.4,134.0,119.1,116.4,104.1,82.2,73.1,32.2,29.0,23.8,23.7.
example 22
Synthesis of 4- (((1S,2R) -2-hydroxycyclohexyl) oxy) benzonitrile of the formula
Figure BDA0001574321160000132
In this example, diethylene glycol of example 1 was replaced with equimolar cis-1, 2-cyclohexanediol, and the procedure was otherwise the same as in example 1, to give a pure product of 4- (((1S,2R) -2-hydroxycyclohexyl) oxy) benzonitrile in 91% yield and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.58(d,J＝8.8Hz,2H),6.99(d,J＝8.8Hz,2H),4.49-4.46(m,1H),3.97-3.94(m,1H),2.00-1.89(m,3H),1.76-1.60(m,4H),1.44-1.34(m,2H)；13C NMR(100MHz,CDCl3):161.0,134.1,119.1,116.5,104.2,77.6,69.3,30.4,26.3,21.4.
example 23
Synthesis of tert-butyl (2- (4-cyanophenoxy) ethyl) (2-hydroxyethyl) carbamate having the formula
Figure BDA0001574321160000133
In this example, the reaction time was extended to 24 hours by replacing diethylene glycol in example 1 with equimolar tert-butyl bis (2-hydroxyethyl) carbamate, and the other steps were the same as in example 1, to obtain pure tert-butyl (2- (4-cyanophenoxy) ethyl) (2-hydroxyethyl) carbamate in 82% yield and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.57(d,J＝8.4Hz,2H),6.94(d,J＝8.4Hz,2H),4.17(d,J＝25.4Hz,2H),3.77(br,2H),3.66(br,2H),3.50(br,2H),2.63(d,J＝304.6Hz,1H),1.45(s,9H)；13C NMR(100MHz,CDCl3):161.7,156.1(d,J＝104.0Hz),134.0,119.0,115.1,104.4,80.6(d,J＝17.1Hz),66.9,62.01(d,J＝59.1Hz),51.7,48.1,28.4.
example 24
Synthesizing 4- (3-hydroxypropoxy) benzonitrile with the structural formula
Figure BDA0001574321160000141
In this example, the diethylene glycol of example 1 was replaced by equimolar 1, 3-propanediol, and the other steps were the same as in example 1 except that the developing solvent was petroleum ether/ethyl acetate (4:1), to obtain pure 4- (3-hydroxypropoxy) benzonitrile in 85% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.53(d,J＝8.8Hz,2H),6.93(d,J＝8.8Hz,2H),4.14(t,J＝6.4Hz,2H),3.82(t,J＝5.6Hz,2H),2.07-2.00(m,3H)；13C NMR(100MHz,CDCl3):162.1,133.9,119.1,115.1,103.7,65.4,59.2,31.7.
example 25
Synthesis of 4- (4-hydroxybutoxy) benzonitrile of the formula
Figure BDA0001574321160000142
In this example, the procedure is the same as in example 1 except that the diethylene glycol in example 1 is replaced by equimolar 1, 4-butanediol and the developing solvent petroleum ether/ethyl acetate (4:1) is used, to obtain pure 4- (4-hydroxybutoxy) benzonitrile in 83% yield, and the structural characterization data are as follows:1H NMR(400MHz,CDCl3):7.57(d,J＝8.8Hz,2H),6.93(d,J＝8.8Hz,2H),4.05(t,J＝6.4Hz,2H),3.73(t,J＝6.4Hz,2H),1.95-1.88(m,2H),1.79-1.72(m,2H),1.60(br,1H)；13C NMR(100MHz,CDCl3):162.2,133.8,119.1,115.1,103.5,68.0,62.1,28.9,25.4.
NiBr in the above examples2Can be replaced by bis (1, 5-cyclooctadiene) nickel, nickel chloride, nickel iodide, nickel acetate or nickel trifluoromethanesulfonate; white light can be replaced by blue light or green light; the photosensitizer BODIPY 1b can be replaced by BODIPY 1a and BODIPY 1 c; n, N-dicyclohexylmethylamine may be N, N-dimethylcyclohexylamine, N-diethylcyclohexylamine, N-dimethylisopropylamine or 1-azabicyclo [2.2.2]]Octane and the solvent N, N-dimethylformamide may be replaced by N, N-diethylformamide, N-dimethylacetamide or acetonitrile. The above modifications all achieve the object of the invention to obtain a product yield similar to the above examples.

Claims (6)

1. A method for photo/nickel concerted catalysis of monoarylation of diol is characterized in that: adding bromoarene shown as a formula I, a diol compound shown as II-1, II-2 or II-3, a nickel source, a BODIPY organic photosensitizer and alkali into an organic solvent, carrying out cross coupling reaction under the conditions of no water and no oxygen, illumination and stirring at 40-60 ℃, after the reaction is completed, carrying out quenching reaction by using water, and separating and purifying to obtain diol monoaryl ether shown as III-1, III-2 or III-3;
Figure DEST_PATH_IMAGE002
in the formula, R1、R2Each independent representative H, C1～C4Any one of alkyl and phenyl, and X represents CH2O or N-Ts, Y represents CH2Or N-Boc, m is an integer of 0-11, and N is an integer of 0-2;
the nickel source is any one of bis (1, 5-cyclooctadiene) nickel, nickel chloride, nickel bromide, nickel iodide, nickel acetate and nickel trifluoromethanesulfonate;
the BODIPY organic photosensitizer is any one of the following 1 a-1 c:
Figure DEST_PATH_IMAGE004
。
2. the photo/nickel co-catalyzed monoarylation of glycols according to claim 1, wherein: ar represents phenyl, cyano-substituted phenyl, C1～C4Alkyl acyl substituted phenyl, aldehyde substituted phenyl, halogenated phenyl, C1～C4Alkoxy acyl substituted phenyl, trifluoromethyl substituted phenyl,Any one of naphthyl.
3. The photo/nickel co-catalyzed monoarylation of glycols according to claim 1, wherein: the molar ratio of the brominated aromatic hydrocarbon to the diol compound to the nickel source to the BODIPY organic photosensitizer to the alkali is 1: 1.3-1.5: 0.02-0.20: 0.0001-0.01: 1.5-2.0.
4. The photo/nickel co-catalyzed monoarylation of a diol according to any of claims 1 to 3, wherein: the base isN,N-dicyclohexylmethylamine,N,N-dimethylcyclohexylamine,N,N-diethyl cyclohexylamine,N,N-dimethylisopropylamine, 1-azabicyclo [2.2.2]Octane.
5. The photo/nickel co-catalyzed monoarylation of glycols according to claim 1, wherein: the light source adopted for illumination is white light, blue light or green light.
6. The photo/nickel co-catalyzed monoarylation of glycols according to claim 1, wherein: the organic solvent isN,N-dimethylformamide,N,N-diethylformamide,N,N-dimethylacetamide or acetonitrile.
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