CN114149380A - Novel preparation method of 2-aryl benzoxazole series compounds - Google Patents
Novel preparation method of 2-aryl benzoxazole series compounds Download PDFInfo
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Abstract
The invention discloses a novel preparation method of 2-aryl benzoxazole series compounds, belonging to the technical field of organic chemistry. The method adopts o-isocyano diaryl ether as a substrate, and reacts for 1 to 3 hours in DMF solvent at the temperature of 100 ℃ under the action of ferric trichloride, tert-butyl peroxide and triethylamine to synthesize the 2-aryl benzoxazole series compound. 2-aryl benzoxazole series compounds are constructed by recombining aryl connected with oxygen in a substrate to imine carbon, so that the atom utilization rate is effectively improved, and inconvenience brought to post-treatment of reaction by the release of atoms in the substrate is avoided. The reaction conditions are mild, the reaction time is short, the region selection is good, and the substrate applicability is wide.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a novel method for preparing 2-aryl benzoxazole series compounds.
Background
The 2-arylbenzoxazole series compounds have potential biological activities such as antibacterial, anti-inflammatory and anticancer activities, and are widely found in natural products, bioactive compounds and medicines ((a) Wang, X.; Chen, Y.; Song, H.; Liu, Y.; Wang, Q.Org.Lett.2020,22,9331.(b) Demmer, C.S.; Bunch, L.Eur.J.Med.Chem.2015,97,778.(c) Seth, K.; Garg, S.K.; Kumar, R.; Purohit, P.; Meena, V.S.; Goyal R.; Banerjee, U.C.; Chakraborrti, A.K.ACS.Chem.Chett.2014, 5,512. (d.) Labib, M.B., Phepe.J.20176. Bio.E.;. E.S. 67). Thus, chemists have been working on the synthesis of 2-arylbenzoxazole series compounds. The conventional methods mainly employ condensation of 2-aminophenol and carboxylic acid derivatives or C-H functionalization based on benzoxazole substrates, although these methods can synthesize 2-arylbenzoxazole series compounds, they often have poor atom utilization or use expensive metal catalysts and ligands ((a) Le, H.A.N.; Nguyen, L.H.; Nguyen, Q.N.B.; Nguyen, H.T.; Nguyen, K.Q.; Tran, P.H.Catal.Commun.2020,145,106120.(b) Luo, Z.; Wu, H.L., Li, Y.; Chen, Y.; Nie, J.; Lu S.; Zhu, Y.; Zeng, Z.Adv.Synth.C.2019, 361,4117.(C) Zhang, P.S.; Chehang, W.2017. H.; Chen.84, W.H.J.; U.8. U.H.J.; Chehang. In order to improve the atom utilization rate, the development of a novel and efficient method for preparing the 2-arylbenzoxazole series compounds has important theoretical research significance and application value.
Disclosure of Invention
In order to solve the defects in the prior art, the invention aims to provide a method for constructing a 2-aryl benzoxazole series compound by using o-isocyanodiaryl ether as a substrate, wherein an aryl connected with oxygen is transferred to imine carbon. The reaction is efficient and green, avoids the waste of atoms in a substrate, and simultaneously avoids the inconvenience brought to the post-treatment of the reaction due to leaving of the atoms.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a new preparation method of 2-aryl benzoxazole series compounds by using o-isocyano diaryl ether as a reaction substrate in the air is characterized in that: under the air atmosphere, 0.9-1.1 equivalent of o-isocyano diaryl ether is used as a reaction substrate, 18-22 mol% of transition metal catalyst, 1.8-2.2 equivalents of oxidant and 0.9-1.1 equivalent of alkali are added, the mixture is heated in an organic solvent to 90-110 ℃ for reaction for 1-3 hours, and then 2-arylbenzoxazole series compounds can be efficiently prepared, the reaction process is monitored by TLC, ethyl acetate is used for extraction for three times after the reaction is finished, organic phases are combined, anhydrous sodium sulfate is used for drying the organic phases, and after decompression and spin drying, the target product is purified by flash column chromatography;
further, the o-isocyanodiaryl ether is 1-isocyano-2-phenoxybenzene, 1-isocyano-2- (o-tolyloxy) benzene, 1- (3-fluorophenoxy) -2-isocyanobenzene, 1-isocyano-2- (3- (trifluoromethyl) phenoxy) benzene, 1-isocyano-2- (p-tolyloxy) benzene, 1- (tert-butyl) -2- (2-isocyano-phenoxy) benzene, 2- (2-isocyano-phenoxy) -1,1' -biphenyl, 1- (2-isocyano-phenoxy) naphthalene, 2- (2-isocyano-phenoxy) pyridine, 2-bromo-1- (2-isocyano-phenoxy) -4-toluene, 2-isocyano-3-phenoxypyridine, 2-isocyano-1-methyl-3-phenoxybenzene or 4-chloro-2-isocyano-1-phenoxybenzene, and the like.
Specifically, the o-isocyano diaryl ether is used as a reaction substrate to synthesize the 2-aryl benzoxazole series compound, and the reaction requires aryl with isocyano ortho-position connected with oxygen to participate in the reaction.
Preferably, the transition metal catalyst is ferric chloride, ferrous chloride or cupric chloride, wherein the ferric chloride has the best effect.
Preferably, the oxidizing agent is tert-butyl peroxide or potassium persulfate, with tert-butyl peroxide being most preferred.
Preferably, the base is any one of 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU), triethylamine and potassium carbonate, wherein triethylamine is most effective.
Preferably, the solvent is N, N-Dimethylformamide (DMF) or tetrahydrofuran, with DMF being most effective.
Preferably, the solvent is used in an amount such that the concentration of the o-isocyanatodiaryl ether is 0.1M.
The reaction equation of the present invention is as follows:
wherein R is1Hydrogen, methyl, tert-butyl, methoxy, tert-butyl, trifluoromethyl, halogen atom and the like; in addition, R1The attached aryl group may be a 1-naphthyl or 2-naphthyl group.
Wherein R is2Hydrogen, methyl, chlorine and the like.
Wherein X and Y are carbon atoms or nitrogen atoms.
The specific operation is as follows: under the air atmosphere, 0.9-1.1 equivalent of o-isocyano diaryl ether is taken as a reaction substrate, 18-22mol percent of ferric trichloride, 1.8-2.2 equivalent of tert-butyl peroxide and 0.9-1.1 equivalent of triethylamine are added, and the mixture reacts for 1-3 hours at 90-110 ℃ in a DMF solvent to prepare the 2-arylbenzoxazole series compound. The reaction process is monitored by TLC, ethyl acetate is adopted for extraction for three times after the reaction is finished, organic phases are combined, anhydrous sodium sulfate is used for drying, after decompression and spin drying, the target product is purified by flash column chromatography.
The principle of the invention comprises the following steps: the method comprises the following steps of taking o-isocyano diaryl ether as a reaction substrate, taking ferric trichloride as a catalyst, taking tert-butyl peroxide as an oxidant and taking triethylamine as a base, and reacting in a DMF (dimethyl formamide) solvent at the temperature of 100 ℃. In this catalytic system, the generated N, N-dimethylformyl radical firstly carries out radical addition to isocyano, then carries out ispo attack cyclization to aryl connected with oxygen, then the aryl connected with oxygen is transferred to imine carbon to generate 2-aryl benzoxazole series compound, and the released N, N-dimethylformyl radical abstracts hydrogen to generate DMF again.
In the present invention, in FeCl3/TBHP/E3Under an N catalytic system, the o-isocyano diaryl ether can be efficiently converted in a DMF solvent to generate 2-aryl benzoxazole series compounds. The reaction is simple and convenient to operate, and the atom utilization rate is high; meanwhile, the method has high regioselectivity and wide substrate applicability, and the reaction time is short and only needs 1 to 3 hours.
The invention has the beneficial effects that:
1) the invention uses cheap metal catalyst, avoids the use of expensive metal catalyst such as palladium and ligand, and greatly reduces the reaction cost.
2) The aryl group linked to the oxygen in the present invention "recombines" to the iminocarbonyl group, the reaction is novel, efficient and green, avoiding the waste of atoms in the substrate and the inconvenience of the post-treatment of the reaction due to the release of atoms in the substrate.
3) The method has the advantages of simple and convenient operation, wide substrate adaptability, good regioselectivity and short reaction time.
4) The 2-aryl benzoxazole series compounds generated by the method have potential biological activity and potential application prospect in the aspect of medicine.
Detailed description of the preferred embodiments
The invention is further illustrated by the following examples, which are intended to be illustrative of the invention and are not to be construed as limiting the invention.
Example 1
1-isocyano-2-phenoxybenzene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) were added to the reaction tube under an air atmosphere, and then DMF solution was added to make the concentration of 1-isocyano-2-phenoxybenzene 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, and the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, decompression spin drying, and purifying with fast chromatographic column to obtain pure 2-phenylbenzo [ d ]]Oxazole 2 a. Isolation yield: 88 percent.
1HNMR(400MHz,CDCl3)δ8.31–8.22(m,2H),7.82–7.75(m,1H),7.62–7.56(m,1H),7.56–7.48(m,3H),7.40–7.32(m,2H).
13CNMR(100MHz,CDCl3)δ163.07,150.80,142.15,131.52,128.92,127.65,127.22,125.11,124.59,120.04,110.60.
Example 2
1-isocyano-2- (o-tolyloxy) benzene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) were added to the reaction tube under an air atmosphere, and then a DMF solution was added to make the concentration of 1-isocyano-2- (o-tolyloxy) benzene 0.1M, and reacted at 100 ℃ for 1 to 3 hours, and the specific reaction time was monitored by TLC. After the reaction is finished, acetic acid is adopted as a reaction liquidExtracting with ethyl ester for three times, mixing organic phases, and extracting with anhydrous Na2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure product 2- (o-tolyl) benzo [ d]Oxazole 2 b. Isolation yield: 95 percent.
1HNMR(400MHz,CDCl3)δ8.23–8.16(m,1H),7.85–7.79(m,1H),7.64–7.56(m,1H),7.45–7.32(m,5H),2.83(s,3H).
13CNMR(100MHz,CDCl3)δ163.43,150.34,142.17,138.87,131.79,130.90,129.97,126.28,126.06,125.01,124.37,120.16,110.48,22.17.
Example 2 mainly examined the suitability of substrates with electron donating groups attached ortho to the phenyl ring. The results of the examples show that the 2- (o-tolyl) benzo [ d ] oxazole can be obtained in high yield from a substrate having an electron-donating group ortho-bonded to the benzene ring.
Example 3
To a reaction tube, 1- (3-fluorophenoxy) -2-isocyanobenzene (0.18mmol,0.9equiv), ferric trichloride (0.036mmol,18 mol%), t-butanol peroxide (0.36mmol,1.8equiv) and triethylamine (0.18mmol,0.9equiv) were added under an air atmosphere, followed by addition of a DMF solution to give a 1- (3-fluorophenoxy) -2-isocyanobenzene concentration of 0.1M, and reaction was carried out at 100 ℃ for 1 to 3 hours, and the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, decompressing, spin-drying and purifying by a fast chromatographic column to obtain a pure product 2- (3-fluorophenyl) benzo [ d]Oxazole 2 c. Isolation yield: 77 percent.
1HNMR(400MHz,CDCl3)δ7.96(d,J＝7.7Hz,1H),7.86(d,J＝9.4Hz,1H),7.75–7.67(m,1H),7.55–7.47(m,1H),7.46–7.36(m,1H),7.34–7.24(m,2H),7.21–7.10(m,1H).
13CNMR(100MHz,CDCl3)δ162.92(d,J＝245.3Hz),161.80(d,J＝3.5Hz),150.77,141.94,130.64(d,J＝7.7Hz),129.21(d,J＝8.5Hz),125.52,124.80,123.33(d,J＝3.1Hz),120.24,118.51(d,J＝20.9Hz),114.56(d,J＝23.8Hz),110.71.
Example 3 mainly investigates the suitability of a benzene ring to connect to an electron withdrawing group substrate. The results of the examples show that the attachment of an electron withdrawing group substrate is also amenable to this reaction to give 2- (3-fluorophenyl) benzo [ d ] oxazole.
Example 4
1-isocyano-2- (3- (trifluoromethyl) phenoxy) benzene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) were added to the reaction tube under an air atmosphere, and then DMF solution was added to make the concentration of 1-isocyano-2- (3- (trifluoromethyl) phenoxy) benzene 0.1M, and reacted at 100 ℃ for 1 to 3 hours, and the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure product 2- (3- (trifluoromethyl) phenyl) benzo [ d]An oxazole 2 d. Isolation yield: 68 percent.
1HNMR(400MHz,CDCl3)δ8.43(s,1H),8.33(d,J＝7.8Hz,1H),7.75–7.64(m,2H),7.61–7.45(m,2H),7.35–7.24(m,2H).
13CNMR(100MHz,CDCl3)δ161.48,150.83,141.89,131.65(q,J＝32.6Hz),130.61,129.52,128.08,127.89(q,J＝3.5Hz),125.70,124.91,124.50(q,J＝3.9Hz),123.71(q,J＝270.9Hz),120.32,110.75.
Example 4 mainly investigating the benzene ring-linked strongly electron-withdrawing CF3Adaptability of the radical substrate. Example results show that linking CF3The radical substrate is likewise adapted to this reaction to give 2- (3- (trifluoromethyl) phenyl) benzo [ d]An oxazole.
Example 5
1-isocyano-2- (p-tolyloxy) benzene (0.22mmol,1.1equiv), ferric trichloride (0.044mmol,22 mol%), t-butanol peroxide (0.44mmol,2.2equiv) and triethylamine (0.22mmol,1.1equiv) were added to the reaction tube under an air atmosphere, and then DMF solution was added to make the concentration of 1-isocyano-2- (p-tolyloxy) benzene 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, and the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure product 2- (p-tolyl) benzo [ d]Oxazole 2 e. Isolation yield: 88 percent.
1HNMR(400MHz,CDCl3)δ8.14(d,J＝8.1Hz,2H),7.80–7.73(m,1H),7.59–7.53(m,1H),7.39–7.29(m,4H),2.43(s,3H).
13CNMR(100MHz,CDCl3)δ163.31,150.71,142.20,142.06,129.65,127.61,124.87,124.49,124.42,119.85,110.50,21.64.
Example 5 mainly investigates the suitability of substrates with electron donating groups attached to the para position of the phenyl ring. The results of the examples show that a substrate having an electron-donating group bonded to the para-position of the benzene ring can also give 2- (p-tolyl) benzo [ d ] oxazole in high yield.
Example 6
To the reaction tube were added 1- (tert-butyl) -2- (2-isocyanophenoxy) benzene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) under an air atmosphere, followed by addition of DMF solution to give a 1- (tert-butyl) -2- (2-isocyanophenoxy) benzene concentration of 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, with the specific reaction time monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure 2- (2- (tert-butyl) benzene productRadical) benzo [ d]An oxazole 2 f. Isolation yield: 51 percent.
1HNMR(400MHz,CDCl3)δ7.86–7.78(m,1H),7.66–7.56(m,2H),7.53–7.45(m,2H),7.44–7.37(m,2H),7.30(t,J＝7.4Hz,1H),1.32(s,9H).
13CNMR(100MHz,CDCl3)δ165.48,150.47,150.43,141.58,132.44,130.65,127.09,127.04,125.50,125.14,124.49,120.30,110.72,36.20,31.56.
HRMS(ESI)m/zcalcdforC17H18NO+(M+H)+252.1383,found252.1380.
Example 6 mainly investigates the suitability of a benzene ring to connect to a substrate with a strong steric blocking group (tert-butyl). The results of the examples show that a strongly sterically hindered substrate can also accommodate this reaction to give 2- (2- (tert-butyl) phenyl) benzo [ d ] oxazole.
Example 7
To the reaction tube were added 2- (2-isocyano-phenoxy) -1,1 '-biphenyl (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) under an air atmosphere, followed by addition of DMF solution to make the concentration of 2- (2-isocyano-phenoxy) -1,1' -biphenyl 0.1M, and reacted at 100 ℃ for 1-3 hours, the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, rotary drying under reduced pressure, and purifying with rapid chromatographic column to obtain pure product 2- (2- (1,1' -biphenyl) benzo [ d]And (5) oxazole (2 g). Isolation yield: 83 percent.
1HNMR(400MHz,CDCl3)δ8.02(d,J＝7.8Hz,1H),7.63(d,J＝7.6Hz,1H),7.52–7.46(m,1H),7.44–7.36(m,2H),7.27–7.12(m,8H).
13CNMR(100MHz,CDCl3)δ163.89,150.75,142.48,141.70,140.99,131.17,131.01,128.83,128.15,127.56,127.29,126.31,124.94,124.34,120.10,110.56.
Example 7 mainly investigates that a biphenylyl substrate linked to oxygen can also accommodate this reaction to give 2- (2- (1,1' -biphenyl) benzo [ d ] oxazole, such 2-biphenylbenzoxazole compounds having anti-inflammatory activity and selectively inhibiting cyclooxygenase-2 (COX-2).
Example 8
1- (2-Isocyanophenoxy) naphthalene (0.22mmol,1.1equiv), ferric trichloride (0.044mmol,22 mol%), t-butanol peroxide (0.44mmol,2.2equiv) and triethylamine (0.22mmol,1.1equiv) were added to a reaction tube under an air atmosphere, and then a DMF solution was added to make the concentration of 1- (2-isocyanophenoxy) naphthalene 0.1M, and reacted at 100 ℃ for 1 to 3 hours, the specific reaction time was monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, decompression drying, purifying with fast chromatographic column to obtain pure 2- (naphthalene-1-yl) benzo [ d ] product]And (5) oxazole for 2 h. Isolation yield: 96 percent.
1HNMR(400MHz,CDCl3)δ9.51(d,J＝8.6Hz,1H),8.44(d,J＝7.3Hz,1H),8.03(d,J＝8.2Hz,1H),7.97–7.88(m,2H),7.78–7.68(m,1H),7.68–7.63(m,1H),7.68–7.63(m,2H),7.63–7.57(m,2H).
13CNMR(100MHz,CDCl3)δ162.85,150.22,142.38,134.01,132.33,130.75,129.35,128.70,127.94,126.48,126.35,125.31,124.96,124.53,123.65,120.32,110.54.
Example 8 primarily investigates the suitability of a phenyl group attached to an oxygen for attachment to a 1-naphthyl substrate. The results of the examples show that the oxygen-linked 1-naphthyl substrate is well-suited to give 2- (naphthalen-1-yl) benzo [ d ] oxazole in high yield of 96%.
Example 9
To the reaction tube were added 2- (2-isocyano phenoxy) pyridine (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) under an air atmosphere, followed by addition of DMF solution to give a 2- (2-isocyano phenoxy) pyridine concentration of 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, the specific reaction time being monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure product 2- (pyridine-2-yl) benzo [ d]And (3) oxazole 2 i. Isolation yield: 45 percent.
1HNMR(400MHz,CDCl3)δ8.82(d,J＝3.2Hz,1H),8.36(d,J＝7.9Hz,1H),7.89(t,J＝7.7Hz,1H),7.85–7.78(m,1H),7.74–7.61(m,1H),7.54–7.33(m,3H).
13CNMR(100MHz,CDCl3)δ161.44,151.08,150.30,146.07,141.79,137.11,126.06,125.59,124.95,123.46,120.65,111.25.
Example 9 mainly investigates the adaptivity of heterocyclic substrates linked to oxygen. The results of the examples show that heterocyclic substrates attached to oxygen can also accommodate this reaction to form 2- (pyridin-2-yl) benzo [ d ] oxazole.
Example 10
To a reaction tube were added 2-bromo-1- (2-isocyanatophenoxy) -4-toluene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0equiv) and triethylamine (0.2mmol,1.0equiv) under an air atmosphere, followed by addition of DMF solution to give a concentration of 2-bromo-1- (2-isocyanatophenoxy) -4-toluene of 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, the specific reaction time being monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, vacuum spin-drying, and purifying with flash chromatography column to obtain pure product 2- (2-bromo-4-methylphenyl) benzo [ d]Oxazole 2 j. Isolation yield: 78 percent.
1HNMR(400MHz,CDCl3)δ7.98(d,J＝8.0Hz,1H),7.88–7.80(m,1H),7.65–7.57(m,2H),7.42–7.34(m,2H),7.26(d,J＝7.5Hz,1H),2.40(s,3H).
13CNMR(100MHz,CDCl3)δ163.42,150.31,142.16,138.88,131.82,130.93,129.96,126.25,126.09,125.04,124.39,120.17,110.51,22.25.
HRMS(ESI)m/zcalcdforC14H11BrNO+(M+H)+288.0019,found288.0010.
Example 10 essentially examines the applicability of a phenyl group attached to oxygen to substrates containing both electron donating and electron withdrawing groups in this reaction. The results of the examples show that these substrates can also be reacted to give the desired product 2- (2-bromo-4-methylphenyl) benzo [ d ] oxazole.
Example 11
To the reaction tube were added 2-isocyano-3-phenoxypyridine (0.18mmol,0.9equiv), ferric trichloride (0.036mmol,18 mol%), t-butanol peroxide (0.36mmol,1.8equiv) and triethylamine (0.18mmol,0.9equiv) under an air atmosphere, followed by addition of DMF solution to give a concentration of 0.1M 2-isocyano-3-phenoxypyridine, and the reaction was carried out at 100 ℃ for 1 to 3 hours, the specific reaction time being monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, rotary drying under reduced pressure, and subjecting to flash chromatography to obtain pure product 2-phenyloxazolo [4,5-b]Pyridine 2 k. Isolation yield: 56 percent.
1HNMR(400MHz,CDCl3)δ8.58(d,J＝4.0Hz,1H),8.32(d,J＝6.7Hz,2H),7.87(dd,J＝8.0,1.0Hz,1H),7.66–7.48(m,3H),7.36–7.27(m,1H).
13CNMR(100MHz,CDCl3)δ165.70,156.38,146.69,143.14,132.48,129.04,128.16,126.48,120.08,118.19.
Example 11 deals primarily with the suitability of isocyanated heterocyclic substrates for this reaction. The results of the examples show that an additional isocyano-linked heterocyclic substrate can also react to form 2-phenyloxazolo [4,5-b ] pyridine.
Example 12
To the reaction tube were added 2-isocyano-1-methyl-3-phenoxybenzene (0.22mmol,1.1equiv), ferric trichloride (0.044mmol,22 mol%), t-butanol peroxide (0.44mmol,2.2equiv) and triethylamine (0.22mmol,1.1equiv) under an air atmosphere, followed by addition of DMF solution to make the concentration of 2-isocyano-1-methyl-3-phenoxybenzene 0.1M, and the reaction was carried out at 100 ℃ for 1 to 3 hours, the specific reaction time being monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, decompressing, spin-drying and passing through a fast chromatographic column to obtain a pure product 4-methyl-2-phenylbenzo [ d]Oxazole 2 l. Isolation yield: 83 percent.
1HNMR(400MHz,CDCl3)δ8.25–8.12(m,2H),7.49–7.37(m,3H),7.31(d,J＝8.0Hz,1H),7.14(t,J＝7.6Hz,1H),7.05(d,J＝7.4Hz,1H),2.59(s,3H).
13CNMR(100MHz,CDCl3)δ161.22,149.49,140.39,130.21,129.55,127.78,126.55,126.40,123.99,123.69,106.79,15.54.
Example 12 deals primarily with the applicability of electron donating groups on the benzene ring attached to isocyanide for this reaction. The results of the examples show that the same reaction with an electron-donating group on the benzene ring additionally bonded to isocyanide can give 4-methyl-2-phenylbenzo [ d ] oxazole.
Example 13
To the reaction tube in an air atmosphere were added 4-chloro-2-isocyano-1-phenoxybenzene (0.2mmol,1.0equiv), ferric trichloride (0.04mmol,20 mol%), t-butanol peroxide (0.4mmol,2.0 equ)iv) and triethylamine (0.2mmol,1.0equiv), followed by addition of DMF solution to give a concentration of 4-chloro-2-isocyano-1-phenoxybenzene of 0.1M, and reaction at 100 ℃ for 1-3 hours, the specific reaction time being monitored by TLC. After the reaction is finished, the reaction liquid is extracted for three times by ethyl acetate, organic phases are combined, and anhydrous Na is used2SO4Drying, decompression spin drying, and fast chromatographic column to obtain pure 5-chloro-2-phenylbenzo [ d ]]Oxazole 2 m. Isolation yield: 73 percent.
1HNMR(400MHz,CDCl3)δ8.29–8.16(m,2H),7.74(d,J＝1.7Hz,1H),7.61–7.44(m,4H),7.31(dd,J＝8.6,1.9Hz,1H).
13CNMR(100MHz,CDCl3)δ164.36,149.35,143.26,131.93,130.05,128.99,127.76,126.70,125.37,119.98,111.30.
Example 13 deals primarily with the applicability of electron withdrawing groups on the benzene ring attached to isocyanide for this reaction. The results of the examples show that an electron-withdrawing group on the benzene ring additionally bonded to isocyanide can likewise react to give 5-chloro-2-phenylbenzo [ d ] oxazole.
Claims (9)
1. A new preparation method of 2-aryl benzoxazole series compounds is characterized in that: in the air atmosphere, 0.9-1.1 equivalent of o-isocyano diaryl ether is used as a reaction substrate, 18-22 mol% of transition metal catalyst, 1.8-2.2 equivalents of oxidant and 0.9-1.1 equivalent of alkali are added, the mixture is heated in an organic solvent to 90-110 ℃ for reaction for 1-3 hours, and then 2-arylbenzoxazole series compounds can be efficiently prepared.
The reaction equation is as follows:
wherein R is1Hydrogen, methyl, tert-butyl, methoxy, trifluoromethyl or halogen atom; in addition, theR1The attached aryl group may also be a 1-naphthyl or 2-naphthyl group;
wherein R is2Hydrogen, methyl or chlorine;
wherein X and Y can be carbon atoms or nitrogen atoms.
2. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the preferable molar ratio of the substrate raw material o-isocyanodiaryl ether, the transition metal catalyst, the oxidant and the alkali is 1:0.2:2: 1.
3. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the transition metal catalyst is ferric chloride, ferrous chloride or cupric chloride.
4. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the oxidant is tert-butyl peroxide or potassium persulfate.
5. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the base is 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU), triethylamine or potassium carbonate.
6. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the solvent is N, N-Dimethylformamide (DMF) or tetrahydrofuran.
7. The process for producing a 2-arylbenzoxazole series compound according to claim 1, characterized in that: the o-isocyanatodiaryl ether is 1-isocyano-2-phenoxybenzene, 1-isocyano-2- (o-tolyloxy) benzene, 1- (3-fluorophenoxy) -2-isocyanobenzene, 1-isocyano-2- (3- (trifluoromethyl) phenoxy) benzene, 1-isocyano-2- (p-tolyloxy) benzene, 1- (tert-butyl) -2- (2-isocyano-phenoxy) benzene, 2- (2-isocyano-phenoxy) -1,1' -biphenyl, 1- (2-isocyano-phenoxy) naphthalene, 2- (2-isocyano-phenoxy) pyridine, 2-bromo-1- (2-isocyano-phenoxy) -4-toluene, 2-isocyano-3-phenoxypyridine, 2-isocyano-1-methyl-3-phenoxybenzene or 4-chloro-2-isocyano-1-phenoxybenzene, and the like.
8. The process for producing a 2-arylbenzoxazole series compound according to claim 3, characterized in that: the transition metal catalyst is most preferably ferric chloride.
9. A novel process for the preparation of a compound of the 2-arylbenzoxazole series according to claim 1, characterized in that: the optimal preparation method comprises the following steps: under the air atmosphere, 1.0 equivalent of o-isocyano diaryl ether is taken as a reaction substrate, 20mol percent of ferric trichloride, 2.0 equivalents of tert-butyl peroxide and 1.0 equivalent of triethylamine are added, and the reaction is carried out in DMF solvent for 1-3 hours at 100 ℃ to prepare the 2-arylbenzoxazole series compound. The reaction process is monitored by TLC, ethyl acetate is adopted for extraction for three times after the reaction is finished, organic phases are combined, anhydrous sodium sulfate is used for drying, after decompression and spin drying, the target product is purified by flash column chromatography.
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