CN116589472A - Benzofuran [3,2-d ] pyrimidine-2-amine compound and preparation method and application thereof - Google Patents
Benzofuran [3,2-d ] pyrimidine-2-amine compound and preparation method and application thereof Download PDFInfo
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- benzofuran
- pyrimidine
- amine compound
- hydrofluoric acid
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- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 title claims abstract description 105
- -1 pyrimidine-2-amine compound Chemical class 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 21
- 238000003756 stirring Methods 0.000 claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 17
- 238000001308 synthesis method Methods 0.000 claims abstract description 16
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical class F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 239000000575 pesticide Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- NTJBWZHVSJNKAD-UHFFFAOYSA-N triethylazanium;fluoride Chemical compound [F-].CC[NH+](CC)CC NTJBWZHVSJNKAD-UHFFFAOYSA-N 0.000 claims description 11
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 10
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 abstract description 31
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical class NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 abstract description 31
- 230000000749 insecticidal effect Effects 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 2
- 238000012216 screening Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 238000004440 column chromatography Methods 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 238000010791 quenching Methods 0.000 description 8
- 230000000171 quenching effect Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 241000500437 Plutella xylostella Species 0.000 description 7
- 238000010586 diagram Methods 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 3
- 230000009471 action Effects 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000006352 cycloaddition reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000007115 1,4-cycloaddition reaction Methods 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000003396 histamine H4 receptor antagonist Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P7/00—Arthropodicides
- A01P7/04—Insecticides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Pest Control & Pesticides (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Insects & Arthropods (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The application belongs to the field of chemical pesticides, relates to synthesis of benzofuran [3,2-d ] pyrimidine-2-amine compounds, and in particular relates to a benzofuran [3,2-d ] pyrimidine-2-amine compound, and a preparation method and application thereof. The application prepares the benzofuran [3,2-d ] pyrimidine-2-amine compound by mixing and stirring a 2-styryl-3-sulfonamide compound, alkali and hydrofluoric acid salt in a solvent, and then adding an N-aryl-N-cyano-p-toluenesulfonamide compound for synthesis reaction. Compared with the traditional synthesis method, the method has the advantages of easy preparation of raw materials, highest 99% yield, mild reaction conditions, simple operation and the like, and the synthesized benzofuran [3,2-d ] pyrimidine-2-amine compound has good insecticidal activity through insecticidal activity screening, so that the method has important significance for the synthesis and application research of the compound.
Description
Technical Field
The application belongs to the field of chemical pesticides, relates to synthesis of benzofuran [3,2-d ] pyrimidine-2-amine compounds, and in particular relates to a benzofuran [3,2-d ] pyrimidine-2-amine compound, and a preparation method and application thereof.
Background
The fused ring backbone containing both oxygen and nitrogen atoms is a very important class of heterocyclic compounds that are widely found in natural products and biologically active molecules (J.Med.Chem.2006, 49,4568;Eur.J.Med.Chem.2015,97,388.). Wherein benzofuran [3,2-d ]]Also, the pyrimidine-2-amine compound shows excellent biological activity, such as histamine H 4 Receptor antagonist activity (bioorg. Med. Chem. Lett.2011,21,6577.) and antitumor activity (synth. Commun.2022,52,994.). The construction and synthesis of the framework by utilizing the carbon-nitrogen bond has potential application value in the aspects of medicine synthesis and organic synthesis methodologies (chem. Commun.2018,54,5154.)
The N-aryl-N-cyano-p-toluenesulfonamide compound is widely applied to synthesis of nitrogen-containing heterocyclic compounds through cyanamide anion intermediates, and can be used for synthesizing a series of important nitrogen-containing heterocyclic compounds (Org.Lett.2016, 18,1100;J.Org.Chem,2021,86,3546;Org.Chem Front.2022,9,1574). The benzofuran [3,2-d ] pyrimidine-2-amine compound has potential biological activity, and has important significance in development. In recent years, few synthesis methods of benzofuran [3,2-d ] pyrimidine-2-amine compounds have been reported, and the existing synthesis methods have the defects of complex substrate preparation (org.lett.2012, 14,2398.), long route (synth.Commun.2022, 52,994.), harsh reaction conditions (bioorg.med.chem.lett.2010, 20,2516.), and the like, and have low synthesis efficiency. Therefore, the development of a simple, efficient and environment-friendly method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound has high practical value.
Disclosure of Invention
In order to solve the technical problems, the application provides a benzofuran [3,2-d ] pyrimidine-2-amine compound, a preparation method and application thereof, and the cycloaddition reaction of an N-aryl-N-cyano-p-toluenesulfonamide compound and 2-styryl-3-sulfonylbenzofuran is realized for the first time, so as to construct a benzofuran [3,2-d ] pyrimidine-2-amine skeleton. The method has important significance for researching cycloaddition reaction of the N-aryl-N-cyano-p-toluenesulfonyl compound participated by the carbodiimide anion intermediate.
The technical scheme of the application is realized as follows:
the application provides a benzofuran [3,2-d ]]The structural formula of the pyrimidine-2-amine compound is as follows:wherein R is 1 Selected from any one of phenyl and substituted phenyl, R 3 Selected from any one of phenyl, substituted phenyl and naphthyl.
Preferably, the present application claims benzofuran [3,2-d ] pyrimidine-2-amine compounds of the following classes:
wherein X is halogen,Wherein X is halogen, -/->
The application also provides a synthesis method of the benzofuran [3,2-d ] pyrimidine-2-amine compound, which comprises the following steps: dissolving an N-aryl-N cyano-p-toluenesulfonamide compound, alkali and hydrofluoric acid salt in a solvent, mixing and stirring for 10-30 minutes, adding a 2-styryl-3-sulfamido benzofuran compound for continuous synthesis reaction, and obtaining a benzofuran [3,2-d ] pyrimidine-2-amine compound;
the synthetic route is as follows:
the structural formula of the 2-styryl-3-sulfonamide benzofuran compound is as follows:wherein R is 1 Any one selected from phenyl and substituted phenyl; r is R 2 Any one selected from benzenesulfonyl, p-toluenesulfonyl and p-nitrobenzenesulfonyl; the structural formula of the N-aryl-N-cyano-p-toluenesulfonamide compound is as follows: />Wherein R is 3 Selected from any one of phenyl, substituted phenyl and naphthyl.
The mass ratio of the 2-styryl-3-sulfonamide benzofuran compound, the N-aryl-N-cyano-p-toluenesulfonyl compound, the base and the hydrofluoric acid salt is as follows: 1: (1-5): (2-5): (2-5).
The above base is selected from any one of potassium carbonate, cesium carbonate, sodium carbonate and triethylamine.
The hydrofluoric acid salt is selected from any one of triethylamine hydrofluoric acid salt, pyridine hydrofluoric acid salt and tetra-n-butyl ammonium bifluoride hydrofluoric acid salt.
The alkali and hydrofluoric acid salt is cesium carbonate and triethylamine hydrofluoric acid salt.
The synthesis process includes dissolving N-aryl-N cyano-p-toluenesulfonamide compound, alkali and hydrofluoric acid salt in solvent, mixing and stirring for 10-30 min, adding 2-styryl-3-sulfonamide benzofuran compound and continuing the synthesis reaction.
The temperature of the synthesis reaction is-10-50 ℃.
The synthesis reaction system also comprises a solvent.
The solvent is selected from one of acetonitrile, dichloromethane, 1, 2-dichloroethane, toluene, 1, 4-dioxane and ethyl acetate.
The addition amount of the solvent is 0.02-2mol/L based on the reaction system.
The application has the following beneficial effects:
1. the application firstly uses N-aryl-N-cyano-p-toluenesulfonamide compound and 2-styryl-3-sulfonylbenzofuran compound as raw materials, and the benzofuran [3,2-d ] pyrimidine-2-amine compound is generated by reaction under the action of alkali and hydrofluoride, and the reaction of alternative substrates is wider; the mechanism for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound is as follows: the mechanism of the [4+2] cycloaddition reaction of a 2-styryl-3-sulfonylbenzofuran compound with an N-aryl-N-cyano-p-toluenesulfonamide compound is as follows: removing p-toluenesulfonyl from N-aryl-N-cyano-p-toluenesulfonamide under the action of fluoride ion to obtain a carbodiimide anion intermediate, and carrying out a series Michael addition/ring closure/aromatization process on the carbodiimide anion intermediate and a 2-styryl-3-sulfonylbenzofuran compound to obtain a benzofuran [3,2-d ] pyrimidine-2-amine compound.
2. Compared with the traditional synthesis method, the method has the advantages of easy preparation of raw materials, highest 99% yield, mild reaction conditions, simple operation and the like, and the synthesized benzofuran [3,2-d ] pyrimidine-2-amine compound has good insecticidal activity through insecticidal activity screening, so that the method has important significance for the synthesis and application research of the compound.
Drawings
In order to more clearly illustrate the embodiments of the application or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of example 1 1 H NMR chart。
FIG. 2 is a schematic diagram of example 1 13 C NMR chart.
FIG. 3 is a schematic diagram of example 2 1 H NMR chart.
FIG. 4 is a schematic diagram of example 2 13 C NMR chart.
FIG. 5 is a diagram of example 3 1 H NMR chart.
FIG. 6 is a diagram of example 3 13 C NMR chart.
Detailed Description
The technical solutions of the present application will be clearly and completely described in conjunction with the embodiments of the present application, and it is apparent that the described embodiments are only some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without any inventive effort, are intended to be within the scope of the application.
Example 1
The synthesis method of the N, 4-diphenyl benzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 82mg of N-phenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 32mg of triethylamine hydrofluoric acid salt, 2mL of acetonitrile, and stirring at 25℃for 10 minutes was further carried out, 75mg of 2-styryl-3-p-methanesulfonamide benzofuran was further added, and stirring was continued at 25℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N, 4-diphenyl benzofuran [3,2-d ]]67mg of pure and pure pyrimidine-2-amine product is obtained, the yield is 99%, and the structural formula is as follows:n, 4-diphenylbenzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(600MHz,CDCl 3 )δ8.57(d,J＝8.4Hz,2H),8.18(d,J＝7.8Hz,1H),7.82(d,J＝7.8Hz,2H),7.65-7.64(m,2H),7.60(t,J＝7.2Hz,2H),7.55(t,J＝7.2Hz,1H),7.44-7.36(m,4H),7.05(t,J＝7.2Hz,1H)ppm； 13 C NMR(151MHz,CDCl 3 )δ158.7,156.8,152.7,148.1,141.2,140.6,134.6,131.5,131.2,129.3,129.1,128.9,123.8,122.5,122.1,122.0,118.7,112.9ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 16 N 3 O 338.1288,found:338.1297.
Which is a kind of 1 H NMR chart 13 The C NMR chart is shown in FIG. 1 and FIG. 2.
Example 2
The synthesis method of the N-p-methoxyphenyl-4-phenylbenzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 91mg of N-p-methoxyphenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 32mg of triethylamine hydrofluoric acid salt, 2mL of acetonitrile, and stirring at 25℃for 10 minutes, 75mg of 2-styryl-3-p-methanesulfonamide benzofuran was added, and stirring was continued at 50℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-p-methoxyphenyl-4-phenylbenzofuran [3,2-d ]]64mg of pure and pure pyrimidine-2-amine product with the yield of 90 percent has the structural formula:
n-p-methoxyphenyl-4-phenylbenzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(600MHz,DMSO-d 6 )δ9.60(s,1H),8.48(d,J＝7.2Hz,2H),8.11(d,J＝7.8Hz,1H),7.84-7.81(m,3H),7.74(t,J＝7.8Hz,1H),7.66(t,J＝7.8Hz,2H),7.61(t,J＝7.2Hz,1H),7.50(t,J＝7.8Hz,1H),6.94(d,J＝9.0Hz,2H),3.75(s,3H)ppm； 13 C NMR(151MHz,DMSO-d 6 )δ157.8,157.1,154.0,151.9,146.9,139.8,134.3,134.1,131.8,131.1,128.9,128.6,124.0,121.8,121.2,120.1,113.8,113.0,55.2ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 18 N 3 O 2 368.1394,found 368.1398.
Which is a kind of 1 H NMR chart 13 The C NMR chart is shown in FIG. 3 and FIG. 4.
Example 3
The synthesis method of the N-p-methylphenyl-4-phenylbenzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken and N-p-methylphenyl-N-cyano-p-toluenesulfonyl 8 was added6mg of potassium carbonate 80mg, triethylamine hydrofluoride 32mg, acetonitrile 2mL,25℃for 10 minutes, 2-styryl-3-p-methanesulfonamide benzofuran 75mg, and 25℃for 24 hours were added. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-p-methylphenyl-4-phenylbenzofuran [3,2-d ]]And 70mg of pure pyrimidine-2-amine, with 99% yield, and the structural formula is:
n-p-methylphenyl-4-phenylbenzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(600MHz,CDCl 3 )δ8.55(d,J＝7.8Hz,2H),8.15(d,J＝7.8Hz,1H),7.68(d,J＝7.8Hz,2H),7.64-7.62(m,2H),7.58(t,J＝7.8Hz,2H),7.54(t,J＝7.2Hz,1H),7.41-7.39(m,1H),7.29(s,1H),7.19(d,J＝8.4Hz,2H),2.35(s,3H)ppm； 13 C NMR(151MHz,CDCl 3 )δ158.6,157.0,152.6,148.0,141.1,138.0,134.7,131.5,131.4,131.1,129.5,129.2,128.9,123.7,122.4,122.0,118.9,112.8,20.9ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 18 N 3 O 352.1444,found 352.1463.
Which is a kind of 1 H NMR chart 13 The C NMR chart is shown in FIG. 5 and FIG. 6.
Example 4
The synthesis method of the N-p-fluorophenyl-4-phenylbenzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 87mg of N-p-fluorophenyl-N-cyano-p-toluenesulfonyl, 64mg of sodium carbonate, 32mg of triethylamine hydrofluoric acid salt, 2mL of acetonitrile, stirring at 25℃for 10 minutes, and 75mg of 2-styryl-3-p-methanesulfonamide benzofuran were added and stirring was continued at 25℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-p-fluorophenyl-4-phenylbenzofuran [3,2-d ]]And 70mg of pure pyrimidine-2-amine, with 99% yield, and the structural formula is:
n-p-fluorophenyl-4-phenylbenzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(400MHz,CDCl 3 )δ8.54-8.52(m,2H),8.15(d,J＝8.0Hz,1H),7.74-7.71(m,2H),7.67-7.53(m,5H),7.44-7.40(m,1H),7.34(s,1H),7.10-7.05(m,2H)ppm； 13 C NMR(151MHz,CDCl 3 )δ158.7,158.3(d,J＝240.1Hz),156.8,152.6,148.1,141.2,136.6(d,J＝3.0Hz),134.5,131.5,131.2,129.2,128.9,123.7,122.4,121.9,120.3(d,J＝7.6Hz),115.6(d,J＝22.7Hz),112.9ppm； 19 F NMR(565MHz,CDCl 3 )δ-121.6ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 15 FN 3 O 356.1194,found356.1183.
Example 5
The synthesis method of the N-phenyl-4-p-chlorophenyl benzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 82mg of N-phenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 28mg of pyridine hydrofluoric acid salt, 2mL of toluene and stirring at 25℃for 10 minutes, 82mg of 2-p-chlorostyryl-3-p-methanesulfonamide benzofuran was added, and stirring was continued at-10℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-phenyl-4-p-chlorophenyl benzofuran [3,2-d ]]36mg of pure and pure pyrimidine-2-amine with the yield of 49 percent has the structural formula:
n-phenyl-4-p-chlorophenyl-benzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(400MHz,DMSO-d 6 )δ9.83(s,1H),8.47(d,J＝8.4Hz,2H),8.12(d,J＝7.6Hz,1H),7.93(d,J＝8.0Hz,2H),7.84-7.70(m,4H),7.51(t,J＝7.2Hz,1H),7.36(t,J＝7.6Hz,2H),6.99(t,J＝7.6Hz,1H)ppm； 13 C NMR(151MHz,DMSO-d 6 )δ157.9,156.7,152.1,145.5,141.0,139.8,136.0,132.8,132.0,130.2,129.7,129.1,128.5,124.1,121.9,121.1,118.4,113.0ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 15 ClN 3 O 372.0898,found 372.0910.
Example 6
The synthesis method of the N-phenyl-4-p-bromophenyl benzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 82mg of N-phenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 32mg of triethylamine hydrofluoric acid, 2mL of acetonitrile, and stirring at 25℃for 10 minutes was carried out, 91mg of 2-p-bromostyryl-3-p-methanesulfonamide benzofuran was added, and stirring was continued at 25℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-phenyl-4-p-bromophenyl benzofuran [3,2-d ]]And 63mg of pure pyrimidine-2-amine, 76% yield, and the structural formula is:
n-phenyl-4-p-bromophenyl-benzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(600MHz,CDCl 3 )δ8.42(d,J＝9.0Hz,2H),8.16(d,J＝7.8Hz,1H),7.77(d,J＝7.8Hz,2H),7.70(d,J＝8.4Hz,2H),7.66-7.61(m,2H),7.44-7.37(m,3H),7.31(s,1H),7.06(t,J＝7.8Hz,1H)ppm； 13 C NMR(151MHz,CDCl 3 )δ158.7,156.8,153.0,146.7,141.0,140.4,133.5,132.2,131.7,130.7,129.1,125.9,123.9,122.5,122.2,121.9,118.7,112.9ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 15 Br 79 N 3 O416.0393,found 416.0388.
Example 7
The synthesis method of the N-phenyl-4-m-chlorophenyl benzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 82mg of N-phenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 32mg of triethylamine hydrofluoric acid salt, 2mL of acetonitrile, and stirring at 25℃for 10 minutes was carried out, 82mg of 2-m-chlorostyryl-3-p-methanesulfonamide benzofuran was added, and stirring was continued at 25℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-phenyl-4-m-chlorophenyl benzofuran [3,2-d ]]And 71mg of pure pyrimidine-2-amine, with 96% yield, and the structural formula is as follows:
n-phenyl-4-m-chlorophenyl benzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(600MHz,DMSO-d 6 )δ9.81(s,1H),8.43-8.40(m,2H),8.10(d,J＝7.8Hz,1H),7.92(d,J＝7.8Hz,2H),7.82(d,J＝7.8Hz,1H),7.76-7.73(m,1H),7.68-7.64(m,2H),7.50(t,J＝7.8Hz,1H),7.36(t,J＝7.8Hz,2H),7.00(t,J＝7.2Hz,1H)ppm； 13 C NMR(151MHz,DMSO-d 6 )δ157.9,156.6,152.2,144.9,140.9,139.8,135.9,133.7,132.0,130.81,130.76,128.4,127.8,127.2,124.0,121.8,121.1,120.9,118.4,113.0ppm；HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 15 ClN 3 O 372.0898,found 372.0892.
Example 8
The synthesis method of the N-phenyl-4-furyl benzofuran [3,2-d ] pyrimidine-2-amine comprises the following steps:
a25 mL reaction flask was taken, 82mg of N-phenyl-N-cyano-p-toluenesulfonyl, 65mg of cesium carbonate, 32mg of triethylamine hydrofluoric acid salt, 2mL of acetonitrile, and stirring at 25℃for 10 minutes was carried out, 73mg of 2-furyl3-p-methanesulfonamide benzofuran was added, and stirring was continued at 25℃for 24 hours. After the reaction is finished, adding 10mL of water for quenching reaction, adding ethyl acetate for extraction for three times, combining organic phases, and separating by column chromatography to obtain N-phenyl-4-furyl benzofuran [3,2-d ]]49mg of pure and pure pyrimidine-2-amine product with the yield of 75 percent has the structural formula:
n-phenyl-4-furanylbenzofuran [3,2-d ]]Pure product of pyrimidine-2-amine 1 H NMR(400MHz,CDCl 3 )δ8.17(d,J＝8.0Hz,1H),7.82(d,J＝8.0Hz,2H),7.77(d,J＝0.8Hz 1H),7.64-7.63(m,3H),7.44-7.36(m,4H),7.05(t,J＝7.6Hz,1H),6.70-6.69(m,1H)ppm； 13 C NMR(100MHz,CDCl 3 )δ158.7,156.7,151.9,148.4,145.8,140.5,139.6,138.5,131.4,129.1,123.8,122.4,122.1,122.0,118.5,116.8,112.9,112.7ppm；IR(KBr):v 3449,2832,1593,1538,1497,1440,1356,1204,1083,744cm -1 ；HRMS(ESI)m/z:[M+H] + Calcd for C 20 H 14 N 3 O 2 328.1081,found 328.1095.
Examples of the effects
To verify the benzofuran [3,2-d ] synthesized according to the synthesis method of this example]The biological activity of the pyrimidine-2-amine compound is screened by adopting an Airbrush spraying method, and the insecticidal activity of the synthesized compound on plutella xylostella at different concentrations is achieved. Experiments show that most of the compounds are in the range of 5 mg.L -1 Has good insecticidal activity to three-instar larvae of plutella xylostella, and is 2.5 mg.L -1 Has certain insecticidal activity to the three-instar larvae of plutella xylostella, wherein the N-p-fluorophenyl-4-phenylbenzofuran [3,2-d ] prepared in example 4]The best insecticidal effect of the pyrimidine-2-amine on the three-instar larvae of plutella xylostella is shown in table 1;
TABLE 1 mortality value of benzofuran [3,2-d ] pyrimidine-2-amine on Plutella xylostella
As can be seen from table 1: benzofuran [3,2-d ] synthesized by the method]Pyrimidin-2-amine compound in 5 mg.L -1 The mortality rate of the compound 3, the compound 4 and the compound 5 to the three-instar larvae of plutella xylostella is over 90 percent, wherein the compound 3, the compound 4 and the compound 5 reach 100 percent, and the insecticidal activity of the compound is equivalent to that of abamectin. At 2.5 mg.L -1 Has a certain lethality to the three-instar larvae of plutella xylostella. The result shows that the benzofuran [3,2-d ] synthesized by the synthesis method]The pyrimidine-2-amine compound has good insecticidal activity.
The foregoing description of the preferred embodiments of the application is not intended to be limiting, but rather is intended to cover all modifications, equivalents, alternatives, and improvements that fall within the spirit and scope of the application.
Claims (10)
1. A benzofuran [3,2-d ] pyrimidine-2-amine compound having the formula:
wherein: r is R 1 Any one selected from phenyl and substituted phenyl; r is R 3 Selected from any one of phenyl, substituted phenyl and naphthyl.
2. Benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 1, having any one of the following structural formulae:
wherein X is halogen,Wherein X is halogen or->
3. The synthesis method of the benzofuran [3,2-d ] pyrimidine-2-amine compound as claimed in claim 1 or 2, which is characterized by comprising the following steps: 2-styryl-3-sulfonamide benzofuran compound, alkali and hydrofluoric acid salt are mixed and stirred in a solvent, and then N-aryl-N-cyano-p-toluenesulfonamide compound is added for synthesis reaction, so that benzofuran [3,2-d ] pyrimidine-2-amine compound is prepared.
4. The method for synthesizing benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 3, wherein: the mass ratio of the 2-styryl-3-sulfonamide benzofuran compound, the N-aryl-N-cyano-p-toluenesulfonyl compound, the alkali and the hydrofluoric acid salt is 1 (1-5): 2-5.
5. The method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 4, wherein the method comprises the following steps: the base is selected from any one of potassium carbonate, cesium carbonate, sodium carbonate and triethylamine.
6. The method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 5, wherein the method comprises the following steps: the hydrofluoric acid salt is selected from any one of triethylamine hydrofluoric acid salt, pyridine hydrofluoric acid salt and tetra-n-butyl ammonium bifluoride hydrofluoric acid salt.
7. The method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 6, wherein the method comprises the following steps: the base is cesium carbonate; the hydrofluoric acid salt is triethylamine hydrofluoric acid salt.
8. The method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound according to any one of claims 1 to 7, wherein the method comprises the following steps: the mixing and stirring time is 10-30 min; the temperature of the synthesis reaction is between-10 and 50 ℃ and the time is 24 hours.
9. The method for synthesizing the benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 6, wherein the method comprises the following steps: the solvent is selected from any one of acetonitrile, dichloromethane, 1, 2-dichloroethane, toluene, 1, 4-dioxane and ethyl acetate.
10. Use of a benzofuran [3,2-d ] pyrimidine-2-amine compound according to claim 1 in the preparation of a pesticide.
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