CN110016019A - A kind of furodiazole derivative and the preparation method and application thereof based on benzofuranol - Google Patents

A kind of furodiazole derivative and the preparation method and application thereof based on benzofuranol Download PDF

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CN110016019A
CN110016019A CN201910360331.9A CN201910360331A CN110016019A CN 110016019 A CN110016019 A CN 110016019A CN 201910360331 A CN201910360331 A CN 201910360331A CN 110016019 A CN110016019 A CN 110016019A
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dimethyl
base
oxygroup
preparation
dihydrobenzofuranes
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CN110016019B (en
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李婉
李胜男
武世杰
朱华结
田胜尼
冯珂
曹飞
李龙飞
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Hebei University
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Hebei University
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    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Abstract

The present invention provides the furodiazole derivatives and the preparation method and application thereof shown in a kind of formula (I) based on benzofuranol, and in formula, R is selected from 4-CN-C6H4、4‑F‑C6H4, 4-Cl-C6H4、4‑Br‑C6H4、3‑F‑C6H4、3‑Br‑C6H4、4‑NO2‑C6H4、3‑NO2‑C6H4、2‑Br‑C6H4、3‑CH3‑C6H4、4‑CH3‑C6H4、4‑OMe‑C6H4、3‑OMe‑C6H4、2‑OMe‑C6H4, phenyl, isopropyl, cyclohexyl, styryl, furyl, thienyl or naphthalene.The compound of the present invention and its pharmaceutically acceptable salt show higher inhibitory activity to weeds such as barnyard grasses, and will not damage to crop, provide new selection to eliminate weeds.

Description

A kind of furodiazole derivative and the preparation method and application thereof based on benzofuranol
Technical field
The present invention relates to a kind of compound, preparation method and applications, and in particular to a kind of oxadiazoles based on benzofuranol Analog derivative and the preparation method and application thereof.
Background technique
China is world food production and consumption big country, improve Per Unit Area Grain Yield be guarantee one of China's grain security very Important approach.Weeds are to lead to one of principal element of crop production reduction, the exploitation of organic chemistry herbicide and are answered on a large scale It is lost with agricultural economy caused by weeds can be greatly reduced.Existing herbicide has more than 500 kinds, but due to long-term It reuses, many weeds produce resistance to the herbicide of multiple types, multiple kinds in recent years, therefore, develop new Herbicide is imperative.
1,3,4- oxadiazoles is the five-ring heterocycles of the atom containing O and N, has extensive medicine and pesticide activity, and such as anti-inflammatory resists Bacterium and coordinate plant growth isoreactivity.Research of 1,3, the 4- furodiazole compound in terms of herbicide is more, for example, Yang little Hong Deng using dehydroabietic acid as raw material, 2- substituted thioethers -5- dehydrogenation pine has been obtained through esterification, hydrazinolysis, cyclization and nucleophilic substitution Perfume base-, 3,4- furodiazole compounds test activity using small-radius curve track, the results showed that part of compounds has one to barnyard grass rhizome Fixed inhibitory activity；Chen Hansong etc. has synthesized 2- substitution -5- pyrazolyl -1,3,4- furodiazole compound, to barnyard grass and rape There is certain inhibitory activity；The 3- (pyrimidine radicals -2) -1 of Zhu You congruence report, 3,4- oxadiazoles -2 (3H) -one derivatives, using oil Dish Plating and barnyard grass small-radius curve track are tested, and part of compounds shows certain activity of weeding.But above-mentioned 1,3,4- dislike Diazoles compound is not preparation method complexity, is exactly that activity of weeding is low, therefore, it is necessary to develop new 1,3,4- furodiazoles It closes object and is used for weeding field.
Summary of the invention
It is an object of the invention to provide a kind of furodiazole derivative based on benzofuranol, to barnyard grass under low dosage With inhibitory activity, new selection is provided for the exploitation of herbicide.
The object of the present invention is achieved like this:
A kind of formula (I) compound represented or its pharmaceutically acceptable salt,
Wherein, R is selected from 4-CN-C6H4、4-F-C6H4, 4-Cl-C6H4、4-Br-C6H4、3-F-C6H4、3-Br-C6H4、4- NO2-C6H4、3-NO2-C6H4、2-Br-C6H4、3-CH3-C6H4、4-CH3-C6H4、4-OMe-C6H4、3-OMe-C6H4、2-OMe- C6H4, phenyl, isopropyl, cyclohexyl, styryl, furyl, thienyl or naphthalene.
Preferably, the compound is selected from:
The present invention also provides the preparation methods of formula (I) compound represented, comprising the following steps:
(1) compound A (benzofuranol) is dissolved in anhydrous DMF, K is added2CO3It is stirred at room temperature to dissolution, observes solution colour, It is faded to by light green color deep blackish green, ultimately becomes black, be added ethyl chloroacetate, catalytic amount KI, agitating and heating 6- at 60 DEG C 8h, TLC detection.After reaction, add a small amount of water stirring 5min, ethyl acetate extraction, organic phase anhydrous Na SO4It is dry, rotation It is dry.Petroleum ether: ethyl acetate=40: 1 column chromatography obtains intermediate product B sterling, is buff thick liquid.Compound A and chloroethene The molar ratio of acetoacetic ester is 1: 1.5；
(2) intermediate product B is dissolved in dehydrated alcohol, hydrazine hydrate (80% mass fraction), ice is added dropwise under condition of ice bath dropwise 5min is stirred under the conditions of bath.60 DEG C of agitating and heating 2h, TLC monitorings.After reaction, methylene chloride extracts, and solvent is spin-dried for, is added Water has crystal precipitation, filters.Ethyl alcohol recrystallization obtains intermediate product C sterling, is white crystal.Intermediate product B and hydrazine hydrate Molar ratio is 1: 2.5；
(3) intermediate product C is dissolved in dehydrated alcohol, aldehyde, 60 DEG C of agitating and heating 6-8h, TLC monitorings is added after stirring and dissolving. It after fully reacting, filters, faint yellow sticky shape solid is obtained after being spin-dried for.(V is chromatographed through columnMethylene chloride∶VMethanol=160: 1), rotating to obtain the final product Intermediate product D.The molar ratio of intermediate product C and aldehyde is 1: 1.2；
(4) intermediate product D is dissolved in dehydrated alcohol, after 40 DEG C of stirrings are completely dissolved, iodobenzene diethylester is added, stirs back Flow 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloro respectively Methane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains white crystal, target product as of the invention.
Reaction equation is as follows:
On the other hand, the present invention provides the compound or its pharmaceutically acceptable salt answering in herbicide drug With the drug has stronger inhibitory activity to weeds such as barnyard grasses.
In another aspect, the present invention provides a kind of composition pesticide, it includes compound of the present invention or its pharmaceutically Acceptable salt is as effective ingredient and one or more pharmaceutically acceptable auxiliary materials.
Composition pesticide provided by the invention contains permits on above compound and its pharmaceutically acceptable salt, pharmaceutics Carrier or the mixed combination with pharmaceutical excipient or diluent using such compound as active constituent.
The various dosage forms of composition pesticide provided by the invention can be prepared according to the conventional production process of pesticide field, example It mixes active constituent with one or more carriers, is then made into required dosage form.
The compound of the present invention and its pharmaceutically acceptable salt show higher inhibitory activity to weeds such as barnyard grasses, and Crop will not be damaged, provide new selection to eliminate weeds.Meanwhile the preparation method of the compounds of this invention is simple, produces Rate is high, and cost is relatively low, easy to promote and utilize.
Specific embodiment
Below with reference to embodiment, the present invention is further elaborated, the process being not described in detail in the following embodiments and Method is conventional method well known in the art, and raw materials used or reagent is unless otherwise stated commercially available product in embodiment, can be led to Commercial channel is crossed to buy.
Embodiment 1
Ethyl -2- ((2,2- dimethyl -2,3-2,3- Dihydrobenzofuranes -7- base) oxygroup) ethyl acetate (compound B) Synthesis:
Compound A is dissolved in anhydrous DMF, K is added2CO3It is stirred at room temperature to dissolution, addition ethyl chloroacetate, catalytic amount KI, Agitating and heating 6-8h at 60 DEG C, TLC detection.After reaction, add a small amount of water stirring 5min, ethyl acetate extraction, organic phase is used Anhydrous Na SO4It is dry, it is spin-dried for.Petroleum ether: ethyl acetate=40: 1 column chromatography obtains intermediate product B sterling, is yellow viscous fluid Body, yield 90%.The molar ratio of compound A and ethyl chloroacetate is 1: 1.5；MS-ESI,m/z 273.28[M+Na]+.HR- MS-EI m/z calcd for C14H18O4[M+H]+250.2925 found 250.2940；1H NMR(600MHz,CDCl3)δ 6.80 (d, J=7.1Hz, 1H), 6.75-6.68 (m, 2H), 4.71 (s, 2H), 4.24 (q, J=7.1Hz, 2H), 3.01 (s, 2H), 1.50 (s, 6H), 1.28 (t, J=7.1Hz, 3H)；13C NHR(150MHz,CDCl3)δ169.34,147.66,142.65, 129.02,120.30,118.79,114.46,87.61,66.72,61.11,43.14,28.19,14.17。
Embodiment 2
The synthesis of 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide (compound C):
Intermediate product B is dissolved in dehydrated alcohol, hydrazine hydrate (80% mass fraction), ice bath item is added dropwise under condition of ice bath dropwise 5min is stirred under part.60 DEG C of agitating and heating 2h, TLC monitorings.After reaction, methylene chloride extracts, and solvent is spin-dried for, water is added, There is crystal precipitation, filters.Ethyl alcohol recrystallization obtains intermediate product C, white crystal, yield 93%.Intermediate product B and hydrazine hydrate Molar ratio is 1: 2.5；MS-ESI,m/z 259.26[M+Na]+.HR-MS-EI m/z calcd for C12H16N2O3[M+H]+ 236.2695,found236.2710；1H NMR(600MHz,CDCl3) δ 8.13 (s, 1H), 6.86 (d, J=7.2Hz, 1H), 6.77 (t, J=7.7Hz, 1H), 6.73 (d, J=8.0Hz, 1H), 4.65 (s, 2H), 3.90 (s, 2H), 3.05 (s, 2H), 1.52 (s,6H)。
Embodiment 3
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzylidene) acetyl The preparation of hydrazine:
2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide is dissolved in 50ml ethyl alcohol, 2.88mmol 4-Fluorobenzaldehyde is added after stirring and dissolving, 60 DEG C of heating stirring 6-8h, TLC monitorings of oil bath pan after fully reacting, are taken out Filter, obtains faint yellow sticky shape solid crude product 0.74g after being spin-dried for, crude product chromatographs (V through columnMethylene chloride∶VMethanol=160: 1), obtaining (E)- 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzylidene) acethydrazide 0.54g. M.p.145.9-146.5 DEG C, yield 90.1%,1H NMR(600MHz,CDCl3)δ9.92(s,1H),8.13(s,1H),7.63 (d, J=8.4Hz, 2H), 7.30 (d, J=8.4Hz, 2H), 6.84-6.79 (m, 1H), 6.73 (d, J=6.3Hz, 2H), 4.67 (s,2H),2.99(s,2H),1.46(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(4- Fluorophenyl) the preparation of -1,3,4-oxadiazole:
2.16mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.59mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow solid 0.69g, as target product, yield 94.2%. MS-ESI,m/z 363.11[M+Na]+.HR-MS-EI m/z calcd for C19H17FN2O3[M+H]+341.1288, found341.1301.m.p.139-141℃；1H NMR(600MHz,CDCl3) δ 8.01 (d, J=8.6Hz, 2H), 7.49 (d, J =8.6Hz, 2H), 6.92 (d, J=8.1Hz, 1H), 6.85 (d, J=7.4Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.41 (s,2H),3.02(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ164.94,162.79,148.09, 142.08,138.28,129.48,129.30,128.38,122.13,120.55,119.68,115.16,87.98,61.37, 43.10,28.20。
Embodiment 4
2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- ((1E, 2E) -3- phenyl arlydene) The preparation of acethydrazide:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol cortex cinnamomi aldehyde reaction 6-8h obtain 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygen Base)-N'- ((1E, 2E) -3- phenyl arlydene) acethydrazide yellow solid 0.77g, m.p.142.3-144.2 DEG C, yield 92.1%；1H NMR(600MHz,CDCl3) δ 9.87 (s, 1H), 7.86 (d, J=9.2Hz, 1H), 7.38 (d, J=7.3Hz, 2H), 7.29 (t, J=7.4Hz, 2H), 7.25 (d, J=7.2Hz, 1H), 6.82 (dd, J=10.1,5.6Hz, 2H), 6.73 (d, J=4.7Hz, 2H), 4.66 (s, 2H), 2.99 (s, 2H), 1.46 (s, 6H).
(E)-2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5- The preparation of styryl-1,3,4-oxadiazole:
2.21mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.65mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains pale yellow powder 0.72g, as target product, yield 94.1%. MS-ESI,m/z 371.14[M+Na]+.HR-MS-EI m/z calcd for C21H20N2O3[M+H]+349.1534, found349.1552.m.p.138-140℃；1H NMR(600MHz,CDCl3)δ1.41(s,6H,2×CH3),2.93(s,2H, CH2),5.33(s,2H,CH2), 7.98 (d, J=6Hz, 2H, C6H52,5H), 7.438 (d, J=7.2Hz, 1H, C6H5 4H), 7.409(t,2H,C6H53,5H), 6.840 (d, J=7.8Hz, 1H, C6H34H), 6.753 (d, J=7.8Hz, 1H, C6H3, 6H),6.669(t,1H,C6H35H)；13C NMR(151MHz,CDCl3)δ165.35,162.05,143.04,139.90, 137.40,134.65,129.03,128.59,128.54,127.58,126.53,126.47,120.55,109.68,87.96, 61.44,43.12,28.21。
Embodiment 5
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (naphthalene -1- methylene) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 1- how aldehyde reaction 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) Oxygroup)-N'- (naphthalene -1- methylene) acethydrazide yellow solid 0.81g, m.p.145.1-146.4 DEG C, yield 90.4%；1H NMR(600MHz,CDCl3) δ 8.91 (s, 1H), 8.58 (d, J=8.5Hz, 1H), 8.00 (d, J=7.1Hz, 1H), 7.82 (dd, J=15.4,8.2Hz, 2H), 7.53 (t, J=7.6Hz, 1H), 7.44 (dd, J=16.7,8.6Hz, 2H), 6.81 (d, J= 6.9Hz, 1H), 6.75 (dt, J=18.3,7.0Hz, 2H), 4.68 (s, 2H), 3.01 (s, 2H), 1.50 (s, 6H).
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5- (naphthalen-2-yl) preparation of -1,3,4-oxadiazole:
2.17mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.60mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow solid 0.77g, as target product, yield 95.5%. MS-ESI,m/z 395.14[M+Na]+.HR-MS-EI m/z calcd for C23H20N2O4[M+H]+373.1537, found373.1552.m.p.134-136℃；1H NMR(600MHz,CDCl3) δ 9.18 (d, J=8.6Hz, 1H), 8.21 (d, J =7.2Hz, 1H), 8.04 (d, J=8.2Hz, 1H), 7.93 (d, J=8.1Hz, 1H), 7.67 (t, J=7.7Hz, 1H), 7.58 (dt, J=12.4,7.8Hz, 2H), 6.97 (d, J=8.1Hz, 1H), 6.86 (d, J=7.4Hz, 1H), 6.77 (t, J= 7.8Hz,1H),5.49(s,2H),3.03(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ165.75, 162.29,148.17,142.16,133.83,132.81,130.05,129.30,128.21,126.73,126.17,124.85, 120.57,120.22,119.66,115.35,87.97,61.48,43.12,28.21。
Embodiment 6
(E)-N'- (4- chlorine benzal)-2-((2,2- dimethyl-2,3- Dihydrobenzofuranes-7- base) oxygroup) acethydrazide Preparation:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 4-Fluorobenzaldehyde react 6-8h, obtain (E)-N'- (4- chlorine benzal) -2- ((2,2- dimethyl -2, 3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide white solid 0.76g, m.p.141.7-143.5 DEG C, yield 88.3%；1H NMR(600MHz,CDCl3) δ 10.07 (s, 1H), 8.11 (s, 1H), 7.60 (d, J=8.5Hz, 2H), 7.27 (d, J=8.4Hz, 2H),6.82–6.77(m,1H),6.74–6.71(m,2H),4.65(s,2H),2.98(s,2H),1.45(s,6H)。
2-(4-chlorophenyl)-5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy) Methyl) the preparation of -1,3,4-oxadiazole:
2.12mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.54mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains white powder 0.72g, as target product, yield 95.1%. MS-ESI,m/z 379.08[M+Na]+.HR-MS-EI m/z calcd for C19H17ClN2O3[M+H]+357.0990,found 357.1006.m.p.141-143℃；1H NMR(600MHz,CDCl3) δ 8.20 (d, J=8.5Hz, 2H), 7.82 (d, J= 8.5Hz, 2H), 6.91 (d, J=8.1Hz, 1H), 6.86 (d, J=6.8Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.44 (s, 2H),3.03(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ164.94,162.80,148.09,142.08, 138.28,129.48,129.33,128.38,122.13,120.55,119.69,115.17,87.98,61.38,43.10, 28.20。
Embodiment 7
(E)-N'- (4- bromine benzal) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide Preparation:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol p-bromobenzaldehyde react 6-8h, obtain (E)-N'- (4- bromine benzal) -2- ((2,2- dimethyl -2, 3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide white solid 0.86g, m.p.142.3-144.2 DEG C, yield 94.5%；1H NMR(600MHz,CDCl3) δ 10.02 (s, 1H), 8.11 (s, 1H), 7.55 (d, J=8.4Hz, 2H), 7.45 (d, J=8.4Hz, 2H), 6.81 (dd, J=5.3,3.2Hz, 1H), 6.74-6.71 (m, 2H), 4.66 (s, 2H), 2.99 (s, 2H), 1.46 (s, 6H)。
2-(4-bromophenyl)-5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy) Methyl) the preparation of -1,3,4-oxadiazole:
2.13mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.56mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains white powder 0.81g, as target product, yield 95.1%. MS-ESI,m/z 423.03[M+Na]+.HR-MS-EI m/z calcd for C19H17BrN2O3[M+H]+401.0484, found401.0510.m.p.143-145℃；1H NMR(600MHz,CDCl3) δ 7.94 (d, J=8.6Hz, 2H), 7.65 (d, J =8.6Hz, 2H), 6.92 (d, J=8.1Hz, 1H), 6.85 (d, J=8.1Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.41 (s,2H),3.02(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ165.04,162.82,148.09, 142.08,132.44,129.30,128.51,126.72,122.57,120.55,119.69,115.16,87.99,61.38, 43.10,28.20。
Embodiment 8
(E)-N'- (2- bromine benzal) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide Preparation:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 2- bromobenzaldehyde react 6-8h, obtain (E)-N'- (2- bromine benzal) -2- ((2,2- dimethyl -2, 3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide white solid 0.92g, m.p.141.3-143.2 DEG C, yield 95.1%；1H NMR(600MHz,CDCl3) δ 8.10 (d, J=6.6Hz, 1H), 7.48 (d, J=7.9Hz, 1H), 7.25 (s, 1H), 7.21- 7.10 (m, 2H), 6.81 (d, J=6.5Hz, 1H), 6.77-6.67 (m, 2H), 4.68 (s, 2H), 2.98 (s, 2H), 1.47 (s, 6H)。
2-(2-bromophenyl)-5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy) Methyl) the preparation of -1,3,4-oxadiazole:
2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (2- bromobenzene methylene Base) acetyl hydrazone is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.74mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains white powder 0.87g, as target product, yield 95%.MS- ESI,m/z 423.03[M+Na]+.HR-MS-EI m/z calcd for C19H17BrN2O3[M+H]+401.0484,found 401.0501.m.p.143-145℃；1H NMR(600MHz,CDCl3) δ 7.92 (d, J=7.8Hz, 1H), 7.73 (d, J= 8.0Hz, 1H), 7.44 (t, J=7.6Hz, 1H), 7.37 (t, J=8.5Hz, 1H), 6.92 (d, J=8.1Hz, 1H), 6.84 (d, J=7.3Hz, 1H), 6.75 (t, J=7.8Hz, 1H), 5.45 (s, 2H), 3.02 (s, 2H), 1.49 (s, 6H)；13C NMR (151MHz,CDCl3)δ164.56,163.16,148.11,142.09,134.58,132.62,131.72,129.29, 127.56,125.06,121.76,120.53,119.63,115.37,87.95,61.36,43.09,28.21。
Embodiment 9
(E)-N'- (3- bromine benzal) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide Preparation:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 3- bromobenzaldehyde react 6-8h, obtain (E)-N'- (3- bromine benzal) -2- ((2,2- dimethyl -2, 3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide white solid 0.93g, m.p.143.3-145.2 DEG C, yield 94.6%；1H NMR(600MHz,CDCl3) δ 9.99 (s, 1H), 8.10 (s, 1H), 7.87 (s, 1H), 7.57 (d, J=7.7Hz, 1H), 7.45 (d, J=8.0Hz, 1H), 7.19 (d, J=2.0Hz, 1H), 6.82 (dd, J=5.6,1.9Hz, 1H), 6.75-6.72 (m, 2H), 4.67(s,2H),2.99(s,2H),1.46(s,6H)。
2-(3-bromophenyl)-5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy) Methyl) the preparation of -1,3,4-oxadiazole (SN-A-1):
2.31mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- bromobenzene methylene Base) acetyl hydrazone is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.77mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains white powder 0.88g, as target product, yield 95%.MS- ESI,m/z 423.03[M+Na]+.HR-MS-EI m/z calcd for C19H17BrN2O3[M+H]+401.0491,found 401.0501.m.p.143-145℃；1H NMR(600MHz,CDCl3)δ1.51(s,6H,2×CH3),3.02(s,2H,CH2), 5.42(s,2H,CH2),6.76(t,1H,C6H35H), 6.85 (d, J=6Hz, 1H, C6H34H), 6.91 (d, J=6Hz, 1H, C6H36H), 7.38 (t, 1H, C6H45H), 7.66 (d, J=7.2Hz, 1H, C6H46H), 8.02 (s, 1H, C6H42H)；13C NMR(151MHz,CDCl3)δ164.44,162.99,148.12,142.04,134.91,130.64,129.98,129.34, 125.61,125.47,123.10,120.56,119.74,115.27,88.01,61.41,43.10,28.20。
Embodiment 10
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- fluorobenzylidene) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 3- fluorobenzaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- Base) oxygroup)-N'- (3- fluorobenzylidene) acethydrazide white solid 0.78g, m.p.144.9-146.5 DEG C, yield 94.6%；1H NMR(600MHz,CDCl3) δ 10.02 (d, J=32.4Hz, 1H), 8.13 (s, 1H), 7.88 (s, 1H), 7.58 (d, J= 7.7Hz, 1H), 7.44 (t, J=7.6Hz, 1H), 6.85-6.78 (m, 1H), 6.74-6.78 (m, 2H), 4.67 (s, 2H), 2.99 (s,2H),1.46(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(3- Fluorophenyl) the preparation of -1,3,4-oxadiazole:
2.27mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- fluorobenzene methylene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.72mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains pale yellow powder 0.72g, as target product, yield 93%. MS-ESI,m/z363.11[M+Na]+.HR-MS-EI m/z calcd for C19H17FN2O3[M+H]+341.1288,found 341.1301.m.p.139-141℃；1H NMR(600MHz,CDCl3) δ 7.87 (d, J=7.8Hz, 1H), 7.77 (d, J= 13.0Hz, 1H), 7.48 (t, J=8.0Hz, 1H), 7.25 (s, 1H), 6.92 (d, J=8.1Hz, 1H), 6.85 (d, J= 6.8Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.42 (s, 2H), 3.02 (s, 2H), 1.49 (s, 6H)；13C NMR(151MHz, CDCl3)δ163.65,162.95,162.00,148.12,142.07,129.32,125.56,122.89,122.87,120.55, 119.71,115.25,114.26,114.09,87.99,61.40,43.10,28.19。
Embodiment 11
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- nitro benzylidene) second The preparation of hydrazides:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol paranitrobenzaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes - 7- yl) oxygroup)-N'- (4- nitro benzylidene) acethydrazide yellow solid 0.84g, m.p.138.6-140.7 DEG C, yield 95.2%；1H NMR(600MHz,CDCl3) δ 10.39 (s, 1H), 8.40 (s, 1H), 8.26 (d, J=8.7Hz, 2H), 7.94 (d, J=8.7Hz, 2H), 6.90 (d, J=6.0Hz, 1H), 6.85-6.78 (m, 2H), 4.75 (s, 2H), 3.08 (s, 2H), 1.55 (s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(4- Nitrophenyl) the preparation of -1,3,4-oxadiazole:
(4- nitrobenzene is sub- by 2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- Methyl) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.74mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.79g, as target product, yield 94%.MS- ESI,m/z 390.11[M+Na]+.HR-MS-EI m/z calcd for C19H17N3O5[M+H]+368.1231 found368.1246.m.p.146-148℃；1H NMR(600MHz,CDCl3) δ 8.40 (d, J=8.8Hz, 2H), 8.29 (d, J =8.8Hz, 2H), 6.94 (d, J=8.1Hz, 1H), 6.89 (d, J=7.4Hz, 1H), 6.79 (t, J=7.8Hz, 1H), 5.47 (s,2H),3.05(s,2H),1.51(s,6H)；13C NMR(151MHz,CDCl3)δ163.97,163.68,149.74, 148.06,141.96,129.41,129.10,128.05,124.38,120.58,119.84,115.19,88.07,61.35, 43.06,28.19。
Embodiment 12
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (thiophene -2- methylene) second The preparation of hydrazides:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol thiophene 2- formaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- Base) oxygroup)-N'- (thiophene -2- methylene) acethydrazide brown solid 0.75g, m.p.139.5-141.3 DEG C, yield 95%；1H NMR(600MHz,CDCl3) δ 8.52 (s, 1H), 7.30 (d, J=21.6Hz, 1H), 7.21 (d, J=19.2Hz, 1H), 6.98-6.95 (m, 1H), 6.82-6.77 (m, 1H), 6.71 (d, J=4.5Hz, 2H), 4.63 (s, 2H), 2.97 (s, 2H), 1.45(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(thiophen- 2-yl) the preparation of -1,3,4-oxadiazole:
2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (thiophene -2- base Methylene) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.73mmol iodobenzene diethylester is added, stirs back Flow 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloro respectively Methane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow solid 0.72g, as target product, yield 95.6%. MS-ESI,m/z 351.08[M+Na]+.HR-MS-EI m/z calcd for C17H16N2O3S[M+H]+329.0445, found329.0960.m.p.129-131℃；1H NMR(600MHz,CDCl3) δ 7.78 (d, J=2.7Hz, 1H), 7.56 (d, J =5.9Hz, 1H), 7.22-7.11 (m, 1H), 6.92 (d, J=8.1Hz, 1H), 6.85 (d, J=7.3Hz, 1H), 6.75 (t, J =7.8Hz, 1H), 5.39 (s, 2H), 3.02 (s, 2H), 1.49 (s, 6H)；13C NMR(151MHz,CDCl3)δ162.03, 161.97,148.11,142.08,130.49,130.28,129.27,128.17,124.89,120.54,119.65,115.24, 87.96,61.29,43.10,28.19。
Embodiment 13
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- methylbenzilidene) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 3- tolyl aldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup)-N'- (3- methylbenzilidene) acethydrazide white solid 0.77g, m.p.131.9-133.8 DEG C, yield 95.2%；1H NMR(600MHz,CDCl3) δ 10.07 (s, 1H), 8.09 (s, 1H), 7.58 (s, 1H), 7.42 (d, J=7.6Hz, 1H), 7.21-7.18 (m, 1H), 7.14 (d, J=7.5Hz, 1H), 6.80 (dd, J=5.3,3.1Hz, 1H), 6.75-6.71 (m, 2H),4.65(s,2H),2.98(s,2H),2.29(s,3H),1.46(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(m-tolyl)- The preparation of 1,3,4-oxadiazole:
2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- Methylbenzylidene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.74mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.73g, as target product, yield 95.1%. MS-ESI,m/z359.14[M+Na]+.HR-MS-EI m/z calcd for C20H20N2O3[M+H]+337.1535, found337.1552.m.p.131-139℃；1H NMR(600MHz,CDCl3) δ 7.93 (s, 1H), 7.88 (d, J=7.5Hz, 1H), 7.41 (t, J=7.6Hz, 1H), 7.37 (d, J=7.6Hz, 1H), 6.95 (d, J=8.1Hz, 1H), 6.87 (d, J= 7.3Hz, 1H), 6.78 (t, J=7.7Hz, 1H), 5.43 (s, 2H), 3.04 (s, 2H), 2.45 (s, 3H), 1.52 (s, 6H)；13C NMR(151MHz,CDCl3)δ165.89,162.54,148.14,138.94,132.73,129.23,128.94,127.64, 124.25,123.50,120.52,119.59,115.19,87.93,61.44,43.11,28.19,21.29。
Embodiment 14
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- methylbenzilidene) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 4- tolyl aldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup)-N'- (4- methylbenzilidene) acethydrazide 0.77g, m.p.131.6-133.7 DEG C, yield 94.8%；1H NMR(600MHz,CDCl3) δ 9.90 (s, 1H), 8.08 (s, 1H), 7.58 (d, J=8.0Hz, 2H), 7.13 (d, J=7.9Hz, 2H), 6.81 (d, J=6.5Hz, 1H), 6.74-6.70 (m, 2H), 4.66 (s, 2H), 2.30 (s, 3H), 1.46 (s, 6H).
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(p-tolyl)- The preparation of 1,3,4-oxadiazole:
2.29mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- Methylbenzylidene Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.75mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.73g, as target product, yield 95.1%. MS-ESI,m/z359.14[M+Na]+.HR-MS-EI m/z calcd for C20H20N2O3[M+H]+337.1537, found337.1552.m.p.137-139℃；1H NMR(600MHz,CDCl3) δ 7.86 (d, J=8.2Hz, 2H), 7.21 (d, J =8.1Hz, 2H), 6.84 (d, J=8.1Hz, 1H), 6.75 (d, J=8.0Hz, 1H), 6.66 (t, J=7.8Hz, 1H), 5.31 (s,2H),2.93(s,2H),2.33(s,3H),1.40(s,6H)；13C NMR(151MHz,CDCl3)δ165.87,162.37, 148.11,142.50,142.17,129.75,129.22,127.06,120.89,120.53,119.58,115.19,87.91, 61.42,43.11,28.19,21.64。
Embodiment 15
(E) -2- (2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (4- benzylidene) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 4-methoxybenzaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup)-N'- (4- benzylidene) acethydrazide white solid 0.81g, m.p.133.5-134.8 DEG C, yield 95.4%；1H NMR(600MHz,CDCl3) δ 8.12 (s, 1H), 7.35-7.19 (m, 2H), 7.16 (d, J=7.3Hz, 2H), 6.91–6.85(m,1H),6.80(s,1H),6.73(s,1H),4.65(s,2H),3.76(s,3H),2.98(s,2H),1.45 (s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(4- Methoxyphenyl) the preparation of -1,3,4-oxadiazole:
2.28mmol (E) -2- (2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) (4- methoxyl group is sub- by-N'- Benzyl) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.75mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.76g, as target product, yield 95.1%. MS-ESI,m/z 375.13[M+Na]+.HR-MS-EI m/z calcd for C20H20N2O4[M+H]+353.1487,found 353.1501.m.p.136-158℃；1H NMR(600MHz,CDCl3) δ 7.95 (d, J=8.1Hz, 2H), 7.30 (d, J= 8.1Hz, 2H), 6.93 (d, J=8.1Hz, 1H), 6.84 (d, J=7.4Hz, 1H), 6.75 (t, J=7.8Hz, 1H), 5.40 (s, 2H),3.02(s,2H),2.42(s,3H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ165.89,162.37, 148.11,142.50,142.17,129.75,129.22,127.07,120.89,120.53,119.57,115.18,87.92, 61.42,43.12,28.19,21.64。
Embodiment 16
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (3- benzylidene) second The preparation of hydrazides:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 3- methoxybenzaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup)-N'- (3- benzylidene) acethydrazide white solid 0.81g, m.p.132.5-134.7 DEG C, yield 95.4%；1H NMR(600MHz,CDCl3) δ 8.11 (s, 1H), 7.29 (s, 1H), 7.20 (dd, J=14.3,6.1Hz, 2H), 7.16 (d, J=7.4Hz, 1H), 6.87 (d, J=8.2Hz, 1H), 6.80 (d, J=6.4Hz, 1H), 6.72-6.67 (m, 1H), 4.66(s,2H),3.75(s,3H),2.97(s,2H),1.45(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(3- Methoxyphenyl) the preparation of -1,3,4-oxadiazole:
(3- methoxyl group is sub- by 2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- Benzyl) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.74mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.76g, as target product.MS-ESI,m/ z375.13[M+Na]+.HR-MS-EI m/z calcd for C20H20N2O4[M+H]+353.1487,found353.1501。 m.p.134-158℃；1HNMR(600MHz,CDCl3) δ 7.64 (d, J=7.7Hz, 1H), 7.59 (s, 1H), 7.40 (t, J= 8.0Hz, 1H), 7.08 (d, J=10.8Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.85 (d, J=6.7Hz, 1H), 6.75 (t, J=7.8Hz, 1H), 5.41 (s, 2H), 3.88 (s, 3H), 3.02 (s, 2H), 1.49 (s, 6H)；13C NMR(151MHz, CDCl3)δ165.70,162.66,159.97,148.10,142.13,130.20,129.25,124.74,120.54,119.61, 119.54,115.19,111.52,87.95,61.40,55.53,43.11,28.19。
Embodiment 17
(E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- (2- benzylidene) second The preparation of hydrazides:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 2- methoxybenzaldehyde react 6-8h, obtain (E) -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup)-N'- (2- benzylidene) acethydrazide white solid 0.81g, m.p.132.4-134.8 DEG C, yield 95%；1H NMR(600MHz,CDCl3) δ 10.09 (s, 1H), 8.46 (s, 1H), 7.97 (d, J=7.7Hz, 1H), 7.21 (t, J =7.8Hz, 1H), 6.82 (t, J=7.5Hz, 1H), 6.75 (d, J=7.7Hz, 2H), 6.70 (d, J=7.9Hz, 1H), 6.68- 6.65(m,1H),4.62(s,2H),3.69(s,3H),2.91(s,2H),1.41(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-(2- Methoxyphenyl) the preparation of -1,3,4-oxadiazole:
(2- methoxyl group is sub- by 2.28mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- Benzyl) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.74mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.76g, as target product, yield 95.1%. MS-ESI,m/z 375.13[M+Na]+.HR-MS-EI m/z calcd for C20H20N2O4[M+H]+353.1487, found353.1501.m.p.136-158℃；1H NMR(600MHz,CDCl3) δ 7.93 (d, J=7.6Hz, 1H), 7.50 (t, J =7.2Hz, 1H), 7.13-6.99 (m, 2H), 6.94 (d, J=8.1Hz, 1H), 6.83 (d, J=7.3Hz, 1H), 6.75 (t, J =7.8Hz, 1H), 5.42 (s, 2H), 3.95 (s, 3H), 3.02 (s, 2H), 1.49 (s, 6H)；13C NMR(151MHz,CDCl3)δ 164.38,162.35,158.09,157.96,148.05,142.30,142.17,133.23,130.64,129.14,120.70, 120.48,119.44,115.14,112.79,111.91,87.87,61.41,55.97,43.13,28.20。
Embodiment 18
(E)-N'- (cyclohexylmethylene) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol cyclohexanecarboxaldehyde react 6-8h, obtain (E)-N'- (cyclohexylmethylene) -2- ((2,2- dimethyl - 2,3- Dihydrobenzofuranes -7- bases) oxygroup) acethydrazide white solid 0.70g, m.p.133.5-134.8 DEG C, yield 95.1%；1H NMR(600MHz,CDCl3) δ 9.54 (s, 1H), 6.84-6.77 (m, 1H), 6.72 (d, J=4.7Hz, 2H), 4.60 (s, 2H), 2.98 (s, 2H), 2.43-2.27 (m, 1H), 1.77 (d, J=12.1Hz, 2H), 1.72-1.66 (m, 2H), 1.44 (s, 6H),1.26–1.14(m,6H)。
2-cyclohexyl-5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy) Methyl) the preparation of -1,3,4-oxadiazole:
(2- methoxyl group is sub- by 2.13mmol (E) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup)-N'- Benzyl) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.56mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow solid 0.67g, as target product, yield 95.1%. MS-ESI,m/z 351.17[M+Na]+.HR-MS-EI m/z calcd for C19H24N2O3[M+H]+329.1851, found329.1865.m.p.122-124℃；1H NMR(600MHz,CDCl3) δ 6.79 (d, J=8.1Hz, 1H), 6.76 (d, J =6.7Hz, 1H), 6.66 (t, J=7.8Hz, 1H), 5.23 (s, 2H), 2.94 (s, 2H), 2.85-2.80 (m, 1H), 2.03- 1.97 (m, 2H), 1.78-1.72 (m, 2H), 1.66-1.61 (m, 1H), 1.53 (qd, J=12.4,3.3Hz, 2H), 1.42 (s, 6H),1.35–1.26(m,2H),1.26–1.20(m,1H)；13C NMR(151MHz,CDCl3)δ171.12,162.42, 148.07,142.20,129.18,120.46,119.49,115.18,87.87,61.39,43.10,35.18,30.00, 28.19,25.55,25.33。
Embodiment 19
(E)-N'- (4- cyano benzal) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acetyl The preparation of hydrazine:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol 4- cyanobenzaldehyde react 6-8h, obtain (E)-N'- (4- cyano benzal) -2- ((2,2- diformazans Base -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide yellow solid 0.80g, m.p.131.9-133.9 DEG C, yield 95% ；1H NMR(600MHz,CDCl3) δ 10.10 (s, 1H), 8.25 (s, 1H), 7.79 (d, J=8.2Hz, 2H), 7.62 (d, J= 8.2Hz, 2H), 6.82 (dd, J=8.1,4.6Hz, 1H), 6.77-6.72 (m, 2H), 4.68 (s, 2H), 3.00 (s, 2H), 1.47 (s,6H)。
4-(5-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-1,3,4- Oxadiazol-2-yl) the preparation of benzonitrile:
2.29mmol (E)-N'- (4- cyano benzal) -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygen Base) acethydrazide is dissolved in dehydrated alcohol, and after 40 DEG C of stirrings are completely dissolved, 2.75mmol iodobenzene diethylester is added, is stirred at reflux 0.5h, TLC monitoring.After fully reacting, cold filtration, revolving uses methylene chloride: methanol (V: V)=150: 1, dichloromethane respectively Alkane: the methylene chloride column chromatography of methanol (V: V)=60: 1 obtains yellow powder 0.76g, as target product, yield 95.1%. MS-ESI,m/z 370.12[M+Na]+.HR-MS-EI m/z calcd for C20H17N3O3[M+H]+348.1333, found348.1348.m.p.142-144℃；1H NMR(600MHz,CDCl3) δ 8.20 (d, J=8.5Hz, 2H), 7.82 (d, J =8.5Hz, 2H), 6.91 (d, J=8.1Hz, 1H), 6.86 (d, J=6.8Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.44 (s,2H),3.03(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ164.19,163.51,148.08, 141.99,132.87,129.97,129.41,127.57,120.58,119.83,117.79,115.51,115.23,88.05, 61.37,43.08,28.19。
Embodiment 20
(E) preparation of-N'- benzyl -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide:
Preparation method is the same as embodiment 3,2.4mmol 2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) Acethydrazide and 2.88mmol benzaldehyde react 6-8h, obtain (E)-N'- benzyl -2- ((2,2- dimethyl -2,3- dihydrobenzo furans Mutter -7- base) oxygroup) acethydrazide white solid 0.71g, m.p.132.2-134.5 DEG C, yield 91%；1H NMR(600MHz, CDCl3) δ 8.14 (s, 1H), 7.72-7.64 (m, 2H), 7.33-7.30 (m, 3H), 6.81 (d, J=6.6Hz, 1H), 6.75- 6.70(m,2H),4.66(s,2H),2.98(s,2H),1.46(s,6H)。
2-(((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)methyl)-5-phenyl-1, The preparation of 3,4-oxadiazole:
2.18mmol (E)-N'- benzyl -2- ((2,2- dimethyl -2,3- Dihydrobenzofuranes -7- base) oxygroup) acethydrazide It is dissolved in dehydrated alcohol, after 40 DEG C of stirrings are completely dissolved, 2.62mmol iodobenzene diethylester is added, be stirred at reflux 0.5h, TLC prison It surveys.After fully reacting, cold filtration, revolving, respectively with methylene chloride: methanol (V: V)=150: 1, methylene chloride: methanol (V: V methylene chloride column chromatography)=60: 1, obtains white solid 0.67g, as target product, yield 95.1%.MS-ESI,m/z 345.12[M+Na]+.HR-MS-EI m/z calcd for C19H18N2O3[M+H]+323.1378,found 323.1396。 m.p.131-133℃；1H NMR(600MHz,CDCl3) δ 8.07 (d, J=7.1Hz, 2H), 7.52 (dt, J=24.8,7.2Hz, 3H), 6.93 (d, J=8.1Hz, 1H), 6.85 (d, J=7.4Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 5.42 (s, 2H), 3.02(s,2H),1.49(s,6H)；13C NMR(151MHz,CDCl3)δ165.74,162.65,148.11,142.14, 131.93,129.26,129.05,127.12,123.66,120.54,119.62,115.19,87.95,61.42,43.11, 28.19。
Embodiment 21: the Herbicidal of 3~20 products therefrom of the embodiment of the present invention.
Target compound is configured to the medical fluid that concentration is 500mg/L, preliminary growth is carried out to barnyard grass using Plating Inhibitory activity test.Tile 2 filter papers in the culture dish that diameter is 9cm, is subsequently poured into medical fluid 10mL, then uniformly place 30 Grain barnyard grass seed guarantees that every seed leaching medicine is uniform.Make blank control with equal amount of distilled water.Culture dish is put into growth cabinet Middle culture, temperature are 25 DEG C, and investigation grows the root long and stem length of 10 plants of most luxuriant plants after illumination daily 8h, 7d after culture 3d And whole germination, effect is calculated as follows, carries out pharmaceutical control and administration evaluation.
Effect=[(blank-processing/blank] × 100%,
Effect is that positive value illustrates that medicament is inhibited, illustrates that medicament has facilitation for negative value.Inhibitory activity is commented Price card is quasi-: A grades, >=90%；B grades, 70%~89%；C grades, 50%~69%；D grades, < 50%.
General sieve result is tabulated below when dosage is 500mg/L.
The activity of weeding test result (500mg/L) of the compounds of this invention

Claims (5)

1. a kind of formula (I) compound represented or its pharmaceutically acceptable salt:
Wherein, R is selected from 4-CN-C6H4、4-F-C6H4, 4-Cl-C6H4、4-Br-C6H4、3-F-C6H4、3-Br-C6H4、4-NO2- C6H4、3-NO2-C6H4、2-Br-C6H4、3-CH3-C6H4、4-CH3-C6H4、4-OMe-C6H4、3-OMe-C6H4、2-OMe-C6H4, benzene Base, isopropyl, cyclohexyl, styryl, furyl, thienyl or naphthalene.
2. compound according to claim 1 or its pharmaceutically acceptable salt, which is characterized in that be selected from following compound One of:
3. the preparation method of compound described in claim 1 or its pharmaceutically acceptable salt, which is characterized in that reaction process Include:
Wherein, R is as defined above.
4. a kind of compound described in claim 1 or its pharmaceutically acceptable salt answering in terms of preparing herbicide drug With.
5. composition pesticide, which is characterized in that include formula (I) compound represented or its pharmaceutically acceptable salt and one kind Or a variety of pharmaceutically acceptable auxiliary materials.
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