CN104642314B - Application of N-furan phenol methyl ether-5-yl) chromene-4-amide as sterilizing agent - Google Patents

Application of N-furan phenol methyl ether-5-yl) chromene-4-amide as sterilizing agent Download PDF

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CN104642314B
CN104642314B CN201510064670.4A CN201510064670A CN104642314B CN 104642314 B CN104642314 B CN 104642314B CN 201510064670 A CN201510064670 A CN 201510064670A CN 104642314 B CN104642314 B CN 104642314B
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amide
preparation
benzopyran
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alpha
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CN104642314A (en
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杨泽慧
邵丹凤
陈晓东
胡艾希
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Ningbo University of Technology
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Abstract

The invention relate to application of N-furan phenol methyl ether-5-yl) chromene-4-amide as shown in the chemical formulas I, II or III in specification in preparation of a sterilizing agent, wherein X1 is selected from hydrogen, C1-C2 alkyl, C3-C4 linear chain alkyl or C3-C4 branch chain alkyl, C1-C2 alkoxy, C3-C4 linear chain alkoxy or C3-C4 branch alkoxy; X2-X7 are selected from hydrogen, C1-C2 alkyl, C3-C4 linear chain alkyl or C3-C4 bran chain alkyl.

Description

Application of N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide as antibacterial
Technical field
The present invention relates to the new application of compound, specifically N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide is in system Application in standby antibacterial.
Background technology
Benzofuranol (chemical name 2,2- dimethyl -2,3- Dihydrobenzofuranes phenol) is production carbofuran, pacifies prestige and rosickyite well The important intermediate of the large-tonnage carbamate chemicals for agriculture such as carbofuran.Carbamate chemicals for agriculture activity is high, is widely used, but Toxicity is larger, it is therefore desirable to develop that toxicity is relatively low, active preferable substitute products, to meet the demand in market.World's novel pesticide Part energy is transferred to the existing pesticide intermediate compound of exploitation as pesticide new variety in preventing and treating entomogenous fungi grass for initiative company The purposes of aspect.Chinese patent describes the non-amino formate ester pesticide based on benzofuranol research and development：4- (benzofuran -5- Base) -2- fragrant amino thiazoles and preparation method and application, ZL201010553848.9,2012.7.4 is authorized；5- [2- (benzyl imido Base) thiazole-4-yl] used as the application for preparing antibacterial, ZL201110102467.3,2013.3.27 is authorized furan 2, 2-Oxydiphenol；5- [2- (benzyl imino group) thiazole-4-yl] furan 2, 2-Oxydiphenol and its as the application for preparing insecticide, ZL201110102455.0, 2013.6.12 authorize；5- (2- fragrant amino thiazole-4-yls) benzofuranol ether compounds with activity of weeding and preparation method, CN102603726A, 2012.7.25 are disclosed；4- (benzofuran -5- bases) -2- phenylaminos thiazoles as antibacterial application, CN103141486B, 2014.5.28 are authorized.Tan Xiaosong describes 7 introducing active groups on benzofuranol ring and has synthesized benzofuranol Phosphorylation derivates, the compound have certain insecticidal activity [Tan Xiaosong, Master's thesis, Central China Normal University, Wuhan, 2000]；He Qixi describes to introduce oximes group on benzofuranol 7, has synthesized benzofuranol oxime ether derivatives；In finite concentration Under, the compound shows certain bacteriostatic activity [He Qixi, Master's thesis, Hunan University, Changsha, 2009].
Chinese invention patent describes the preparation of N- [4- (benzofuran -5- bases) thiazol-2-yl] amide and its conduct is killed The application [CN103342703A, 2013.10.9 are disclosed] of microbial inoculum；Chinese invention patent describe N- (2,3- Dihydrobenzofuranes- 5- yls) .alpha.-5:6-benzopyran -4- amide preparation and active anticancer [CN103626747A, 2014.3.12 are disclosed].
The content of the invention
It is an object of the invention to provide N- (benzofuranol methyl ether -5- bases) benzo shown in chemical constitution Formulas I, II or III Application of the pyrans -4- amide in antibacterial is prepared：
Wherein, X1It is selected from：Hydrogen, C1~C2Alkyl, C3~C4Straight chained alkyl or C3~C4Branched alkyl, C1~C2Alkoxyl, C3 ~C4Unbranched alkoxy or C3~C4Branched alkoxy；X2~X7It is selected from：Hydrogen, C1~C2Alkyl, C3~C4Straight chained alkyl or C3~C4 Branched alkyl.
It is an object of the invention to provide N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- shown in chemical constitution formula IV Application of the amide in antibacterial is prepared：
Wherein, X1It is selected from：Hydrogen, C1~C2Alkyl, C3~C4Straight chained alkyl or C3~C4Branched alkyl；C1~C2Alkoxyl, C3 ~C4Unbranched alkoxy or C3~C4Branched alkoxy.
Object of the present invention is to provide N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) benzene And pyrans -4- amide, N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -8- methyl .alpha.-5:6-benzopyran -4- Amide N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -8- methoxychromen -4- amide and N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) benzo [h] .alpha.-5:6-benzopyran -4- amide kills rice stricture of vagina in preparation Application in the antibacterial of rot bacterium.
The present invention has the advantage that compared with prior art：
Present invention firstly discovers that N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide has higher bactericidal activity.
Specific embodiment
Following examples are intended to illustrate rather than limitation of the invention further.
Embodiment 1
The preparation of benzodihydropyran -4- carboxylic acids (1)
By Chinese invention patent [CN103626747A, 2014.3.12 are disclosed] prepare compound 1A~10A.
16.90g compound 1A, 23.10g 1,2-PDs, 1.50g p-methyl benzenesulfonic acid, 100mL toluene is refluxed 8.0h, TLC tracking ketal reaction is finished, and obtains compound 1B, when ketal reaction liquid is cooled to 80~90 DEG C, is added 1.60g Zinc Oxide, heating distributes part toluene, makes temperature in bottle be increased to 126~130 DEG C, insulation reaction 4.0h, TLC with Completely, sucking filtration, vacuum distillation removes toluene, obtains pale red oily mater for track rearrangement reaction.It is subsequently adding 60mL30% hydrogen-oxygens Change sodium water solution, 80mL methanol solutions, back flow reaction 4.0h, TLC monitoring reactions are complete, and 100mL cold water is added in reactant liquor, take out Filter, filtrate is washed with 50mL dichloromethane, and water layer dilute hydrochloric acid adjusts pH2,100mL ethyl acetate to extract, anhydrous sodium sulfate drying, It is spin-dried for obtaining solid benzodihydropyran -4- carboxylic acid 11.2g, yield 83.9%, m.p.93~95 DEG C；1H NMR(CDCl3, 400MHz)δ：2.12~2.18 (m, 1H, 3-H), 2.30~2.35 (m, 1H, 3-H), 3.81 (t, J=4.8Hz, 1H, 4-H), 4.24~4.27 (m, 2H, 2-H), 6.85 (d, J=8.4Hz, 1H, 8-H), 6.89 (t, J=7.6Hz, 1H, 6-H), 7.17 (t, J =8.4Hz, 1H, 7-H), 7.27 (d, J=7.6Hz, 1H, 5-H).
Embodiment 2
The preparation of 8- methyl benzodihydropyran -4- carboxylic acids (2)
By the operational approach of embodiment 1,5.10g compounds 2A and 5.00g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid are anti- 8.0h is answered, compound 2B is obtained, 1.00g Zinc Oxide is added, 2.0h is reacted, pale red oily mater is obtained.It is subsequently adding 30mL 30% NaOH aqueous solutions, 40mL methanol solutions reaction 4.0h, obtain 8- methyl benzodihydropyran -4- carboxylic acids, yield 83.2%, M.p.103~104 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.09~2.17 (m, 1H, 3-H), 2.18 (s, 3H, CH3), 2.28 ~2.34 (m, 1H, 3-H), 3.81 (t, J=6.0Hz, 1H, 4-H), 4.26~4.29 (m, 2H, 2-H), 6.79 (t, J= 7.2Hz, 1H, 6-H), 7.04 (d, J=7.6Hz, 1H, 7-H), 7.11 (d, J=7.6Hz, 1H, 5-H).
Embodiment 3
The preparation of 7- methyl benzodihydropyran -4- carboxylic acids (3)
By the operational approach of embodiment 1,10.20g compounds 3A and 11.30g 1,2-PDs and 1.50g p-methyl benzenesulfonic acid Reaction 8.0h, obtains compound 3B.1.00g Zinc Oxide is added, 2.0h is reacted, pale red oily mater is obtained.It is subsequently adding 40mL 30%NaOH aqueous solutions, 60mL methanol solutions reaction 4.0h, obtain 7- methyl benzodihydropyran -4- carboxylic acids, yield 65.0%, M.p.110~111 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.10~2.18 (m, 1H, 3-H), 2.28 (s, 3H, 7-CH3), 2.29~2.34 (m, 1H, 3-H), 3.78 (t, J=4.8Hz, 1H, 4-H), 4.21~4.25 (m, 2H, 2-H), 6.67 (s, 1H, 8-H), 6.72 (d, J=8.0Hz, 1H, 6-H), 7.15 (d, J=8.0Hz, 1H, 5-H).
Embodiment 4
The preparation of 6- methyl .alpha.-5:6-benzopyran -4- carboxylic acids (4)
By the operational approach of embodiment 1,5.10g compounds 4A and 6.20g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid are anti- 8.0h is answered, compound 4B is obtained, 1.00g Zinc Oxide is added, 2.0h is reacted, pale red oily mater is obtained.It is subsequently adding 40mL 30% NaOH aqueous solutions, 60mL methanol solutions reaction 4.0h, obtain 6- methyl .alpha.-5:6-benzopyran -4- carboxylic acids, yield 91.9%, and m.p.116~ 117℃；1HNMR(CDCl3, 400MHz) and δ：2.09~2.18 (m, 1H, 3-H), 2.26 (s, 3H, 6-CH3), 2.28~2.34 (m, 1H, 3-H), 3.78 (t, J=8.4Hz, 1H, 4-H), 4.19~4.28 (m, 2H, 2-H), 6.75 (d, J=8.4Hz, 1H, 8-H), 6.98 (dd, J=2.0,8.4Hz, 1H, 7-H), 7.07 (d, J=2.0Hz, 1H, 5-H).
Embodiment 5
The preparation of 8- methoxychromens -4- carboxylic acids (5)
By the operational approach of embodiment 1,2.70g compounds 5A and 2.50g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid are anti- 8.0h is answered, compound 5B is obtained, 1.00g Zinc Oxide is added, 2.0h is reacted, pale red oily mater is obtained.It is subsequently adding 40mL 30% NaOH aqueous solutions, 60mL methanol solutions reaction 4.0h, obtain 8- methoxychromen -4- carboxylic acids, yield 34.8%, m.p.105 ~107 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.12~2.21 (m, 1H, 3-H), 2.31~2.37 (m, 1H, 3-H), 3.78 (t, J=4.8Hz, 1H, 4-H), 3.78 (s, 3H, 8-OCH3), 4.29~4.39 (m, 2H, 2-H), 6.79 (dd, J=2.0, 7.6Hz, 1H, 7-H), 7.17 (t, J=7.6Hz, 1H, 6-H), 6.89 (dd, J=2.0,7.6Hz, 1H, 5-H).
Embodiment 6
The preparation of 7- methoxychromens -4- carboxylic acids (6)
By the operational approach of embodiment 1,8.10g compounds 6A and 7.90g 1,2-PDs and 1.50g p-methyl benzenesulfonic acid, obtain Compound 6B, adds 1.00g Zinc Oxide, reacts 2.0h, obtains pale red oily mater.It is subsequently adding 40mL 30%NaOH water-soluble Liquid, 60mL methanol solutions reaction 4.0h, obtains pale yellow oil 7- methoxychromen -4- carboxylic acids, yield 68.9%；1H NMR(CDCl3, 400MHz) and δ：2.09~2.14 (m, 1H, 3-H), 2.28~2.32 (m, 1H, 3-H), 3.76 (s, 3H, 7- OCH3), 3.78 (t, J=4.8Hz, 1H, 4-H), 4.22~4.25 (m, 2H, 2-H), 6.39 (d, J=2.4Hz, 1H, 8-H), 6.50 (dd, J=2.4,8.8Hz, 1H, 6-H), 7.17 (d, J=8.8Hz, 1H, 5-H).
Embodiment 7
The preparation of 6- methoxychromens -4- carboxylic acids (7)
By the operational approach of embodiment 1,5.40g compounds 7A and 6.20g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid, obtain Compound 7B, adds 1.00g Zinc Oxide, reacts 2.0h, obtains pale red oily mater.40mL 30%NaOH aqueous solutions are added, 60mL methanol solutions react 4.0h, obtain 6- methoxychromen -4- carboxylic acids, yield 67.0%, m.p.103~104 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.09~2.18 (m, 1H, 3-H), 2.26~2.34 (m, 1H, 3-H), 3.75 (s, 3H, 6- OCH3), 3.78 (t, J=4.8Hz, 1H, 4-H), 4.20~4.23 (m, 2H, 2-H), 6.77~6.82 (m, 3H, 7-H, 8-H, 5- H)。
Embodiment 8
The preparation of 6- chlorine .alpha.-5:6-benzopyran -4- carboxylic acids (8)
By the operational approach of embodiment 1,5.50g compounds 8A and 4.60g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid, obtain Compound 8B, adds 1.00g Zinc Oxide, reacts 2.0h, obtains pale red oily mater.It is subsequently adding 40mL 30%NaOH water-soluble Liquid, 60mL methanol solutions reaction 4.0h, obtains 6- chlorine .alpha.-5:6-benzopyran -4- carboxylic acids, yield 70.2%, m.p.90~92 DEG C；1H NMR (CDCl3, 400MHz) and δ：2.08~2.17 (m, 1H, 3-H), 2.29~2.36 (m, 1H, 3-H), 3.78 (t, J=8.4Hz, 1H, 4-H), 4.22~4.27 (m, 2H, 2-H), 6.78 (d, J=8.8Hz, 1H, 8-H), 7.13 (dd, J=2.4,8.8Hz, 1H, 7- H), 7.28 (d, J=2.4Hz, 1H, 5-H).
Embodiment 9
The preparation of 3,4- dihydros -2H- benzos [h] .alpha.-5:6-benzopyran -4- carboxylic acids (9)
By the operational approach of embodiment 1,5.80g compounds 9A and 4.70g1,2- Propylene Glycol and 1.00g p-methyl benzenesulfonic acid, instead 8.0h is answered, compound 9B is obtained, 1.00g Zinc Oxide is added, 2.0h is reacted, pale red oily mater is obtained.It is subsequently adding 40mL 30% NaOH aqueous solutions, 60mL methanol solutions reaction 4.0h, obtain 3,4- dihydro -2H- benzos [h] .alpha.-5:6-benzopyran -4- carboxylic acids, yield 54.0%, m.p.173~174 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.19~2.28 (m, 1H, 3-H), 2.39~2.46 (m, 1H, 3-H), 3.91 (t, J=4.4Hz, 1H, 4-H), 4.38~4.51 (m, 2H, 2-H), 7.32~7.38 (m, 2H, 7-H, 6- H), 7.44~7.48 (m, 2H, 9-H, 10-H), 7.73~7.75 (m, 1H, 8-H), 8.16~8.19 (m, 1H, 11-H).
Embodiment 10
The preparation of 3,4- dihydros -2H- benzos [g] .alpha.-5:6-benzopyran -4- carboxylic acids (10)
By the operational approach of embodiment 1,2.90g compounds 10A and 2.40g 1,2-PDs and 0.50g p-methyl benzenesulfonic acid, Reaction 8.0h, obtains compound 10B, adds 1.00g Zinc Oxide, reacts 2.0h, obtains pale red oily mater.It is subsequently adding 40mL 30%NaOH aqueous solutions, 60mL methanol solutions reaction 4.0h, obtain 3,4- dihydro -2H- benzos [g] .alpha.-5:6-benzopyran -4- carboxylic acids, yield 52.2%, m.p.170~171 DEG C；1H NMR(CDCl3, 400MHz) and δ：2.21~2.30 (m, 1H, 3-H), 2.37~2.44 (m, 1H, 3-H), 4.07 (t, J=5.2Hz, 1H, 4-H), 4.28~4.32 (m, 1H, 2-H), 4.34~4.41 (m, 1H, 2-H), 7.24 (s, 1H, 10-H), 7.28 (t, J=8.0Hz, 1H, 7-H), 7.38 (t, J=8.0Hz, 1H, 8-H), 7.66 (d, J= 8.0Hz, 1H, 9-H), 7.71 (d, J=8.0Hz, 1H, 6-H), 7.78 (s, 1H, 5-H).
Embodiment 11
The system of N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) .alpha.-5:6-benzopyran -4- amide (11) It is standby
(1) 2,2- dimethyl -7- methoxyl group -5- nitro -2, the preparation of 3- Dihydrobenzofuranes (21)
17.80g compounds 21,50mL dichloromethane solutions are stirred at -5 DEG C, and Deca 10mL concentrated nitric acid, 30min is dripped Finish, temperature rises to 10 DEG C, continue to react 30min, TLC monitoring reactions are complete, reactant liquor washing, dichloromethane extraction, anhydrous sulfur Sour sodium is dried, and dehydrated alcohol recrystallization obtains yellow solid 2,2- dimethyl -7- methoxyl group -5- nitro -2,3- Dihydrobenzofuranes (21) 19.20g, yield 92.6%, m.p.124~126 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.57 (s, 6H, 2 × CH3), 3.11 (s, 2H, 3-H), 3.95 (s, 3H, 7-OCH3), 7.70 (d, J=2.4Hz, 1H, 6-H), 7.77 (d, J=2.4Hz, 1H, 4-H)。
(2) 2,2- dimethyl -7- methoxyl group -2, the preparation of 3- Dihydrobenzofuranes -5- amine (22)
6.00g compounds 22 (27.00mmol), 60mL methanol, Raney's nickel, the hydration of Deca 12.00g 80% at 20 DEG C Drop finishes in hydrazine, 1.0h, continues to react 30min, and TLC monitoring reactions are complete, and sucking filtration reclaims Raney's nickel, and filtrate is spin-dried for, with 50mL bis- Chloromethanes dissolve, 100mL water washings, and 50mL dichloromethane is extracted 3 times, anhydrous sodium sulfate drying, filter, and are spin-dried for, and dry 2, 2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- amine (22) 4.92g, yield 94.5%, m.p.126~128 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.47 (s, 6H, 2 × CH3), 2.94 (s, 2H, 3-H), 3.34 (s, 2H, NH2), 3.81 (s, 3H, 7-OCH3), 6.17 (s, 2H, 4-H, 6-H).
(3) N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) .alpha.-5:6-benzopyran -4- amide (23a) Preparation
0.59g compounds 1,0.66g compounds 22,20mL dichloromethane, 0.67g DCC, 0.09g DMAP are stirred at room temperature 1.0h, TLC monitoring reaction is complete；Sucking filtration, is spin-dried for, and dehydrated alcohol recrystallization obtains 0.40g white solids 11, yield 33.3%, M.p.178~180 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.16~2.25 (m, 1H, 3-H), 2.54~2.60 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.77 (t, J=4.8Hz, 1H, 4-H), 3.84 (s, 3H, 7 '- OCH3), 4.09~4.15 (m, 1H, 2-H), 4.29~4.34 (m, 1H, 2-H), the 6.74 (- H of d, J=2.0Hz, 1H, 6 '), 6.93 (dd, J=2.0,8.0Hz, 1H, 8-H), the 6.94 (- H of d, J=2.0Hz, 1H, 4 '), 6.95~6.99 (m, 1H, 7-H), 7.17 (s, 1H, NH), 7.19 (dd, J=2.0,8.0Hz, 1H, 5-H), 7.24~7.29 (m, 1H, 6-H).
Embodiment 12
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -8- methyl .alpha.-5:6-benzopyran -4- amide (12) preparation
By the preparation method of embodiment 11,3.30mmol compounds 2,3.40mmol compounds 22,1.0h is reacted, obtain white Solid 12, yield 53.4%, m.p.190~192 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.15 ~2.20 (m, 1H, 3-H), 2.22 (s, 3H, 8-CH3), 2.54~2.60 (m, 1H, 3-H), the 2.96 (- H of s, 2H, 3 '), 3.76 (t, J=4.8Hz, 1H, 4-H), the 3.83 (- OCH of s, 3H, 7 '3), 4.08~4.14 (m, 1H, 2-H), 4.34~4.39 (m, 1H, 2-H), the 6.73 (- H of d, J=2.0Hz, 1H, 6 '), 6.87 (t, J=7.6Hz, 1H, 6-H), 6.95 (d, J=2.0Hz, 1H, 4 '- H), 7.03 (d, J=7.6Hz, 1H, 7-H), 7.12 (d, J=7.6Hz, 1H, 5-H), 7.21 (s, 1H, NH).
Embodiment 13
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -7- methyl .alpha.-5:6-benzopyran -4- amide (13) preparation
By the preparation method of embodiment 11,3.30mmol compounds 3,3.40mmol compounds 22,1.0h is reacted, obtain white Solid 13, yield 36.6%, m.p.195~197 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.14 ~2.23 (m, 1H, 3-H), 2.33 (s, 3H, 7-CH3), 2.51~2.56 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.73 (t, J=4.8Hz, 1H, 4-H), the 3.84 (- OCH of s, 3H, 7 '3), 4.05~4.11 (m, 1H, 2-H), 4.26~4.32 (m, 1H, 2-H), 6, the 74 (- H of s, 2H, 6 ', 8-H), 6.78 (d, J=8.0Hz, 1H, 6-H), the 6.95 (- H of d, J=2.0Hz, 1H, 4 '), 7.06 (d, J=8.0Hz, 1H, 5-H), 7.21 (s, 1H, NH).
Embodiment 14
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -6- methyl .alpha.-5:6-benzopyran -4- amide (14) preparation
By the preparation method of embodiment 11,3.30mmol compounds 4,3.40mmol compounds 22,1.0h is reacted, obtain white Solid 14, yield 39.5%, m.p.208~209 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.14 ~2.23 (m, 1H, 3-H), 2.33 (s, 3H, 6-CH3), 2.51~2.56 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.73 (t, J=4.8Hz, 1H, 4-H), the 3.84 (- OCH of s, 3H, 7 '3), 4.06~4.13 (m, 1H, 2-H), 4.26~4.32 (m, 1H, 2-H), the 6.74 (- H of s, 1H, 6 '), 6.78 (d, J=8.0Hz, 1H, 8-H), 6.96~the 6.97 (- H of m, 1H, 5-H, 4 '), 7.06 (dd, J=2.0,8.0Hz, 1H, 7-H), 7.19 (s, 1H, NH).
Embodiment 15
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -8- methoxychromen -4- amide (15) preparation
By the preparation method of embodiment 11,3.30mmol compounds 5,3.40mmol compounds 22,0.7h is reacted, obtain white Solid 15, yield 51.8%, m.p.212~214 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.17 ~2.26 (m, 1H, 3-H), 2.56~2.62 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.78 (t, J=4.8Hz, 1H, 4- H), the 3.83 (- OCH of s, 3H, 7 '3), 3.92 (s, 3H, 8-OCH3), 4.13~4.20 (m, 1H, 2-H), 4.43~4.48 (m, 1H, 2-H), the 6.75 (- H of d, J=1.2Hz, 1H, 6 '), 6.80 (dd, J=1.2,8.0Hz, 1H, 7-H), 6.86~6.96 (m, 3H, 6- - the H of H, 5-H, 4 '), 7.19 (s, 1H, NH).
Embodiment 16
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -7- methoxychromen -4- amide (16) preparation
By the preparation method of embodiment 11,3.30mmol compounds 6,3.40mmol compounds 22,0.3h is reacted, obtain white Solid 16, yield 55.4%, m.p.166~167 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.15 ~2.22 (m, 1H, 3-H), 2.51~2.56 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.70 (t, J=4.4Hz, 1H, 4- H), the 3.81 (- OCH of s, 3H, 7 '3), 3.84 (s, 3H, 7-OCH3), 4.04~4.11 (m, 1H, 2-H), 4.28~4.32 (m, 1H, 2-H), 6.47 (d, J=2.8Hz, 1H, 8-H), 6.57 (dd, J=2.8,8.4Hz, 1H, 6-H), 6.76 (d, J=2.0Hz, 1H, 6 '-H), the 6.94 (- H of d, J=2.0Hz, 1H, 4 '), 7.07 (d, J=8.4Hz, 1H, 5-H), 7.20 (s, 1H, NH).
Embodiment 17
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -6- methoxychromen -4- amide (17) preparation
By the preparation method of embodiment 11,3.30mmol compounds 7,3.40mmol compounds 22,1.0h is reacted, obtain white Solid 17, yield 80.2%, m.p.173~174 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.48 (s, 6H, 2 × CH3), 2.15 ~2.25 (m, 1H, 3-H), 2.49~2.56 (m, 1H, 3-H), the 2.97 (- H of s, 2H, 3 '), 3.73 (t, J=4.8Hz, 1H, 4- H), 3.78 (s, 3H, 6-OCH3), the 3.84 (- OCH of s, 3H, 7 '3), 4.05~4.12 (m, 1H, 2-H), 4.25~4.29 (m, 1H, 2-H), the 6.70 (- H of d, J=2.0Hz, 1H, 6 '), the 6.75 (- H of d, J=2.0Hz, 1H, 4 '), 6.83~6.88 (m, 2H, 7-H, 8- H), 6.95 (d, J=2.4Hz, 1H, 5-H), 7.20 (s, 1H, NH).
Embodiment 18
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) -6- chlorine .alpha.-5:6-benzopyran -4- amide (18) Preparation
By the preparation method of embodiment 11,3.30mmol compounds 8,3.40mmol compounds 22,0.6h is reacted, obtain white Solid 18, yield 64.0%, m.p.163~165 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.49 (s, 6H, 2 × CH3), 2.12 ~2.22 (m, 1H, 3-H), 2.50~2.56 (m, 1H, 3-H), the 2.99 (- H of s, 2H, 3 '), 3.74 (t, J=4.4Hz, 1H, 4- H), the 3.85 (- OCH of s, 3H, 7 '3), 4.12~4.19 (m, 1H, 2-H), 4.28~4.32 (m, 1H, 2-H), 6.78 (d, J= - the H of 1.6Hz, 1H, 6 '), 6.86 (d, J=8.4Hz, 1H, 8-H), the 6.96 (- H of d, J=1.6Hz, 1H, 4 '), 7.16 (s, 1H, NH), 7.17 (d, J=2.8Hz, 1H, 5-H), 7.21 (dd, J=2.8,8.4Hz, 1H, 6-H).
Embodiment 19
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) benzo [h] .alpha.-5:6-benzopyran -4- amide (19) preparation
By the preparation method of embodiment 11,3.30mmol compound 19i, 3.40mmol compounds 22,0.6h is reacted, obtain white Color solid 19, yield 57.9%, m.p.245~247 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.47 (s, 6H, 2 × CH3), 2.28~2.37 (m, 1H, 3-H), 2.63~2.67 (m, 1H, 3-H), the 2.95 (- H of s, 2H, 3 '), the 3.81 (- OCH of s, 3H, 7 '3), 3.70 (t, J=4.4Hz, 1H, 4-H), 4.24~4.30 (m, 1H, 2-H), 4.54~4.59 (m, 1H, 2-H), 6.77 (d, J= - the H of 2.0Hz, 1H, 6 '), the 6.88 (- H of d, J=2.0Hz, 1H, 4 '), 7.16 (s, 1H, NH), 7.24 (d, J=8.4Hz, 1H, 5- H), 7.46 (d, J=8.4Hz, 1H, 6-H), 7.52~7.56 (m, 2H, 8-H, 9-H), 7.80~7.82 (m, 1H, 7-H), 8.22 ~8.25 (m, 1H, 10-H).
Embodiment 20
N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) benzo [g] .alpha.-5:6-benzopyran -4- amide (20) preparation
By the preparation method of embodiment 11,3.30mmol compounds 10,3.40mmol compounds 22,1.0h is reacted, obtain white Color solid 20, yield 54.2%, m.p.208~210 DEG C；1H NMR(CDCl3, 400MHz) and δ：1.47 (s, 6H, 2 × CH3), 2.25~2.33 (m, 1H, 3-H), 2.65~2.71 (m, 1H, 3-H), the 2.95 (- H of s, 2H, 3 '), the 3.81 (- OCH of s, 3H, 7 '3), 4.03 (t, J=4.4Hz, 1H, 4-H), 4.19~4.26 (m, 1H, 2-H), 4.36~4.41 (m, 1H, 2-H), 6.73 (s, 1H, 10-H), 6.91 (s, 1H, 5-H), 7.20 (s, 1H, NH), the 7.32 (- H of s, 1H, 6 '), 7.35 (t, J=8.0Hz, 1H, 7-H), 7.45 (t, J=8.0Hz, 1H, 8-H), 7.72~the 7.77 (- H of m, 3H, 4 ', 6-H, 9-H).
Embodiment 21
The bactericidal activity of N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide is determined
1 test objective
Determine noval chemical compound virulence to various pathogen under for examination concentration indoors, preliminary assessment its sterilization is lived Property.
2 experimental conditions
2.1 for examination target
Rhizoctonia solani Kuhn (Rhizoctonia solani)；Strain is maintained in refrigerator (4-8 DEG C), 2-3 days before test It is inoculated in culture dish from test tube slant, cultivates under preference temperature and be for experiment.Experiment culture medium is potato agar Culture medium (PDA).
2.2 condition of culture
For try target and test after target condition of culture be 25 ± 5 DEG C of temperature, relative humidity 65 ± 5%
2.3 instrument and equipment
Beaker, pipet, graduated cylinder, culture dish, high-pressure sterilizing pot, constant temperature biochemical cultivation case etc..
3 EXPERIMENTAL DESIGN
3.1 test medicine：N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide (I~III)：
Wherein, X1It is selected from：Hydrogen, C1~C2Alkyl, C3~C4Straight chained alkyl or C3~C4Branched alkyl, C1~C2Alkoxyl, C3 ~C4Unbranched alkoxy or C3~C4Branched alkoxy；X2~X7It is selected from：Hydrogen, C1~C2Alkyl, C3~C4Straight chained alkyl or C3~C4 Branched alkyl.
3.2 experimental concentration
Broad Bean Leaves method drug concentration sets 500mg/L.
3.3 medicaments are prepared
Active compound：Aequum is weighed with a ten thousandth electronic balance；Solvent：DMF (DMF), 0.2%；Breast Agent：Tween 80,0.1%；
General sieve is determined：0.0500g samples are accurately weighed, is dissolved with 0.20mLDMF, add emulsifying agent containing 0.1%Tween80 Sterilized water 98.8ml, stir, be configured to 500mg/L strength solutions standby.
4 test methods
Rhizoctonia solani Kuhn：Broad Bean Leaves method is adopted with reference to the raw standard method NY/T1156.5-2006 that surveys, clip Semen Viciae fabae is susceptible The blade of kind, in putting culture dish, with aerosol apparatus by the wet vacuum side of blade of 500mg/L compound liquid medicine jets, after natural air drying, with connecing Plant device and the one side that a diameter of 6.0mm bacteria cakes have mycelia is inoculated in into process central vane, protectiveness is tested 24 after chemicals treatment Hour inoculation, is placed in growth cabinet after inoculation, trains under conditions of 26~28 DEG C of temperature, relative humidity 80%~90% Support.Depending on blank incidence, prevention effect is calculated.
5 fungicidal activity evaluations
Rhizoctonia solani Kuhn：Depending on blank incidence surveying record lesion diameter, prevention effect (%) is calculated.
In formula：P represents prevention effect, D0Represent blank lesion diameter, D1Represent and process lesion diameter.
According to survey data, formula (1) calculates prevention effect.
In formula：P represents prevention effect, and CK represents blank disease index, and PT represents chemicals treatment disease index.
N- (benzofuranol methyl ether -5- bases) the general sieve result of .alpha.-5:6-benzopyran -4- amide bactericidal activities：N- (2,2- dimethyl -7- first Epoxide -2,3- Dihydrobenzofuranes -5- bases) .alpha.-5:6-benzopyran -4- amide, N- (2,2- dimethyl -7- methoxyl group -2,3- dihydrobenzenes And furan -5- bases) -8- methyl .alpha.-5:6-benzopyran -4- amide N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- Base) -8- methoxychromen -4- amide and N- (2,2- dimethyl -7- methoxyl group -2,3- Dihydrobenzofuranes -5- bases) benzene And [h] .alpha.-5:6-benzopyran -4- amide is respectively 85.6%, 80.4%, 71.0% to the prevention effect of Rhizoctonia solani Kuhn (500mg/L) With 64.9%.
Active testing result shows that there is N- (benzofuranol methyl ether -5- bases) .alpha.-5:6-benzopyran -4- amide good sterilization to live Property, can be used to prepare antibacterial.

Claims (2)

1. application of the compound shown in chemical constitution Formulas I in the antibacterial for killing Rhizoctonia solani Kuhn is prepared：
Wherein, X1It is selected from：Hydrogen, methyl or methoxy；X2~X4It is selected from：Hydrogen.
2. application of the compound shown in chemical constitution Formula II in the bacterium antibacterial for killing the sheath and culm blight of rice is prepared：
Wherein, X2~X7It is selected from：Hydrogen.
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