CN102584810B - Benzothiazole ketone compound and application thereof - Google Patents
Benzothiazole ketone compound and application thereof Download PDFInfo
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Abstract
The invention discloses a 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2(3H)-ketone compound, the structure is shown in the formula (I). Further application of the compound as a bacteriacide is disclosed.
Description
(1) technical field
The present invention relates to a kind of 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds and application thereof.
(2) background technology
As a member in fused heterocycle system, benzothiazole derivant has biological activity widely, as desinsection (Pharmazie, 2003,58,527), sterilization (Molecules, 1997,2,36), antiviral (organic chemistry, 2007,27,279) (U.S.Patent 5424443 in, weeding, 1995-06-13) and plant growth regulating (J.Agric.Food Chem., 1981,29,640) isoreactivity plays an important role in novel pesticide initiative.Simultaneously, 1,3,4-oxadiazole analog derivative also has the biological activity of wide spectrum, as desinsection (Pest Manage Sci., 2003,59,933) (U.S.Patent 4124373 in, weeding, 1978-11-07) and sterilization (Eur.J.Med.Chem., 1996,31,819) isoreactivity, and part 1, the successful commercialization of 3,4-oxadiazole compounds, as Sha Chong Ji Evil worm ketone (agricultural chemicals collected translation, 1989,55), Chu Cao Ji Evil humulone (world pesticide, 2006,28 (6): 15) etc. 11 (6):.In view of benzothiazole and 1,3,4-oxadiazole compounds all have excellent activity, utilize the synthetic novel benzothiazole compound that contains 1,3,4-oxadiazole rings that has both structures concurrently of active substructure joining method design, be expected to have good biological activity.As (E-J.Chem. such as B.Rajeeva, 2009,6 (3), 775) a series of benzothiazole oxadiazoles compounds have been synthesized, raw survey result show its under 100mg/L concentration to subtilis (Bacillus subtilis), bacillus pumilus (Bacillus pumilus), intestinal bacteria (Escherichia coli) and Pseudomonas aeruginosa (Pseudomonas aeruginosa) all have certain restraining effect.
The serial 3-that the present invention designs and synthesizes ((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds, its structure and bioactivity research have been showed no bibliographical information.
(3) summary of the invention
The object of the present invention is to provide a kind of 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds and uses thereof.
The technical solution used in the present invention is:
A kind of 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds, structure is suc as formula shown in (I):
In formula (I), it is monosubstituted, polysubstituted or be not substituted that H on phenyl ring is substituted base Rn, n is 0～5 integer, n represents the number of substituent R on phenyl ring, during n=0, represent that the H on phenyl ring is not substituted, during n=1, it is monosubstituted that H on expression phenyl ring is substituted base R, n=2～5 o'clock, it is polysubstituted that the H on expression phenyl ring is substituted base Rn, and the substituent R on different the position of substitution can be identical or different, described substituent R is the alkyl of C1～C8, the alkoxyl group of C1～C3, halogen or nitro, and described halogen is F, Cl, Br or I.
When the H on described phenyl ring is not substituted, representing does not have substituting group on phenyl ring.
Described substituent R is preferably 1～2, i.e. n=1～2 in preferred Rn.
Further, described substituent R is preferably alkyl, methoxyl group, F, Cl, Br or the nitro of C1～C5, more preferably methyl, ethyl, n-propyl, sec.-propyl, the tertiary butyl, n-pentyl, F, Cl, nitro or methoxyl group.
More specifically described substituent R n most preferably be adjacent methyl, a methyl, to methyl, to ethyl, to n-propyl, p-isopropyl, to the tertiary butyl, to n-pentyl, m-chloro, 2,4-dichloro, a fluorine, to fluorine, O-methoxy, to methoxyl group or a nitro.
The present invention also provides described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) preparation method of benzo [d] thiazole-2 (3H)-one compounds, described method is: suc as formula the 2-shown in (II) (2-oxo benzo [d] thiazole-3-yl) acethydrazide with suc as formula the benzoic acid derivative shown in (III), in phosphorus oxychloride, under reflux state, carry out ring-closure reaction, after TLC monitoring to reaction finishes, reaction solution separation and purification makes suc as formula 3-((5-aryl-1 shown in (I), 3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds;
In formula (III), the H on phenyl ring is substituted base R and replaces or be not substituted, the combination of one or more in the alkyl that described substituent R is C1～C8, the alkoxyl group of C1～C3, halogen or nitro, and described halogen is F, Cl, Br or I;
Described is 1: 1.0～1.3: 10.0～50.0 suc as formula the 2-shown in (II) (2-oxo benzo [d] thiazole-3-yl) acethydrazide, suc as formula the ratio of the amount of substance that feeds intake of the benzoic acid derivative shown in (III), phosphorus oxychloride; Be preferably 1: 1.0～1.1: 20.0～35.0.
The present invention adopts thin-layer chromatography (TLC) method monitoring reaction performance, and the reaction times is generally 3～12 hours.The concrete reaction times is relevant with reactant.
The method of reaction solution separation and purification of the present invention is: after reaction finishes, the concentrated phosphorus oxychloride of removing of reaction solution, resistates makes suc as formula 3-((5-aryl-1 shown in (I) with recrystallization solvent recrystallization, 3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds.
Described recrystallization solvent is preferably one or more the mixed solution in ethanol, ethyl acetate, normal hexane, sherwood oil.
Of the present invention can reference (Il Farmaco suc as formula the 2-shown in (II) (2-oxo benzo [d] thiazole-3-yl) acethydrazide, 1999,54:842-845) method is synthesized: 2 (3H)-benzothiazolones, salt of wormwood and acetone are dropped into reaction flask, drip methyl chloroacetate, drip and finish, reflux 4 hours, the ratio of the amount of substance of 2 (3H)-benzothiazolones, salt of wormwood, methyl chloroacetate is 1: 1.15: 1.1.Reaction solution is cooling, pours frozen water into, stirs 1 hour, filters, and filter cake washing, obtains 2-(2-oxo benzo [d] thiazole-3-yl) methyl acetate.2-(2-oxo benzo [d] thiazole-3-yl) methyl acetate and 85% hydrazine hydrate are dissolved in ethanol, reflux 24 hours, reaction solution is cooling, filter, filter cake washing, be dried and obtain 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide, the ratio of the amount of substance of described-(2-oxo benzo [d] thiazole-3-yl) methyl acetate and 85% hydrazine hydrate is 1: 20.
3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds described in the present invention also provides is as the application of sterilant.The fungicidal activity that contriver adopts pastille potato agar substratum (PDA) method to carry out melon anthrax bacteria (Cucurbit anthracnose), melon ash arrhizus bacteria (Cinerea Botrytis) and rice sheath blight disease (Rhizoctonia solani) to synthetic compound is in an embodiment measured, and general sieve concentration is 50mg/L.Life is surveyed result and is shown, compound (I) all shows certain inhibition activity to all for examination bacterial classifications; Compound I d (Rn=is to methyl), Im (Rn=is to fluorine), Io (Rn=is to methoxyl group) are to the inhibiting rate of melon anthrax bacteria all more than 50%, and wherein the inhibiting rate of Id is 70.63%; Compound I j (Rn=m-chloro), Im (Rn=is to fluorine), In (Rn=O-methoxy), Io (Rn=is to methoxyl group) are to the inhibiting rate of melon ash arrhizus bacteria all more than 70%, and wherein the inhibiting rate of Im, Io is all greater than 80%; (phenyl ring unsubstituted, n=0), Il (fluorine between Rn=), Im (Rn=is to fluorine) be to the inhibiting rate of rice sheath blight disease all more than 50%, wherein the inhibiting rate of Il is 87.37% to Compound I a.
Compared with prior art, beneficial effect of the present invention is embodied in:
The invention provides the novel 3-of a class ((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds, this compounds preparation is simple, shows good bacteriostatic activity.
(4) embodiment
Below in conjunction with embodiment, the invention will be further described, but protection scope of the present invention is not limited to this.
(phenyl ring is without replacement, n=0) synthetic for embodiment 1 derivative I a
2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide reference (Il Farmaco, 1999,54:842-845) method is synthetic: 2 (3H)-benzothiazolones (0.1mol), salt of wormwood (0.115mol) and acetone (180mL) are dropped into reaction flask, drip methyl chloroacetate (0.11mol), drip and finish, reflux 4 hours.Reaction solution is cooling, pours frozen water into, stirs 1 hour, filters, and filter cake washing, obtains 2-(2-oxo benzo [d] thiazole-3-yl) methyl acetate: white solid, 20.5g, yield 92.0%, m.p.91-92 ℃ of (literature value: 92-94 ℃).2-(2-oxo benzo [d] thiazole-3-yl) methyl acetate (0.01mol) and 85% hydrazine hydrate (0.2mol) are dissolved in to 100mL ethanol, reflux 24 hours, reaction solution is cooling, filter, filter cake washing, dry 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide that obtains: white solid, 1.86g, yield 83.5%, m.p.211-212 ℃ (literature value: 211 ℃).
2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), phenylformic acid (10mmol) are added in 50mL reaction flask, then add phosphorus oxychloride (200mmol), stir, be heated to reflux, react 5 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.02g, i.e. derivative I a.166～168 ℃ of fusing points, yield is 65.2%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：5.47(s，2H，CH
2)，7.21～8.03(m，9H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
11N
3O
2S：C，62.12；H，3.58；N，13.58；found：C，62.31；H，3.55；N，13.62。
Embodiment 2 derivative I b's (the adjacent methyl of Rn=) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), o-toluic acid (10mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (200mmol), stirring, be heated to reflux, react 6 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.09g, i.e. derivative I b.187～189 ℃ of fusing points, yield is 64.7%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：2.65(s，3H，CH
3)，5.48(s，2H，CH
2)，7.21～7.90(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
17H
13N
3O
2S：C，63.14；H，4.05；N，12.99；found：C，63.33；H，4.03；N，13.04。
Embodiment 3 derivative I c's (methyl between Rn=) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), m-methyl benzoic acid (11mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (250mmol), stirring, be heated to reflux, react 9 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 15mL re-crystallizing in ethyl acetate, obtains faint yellow solid 2.35g, i.e. derivative I c.146～148 ℃ of fusing points, yield is 72.7%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：2.65(s，3H，CH
3)，5.48(s，2H，CH
2)，7.21～7.90(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
17H
13N
3O
2S：C，63.14；H，4.05；N，12.99；found：C，63.37；H，4.03；N，13.03。
Embodiment 4 derivative I d's (Rn=is to methyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), p-methylbenzoic acid (10.5mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (300mmol), stirring, be heated to reflux, react 12 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and 15mL normal hexane recrystallization for resistates, obtains faint yellow solid 2.37g, i.e. derivative I d.183～185 ℃ of fusing points, yield is 73.4%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：2.42(s，3H，CH
3)，5.45(s，2H，CH
2)，7.20～7.91(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
17H
13N
3O
2S：C，63.14；H，4.05；N，12.99；found：C，63.29；H，4.03；N，12.95。
Embodiment 5 derivative I e's (Rn=is to ethyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), ethyl benzoate (11mmol) is added in 50mL reaction flask, then add phosphorus oxychloride (350mmol), stir, be heated to reflux, react 12 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and 15mL sherwood oil recrystallization for resistates, obtains faint yellow solid 2.41g, i.e. derivative I e.174～176 ℃ of fusing points, yield is 71.3%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：1.31(t，J＝7.5，3H，CH
2 CH 3 )，2.42(s，3H，CH
3)，5.45(s，2H，CH
2)，7.20～7.91(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
18H
15N
3O
2S：C，64.08；H，4.48；N，12.45；found：C，64.20；H，4.44；N，12.52。
Embodiment 6 derivative I f's (Rn=is to n-propyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), align propylbenzoic acid (10.6mmol) and add in 50mL reaction flask, then add phosphorus oxychloride (250mmol), stir, be heated to reflux, react 7 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 15mL ethyl alcohol recrystallization, obtains faint yellow solid 2.45g, i.e. derivative I f.145～147 ℃ of fusing points, yield is 69.7%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：0.95(t，J＝7.5Hz，3H，CH
3)，1.65～1.69(m，2H，CH
2 CH 2 CH
3)，2.65(t，J＝7.5Hz，2H，
CH 2 CH
2CH
3)，5.45(s，2H，CH
2)，7.20～7.93(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
19H
17N
3O
2S：C，64.94；H，4.88；N，11.96；found：C，65.06；H，4.85；N，12.01。
Embodiment 7 derivative I g's (Rn=p-isopropyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), cuminic acid (10.8mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (240mmol), stirring, be heated to reflux, react 10 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and 20mL sherwood oil recrystallization for resistates, obtains faint yellow solid 2.36g, i.e. derivative I g.143～145 ℃ of fusing points, yield is 67.2%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：1.27(d，J＝7.0Hz，6H，CH
(CH 3 ) 2 )，2.94～2.99(m，1H，
CH(CH
3)
2)，5.46(s，2H，CH
2)，7.20～7.94(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
19H
17N
3O
2S：C，64.94；H，4.88；N，11.96；found：C，65.09；H，4.86；N，12.04。
Embodiment 8 derivative I h's (Rn=is to the tertiary butyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), p-tert-butyl benzoic acid (10mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (200mmol), stirring, be heated to reflux, react 12 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and the mixed solution recrystallization of 10mL ethyl acetate and 5mL ethanol for resistates, obtains faint yellow solid 2.25g, i.e. derivative I h.188～190 ℃ of fusing points, yield is 61.6%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：1.35(s，9H，C
(CH 3 ) 3 )，5.46(s，2H，CH
2)，7.21～7.95(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
20H
19N
3O
2S：C，65.73；H，5.24；N，11.50；found：C，65.81；H，5.22；N，11.54。
Embodiment 9 derivative I i's (Rn=is to n-pentyl) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), n-amylbenzene formic acid (11mmol) is added in 50mL reaction flask, then add phosphorus oxychloride (350mmol), stir, be heated to reflux, react 12 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and the mixed solution recrystallization of 10mL ethanol and 10mL normal hexane for resistates, obtains faint yellow solid 2.92g, i.e. derivative I i.196～198 ℃ of fusing points, yield is 77.0%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：0.90(t，J＝7.0Hz，3H，CH
3)，1.32～1.65(m，6H，CH
2 (CH 2 ) 3 CH
3)，2.66(t，J＝7.5Hz，2H，
CH 2 (CH
2)
3CH
3)，5.46(s，2H，CH
2)，7.21～7.93(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
21H
21N
3O
2S：C，66.47；H，5.58；N，11.07；found：C，66.54；H，5.55；N，11.11。
Embodiment 10 derivative I j's (Rn=m-chloro) is synthetic
2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), m-chlorobenzoic acid (10mmol) are added in 50mL reaction flask, then add phosphorus oxychloride (200mmol), stir, be heated to reflux, react 3 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and the mixed solution recrystallization of 10mL sherwood oil and 5mL normal hexane for resistates, obtains faint yellow solid 2.77g, i.e. derivative I j.171～173 ℃ of fusing points, yield is 80.5%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：5.47(s，2H，CH
2)，7.21～8.02(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
10ClN
3O
2S：C，55.90；H，2.93；N，12.22；found：C，56.07；H，2.91；N，12.27。
Embodiment 11 derivative I k's (Rn=2,4-dichloro) is synthetic
2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), 2,4 dichloro benzene formic acid (10.5mmol) are added in 50mL reaction flask, add again phosphorus oxychloride (300mmol), stir, be heated to reflux, react 12 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 20mL ethyl alcohol recrystallization, obtains faint yellow solid 3.20g, i.e. derivative I k.162～163 ℃ of fusing points, yield is 84.6%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：5.49(s，2H，CH
2)，7.21～7.93(m，7H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
9Cl
2N
3O
2S：C，50.81；H，2.40；N，11.11；found：C，50.97；H，2.38；N，11.15。
Embodiment 12 derivative I l's (fluorine between Rn=) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), m-fluorobenzoic acid (10.5mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (300mmol), stirring, be heated to reflux, react 8 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 15mL ethyl alcohol recrystallization, obtains faint yellow solid 2.75g, i.e. derivative I l.174～176 ℃ of fusing points, yield is 84.0%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：5.47(s，2H，CH
2)，7.21～7.83(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
10FN
3O
2S：C，58.71；H，3.08；N，12.84；found：C，58.85；H，3.06；N，12.80。
Embodiment 13 derivative I m's (Rn=is to fluorine) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), parafluorobenzoic acid (10.2mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (280mmol), stirring, be heated to reflux, react 11 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 20mL re-crystallizing in ethyl acetate, obtains faint yellow solid 2.68g, i.e. derivative I m.192～194 ℃ of fusing points, yield is 82.0%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：5.46(s，2H，CH
2)，7.17～8.05(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
10FN
3O
2S：C，58.71；H，3.08；N，12.84；found：C，58.82；H，3.07；N，12.88。
Embodiment 14 derivative I n's (Rn=O-methoxy) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), o-methoxybenzoic acid (11mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (250mmol), stirring, be heated to reflux, react 3 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.0g, i.e. derivative I n.173～174 ℃ of fusing points, yield is 59.0%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：3.92(s，3H，OCH
3)，5.47(s，2H，CH
2)，7.02～7.89(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
17H
13N
3O
3S：C，60.17；H，3.86；N，12.38；found：C，60.33；H，3.88；N，12.46。
Embodiment 15 derivative I o's (Rn=is to methoxyl group) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), anisic acid (11mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (200mmol), stirring, be heated to reflux, react 12 hours.TLC detects to reaction end, and reaction solution is concentrated sloughs phosphorus oxychloride, and resistates 10mL ethyl alcohol recrystallization, obtains faint yellow solid 3.22g, i.e. derivative I o.142～143 ℃ of fusing points, yield is 95.0%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(CDCl
3)δ：3.88(s，3H，OCH
3)，5.44(s，2H，CH
2)，6.98～7.97(m，8H，Ar-H)；Elemental?anal.(％)，calcd.for?C
17H
13N
3O
3S：C，60.17；H，3.86；N，12.38；found：C，60.38；H，3.82；N，12.44。
Embodiment 16 derivative I p's (nitro between Rn=) is synthetic
By 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide (2.25g, 10mmol), M-NITROBENZOIC ACID (10mmol) adds in 50mL reaction flask, then adds phosphorus oxychloride (350mmol), stirring, be heated to reflux, react 8 hours.TLC detects to reaction end, the concentrated phosphorus oxychloride of sloughing of reaction solution, and 20mL sherwood oil recrystallization for resistates, obtains faint yellow solid 3.20g, i.e. derivative I p.158～160 ℃ of fusing points, yield is 90.3%.
This compound
1h NMR and ultimate analysis data are as described below,
1H?NMR(DMSO-d
6)δ：5.51(s，2H，CH
2)，7.22～8.38(m，8H，Ar-H)；
Elemental?anal.(％)，calcd.for?C
16H
10N
4O
4S：C，54.23；H，2.84；N，15.81；found：C，54.40；H，2.82；N，15.87。
Embodiment 17 fungicidal activity tests
For trying target: melon anthrax bacteria (Cucurbit anthracnose), melon ash arrhizus bacteria (Cinerea Botrytis) and rice sheath blight disease (Rhizoctonia solani), above-mentioned bacterial classification is stored in 4～8 ℃ of refrigerators, testing front 2～3d is inoculated in culture dish from test tube slant, under optimal temperature, cultivate, standby.
Recovery room culture condition: the culture temperature for target after examination target and application of sample is 25 ± 5 ℃, and relative humidity is 65 ± 5%.
Adopt pastille potato agar substratum (PDA) method the synthetic compound of embodiment 1～16 and contrast medicament tricyclazole to be carried out to the fungicidal activity mensuration of above-mentioned target fungus, general sieve concentration is 50mg/L.
Concrete, testing method is evaluated SOP > > with reference to < < pesticide bioactivity.
Melon anthrax bacteria, melon ash arrhizus bacteria and rice sheath blight disease: with reference to the raw standard method NY/T1156.2-2006 that surveys, adopt pastille medium therapy: get each 500mg/L compound liquid 2mL, add in the PDA of the 18mL that is cooled to 45 ℃, making final concentration is the pastille culture medium flat plate of 50mg/L.Then from cultured test germ colony edge, get 6.5mm diameter mycelia piece, move on pastille substratum, every processing repeats for 4 times.Be disposed, the constant temperature biochemical cultivation case that is placed in 28 ℃ is cultivated, and after 4 days, measures colony diameter, calculates growth inhibition ratio.
Growth inhibition ratio (%)=[(blank colony diameter-processing colony diameter)/blank colony diameter] * 100%
Test result is in Table 1.
The fungicidal activity of table 13-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds
Claims (9)
1. a 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds, structure as shown in the formula (I):
In formula (I), it is monosubstituted, polysubstituted or be not substituted that H on phenyl ring is substituted base R, n is 0～5 integer, n represents the number of substituent R on phenyl ring, during n=0, represent that the H on phenyl ring is not substituted, during n=1, it is monosubstituted that H on expression phenyl ring is substituted base R, n=2～5 o'clock, it is polysubstituted that the H on expression phenyl ring is substituted base R, and the substituent R on different the position of substitution can be identical or different, described substituent R is the alkyl of C1～C8, the alkoxyl group of C1～C3, halogen or nitro, and described halogen is F, Cl, Br or I.
2. compound as claimed in claim 1, is characterized in that n=1～2 in described substituent R n.
3. compound as claimed in claim 1, is characterized in that described substituent R is alkyl, methoxyl group, F, Cl, Br or the nitro of C1～C5.
4. compound as claimed in claim 1, is characterized in that described substituent R is methyl, ethyl, n-propyl, sec.-propyl, the tertiary butyl, n-pentyl, F, Cl, nitro or methoxyl group.
5. compound as claimed in claim 1, it is characterized in that described substituent R n be adjacent methyl, a methyl, to methyl, to ethyl, to n-propyl, p-isopropyl, to the tertiary butyl, to n-pentyl, m-chloro, 2,4-dichloro, a fluorine, to fluorine, O-methoxy, to methoxyl group or a nitro.
6. 3-as claimed in claim 1 ((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds is as the application of sterilant, it is characterized in that described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds is as the application of the sterilant of melon anthrax bacteria (Cucurbit anthracnose), ash arrhizus bacteria (Cinerea Botrytis) or rice sheath blight disease (Rhizoctonia solani).
7. application as claimed in claim 6, it is characterized in that described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds is as the application of the sterilant of melon anthrax bacteria, described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) as shown in the formula (I), substituent R is to methyl, to fluorine or to methoxyl group to benzo [d] thiazole-2 (3H)-one compounds.
8. application as claimed in claim 6, it is characterized in that described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds is as the application of the sterilant of ash arrhizus bacteria, described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) as shown in the formula (I), substituent R is m-chloro to benzo [d] thiazole-2 (3H)-one compounds, to fluorine, to methoxyl group or O-methoxy.
9. application as claimed in claim 6, it is characterized in that described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-one compounds is as the application of the sterilant of rice sheath blight disease, benzo [d] thiazole-2 (3H)-one compounds as shown in the formula (I) for described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl), substituent R is to fluorine, a fluorine, or n=0.
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