CN102584810A - 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)-ketone compounds and application thereof.
(2) background technology
As a member in the fused heterocycle system, benzothiazole derivant has wide biological activity, like desinsection (Pharmazie, 2003,58; 527), sterilization (Molecules, 1997,2,36), antiviral (organic chemistry; 2007,27,279), (U.S.Patent 5424443,1995-06-13) and plant growth regulating (J.Agric.Food Chem. in weeding; 1981,29,640) isoreactivity plays an important role in the novel pesticide initiative.Meanwhile, 1,3,4 - oxadiazole derivative also has a broad spectrum of biological activity, such as insecticides (Pest? Manage? Sci., 2003,59,933), weeding (USPatent? 4124373,1978-11 -07) and sterilization (Eur.J.Med.Chem., 1996,31,819) and other active, and some 1,3,4 - oxadiazole compounds have been successfully commercialized, such as pesticides evil insects ketone ( Renditions of pesticides, 1989,11 (6): 55), herbicides oxadiazon (World pesticides, 2006,28 (6): 15) and so on.In view of benzothiazole and 1,3,4-oxadiazole compounds all has excellent activity, utilizes synthetic the novel of both structures of active substructure joining method design to contain 1,3, and the benzothiazole compound of 4-oxadiazole ring is expected to have biological activity preferably.Like (E-J.Chem. such as B.Rajeeva; 2009; 6 (3), 775) synthesized a series of benzothiazole oxadiazoles compounds, give birth to survey the 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)-ketone compounds, its structure and bioactivity research are not all seen has 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)-ketone compounds and uses thereof.
The technical scheme that the present invention adopts is:
A kind of 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds, structure is suc as formula shown in (I):
In the formula (I), the H on the phenyl ring be substituted basic Rn singly replace, polysubstituted or be not substituted, n is 0～5 integer; N representes the number of substituent R on the phenyl ring, and during n=0, the H on the expression phenyl ring is not substituted; During n=1, the H of expression on the phenyl ring is substituted that basic R is single to be replaced, n=2～5 o'clock; It is polysubstituted that H on the expression phenyl ring is substituted basic Rn; Substituent R on different the position of substitution can be identical or different, and said substituent R is the alkyl of C1～C8, alkoxyl group, halogen or the nitro of C1～C3, and said halogen is F, Cl, Br or I.
When the H on the said phenyl ring was not substituted, promptly representing did not have substituting group on the phenyl ring.
Described substituent R is preferably 1～2, n=1～2 among the promptly preferred Rn.
Further, said 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.
Said more specifically substituent R n most preferably is 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 a methoxyl group or a nitro.
The present invention also provides said 3-((5-aryl-1; 3; 4-oxadiazole-2-yl) preparation method of benzo [d] thiazole-2 (3H)-ketone compounds methyl); Said method is: suc as formula the 2-shown in (II) (2-oxo benzo [d] thiazole-3-yl) acethydrazide with in POCl3, under reflux state, carry out ring-closure reaction suc as formula the benzoic acid derivative shown in (III), after TLC monitoring to reaction finished, the reaction solution separation and purification made suc as formula 3-((the 5-aryl-1 shown in (I); 3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds;
In the formula (III), the H on the phenyl ring is substituted basic R and replaces or be not substituted, and said substituent R is one or more the combination in alkoxyl group, halogen or the nitro of alkyl, C1～C3 of C1～C8, and said halogen is F, Cl, Br or I;
Said 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), POCl3; 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 according to the invention is: after reaction finishes; Reaction solution concentrates removes POCl3; Resistates makes benzo [d] thiazole-2 (3H)-ketone compounds suc as formula the 3-shown in (I) ((5-aryl-1,3,4-oxadiazole-2-yl) methyl) with the recrystallization solvent recrystallization.
Said recrystallization solvent is preferably one or more the mixed solution in ethanol, ETHYLE ACETATE, normal hexane, the sherwood oil.
According to the invention suc as formula the 2-shown in (II) (2-oxo benzo [d] thiazole-3-yl) but acethydrazide reference (Il Farmaco; 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.Frozen water is poured in the reaction solution cooling into, stirs 1 hour, filters, and the 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 80 are dissolved in the ethanol; Reflux 24 hours; The reaction solution cooling is filtered, the filter cake washing; Drying obtains 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide, and the ratio of the amount of substance of said-(2-oxo benzo [d] thiazole-3-yl) methyl acetate and 85% Hydrazine Hydrate 80 is 1: 20.
The present invention also provides the application of described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds as sterilant.The contriver adopts pastille potato agar substratum (PDA) method that the fungicidal activity that the synthetic compound has carried out melon anthrax bacteria (Cucurbit anthracnose), melon ash arrhizus bacteria (Cinerea Botrytis) and rice sheath blight disease (Rhizoctonia solani) is measured in an embodiment, and general sieve concentration is 50mg/L.Give birth to the survey result and show, compound (I) supplies examination bacterial classifications all to show certain inhibition activity to all; All more than 50%, wherein the inhibiting rate of Id is 70.63% to the inhibiting rate of melon anthrax bacteria for compound I d (Rn=is to methyl), Im (Rn=is to fluorine), Io (Rn=is to methoxyl group); All more than 70%, wherein the inhibiting rate of Im, Io is all greater than 80% to the inhibiting rate of melon ash arrhizus bacteria for compound I j (Rn=m-chloro), Im (Rn=is to fluorine), In (Rn=O-methoxy), Io (Rn=is to methoxyl group); Compound I a (the phenyl ring unsubstituted, n=0), all more than 50%, wherein the inhibiting rate of Il is 87.37% to the inhibiting rate of rice sheath blight disease for Il (fluorine between Rn=), Im (Rn=is to fluorine).
Compared with prior art, beneficial effect of the present invention is embodied in:
The invention provides one type of novel 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds, such compound is simple, shows bacteriostatic activity preferably.
(4) embodiment
Below in conjunction with embodiment the present invention is described further, but protection scope of the present invention is not limited to this.
(phenyl ring does not have replacement to embodiment 1 derivative I a, n=0) synthetic
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.Frozen water is poured in the reaction solution cooling into, stirs 1 hour, filters, and the 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 ℃ (literature value: 92-94 ℃).2-(2-oxo benzo [d] thiazole-3-yl) methyl acetate (0.01mol) and 85% Hydrazine Hydrate 80 (0.2mol) are dissolved in 100mL ethanol, reflux 24 hours, reaction solution cooling; Filter; The filter cake washing, drying obtains 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide: white solid, 1.86g; Yield 83.5%, m.p.211-212 ℃ (literature value: 211 ℃).
(2.25g 10mmol), phenylformic acid (10mmol) adds in the 50mL reaction flask, adds POCl3 (200mmol) again, stirs, and is heated to backflow, reacted 5 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.02g, i.e. derivative I a.166～168 ℃ of fusing points, yield are 65.2%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), o-toluic acid (10mmol) adds in the 50mL reaction flask, adds POCl3 (200mmol) again, stirs, and is heated to backflow, reacted 6 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.09g, i.e. derivative I b.187～189 ℃ of fusing points, yield are 64.7%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), m-methyl benzoic acid (11mmol) adds in the 50mL reaction flask, adds POCl3 (250mmol) again, stirs, and is heated to backflow, reacted 9 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 15mL re-crystallizing in ethyl acetate, obtains faint yellow solid 2.35g, i.e. derivative I c.146～148 ℃ of fusing points, yield are 72.7%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), p-methylbenzoic acid (10.5mmol) adds in the 50mL reaction flask, adds POCl3 (300mmol) again, stirs, and is heated to backflow, reacted 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.37g with 15mL normal hexane recrystallization, i.e. derivative I d.183～185 ℃ of fusing points, yield are 73.4%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), ethyl benzoate (11mmol) is added in the 50mL reaction flask, adds POCl3 (350mmol) again, stirs, and is heated to backflow, reacts 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.41g with 15mL sherwood oil recrystallization, i.e. derivative I e.174～176 ℃ of fusing points, yield are 71.3%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), align propylbenzoic acid (10.6mmol) and add in the 50mL reaction flask, adds POCl3 (250mmol) again, stirs, and is heated to backflow, reacts 7 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 15mL ethyl alcohol recrystallization, obtains faint yellow solid 2.45g, i.e. derivative I f.145～147 ℃ of fusing points, yield are 69.7%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), cuminic acid (10.8mmol) adds in the 50mL reaction flask, adds POCl3 (240mmol) again, stirs, and is heated to backflow, reacted 10 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.36g with 20mL sherwood oil recrystallization, i.e. derivative I g.143～145 ℃ of fusing points, yield are 67.2%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), p-tert-butyl benzoic acid (10mmol) adds in the 50mL reaction flask, adds POCl3 (200mmol) again, stirs, and is heated to backflow, reacted 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.25g, i.e. derivative I h with 10mL ETHYLE ACETATE and 5mL alcoholic acid mixed solution recrystallization.188～190 ℃ of fusing points, yield are 61.6%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), n-amylbenzene formic acid (11mmol) is added in the 50mL reaction flask, adds POCl3 (350mmol) again, stirs, and is heated to backflow, reacts 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.92g with the mixed solution recrystallization of 10mL ethanol and 10mL normal hexane, i.e. derivative I i.196～198 ℃ of fusing points, yield are 77.0%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), m-chlorobenzoic acid (10mmol) adds in the 50mL reaction flask, adds POCl3 (200mmol) again, stirs, and is heated to backflow, reacted 3 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 2.77g with the mixed solution recrystallization of 10mL sherwood oil and 5mL normal hexane, i.e. derivative I j.171～173 ℃ of fusing points, yield are 80.5%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), 2,4 dichloro benzene formic acid (10.5mmol) adds in the 50mL reaction flask, adds POCl3 (300mmol) again, stirs, and is heated to backflow, reacted 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 20mL ethyl alcohol recrystallization, obtains faint yellow solid 3.20g, i.e. derivative I k.162～163 ℃ of fusing points, yield are 84.6%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), a fluorobenzoic acid (10.5mmol) adds in the 50mL reaction flask, adds POCl3 (300mmol) again, stirs, and is heated to backflow, reacted 8 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 15mL ethyl alcohol recrystallization, obtains faint yellow solid 2.75g, i.e. derivative I l.174～176 ℃ of fusing points, yield are 84.0%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), parafluorobenzoic acid (10.2mmol) adds in the 50mL reaction flask, adds POCl3 (280mmol) again, stirs, and is heated to backflow, reacted 11 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 20mL re-crystallizing in ethyl acetate, obtains faint yellow solid 2.68g, i.e. derivative I m.192～194 ℃ of fusing points, yield are 82.0%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), o-methoxybenzoic acid (11mmol) adds in the 50mL reaction flask, adds POCl3 (250mmol) again, stirs, and is heated to backflow, reacted 3 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 10mL ethyl alcohol recrystallization, obtains faint yellow solid 2.0g, i.e. derivative I n.173～174 ℃ of fusing points, yield are 59.0%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), anisic acid (11mmol) adds in the 50mL reaction flask, adds POCl3 (200mmol) again, stirs, and is heated to backflow, reacted 12 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates is used the 10mL ethyl alcohol recrystallization, obtains faint yellow solid 3.22g, i.e. derivative I o.142～143 ℃ of fusing points, yield are 95.0%.
This compound
1H NMR and ultimate analysis data are 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
(2.25g 10mmol), M-NITROBENZOIC ACID (10mmol) adds in the 50mL reaction flask, adds POCl3 (350mmol) again, stirs, and is heated to backflow, reacted 8 hours with 2-(2-oxo benzo [d] thiazole-3-yl) acethydrazide.TLC detects to the reaction end, and reaction solution concentrates and sloughs POCl3, and resistates obtains faint yellow solid 3.20g with 20mL sherwood oil recrystallization, i.e. derivative I p.158～160 ℃ of fusing points, yield are 90.3%.
This compound
1H NMR and ultimate analysis data are 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。
The test of embodiment 17 fungicidal activities
Supply the examination 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 preceding 2～3d is inoculated in the petridish from the test tube slant; Cultivate under the optimal temperature, subsequent use.
The recovery room culture condition: the culture temperature of target is 25 ± 5 ℃ behind confession examination target and the application of sample, and relative humidity is 65 ± 5%.
Employing pastille potato agar substratum (PDA) method is to embodiment 1～16 synthetic compound and contrast the fungicidal activity mensuration that the medicament tricyclazole has carried out above-mentioned target germ, and general sieve concentration is 50mg/L.
Concrete, testing method is with reference to " pesticide bioactivity is estimated SOP ".
Melon anthrax bacteria, melon ash arrhizus bacteria and rice sheath blight disease: with reference to giving birth to the accurate method NY/T1156.2-2006 of mark; Adopt the pastille medium therapy: get each 500mg/L compound soup 2mL; Add among the PDA of the 18mL that is cooled to 45 ℃, processing final concentration is the pastille culture medium flat plate of 50mg/L.Get 6.5mm diameter mycelia piece from cultured test germ colony edge then, move on the pastille substratum, every processing repeats for 4 times.Dispose, place 28 ℃ the biochemical incubator of constant temperature to cultivate, measure colony diameter after 4 days, calculate growth inhibition ratio.
Growth inhibition ratio (%)=[(blank colony diameter-processing colony diameter)/blank colony diameter] * 100%
Test result is seen table 1.
The fungicidal activity of table 13-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds
Claims (10)
1. a 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds, structure is suc as formula shown in (I):
In the formula (I), the H on the phenyl ring be substituted basic Rn singly replace, polysubstituted or be not substituted, n is 0～5 integer; N representes the number of substituent R on the phenyl ring, and during n=0, the H on the expression phenyl ring is not substituted; During n=1, the H of expression on the phenyl ring is substituted that basic R is single to be replaced, n=2～5 o'clock; It is polysubstituted that H on the expression phenyl ring is substituted basic Rn; Substituent R on different the position of substitution can be identical or different, and said substituent R is the alkyl of C1～C8, alkoxyl group, halogen or the nitro of C1～C3, and said halogen is F, Cl, Br or I.
2. compound as claimed in claim 1 is characterized in that n=1～2 among the said substituent R n.
3. compound as claimed in claim 1 is characterized in that said 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 said 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 said 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 a 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)-ketone compounds is as the application of sterilant.
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)-ketone compounds is as the application of the sterilant of melon anthrax bacteria (Cucurbit anthracnose), melon ash arrhizus bacteria (Cinerea Botrytis) or rice sheath blight disease (Rhizoctonia solani).
8. application as claimed in claim 7; It is characterized in that of the application of described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds as the sterilant of melon anthrax bacteria; Said 3-((5-aryl-1; 3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds is suc as formula shown in (I), and substituent R n is to methyl, to fluorine or to methoxyl group.
9. application as claimed in claim 7; It is characterized in that of the application of described 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds as the sterilant of melon ash arrhizus bacteria; Said 3-((5-aryl-1; 3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds is suc as formula shown in (I), and substituent R n is m-chloro, to fluorine, to methoxyl group or O-methoxy.
10. application as claimed in claim 7 is characterized in that described 3-((5-aryl-1,3; 4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds is as the application of the sterilant of rice sheath blight disease; Said 3-((5-aryl-1,3,4-oxadiazole-2-yl) methyl) benzo [d] thiazole-2 (3H)-ketone compounds is suc as formula shown in (I); Substituent R n is to fluorine, a fluorine, or n=0.
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| CN103848827A (en) * | 2012-11-30 | 2014-06-11 | 南京大学 | Application of benzotriazole derivatives in anti-cancer drugs |
| CN103848826A (en) * | 2012-11-30 | 2014-06-11 | 南京大学 | Preparation method and use of 1,3,4-oxadiazole derivative having benzotriazole structure |
| CN104177350A (en) * | 2014-07-28 | 2014-12-03 | 天津普茂科技发展有限公司 | Bitriazole phenyl-substituted oxadiazole compound and preparation method and application thereof |
| CN109020916A (en) * | 2018-10-15 | 2018-12-18 | 浙江工业大学 | A kind of substitution benzothiazole C2 alkyl derivative and its application |
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| US20090305285A1 (en) * | 2008-06-10 | 2009-12-10 | Shenzhen Mindray Bio-Medical Electronics Co., Ltd. | Asymmetric cyanine compounds, their preparation methods and their uses |
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| US20090305285A1 (en) * | 2008-06-10 | 2009-12-10 | Shenzhen Mindray Bio-Medical Electronics Co., Ltd. | Asymmetric cyanine compounds, their preparation methods and their uses |
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| CN103848826A (en) * | 2012-11-30 | 2014-06-11 | 南京大学 | Preparation method and use of 1,3,4-oxadiazole derivative having benzotriazole structure |
| CN104177350A (en) * | 2014-07-28 | 2014-12-03 | 天津普茂科技发展有限公司 | Bitriazole phenyl-substituted oxadiazole compound and preparation method and application thereof |
| CN109020916A (en) * | 2018-10-15 | 2018-12-18 | 浙江工业大学 | A kind of substitution benzothiazole C2 alkyl derivative and its application |
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