CN105418496B - A kind of 3- chloride-2-hydrazinopyridines derivative and preparation method and application - Google Patents
A kind of 3- chloride-2-hydrazinopyridines derivative and preparation method and application Download PDFInfo
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- CN105418496B CN105418496B CN201510610803.3A CN201510610803A CN105418496B CN 105418496 B CN105418496 B CN 105418496B CN 201510610803 A CN201510610803 A CN 201510610803A CN 105418496 B CN105418496 B CN 105418496B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
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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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
Abstract
The present invention relates to a kind of 2 hydrazino pyridine derivatives of i.e. 3 chlorine of the new acylhydrazone containing pyridine ring and preparation method and application.3 chlorine, 2 hydrazino pyridine is made by 2,3 dichloropyridines and the reaction of hydrazine hydrate water in it, and 3 chlorine, 2 hydrazino pyridine is reacted with aldehyde under acetic acid catalysis effect is made 3 chlorine, 2 hydrazino pyridine derivative.Its preparation method is simple and convenient to operate, obtained compound shows bacterial spot of tomato preferable inhibition under 100 μ g/ml concentration, inhibiting rate is up to 82.54%, and preferable inhibition is shown to cucumber fusarium axysporum, and inhibiting rate is up to 71.11%；Compound of the present invention is the noval chemical compound with bactericidal activity, is provided the foundation for the research and development of novel pesticide.
Description
Technical field
The present invention relates to a kind of new acylhydrazone containing pyridine ring, that is, 3- chloride-2-hydrazinopyridines derivative and its systems
Preparation Method and application.
Background technology
Nowadays, nitrogen heterocyclic ring is critically important structure in many fields, particularly in terms of pesticide and medicine.To being at present
Only, about 90% insecticide and drug contain heterocycle structure.Pyridine ring is typical plane aroma system, in extensive chemical field
It plays an important role.Pyridine derivate is one kind most in the heterocyclic compound of bioactivity, and their synthesis derives
Object has broad-spectrum biological activity, including activity of weeding, bactericidal activity, antiproliferation, antioxidation activity, antimicrobial work
Property, antitumor activity etc..And some of which has been developed to drug or insecticide.In terms of antifungal activity,
Some pyridine derivates can inhibit Powdery Mildew, apple rot pathogen, ash arrhizus bacteria etc..
In addition, schiff base structure is considered as an important core in terms of drug discovery, hydrazone class is particularly.According to report
Road, hydrazone analog derivative have shown various bioactivity, such as anti-amoeba activity, urease inhibiting activity, antitumor work
Property, insecticidal activity, antifungal activity etc..
The content of the invention
For the above-mentioned problems in the prior art, the object of the present invention is to provide a kind of 3- with bactericidal activity
Chloride-2-hydrazinopyridine derivative and preparation method and application has synthesized a series of noval chemical compounds by easier method, this
Some in a little compounds explore method and technology of preparing with good bactericidal activity for the synthesis of novel pesticide.
The technology incidence of criminal offenses that the present invention uses is：
The present invention provides one kind such as formula（Ⅰ）Shown 3- chloride-2-hydrazinopyridines class compound,
Formula（Ⅰ）In：R is phenyl or substituted-phenyl, and the substituent group of the substituted-phenyl is halogen, methoxyl group, nitro, first
Base, hydroxyl, trifluoromethyl.
Further, preferably described formula（Ⅰ）Middle R is one of following：2- nitrobenzophenones, 2- aminomethyl phenyls, 2- methoxyphenyls,
3,4- Dimethoxyphenyls, 2- hydroxy phenyls, 5- methoxyl group -2- hydroxy phenyls, 3- chlorphenyls, 4- fluorophenyls, 4- trifluoromethyls
Phenyl, 3- nitrobenzophenones.
The present invention also provides a kind of formulas（Ⅰ）The preparation method of shown 3- chloride-2-hydrazinopyridines class compound, the method bag
Include following steps：（1）85% hydrazine hydrate solution is added dropwise into 2,3- dichloropyridines, in organic solvent A, is heated to reflux making
The formula of obtaining（Ⅱ）Shown 3- chloride-2-hydrazinopyridines；The dosage of the hydrazine hydrate aqueous solution is with the gauge of hydrazine hydrate substance；It is described organic
Solvent A be n,N-Dimethylformamide, tetrahydrofuran, Isosorbide-5-Nitrae-dioxane or ethyl alcohol in one or more, preferred alcohol；Institute
The ratio between amount of 2,3- dichloropyridines and hydrazine hydrate substance is stated as 1:2 ~ 5, preferably 1:4；The organic solvent A volumetric usage is with 2,3-
The amount of dichloropyridine substance is calculated as 20 ~ 50ml/mmol, preferably 40ml/mmol；（2）Aldehyde solution is added to formula（Ⅱ）Shown 3-
In chloride-2-hydrazinopyridine solution, under acetic acid catalysis effect, in organic solvent B, stirring at room temperature.It is monitored with thin-layer chromatography
Reaction process.It filters after reaction, with ethyl alcohol recrystallization, formula is made（Ⅰ）The shown hydrazone compounds containing pyridine ring；It is described
Recrystallization solvent be petroleum ether, methanol, n-hexane or ethyl alcohol in one or more, preferred alcohol；The aldehyde for phenyl aldehyde or
Substituted-phenyl aldehyde；The same organic solvent A of organic solvent B, preferred alcohol；The formula（Ⅱ）Shown 3- chloride-2-hydrazinopyridines with
Aldehyde, the ratio between the amount of substance of acetic acid are 1:1~2:0.1 ~ 0.2, preferably 1:1:0.1；Organic solvent B volumetric usage is with formula（Ⅱ）Institute
Show that the amount of the substance of 3- chloride-2-hydrazinopyridines is calculated as 5 ~ 15ml/mmol, preferably 10ml/mmol.
The reaction process of 3- chloride-2-hydrazinopyridines class compound of the present invention is as follows：
。
The present invention also provides a kind of formulas（Ⅰ）Shown 3- chloride-2-hydrazinopyridines class compound is in fungicide is prepared
Be prevention bacterial spot of tomato using, the specific fungicide,（Stemphylium lycopersici (Enjoji)
Yamamoto）, cucumber fusarium axysporum（Fusarium oxysporum s.p.cucumebrium）, botrytis cinerea
（Botrytis cinerea ）Fungicide.
Further, formula of the present invention（Ⅰ）Concentration of the shown 3- chloride-2-hydrazinopyridines class compound in fungicide is prepared
For 100 ~ 500ppm.
Further, formula of the present invention（Ⅰ）Shown 3- chloride-2-hydrazinopyridines class compound is preparing prevention tomato bacterial
Application in angular leaf spot fungicide, the formula（Ⅰ）Shown compound is（Ⅰ-1~10）Shown compound, most preferably（Ⅰ-8）It is shown
Compound.
Further, formula of the present invention（Ⅰ）Shown 3- chloride-2-hydrazinopyridines class compound is preparing prevention cucumber fusarium axysporum
Application in bacterium fungicide, the formula（Ⅰ）Shown compound is（Ⅰ-1~10）Shown compound, most preferably（Ⅰ-5）Shown chemical combination
Object.
Compared with prior art, the beneficial effects are mainly as follows：The present invention provides a kind of chloro- 2- diazanyls of 3-
Pyridine derivate and preparation method thereof prepares the application in fungicide with it, and its preparation method is simple and convenient to operate, obtained change
It closes object and preferable inhibition is shown to S. lycopersici under 100 μ g/ml concentration, inhibiting rate is up to 82.54%, to sharp spore
Sickle-like bacteria and cucumber fusarium axysporum show preferable inhibition, and inhibiting rate is up to 71.11%；Compound of the present invention is
Noval chemical compound with bactericidal activity provides the foundation for the research and development of novel pesticide.
Specific embodiment
With reference to specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in
This：
The chloro- 2- of 1 3- of embodiment (2- (2- nitrobenzophenones）Diazanyl）The preparation of pyridine
（1）3- chloride-2-hydrazinopyridine formulas（Ⅱ）Synthesis：
By 2,3- dichloropyridines（7.5mmol）, it is dissolved in n,N-Dimethylformamide（300ml）, hydrazine hydrate is added dropwise
（60mmol）, 72h is heated to reflux, formula is made（Ⅱ）Shown 3- chloride-2-hydrazinopyridines；
（2）3- chloride-2-hydrazinopyridine derivative formulas（Ⅰ）Synthesis：
By formula（Ⅱ）Shown 3- chloride-2-hydrazinopyridines（143.5mg,1mmol）, ethyl alcohol（10ml）, acetic acid（0.2mmol）And
2- nitrobenzaldehydes（1mmol）It is uniformly mixed and reaction is stirred at room temperature, reaction process is monitored to the chloro- 2- hydrazines of 3- with thin-layer chromatography
The reaction was complete for yl pyridines, filters, and target compounds of formula is made in petroleum ether recrystallization（Ⅰ-1）The shown chloro- 2- of 3- (2- (2- nitrobenzenes
Base）Diazanyl）Pyridine, yield 71%, m.p. 221-224 DEG C, formula（Ⅰ-1）The shown chloro- 2- of 3- (2- (2- nitrobenzophenones）Diazanyl）Pyrrole
Pyridine structural formula is as follows：
。
The chloro- 2- of 3- (2- (2- nitrobenzophenones）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 6.87(d, J
= 4.8 Hz, 1H, Py-H), 7.49(t, J = 4.8 Hz, 1H, Ph-H), 7.61-7.66(m, 3H, Ph-H),
8.30(t, J = 6.3 Hz, 1H, Py-H), 8.38(t, J = 7.8 Hz, 1H, Py-H), 8.63 (s, 1H, N=
CH-), 9.12(s, 1H, NH); ESI-MS: 275 [M-H]-; Elemental Analysis for C12H9ClN4O2:
C, 52.09; H, 3.28; N, 20.25; found: C 52.13, H 3.33, N 20.15。
The chloro- 2- of 2 3- of embodiment（2-（2- aminomethyl phenyls）Diazanyl）The preparation of pyridine
（1）3- chloride-2-hydrazinopyridine formulas（Ⅱ）Synthesis：
By 2,3- dichloropyridines（7.5mmol）, it is dissolved in ethyl alcohol（300ml）, hydrazine hydrate is added dropwise（30mmol）, heat back
72h is flowed, formula is made（Ⅱ）Shown 3- chloride-2-hydrazinopyridines；
（2）3- chloride-2-hydrazinopyridine derivative formulas（Ⅰ）Synthesis：
By formula（Ⅱ）Shown 3- chloride-2-hydrazinopyridines（143.5mg,1mmol）, ethyl alcohol（10ml）, acetic acid（0.1mmol）And
2- tolyl aldehydes（1mmol）It is uniformly mixed and reaction is stirred at room temperature, reaction process is monitored to the chloro- 2- hydrazines of 3- with thin-layer chromatography
The reaction was complete for yl pyridines, filters, ethyl alcohol recrystallization, and target compounds of formula is made（Ⅰ-2）The chloro- 2- of shown 3-（2-（2- methylbenzenes
Base）Diazanyl）Pyridine, yield 86%, m.p. 145-148 DEG C.
The chloro- 2- of 3-（2-（2- aminomethyl phenyls）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 2.37(s,
3H, CH3), 6.73(d, J=7.0Hz, 1H, Py-H), 7.15(d, J = 6.8 Hz, 1H, Ph-H), 7.24(s,
1H, Ph-H), 7.50~7.52(m, 2H, Ph-H), 7.68(d, J = 6.9 Hz, 1H, Py), 8.09(s, 1H, N
=CH-), 8.28(d, J = 6.5 Hz, 1H, Py), 9.01(s, 1H, NH); ESI-MS: 244 [M-H]-;
Elemental Analysis for C13H12ClN3: C, 63.55; H, 4.92; N, 17.10; found: C 63.78,
H 5.01, N 17.15。
The chloro- 2- of 3 3- of embodiment（2-（2- methoxyphenyls）Diazanyl）The preparation of pyridine
By 1 step 1 of embodiment）In organic solvent be changed to Isosorbide-5-Nitrae-dioxane, 2,3- dichloropyridines and hydrazine hydrate substance
The ratio between amount be 1:5, with the gauge of 2,3- dichloropyridine substances, the volume of Isosorbide-5-Nitrae-dioxane is 50ml/mmol,
Step（2）Middle 2- nitrobenzaldehydes change the Benzaldehyde,2-methoxy of 1mmol, 3- chloride-2-hydrazinopyridines and 2- first into
Oxygroup benzaldehyde, the ratio between the amount of substance of acetic acid are 1:1.5:0.15, organic solvent be Isosorbide-5-Nitrae-dioxane, volumetric usage with
Formula（Ⅱ）The amount of the substance of shown 3- chloride-2-hydrazinopyridines is calculated as 15ml/mmol, other operations are obtained with embodiment 1 such as formula
（Ⅰ-3）The chloro- 2- of shown 3-（2-（2- methoxyphenyls）Diazanyl）Pyridine, yield 63%, m.p. 178-180 DEG C,
。
The chloro- 2- of 3-（2-（2- methoxyphenyls）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 3.90(s,
3H, -OCH3), 6.76(d, J=7.4Hz, 1H, Py-H), 6.91(t, J = 8.3 Hz, 1H, Ph-H), 7.34
(t, J = 8.4 Hz, 1H, Ph-H), 7.43(t, J = 8.3 Hz, 1H, Ph-H), 7.58(t, J = 7.8 Hz,
1H, Ph-H), 8.16(d, J = 6.9 Hz, 1H, Py), 8.28(d, J = 4.3 Hz, 1H, Py), 8.45(s,
1H, N=CH-), 9.11(s, 1H, NH); ESI-MS: 260 [M-H]-; Elemental Analysis for
C13H12ClN3O: C, 59.66; H, 4.62; N, 16.06; found: C 59.87, H 4.78, N 15.89。
The chloro- 2- of 4 3- of embodiment（2-（3,4- Dimethoxyphenyls）Diazanyl）The preparation of pyridine
By 1 step 1 of embodiment）In organic solvent be changed to 1,4- dioxane and mixed with isometric ratio of tetrahydrofuran
The ratio between amount of object, 2,3- dichloropyridines and hydrazine hydrate substance is 1:3, with the gauge of 2,3- dichloropyridine substances, Isosorbide-5-Nitrae-dioxy six
The volume of ring and tetrahydrofuran compound is 30ml/mmol,
Step（2）Middle 2- nitrobenzaldehydes change the Veratraldehyde of 1mmol into, 3- chloride-2-hydrazinopyridines with
3,4- dimethoxy benzaldehydes, the ratio between the amount of substance of acetic acid are 1:2:0.12, organic solvent is Isosorbide-5-Nitrae-dioxane and tetrahydrochysene
Furans it is isometric than mixture, volumetric usage is with formula（Ⅱ）The amount of the substance of shown 3- chloride-2-hydrazinopyridines is calculated as 15ml/
Mmol, other operations are obtained with embodiment 1 such as formula（Ⅰ-4）The chloro- 2- of shown 3-（2-（3,4- Dimethoxyphenyls）Diazanyl）Pyrrole
Pyridine, yield 57%, m.p. 224-226 DEG C,
。
The chloro- 2- of 3-（2-（3,4- Dimethoxyphenyls）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 3.94
(s, 3H, -OCH3), 3.97(s, 3H, -OCH3), 6.75(t, J=7.8Hz, 1H, Py-H), 6.87(d, J =
8.2 Hz, 1H, Ph-H), 6.91 (d, J = 8.2 Hz, 1H, Ph-H), 7.49(s, 1H, Ph-H), 7.54(d,J = 5.8 Hz, 1H, Py), 7.97(s, 1H, N=CH-), 8.28(d, J = 3.6 Hz, 1H, Py), 8.60(s,
1H, NH); ESI-MS: 290 [M-H]-; Elemental Analysis for C14H14ClN3O2: C, 57.64; H,
4.84; N, 14.40; found: C 57.88, H 5.00, N 14.56。
5 2- of embodiment（（3- chloride-2-hydrazinopyridines）Base）The preparation of phenol
By 1 step 1 of embodiment）In organic solvent be changed to n,N-Dimethylformamide, 2,3- dichloropyridines and hydrazine hydrate
The ratio between amount of substance is 1:4, with the gauge of 2,3- dichloropyridine substances, the volume of n,N-Dimethylformamide is 40ml/
Mmol,
Step（2）Middle 2- nitrobenzaldehydes change the Benzaldehyde,2-hydroxy of 1mmol, 3- chloride-2-hydrazinopyridines and 2- hydroxyls into
Benzaldehyde, the ratio between the amount of substance of acetic acid are 1:1.0:0.1, organic solvent is n,N-Dimethylformamide, volumetric usage with
Formula（Ⅱ）The amount of the substance of shown 3- chloride-2-hydrazinopyridines is calculated as 12ml/mmol, and recrystallization solvent is the bodies such as n-hexane and ethyl alcohol
Product mixture, other operations are obtained with embodiment 1 such as formula（Ⅰ-5）Shown 2-（（3- chloride-2-hydrazinopyridines）Base）Phenol, production
Rate 84%, m.p. 182-183 DEG C,
。
2-（（3- chloride-2-hydrazinopyridines）Base）Phenol：1H NMR (CDCl3, 400 MHz), δ: 6.77(t, J=
6.4Hz, 1H, Py-H), 7.35~7.36(m, 2H, Ph-H), 7.49 (s, 1H, Ph-H), 7.60(d, J = 7.7
Hz, 1H, Py), 8.18(s, 1H, N=CH-), 8.32(d, J = 5.4 Hz, 1H, Py), 9.02(s, 1H,
NH); ESI-MS: 299 [M-H]-; Elemental Analysis for C12H8Cl3N3: C, 47.95; H, 2.68;
N, 13.98; found: C 47.76, H 2.87, N 13.78。
6 3- methoxyl groups -2- of embodiment（（3- chloride-2-hydrazinopyridines）Base）The preparation of phenol
By 1 step of embodiment（2）In 2- nitrobenzaldehydes change 5- methoxyl groups-Benzaldehyde,2-hydroxy of 1mmol into, other
Operation obtains 3- methoxyl groups -2- with embodiment 1（（3- chloride-2-hydrazinopyridines）Base）Phenol, yield 88%, m.p. 168-169
℃。
。
3- methoxyl groups -2-（（3- chloride-2-hydrazinopyridines）Base）Phenol：1H NMR (CDCl3, 400 MHz), δ: 6.89
(t, J=7.5Hz, 1H, Py-H), 7.01~7.04(m, 1H, Ph-H), 7.20(d, J = 7.6 Hz, 1H, Ph-
H), 7.24~7.28(m, 1H, Ph-H), 7.35~7.41(m, 1H, Ph-H), 7.58(d, J = 7.7 Hz, 1H,
Py), 8.13(s, 1H, N=CH-), 8.32(d, J = 4.8 Hz, 1H, Py), 8.71(s, 1H, NH); ESI-
MS: 247 [M-H]-; Elemental Analysis for C12H10ClN3O: C, 58.19; H, 4.07; N,
16.97; found: C 58.24, H 4.17, N 17.10。
The chloro- 2- of 7 3- of embodiment（2-（3- chlorphenyls）Diazanyl）The preparation of pyridine
By 1 step of embodiment（2）In 2- nitrobenzaldehydes change the 3- chlorobenzaldehydes of 1mmol into, other operations are the same as implementing
Example 1 obtains the chloro- 2- of 3-（2-（3- chlorphenyls）Diazanyl）Pyridine, yield 81%, m.p. 129-130 DEG C.
。
The chloro- 2- of 3-（2-（3- chlorphenyls）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 3.82(s, 3H,
OCH3), 6.52(s, 1H, Ph-H), 6.77(t, J=7.6Hz, 1H, Py-H), 7.10(d, J = 8.5 Hz, 1H,
Ph-H), 7.21(d, J = 7.6 Hz, 1H, Ph-H), 7.56(d, J = 7.7 Hz, 1H, Py), 8.08(s,
1H, N=CH-), 8.23(d, J = 4.8 Hz, 1H, Py), 8.58(s, 1H, NH); ESI-MS: 276 [M-H]-;
Elemental Analysis for C13H12ClN3O2: C, 56.22; H, 4.36; N, 15.13; found: C
56.32, H 4.44, N 15.23。
The chloro- 2- of 8 3- of embodiment（2-（4- fluorophenyls）Diazanyl）The preparation of pyridine
By 1 step of embodiment（2）In 2- nitrobenzaldehydes change the 4- fluorobenzaldehydes of 1mmol into, other operations are the same as implementing
Example 1 obtains formula（Ⅰ-8）The chloro- 2- of shown 3-（2-（4- fluorophenyls）Diazanyl）Pyridine, yield 74%, m.p. 200-201 DEG C.
。
The chloro- 2- of 3-（2-（4- fluorophenyls）Diazanyl）Pyridine：1H NMR (DMSO, 400 MHz), δ: 6.84(t, J=
5.1Hz, 1H, Py-H), 7.27(d, J = 8.7 Hz, 2H, Ph-H), 7.73~7.77(m, 3H, Ph-H and
Py), 8.20(d, J = 3.4 Hz, 1H, Py), 8.42(s, 1H, N=CH-), 10.50(s, 1H, NH); ESI-
MS: 248 [M-H]-; Elemental Analysis for C12H9ClFN3: C, 57.73; H, 3.63; N, 16.83;
found: C 57.89, H 3.47, N 16.62.
The chloro- 2- of 9 3- of embodiment（2-（4- trifluoromethyls）Diazanyl）The preparation of pyridine
By 1 step of embodiment（2）In 2- nitrobenzaldehydes change the 4- trifluoromethylated benzaldehydes of 1mmol into, other operations
With embodiment 1, obtain such as formula（Ⅰ-9）The chloro- 2- of shown 3-（2-（4- trifluoromethyls）Diazanyl）Pyridine, yield 69%, m.p.
135-136℃。
。
The chloro- 2- of 3-（2-（4- trifluoromethyls）Diazanyl）Pyridine：1H NMR (DMSO, 400 MHz), δ: 6.62
(t, J=5.9Hz, 1H, Py-H), 7.48(d, J = 8.7 Hz, 2H, Ph-H), 7.58~7.65(m, 3H, Ph-H
and Py), 8.05(d, J = 4.1 Hz, 1H, Py), 8.16(s, 1H, N=CH-), 10.55(s, 1H, NH);
ESI-MS: 299 [M-H]-; Elemental Analysis for C13H9ClF3N3: C, 52.10; H, 3.03; N,
14.02; found: C 52.22, H 3.17, N 13.98。
The chloro- 2- of 10 3- of embodiment（2-（3- nitrobenzophenones）Diazanyl）The preparation of pyridine
By 1 step of embodiment（2）In 2- nitrobenzaldehydes change the 3- nitrobenzaldehydes of 1mmol into, other operations are the same as real
Example 1 is applied, is obtained such as formula（Ⅰ-10）The chloro- 2- of shown 3-（2-（3- nitrobenzophenones）Diazanyl）Pyridine, yield 71%, m.p. 99-
101℃。
。
The chloro- 2- of 3-（2-（3- nitrobenzophenones）Diazanyl）Pyridine：1H NMR (CDCl3, 400 MHz), δ: 6.87(t, J
= 7.6 Hz, 1H, Py-H), 7.60(t, J = 7.8 Hz, 1H, Ph-H), 7.64(d, J = 7.5 Hz, 1H,
Ph-H), 8.13(s, 1H, Ph-H), 8.20~8.24(m, 2H, Ph-H and Py), 8.54(s, 1H, N=CH-),
8.78(s, 1H, NH); ESI-MS: 275 [M-H]-; Elemental Analysis for C12H9ClN4O2: C,
52.09; H, 3.28; N, 20.25; found: C 52.13, H 3.54, N 20.22.
11 bactericidal activity of embodiment is tested
Subjects：Bacterial spot of tomato, cucumber fusarium axysporum, graw mold of tomato.
Test method：Using pot experiment method.Respectively by cucumber seeds and tomato seeds after 50 DEG C are impregnated, after vernalization
It is seeded in pot for growing seedlings, to be grown to 2 true leaves are for experiment.
Medicament prepares：For reagent：It gets it filled and is made into 100ppm, take 89 kinds of each 5mg of compound, add 10% again after adding acetone solution
POLYSORBATE 80, finally plus water fully dissolves.Because 100ppm be 100mg/L so amount of water=5mg*1000/100mg=50ml, because having
Final content≤1% of solvent so plus acetone amount=50ml*1%=0.5ml（Dissolving）, because the final content of tween is 0.1% institute
Should have 0.05 ml of tween in 50 ml water, i.e.,：10% tween, 0.05 ml. should be added
Comparison medicament：3% Zhongshengmycin WP → 800 times liquid 0.01g medicine+8ml water
75% thiophanate methyl WP → 1000 times liquid 0.01g medicine+15ml water
50% cyprodinil water dispersible granule → 1000 times liquid 0.01g medicine+15ml water
Application method：In bacterial spot of tomato and graw mold of tomato experiment, when tomato seedling grows two panels compound leaf, with spray
Pot uniformly sprays reagent agent and comparison medicament on for examination plant.
In cucumber fusarium axysporum experiment, cucumber seeds are soaked in after respectively handling 2h and carry out inoculation processing.
Inoculation method：
Bacterial spot of tomato is inoculated with using bacteria suspension spray-on process：Cultured bacterial spot of tomato bacterium is converted into steaming
Distilled water is diluted to 3 × 107Cfu/ml bacteria suspensions, with watering can spray inoculation.Moisturizing culture after inoculation.
Graw mold of tomato is inoculated with using mycelium inoculation is beaten：Fluid nutrient medium and fungus block are separated by filtered through gauze, used
Crusher smashes the fungus block of the culture medium with a small amount of liquid, then is mixed with filtered fluid nutrient medium with the fungus block smashed
It is made into certain density solution, and with spectrophotometric determination solution light transmittance（λ=630nm, OD=9.8）.
Cucumber fusarium axysporum is inoculated with using Baconic's method for soaking seed：Will in PD culture mediums cultured cucumber fusarium axysporum gauze
Mycelia is filtered, adjusts spore concentration to 1 × 106Cfu/ml impregnates seed.
Disease investigation is carried out after clear water is fully fallen ill, and calculates disease index and control effect.
Bactericidal activity test result is as shown in table 1.
The bactericidal activity of each compound under 1 100ppm of table（% preventive effects）
It draws, tomato bacterial angular leaf spot is all shown under 100 μ g/mL of compound of the present invention good from table 1
Inhibition, especially compound（I-4）76.19%, compound（I-6）63.10%, compound（I-7）77.38% and compound
（I-8）82.54% pair its show preferable inhibition, other compounds also all show the good inhibition to fungi, change
Close object（I-1~10）Good inhibition is all shown to cucumber fusarium axysporum.
Claims (14)
- A kind of 1. 3- chloride-2-hydrazinopyridines derivative, it is characterised in that its structural formula such as formula（Ⅰ）It is shown：Formula（Ⅰ）In：R for phenyl or 2- nitrobenzophenones, 2- aminomethyl phenyls, 2- methoxyphenyls, 2- hydroxy phenyls, 5- methoxyl groups- 2- hydroxy phenyls, 3- chlorphenyls, 3- nitrobenzophenones.
- 2. a kind of preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 1, it is characterised in that including such as Lower step：1）85% hydrazine hydrate aqueous solution is added dropwise into 2,3- dichloropyridines, in organic solvent A, is heated to reflux being made such as formula （Ⅱ）Shown 3- chloride-2-hydrazinopyridines solution；2）Aldehyde solution is added in into step 1）Obtained formula（Ⅱ）In shown 3- chloride-2-hydrazinopyridine solution, make in acetic acid catalysis Under, in organic solvent B, stirring at room temperature, reaction process is monitored with thin-layer chromatography, filters and recrystallizes after reaction, It is made such as formula（Ⅰ）The shown hydrazone compounds containing pyridine ring.
- 3. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that the hydrazine hydrate For the dosage of aqueous solution with the gauge of hydrazine hydrate substance, the ratio between 2, the 3- dichloropyridines and amount of hydrazine hydrate substance are 1:2~5.
- 4. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that the hydrazine hydrate For the dosage of aqueous solution with the gauge of hydrazine hydrate substance, the ratio between 2, the 3- dichloropyridines and amount of hydrazine hydrate substance are 1:4.
- 5. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 1）Have Solvent A and step 2）In organic solvent B it is identical, organic solvent is respectively selected from n,N-Dimethylformamide, tetrahydrofuran, 1, One or more in 4- dioxane or ethyl alcohol.
- 6. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 1）Have Solvent A and step 2）In organic solvent B it is identical, organic solvent is ethyl alcohol.
- 7. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 1）In Organic solvent A volumetric usage is calculated as 20 ~ 50ml/mmol with the amount of 2,3- dichloropyridine substances；Step 2）In organic solvent B body Product dosage is with formula（Ⅱ）The amount of the substance of shown 3- chloride-2-hydrazinopyridines is calculated as 5 ~ 15ml/mmol.
- 8. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 1）In Organic solvent A volumetric usage is calculated as 40ml/mmol with the amount of 2,3- dichloropyridine substances；Step 2）In organic solvent B volume Dosage is with formula（Ⅱ）The amount of the substance of shown 3- chloride-2-hydrazinopyridines is calculated as 10ml/mmol.
- 9. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 2）It is middle heavy Recrystallisation solvent is the one or more in petroleum ether, methanol, n-hexane or ethyl alcohol.
- 10. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 2）In Recrystallization solvent is ethyl alcohol.
- 11. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that step 2）Institute Aldehyde is stated as phenyl aldehyde or substituted-phenyl aldehyde.
- 12. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that the 3- is chloro- 2- hydrazino pyridines and aldehyde, the ratio between the amount of substance of acetic acid are 1:1~2:0.1~0.2.
- 13. the preparation method of 3- chloride-2-hydrazinopyridines derivative according to claim 2, it is characterised in that the 3- is chloro- 2- hydrazino pyridines and aldehyde, the ratio between the amount of substance of acetic acid are 1:1:0.1.
- 14. a kind of 3- chlorine 2- hydrazino pyridine class compounds according to claim 1 are preparing inhibition tomato bacterial spot Application in the fungicide of disease.
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Citations (5)
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| US4997835A (en) * | 1987-05-14 | 1991-03-05 | Schaper Klaus Juergen | Substituted 2-acylpyridine-α-(N)-hetarlyhydrazones and medicaments containing the same |
| CN1052238A (en) * | 1989-11-30 | 1991-06-19 | 先灵公司 | Replace 1,2, N '-(2-pyridine radicals) the aldehyde hydrazone of 4-triazol [4,3-α] pyridine and replacement and as herbicide applications |
| EP0684226A1 (en) * | 1991-02-20 | 1995-11-29 | BASF Aktiengesellschaft | Imino-substituted phenyl derivatives, their preparation and fungicides containing them |
| CN1372549A (en) * | 1999-08-18 | 2002-10-02 | 阿方蒂农科有限公司 | Fungicidies |
| CN102249991A (en) * | 2011-06-01 | 2011-11-23 | 河南中医学院 | Method for high-yield synthesis of 3-chloride-2-hydrazinopyridine |
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2015
- 2015-09-23 CN CN201510610803.3A patent/CN105418496B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4997835A (en) * | 1987-05-14 | 1991-03-05 | Schaper Klaus Juergen | Substituted 2-acylpyridine-α-(N)-hetarlyhydrazones and medicaments containing the same |
| CN1052238A (en) * | 1989-11-30 | 1991-06-19 | 先灵公司 | Replace 1,2, N '-(2-pyridine radicals) the aldehyde hydrazone of 4-triazol [4,3-α] pyridine and replacement and as herbicide applications |
| EP0684226A1 (en) * | 1991-02-20 | 1995-11-29 | BASF Aktiengesellschaft | Imino-substituted phenyl derivatives, their preparation and fungicides containing them |
| CN1372549A (en) * | 1999-08-18 | 2002-10-02 | 阿方蒂农科有限公司 | Fungicidies |
| CN102249991A (en) * | 2011-06-01 | 2011-11-23 | 河南中医学院 | Method for high-yield synthesis of 3-chloride-2-hydrazinopyridine |
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