CN102442946A - 3-cyan-5-(4-pyridyl)-N-n-propyl-pyridone, its preparation method and its application - Google Patents

Abstract

The invention relates to 3-cyan-5-(4-pyridyl)-N-n-propyl-pyridone, its preparation method and its application. The 3-cyan-5-(4-pyridyl)-N-n-propyl-pyridone has a structural formula shown in the following formula I: I. The invention has the beneficial effect that the compound 3-cyan-5-(4-pyridyl)-N-n-propyl-pyridone possessing bactericidal activity can be used as a green chemical pesticide, and has large development potential.

Description

3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone

Technical field

The present invention relates to 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone.

Background technology

In recent years, various germs are more and more serious to causing harm of plant, lawn brown spot cause of disease be dry thread Pyrenomycetes ( Rhizoctonia solani Kuhn), belong to Deuteromycotina hyphomycetes agonomycetales Rhizoctonia.It is extremely wide that this bacterium is infected scope, comprises forest nursery stock, vegetables, flowers and crop, almost infects all lawn grass varieties.The lawn brown spot is a kind of important turfgrass disease, during cold, warm season grassplot worldwide is careless generation is arranged all, especially takes place very general in the U.S., Canada, Europe and Japan.According to investigations, generally about 30%, heavy person can reach more than 50% this disease sickness rate, has had a strong impact on the lawn greening achievement.The State Administration of Forestry classified it as domestic forestry quarantine harmful organisms in 2004, had therefore caused the great attention of productions at different levels and control department.China is because the Lawn Industry development is later; Research to the lawn disease is at the early-stage, and the few and system not of data lacks theoretical direction to the control of disease; Prevention Technique is single; Generally be to spray medicine weekly once with systemic fungicide in period of disease, greatly waste of manpower and material resources, control effect is undesirable again.Therefore, developing the agricultural chemicals that has lawn brown spot fungicidal activity has important practical significance.

In recent years, in the research of agricultural chemicals, presenting a kind of new trend both at home and abroad, is exactly that nitrogen-containing heterocycle compound has obtained widespread use on agricultural chemicals.Because nitrogenous agricultural chemicals has characteristics such as selectivity height, activity is good, consumption is little, toxicity is low, the environmental facies dissolubility is good, makes that research, exploitation, the application of nitrogen heterocyclic ring agricultural chemicals are very extensive.Pyridine compounds and their is a compounds very important in the nitrogen heterocyclic ring, and it is simple in structure, and is active good.Pyridine ring is a pharmacophore with strong pharmacologically active, and is well-known, and behind the introducing pyridine ring, very important antibiotic, antitumor and antiviral isoreactivity can appear in chemical compound lot in the molecule of compound.

As a kind of new compound, bibliographical information is not seen in 3-cyanic acid-5-(4-the pyridyl)-preparation method of N-n-propyl-pyridone and the application of fungicidal activity as yet.

Summary of the invention

Problem to be solved by this invention is to propose a kind of new compound 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone to bacteria-treating.

Another object of the present invention provides the preparation method of 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone.

Of the present invention also have a purpose to provide the application of 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone as sterilant.

The present invention solves the problems of the technologies described above the solution that is adopted: 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone, and it has the represented structural formula of following formula I:

I

3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone preparing method's the technical scheme that is adopted is: the preparation method of 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone is characterized in that including following reactions step:

1) 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is synthetic

In reaction vessel, add DMF, slowly drip POCl3 during ice bath stirs, temperature remains on 5-15 ℃, after dropwising temperature is remained on 0-10 ℃; Then the 4-picoline slowly is added dropwise in the reaction vessel, continues reaction 1.5-4h, reaction is poured mixed solution in the frozen water into after finishing, and uses 30% NaOH neutralization solution to neutral then; Filter, under 5-15 ℃, in filtrating, add Malonamide nitrile; Use the Ethanol Treatment reaction solution behind the reaction 2-5h, be cooled to 0-10 ℃ again, with vinegar acid for adjusting pH value 5-8; Separate out the beige solid, filter the back, obtain 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone also with the washing with alcohol of 3X20mL;

Wherein count to 4-picoline: POCl3=1:1-6 in molar ratio;

2) 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone is synthetic

With DMF 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is got and to be dissolved in the reaction vessel and to stir; Then t-BuOK is joined retort step by step, after stirring with positive N-PROPYLE BROMIDE with being added drop-wise in the reaction there-necked flask 20-40 ℃ of stirring reaction 3-6h after the DMF dissolving; Reaction process is monitored with the TCL tlc; Question response with the method purification title product of silica gel column chromatography, finally obtains 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone after finishing;

Wherein count 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone: t-BuOK in molar ratio: positive N-PROPYLE BROMIDE=1:1-2:1-2.

The reaction formula that the present invention prepares process is:

Beneficial effect of the present invention is: the present invention has chemical compound 3-cyano-5-(4-the pyridyl)-N-n-propyl-pyridone of fungicidal activity, can be used as the Green Chemistry sterilant, and bigger development potentiality is arranged.

Embodiment

Further introduce the present invention through embodiment below, but embodiment can not be construed as limiting the invention.

Embodiment 1

(1) midbody 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is synthetic

The DMF that in the there-necked flask of 100mL, adds 31.4g (0.43mol) slowly drips 24.76g (0.16mol) POCl3 during ice bath stirs, in dripping the POCl3 process, react violent, and rate of rise in temperature is obvious, drips POCl ₃Shi Wendu remains on 10 ℃, POCl ₃After dropwising temperature is remained on 0-10 ℃, then 5g (0.054mol) 4-picoline slowly is added dropwise in the there-necked flask with constant voltage titration funnel, maintenance reaction 2 hours; The reaction process color can deepen, and pours mixed solution into frozen water after reaction finishes, and uses 30% NaOH neutralization solution to neutral then; Remove by filter inorganic salt, under 10-15 ℃, in filtrating, add the Malonamide nitrile that 9.33g (0.098mol) pulverizes; Then 30% the NaOH drips of solution of 13.3mL being added retort stirs; React after 3 hours with the Ethanol Treatment reaction solution of 56mL, be cooled to 0-10 ℃ after, use 36% vinegar acid for adjusting pH value to 6 again; Separate out the beige solid, filter the back and with the washing with alcohol of 3X20mL.Obtain 8.2g beige solid, productive rate 83.4%.

(2) 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone is synthetic

With the DMF of 20mL 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is got in the there-necked flask that 2g (0.01mol) is dissolved in 100mL and to be stirred; T-BuOK with 1.34g (0.012mol) joins retort step by step then; Be added drop-wise in the reaction there-necked flask stirring at room reaction 5 hours after the DMF dissolving of positive N-PROPYLE BROMIDE with 1.45g (0.012mol) then after stirring with 15mL.Reaction process is with the monitoring of TCL tlc, and question response with the method purification title product of silica gel column chromatography, finally obtains 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone and obtains 1.1g, productive rate 46.0% after finishing.m.p.99℃-101℃，? ¹HNMR?δ：8.69-8.71（m，2H，PyH），7.51-7.62（m，2H，PyH），7.71（s，1H，PyH），7.92（s，1H，PyH），4.41-4.43（m，2H，N-CH2），1.83-1.86（m，2H，-CH2-），1.05-1.09（m，3H，-CH3）；MS?m/z：287.0（M+，100%）；Anal.?calcd?for?C ₁₄H ₁₃N ₃O：C?70.28，H?5.48，N?17.56；found?C?70.61，H?5.67，N?17.75。

Embodiment 2

With the DMF of 30mL the midbody 3-cyanic acid-5-(4-pyridyl) that obtains among the embodiment 1-N (1H) pyridone is got in the there-necked flask that 2g (0.01mol) dissolving back adds 100mL and to be stirred; T-BuOK with 1.34g (0.012mol) joins retort step by step then; After stirring then with being added drop-wise in the reaction there-necked flask after the DMF dissolving of the positive N-PROPYLE BROMIDE of 1.45g (0.012mol) with 20mL, 25 ℃ of stirring reactions 6 hours.Reaction process is with the monitoring of TCL tlc, and question response with the method purification title product of silica gel column chromatography, finally obtains 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone and obtains 1g, productive rate 45% after finishing.

Embodiment 3

With the DMF of 10mL 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is got in the there-necked flask that 2g (0.01mol) is dissolved in 100mL and to be stirred; T-BuOK with 1.34g (0.012mol) joins retort step by step then; After stirring then with being added drop-wise in the reaction there-necked flask after the DMF dissolving of the positive N-PROPYLE BROMIDE of 1.45g (0.012mol) with 10mL, 20 ℃ of stirring reactions 7 hours.Reaction process is with the monitoring of TCL tlc, and question response with the method purification title product of silica gel column chromatography, finally obtains 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone and obtains 0.9g, productive rate 44.0% after finishing.

Embodiment 4

Adopt toxic medium culture method to measure the bacteriostatic activity of 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone (compound of preparation among the embodiment 1).On the aseptic technique platform, draw the solution that 1ml (100 μ g/ml) prepares and add in the 7.5cm petridish, do blank, inject 9ml thawing PDA substratum well with the 10ml glass syringe of sterilize then with sterile purified water with liquid-transfering gun; Soup and substratum are mixed in petridish; Room temperature is cooled off, and inoculates the lawn brown patch germ of diameter 5mm again in position, petridish middle, and 3 repetitions are done in each processing; To inoculate good petridish at last and put into 28 ℃ the about 30-40h of constant incubator cultivation; Treat that blank when covering with, measures colony diameter with ruler, each petridish is with right-angled intersection method measurement 2 times; Average, calculate the bacteriostasis rate of medicament at last.

Chemical compound 3-cyano-5-(4-pyridyl)-N-n-propyl-pyridone inhibiting rate to the lawn brown patch germ under the concentration of 100 μ g/ml is 67%, has outstanding bacteriostatic activity.

Embodiment 5

On the aseptic technique platform, draw the sample solution that 1 mL (100 μ g/ml) prepares and add in the sterilization petridish, replace soup to compare (CK), add 9 mL with asepsis injector again and dissolve back about 50 ℃ PDA substratum and uniform mixing with equivalent acetone-tween solution with liquid-transfering gun; To be cooled to room temperature, get the eugonic bacterial classification of colony edge with 5 mm punch tool, with inoculating needle inoculation bacterium cake; Mycelia faces down, and repeats 3 times, and the constant incubator that places 28 ℃ is cultivated (lawn brown patch germ cultivation 24～28 hours; Cotton-wilt fusarium was cultivated 5-6 days); Measure colony diameter with vernier callipers according to the right-angled intersection method, and deduct 5 mm bacterium cake diameters, 3 repetitions as the bacterium colony true diameter; Average, calculate bacteriostasis rate.

Chemical compound 3-cyano-5-(4-pyridyl)-N-n-propyl-pyridone inhibiting rate to the lawn brown patch germ under the concentration of 100 μ g/ml is 78%, has outstanding bacteriostatic activity.

Embodiment 6

Chemical compound 3-cyano-5-(4-pyridyl)-N-n-propyl-pyridone (compound of preparation among the embodiment 1) and auxiliary agents such as wilkinite, white carbon black, sodium lignosulfonate are processed the wettable powder of 10-50% with different ratios; Certain water yield is diluted to the finite concentration spraying, can be same as the field disease control.

Claims (3)

1.3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone, it has the represented structural formula of following formula I:

I 。

2.3-the preparation method of cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone is characterized in that including following reactions step:

1) 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is synthetic

In reaction vessel, add DMF, slowly drip POCl3 during ice bath stirs, temperature remains on 5-15 ℃, after dropwising temperature is remained on 0-10 ℃; Then the 4-picoline slowly is added dropwise in the reaction vessel, continues reaction 1.5-4h, reaction is poured mixed solution in the frozen water into after finishing, and uses 30% NaOH neutralization solution to neutral then; Filter, under 5-15 ℃, in filtrating, add Malonamide nitrile; Use the Ethanol Treatment reaction solution behind the reaction 2-5h, be cooled to 0-10 ℃ again, with vinegar acid for adjusting pH value 5-8; Separate out the beige solid, filter the back, obtain 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone also with the washing with alcohol of 3X20mL;

Wherein count to 4-picoline: POCl3=1:1-6 in molar ratio;

2) 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone is synthetic

With DMF 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone is got and to be dissolved in the reaction vessel and to stir; Then t-BuOK is joined retort step by step, after stirring with positive N-PROPYLE BROMIDE with being added drop-wise in the reaction there-necked flask 20-40 ℃ of stirring reaction 3-6h after the DMF dissolving; Reaction process is monitored with the TCL tlc; Question response with the method purification title product of silica gel column chromatography, finally obtains 3-cyanic acid-5-(4-pyridyl)-N-n-propyl-pyridone after finishing;

Wherein count 3-cyanic acid-5-(4-pyridyl)-N (1H) pyridone: t-BuOK in molar ratio: positive N-PROPYLE BROMIDE=1:1-2:1-2.

3. the described 3-cyanic acid-5-of claim 1 (4-pyridyl)-N-n-propyl-pyridone is as the application of sterilant.