CN1331080A - Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds - Google Patents
Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds Download PDFInfo
- Publication number
- CN1331080A CN1331080A CN 00114649 CN00114649A CN1331080A CN 1331080 A CN1331080 A CN 1331080A CN 00114649 CN00114649 CN 00114649 CN 00114649 A CN00114649 A CN 00114649A CN 1331080 A CN1331080 A CN 1331080A
- Authority
- CN
- China
- Prior art keywords
- reaction
- compound
- general formula
- formula
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
A process for synthesizing a triazolo-pyrimido-thioacytyl hydrozone compound with antibacterial activity is disclosed. The said compound has obvious unique activity to kill the rice Hypochnus when its concentration is 50-200 ppm, so it can be used as disinfectant.
Description
Minute Organic Synthesis technical field under the present invention.
U.S. DOW company had applied for 1,2 in 1985, the synthetic and weeding activity patent (EP142152) of 4-triazolo [1,5-a] pyrimidine sulfonyl aminated compounds, thus make the triazolo pyrimidine analog derivative become the interior another research focus of pesticide field.At present, this compounds mainly is used as weedicide, and as DE498 (Flumetsulam), DE511, TP4189 etc., and the compound that contains the triazolo pyrimidine structural unit is as the report of sterilant rarely found (EP550113,1993).
The objective of the invention is to explore fungicidal activity compound preferably, novel triazolopyrimidines acylhydrazone analog derivative that a class has fungicidal activity and preparation method thereof is provided.
The novel acylhydrazone compounds-1,2 of a class that the present invention proposes, 4-triazolo [1,5-a] pyrimidine-2-thioacetyl hydrazone, its general structure following (I)
X, Y, Z represent hydrogen, alkyl, aryl, trifluoromethyl, alkoxyl group, aryloxy, halogen in the formula
R
1, R
2Expression hydrogen, alkyl, aryl, heterocyclic aryl
Formula provided by the invention (I) compound has obvious specificity to kill activity to Rhizoctonia solani Kuhn, thereby can be used as the effective constituent of sterilant.
With the preparation method of the triazolo pyrimidine thioacetyl hydrazone of general formula (I) expression is that the represented compound of the represented compound of general formula (II) and general formula (III) is reacted.
(X, Y, Z, R in the formula
1, R
2Identical with the definition in the general formula (I))
In the above-mentioned reaction, triazolo pyrimidine-2-thioacetyl hydrazine (II) is 1: 1～1.2 with the amount proportioning of the reactant species of aldehydes or ketones (III), and reaction solvent adopts organic solvents such as methyl alcohol, ethanol.In the presence of an acidic catalyst, reacted 2～30 hours down at 60～80 ℃, can obtain good yield.
Preparation method with the triazolo pyrimidine-2-thioacetyl hydrazine of general formula (II) expression reacts general formula (IV) represented compound and hydrazine hydrate.
(X, Y in the formula, Z are identical with the definition of general formula (I), R
3Expression CH
3, C
2H
5)
In the above-mentioned reaction, the amount proportioning of the reactant species of triazolo pyrimidine-2-thioacetate and hydrazine hydrate is 1: 6～8, and reaction solvent adopts organic solvents such as methyl alcohol, ethanol, refluxes 4～6 hours down at 60～80 ℃, can obtain good yield.
Preparation with the triazolo pyrimidine-2-thioacetate of general formula (IV) expression is divided into following two kinds of methods according to the difference of X, Z:
Method A: be that the compound of represented compound of logical formula V and general formula (VI) expression is reacted
(R in the formula
3Expression CH
3, C
2H
5, X, Z represent alkyl, aryl, trifluoromethyl, Y represents hydrogen, alkyl, aryl, halogen)
In the above-mentioned reaction, 5-amino-1,2,4-triazole-3-thioacetate (V) and 1, the amount proportioning of the reactant species of 3-diketone is 1: 1～1.2, reaction solvent adopts glacial acetic acid, do at piperidines under the condition of catalyzer, refluxed 16～18 hours, can obtain yield preferably at 110～118 ℃.
Method B: be to make the compound of represented compound of logical formula V and general formula (VII) expression react (1), obtain the compound of general formula (VIII) expression, this compound and POCl
3Reaction (2) obtains compound (IX).Compound (IX) and sodium alkoxide or phenol sodium reaction (3), get final product the represented compound of general formula (IV).
(R, R in the formula
3Expression CH
3, C
2H
5, Y represents hydrogen, alkyl, aryl, X, Z represent alkoxyl group, aryloxy)
In the above-mentioned reaction (1), 5-amino-1,2,4-triazole-3-thioacetate (V) is 1: 1～1.2 with the amount proportioning of the reactant species of diester malonate, reaction solvent adopts organic solvents such as dehydrated alcohol, methyl alcohol, in the presence of first (second) sodium alkoxide, refluxes 48～60 hours down at 60～80 ℃, cooling, suction filtration, solid is soluble in water, uses hcl acidifying then, suction filtration gets compound (VIII); In the above-mentioned reaction (2), compound (VIII) is 1: 3～5 with the amount proportioning of the reactant species of phosphorus oxychloride, reaction solvent adopts acetonitrile, reacted under the room temperature 15～20 hours, and filtered, add frozen water and ethylene dichloride behind the filtrate precipitation, tell organic phase, anhydrous magnesium sulfate drying concentrates, and gets compound (IX); In the above-mentioned reaction (3), compound (IX) is 1: 2.2～2.5 with the amount proportioning of the reactant species of alcohol (phenol) sodium, and reaction solvent adopts organic solvents such as methyl alcohol, ethanol, room temperature reaction 2～3 hours adds suitable quantity of water, neutralizes with hydrochloric acid then, suction filtration gets compound (IV).
Specifically describe the preparation method of (I) of the present invention, (II), (IV) formula compound below by embodiment.
Embodiment 1
Preparation
With the 5-amino-1,2 of 0.5mol, 4-triazole-3-ethyl thioacetate and 1500ml glacial acetic acid add in the reaction flask, add methyl ethyl diketone, the 4.8ml piperidines of 0.5mol again, temperature rising reflux 16～18 hours, cooling, suction filtration, white solid, yield 90%, m.p.142～143 ℃.
Ultimate analysis: calculated value C% 49.62 H% 5.62 N% 21.05
Measured value C% 49.18 H% 5.83 N% 21.33
Embodiment 2
Preparation
With the 5-amino-1,2 of 0.5mol, the dimethyl malonate of 4-triazole-3-ethyl thioacetate and 0.5mol is dissolved in the 200ml dehydrated alcohol, the methanol solution that contains 25% sodium methylate that adds 215g again, back flow reaction 60 hours, cooling, suction filtration, dehydrated alcohol is washed twice, solid is used the 1000ml water dissolution earlier, uses the concentrated hydrochloric acid acidifying again, and suction filtration gets white solid, yield 82%, m.p.99～100 ℃.
Ultimate analysis: calculated value C% 40.03 H% 3.70 N% 20.74
Measured value C% 40.35 H% 3.23 N% 21.05
Embodiment 3
Preparation
With 5 of 0.5mol, 7-dihydroxyl-1,2, the phosphorus oxychloride of 4-triazolo [1,5-a] pyrimidine-2-ethyl thioacetate and 1.5mol adds in the acetonitrile of 1200ml, refluxes 3 hours, placement is spent the night, and filters, and filtrate is sloughed solvent, the frozen water and the methylene dichloride that add equivalent then, tell organic phase, use anhydrous magnesium sulfate drying, be concentrated into and separate out crystal, yield 81%, m.p.79～80 ℃.
Ultimate analysis: calculated value C% 35.19 H% 2.61 N% 18.20
Measured value C% 35.02 H% 2.32 N% 18.55
Embodiment 4
Preparation
With 5 of 0.05mol, 7-two chloro-1,2,4-triazolo [1,5-a] pyrimidine-2-ethyl thioacetate and 60ml methyl alcohol adds in the reaction flask, add the methanol solution that 23.5g (0.11mol) contains 25% sodium methylate under stirring, reaction adds 100ml water under the room temperature after 2 hours, and the hydrochloric acid with 3N neutralizes again, suction filtration, white solid, yield 84%, m.p.168～169 ℃.
Ultimate analysis: calculated value C% 44.30 H% 4.70 N% 18.79
Measured value C% 44.02 H% 4.33 N% 18.35
Embodiment 5
Preparation
With 5 of 0.05mol, 7-dimethyl-1,2,4-triazolo [1,5-a] pyrimidine-2-ethyl thioacetate, 200ml dehydrated alcohol add in the 250ml reaction flask, stir, the hydrazine hydrate that adds 40ml (about 0.35mol) 85% again, temperature rising reflux reaction 2～4 hours, suction filtration, ethanol is washed twice, white crystal, yield 93.2%, m.p.201.5～203 ℃.
Ultimate analysis: calculated value C% 42.86 H% 4.76 N% 33.33
Measured value C% 42.62 H% 4.62 N% 33.05
Embodiment 6
Preparation
With the acethydrazide of 5mmol, 50ml dehydrated alcohol and 6mmol3-chlorobenzaldehyde add respectively in the reaction flask, stir, and add 15dHAc again, temperature rising reflux 2 hours, cooling, suction filtration, solid chloroform recrystallization, pure product are white crystal, yield 96.1%, m.p.206～208 ℃.
Ultimate analysis: calculated value C% 51.27 H% 4.01 N% 22.43
Measured value C% 51.43 H% 4.36 N% 22.15
1HNMR(δ，ppm)2.49，2.53(2s，3H，5-CH
3)，2.63，2.65(2s，3H，7-CH
3)，
4.12，4.54(2s，2H，SCH
2)，7.08(S，1H，6-H)，
7.43-7.46(m，3H，Ar-H)，7.73(S，1H，Ar-H)，
8.00(2s，1H，CH)，11.8(2S，1H，NH)
Embodiment 7
Preparation
With the acethydrazide of 5mmol, 50ml dehydrated alcohol and 6mmol methyl phenyl ketone add respectively in the reaction flask, stir, and add 15dHAc again, temperature rising reflux 24 hours, cooling, suction filtration, white crystal, yield 94.9%, m.p.197～199 ℃.
Ultimate analysis: calculated value C% 57.63 H% 5.08 N% 23.73
Measured value C% 57.43 H% 5.36 N% 23.55
1HNMR(δ，ppm)2.49，2.52(2s，3H，5-CH
3)，2.63，2.65(2s，3H，7-CH
3)
4.13，4.55(2s，2H，SCH
2)，7.07(s，1H，6-H)，
7.37-7.57(m，5H，Ar-H)，11.8(2s，1H，NH)
Adopt above-mentioned similar approach can prepare other compound equally.Listedly in the table 1 be synthetic part of compounds of the present invention.
The implication of ellipsis in the table: Me-methyl, Ph-phenyl, Fr-2-furyl, Th-2-thienyl, Py-pyridyl
Table 1
No. R
1 R
2 X Y Z
1 H Ph Me H Me
2 H 4-FPh Me H Me
3 H 4-OCH
3Ph Me H Me
4 H 4-ClPh Me H Me
5 H 2-ClPh Me H Me
6 H 3-ClPh Me H Me
7 H 2-FPh Me H Me
8 H 4-MePh Me H Me
9 H 2-NO
2Ph Me H Me
10 H 4-OHPh Me H Me
11 H 4-NMe
2Ph Me H Me
12 H 2-F，6-ClPh Me H Me
13 H 3-BrPh Me H Me
14 Me Ph Me H Me
15 H 4-NO
2Ph Me H Me
16 H 3-NO
2Ph Me H Me
17 H Fr Me H Me
18 H Th Me H Me
19 H 4-ClPh OCH
3 H OCH
3
20 H 4-NO
2Ph OCH
3 H OCH
3
21 H Ph CF
3 H CF
3
22 H 2-ClPh Cl H Cl
23 H 2-ClPh Me Cl Me
24 H 2-Py Me H Me
25 H 3-Py Me H Me
26 H 4-Py Me H Me
From following test as can be seen, formula of the present invention (I) compound has very strong specificity to Rhizoctonia solani Kuhn and kills activity.
Embodiment 8
Fungicidal activity test (isolated activity method)
The sterilising medium that 10ml is contained 50ppm soup to be measured is put into culture dish, and level leaves standstill, and is that the punch tool of 5mm is got the agar block that carries disease germs and put into culture dish with diameter then, and mycelia faces down; Put into 25 ± 2 ℃ growth cabinet, establish blank, check after 48～72 hours and calculate inhibiting rate by the bacterial plaque growing state.Table 2 is the measurement result of part (I) formula compound.
Table 2
No. the red asparagus of the withered apple wheel wheat of concentration (ppm) paddy rice line cotton is brown
The rot bacterium germ line germ mildew bacterial plaque germ that withers
1 50 60 15 0 8 2
2 50 80 0 0 8 2
3 50 96 35 0 19 24
4 50 90 35 0 14 2
5 50 90 0 0 3 2
6 50 95 35 0 19 0
7 50 95 25 0 0 2
8 50 98 25 0 3 0
9 50 97 10 0 0 0
10 50 97 25 0 0 0
11 50 93 25 0 19 0
12 50 90 25 0 0 0
13 50 98 30 0 3 11
14 50 95 50 0 19 16
15 50 95 50 0 19 11
16 50 98 50 0 19 0
20 50 93 48 0 20 13
21 50 96 52 0 22 15
22 50 90 43 0 17 16
When compound of the present invention uses as sterilant, can be with carrier or the mixing diluents that allows in compound of the present invention and other plant protection, whereby with the normally used various formulations of its furnishing, wait as pulvis, granule, aqueous emulsion and to use, also can mix and use or simultaneously and use with other sterilant.
Claims (11)
1, a compounds is characterized in that 1,2, the synthetic and fungicidal activity of 4-triazolo [1,5-a] pyrimidine-2-thioacetyl hydrazone compound.
2, compound according to claim 1, it is characterized in that having general formula (I) expression structure
In the formula: X, Y, Z represent hydrogen, alkyl, aryl, trifluoromethyl, alkoxyl group, aryloxy, halogen
R
1, R
2Expression hydrogen, alkyl, aryl, heterocyclic aryl
3, the preparation method of the compound by general formula (I) expression according to claim 2 is characterized in that making the represented compound of represented compound of general formula (II) and general formula (III) to react.
4, reaction according to claim 3, the amount proportioning that it is characterized in that the reactant species of triazolo pyrimidine-2-thioacetyl hydrazine and aldehydes or ketones is 1: 1～1.2, reaction solvent adopts organic solvents such as methyl alcohol, ethanol, in the presence of an acidic catalyst, temperature of reaction is 60～80 ℃, and the reaction times is 2～30 hours.
5, the preparation method of the triazolo pyrimidine-2-thioacetyl hydrazine with general formula (II) expression according to claim 3 is characterized in that making the represented compound of general formula (IV)
(R in the formula
3Expression CH
3, C
2H
5) react with hydrazine hydrate.
6, reaction according to claim 5, the amount proportioning that it is characterized in that the reactant species of triazolo pyrimidine-2-thioacetate and hydrazine hydrate is 1: 6～8, reaction solvent adopts organic solvents such as methyl alcohol, ethanol, and temperature of reaction is 60～80 ℃, and the reaction times is 4～6 hours.
7,, it is characterized in that making the logical represented compound of formula V according to the preparation method (method A) of the described compound of claim 5 (IV)
Compound with following general formula (VI) expression
(X, Z represent alkyl, aryl, trifluoromethyl in the formula, and Y represents hydrogen, alkyl, aryl, halogen) reacts.
8, reaction according to claim 7, it is characterized in that 5-amino-1,2,4-triazole-3-thioacetate (V) and 1, the amount proportioning of the reactant species of 3-diketone is 1: 1～1.2, and reaction solvent adopts glacial acetic acid, and piperidines is made catalyzer, temperature of reaction is 110～118 ℃, and the reaction times is 16～18 hours.
9,, it is characterized in that making the compound of represented compound of logical formula V and following general formula (VII) expression according to the preparation method (method B) of the described compound of claim 5 (IV)
(R represents CH in the formula
3, C
2H
5,, Y represents hydrogen, alkyl, aryl) react, obtain the compound of following general formula (VIII) expression
(R in the formula
3Identical with the definition in the general formula (IV), Y is identical with the definition in the general formula (VII)), this compound and POCl
3Reaction obtains compound (IX).Compound (IX) and sodium alkoxide or the reaction of phenol sodium, get final product the represented compound (wherein X, Z represent alkoxyl group, aryloxy) of general formula (IV)
10, reaction according to claim 9, it is characterized in that (1) 5-amino-1,2,4-triazole-3-thioacetate (V) is 1: 1～1.2 with the amount proportioning of the reactant species of diester malonate, reaction solvent adopts organic solvents such as dehydrated alcohol, methyl alcohol, first (second) sodium alkoxide is made catalyzer, and temperature of reaction is 60～80 ℃, and the reaction times is 48～60 hours; (2) 5,7-dihydroxyl-1,2, the amount proportioning of the reactant species of 4-triazolo [1,5-a] pyrimidine-2-thioacetate and phosphorus oxychloride is 1: 3～5, and reaction solvent adopts acetonitrile, and temperature of reaction is a room temperature, and the reaction times is 15～20 hours; (3) 5,7-two chloro-1,2,4-triazolo [1,5-a] pyrimidine-2-thioacetate is 1: 2.2～2.5 with the amount proportioning of the reactant species of alcohol (phenol) sodium, and reaction solvent adopts organic solvents such as methyl alcohol, ethanol, temperature of reaction is a room temperature, and the reaction times is 2～3 hours.
11,, it is characterized in that under the concentration of 50ppm～200ppm, Rhizoctonia solani Kuhn being had obvious specificity killing activity according to the fungicidal activity of the described compound of claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001146491A CN1137893C (en) | 2000-06-22 | 2000-06-22 | Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001146491A CN1137893C (en) | 2000-06-22 | 2000-06-22 | Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03142825 Division CN1219781C (en) | 2000-06-22 | 2000-06-22 | 2-alkoxycarbonylmethylthiotriazolopyrimidine compound and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1331080A true CN1331080A (en) | 2002-01-16 |
| CN1137893C CN1137893C (en) | 2004-02-11 |
Family
ID=4584298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB001146491A Expired - Fee Related CN1137893C (en) | 2000-06-22 | 2000-06-22 | Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1137893C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318429C (en) * | 2005-07-25 | 2007-05-30 | 华中师范大学 | Substitution thieno[3',2':5,6]-pyridino[4,3-d]-pyrimidine-4(3H)-ketone and preparation method |
| CN100500665C (en) * | 2006-11-30 | 2009-06-17 | 浙江工业大学 | Triazolo-pyrimido-thioacetamide compounds, preparation method and uses |
| CN103113316A (en) * | 2013-03-13 | 2013-05-22 | 湖南大学 | 2-[1-(1,2,4-triazole-1-yl)butyl-2-methylene aminooxy] acethydrazide as well as preparation method and application thereof |
-
2000
- 2000-06-22 CN CNB001146491A patent/CN1137893C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318429C (en) * | 2005-07-25 | 2007-05-30 | 华中师范大学 | Substitution thieno[3',2':5,6]-pyridino[4,3-d]-pyrimidine-4(3H)-ketone and preparation method |
| CN100500665C (en) * | 2006-11-30 | 2009-06-17 | 浙江工业大学 | Triazolo-pyrimido-thioacetamide compounds, preparation method and uses |
| CN103113316A (en) * | 2013-03-13 | 2013-05-22 | 湖南大学 | 2-[1-(1,2,4-triazole-1-yl)butyl-2-methylene aminooxy] acethydrazide as well as preparation method and application thereof |
| CN103113316B (en) * | 2013-03-13 | 2014-07-30 | 湖南大学 | 2-[1-(1,2,4-triazole-1-yl)butyl-2-methylene aminooxy] acethydrazide as well as preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1137893C (en) | 2004-02-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1073112C (en) | Possibly substituted 8-cyano-cyclopropyl-7-(2,8-diazabicyclo-[4,3,0]-nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolin carboxylic acids and their derivatives | |
| CN1257904C (en) | 5-halogen-6-phenyl-7-fluoroalkylamino-triazolopyrimidines as fungicides | |
| JPH11322721A (en) | Production of cyclic 4-oxamidine | |
| CN1137893C (en) | Syntehsis and activity of triazolo-pyrimido-thioacetyl hydrazone compounds | |
| CN1019911C (en) | Benzoxazine derivative and processes for preparing same | |
| CN1178942C (en) | Penicillin crystal and process for producing the same | |
| CN1091444C (en) | Heterocycle substituted isoxazoline compounds used as disinfectant | |
| CN1127505C (en) | Synthesis and activity of diheterocyclic compounds | |
| NZ208896A (en) | Benzazepine and benzoxazepine derivatives and pharmaceutical compositions | |
| CN1687061A (en) | Compound of isobioquin group and application thereof | |
| JP2005508954A5 (en) | ||
| CN1020905C (en) | Method for preparation of azolyl-derivatives having fungicidal activity | |
| CN1023560C (en) | Process for preparation of (-)-1 beta-ethyl-1 alpha-hydroxymethyl-1,2,3,4,6,7,12,12ba-octahydroindolo [2,3-a] quinolizine | |
| CN86103679A (en) | The preparation method of phenanthrene derivatives | |
| CN1680342A (en) | Diazosulfide derivative and its synthesis and screening method for inducing anti-disease activity | |
| JPH06340643A (en) | Oxazole or thiazole derivative, its production and herbicide | |
| MX2012004844A (en) | Process for the preparation of 5-(2-amino-pyrimidin-4-yl)-2-aryl- 1h-pyrrole-3-carboxamides. | |
| CN1401648A (en) | Heterocycle substd. condensed heterocyclic derivs. with bioactivity | |
| CN1062907A (en) | 2-(3-oxo pyridine base)-1,3-dioxolane and two hydride compounds, composition and control fungi method | |
| NZ206007A (en) | Benzotriazole derivatives and fungicidal compositions | |
| CN1077950A (en) | The nitrogenous 6 Yuans aromatic nucleus carboxylic acid amide derivatives of N-alkylsulfonyl and salt and noxious organism control agent | |
| CN1524859A (en) | Phenoxazones, preparing process and pharmaceutical uses thereof | |
| CN88101740A (en) | 4, 5-dihydro-1H-1, 2, 4-triazole-3-carboxamide derivatives and herbicidal compositions thereof | |
| EP0532126B1 (en) | Heterocyclic derivatives of alkoxyacrylates with fungicidal activity | |
| CN1814598A (en) | Valienamine A-4,7,4',7'-diacetal or ketone compound, and its preparation and use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |