CN104478810A - Synthetic method for 3,6-dihydroxypyridazine - Google Patents
Synthetic method for 3,6-dihydroxypyridazine Download PDFInfo
- Publication number
- CN104478810A CN104478810A CN201410615303.4A CN201410615303A CN104478810A CN 104478810 A CN104478810 A CN 104478810A CN 201410615303 A CN201410615303 A CN 201410615303A CN 104478810 A CN104478810 A CN 104478810A
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- Prior art keywords
- synthetic method
- maleic anhydride
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- dihydroxy
- reaction
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D237/14—Oxygen atoms
- C07D237/16—Two oxygen atoms
Abstract
A related synthetic method for 3,6-dihydroxypyridazine comprises the following steps: taking maleic anhydride and hydrazine hydrate as raw materials, controlling the molar ratio of maleic anhydride to hydrazine hydrate to be 1:0.5-3, reacting in a proper solvent at 0-150 DEG C for 1-28 h, and purifying to obtain a pure product 3,6-dihydroxypyridazine. The feeding amount of the reactants and the solvent is controlled to enable the weight ratio of maleic anhydride to the solvent to be 1:1-10. The reaction raw materials are easily obtained, the price is reasonable, the reaction conditions are mild, the synthetic method is easy to operate and easy to control, post-treatment is simple, and the product is stable in quality and high in purity.
Description
(1) technical field
The present invention relates to a kind of pyridazine derivatives, be specifically related to a kind of synthetic method of 3,6-dihydroxy pyridazine.
(2) background technology
3,6-dihydroxy pyridazine, proterties: white crystals, decomposition temperature (DEG C): 260, fusing point (DEG C): 296 ~ 298, density (g/mL, 25 DEG C): 1.60, solvability: when 25 DEG C, solubleness is about 0.6% in water, solubleness is 0.1% in ethanol, is 2.4% in dimethyl formamide.Its sodium, potassium and ammonium salt and organic phosphate soluble in water.Be heated to 260 DEG C start to decompose.Be dissolved in hot water, be slightly dissolved in hot ethanol.
Toxicology data: rat acute LD50 of passing through mouth 1400mg/kg, its sodium salt is 6950mg/kg, and the liquor-saturated amine salt of diethyl is 2340mg/kg, has no stimulation.Feed rat with the word material containing 5% former medicine and do not occur toxicity symptom in 2 years, have no teratogenesis, carcinogenic, mutagenicity.To fish low toxicity, be jealous of fish LC5075mg/L.Nontoxic to honeybee.
A kind of material excitatory of 3,6-dihydroxy pyridazine.Hormesis is had to eyes, respiratory tract and skin.Dress suitable protective clothing, gloves use safety glasses or face shield.
Purposes:
1. be agriculturally selective herbicide and temporary plant growth inhibitor.Medicament enters plant by blade face stratum corneum, reduces photosynthesis; Osmotic pressure and Evaporation, can suppress the growth of bud consumingly.For preventing potato; Onion; Garlic and radish storage period germinate, and have the effect suppressing crop life and prolongation to be bloomed, and also can be used for bare place weeding.The tautomerism of these product is 3,6-dihydroxy pyridazine (3,6-Dihydroxypyridazine).It is the intermediate of sulfa drugs sulfamethoxypyridazine.
2. plant-growth regulator.Sucked by blade face or root, conducted by xylem and phloem, T suppression cell divides and suppresses plant-growth.0.1% ~ 0.05% liquid can prevent and kill off dogstail and lawn, orchard and waterside weeds; 0.025% liquid suppresses onion and potato to germinate storage period; 0.1% ~ 0.05% liquid suppresses and delays tobacco side blastogenesis length and keep oranges and tangerines seedling from frostbite.
Synthetic method:
Reacted by MALEIC ANHYDRIDE and hydrazine hydrate and obtained.In reactor, drop into water and 40% hydrazine hydrate, stir lower dropping 30% hydrochloric acid of cooling, temperature controls below 20 DEG C, be 6.2-6.4 to pH value, drop into MALEIC ANHYDRIDE, be slowly warming up to 106-110 DEG C, backflow 2h, be cooled to 5 DEG C, rejection filter, filter cake frozen water is washed till pH 4.8-5.1, dry, obtain maleic hydrazide, yield 97%.
(3) summary of the invention
The present invention needs the problem solved to be for prior art, and provide a kind of technique advantages of simple, cost low, product purity is high, is suitable for the synthetic method of industrialized 3,6-dihydroxy pyridazines.
The present invention is achieved through the following technical solutions:
A kind of synthetic method of 3,6-dihydroxy pyridazine, its special character is: comprise the following steps:
With MALEIC ANHYDRIDE and hydrazine hydrate for raw material, the ratio of the two amount of substance is 1:0.5-3, in suitable solvent, in 0-150 DEG C of reaction 1-28 hour, sterling 3 is obtained after purifying, 6-dihydroxy pyridazine, the charging capacity of reactant and solvent is MALEIC ANHYDRIDE: solvent=1:1-10, is more than weight ratio.
In the synthetic method of 3,6-dihydroxy pyridazines of the present invention, described solvent is one or both in chloroform, ethanol, ethyl acetate, DMF, first alcohol and water.
The synthetic method of 3,6-dihydroxy pyridazines of the present invention, in described step, purification step is evaporation concentration, recrystallization, and silica gel column chromatography is separated.
Beneficial effect of the present invention: reaction raw materials compares and is easy to get, reasonable price, reaction conditions is gentle, easy handling, is easy to control, and aftertreatment is simple, and constant product quality, purity is high.
(4) embodiment
Embodiment 1:
MALEIC ANHYDRIDE (1.96g, 20mmol) is added, hydrazine hydrate (2.0g, 40mmol), ethanol 15ml in 100mL single necked round bottom flask.Mixture in reaction flask stirring reaction 6 hours at 70 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 87.92%, purity 98.94% (GC), fusing point 298.6 DEG C-299.8 DEG C (299 DEG C-300 DEG C, document).Nuclear magnetic resonance spectroscopy: 1H NMR (deuterated DMSO): 6.935 ppm (s, 1H), 3.548 ppm (s, 1H).
Embodiment 2:
MALEIC ANHYDRIDE (1.96g, 20mmol) is added, hydrazine hydrate (2.0g, 40mmol), methyl alcohol 10ml in 100mL single necked round bottom flask.Mixture in reaction flask stirring reaction 6 hours at 70 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 92.30%, purity 99.01% (GC), fusing point 298.6 DEG C-299.8 DEG C (299 DEG C-300 DEG C, document).
Embodiment 3:
MALEIC ANHYDRIDE (19.6g, 200mmol) is added, hydrazine hydrate (18g, 360mmol), ethyl acetate 120ml in 500mL single necked round bottom flask.Mixture in reaction flask stirring reaction 5 hours at 80 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 89.45%.
Embodiment 4:
MALEIC ANHYDRIDE (19.6g, 200mmol) is added, hydrazine hydrate (18g, 360mmol), ethyl acetate 100ml in 500mL single necked round bottom flask.Mixture in reaction flask stirring reaction 6 hours at 70 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 91.12%.
Embodiment 5:
In 1000mL single necked round bottom flask, add MALEIC ANHYDRIDE (58.80g, 600mmol), hydrazine hydrate (54g, 1080mmol), second alcohol and water is 300ml, wherein ethanol 100ml altogether.Mixture in reaction flask stirring reaction 4 hours at 80 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 86.70%.
Embodiment 6:
MALEIC ANHYDRIDE (19.6g, 200mmol) is added, hydrazine hydrate (5g, 100mmol), DMF 100ml in 500mL single necked round bottom flask.Mixture in reaction flask stirring reaction 28 hours at 0 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 82.35%.
Embodiment 7:
MALEIC ANHYDRIDE (19.6g, 200mmol) is added, hydrazine hydrate (30g, 600mmol), DMF 195ml in 500mL single necked round bottom flask.Mixture in reaction flask stirring reaction 1 hour at 150 DEG C.TLC and GC determines that reaction completes.After reaction terminates, revolve and steam except desolventizing, obtain thick product, be separated with silica gel column chromatography and obtain straight product 3,6-dihydroxy pyridazine, after drying, calculated yield 95.63%.
Claims (3)
1. the synthetic method of a dihydroxy pyridazine, is characterized in that: comprise the following steps:
With MALEIC ANHYDRIDE and hydrazine hydrate for raw material, the ratio of the two amount of substance is 1:0.5-3, in suitable solvent, in 0-150 DEG C of reaction 1-28 hour, sterling 3 is obtained after purifying, 6-dihydroxy pyridazine, the charging capacity of reactant and solvent is MALEIC ANHYDRIDE: solvent=1:1-10, is more than weight ratio.
2. the synthetic method of 3,6-dihydroxy pyridazines according to claim 1, is characterized in that: described solvent is one or both in chloroform, ethanol, ethyl acetate, DMF, first alcohol and water.
3. the synthetic method of 3,6-dihydroxy pyridazines according to claim 1 and 2, is characterized in that: in described step, purification step is evaporation concentration, recrystallization, and silica gel column chromatography is separated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410615303.4A CN104478810A (en) | 2014-11-05 | 2014-11-05 | Synthetic method for 3,6-dihydroxypyridazine |
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| CN201410615303.4A CN104478810A (en) | 2014-11-05 | 2014-11-05 | Synthetic method for 3,6-dihydroxypyridazine |
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| CN104478810A true CN104478810A (en) | 2015-04-01 |
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| CN201410615303.4A Pending CN104478810A (en) | 2014-11-05 | 2014-11-05 | Synthetic method for 3,6-dihydroxypyridazine |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105924401A (en) * | 2016-05-08 | 2016-09-07 | 邯郸市赵都精细化工有限公司 | Maleic hydrazide synthetic process |
| CN105949132A (en) * | 2016-05-08 | 2016-09-21 | 邯郸市赵都精细化工有限公司 | Making method of maleic hydrazide |
| CN111285811A (en) * | 2020-02-14 | 2020-06-16 | 邯郸市赵都精细化工有限公司 | Preparation method of 3, 6-dihydroxypyridazine |
| CN113698355A (en) * | 2021-08-30 | 2021-11-26 | 郑州华赞医药科技有限公司 | Synthesis method of 4, 5-dihydroxypyridazine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735154A (en) * | 2008-11-10 | 2010-06-16 | 亚邦化工集团有限公司 | Method for preparing maleichydrazide |
| CN102108063A (en) * | 2011-04-01 | 2011-06-29 | 连云港市金囤农化有限公司 | Method for preparing maleic hydrazide |
-
2014
- 2014-11-05 CN CN201410615303.4A patent/CN104478810A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101735154A (en) * | 2008-11-10 | 2010-06-16 | 亚邦化工集团有限公司 | Method for preparing maleichydrazide |
| CN102108063A (en) * | 2011-04-01 | 2011-06-29 | 连云港市金囤农化有限公司 | Method for preparing maleic hydrazide |
Non-Patent Citations (1)
| Title |
|---|
| 陈春光 等: "咪唑并［1，2-b］哒嗪的合成", 《精细化工》, vol. 29, no. 8, 31 August 2012 (2012-08-31), pages 783 - 786 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105924401A (en) * | 2016-05-08 | 2016-09-07 | 邯郸市赵都精细化工有限公司 | Maleic hydrazide synthetic process |
| CN105949132A (en) * | 2016-05-08 | 2016-09-21 | 邯郸市赵都精细化工有限公司 | Making method of maleic hydrazide |
| CN111285811A (en) * | 2020-02-14 | 2020-06-16 | 邯郸市赵都精细化工有限公司 | Preparation method of 3, 6-dihydroxypyridazine |
| CN113698355A (en) * | 2021-08-30 | 2021-11-26 | 郑州华赞医药科技有限公司 | Synthesis method of 4, 5-dihydroxypyridazine |
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