WO2007137462A1 - Acryloylmorpholine, son procédé de préparation et son application - Google Patents

Acryloylmorpholine, son procédé de préparation et son application Download PDF

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Publication number
WO2007137462A1
WO2007137462A1 PCT/CN2006/003086 CN2006003086W WO2007137462A1 WO 2007137462 A1 WO2007137462 A1 WO 2007137462A1 CN 2006003086 W CN2006003086 W CN 2006003086W WO 2007137462 A1 WO2007137462 A1 WO 2007137462A1
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WO
WIPO (PCT)
Prior art keywords
tert
reaction
morpholine
chloro
acryloyl
Prior art date
Application number
PCT/CN2006/003086
Other languages
English (en)
Chinese (zh)
Inventor
Zhaohai Qin
Changwei Mu
Zefang Li
Nan Li
Bin Fu
Shusheng Zhang
Yumei Xiao
Original Assignee
China Agricultural University
Jiangsu Frey Agrochemicals Co., Ltd.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from CN 200610081550 external-priority patent/CN1939128A/zh
Application filed by China Agricultural University, Jiangsu Frey Agrochemicals Co., Ltd. filed Critical China Agricultural University
Publication of WO2007137462A1 publication Critical patent/WO2007137462A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/84—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,4

Definitions

  • the invention relates to an acryloylmorpholine and a preparation method and application thereof.
  • the acryloylmorpholine provided by the present invention which is named pyromorph, is (E) -4- [3-(2-chloropyridyl-4-yl) 3-(4-tert-butyl) of the formula (I) Phenyl) acryloyl]morpholine:
  • Another object of the present invention is to provide a process for preparing (E)-4-[3-(2-chloropyridin-4-yl)-3-
  • the method for preparing (E)-4-[3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine comprises the following steps -
  • the 2-chloroisonicotinyl chloride can be prepared according to a conventional method, such as 2-amino-4-methylpyridine by a Sandmeyer reaction to obtain 2-chloro-4-methylpyridine, which is oxidized to form 2-chloroisonicotinic acid, and then It is obtained by reaction with S0C1 2 .
  • the 2-chloroisonicotinyl chloride can also be prepared as follows: by N-oxidized isonicotinic acid, P0C1 3 and ? ⁇ 5 5 The halogenation reaction was carried out to obtain 2-chloroisonicotinyl chloride.
  • N-oxidized isonicotinic acid can be obtained by oxidation of isonicotinic acid via 0 2 according to a conventional method.
  • the 2-chloroisonicotinyl chloride can be purified by the following methods a) or b):
  • the molar ratio of the 2-chloroisonicotinoyl chloride, the catalyst and the t-butylbenzene may be 1: 1-4: 1-8; preferably 1: 1. 2-3: 1-4; preferably 1: 1 53: 2.
  • the reaction temperature of the Friedel-Crafts acylation reaction may be from -10 to 70 ° C, preferably 10 ° C.
  • the reaction time of the Friedel-Crafts acylation reaction may be 4 to 24 hours, preferably 10 hours.
  • the 2-chloro-4-(4-tert-butylbenzoyl)pyridine is purified by the following method: after the reaction, adding ice water, or ice water and hydrochloric acid, or ice water and sulfuric acid, and then extracting with an organic solvent
  • the aqueous phase, the organic solvent phase and the tert-butylbenzene phase are combined, the organic solvent and the tert-butylbenzene are removed, and the obtained residue is recrystallized from petroleum ether or 80% ethanol or ethyl acetate. That is, 2-chloro-4-(4-tert-butylbenzoyl)pyridine; the organic solvent is chloroform or carbon tetrachloride or chlorobenzene.
  • the 2-chloro-4-(4-tert-butylbenzoyl)pyridine and the diethoxyphosphinoacetylmorpholine are as follows
  • the Wittig- Horner reaction is carried out by reacting 2-chloro-4-(4-tert-butylbenzoyl)pyridine, dimethoxyphosphinoacetylmorpholine, an organic solvent and a catalyst to obtain (E)- 4- [ 3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine;
  • the organic solvent is tetrahydrofuran, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, 1, 4-dioxane, etc.; the catalyst is NaH, sodium ethoxide, potassium t-butoxide, NaOH, K0H and so on.
  • the Wittig-Horner reaction temperature may be from 0 to 40 ° C, preferably from 10 to 15 ° C.
  • the reaction time of the Wittig- Horner reaction may be from 3 to 15 hours, preferably from 6 to 8 hours.
  • the (E)-4-[3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine was purified by the following method: After the reaction was completed, the The organic solvent is recrystallized from absolute ethanol, ethyl acetate or acetone to give (E)-4 [3-(2-chloropyridin-4-yl)-3-(4-tert. Butylphenyl) acryloyl]morpholine.
  • diethoxyphosphinoacetylmorpholine can be obtained commercially, or can be substituted by chloroacetylmorpholine and triethyl phosphite to obtain diethoxyphosphinoacetylmorpholine.
  • chloroacetylmorpholine can also be obtained commercially, or can be prepared by using morpholine as a raw material, for example, morpholine and chloroacetyl chloride are substituted to obtain chloroacetylmorpholine.
  • the botanical bactericide provided by the present invention is composed of an active ingredient and an auxiliary material, wherein the active ingredient is the (E)-4-[3-(2-chloropyridin-4-yl)-3-(4-tert. Butylphenyl) acryloyl]morpholine.
  • the bactericidal agent may be in the form of a powder, a micropowder, a wettable powder, an emulsifiable concentrate, a suspending agent, a liquid or an aerosol.
  • the bactericides of these dosage forms can be prepared according to conventional methods.
  • the adjuvant may be surfactant No. 0203, sodium lignosulfonate, xanthan gum, bentonite, paraformaldehyde and water; the (E) -4- [3 - (2-Chloropyridine-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine with surfactant, sodium lignosulfonate, xanthan gum, bentonite, paraformaldehyde and water
  • the mass ratio may be 20: 1-5: 1-5: 0.05 - 0.5: 1-5: 0.1 - 0.6: 60-75; preferably 20: 2-4: 2 - 4: 0.1 - 0.2: 2 - 4 : 0.2-0.4: 68-72; most preferably 20: 3: 3: 0.15: 3: 0.3: 70.55.
  • Example 1 provides a method for preparing (E)-4-[3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine, which The method is obtained by a series of reactions such as oxidation, halogenation, Friedel-Craft acylation and Wittig- Horner, starting from isonicotinic acid.
  • This embodiment provides a method for preparing (E)-4-[3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine, which is Using isonicotinic acid as a starting material, it is obtained by a series of reactions such as oxidation, halogenation, Friedel-Craft acylation and Wittig-Horner.
  • the synthetic route is as follows -
  • the acid chloride (5.63 mol) was further reacted at 10 ° C for 10 h after the addition, and then the reaction solution was poured into a solution consisting of 2 L of concentrated hydrochloric acid and 10 L of ice water, thoroughly stirred, and the aqueous phase was extracted with chloroform.
  • the chloroform phase and the tert-butylbenzene phase are combined, washed with water, dried, and the solvent is evaporated, and the residue is crystallized from petroleum ether to give 1103 g of white solid as 2-chloro-4-(4-tert-butylbenzoyl) Pyridine, which has the structural formula of Formula 2 in the above synthetic route.
  • the precipitate was removed by filtration, and the filtrate was washed with toluene, and the filtrate was evaporated to dryness and then evaporated. 148-154 ° C / 10 mmHg fraction, the fraction is chloroacetylmorpholine. The fraction had a mass of 85 g and a yield of 87%.
  • Activity assays were performed using the growth rate method. 2. 4 mL of a concentration of 5000 g/mL of reagent (indoor activity assay) was mixed with 117. 6 mL of melted PDA medium to prepare a concentration of 100 ⁇ /mL of toxic medium (120 mL). Using a doubling dilution method, 60 mL of the toxic medium was placed into 4 petri dishes of 9 cm in diameter, 15 mL/dish, to prepare a toxic PDA plate.
  • Dimethomorph, chlorothalonil and carbendazim were used as control agents, and a blank control was set up, 4 times.
  • the cultured bacteria After the toxic medium was condensed, the cultured bacteria with a diameter of 0.5 cm. Store in a 25 ° C incubator. After the colonies in the blank control were sufficiently grown, the diameters of the colonies of each treatment were measured by the cross method, and the average value was taken.
  • Inhibition rate average diameter of blank control colonies - average diameter of treated colonies / average diameter of blank control colonies * 100%.
  • Test agent 20% pyromoline suspension.
  • the treatment agents and water were sprayed in the early stage of late growth stage of tomato growth or the initial stage of downy mildew in the middle of cucumber growth, and the disease was investigated 10 days after spraying. According to the 0, 1, 3, 5, 7, and 9 methods, the number of diseased leaves was counted, and the diseased leaf rate, disease index, and control effect were calculated. The control effect was statistically analyzed using a new re-level difference test.
  • Level 1 The area of the lesions accounts for less than 5% of the entire leaf area
  • Level 3 The area of the lesions accounts for 6%-10% of the total leaf area ;
  • Level 5 The area of the lesions accounts for 11% - 20% of the total leaf area
  • Level 7 The area of the lesions accounts for 21% - 50% of the total leaf area
  • Grade 9 The area of the lesions accounts for more than 50% of the total leaf area
  • Treatment dosage (AI, re-investigation of leaf disease disease rate control effect average prevention 5% difference g/667m 2 ) total number of leaves (%) index (%) effect (%) significant number
  • Treatment dose investigation leaf disease number disease leaf rate condition refers to prevention effect average prevention 5% difference (AI, total number of pieces (%) number (%) effect (%) heterogeneous g/667m 2 )
  • the pepper blight test consists of 6 treatments: the effective dose is 15g pyroline/mu; the effective dose is 20g pyroline/mu; the effective dose is 25g pyroline/mu; the effective dose is 30g pyrmorphine/mu; effective dose It is 35g pyromorpholine/mu; 50% Anke wettable powder (effective dose 20g/mu) is used as a control; at the same time, clear water control (blank control, only spray water). Four repetitions, each processing is randomly arranged.
  • the pepper blight test was carried out by spraying each treatment agent and clear water in the initial stage of pepper growth, and the disease was investigated 14 days, 21 days, 28 days and 35 days after the spraying, and the drug efficacy was statistically analyzed.
  • Table 2 - Table 4 shows that pyromorph ((E)-4-[3-(2-chloropyridin-4-yl) 3-(4-t-butylphenyl)acryloyl]morpholine) is in 15-30 g
  • the effective dose of pyroline/mu has excellent control effect on crop diseases such as tomato late blight, cucumber downy mildew and Phytophthora capsici.
  • the present invention expands the bactericidal spectrum by introducing a pyridine ring into the parent structure (acryloyl morpholine), and also enhances the inhibitory activity against spore germination.
  • (E) -4- [3-(2-chloropyridin-4-yl)-3-(4-tert-butylphenyl)acryloyl]morpholine of the invention against tomato late blight, cucumber downy mildew, standing Plant pathogens such as blight and pepper blight have excellent control effects.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne une acryloylmorpholine, son procédé d'application et son application. Cette acryloylmorpholine est de la (E)-4-[3(2-chloropyridin-4-yl)-3-(4-t-butylphényl)acryloyl]morpholine. Son procédé de préparation consiste 1) à faire réagir du chlorure de 2-chloro-isonicotinoyle et du t-butyle benzène par acylation de Friedel-Crafts afin d'obtenir de la 2-chloro-4-(4-t-butylbenzoyl)pyridine, puis 2) à faire réagir la 2-chloro-4-(4-t-butylbenzoyl)pyridine et de la diméthoxyphosphine acétomorpholine par réaction de Wittig-Horner afin d'obtenir de la (E)-4-[3(2-chloropyridin-4-yl)-3-(4-t-butylphényl)acryloyl]morpholine. L'acryloylmorpholine a un effet préventif efficace contre les champignons tels que Phytophthora infestans (Mont.) de Bary, Pseudoperonospora cubensis (Berk. et Curt.) Rostov, Phytophthora capsici Leonian et analogue, lorsqu'elle est utilisée en doses de 15-30 g/mu.
PCT/CN2006/003086 2006-05-26 2006-11-16 Acryloylmorpholine, son procédé de préparation et son application WO2007137462A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN200610081550.6 2006-05-26
CN 200610081550 CN1939128A (zh) 2005-09-27 2006-05-26 吡吗啉(Pyrimorph)——一种新的农用杀菌剂

Publications (1)

Publication Number Publication Date
WO2007137462A1 true WO2007137462A1 (fr) 2007-12-06

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114560830A (zh) * 2022-03-01 2022-05-31 徐韶康 一种立体异构体的烯酰吗啉的制备方法及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954497A (en) * 1988-02-22 1990-09-04 Takeda Chemical Industries, Ltd. Acrylic acid morpholides and fungicidal compositions
CN1566095A (zh) * 2003-07-01 2005-01-19 中国农业大学 4－[3－(吡啶－4－基)－3－取代苯基丙烯酰]吗啉——一类新型杀菌剂

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954497A (en) * 1988-02-22 1990-09-04 Takeda Chemical Industries, Ltd. Acrylic acid morpholides and fungicidal compositions
CN1566095A (zh) * 2003-07-01 2005-01-19 中国农业大学 4－[3－(吡啶－4－基)－3－取代苯基丙烯酰]吗啉——一类新型杀菌剂

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114560830A (zh) * 2022-03-01 2022-05-31 徐韶康 一种立体异构体的烯酰吗啉的制备方法及其应用

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