CN104277000A - Abscisic acid receptor stimulant raw drug and preparation method thereof - Google Patents
Abscisic acid receptor stimulant raw drug and preparation method thereof Download PDFInfo
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- CN104277000A CN104277000A CN201410587596.XA CN201410587596A CN104277000A CN 104277000 A CN104277000 A CN 104277000A CN 201410587596 A CN201410587596 A CN 201410587596A CN 104277000 A CN104277000 A CN 104277000A
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- quinolinone
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- propyl group
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- TZOYXRMEFDYWDQ-UHFFFAOYSA-N O=C1Nc2ccccc2CC1 Chemical compound O=C1Nc2ccccc2CC1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 2
- WUMCZVXYJVHZQR-UHFFFAOYSA-N CCCN(C(CCc1c2)=O)c1ccc2N Chemical compound CCCN(C(CCc1c2)=O)c1ccc2N WUMCZVXYJVHZQR-UHFFFAOYSA-N 0.000 description 1
- OINPVHCXKBNQGI-UHFFFAOYSA-N CCCN(C(CCc1c2)=O)c1ccc2[N+]([O-])=O Chemical compound CCCN(C(CCc1c2)=O)c1ccc2[N+]([O-])=O OINPVHCXKBNQGI-UHFFFAOYSA-N 0.000 description 1
- VZBLACDJDBVCAB-UHFFFAOYSA-N CCCN1c2ccccc2CCC1=O Chemical compound CCCN1c2ccccc2CCC1=O VZBLACDJDBVCAB-UHFFFAOYSA-N 0.000 description 1
- FRENKHPDAXPFFW-UHFFFAOYSA-N Cc1cc(N(CC=C)C(CC2)=O)c2cc1 Chemical compound Cc1cc(N(CC=C)C(CC2)=O)c2cc1 FRENKHPDAXPFFW-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/30—Isothioureas
- C07C335/32—Isothioureas having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an abscisic acid receptor stimulant raw drug and a preparation method thereof. The preparation method of the abscisic acid receptor stimulant raw drug comprises the following steps: adding quinolinone and halogenated propane into N, N-dimethyl formamide, and performing alkylation reaction to generate N-propyl quinolinone by taking sodium hydride as a catalyst; adding N-propyl quinolinone into dichloromethane, then, adding fuming nitric acid, and performing nitratlon reaction to generate 7-nitryl-propyl quinolinone; adding 7-nitryl-N-propyl quinolinone into an organic solvent ethanol, then, adding hydrochloric acid and iron powder, and performing hydrogenation reduction reaction to generate 7-amino-N-propyl quinolinone; adding 7-amino-N-propyl quinolinone into an organic solvent acetonitrile, then, adding 4-methyl benzylsulfonyl chloride, performing condensation reaction to generate N-(2-carbonyl-1-propyl-1,2,3,4-4H-quinolinone-6-)-4-p-methyl sulfamide, namely a abscisic acid receptor stimulant by taking N, N-diisopropylethylamine as a catalyst. The method has a relatively high yield; the prepared abscisic acid receptor stimulant raw drug is free of an optical isomer, easy to purify and relatively low in cost.
Description
Technical field
The present invention relates to plant-growth regulator field, specifically former medicine of a kind of ABA Receptor agonist and preparation method thereof.
Background technology
China's drought becomes more general and serious in recent years, except the long-term lack of water in northwest, North China drought frequently except, also improve a lot to weighing non-irrigated frequency in the Yangtze valley, Huanghuai Area locally occur, cause the crop significantly underproduction, even face total crop failure, arid becomes the primary environment factor of restriction crop production day by day.
Though traditional Drought-resistant Breeding achieves some achievements, be limited in target species and lack suitable heritable variation, so selection cross crop drought resistance kind is made slow progress always.In addition, because the drought resistance mechanism of plant is more complicated, relate to polygenic coordinated regulation, the security of genetically modified food there is no final conclusion in addition, so also there is larger difficulty and obstruction by genetic engineering modified raising crop drought resistance.Large quantity research shows that dormin improves crop to the adaptive faculty of arid and survival rate by reducing the approach such as transpiration rate, raising osmotic adjustment ability, enhancing antioxidant system vigor.The resistance that dormin is being applied to enhancing crop holds out broad prospects, and can produce huge economic benefit and social benefit.But the PBI 58 optical configuration be present in plant materials is only +/-cis and trans-ABA, traditional chemical synthesis production cost is higher, due to the difference in the price of costliness and activity, dormin is not widely used in agriculture production always, and various countries scientist is in the method finding the production of S-ABA cheapness.
Summary of the invention
The object of the present invention is to provide a kind of Crop preparation method that is good, the former medicine of ABA Receptor agonist safely and efficiently, to solve the problem proposed in above-mentioned background technology.
For achieving the above object, the invention provides following technical scheme:
The former medicine of a kind of ABA Receptor agonist, comprise according to the raw material of molfraction: quinolinone 1-2 part, sodium hydride 4.5-5.5 part, halogenopropane 5-10 part, nitrosonitric acid 40-50 part, hydrochloric acid 1.5-5.5 part, iron powder 4.5-5.5 part, 4-methyl benzyl SULPHURYL CHLORIDE 1-2 part, DIPEA 1.4-1.6 part.
As the further scheme of the present invention: the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE comprises the steps:
(1) get a certain amount of
join in acetonitrile, then slowly add thiocarbamide and acid binding agent salt of wormwood;
(2) reflux in ethanol 3.5-4.5h, filters, and concentratedly obtains intermediate product
; Reaction equation is:
；
(3) by intermediate product
join in acetonitrile, then add sodium perchlorate and concentrated hydrochloric acid or pass into chlorine, vigorous stirring, concentrate after making reaction carry out 6-8h, then with sherwood oil and salt solution extraction, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
。
Comprise according to the raw material of molfraction in the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE:
1-2 part, thiocarbamide 1.2-1.5 part, acid binding agent salt of wormwood 1.2-1.8 part, sodium perchlorate 5-6 part, concentrated hydrochloric acid 6-15 part.
As the further scheme of the present invention: the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE comprises the steps:
(1) get a certain amount of
join in acetonitrile, then slowly add thioacetic acid potassium and acid binding agent salt of wormwood;
(2) at room temperature stir 0.8-1.2h, filter, carry out after washing two times with saturated common salt concentrated obtaining intermediate product
; Reaction equation is:
；
(3) by intermediate product
join in acetonitrile, then under air-proof condition, slowly pass into dry chlorine gas, make chlorine can recycle simultaneously, ventilation 4-6h, concentrates after stopped reaction, then extracts with sherwood oil and salt solution, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
。
Comprise according to the raw material of molfraction in the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE:
1-2 part, thioacetic acid potassium 1.5-3.2 part, acid binding agent salt of wormwood 1.5-3.2 part.
As the further scheme of the present invention: the preparation method of the former medicine of described ABA Receptor agonist, comprises the steps:
(1) raw material is taken: take each raw material according to molfraction;
(2) prepare N-propyl group quinolinone: A, add in organic solvent DMF by quinolinone, at-6--4 DEG C, stir 0.5-1h; B, under argon shield environment, add sodium hydride as catalyzer in batches, add rear stirring 0.5-1h; C, in solution, instill iodopropane, at room temperature react 11-13h; D, adding water makes reaction cancellation and is extracted with ethyl acetate reaction product three times, extracts the organic layer obtained be merged together each time, with saturated sodium-chloride water solution, the organic layer after merging is washed one time, then carries out drying by anhydrous sodium sulphate; E, utilize chromatography column to carry out chromatographic separation reaction product, obtain alkylation reaction product N-propyl group quinolinone; Reaction equation is:
；
(3) prepare 7-nitro-N-propyl group quinolinone: A, join in organic solvent dichloromethane by N-propyl group quinolinone, at-6--4 DEG C, stir 0.5-1h; B, slowly nitrosonitric acid is instilled in solution with dropping funnel, at-1-1 DEG C, react 2-3h; C, adding water makes reaction cancellation and by dichloromethane extraction reaction product three times, is merged together by the organic layer that each extraction obtains, washes one time respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution; D, utilize chromatography column to carry out chromatographic separation reaction product, obtain nitration reaction product 7-nitro-N-propyl group quinolinone; Reaction equation is:
；
(4) prepare 7-amino-N-propyl group quinolinone: A, to be joined in organic solvent ethanol by 7-nitro-N-propyl group quinolinone, then add the hydrochloric acid of iron powder and 6mol/L, be heated to 65-70 DEG C, backflow 3-4h, after reactant cooling, be spin-dried for solvent; B, add in above-mentioned solution 10% aqueous sodium hydroxide solution and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained to be merged together, wash one time with saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for; C, utilize chromatography column to carry out chromatographic separation reaction product, obtain hydro-reduction reaction product 7-amino-N-propyl group quinolinone; Reaction equation is:
；
(5) prepare ABA Receptor agonist: A, 7-amino-N-propyl group quinolinone and 4-methyl benzyl SULPHURYL CHLORIDE to be added in organic solvent acetonitrile, then add DIPEA as catalyzer, keep stirring at room temperature 5.5-7.5h; B, be spin-dried for solvent, add water and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained and be merged together, wash one time with saturated sodium-chloride water solution, then carry out drying by anhydrous sodium sulphate; C, utilize chromatography column to carry out chromatographic separation reaction product, obtain through condensation reaction products N-(2-carbonyl-1-propyl group-1,2,3,4-4H-quinolinone-6-)-4-to methylsulfonamides, i.e. ABA Receptor agonist; Reaction equation is:
。
As the further scheme of the present invention: described chromatography column comprises sherwood oil and ethyl acetate.
As the further scheme of the present invention: the weight ratio of described step (2) and step (3) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 10:1.
As the further scheme of the present invention: the weight ratio of described step (4) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 3:1.
As the present invention's further scheme: the weight ratio of described step (5) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 5:1.
Compared with prior art, the invention has the beneficial effects as follows:
ABA Receptor agonist prepared by the present invention is a kind of micromolecular compound with dormin activity, spray and can significantly improve the adaptive faculty of plant to drought environment after plant, ABA Receptor agonist structure simply and there is not optically active isomer, be easy to synthetic and purifying, cost is lower, the aminoacid sequence of its acceptor is very conservative in higher plant, and therefore ABA Receptor agonist transforms without the need to carrying out the farm crop that namely can be applicable to multiple types.
The former medical instrument of ABA Receptor agonist have active high, Crop is good, safe and efficient, the adaptive faculty of crop to arid can be significantly improved, and by cleaning and chromatographic separation the reaction product of each step gained in the present invention, then as the raw material of next step reaction, improve purity and the yield of product; On the other hand, the use of catalyzer facilitates the generation of target product, decreases by product, also improves purity and the yield of product.
Embodiment
Be described in more detail below in conjunction with the technical scheme of embodiment to this patent.
Embodiment 1
The former medicine of a kind of ABA Receptor agonist, comprises according to the raw material of molfraction: quinolinone 1 part, sodium hydride 4.5 parts, iodopropane 5 parts, nitrosonitric acid 40 parts, hydrochloric acid 1.5 parts, iron powder 4.5 parts,
1-2 part, thiocarbamide 1.2 parts, 1.2 parts, acid binding agent salt of wormwood, sodium perchlorate 5 parts, concentrated hydrochloric acid 6 parts, DIPEA 1.4 parts.
The preparation method of the former medicine of described ABA Receptor agonist, comprises the steps:
(1) raw material is taken: take each raw material according to molfraction;
(2) prepare N-propyl group quinolinone: A, add in organic solvent DMF by quinolinone, at-6 DEG C, stir 0.5h; B, under argon shield environment, add sodium hydride as catalyzer in batches, add rear stirring 0.5h; C, in solution, instill halogenopropane, at room temperature react 11h; D, adding water makes reaction cancellation and is extracted with ethyl acetate reaction product three times, extracts the organic layer obtained be merged together each time, with saturated sodium-chloride water solution, the organic layer after merging is washed one time, then carries out drying by anhydrous sodium sulphate; E, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain alkylation reaction product N-propyl group quinolinone; Reaction equation is:
；
(3) prepare 7-nitro-N-propyl group quinolinone: A, join in organic solvent dichloromethane by N-propyl group quinolinone, at-6 DEG C, stir 0.5-1h; B, slowly nitrosonitric acid is instilled in solution with dropping funnel, at-1 DEG C, react 2h; C, adding water makes reaction cancellation and by dichloromethane extraction reaction product three times, is merged together by the organic layer that each extraction obtains, washes one time respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution; D, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain nitration reaction product 7-nitro-N-propyl group quinolinone; Reaction equation is:
；
(4) prepare 7-amino-N-propyl group quinolinone: A, to be joined in organic solvent ethanol by 7-nitro-N-propyl group quinolinone, then add the hydrochloric acid of iron powder and 6mol/L, be heated to 65 DEG C, backflow 3h, after reactant cooling, be spin-dried for solvent; B, add in above-mentioned solution 10% aqueous sodium hydroxide solution and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained to be merged together, wash one time with saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 3:1 reaction product carry out chromatographic separation, obtain hydro-reduction reaction product 7-amino-N-propyl group quinolinone; Reaction equation is:
；
(5) 4-methyl benzyl SULPHURYL CHLORIDE is prepared: get a certain amount of
join in acetonitrile, then slowly add thiocarbamide and acid binding agent salt of wormwood;
Reflux in ethanol 3.5h, filters, and concentratedly obtains intermediate product
; Reaction equation is:
；
(3) by intermediate product
join in acetonitrile, then add sodium perchlorate and concentrated hydrochloric acid or pass into chlorine, vigorous stirring, concentrate after making reaction carry out 6h, then with sherwood oil and salt solution extraction, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
。
(6) prepare ABA Receptor agonist: A, 7-amino-N-propyl group quinolinone and 4-methyl benzyl SULPHURYL CHLORIDE to be added in organic solvent acetonitrile, then add DIPEA as catalyzer, keep stirring at room temperature 5.5h; B, be spin-dried for solvent, add water and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained and be merged together, wash one time with saturated sodium-chloride water solution, then carry out drying by anhydrous sodium sulphate; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 5:1 reaction product carry out chromatographic separation, obtain through condensation reaction products N-(2-carbonyl-1-propyl group-1,2,3,4-4H-quinolinone-6-)-4-to methylsulfonamides, i.e. ABA Receptor agonist; Reaction equation is:
。
Embodiment 2
The former medicine of a kind of ABA Receptor agonist, comprises according to the raw material of molfraction: quinolinone 1.5 parts, sodium hydride 5 parts, iodopropane 7 parts, nitrosonitric acid 45 parts, hydrochloric acid 3 parts, iron powder 5 parts,
2 parts, thiocarbamide 1.5 parts, 1.8 parts, acid binding agent salt of wormwood, sodium perchlorate 6 parts, concentrated hydrochloric acid 15 parts, DIPEA 1.5 parts.
The preparation method of the former medicine of described ABA Receptor agonist, comprises the steps:
(1) raw material is taken: take each raw material according to molfraction;
(2) prepare N-propyl group quinolinone: A, add in organic solvent DMF by quinolinone, at-5 DEG C, stir 0.8h; B, under argon shield environment, add sodium hydride as catalyzer in batches, add rear stirring 0.8h; C, in solution, instill iodopropane, at room temperature react 12h; D, adding water makes reaction cancellation and is extracted with ethyl acetate reaction product three times, extracts the organic layer obtained be merged together each time, with saturated sodium-chloride water solution, the organic layer after merging is washed one time, then carries out drying by anhydrous sodium sulphate; E, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain alkylation reaction product N-propyl group quinolinone; Reaction equation is:
；
(3) prepare 7-nitro-N-propyl group quinolinone: A, join in organic solvent dichloromethane by N-propyl group quinolinone, at-5 DEG C, stir 0.8h; B, slowly nitrosonitric acid is instilled in solution with dropping funnel, at 0 DEG C, react 2.5h; C, adding water makes reaction cancellation and by dichloromethane extraction reaction product three times, is merged together by the organic layer that each extraction obtains, washes one time respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution; D, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain nitration reaction product 7-nitro-N-propyl group quinolinone; Reaction equation is:
；
(4) prepare 7-amino-N-propyl group quinolinone: A, to be joined in organic solvent ethanol by 7-nitro-N-propyl group quinolinone, then add the hydrochloric acid of iron powder and 6mol/L, be heated to 68 DEG C, backflow 3.5h, after reactant cooling, be spin-dried for solvent; B, add in above-mentioned solution 10% aqueous sodium hydroxide solution and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained to be merged together, wash one time with saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 3:1 reaction product carry out chromatographic separation, obtain hydro-reduction reaction product 7-amino-N-propyl group quinolinone; Reaction equation is:
；
(5) 4-methyl benzyl SULPHURYL CHLORIDE is prepared: will
join in acetonitrile, then slowly add thiocarbamide and acid binding agent salt of wormwood;
Reflux 4.5h in ethanol, filters, and concentrates and obtain intermediate product
; Reaction equation is:
；
By intermediate product
join in acetonitrile, then add sodium perchlorate and concentrated hydrochloric acid, vigorous stirring, concentrate after making reaction carry out 6h, then with sherwood oil and salt solution extraction, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
；
(6) prepare ABA Receptor agonist: A, 7-amino-N-propyl group quinolinone and 4-methyl benzyl SULPHURYL CHLORIDE to be added in organic solvent acetonitrile, then add DIPEA as catalyzer, keep stirring at room temperature 6.5h; B, be spin-dried for solvent, add water and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained and be merged together, wash one time with saturated sodium-chloride water solution, then carry out drying by anhydrous sodium sulphate; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 5:1 reaction product carry out chromatographic separation, obtain through condensation reaction products N-(2-carbonyl-1-propyl group-1,2,3,4-4H-quinolinone-6-)-4-to methylsulfonamides, i.e. ABA Receptor agonist; Reaction equation is:
。
Embodiment 3
The former medicine of a kind of ABA Receptor agonist, comprises according to the raw material of molfraction: quinolinone 2 parts, sodium hydride 5.5 parts, iodopropane 10 parts, nitrosonitric acid 50 parts, hydrochloric acid 5.5 parts, iron powder 5.5 parts,
1 part, thioacetic acid potassium 1.5 parts, 1.5 parts, acid binding agent salt of wormwood, DIPEA 1.6 parts.
The preparation method of the former medicine of described ABA Receptor agonist, comprises the steps:
(1) raw material is taken: take each raw material according to molfraction;
(2) prepare N-propyl group quinolinone: A, add in organic solvent DMF by quinolinone, at-4 DEG C, stir 1h; B, under argon shield environment, add sodium hydride as catalyzer in batches, add rear stirring 1h; C, in solution, instill iodopropane, at room temperature react 13h; D, adding water makes reaction cancellation and is extracted with ethyl acetate reaction product three times, extracts the organic layer obtained be merged together each time, with saturated sodium-chloride water solution, the organic layer after merging is washed one time, then carries out drying by anhydrous sodium sulphate; E, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain alkylation reaction product N-propyl group quinolinone; Reaction equation is:
；
(3) prepare 7-nitro-N-propyl group quinolinone: A, join in organic solvent dichloromethane by N-propyl group quinolinone, at-4 DEG C, stir 1h; B, slowly nitrosonitric acid is instilled in solution with dropping funnel, at 1 DEG C, react 3h; C, adding water makes reaction cancellation and by dichloromethane extraction reaction product three times, is merged together by the organic layer that each extraction obtains, washes one time respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution; D, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 10:1 reaction product carry out chromatographic separation, obtain nitration reaction product 7-nitro-N-propyl group quinolinone; Reaction equation is:
；
(4) prepare 7-amino-N-propyl group quinolinone: A, to be joined in organic solvent ethanol by 7-nitro-N-propyl group quinolinone, then add the hydrochloric acid of iron powder and 6mol/L, be heated to 70 DEG C, backflow 4h, after reactant cooling, be spin-dried for solvent; B, add in above-mentioned solution 10% aqueous sodium hydroxide solution and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained to be merged together, wash one time with saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 3:1 reaction product carry out chromatographic separation, obtain hydro-reduction reaction product 7-amino-N-propyl group quinolinone; Reaction equation is:
；
(5) 4-methyl benzyl SULPHURYL CHLORIDE is prepared: will
join in acetonitrile, then slowly add thioacetic acid potassium and acid binding agent salt of wormwood;
At room temperature stir 0.8h, filter, carry out after washing two times with saturated common salt concentrated obtaining intermediate product
; Reaction equation is:
；
By intermediate product
join in acetonitrile, then under air-proof condition, slowly pass into dry chlorine gas, make chlorine can recycle simultaneously, ventilation 4h, concentrates after stopped reaction, then extracts with sherwood oil and salt solution, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
；
(6) prepare ABA Receptor agonist: A, 7-amino-N-propyl group quinolinone and 4-methyl benzyl SULPHURYL CHLORIDE to be added in organic solvent acetonitrile, then add DIPEA as catalyzer, keep stirring at room temperature 7.5h; B, be spin-dried for solvent, add water and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained and be merged together, wash one time with saturated sodium-chloride water solution, then carry out drying by anhydrous sodium sulphate; C, the chromatography column utilizing the weight ratio of sherwood oil and ethyl acetate to be 5:1 reaction product carry out chromatographic separation, obtain through condensation reaction products N-(2-carbonyl-1-propyl group-1,2,3,4-4H-quinolinone-6-)-4-to methylsulfonamides, i.e. ABA Receptor agonist; Reaction equation is:
ABA Receptor agonist prepared by the present invention is a kind of micromolecular compound with dormin activity, spray and can significantly improve the adaptive faculty of plant to drought environment after plant, ABA Receptor agonist structure simply and there is not optically active isomer, be easy to synthetic and purifying, cost is lower, the aminoacid sequence of its acceptor is very conservative in higher plant, and therefore ABA Receptor agonist transforms without the need to carrying out the farm crop that namely can be applicable to multiple types.
The former medical instrument of ABA Receptor agonist have active high, Crop is good, safe and efficient, the adaptive faculty of crop to arid can be significantly improved, and by cleaning and chromatographic separation the reaction product of each step gained in the present invention, then as the raw material of next step reaction, improve purity and the yield of product; On the other hand, the use of catalyzer facilitates the generation of target product, decreases by product, also improves purity and the yield of product.
Above the better embodiment of this patent is explained in detail, but this patent is not limited to above-mentioned embodiment, in the ken that one skilled in the relevant art possesses, various change can also be made under the prerequisite not departing from this patent aim.
Claims (10)
1. the former medicine of ABA Receptor agonist, it is characterized in that, comprise according to the raw material of molfraction: quinolinone 1-2 part, sodium hydride 4.5-5.5 part, halogenopropane 5-10 part, nitrosonitric acid 40-50 part, hydrochloric acid 1.5-5.5 part, iron powder 4.5-5.5 part, 4-methyl benzyl SULPHURYL CHLORIDE 1-2 part, DIPEA 1.4-1.6 part.
2. the former medicine of ABA Receptor agonist according to claim 1, is characterized in that, the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE comprises the steps:
(1) get a certain amount of
join in acetonitrile, then slowly add thiocarbamide and acid binding agent salt of wormwood;
(2) reflux in ethanol 3.5-4.5h, filters, and concentratedly obtains intermediate product
; Reaction equation is:
；
(3) by intermediate product
join in acetonitrile, then add sodium perchlorate and concentrated hydrochloric acid or pass into chlorine, vigorous stirring, concentrate after making reaction carry out 6-8h, then with sherwood oil and salt solution extraction, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
。
3. the former medicine of ABA Receptor agonist according to claim 2, is characterized in that, comprises in the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE according to the raw material of molfraction:
1-2 part, thiocarbamide 1.2-1.5 part, acid binding agent salt of wormwood 1.2-1.8 part, sodium perchlorate 5-6 part, concentrated hydrochloric acid 6-15 part.
4. the former medicine of ABA Receptor agonist according to claim 1, is characterized in that, the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE comprises the steps:
(1) get a certain amount of
join in acetonitrile, then slowly add thioacetic acid potassium and acid binding agent salt of wormwood;
(2) at room temperature stir 0.8-1.2h, filter, carry out after washing two times with saturated common salt concentrated obtaining intermediate product
; Reaction equation is:
；
(3) by intermediate product
join in acetonitrile, then under air-proof condition, slowly pass into dry chlorine gas, make chlorine can recycle simultaneously, ventilation 4-6h, concentrates after stopped reaction, then extracts with sherwood oil and salt solution, obtain product
, namely obtain methyl benzyl SULPHURYL CHLORIDE; Reaction equation is:
。
5. the former medicine of ABA Receptor agonist according to claim 4, is characterized in that, comprises in the preparation method of described 4-methyl benzyl SULPHURYL CHLORIDE according to the raw material of molfraction:
1-2 part, thioacetic acid potassium 1.5-3.2 part, acid binding agent salt of wormwood 1.5-3.2 part.
6. a preparation method for the former medicine of ABA Receptor agonist adopting one of claim 1-4 described, is characterized in that, comprise the steps:
(1) raw material is taken: take each raw material according to molfraction;
(2) prepare N-propyl group quinolinone: A, add in organic solvent DMF by quinolinone, at-6--4 DEG C, stir 0.5-1h; B, under argon shield environment, add sodium hydride as catalyzer in batches, add rear stirring 0.5-1h; C, in solution, instill halogenopropane, at room temperature react 11-13h; D, adding water makes reaction cancellation and is extracted with ethyl acetate reaction product three times, extracts the organic layer obtained be merged together each time, with saturated sodium-chloride water solution, the organic layer after merging is washed one time, then carries out drying by anhydrous sodium sulphate; E, utilize chromatography column to carry out chromatographic separation reaction product, obtain alkylation reaction product N-propyl group quinolinone; Reaction equation is:
；
(3) prepare 7-nitro-N-propyl group quinolinone: A, join in organic solvent dichloromethane by N-propyl group quinolinone, at-6--4 DEG C, stir 0.5-1h; B, slowly nitrosonitric acid is instilled in solution with dropping funnel, at-1-1 DEG C, react 2-3h; C, adding water makes reaction cancellation and by dichloromethane extraction reaction product three times, is merged together by the organic layer that each extraction obtains, washes one time respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution; D, utilize chromatography column to carry out chromatographic separation reaction product, obtain nitration reaction product 7-nitro-N-propyl group quinolinone; Reaction equation is:
；
(4) prepare 7-amino-N-propyl group quinolinone: A, to be joined in organic solvent ethanol by 7-nitro-N-propyl group quinolinone, then add the hydrochloric acid of iron powder and 6mol/L, be heated to 65-70 DEG C, backflow 3-4h, after reactant cooling, be spin-dried for solvent; B, add in above-mentioned solution 10% aqueous sodium hydroxide solution and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained to be merged together, wash one time with saturated sodium bicarbonate aqueous solution and saturated sodium-chloride water solution respectively, then carry out drying by anhydrous sodium sulphate, be spin-dried for; C, utilize chromatography column to carry out chromatographic separation reaction product, obtain hydro-reduction reaction product 7-amino-N-propyl group quinolinone; Reaction equation is:
；
(5) prepare ABA Receptor agonist: A, 7-amino-N-propyl group quinolinone and 4-methyl benzyl SULPHURYL CHLORIDE to be added in organic solvent acetonitrile, then add DIPEA as catalyzer, keep stirring at room temperature 5.5-7.5h; B, be spin-dried for solvent, add water and be extracted with ethyl acetate reaction product three times, extract each time the organic layer obtained and be merged together, wash one time with saturated sodium-chloride water solution, then carry out drying by anhydrous sodium sulphate; C, utilize chromatography column to carry out chromatographic separation reaction product, obtain through condensation reaction products N-(2-carbonyl-1-propyl group-1,2,3,4-4H-quinolinone-6-)-4-to methylsulfonamides, i.e. ABA Receptor agonist; Reaction equation is:
。
7. the preparation method of the former medicine of ABA Receptor agonist according to claim 5, it is characterized in that, described chromatography column comprises sherwood oil and ethyl acetate.
8., according to the preparation method of the arbitrary described former medicine of ABA Receptor agonist of claim 6-7, it is characterized in that, the weight ratio of described step (2) and step (3) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 10:1.
9., according to the preparation method of the arbitrary described former medicine of ABA Receptor agonist of claim 6-7, it is characterized in that, the weight ratio of described step (4) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 3:1.
10., according to the preparation method of the arbitrary described former medicine of ABA Receptor agonist of claim 6-7, it is characterized in that, the weight ratio of described step (5) interior chromatography column PetroChina Company Limited. ether and ethyl acetate is 5:1.
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| CN107501142A (en) * | 2017-08-29 | 2017-12-22 | 厦门大学 | Reduce chemical linkers and its preparation and purposes of the response type containing double disulfide bond |
| CN108822002A (en) * | 2018-06-21 | 2018-11-16 | 中南大学 | A kind of method of ultrasonic wave added synthesis N- aryl sulfonic acid amides |
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| CN112778197A (en) * | 2019-11-09 | 2021-05-11 | 邵阳学院 | Preparation method of novel abscisic acid agonist AM1 |
| CN112794818A (en) * | 2019-11-13 | 2021-05-14 | 邵阳学院 | Preparation method of N-propylaminoquinolinone and application of N-propylaminoquinolinone in synthesis of abscisic acid agonist AM1 and derivatives thereof |
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| CN107207440A (en) * | 2015-02-09 | 2017-09-26 | 先正达参股股份有限公司 | It is used as the dihydroquinazoline compound of 2 oxo 3,4 of plant growth regulator |
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| CN109414019A (en) * | 2016-07-05 | 2019-03-01 | 先正达参股股份有限公司 | Plant growth regulator compound |
| CN109414019B (en) * | 2016-07-05 | 2021-04-30 | 先正达参股股份有限公司 | Plant growth regulator compounds |
| CN107501142A (en) * | 2017-08-29 | 2017-12-22 | 厦门大学 | Reduce chemical linkers and its preparation and purposes of the response type containing double disulfide bond |
| CN107501142B (en) * | 2017-08-29 | 2019-11-08 | 厦门大学 | Restore chemical linkers and its preparation and purposes of the response type containing double disulfide bond |
| CN108822002A (en) * | 2018-06-21 | 2018-11-16 | 中南大学 | A kind of method of ultrasonic wave added synthesis N- aryl sulfonic acid amides |
| CN108822002B (en) * | 2018-06-21 | 2020-05-05 | 中南大学 | Method for synthesizing N-aryl sulfonamide under assistance of ultrasonic waves |
| CN112778197A (en) * | 2019-11-09 | 2021-05-11 | 邵阳学院 | Preparation method of novel abscisic acid agonist AM1 |
| CN112794818A (en) * | 2019-11-13 | 2021-05-14 | 邵阳学院 | Preparation method of N-propylaminoquinolinone and application of N-propylaminoquinolinone in synthesis of abscisic acid agonist AM1 and derivatives thereof |
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