CN103467300B - A kind of synthetic method of o-nitrobenzaldehyde compounds - Google Patents
A kind of synthetic method of o-nitrobenzaldehyde compounds Download PDFInfo
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- ZCROZEYLZBEUAK-UHFFFAOYSA-N [O-][N+](C(C(C=O)=C1)=CCC1Br)=O Chemical compound [O-][N+](C(C(C=O)=C1)=CCC1Br)=O ZCROZEYLZBEUAK-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention provides a kind of preparation method of o-nitrobenzaldehyde compounds.The present invention is directly starting raw material with compound of benzaldehyde category, first be O-methyl oximido by convert aldehyde groups, then with divalent palladium salt for catalyzer, deposit in case at oxygenant and nitrating agent, realize the C-H activation mono-nitration reaction on oximido ortho position, finally utilize strong organic acid to slough O-methyl oximido and obtain o-nitrobenzaldehyde compounds.Nitrifying method of the present invention has the narrow spectrum advantage in ortho position, nitrated position, and reaction process safety and environmental protection, substrate adaptability are good, and various substituting group can realize ortho-nitration; Directly with various phenyl aldehyde for raw material, reactions steps is simple, is a kind ofly to synthesize the various variation route containing substituent o-nitrobenzaldehyde compounds.
Description
Technical field
The present invention relates to a kind of synthetic method of organic compound, relate in particular to the preparation method with a kind of o-nitrobenzaldehyde compounds.
Background technology
O-nitrobenzaldehyde compounds is a kind of important medicine intermediate, can be used for the raw material of the Cardiovarscular medicines such as synthesizing nitryl pyridine (nifedipine), nisoldipine, encainide, also be important organic synthesis raw material, be widely used in chemical industry.Ortho Nitro Benzaldehyde is main at present take Ortho Nitro Toluene as raw material, obtain through oxidation, hydrolysis or the step such as bromination, hydrolysis, but Ortho Nitro Toluene is obtained by mixed acid nitrification by toluene, need the strong acid such as excessive nitric acid and sulfuric acid as reaction reagent and catalyzer in process, a large amount of heat is released in reaction process, easily cause and produce danger, produce a large amount of waste gas spent acid in this course simultaneously, cause serious environmental problem.In addition, take phenyl aldehyde as raw material, in the mixed solution that the vitriol oil and vinegar are joined, slow dropping benzal diethyl acid anhydrides, intermediate and nitrosonitric acid react, and obtain yellow blocks of solid and add aqueous sodium carbonate, separable go out Ortho Nitro Benzaldehyde and paranitrobenzaldehyde, but in most of the cases adjacency pair position product is difficult to be separated, and this just causes the yield of product Ortho Nitro Benzaldehyde and purity all very low, this method faces a series of serious safety problem and environmental problem that strong acid brings equally simultaneously.
In the market containing various substituent o-nitrobenzaldehyde compounds actually rare be because the locating rule by phenyl ring limits, cause phenyl ring synthesizes containing the more difficult regiospecificity of various substituent o-nitrobenzaldehyde compounds, need longer reactions steps could synthesize corresponding Ortho Nitro Benzaldehyde, and the reactions steps that different substituting groups relates to is different, the method synthesis that neither one is general.
In view of above Problems existing, design a general o-nitrobenzaldehyde compounds synthetic route and seem and be extremely necessary.
Summary of the invention
In the market containing various substituent o-nitrobenzaldehyde compounds actually rare be because the locating rule by phenyl ring limits, cause on phenyl ring containing the more difficult synthesis of various substituent o-nitrobenzaldehyde compounds, need longer reactions steps could synthesize corresponding Ortho Nitro Benzaldehyde, and the reactions steps that different substituting groups relates to is different, the method synthesis that neither one is general.In order to overcome deficiency of the prior art, provide a kind of method of synthesizing o-nitrobenzaldehyde compounds.
Technical scheme of the present invention is:
A synthetic method for o-nitrobenzaldehyde compounds shown in formula IV, described method adopts following steps:
(1) compound of benzaldehyde category shown in formula I, methoxamine hydrochloride, anhydrous sodium acetate, reaction solvent mix, be heated to back flow reaction, TLC tracing detection is to reacting completely, and gained reaction solution a aftertreatment obtains the phenyl aldehyde O-methyloxime compounds shown in formula II;
The ratio of the amount of substance of the compound of benzaldehyde category shown in described formula I, methoxamine hydrochloride is 1:2 ~ 3, preferred 1:2.7;
The ratio of the amount of substance of described methoxamine hydrochloride, anhydrous sodium acetate is 1:1 ~ 2, preferred 1:1.6;
Described reaction solvent is the mixed solvent of ethanol, water volume ratio 1:1 ~ 10, preferred 1:3;
The volumetric usage of described reaction solvent counts 8 ~ 20mL/mmol with the amount of substance of the compound of benzaldehyde category shown in I usually.
The reaction of described step (1) is with TLC tracing detection reaction raw materials to reacting completely, and the usual reaction times is 1 ~ 10 hour, preferably 3 hours.
(2) phenyl aldehyde O-methyloxime compounds, divalent palladium salt catalyst, nitrating agent nitrite, oxygenant and low polar organic solvent shown in formula II step (1) obtained add in sealed pressure vessel successively, airtight reacting by heating at 80 DEG C ~ 130 DEG C (preferably 110 DEG C) temperature, TLC tracing detection is to reacting completely, and gained reaction solution b aftertreatment obtains the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III;
The ratio of the amount of substance of the phenyl aldehyde O-methyloxime compounds shown in described formula II, divalent palladium salt catalyst, nitrating agent nitrite, oxygenant is 1:0.001 ~ 0.2:1 ~ 4:1 ~ 4, preferred 1:0.1:2:2.
Described divalent palladium salt catalyst is selected from the palladium catalysts such as Palladous chloride, two (triphenylphosphine) palladium chloride, palladium diacetate or palladium trifluoroacetate, is preferably palladium diacetate.
Described oxygenant is Potassium Persulphate or potassium peroxymonosulfate, preferred Potassium Persulphate.
Described low polar organic solvent is selected from 1,2-ethylene dichloride, acetonitrile, methylene dichloride or chloroform, is preferably 1,2-ethylene dichloride.
Described nitrating agent nitrite is selected from potassium nitrite, Sodium Nitrite or silver nitrite, is preferably silver nitrite.
The reaction of described step (2) is with TLC tracing detection reaction raw materials to reacting completely, and the usual reaction times is 10 ~ 60 hours, preferably 48 hours.
The volumetric usage of described low polar organic solvent counts 8 ~ 20mL/mmol with the amount of substance of the phenyl aldehyde O-methyloxime compounds shown in formula II usually.
(3) the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III step (2) obtained is dissolved in the mixed solvent of tetrahydrofuran (THF), water, add the formaldehyde solution of strong organic acid, massfraction 30 ~ 40%, airtight be heated to 30 ~ 110 DEG C of (preferably 110 DEG C) temperature under react, TLC tracing detection is to reacting completely, and gained reaction solution c aftertreatment obtains the o-nitrobenzaldehyde compounds shown in formula IV;
The ratio of the amount of substance of the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in described formula III, strong organic acid, formaldehyde is 1:2 ~ 3:3 ~ 6, preferred 1:2:4.
Described strong organic acid is preferably tosic acid.
The reaction of described step (3) is with TLC tracing detection reaction raw materials to reacting completely, and the usual reaction times is 1 ~ 24 hour, preferably 8 hours.
In the mixed solvent of described tetrahydrofuran (THF), water, the volume ratio of tetrahydrofuran (THF), water is generally 8 ~ 15:1, preferred 10:1.
The volumetric usage of the mixed solvent of described tetrahydrofuran (THF), water counts 3 ~ 8mL/mmol with the amount of substance of the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III usually.
In formula I ~ formula IV, R
1, R
2, R
3independently be selected from hydrogen, the alkyl of C1 ~ C5, the alkoxyl group of C1 ~ C5, the ester group of C1 ~ C5, hydroxyl, amido, trifluoromethyl, halogen or phenyl separately; Described halogen is F, Cl, Br or I;
Preferred R
1, R
2, R
3respective is independently hydrogen, trifluoromethyl, Br or Cl.
In described step (1), described reaction solution a post-treating method is: after reaction terminates, reaction solution a adds extraction into ethyl acetate, removes solvent under reduced pressure after getting organic phase drying, obtained phenyl aldehyde O-methyloxime compounds shown in formula II.
In described step (2), described reaction solution b post-treating method is: after reaction terminates, reaction solution b dchloromethane, filter, get after filtrate steaming removal solvent through column chromatography for separation, the mixed solvent being 20:1 with sherwood oil, ethyl acetate volume ratio, for eluent, collects the elutriant containing product, steams and desolventizes the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in obtained formula III.
In described step (3), described reaction solution c post-treating method is: after reaction terminates, reaction solution c adds saturated sodium carbonate solution to pH value for neutral, use extracted with diethyl ether again, get organic phase and remove solvent under reduced pressure after drying, residuum is through column chromatography for separation, and the mixed solvent being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, collect the elutriant containing product, steam and desolventize the o-nitrobenzaldehyde compounds shown in obtained formula IV.
The present invention is directly raw material with compound of benzaldehyde category, by carbonyl is converted into oximido, again with divalent palladium salt for catalyzer, deposit in case at oxygenant and nitrating agent, realize the C-H activation mono-nitration reaction on oximido ortho position, finally again oxime is hydrolyzed to corresponding aldehyde in the effect of acid, thus realizes at the ortho position of compound of benzaldehyde category carbonyl nitratedly obtaining a series of o-nitrobenzaldehyde compounds.
In all examples of the present invention, step (2) although in the consumption of nitrating agent be greater than the consumption of reactant, can not occur excessively nitratedly to wait side reaction, only have the mononitrated product of highly selective to generate all the time.
In the present invention, preferred catalyst is palladium diacetate in step (2), is characterized in that productive rate is high, price is relatively cheap and is easy to preserve and take.
The solvent of the nitration reaction in step (2) is preferably 1,2-ethylene dichloride.Be good with rudimentary property organic solvent, 1,2-ethylene dichloride is the solvent that specific inductivity is low, and its boiling point is relatively high, not volatile, easily stores.
Compared with prior art, the invention has the beneficial effects as follows:
(1) safety and environmental protection, does not produce waste gas waste water.
(2) substrate adaptability is good, and various substituting group can realize ortho-nitration.
(3) nitration reaction regioselectivity is good, has the narrow spectrum advantage in ortho position, nitrated position.
(4) directly with various phenyl aldehyde for raw material, reactions steps is simple, and is a kind ofly synthesize the various variation route containing substituent o-nitrobenzaldehyde compounds.
Embodiment
Be described in further detail the present invention below in conjunction with specific embodiment, protection scope of the present invention is not limited thereto.
Embodiment 1:
Take phenyl aldehyde as raw material, synthesis 2-nitrobenzaldehyde
(1) by phenyl aldehyde 0.530g(5.0mmol), methoxamine hydrochloride 1.12g(13.4mmol), anhydrous sodium acetate 1.804g (22mmol), 15ml ethanol, 45ml water adds in 100ml flask.Mixture is heated to back flow reaction, TLC tracing detection, and after 3 hours, reaction terminates, and gained mixing solutions 3 × 45mL extraction into ethyl acetate, reduces pressure after getting organic phase drying and slough solvent, obtains weak yellow liquid phenyl aldehyde-O-methyloxime 0.641g(95% yield).
(2) by phenyl aldehyde O-methyloxime 67.5mg(0.5mmol), palladium diacetate 11mg(0.05mmol), silver nitrite 154mg(1.0mmol), Potassium Persulphate 270mg(1.0mmol) and 1,2-ethylene dichloride (5ml) add successively in the sealed pressure vessel of 10ml.By mixture reacting by heating in 110 DEG C of oil baths, TLC tracing detection, reaction in 48 hours terminates, reaction solution 10mL dchloromethane, filtration obtains clear liquid, and steaming desolventizes, and is separated by column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1), collect elutriant, steaming desolventizes and obtains weak yellow liquid 2-nitrobenzaldehyde O-methyloxime 50mg(78% yield).
(3) by 2-nitrobenzaldehyde O-methyloxime 90mg(0.5mmol), tosic acid 172mg, react at adding sealed vessel 110 DEG C after 40% formaldehyde solution 150mg 2mlTHF/0.2ml water dissolution, TLC tracing detection, after reaction in 8 hours terminates, reaction solution saturated sodium carbonate solution is neutralized to pH value neutrality, mixed solution is with extracted with diethyl ether (10ml × 3), get organic phase to reduce pressure after anhydrous sodium sulfate drying and slough solvent, residuum column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1) is separated, collect elutriant, steaming desolventizes and obtains weak yellow liquid 2-nitrobenzaldehyde 69mg(95% yield).
Yellow solid; Mp38.9 DEG C; IR (KBr): ν=1528 (NO
2), 1698 (C=O) cm
-1, 2866 (-CO-H) cm
-1;
1hNMR (500MHz, CDCl
3) δ 10.44 (s, 1H), 8.13 (dd, J
1=8.0Hz, J
2=1.0Hz, 1H), 7.97 (dd, J
1=7.5Hz, J
2=1.5Hz, 1H), 7.84 – 7.76 (m, 2H);
13cNMR (125MHz, CDCl
3): δ 188.1,149.6,134.0,133.7,131.4,129.6,124.5.
Embodiment 2:
With 4-trifluoromethylated benzaldehyde for raw material, synthesis 4-trifluoromethyl-2-nitrobenzaldehyde
(1) by 4-trifluoromethylated benzaldehyde 0.870g(5.0mmol), methoxamine hydrochloride 1.12g, anhydrous sodium acetate 1.804g, 15ml ethanol, 45ml water adds in 100ml flask.Mixture is heated to back flow reaction, TLC tracing detection, after 3 hours, reaction terminates, gained mixing solutions 3 × 45mL extraction into ethyl acetate, reduce pressure after getting organic phase drying and slough solvent, obtain weak yellow liquid 4-trifluoromethylated benzaldehyde-O-methyloxime 0.995g(98% yield).
(2) by 4-trifluoromethylated benzaldehyde-O-methyloxime 101.5mg(0.5mmol), palladium diacetate 11mg(0.05mmol), silver nitrite 154mg(1.0mmol), Potassium Persulphate 270mg(1.0mmol) and 1,2-ethylene dichloride (5ml) add successively in the sealed pressure vessel of 10ml.By mixture reacting by heating in 110 DEG C of oil baths, TLC tracing detection, reaction in 48 hours terminates, reaction solution 10mL dchloromethane, filtration obtains clear liquid, steaming desolventizes rear column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) and is separated, and collects elutriant, steams to desolventize to obtain weak yellow liquid 4-trifluoromethyl-2-nitrobenzaldehyde O-methyloxime 95mg(73% yield).
(3) by 4-trifluoromethyl-2-nitrobenzaldehyde O-methyloxime 124mg(0.5mmol), tosic acid 172mg, react at adding sealed vessel 110 DEG C after 40% formaldehyde solution 150mg 2mlTHF/0.2ml water dissolution, TLC tracing detection, reaction in 8 hours terminates, reaction solution saturated sodium carbonate solution is neutralized to pH value neutrality, mixed solution is with extracted with diethyl ether (10ml × 3), get organic phase to reduce pressure after anhydrous sodium sulfate drying and slough solvent, residuum column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1) is separated, collect elutriant, steaming desolventizes and obtains weak yellow liquid 4-trifluoromethyl-2-nitrobenzaldehyde 114mg(95% yield).
Yellow oily liquid; IR (neat): ν=1543 (NO
2), 1705 (C=O) cm
-1, 2891 (-CO-H) cm
-1;
1hNMR (500MHz, CDCl
3) δ 10.49 (s, 1H), 8.43 (s, 1H), 8.09 (q, J=8.2Hz, 2H).
13cNMR (126MHz, CDCl
3): δ 186.9,149.4,135.6 (q, J
f-C=8.7Hz), 134.0,130.9 (q, J
f-C=3.4Hz), 130.8,122.2 (q, J
f-C=271.9Hz), 122.0 (q, J
f-C=3.8Hz).
Embodiment 3:
With 3-bromobenzaldehyde for raw material, the bromo-2-nitrobenzaldehyde of synthesis 5-
(1) by 3-bromobenzaldehyde 0.915g(5.0mmol), methoxamine hydrochloride 1.12g, anhydrous sodium acetate 1.804g, 15ml ethanol, 45ml water adds in 100ml flask.Mixture is heated to back flow reaction, TLC tracing detection, after 3 hours, reaction terminates, gained mixing solutions 3 × 45mL extraction into ethyl acetate, reduce pressure after getting organic phase drying and slough solvent, obtain faint yellow solid 3-bromobenzaldehyde-O-methyloxime 0.994g(98% yield).
(2) by 3-bromobenzaldehyde-O-methyloxime 101.5mg(0.5mmol), palladium diacetate 11mg(0.05mmol), silver nitrite 154mg(1.0mmol), Potassium Persulphate 270mg(1.0mmol) and 1,2-ethylene dichloride (5ml) add successively in the sealed pressure vessel of 10ml.By mixture reacting by heating in 110 DEG C of oil baths, TLC tracing detection, reaction in 48 hours terminates, reaction solution 10mL dchloromethane, filtration obtains clear liquid, steaming desolventizes rear column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) and is separated, and collects elutriant, steams to desolventize to obtain weak yellow liquid 5-bromo-2-nitrobenzaldehyde O-methyloxime 96.7mg(78% yield).
(3) by bromo-for 5-2-nitrobenzaldehyde O-methyloxime 124mg(0.5mmol), tosic acid 172mg, react at adding sealed vessel 110 DEG C after 40% formaldehyde solution 150mg 2mlTHF/0.2ml water dissolution, TLC tracing detection, reaction in 8 hours terminates, reaction solution saturated sodium carbonate solution is neutralized to pH value neutrality, mixed solution is with extracted with diethyl ether (10ml × 3), get organic phase to reduce pressure after anhydrous sodium sulfate drying and slough solvent, residuum column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1) is separated, collect elutriant, steaming desolventizes and obtains yellow solid 5-bromo-2-nitrobenzaldehyde 104mg(95% yield).
Yellow solid; Mp72.9 DEG C; IR (KBr): ν=1522 (NO
2), 1692 (C=O) cm
-1, 2854 (-CO-H) cm
-1;
1hNMR (500MHz, CDCl
3): δ 10.40 (s, 1H), 8.05 (d, J=2.0Hz, 1H), 8.03 (d, J=8.5Hz, 1H), 7.89 (dd, J
1=8.5Hz, J
2=2.0Hz, 1H);
13cNMR (125MHz, CDCl
3): δ 186.7,148.1,136.5,132.6,129.5,126.1
Embodiment 4:
With 3-chlorobenzaldehyde for raw material, the chloro-2-nitrobenzaldehyde of synthesis 5-
(1) by 3-chlorobenzaldehyde 0.700g(5.0mmol), methoxamine hydrochloride 1.12g, anhydrous sodium acetate 1.804g, 15ml ethanol, 45ml water adds in 100ml flask.Mixture is heated to back flow reaction, TLC tracing detection, after 3 hours, reaction terminates, gained mixing solutions 3 × 45mL extraction into ethyl acetate, reduce pressure after getting organic phase drying and slough solvent, obtain yellow solid 3-chlorobenzaldehyde-O-methyloxime 0.828g(98% yield).
(2) by 3-chlorobenzaldehyde O-methyloxime 84mg(0.5mmol), palladium diacetate 11mg(0.05mmol), silver nitrite 154mg(1.0mmol), Potassium Persulphate 270mg(1.0mmol) and 1,2-ethylene dichloride (5ml) add successively in the sealed pressure vessel of 10ml.By mixture reacting by heating in 110 DEG C of oil baths, TLC tracing detection, reaction in 48 hours terminates, reaction solution 10mL dchloromethane, filtration obtains clear liquid, steaming desolventizes rear column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) and is separated, and collects elutriant, steams to desolventize to obtain yellow solid 5-chloro-2-nitrobenzaldehyde O-methyloxime 85mg(80% yield).
(3) by chloro-for 5-2-nitrobenzaldehyde O-methyloxime 107mg(0.5mmol), tosic acid 172mg, react at adding sealed vessel 110 DEG C after 40% formaldehyde solution 150mg 2mlTHF/0.2ml water dissolution, TLC tracing detection, reaction in 8 hours terminates, reaction solution saturated sodium carbonate solution is neutralized to pH value neutrality, mixed solution is with extracted with diethyl ether (10ml × 3), get organic phase to reduce pressure after anhydrous sodium sulfate drying and slough solvent, residuum column chromatography chromatogram method (leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1) is separated, collect elutriant, steaming desolventizes and obtains faint yellow solid 5-chloro-2-nitrobenzaldehyde 87mg(95% yield).
Yellow solid; Mp77.2 DEG C; IR (KBr): ν=1510 (NO
2), 1696 (C=O) cm
-1, 2854 (-CO-H) cm
-1;
1hNMR (500MHz, CDCl
3): δ 10.43 (s, 1H), 8.13 (d, J=8.5Hz, 1H), 7.91 (d, J=2.0Hz, 1H), 7.72 (dd, J
1=8.5Hz, J
2=2.0Hz, 1H);
13cNMR (125MHz, CDCl
3): δ 186.7,147.5,141.2,133.4,132.8,129.6,126.2.
Claims (8)
1. a synthetic method for the o-nitrobenzaldehyde compounds shown in formula IV, is characterized in that described method adopts following steps:
(1) compound of benzaldehyde category shown in formula I, methoxamine hydrochloride, anhydrous sodium acetate, reaction solvent mix, be heated to back flow reaction, TLC tracing detection is to reacting completely, and gained reaction solution a aftertreatment obtains the phenyl aldehyde O-methyloxime compounds shown in formula II;
Described reaction solvent is the mixed solvent of ethanol, water volume ratio 1:1 ~ 10;
(2) phenyl aldehyde O-methyloxime compounds, divalent palladium salt catalyst, nitrating agent nitrite, oxygenant and low polar organic solvent shown in formula II step (1) obtained add in sealed pressure vessel successively, airtight reacting by heating at 80 DEG C ~ 130 DEG C temperature, TLC tracing detection is to reacting completely, and gained reaction solution b aftertreatment obtains the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III;
Described divalent palladium salt catalyst is selected from Palladous chloride, two (triphenylphosphine) palladium chloride, palladium diacetate or palladium trifluoroacetate;
Described oxygenant is Potassium Persulphate or potassium peroxymonosulfate;
Described low polar organic solvent is selected from 1,2-ethylene dichloride;
(3) the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III step (2) obtained is dissolved in the mixed solvent of tetrahydrofuran (THF), water, add the formaldehyde solution of strong organic acid, massfraction 30 ~ 40%, airtight be heated to 30 ~ 110 DEG C of temperature under react, TLC tracing detection is to reacting completely, and gained reaction solution c aftertreatment obtains the o-nitrobenzaldehyde compounds shown in formula IV; Described strong organic acid is tosic acid;
In formula I ~ formula IV, R
1, R
2, R
3independently be selected from hydrogen, the alkyl of C1 ~ C5, the alkoxyl group of C1 ~ C5, the ester group of C1 ~ C5, hydroxyl, amido, trifluoromethyl, halogen or phenyl separately; Described halogen is F, Cl, Br or I.
2. the method for claim 1, is characterized in that described R
1, R
2, R
3respective is independently hydrogen, trifluoromethyl, Br or Cl.
3. the method for claim 1, is characterized in that in described step (1), and the ratio of the amount of substance of the compound of benzaldehyde category shown in described formula I, methoxamine hydrochloride is 1:2 ~ 3; The ratio of the amount of substance of described methoxamine hydrochloride, anhydrous sodium acetate is 1:1 ~ 2.
4. the method for claim 1, it is characterized in that in described step (2), the ratio of the amount of substance of the phenyl aldehyde O-methyloxime compounds shown in described formula II, divalent palladium salt catalyst, nitrating agent nitrite, oxygenant is 1:0.001 ~ 0.2:1 ~ 4:1 ~ 4.
5. the method for claim 1, is characterized in that, in described step (2), described nitrating agent nitrite is selected from potassium nitrite, Sodium Nitrite or silver nitrite.
6. the method for claim 1, is characterized in that in described step (3), and the ratio of the amount of substance of the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in described formula III, strong organic acid, formaldehyde is 1:2 ~ 3:3 ~ 6.
7. the method for claim 1, is characterized in that in described step (3), and in the mixed solvent of described tetrahydrofuran (THF), water, the volume ratio of tetrahydrofuran (THF), water is 8 ~ 15:1.
8. the method for claim 1, it is characterized in that in described step (1), described reaction solution a post-treating method is: after reaction terminates, reaction solution a adds extraction into ethyl acetate, solvent is removed under reduced pressure, obtained phenyl aldehyde O-methyloxime compounds shown in formula II after getting organic phase drying;
In described step (2), described reaction solution b post-treating method is: after reaction terminates, reaction solution b dchloromethane, filter, get after filtrate steaming removal solvent through column chromatography for separation, the mixed solvent being 20:1 with sherwood oil, ethyl acetate volume ratio, for eluent, collects the elutriant containing product, steams and desolventizes the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in obtained formula III;
In described step (3), described reaction solution c post-treating method is: after reaction terminates, reaction solution c adds saturated sodium carbonate solution to pH value for neutral, use extracted with diethyl ether again, get organic phase and remove solvent under reduced pressure after drying, residuum is through column chromatography for separation, and the mixed solvent being 6:1 with sherwood oil, ethyl acetate volume ratio is for eluent, collect the elutriant containing product, steam and desolventize the o-nitrobenzaldehyde compounds shown in obtained formula IV.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1495158A (en) * | 1998-05-11 | 2004-05-12 | �����ɷ� | Intermediate for preparing isoxazolinyl-3-acylbenzene and process for preparing said intermediate |
-
2013
- 2013-08-19 CN CN201310363181.XA patent/CN103467300B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1495158A (en) * | 1998-05-11 | 2004-05-12 | �����ɷ� | Intermediate for preparing isoxazolinyl-3-acylbenzene and process for preparing said intermediate |
Non-Patent Citations (2)
| Title |
|---|
| Palladium-Catalyzed Chelation-Assisted Aromatic C−H Nitration: Regiospecific Synthesis of Nitroarenes Free from the Effect of the Orientation Rules;Wei Zhang et al.;《Journal of Organic Chemistry》;20130520;第78卷;第5932页第1段至第5945页左栏倒数第2段 * |
| The Geometry of Displacements at Nonstereogenic Atoms: The Formal Displacement of Alkoxide from Alkoxyamines by Org anolit hium Reagents;Peter Beak et al.;《Journal of the American Chemical Society》;19861231;第108卷;第6021页右栏倒数第1段至第6022页左栏第1段 * |
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