CN103467300A - Synthesizing method for o-nitrobenzaldehyde compound - Google Patents
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Abstract
The invention provides a preparation method for an o-nitrobenzaldehyde compound. The method directly taking benzaldehyde compounds as starting raw materials comprises the following steps: firstly, converting a formyl group into an O-methyl oximido; secondly, taking divalent palladium salt as a catalyst, and realizing the carbon-hydrogen bond activation single nitration reaction on an o-position of an oximido under the condition that both an oxidant and a nitration agent exist; finally, removing the O-methyl oximido by using strong organic acid to obtain the o-nitrobenzaldehyde compound. The nitration method provided by the invention has the advantage of specificity in the o-position of a nitration position, the reaction process is safe and environment-friendly, the substrate is excellent in adaptability, and various substituents can realize o-position nitration; various benzaldehyde is directly taken as raw materials, so that the reaction steps are simple, and the synthesizing method is a novel route for synthesizing various o-nitrobenzaldehyde compounds containing substituents.
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, the raw material that can be used for the Cardiovarscular medicines such as synthesizing nitryl pyridine (nifedipine), nisoldipine, encainide, be also important organic synthesis raw material, be widely used in chemical industry.Ortho Nitro Benzaldehyde mainly be take Ortho Nitro Toluene at present as raw material, through oxidation, hydrolysis or the steps such as bromination, hydrolysis, obtain, but Ortho Nitro Toluene is made by mixed acid nitrification by toluene, in process, need the strong acid such as excessive nitric acid and sulfuric acid as reaction reagent and catalyzer, emit a large amount of heat in reaction process, easily cause and produce danger, produce in this course a large amount of waste gas spent acid, caused serious environmental problem simultaneously.In addition, take phenyl aldehyde as raw material, in the mixed solution that the vitriol oil and vinegar are joined, slowly drip benzal diethyl acid anhydrides, intermediate reacts with nitrosonitric acid, obtains yellow blocks of solid and adds aqueous sodium carbonate, separablely go out Ortho Nitro Benzaldehyde and paranitrobenzaldehyde, but in most of the cases adjacency pair position product is difficult to separate, this just cause the yield of product Ortho Nitro Benzaldehyde and purity all very low, this method faces a series of serious safety problem and the environmental problem that strong acid brings equally simultaneously.
In the market containing various substituent o-nitrobenzaldehyde compounds actually rare be because the locating rule that is subject to phenyl ring limits, cause containing the more difficult regiospecificity of various substituent o-nitrobenzaldehyde compounds ground, synthesizing on phenyl ring, reactions steps that need to be longer could be synthesized corresponding Ortho Nitro Benzaldehyde, and the reactions steps difference that different substituting groups relates to, the general method of neither one is synthesized.
In view of the problem of above existence, design a general o-nitrobenzaldehyde compounds synthetic route and seem and extremely be necessary.
Summary of the invention
In the market containing various substituent o-nitrobenzaldehyde compounds actually rare be because the locating rule that is subject to phenyl ring limits, cause on phenyl ring more difficult synthetic containing various substituent o-nitrobenzaldehyde compounds, reactions steps that need to be longer could be synthesized corresponding Ortho Nitro Benzaldehyde, and the reactions steps difference that different substituting groups relates to, the general method of neither one is synthesized.In order to overcome deficiency of the prior art, provide a kind of method of synthetic o-nitrobenzaldehyde compounds.
Technical scheme of the present invention is:
The synthetic method of the o-nitrobenzaldehyde compounds shown in a kind of 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 follows the tracks of and detects to reacting completely, and gained reaction solution a aftertreatment makes 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, preferably 1:2.7;
The ratio of the amount of substance of described methoxamine hydrochloride, anhydrous sodium acetate is 1:1～2, preferably 1:1.6;
The mixed solvent that described reaction solvent is ethanol, water volume ratio 1:1～10, preferably 1:3;
The volumetric usage of described reaction solvent is counted 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 followed the tracks of the detection reaction raw material to reacting completely with TLC, and the reaction times is 1～10 hour usually, preferably 3 hours.
(2) phenyl aldehyde O-methyloxime compounds, divalence 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 ℃～130 ℃ (preferably 110 ℃) temperature, TLC follows the tracks of and detects to reacting completely, and gained reaction solution b aftertreatment makes 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, divalence palladium salt catalyst, nitrating agent nitrite, oxygenant is 1:0.001～0.2:1～4:1～4, preferably 1:0.1:2:2.
Described divalence 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, preferably 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 followed the tracks of the detection reaction raw material to reacting completely with TLC, and the reaction times is 10～60 hours usually, preferably 48 hours.
The volumetric usage of described low polar organic solvent is counted 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, the formaldehyde solution that adds strong organic acid, massfraction 30～40%, airtight being heated to reacted at 30～110 ℃ of (preferably 110 ℃) temperature, TLC follows the tracks of and detects to reacting completely, and gained reaction solution c aftertreatment makes 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, preferably 1:2:4.
Described strong organic acid is preferably tosic acid.
The reaction of described step (3) is followed the tracks of the detection reaction raw material to reacting completely with TLC, and the reaction times is 1～24 hour usually, preferably 8 hours.
In the mixed solvent of described tetrahydrofuran (THF), water, the volume ratio of tetrahydrofuran (THF), water is generally 8～15:1, preferably 10:1.
The volumetric usage of the mixed solvent of described tetrahydrofuran (THF), water is counted 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 separately the alkyl of hydrogen, C1～C5, the alkoxyl group of C1～C5, ester group, hydroxyl, amido, trifluoromethyl, halogen or the phenyl of C1～C5; Described halogen is F, Cl, Br or I;
Preferred R
1, R
2, R
3independent separately is hydrogen, trifluoromethyl, Br or Cl.
In described step (1), described reaction solution a post-treating method is: after reaction finishes, reaction solution a adds the ethyl acetate extraction, removes solvent under reduced pressure after getting the organic phase drying, makes the phenyl aldehyde O-methyloxime compounds shown in formula II.
In described step (2), described reaction solution b post-treating method is: after reaction finishes, reaction solution b dilutes with methylene dichloride, filter, get filtrate steaming removal solvent by column chromatography for separation, the mixed solvent that sherwood oil, ethyl acetate volume ratio be 20:1 of take is eluent, collects the elutriant that contains product, steams and desolventizes the Ortho Nitro Benzaldehyde O-methyloxime compounds made shown in formula III.
In described step (3), described reaction solution c post-treating method is: after reaction finishes, it is neutrality that reaction solution c adds saturated sodium carbonate solution to pH value, use again extracted with diethyl ether, get organic phase and remove after drying solvent under reduced pressure, residuum is through column chromatography for separation, and the mixed solvent that sherwood oil, ethyl acetate volume ratio be 6:1 of take is eluent, the elutriant that collection contains product, steaming desolventizes and makes the o-nitrobenzaldehyde compounds shown in formula IV.
The present invention directly be take compound of benzaldehyde category as raw material, by carbonyl is converted into to oximido, the divalence palladium salt of take again is catalyzer, in the situation that oxygenant and nitrating agent exist, realize the C-H activation mono-nitration reaction on the oximido ortho position, finally in sour effect, again oxime is hydrolyzed to corresponding aldehyde, thereby realizes the nitrated a series of o-nitrobenzaldehyde compounds that obtains at the ortho position of compound of benzaldehyde category carbonyl.
In all examples of the present invention, step (2) although in the consumption of nitrating agent be greater than the consumption of reactant, the excessive nitrated side reaction that waits can not occur, only have all the time the mono-nitration product of highly selective to generate.
In the present invention, in step (2), preferred catalyst is palladium diacetate, 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.Take rudimentary property organic solvent as good, and 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, do not produce waste gas waste water.
(2) substrate adaptability is good, and various substituting groups can realize that ortho position is nitrated.
(3) the nitration reaction regioselectivity is good, has the narrow spectrum advantage in ortho position, nitrated position.
(4) directly take various phenyl aldehydes as raw material, reactions steps is simple, and is a kind of synthetic various variation routes containing substituent o-nitrobenzaldehyde compounds.
Embodiment
Below in conjunction with specific embodiment, the present invention is described in further detail, protection scope of the present invention is not limited to this.
Embodiment 1:
Take phenyl aldehyde as raw material, synthetic 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 the 100ml flask.Mixture is heated to back flow reaction, and TLC follows the tracks of detection, and after 3 hours, reaction finishes, and the gained mixing solutions extracts by 3 * 45mL ethyl acetate, and getting after the organic phase drying reduces pressure sloughs 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 ℃ of oil baths, TLC follows the tracks of detection, reaction in 48 hours finishes, 10mL methylene dichloride dilution for reaction solution, filtration obtains clear liquid, and steaming desolventizes, and by column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1), separates, 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, 40% formaldehyde solution 150mg is with adding reaction under 110 ℃ of sealed vessels after 2ml THF/0.2ml water dissolution, TLC follows the tracks of detection, after reaction in 8 hours finishes, it is neutral that reaction solution is neutralized to the pH value with saturated sodium carbonate solution, extracted with diethyl ether for mixed solution (10ml * 3), get organic phase reduces pressure and sloughs solvent after anhydrous sodium sulfate drying, residuum separates by column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1), collect elutriant, steaming desolventizes and obtains weak yellow liquid 2-nitrobenzaldehyde 69mg(95% yield).
Yellow solid; Mp38.9 ℃; IR (KBr): ν=1528 (NO
2), 1698 (C=O) cm
-1, 2866 (CO-H) cm
-1;
1h NMR (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:
Take the 4-trifluoromethylated benzaldehyde as raw material, synthetic 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 the 100ml flask.Mixture is heated to back flow reaction, TLC follows the tracks of detection, and after 3 hours, reaction finishes, and the gained mixing solutions extracts by 3 * 45mL ethyl acetate, getting after the organic phase drying reduces pressure sloughs solvent, obtains 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 ℃ of oil baths, TLC follows the tracks of detection, reaction in 48 hours finishes, 10mL methylene dichloride dilution for reaction solution, filtration obtains clear liquid, steaming desolventizes rear with column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) separation, the collection elutriant, steaming desolventizes and obtains 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, 40% formaldehyde solution 150mg is with adding reaction under 110 ℃ of sealed vessels after 2ml THF/0.2ml water dissolution, TLC follows the tracks of detection, reaction in 8 hours finishes, it is neutral that reaction solution is neutralized to the pH value with saturated sodium carbonate solution, extracted with diethyl ether for mixed solution (10ml * 3), get organic phase reduces pressure and sloughs solvent after anhydrous sodium sulfate drying, residuum separates by column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1), 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;
1h NMR (500MHz, CDCl
3) δ 10.49 (s, 1H), 8.43 (s, 1H), 8.09 (q, J=8.2Hz, 2H).
13c NMR (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:
Take the 3-bromobenzaldehyde as raw material, the synthetic bromo-2-nitrobenzaldehyde of 5-
(1) by 3-bromobenzaldehyde 0.915g(5.0mmol), methoxamine hydrochloride 1.12g, anhydrous sodium acetate 1.804g, 15ml ethanol, 45ml water adds in the 100ml flask.Mixture is heated to back flow reaction, TLC follows the tracks of detection, and after 3 hours, reaction finishes, and the gained mixing solutions extracts by 3 * 45mL ethyl acetate, getting after the organic phase drying reduces pressure sloughs solvent, obtains 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 ℃ of oil baths, TLC follows the tracks of detection, reaction in 48 hours finishes, 10mL methylene dichloride dilution for reaction solution, filtration obtains clear liquid, steaming desolventizes rear with column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) separation, the collection elutriant, steaming desolventizes and obtains the bromo-2-nitrobenzaldehyde of weak yellow liquid 5-O-methyloxime 96.7mg(78% yield).
(3) by the bromo-2-nitrobenzaldehyde of 5-O-methyloxime 124mg(0.5mmol), tosic acid 172mg, 40% formaldehyde solution 150mg is with adding reaction under 110 ℃ of sealed vessels after 2ml THF/0.2ml water dissolution, TLC follows the tracks of detection, reaction in 8 hours finishes, it is neutral that reaction solution is neutralized to the pH value with saturated sodium carbonate solution, extracted with diethyl ether for mixed solution (10ml * 3), get organic phase reduces pressure and sloughs solvent after anhydrous sodium sulfate drying, residuum separates by column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1), collect elutriant, steaming desolventizes and obtains the bromo-2-nitrobenzaldehyde of yellow solid 5-104mg(95% yield).
Yellow solid; Mp72.9 ℃; IR (KBr): ν=1522 (NO
2), 1692 (C=O) cm
-1, 2854 (CO-H) cm
-1;
1h NMR (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);
13c NMR (125MHz, CDCl
3): δ 186.7,148.1, and 136.5,132.6,129.5,126.1
Embodiment 4:
Take the 3-chlorobenzaldehyde as raw material, the synthetic chloro-2-nitrobenzaldehyde of 5-
(1) by 3-chlorobenzaldehyde 0.700g(5.0mmol), methoxamine hydrochloride 1.12g, anhydrous sodium acetate 1.804g, 15ml ethanol, 45ml water adds in the 100ml flask.Mixture is heated to back flow reaction, TLC follows the tracks of detection, and after 3 hours, reaction finishes, and the gained mixing solutions extracts by 3 * 45mL ethyl acetate, getting after the organic phase drying reduces pressure sloughs solvent, obtains 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 ℃ of oil baths, TLC follows the tracks of detection, reaction in 48 hours finishes, 10mL methylene dichloride dilution for reaction solution, filtration obtains clear liquid, steaming desolventizes rear with column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 20:1) separation, the collection elutriant, steaming desolventizes and obtains the chloro-2-nitrobenzaldehyde of yellow solid 5-O-methyloxime 85mg(80% yield).
(3) by the chloro-2-nitrobenzaldehyde of 5-O-methyloxime 107mg(0.5mmol), tosic acid 172mg, 40% formaldehyde solution 150mg is with adding reaction under 110 ℃ of sealed vessels after 2ml THF/0.2ml water dissolution, TLC follows the tracks of detection, reaction in 8 hours finishes, it is neutral that reaction solution is neutralized to the pH value with saturated sodium carbonate solution, extracted with diethyl ether for mixed solution (10ml * 3), get organic phase reduces pressure and sloughs solvent after anhydrous sodium sulfate drying, residuum separates by column chromatography chromatogram method (the leacheate proportioning: sherwood oil is to ethyl acetate volume ratio 6:1), collect elutriant, steaming desolventizes and obtains the chloro-2-nitrobenzaldehyde of faint yellow solid 5-87mg(95% yield).
Yellow solid; Mp77.2 ℃; IR (KBr): ν=1510 (NO
2), 1696 (C=O) cm
-1, 2854 (CO-H) cm
-1;
1h NMR (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);
13c NMR (125MHz, CDCl
3): δ 186.7,147.5, and 141.2,133.4,132.8,129.6,126.2.
Claims (10)
1. the synthetic method of the o-nitrobenzaldehyde compounds shown in a 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 follows the tracks of and detects to reacting completely, and gained reaction solution a aftertreatment makes the phenyl aldehyde O-methyloxime compounds shown in formula II;
The mixed solvent that described reaction solvent is ethanol, water volume ratio 1:1～10;
(2) phenyl aldehyde O-methyloxime compounds, divalence 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 ℃～130 ℃ temperature, TLC follows the tracks of and detects to reacting completely, and gained reaction solution b aftertreatment makes the Ortho Nitro Benzaldehyde O-methyloxime compounds shown in formula III;
Described divalence 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;
(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, the formaldehyde solution that adds strong organic acid, massfraction 30～40%, airtight being heated to reacted at 30～110 ℃ of temperature, TLC follows the tracks of and detects to reacting completely, and gained reaction solution c aftertreatment makes the o-nitrobenzaldehyde compounds shown in formula IV;
In formula I～formula IV, R
1, R
2, R
3independently be selected from separately the alkyl of hydrogen, C1～C5, the alkoxyl group of C1～C5, ester group, hydroxyl, amido, trifluoromethyl, halogen or the phenyl of C1～C5; Described halogen is F, Cl, Br or I.
2. the method for claim 1, is characterized in that described R
1, R
2, R
3independent separately is hydrogen, trifluoromethyl, Br or Cl.
3. the method for claim 1, is characterized in that, in described step (1), 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, divalence 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 low polar organic solvent is selected from 1,2-ethylene dichloride, acetonitrile, methylene dichloride or chloroform.
6. 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.
7. 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.
8. the method for claim 1, is characterized in that, in described step (3), described strong organic acid is tosic acid.
9. 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.
10. the method for claim 1, it is characterized in that in described step (1), described reaction solution a post-treating method is: after reaction finishes, reaction solution a adds the ethyl acetate extraction, remove solvent under reduced pressure after getting the organic phase drying, make the phenyl aldehyde O-methyloxime compounds shown in formula II;
In described step (2), described reaction solution b post-treating method is: after reaction finishes, reaction solution b dilutes with methylene dichloride, filter, get filtrate steaming removal solvent by column chromatography for separation, the mixed solvent that sherwood oil, ethyl acetate volume ratio be 20:1 of take is eluent, collects the elutriant that contains product, steams and desolventizes the Ortho Nitro Benzaldehyde O-methyloxime compounds made shown in formula III;
In described step (3), described reaction solution c post-treating method is: after reaction finishes, it is neutrality that reaction solution c adds saturated sodium carbonate solution to pH value, use again extracted with diethyl ether, get organic phase and remove after drying solvent under reduced pressure, residuum is through column chromatography for separation, and the mixed solvent that sherwood oil, ethyl acetate volume ratio be 6:1 of take is eluent, the elutriant that collection contains product, steaming desolventizes and makes the o-nitrobenzaldehyde compounds shown in formula IV.
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| CN103922909A (en) * | 2014-03-31 | 2014-07-16 | 浙江工业大学 | Method for synthesizing beta-fluoro-alpha,beta-unsaturated ketene compounds |
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| CN103922904B (en) * | 2014-03-31 | 2016-05-18 | 浙江工业大学 | A kind of method of synthetic 2-fluorinated aryl carbonyls |
| CN105777547A (en) * | 2016-04-06 | 2016-07-20 | 岳阳亚王精细化工有限公司 | Synthesis method of m-nitrobenzaldehyde |
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