CN103467300A - Synthesizing method for o-nitrobenzaldehyde compound - Google Patents

Abstract

The invention provides a preparation method of o-nitrobenzaldehyde compounds. The present invention directly uses benzaldehyde compounds as starting materials, first converts the aldehyde group into an O-methyloxime group, and then uses divalent palladium salt as a catalyst to realize the oxime group ortho-position in the presence of an oxidizing agent and a nitrating reagent The carbon-hydrogen bond on the carbon-hydrogen bond activates the mononitration reaction, and finally uses a strong organic acid to remove the O-methyloxime group to obtain o-nitrobenzaldehyde compounds. The nitration method of the present invention has the advantage of ortho-specificity of the nitration position, the reaction process is safe and environmentally friendly, the substrate adaptability is good, and various substituents can realize the ortho-position nitration; various benzaldehydes are directly used as raw materials, and the reaction steps are simple , is a new route for the synthesis of various substituent-containing o-nitrobenzaldehyde compounds.

Description

A kind of synthetic method of o-nitrobenzaldehyde compound

technical field

The invention relates to a method for synthesizing an organic compound, in particular to a method for preparing an o-nitrobenzaldehyde compound. the

Background technique

O-nitrobenzaldehyde compounds are important pharmaceutical intermediates, which can be used to synthesize nitropyridine (Niafedin), nisoldipine, encaramide and other raw materials for the treatment of cardiovascular diseases, and are also important organic synthesis raw materials. Widely used in chemical industry. At present, o-nitrobenzaldehyde is mainly obtained from o-nitrotoluene through oxidation, hydrolysis or bromination, hydrolysis and other steps. However, o-nitrotoluene is obtained from toluene through mixed acid nitration, and excess nitric acid and sulfuric acid are required in the process. Strong acids are used as reaction reagents and catalysts, and a large amount of heat is released during the reaction process, which is likely to cause production hazards. At the same time, a large amount of waste gas and waste acids are produced during this process, causing serious environmental problems. In addition, using benzaldehyde as the raw material, in the mixture of concentrated sulfuric acid and vinegar, slowly add benzylidene diacetic anhydride, the intermediate reacts with fuming nitric acid, and the yellow blocky solid can be separated by adding sodium carbonate aqueous solution. Nitrobenzaldehyde and p-nitrobenzaldehyde, but in most cases the ortho-para product is difficult to separate, which causes the yield and purity of the product o-nitrobenzaldehyde to be very low. A series of serious safety and environmental problems. the

At present, o-nitrobenzaldehyde compounds containing various substituents on the market are rare due to the limitation of the positioning rules of the benzene ring, which makes o-nitrobenzaldehyde compounds containing various substituents on the benzene ring more difficult. Regiospecific synthesis requires longer reaction steps to synthesize the corresponding o-nitrobenzaldehyde, and different substituents involve different reaction steps, so there is no general method for synthesis. the

In view of the above problems, it is necessary to design a general synthetic route of o-nitrobenzaldehyde compounds. the

Contents of the invention

O-nitrobenzaldehyde compounds containing various substituents on the market are rare due to the limitation of the positioning rules of the benzene ring, which makes it difficult to obtain o-nitrobenzaldehyde compounds containing various substituents on the benzene ring. Synthesis requires longer reaction steps to synthesize the corresponding o-nitrobenzaldehyde, and different substituents involve different reaction steps, so there is no general method for synthesis. In order to overcome the deficiencies in the prior art, a method for synthesizing o-nitrobenzaldehyde compounds is provided. the

Technical scheme of the present invention is:

A synthetic method of o-nitrobenzaldehyde compounds shown in formula IV, said method adopts the following steps:

(1) The benzaldehyde compound shown in formula I, methoxyamine hydrochloride, anhydrous sodium acetate, and the reaction solvent are mixed, heated to reflux reaction, TLC tracking detection until the reaction is complete, and the obtained reaction solution a is post-processed to obtain the formula Benzaldehyde O-methyl oxime compounds shown in II;

The ratio of the amount of benzaldehyde compounds shown in the formula I to methoxyamine hydrochloride is 1:2～3, preferably 1:2.7;

The ratio of the amount of substance of the methoxyamine hydrochloride and anhydrous sodium acetate is 1:1～2, preferably 1:1.6;

The reaction solvent is a mixed solvent of ethanol and water with a volume ratio of 1:1 to 10, preferably 1:3;

The volumetric amount of the reaction solvent is usually 8-20 mL/mmol based on the amount of the benzaldehyde compound represented by I. the

The reaction in the step (1) is tracked and detected by TLC until the reaction is complete, usually the reaction time is 1-10 hours, preferably 3 hours. the

(2) Add the benzaldehyde O-methyl oxime compound represented by formula II obtained in step (1), divalent palladium salt catalyst, nitrating reagent nitrite, oxidizing agent and low-polarity organic solvent into a sealed pressure-resistant container in sequence , heat the reaction in a sealed environment at a temperature of 80°C to 130°C (preferably 110°C), track and detect by TLC until the reaction is complete, and post-process the obtained reaction solution b to obtain o-nitrobenzaldehyde O-methyl oximes represented by formula III compound;

The ratio of the amount of the benzaldehyde O-methyl oxime compound shown in the formula II, the divalent palladium salt catalyst, the nitrating reagent nitrite, and the oxidizing agent is 1:0.001～0.2:1～4:1～ 4. Preferably 1:0.1:2:2. the

The divalent palladium salt catalyst is selected from palladium catalysts such as palladium chloride, bis(triphenylphosphine)palladium dichloride, palladium diacetate or palladium trifluoroacetate, and is preferably palladium diacetate. the

The oxidizing agent is potassium persulfate or potassium monopersulfate compound salt, preferably potassium persulfate. the

The low-polarity organic solvent is selected from 1,2-dichloroethane, acetonitrile, dichloromethane or chloroform, preferably 1,2-dichloroethane. the

The nitrite of the nitrating agent is selected from potassium nitrite, sodium nitrite or silver nitrite, preferably silver nitrite. the

The reaction in the step (2) is tracked and detected by TLC until the reaction is complete, usually the reaction time is 10-60 hours, preferably 48 hours. the

The volumetric usage of the low-polarity organic solvent is usually 8-20 mL/mmol based on the amount of the benzaldehyde O-methyl oxime compound represented by formula II. the

(3) Dissolving the o-nitrobenzaldehyde O-methyloxime compound represented by formula III obtained in step (2) in a mixed solvent of tetrahydrofuran and water, adding a strong organic acid and formaldehyde with a mass fraction of 30-40% solution, sealed and heated to 30-110°C (preferably 110°C) for reaction, followed by TLC detection until the reaction is complete, and the obtained reaction solution c is post-processed to obtain the o-nitrobenzaldehyde compound shown in formula IV;

The ratio of the o-nitrobenzaldehyde O-methyloxime compound represented by the formula III, the strong organic acid, and the formaldehyde is 1:2-3:3-6, preferably 1:2:4. the

The strong organic acid is preferably p-toluenesulfonic acid. the

The reaction in the step (3) is tracked and detected by TLC until the reaction is complete, usually the reaction time is 1-24 hours, preferably 8 hours. the

In the mixed solvent of tetrahydrofuran and water, the volume ratio of tetrahydrofuran and water is usually 8 to 15:1, preferably 10:1. the

The volumetric usage of the mixed solvent of tetrahydrofuran and water is usually 3-8 mL/mmol based on the amount of the o-nitrobenzaldehyde O-methyloxime compound represented by formula III. the

In formulas I to IV, R ₁ , R ₂ , and R ₃ are each independently selected from hydrogen, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 ester, hydroxyl, amino, trifluoro Methyl, halogen or phenyl; said halogen is F, Cl, Br or I;

Preferably R ₁ , R ₂ , R ₃ are each independently hydrogen, trifluoromethyl, Br or Cl.

In the step (1), the post-treatment method of the reaction liquid a is as follows: after the reaction, the reaction liquid a is extracted with ethyl acetate, the organic phase is dried, and the solvent is evaporated under reduced pressure to obtain the benzene represented by formula II. Formaldehyde O-methyl oxime compounds. the

In the step (2), the post-treatment method of the reaction liquid b is as follows: after the reaction, the reaction liquid b is diluted with dichloromethane, filtered, and the filtrate is evaporated to remove the solvent and then separated by column chromatography. Ethyl ester volume ratio is that the mixed solvent of 20: 1 is eluent, collects the eluent that contains product, evaporates solvent and makes o-nitrobenzaldehyde O-methyl oxime compound shown in formula III. the

In the step (3), the post-treatment method of the reaction liquid c is as follows: after the reaction, the reaction liquid c is added with saturated sodium carbonate solution until the pH value is neutral, and then extracted with ether, and the organic phase is dried and then decompressed The solvent was evaporated, and the residue was separated by column chromatography, using a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 6:1 as the eluent, and the eluent containing the product was collected, and the solvent was evaporated to obtain the formula IV o-nitrobenzaldehyde compounds. the

The present invention directly uses benzaldehyde compounds as raw materials, converts carbonyl groups into oxime groups, and uses divalent palladium salts as catalysts to activate the carbon-hydrogen bond at the ortho position of the oxime groups in the presence of oxidants and nitrating reagents. Mononitration reaction, and finally the oxime is hydrolyzed to the corresponding aldehyde under the action of acid, so that a series of o-nitrobenzaldehyde compounds can be obtained by nitration at the ortho position of the carbonyl of the benzaldehyde compound. the

In all examples of the present invention, although the amount of nitrating reagent in step (2) is greater than the amount of reactants, side reactions such as excessive nitration will not occur, and only highly selective mono-nitration products will always be generated. the

In the present invention, the preferred catalyst in step (2) is palladium diacetate, which is characterized by high yield, relatively cheap price and easy storage and access. the

The solvent for the nitration reaction in step (2) is preferably 1,2-dichloroethane. Low-grade organic solvents are preferred, and 1,2-dichloroethane is a solvent with a low dielectric constant. It has a relatively high boiling point, is not volatile, and is easy to store. the

Compared with prior art, the beneficial effect of the present invention is:

(1) Safety and environmental protection, no waste gas and waste water. the

(2) The substrate has good adaptability, and various substituents can realize ortho-nitration. the

(3) The regioselectivity of the nitrification reaction is good, and it has the advantage of ortho-specificity of the nitrification position. the

(4) Directly using various benzaldehydes as raw materials, the reaction steps are simple, and it is a new route for synthesizing various o-nitrobenzaldehyde compounds containing substituents. the

Detailed ways

The present invention will be further described in detail below in conjunction with specific examples, and the protection scope of the present invention is not limited thereto. the

Example 1:

Using benzaldehyde as raw material to synthesize 2-nitrobenzaldehyde

(1) Add 0.530g (5.0mmol) of benzaldehyde, 1.12g (13.4mmol) of methoxyamine hydrochloride, 1.804g (22mmol) of anhydrous sodium acetate, 15ml of ethanol, and 45ml of water into a 100ml flask. The mixture was heated to reflux reaction, followed by TLC detection, the reaction was completed after 3 hours, the resulting mixed solution was extracted with 3×45mL ethyl acetate, the organic phase was taken and dried, and the solvent was removed under reduced pressure to obtain a light yellow liquid benzaldehyde-O-methyl Oxime 0.641g (95% yield). the

(2) Add 67.5 mg (0.5 mmol) of benzaldehyde O-methyloxime, 11 mg (0.05 mmol) of palladium diacetate, 154 mg (1.0 mmol) of silver nitrite, 270 mg (1.0 mmol) of potassium persulfate and 1,2-bis Ethyl chloride (5ml) was successively added to a 10ml sealed pressure vessel. The mixture was heated and reacted in an oil bath at 110°C, followed by TLC detection, and the reaction was completed after 48 hours. The reaction liquid was diluted with 10 mL of dichloromethane, filtered to obtain a clear liquid, and the solvent was evaporated, and column chromatography (eluent ratio : Petroleum ether to ethyl acetate volume ratio 20:1) Separation, collect the eluate, distill off the solvent to obtain 50 mg of light yellow liquid 2-nitrobenzaldehyde O-methyl oxime (78% yield). the

(3) Dissolve 2-nitrobenzaldehyde O-methyloxime 90mg (0.5mmol), p-toluenesulfonic acid 172mg, 40% formaldehyde solution 150mg in 2ml THF/0.2ml water, put into a sealed container and react at 110°C, TLC Tracking detection, after 8 hours of reaction, the reaction solution was neutralized with saturated sodium carbonate solution until the pH value was neutral, the mixture was extracted with ether (10ml×3), the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure , and the residue was separated by column chromatography (eluent ratio: petroleum ether to ethyl acetate volume ratio 6:1), collected the eluent, and evaporated the solvent to obtain 69 mg of light yellow liquid 2-nitrobenzaldehyde ( 95% yield). the

Yellow solid; mp38.9℃; IR(KBr):ν=1528(NO ₂ ), 1698(C=O)cm ^-1 , 2866(-CO-H)cm ^-1 ; ¹ H NMR(500MHz, CDCl ₃ )δ10.44(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); ¹³ CNMR(125MHz,CDCl ₃ ):δ188.1,149.6,134.0,133.7,131.4,129.6,124.5.

Example 2:

Synthesis of 4-trifluoromethyl-2-nitrobenzaldehyde from 4-trifluoromethylbenzaldehyde

(1) Add 0.870g (5.0mmol) of 4-trifluoromethylbenzaldehyde, 1.12g of methoxyamine hydrochloride, 1.804g of anhydrous sodium acetate, 15ml of ethanol, and 45ml of water into a 100ml flask. The mixture was heated to reflux reaction, followed by TLC detection, and the reaction was completed after 3 hours. The resulting mixed solution was extracted with 3 × 45mL ethyl acetate, the organic phase was taken and dried, and the solvent was removed under reduced pressure to obtain a light yellow liquid 4-trifluoromethylbenzene Formaldehyde-O-methyloxime 0.995g (98% yield). the

(2) 101.5mg (0.5mmol) of 4-trifluoromethylbenzaldehyde-O-methyloxime, 11mg (0.05mmol) of palladium diacetate, 154mg (1.0mmol) of silver nitrite, 270mg (1.0mmol) of potassium persulfate ) and 1,2-dichloroethane (5ml) were sequentially added to a 10ml sealed pressure vessel. The mixture was heated and reacted in an oil bath at 110°C, followed by TLC detection, and the reaction was completed after 48 hours. The reaction liquid was diluted with 10 mL of dichloromethane, and the clear liquid was obtained by filtration. After the solvent was evaporated, column chromatography (eluent ratio : Petroleum ether to ethyl acetate volume ratio 20:1) to separate, collect the eluate, distill off the solvent to obtain a light yellow liquid 4-trifluoromethyl-2-nitrobenzaldehyde O-methyl oxime 95mg (73% yield Rate). the

(3) Dissolve 4-trifluoromethyl-2-nitrobenzaldehyde O-methyloxime 124mg (0.5mmol), p-toluenesulfonic acid 172mg, 40% formaldehyde solution 150mg in 2ml THF/0.2ml water and add to seal The container was reacted at 110°C, followed by TLC detection, and the reaction was completed after 8 hours. The reaction solution was neutralized with saturated sodium carbonate solution until the pH value was neutral. The mixed solution was extracted with ether (10ml×3), and the organic phase was dried over anhydrous sodium sulfate. After that, the solvent was removed under reduced pressure, and the residue was separated by column chromatography (eluent ratio: petroleum ether to ethyl acetate volume ratio 6:1), the eluate was collected, and the solvent was evaporated to obtain a light yellow liquid 4- Trifluoromethyl-2-nitrobenzaldehyde 114 mg (95% yield). the

Yellow oily liquid; IR(neat):ν=1543(NO ₂ ),1705(C=O)cm ^-1 ,2891(-CO-H)cm ^-1 ; ¹ H NMR(500MHz,CDCl ₃ )δ10.49 (s,1H),8.43(s,1H),8.09(q,J=8.2Hz,2H). ¹³ C NMR(126MHz,CDCl ₃ ):δ186.9,149.4,135.6(q,J _FC =8.7Hz), 134.0, 130.9(q, J _FC =3.4Hz), 130.8, 122.2(q, J _FC =271.9Hz), 122.0(q, J _FC =3.8Hz).

Example 3:

Using 3-bromobenzaldehyde as raw material to synthesize 5-bromo-2-nitrobenzaldehyde

(1) Add 0.915g (5.0mmol) of 3-bromobenzaldehyde, 1.12g of methoxyamine hydrochloride, 1.804g of anhydrous sodium acetate, 15ml of ethanol, and 45ml of water into a 100ml flask. The mixture was heated to reflux reaction, followed by TLC detection, the reaction was completed after 3 hours, the resulting mixed solution was extracted with 3 × 45mL ethyl acetate, the organic phase was taken and dried, and the solvent was removed under reduced pressure to obtain a light yellow solid 3-bromobenzaldehyde-O - Methyloxime 0.994 g (98% yield). the

(2) 101.5mg (0.5mmol) of 3-bromobenzaldehyde-O-methyloxime, 11mg (0.05mmol) of palladium diacetate, 154mg (1.0mmol) of silver nitrite, 270mg (1.0mmol) of potassium persulfate and 1 , 2-dichloroethane (5ml) was sequentially added to a 10ml sealed pressure vessel. The mixture was heated and reacted in an oil bath at 110°C, followed by TLC detection, and the reaction was completed after 48 hours. The reaction liquid was diluted with 10 mL of dichloromethane, and the clear liquid was obtained by filtration. After the solvent was evaporated, column chromatography (eluent ratio : Petroleum ether to ethyl acetate volume ratio 20:1) Separation, collect the eluate, distill off the solvent to obtain 96.7 mg of light yellow liquid 5-bromo-2-nitrobenzaldehyde O-methyl oxime (78% yield) . the

(3) Dissolve 124mg (0.5mmol) of 5-bromo-2-nitrobenzaldehyde O-methyloxime, 172mg p-toluenesulfonic acid, 150mg 40% formaldehyde solution in 2ml THF/0.2ml water and add to a sealed container at 110°C After 8 hours of reaction, the reaction solution was neutralized with saturated sodium carbonate solution until the pH value was neutral. The mixture was extracted with ether (10ml×3), and the organic phase was dried over anhydrous sodium sulfate and then decompressed. The solvent was removed, and the residue was separated by column chromatography (eluent ratio: petroleum ether to ethyl acetate volume ratio 6:1), the eluent was collected, and the solvent was evaporated to obtain a yellow solid 5-bromo-2- Nitrobenzaldehyde 104mg (95% yield). the

Yellow solid; mp72.9℃; IR(KBr):ν=1522(NO ₂ ), 1692(C=O)cm ^-1 , 2854(-CO-H)cm ^-1 ; ¹ H NMR(500MHz, CDCl ₃ ):δ10.40(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); ¹³ C NMR (125MHz, CDCl ₃ ):δ186.7,148.1,136.5,132.6,129.5,126.1

Embodiment 4:

Using 3-chlorobenzaldehyde as raw material to synthesize 5-chloro-2-nitrobenzaldehyde

(1) Add 0.700g (5.0mmol) of 3-chlorobenzaldehyde, 1.12g of methoxyamine hydrochloride, 1.804g of anhydrous sodium acetate, 15ml of ethanol, and 45ml of water into a 100ml flask. The mixture was heated to reflux reaction, followed by TLC detection, the reaction was completed after 3 hours, the resulting mixed solution was extracted with 3 × 45mL ethyl acetate, the organic phase was taken and dried, and the solvent was removed under reduced pressure to obtain a yellow solid 3-chlorobenzaldehyde-O- Methyloxime 0.828g (98% yield). the

(2) 84mg (0.5mmol) of 3-chlorobenzaldehyde O-methyloxime, 11mg (0.05mmol) of palladium diacetate, 154mg (1.0mmol) of silver nitrite, 270mg (1.0mmol) of potassium persulfate and 1,2 - Dichloroethane (5ml) was sequentially added to a 10ml sealed pressure vessel. The mixture was heated and reacted in an oil bath at 110°C, followed by TLC detection, and the reaction was completed after 48 hours. The reaction liquid was diluted with 10 mL of dichloromethane, and the clear liquid was obtained by filtration. After the solvent was evaporated, column chromatography (eluent ratio : Petroleum ether to ethyl acetate volume ratio 20:1) separation, the eluate was collected, and the solvent was evaporated to obtain 85 mg of 5-chloro-2-nitrobenzaldehyde O-methyl oxime as a yellow solid (80% yield). the

(3) Dissolve 5-chloro-2-nitrobenzaldehyde O-methyloxime 107mg (0.5mmol), p-toluenesulfonic acid 172mg, 40% formaldehyde solution 150mg in 2ml THF/0.2ml water and add to a sealed container at 110°C After 8 hours of reaction, the reaction solution was neutralized with saturated sodium carbonate solution until the pH value was neutral. The mixture was extracted with ether (10ml×3), and the organic phase was dried over anhydrous sodium sulfate and then decompressed. The solvent was removed, and the residue was separated by column chromatography (eluent ratio: petroleum ether to ethyl acetate volume ratio 6:1), the eluent was collected, and the solvent was evaporated to obtain a light yellow solid 5-chloro-2 - Nitrobenzaldehyde 87 mg (95% yield). the

Yellow solid; mp77.2℃; IR(KBr):ν=1510(NO ₂ ), 1696(C=O)cm ^-1 , 2854(-CO-H)cm ^-1 ; ¹ H NMR(500MHz, CDCl ₃ ):δ10.43(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); ¹³ C NMR (125MHz, CDCl ₃ ): δ186.7, 147.5, 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.