CN102633646A - New preparation method of 5-nitro-salicylaldehyde - Google Patents
New preparation method of 5-nitro-salicylaldehyde Download PDFInfo
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- CN102633646A CN102633646A CN2012101025806A CN201210102580A CN102633646A CN 102633646 A CN102633646 A CN 102633646A CN 2012101025806 A CN2012101025806 A CN 2012101025806A CN 201210102580 A CN201210102580 A CN 201210102580A CN 102633646 A CN102633646 A CN 102633646A
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Abstract
The invention belongs to the technical field of preparation of chemical intermediates needed by the synthetic process of medicine, dye, pesticide, spice and the like, and particularly relates to a method for preparing 5-nitro-salicylaldehyde by an improved low-temperature nitration method, which takes salicylaldehyde as a raw material; and the 5-nitro-salicylaldehyde is prepared by the improved low-temperature nitration method. In the reaction process, a brand new ternary mixed solvent system consisting of hydrofluoric acid, acetic anhydride and acetic acid is adopted, so that the reaction speed of low-temperature nitration and the yield of the 5-nitro-salicylaldehyde synthesized by the nitration method can be successfully improved. The synthesis conditions of the method can be easily controlled, so that the method is especially suitable for preparing the 5-nitro-salicylaldehyde in a laboratory; and meanwhile, the raw materials are easily obtained, and the production cost is comparatively low, so that the method has certain implementation value and socio-economic benefit.
Description
Technical field
The invention belongs to the preparing technical field of the chemical intermediate in the building-up processes such as medicine, dyestuff, agricultural chemicals and spices, be specially the method for the nitrated 5-of the preparation nitrosalicylaldehyde of low temperature after a kind of improve.
Background technology
The 5-nitrosalicylaldehyde is a kind of chemical intermediate that is widely used in the building-up processes such as medicine, dyestuff, agricultural chemicals and spices.In the development and use of medicine; With the 5-nitrosalicylaldehyde is raw material synthetic Dronedarone (Dronedarone hydrochloride); Chemical name is 2-normal-butyl-3-[4-(the amino propoxy-of 3-di-n-butyl) benzoyl-]-5-methylsulfonyl amido cumarone, is a kind of important drugs of treating cardiovascular disorder; In marine drug chitosan synthetic, adopt the bacteriostatic action of the hydroxypropyl chitosan schiff bases of 5-nitrosalicylaldehyde preparation will be apparently higher than the hydroxypropyl chitosan schiff bases for preparing by salicylic aldehyde merely with resistance of oxidation.And be that raw material synthetic spirobenzopyran has excellent photochromic properties with the 5-nitrosalicylaldehyde, common all among all kinds of bibliographical informations as a kind of novel optical information, optical storage and fluorescent switch material.
With wide material sources, cheap salicylic aldehyde is that raw material prepares the 5-nitrosalicylaldehyde, adopts the low temperature nitrofication process in the past.Reaction process is shown in following equation:
Reaction is a nitrating agent with the nitrosonitric acid, is solvent with the Glacial acetic acid min. 99.5, and in ice-water bath, carries out.This reaction mainly exists the shortcoming of two aspects: the one, and 3 nitro replacements with 5 of salicylic aldehyde are competing reactions; Thereby the content of by product 3-nitrosalicylaldehyde is higher in the nitrosalicylaldehyde that causes synthesizing, and causes very big difficulty for the separation purification in later stage; The 2nd, because the initial reaction very exothermic, for the control reaction must be carried out in ice-water bath, but the speed of reaction under the low temperature is little.Its result has reduced productive rate, is unfavorable for the scale operation of 5-nitrosalicylaldehyde.
Summary of the invention
The present invention is primarily aimed at above-mentioned subject matter; Designed brand-new reaction solvent system; On existing basis, improved the process that nitrofication process prepares the 5-nitrosalicylaldehyde, reduced the generation of by product 3-nitrosalicylaldehyde, and improved the speed of reaction under the low temperature; Thereby simplified separation steps, successfully improved the productive rate of 5-nitrosalicylaldehyde.Concrete synthesis flow is shown in following equation:
Its concrete steps are following:
At room temperature earlier salicylic aldehyde is dissolved in the acid solvent system, in ice-water bath and under the stirring condition, in the regular hour He under the temperature, nitrosonitric acid is added drop-wise in the reaction vessel lentamente then, heat up stage by stage after dropwising, reaction 2h finishes.At last reaction solution is poured in the mixture of ice and water, obtain yellow mercury oxide; Suction filtration obtains nitryl compound; Mixture is isolating to lurid 5-nitrosalicylaldehyde through the water extraction process again.
Its above acid solvent system is the tertiary mixture of hydrofluoric acid, acetic anhydride and acetate.Glacial acetic acid min. 99.5 is as main reaction solvent; Acetic anhydride can improve nitryl positive ion (NO in the nitrifying process as the reaction water-removal additive
2 +) concentration, thereby improve the speed of reaction under the low temperature; The adding of hydrofluoric acid can suppress the 3-position and replace production of by-products.
The process that wherein slowly drips nitrosonitric acid will be accomplished in 2.5h, and controlled temperature is at 5～10 ℃.
Said stage temperature increasing schedule is 8～10 ℃ of reaction 1h down, continues reaction 1h down at 15～20 ℃ then and finishes.
Products obtained therefrom characterizes through ir spectra and H nuclear magnetic resonance spectrum, and concrete data are following:
Ir spectra (KBr, cm
-1): 3069cm
-12883cm
-11664cm
-11625,1581,1472cm
-11514,1339cm
-11287,1186,1090cm
-1921,715,629cm
-1833,780cm
-1
1HNMR spectrum (600MHz, CDCl
3, ppm): 11.61 (s, 1H ,-OH); 10.01 (s, 1H ,-CHO); 8.58 (s, 1H, ArH); 8.42 (m, 1H, ArH); 7.14 (m, 1H, ArH).
Special-effect of the present invention: the ternary solvent system that is designed can obviously reduce the ratio of by product 3-nitrosalicylaldehyde, and has improved speed of reaction nitrated under the low temperature.Thereby improved the productive rate that the salicylic aldehyde nitrofication process prepares the 5-nitrosalicylaldehyde, maximum output has reached 52%.Simplify the separating process of follow-up isomers simultaneously, helped the extensive synthetic of 5-nitrosalicylaldehyde.The production cost of the inventive method is relatively low, has certain implementary value and economic results in society.
Description of drawings
Fig. 1: the ir spectra of product;
Fig. 2: product
1HNMR spectrum;
Fig. 3: the mechanism explaination that ternary solvent system is improved productive rate: the adding of HF, because the hydrogen bond between F and the H is better than the hydrogen bond between O and the H, hydrogen bond has saturability simultaneously, thereby utilizes the occupy-place effect of hydrogen bond, has improved the substituted proportion of products in 5-position.
Embodiment
Following content is only as to further elaboration of the present invention and explanation, and do not lie in the protected content scope of the present invention that limits.
Embodiment 1:
Measure 100ml Glacial acetic acid min. 99.5,12.5g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde respectively and join successively in the 250ml torticollis there-necked flask, in ice-water bath, constantly stir and be cooled to below 5 ℃.The 16.6g nitrosonitric acid is placed constant pressure funnel, and controlled temperature is added drop-wise to nitrosonitric acid in the there-necked flask in 2.5h in 5～10 ℃ of scopes equably.Controlled temperature is warming up to 15～20 ℃ again and continues reaction 1h at 8～10 ℃ of reaction 1h then.While hot reaction soln is poured in the trash ice that fills 500g and the water mixture and stirred, place 5h (or place and spend the night).Suction filtration, washing, drying obtains yellow powder solid 28.3g.Through obtaining lurid 5-nitrosalicylaldehyde powder 14.8g after the water extracting, productive rate is 52%.
Ir spectra (KBr, cm
-1): 3069cm
-12883cm
-11664cm
-11625,1581,1472cm
-11514,1339cm
-11287,1186,1090cm
-1921,715,629cm
-1833,780c
M-1.
1HNMR spectrum (600MHz, CDCl
3, ppm): 11.61 (s, 1H ,-OH); 10.01 (s, 1H ,-CHO); 8.58 (s, 1H, ArH); 8.42 (m, 1H, ArH); 7.14 (m, 1H, ArH).
Embodiment 2:
Measure 100ml Glacial acetic acid min. 99.5,12.5g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde respectively and join successively in the 250ml torticollis there-necked flask, in ice-water bath, constantly stir and be cooled to below 5 ℃.The 16.6g nitrosonitric acid is placed constant pressure funnel, and controlled temperature is added drop-wise to nitrosonitric acid in the there-necked flask in 2.5h in 5～102 scopes equably.Controlled temperature is warming up to 15～20 ℃ again and continues reaction 1h at 8～10 ℃ of reaction 1h then.While hot reaction soln is fallen the people and contain in trash ice and the water mixture of 500g and stir, place 5h (or place and spend the night).Suction filtration, washing, drying obtains yellow powder solid 25.5g.Through obtaining lurid 5-nitrosalicylaldehyde powder 12.7g after the water extracting, productive rate is 50%.
Ir spectra (KBr, cm
-1): 3070cm
-12885cm
-11657cm
-11614,1578,1447cm
-11527,1352cm
-11260,1200,1090cm
-1950,742,629cm
-1825,780cm
-1
1HNMR spectrum (600MHz, CDCl
3, ppm): 11.62 (s, 1H ,-OH); 10.01 (s, 1H ,-CHO); 8.57 (s, 1H, ArH); 8.41 (m, 1H, ArH); 7.12 (m, 1H, ArH).
Embodiment 3:
Measure 100ml Glacial acetic acid min. 99.5,5.0g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde respectively and join successively in the 250ml torticollis there-necked flask, in ice-water bath, constantly stir and be cooled to below 5 ℃.The 16.6g nitrosonitric acid is placed constant pressure funnel, and controlled temperature is added drop-wise to nitrosonitric acid in the there-necked flask in 2.5h in 5～10 ℃ of scopes equably.Controlled temperature is warming up to 15～20 ℃ again and continues reaction 1h at 8～10 ℃ of reaction 1h then.While hot reaction soln is fallen the people and contain in trash ice and the water mixture of 500g and stir, place 5h (or place and spend the night).Suction filtration, washing, drying obtains yellow powder solid 32.0g.Through obtaining lurid 5-nitrosalicylaldehyde powder 12.6g after the water extracting, productive rate is 39%.The reason that this synthetic productive rate reduces significantly is 0.4 times of the usage quantity of the hydrofluoric acid embodiment that has only the front.
Ir spectra (KBr, cm
-1): 3068cm
-12880cm
-11664cm
-11626,1581,1471cm
-11512,1338cm
-11286,1184,1089cm
-1920,716,628em
-1833,779cm
-1
1HNMR spectrum (600MHz, CDCl
3, ppm): 11.62 (s, 1H ,-OH); 10.01 (s, 1H ,-CHO); 8.57 (s, 1H, ArH); 8.41 (m, 1H, ArH); 7.12 (m, 1H, ArH).
Claims (4)
1. the preparation method of a 5-nitrosalicylaldehyde is directly to be raw material with the salicylic aldehyde, gets through the low temperature nitrofication process prepared in reaction after improving, and its concrete step is following:
At room temperature earlier salicylic aldehyde is dissolved in the acid solvent system; Then under ice-water bath and stirring condition; In the regular hour He under the temperature, nitrosonitric acid is added drop-wise in the reaction vessel lentamente, heats up through the stage after dropwising, react after 2 hours and finish; At last reaction solution is poured in the mixture of ice and water, obtain yellow mercury oxide, suction filtration obtains nitryl compound; Separation obtains lurid 5-nitrosalicylaldehyde to mixture through the water extraction process again.
2. preparation method according to claim 1; It is characterized in that; Described acid solvent system is the tertiary mixture of hydrofluoric acid, acetic anhydride and acetate; And the mole proportioning of salicylic aldehyde, hydrofluoric acid, acetic anhydride and nitrating agent concentrated nitric acid is 1: 1.25: 1.25: 1.25, and the consumption of acetate is regulated according to reaction vessel volume.
3. preparation method according to claim 1 is characterized in that, temperature of reaction should be controlled at 5～10 ℃ when dripping nitrosonitric acid.
4. preparation method according to claim 1 is characterized in that, the stage temperature increasing schedule that drips behind the nitrosonitric acid is 8～10 ℃ of reaction 1h down, and then continues reaction 1h down at 15～20 ℃ and finish.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058874A (en) * | 2013-02-05 | 2013-04-24 | 上海煦旻化工科技发展有限公司 | Method for preparing 5-nitrosalicylaldehyde |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009274A1 (en) * | 1994-09-23 | 1996-03-28 | Orion-Yhtymä Oy | New method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde |
| CN101020640A (en) * | 2007-03-15 | 2007-08-22 | 淮阴师范学院 | Prepn process of 3-nitro salicylaldehyde |
| CN102173992A (en) * | 2011-03-21 | 2011-09-07 | 南通大学 | Preparation method of nitrophenol compounds |
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2012
- 2012-04-10 CN CN201210102580.6A patent/CN102633646B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009274A1 (en) * | 1994-09-23 | 1996-03-28 | Orion-Yhtymä Oy | New method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde |
| CN101020640A (en) * | 2007-03-15 | 2007-08-22 | 淮阴师范学院 | Prepn process of 3-nitro salicylaldehyde |
| CN102173992A (en) * | 2011-03-21 | 2011-09-07 | 南通大学 | Preparation method of nitrophenol compounds |
Non-Patent Citations (4)
| Title |
|---|
| 卜鑫宇 等: "5-硝基水杨醛合成方法", 《精细化工中间体》 * |
| 张维庆 等: "5-硝基水杨醛硝化法的改进", 《湖南文理学院学报（自然科学版）》 * |
| 曹志武 等: "5-硝基水杨醛的合成研究", 《广州化工》 * |
| 魏青 等: "5-硝基水杨醛分离纯化方法改良", 《精细化工》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103058874A (en) * | 2013-02-05 | 2013-04-24 | 上海煦旻化工科技发展有限公司 | Method for preparing 5-nitrosalicylaldehyde |
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