CN102633646B - New preparation method of 5-nitro-salicylaldehyde - Google Patents
New preparation method of 5-nitro-salicylaldehyde Download PDFInfo
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- CN102633646B CN102633646B CN201210102580.6A CN201210102580A CN102633646B CN 102633646 B CN102633646 B CN 102633646B CN 201210102580 A CN201210102580 A CN 201210102580A CN 102633646 B CN102633646 B CN 102633646B
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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 improvement.
Background technology
5-nitrosalicylaldehyde is a kind of chemical intermediate being widely used in the building-up processes such as medicine, dyestuff, agricultural chemicals and spices.In the exploitation of medicine, take 5-nitrosalicylaldehyde as the synthetic Dronedarone of raw material (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 Cardiovarscular; In marine drug chitosan synthetic, adopt bacteriostatic action and the resistance of oxidation of hydroxypropyl chitosan schiff bases prepared by 5-nitrosalicylaldehyde will be apparently higher than the hydroxypropyl chitosan schiff bases of being prepared by salicylic aldehyde merely.And there is excellent photochromic properties take 5-nitrosalicylaldehyde as the synthetic spirobenzopyran of raw material, be often seen among all kinds of bibliographical informations as a kind of novel optical information, optical storage and fluorescent switch material.
Prepare 5-nitrosalicylaldehyde take wide material sources, cheap salicylic aldehyde as raw material, adopt low temperature nitrofication process in the past.Reaction process is as shown in following equation:
Reaction, take nitrosonitric acid as nitrating agent, take Glacial acetic acid as solvent, and is carried out in ice-water bath.This reaction mainly exists the shortcoming of two aspects: the one, and 3 of salicylic aldehydes and 5 s' nitro replacement is a competing reaction, thereby the content of by product 3-nitrosalicylaldehyde is higher in the nitrosalicylaldehyde that causes synthesizing, cause very large difficulty to the separating-purifying in later stage; The 2nd, due to initial reaction very exothermic, must in ice-water bath, carry out for controlling reaction, but speed of reaction under 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 mainly for above-mentioned subject matter, design brand-new reaction solvent system, on existing basis, improve nitrofication process and prepared the process of 5-nitrosalicylaldehyde, reduce the generation of by product 3-nitrosalicylaldehyde, and improve the speed of reaction under low temperature, thereby simplify the step separating, successfully improved the productive rate of 5-nitrosalicylaldehyde.Concrete synthesis flow is as shown in following equation:
Its concrete steps are as follows:
At room temperature first salicylic aldehyde is dissolved in acid solvent system, then, in ice-water bath and under the condition stirring, within the regular hour He at temperature, nitrosonitric acid is added drop-wise in reaction vessel lentamente, after dropwising, heat up stage by stage, reaction 2h finishes.Finally reaction solution is poured in mixture of ice and water, obtain yellow mercury oxide; Suction filtration obtains nitryl compound; What mixture separated through water extraction process again arrives lurid 5-nitrosalicylaldehyde.
Its above acid solvent system is the tertiary mixture of hydrofluoric acid, acetic anhydride and acetic acid.Glacial acetic acid is as main reaction solvent; Acetic anhydride, as reaction water-removal agent, can improve nitryl positive ion (NO in nitrifying process
2 +) concentration, thereby improve the speed of reaction under low temperature; Adding of hydrofluoric acid can suppress the generation that 3-position replaces by product.
The process that wherein slowly drips nitrosonitric acid will complete in 2.5h, and controls temperature at 5～10 ℃.
Described stage temperature increasing schedule is to react 1h at 8～10 ℃, then at 15～20 ℃, continues reaction 1h and finishes.
Products obtained therefrom characterizes by infrared spectra and H nuclear magnetic resonance spectrum, and concrete data are as follows:
Infrared spectra (KBr, cm
-1): 3069cm
-1; 2883cm
-1; 1664cm
-1; 1625,1581,1472cm
-1; 1514,1339cm
-1; 1287,1186,1090cm
-1; 921,715,629cm
-1; 833,780cm
-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: designed ternary solvent system can obviously reduce the ratio of by product 3-nitrosalicylaldehyde, and improved speed of reaction nitrated under low temperature.Thereby improved the productive rate that salicylic aldehyde nitrofication process is prepared 5-nitrosalicylaldehyde, maximum output has reached 52%.Simplify the process of the separation of follow-up isomers simultaneously, be conducive to 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.
Accompanying drawing explanation
Fig. 1: the infrared spectra of product;
Fig. 2: product
1hNMR spectrum;
Fig. 3: the mechanism explaination that ternary solvent system is improved to productive rate: HF adds, because the hydrogen bond between F and H is better than the hydrogen bond between O and H, hydrogen bond has saturability simultaneously, thereby utilizes the occupy-place effect of hydrogen bond, has improved the proportion of products that 5-position replaces.
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 respectively 100ml Glacial acetic acid, 12.5g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde and join successively in 250ml torticollis there-necked flask, in ice-water bath, constantly stirring and be cooled to below 5 ℃.16.6g nitrosonitric acid is placed in to constant pressure funnel, controls temperature within the scope of 5～10 ℃, in 2.5h, nitrosonitric acid is added drop-wise in there-necked flask equably.Then control temperature at 8～10 ℃ of reaction 1h, then be warming up to 15～20 ℃ of continuation reaction 1h.While hot reaction soln is poured into fill in the trash ice of 500g and water mixture and stirred, place 5h (or place and spend the night).Suction filtration, washing, dry, obtain yellow powder solid 28.3g.After water extracting, can obtain lurid 5-nitrosalicylaldehyde powder 14.8g, productive rate is 52%.
Infrared spectra (KBr, cm
-1): 3069cm
-1; 2883cm
-1; 1664cm
-1; 1625,1581,1472cm
-1; 1514,1339cm
-1; 1287,1186,1090cm
-1; 921,715,629cm
-1; 833,780c
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 respectively 100ml Glacial acetic acid, 12.5g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde and join successively in 250ml torticollis there-necked flask, in ice-water bath, constantly stirring and be cooled to below 5 ℃.16.6g nitrosonitric acid is placed in to constant pressure funnel, controls temperature in 5～102 scopes, in 2.5h, nitrosonitric acid is added drop-wise in there-necked flask equably.Then control temperature at 8～10 ℃ of reaction 1h, then be warming up to 15～20 ℃ of continuation reaction 1h.The people that while hot reaction soln fallen contains in the trash ice of 500g and water mixture and stirs, and places 5h (or place and spend the night).Suction filtration, washing, dry, obtain yellow powder solid 25.5g.After water extracting, can obtain lurid 5-nitrosalicylaldehyde powder 12.7g, productive rate is 50%.
Infrared spectra (KBr, cm
-1): 3070cm
-1; 2885cm
-1; 1657cm
-1; 1614,1578,1447cm
-1; 1527,1352cm
-1; 1260,1200,1090cm
-1; 950,742,629cm
-1; 825,780cm
-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 respectively 100ml Glacial acetic acid, 5.0g hydrofluoric acid, 25.9g acetic anhydride, 25.7g salicylic aldehyde and join successively in 250ml torticollis there-necked flask, in ice-water bath, constantly stirring and be cooled to below 5 ℃.16.6g nitrosonitric acid is placed in to constant pressure funnel, controls temperature within the scope of 5～10 ℃, in 2.5h, nitrosonitric acid is added drop-wise in there-necked flask equably.Then control temperature at 8～10 ℃ of reaction 1h, then be warming up to 15～20 ℃ of continuation reaction 1h.The people that while hot reaction soln fallen contains in the trash ice of 500g and water mixture and stirs, and places 5h (or place and spend the night).Suction filtration, washing, dry, obtain yellow powder solid 32.0g.After water extracting, can obtain lurid 5-nitrosalicylaldehyde powder 12.6g, productive rate is 39%.The reason that this synthetic productive rate significantly reduces is 0.4 times that the usage quantity of hydrofluoric acid only has embodiment above.
Infrared spectra (KBr, cm
-1): 3068cm
-1; 2880cm
-1; 1664cm
-1; 1626,1581,1471cm
-1; 1512,1338cm
-1; 1286,1184,1089cm
-1; 920,716,628em
-1; 833,779cm
-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 (2)
1. a preparation method for 5-nitrosalicylaldehyde, is directly take salicylic aldehyde as raw material, the low temperature nitrofication process reaction preparation after improving and obtaining, and its concrete step is as follows:
At room temperature first salicylic aldehyde is dissolved in the acid solvent system of tertiary mixture of hydrofluoric acid, acetic anhydride and acetic acid, then under the condition of ice-water bath and stirring, in 2.5h, and control temperature at 5～10 ℃, nitrosonitric acid is added drop-wise in reaction vessel lentamente, after dropwising, control at 8～10 ℃ of temperature and react 1h, and then at 15～20 ℃, continue to finish after reaction 1h; Finally reaction solution is poured in mixture of ice and water, obtain yellow mercury oxide, suction filtration obtains nitryl compound; Mixture separates and obtains lurid 5-nitrosalicylaldehyde through water extraction process again.
2. preparation method according to claim 1, is characterized in that, 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 acetic acid regulates according to reaction vessel volume.
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Citations (3)
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|---|---|---|---|---|
| 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
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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 (7)
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| 5-硝基水杨醛分离纯化方法改良;魏青 等;《精细化工》;20000331;第17卷(第3期);参见对比文件1第178页1.2.2和1.2.3 * |
| 5-硝基水杨醛合成方法;卜鑫宇 等;《精细化工中间体》;20040630;第35卷(第3期);第4-6页 * |
| 5-硝基水杨醛的合成研究;曹志武 等;《广州化工》;20111223;第39卷(第24期);第47-48页 * |
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| 曹志武 等.5-硝基水杨醛的合成研究.《广州化工》.2011,第39卷(第24期),第47-48页. |
| 魏青 等.5-硝基水杨醛分离纯化方法改良.《精细化工》.2000,第17卷(第3期),参见对比文件1第178页1.2.2和1.2.3. |
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