CN1326933A - Process for preparing bromo-ortho-piperonaldehyde - Google Patents
Process for preparing bromo-ortho-piperonaldehyde Download PDFInfo
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- CN1326933A CN1326933A CN 01108553 CN01108553A CN1326933A CN 1326933 A CN1326933 A CN 1326933A CN 01108553 CN01108553 CN 01108553 CN 01108553 A CN01108553 A CN 01108553A CN 1326933 A CN1326933 A CN 1326933A
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Abstract
The present invention relates to heterocyclic compound. Bromo-ortho-piperomaldehyde is prepared with ortho-vanillin as initial material and through three-step process including bromization, demethylation and cyclization. The present invention uses cheap material and conventional equipment to produce the said fine chemical product with high purity and high yield through mild technological conditions and this open one new technological way of producing the important chemical product.
Description
The invention belongs to heterogeneous ring compound, is to contain pentatomic ring in detail, two Sauerstoffatoms is arranged as only ring hetero atom, with a six-membered ring condensed heterocycle compound, is specifically related to its preparation method.
The bromo-ortho piperonylaldehyde, formal name used at school 5-bromo-2,3-methylene dioxo group benzaldehyde (5-Bromo-2,3-methylen-dioxy benzaldehyde), perhaps the 6-bromo-1, and 3-benzo two is disliked luxuriant-4-formaldehyde (6-Bromo-1.3-benzodioxole-4-Carboxaldehyde), molecular formula: C
3H
5BrO
3, structural formula is
The bromo-ortho piperonylaldehyde is a kind of important derivatives of piperonylaldehyde isomers, is important pharmaceutical intermediate, can synthesize the specific medicament of preventing and treating cardiovascular and cerebrovascular diseases with it, is a kind of fine chemical product of high added value.At present, domestic and international research and development to the piperonylaldehyde derivative, mainly concentrate on a few products such as piperonylacetone, heliotrope nitrile, sesamol, methylenedioxyphenyl alkyl oxide, only be confined to as spices, pesticide synergistic and traditional application facet such as anti-oxidant; And for the research and development of ortho position piperonylaldehyde and derivative thereof, its bibliographical information is few, bromo-ortho piperonylaldehyde particularly, and Shang Weijian has the commercialization report both at home and abroad.In all documents that can retrieve, only at Russian magazine " chemistry of heterocyclic compound ", reported the synthetic of this compound on the phase P1183-1188 in 1979 the 9th: Russian original text title is:
ХИМИЯ?ТЕТЕРОСИКЛИЧЕКИХ
СОЕЛИНЕСКИИ1979，N0.9，1183-1188
＂ 3 Π Е К Т Р О φ И Б Н О Е 3 А М Е Ш Е Н И Е у 4-Π Р О И 3 В О Л Н Ь 1 Х В Е О 3 О-1.3-Д И О К С О Π А ＂ is in this research paper, reported with ortho position piperonylaldehyde (promptly 2, the 3-methylene dioxo group benzaldehyde) carries out bromo-reaction, generate the experiment situation of bromo-ortho piperonylaldehyde: generating 5-bromo-2, in the time of 3-methylene dioxo group benzaldehyde product, 6-bromine or 4-bromo 2 are also arranged, two kinds of by products of 3-methylene dioxo group benzaldehyde generate, and promptly generate three kinds of isomerss simultaneously.If obtain commercial bromo-ortho piperonylaldehyde, said synthesis route exists following major defect: 1) 2, and the 3-methylene dioxo group benzaldehyde costs an arm and a leg, and can not carry out the industrial production of bromo-ortho piperonylaldehyde with it as raw material; 2) 2, the bromo-reaction of 3-methylene dioxo group benzaldehyde can generate three kinds of isomerss simultaneously, is difficult to obtain highly purified bromo-ortho piperonylaldehyde product.
The objective of the invention is to,, adopt the relatively inexpensive raw material that is easy to get at above-mentioned the deficiencies in the prior art, start a kind of novel process for preparing the bromo-ortho piperonylaldehyde, make it not only can not produce isomers, the product purity height, and can realize commercialization production.
Take following technical scheme to realize purpose of the present invention.
General technical design of the present invention is: make starting raw material with ortho vanillin, make the bromo-ortho vanillin food grade,1000.000000ine mesh through bromo-reaction earlier, make dihydroxyl bromobenzene formaldehyde through demethylation reaction again, after cyclization makes product bromo-ortho piperonylaldehyde.
Ortho vanillin bromo-ortho vanillin food grade,1000.000000ine mesh dihydroxyl bromobenzene formaldehyde bromo-ortho piperonylaldehyde
One. bromo-reaction
By the weight part proportioning of ortho vanillin, Potassium Bromide, 80% acetum, liquid bromine and dehydrated alcohol=1: 1.6: 13: get the raw materials ready at 1.1: 10, earlier ortho vanillin, Potassium Bromide and 80% acetum are joined in the acid-resistant reacting kettle, stir, be warming up to 100-120 ℃, slowly splash into the liquid bromine then, allow it react 40-80 minute, be discharged into crystalline deposit in the cold rinse bank with being about to reaction solution after being cooled to room temperature, again throw out is filtered and oven dry, use the dehydrated alcohol recrystallization at last, after filtration, dry back obtains red-brown crystalline bromo-ortho vanillin food grade,1000.000000ine mesh;
Two. demethylation reaction
By the weight part proportioning of bromo-ortho vanillin food grade,1000.000000ine mesh, 40% Hydrogen bromide, Glacial acetic acid and toluene=1: 0.8: 2: 10 got the raw materials ready, and earlier bromo-ortho vanillin food grade,1000.000000ine mesh, 40% Hydrogen bromide and Glacial acetic acid are joined in the acid-resistant reacting kettle, use N
2Gas drive is removed the air in the still, and at N
2Be heated to 100-120 ℃ under the protection, allow its back flow reaction 16-20 hour, be discharged into crystalline deposit in the cold rinse bank with being about to reaction solution after being cooled to room temperature, to dissolve with toluene behind the grey black throw out filtration drying, and adding activated carbon decolorizing, be heated to 110 ℃ of backflow 20-30 minutes, and more after filtration, crystallisation by cooling, filtration, obtained the dihydroxyl bromobenzene formaldehyde of yellow crystals;
Three. cyclization
Make condensing agent with two fontanel methane, press dihydroxyl bromobenzene formaldehyde, salt of wormwood, cupric oxide, two fontanel methane, DMF (N, dinethylformamide) and the weight part proportioning of toluene=and 1: 1.9: 0.23: get the raw materials ready at 0.78: 1.5: 10, earlier dihydroxyl bromobenzene formaldehyde, salt of wormwood, cupric oxide, two fontanel methane and DMF are joined in the acid-resistant reacting kettle, use N
2Gas drive is removed the air in the still, at N
2100-120 ℃ of reaction 1-3 hour stirred and is warming up in protection down fast; be cooled to room temperature; again with reacting liquid filtering; change in the still kettle and dissolve resistates with toluene behind the recovery DMF; add activated carbon decolorizing simultaneously; be heated to filtration then, crystallisation by cooling, drying, the bromo-ortho piperonylaldehyde product of acquisition white or pale yellow powder shape 110 ℃ of backflow 20-30 minutes.Condensing agent two the most handy methylene dichloride of fontanel methane or methylene bromides.
Employed acid-resistant reacting kettle among the preparation technology of the present invention can be enamel reaction still or glassed steel reaction vessels, employed chemical industry raw and auxiliary material except that cupric oxide is SILVER REAGENT, all the other available all commercial grades.
The bromo-ortho piperonylaldehyde product that adopts preparation technology of the present invention to produce, 111-114 ℃ of its fusing point; Infrared signature peak (υ maxcm-1): 1696 (S, C=0), 1600,1580,1474,1390 (s, c-c phenyl ring), 1198,1028 (S, C-O-C); Magnetic resonance detection (CDCl3) δ (PPm): 1003 (1H, S, CHO), 7.38 (1H, d, C
6H (1)), 7.13 (1H, d, C
6H (2)), 6.13 (2H, d, O-CH
2O); There is not isomers in the product, purity (bromo-ortho piperonylaldehyde content) 〉=96%; Product is to productive rate 〉=55% of starting raw material ortho vanillin.Bromo-ortho piperonylaldehyde preparation technology of the present invention uses chemical industry raw and auxiliary material and conventional equipment cheap and easy to get, the processing condition gentleness, and the product purity height, the productive rate height can be realized suitability for industrialized production fully.
Embodiment 1
Get 7.6 kilograms of industrial goods ortho vanillin, 11.9 kilograms of Potassium Bromides and 80% acetum are added in the enamel reaction still for 100 kilograms, stir, be warming up to 110 ℃, slowly splash in the still liquid bromine for 8.5 kilograms again, allow it carry out bromo-reaction 60 minutes, be cooled to after the room temperature reaction solution is discharged into and carry out crystalline deposit in the cold rinse bank, again with throw out suction filtration and oven dry, carry out recrystallization for 76 kilograms with dehydrated alcohol then, after filtration, dry back obtains 9.6 kilograms of red-brown crystalline bromo-ortho vanillin food grade,1000.000000ine meshs; With 9.6 kilograms of the bromo-ortho vanillin food grade,1000.000000ine meshs that make, 7.7 kilograms of 40% Hydrogen bromides, Glacial acetic acid joins in the enamel reaction still for 19 kilograms, uses N
2Gas drive is removed the air in the still, and at N
2Be heated to 110 ℃ under the gas shiled, allow its backflow carry out demethylation reaction 18 hours, after being cooled to room temperature reaction solution is discharged into crystalline deposit in the cold rinse bank, with throw out dry after filtration back 96 kilograms of dissolvings of toluene, and adding activated carbon decolorizing, be heated to 110 ℃ and refluxed 30 minutes, more after filtration, crystallisation by cooling, filtration, obtain 6.5 kilograms in the dihydroxyl bromobenzene formaldehyde of yellow crystals; With 6.5 kilograms in the dihydroxyl bromobenzene formaldehyde that makes, 12.4 kilograms in salt of wormwood, 1.5 kilograms of cupric oxide, 5 kilograms of methylene dichloride and DMF9.8 kilogram join in the enamel reaction still, use N
2Gas drive is removed air in the still, and at N
2Gas shiled is stirred fast down and is warming up to 110 ℃; allow it carry out cyclization 2 hours; be cooled to room temperature,, change in the still kettle and dissolve resistates for 65 kilograms with toluene behind the recovery DMF again with reacting liquid filtering; add activated carbon decolorizing simultaneously; be heated to 110 ℃ and refluxed 30 minutes, filtration then, crystallisation by cooling, drying, 4.34 kilograms of the bromo piperonylaldehyde products of acquisition white or pale yellow powder shape; product purity 99%, product is 57% to the productive rate that rises as the raw material ortho vanillin.
Embodiment 2
Get 10 kilograms of industrial goods ortho vanillin, 16 kilograms of Potassium Bromides and 80% acetum join in the enamel reaction still for 130 kilograms, stir, be warming up to 120 ℃, again the liquid bromine slowly splashed in the still for 11 kilograms, allow it carry out bromo-reaction 45 minutes, after being cooled to room temperature reaction solution is discharged into crystalline deposit in the cold rinse bank, with throw out suction filtration and oven dry, carry out recrystallization for 100 kilograms with dehydrated alcohol then again, after filtration, dry back obtains 12.5 kilograms of red-brown crystalline bromo-ortho vanillin food grade,1000.000000ine meshs; 12.5 kilograms of the bromo-ortho vanillin food grade,1000.000000ine meshs, 10 kilograms of 40% Hydrogen bromides, the Glacial acetic acid that make are joined in the enamel reaction still for 25 kilograms, use N
2Gas drive is removed the air in the still, and at N
2Be heated to 120 ℃ under the gas shiled, allow its backflow carry out demethylation reaction 16 hours, after being cooled to room temperature reaction solution is discharged into crystalline deposit in the cold rinse bank, with throw out dry after filtration back 125 kilograms of dissolvings of toluene, and adding activated carbon decolorizing, be heated to 110 ℃ and refluxed 30 minutes, more after filtration, crystallisation by cooling, filtration, obtain 8.2 kilograms in the dihydroxyl bromobenzene formaldehyde of yellow crystals; With 8.2 kilograms in the dihydroxyl bromobenzene formaldehyde that makes, 15.6 kilograms in salt of wormwood, 1.9 kilograms of cupric oxide, 6.4 kilograms of methylene bromides and DMF12.3 kilogram join in the enamel reaction still, use N
2Gas drive is removed air in the still, and at N
2Gas shiled is stirred fast down and is warming up to 120 ℃; allow it carry out cyclization 1 hour; be cooled to room temperature; with reacting liquid filtering, change in the still kettle and dissolve resistates for 82 kilograms with toluene behind the recovery DMF again, add activated carbon decolorizing simultaneously; being heated to 110 ℃ refluxed 30 minutes; 5.6 kilograms of the bromo-ortho piperonylaldehyde products of filtration then, crystallisation by cooling, drying, acquisition white or pale yellow powder shape, product purity 99%, product is 56% to working the productive rate of sending out beginning raw material ortho vanillin.
Claims (3)
1. the preparation technology of a bromo-ortho piperonylaldehyde is characterized in that with the ortho vanillin being starting raw material, form by bromo-reaction, demethylation reaction and three step of cyclization process, wherein:
1) bromo-reaction is the weight part proportioning=1: 1.6: 13 by ortho vanillin, Potassium Bromide, 80% acetum, liquid bromine and dehydrated alcohol: get the raw materials ready at 1.1: 10, earlier ortho vanillin, Potassium Bromide and 80% acetum are joined in the acid-resistant reacting kettle, stir, be warming up to 100-120 ℃, slowly splash into the liquid bromine then, allow it react 40-80 minute, be discharged into crystalline deposit in the cold rinse bank with being about to reaction solution after being cooled to room temperature, again throw out is filtered and oven dry, use the dehydrated alcohol recrystallization at last, after filtration, dry back obtains the bromo-ortho vanillin food grade,1000.000000ine mesh;
2) demethylation reaction is the weight part proportioning=1: 0.8: 2 by bromo-ortho vanillin food grade,1000.000000ine mesh, 40% Hydrogen bromide, Glacial acetic acid and toluene: 10 get the raw materials ready, and earlier bromo-ortho vanillin food grade,1000.000000ine mesh, 40% Hydrogen bromide and Glacial acetic acid are joined in the acid-resistant reacting kettle, use N
2Gas drive is removed the air in the still, and at N
2Be heated to 100-120 ℃ under the protection, allow its back flow reaction 16-20 hour, be discharged into crystalline deposit in the cold rinse bank with being about to reaction solution after being cooled to room temperature, to dissolve with toluene behind the throw out filtration drying, and adding activated carbon decolorizing, be heated to 110 ℃ of backflow 20-30 minutes, and more after filtration, crystallisation by cooling, filtration, obtained dihydroxyl bromobenzene formaldehyde;
3) cyclization is to make condensing agent with two fontanel methane, by the weight part proportioning of dihydroxyl bromobenzene formaldehyde, salt of wormwood, cupric oxide, two fontanel methane, DMF and toluene=1: 1.9: 0.23: get the raw materials ready at 0.78: 1.5: 10, earlier dihydroxyl bromobenzene formaldehyde, salt of wormwood, cupric oxide, two fontanel methane and DMF are joined in the acid-resistant reacting kettle, use N
2Gas drive is removed the air in the still, at N
2100-120 ℃ of reaction 1-3 hour stirred and is warming up in protection down fast; be cooled to room temperature; again with reacting liquid filtering; change in the still kettle and dissolve resistates with toluene behind the recovery DMF; add activated carbon decolorizing simultaneously; be heated to 110 ℃ of backflow 20-30 minutes, filtration then, crystallisation by cooling, drying obtain bromo-ortho piperonylaldehyde product.
2. according to the described bromo-ortho piperonylaldehyde of claim 1 preparation technology, it is characterized in that condensing agent used in cyclization two fontanel methane are methylene dichloride.
3. according to the described bromo-ortho piperonylaldehyde of claim 1 preparation technology, it is characterized in that condensing agent used in cyclization two fontanel methane are methylene bromides.
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| CN 01108553 CN1119342C (en) | 2001-06-19 | 2001-06-19 | Process for preparing bromo-ortho-piperonaldehyde |
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| CN 01108553 CN1119342C (en) | 2001-06-19 | 2001-06-19 | Process for preparing bromo-ortho-piperonaldehyde |
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| CN1119342C CN1119342C (en) | 2003-08-27 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237410A (en) * | 2015-10-26 | 2016-01-13 | 曹仪山 | Method for preparing tetramethyl ammonium bromide |
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2001
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237410A (en) * | 2015-10-26 | 2016-01-13 | 曹仪山 | Method for preparing tetramethyl ammonium bromide |
| CN105237410B (en) * | 2015-10-26 | 2017-08-01 | 曹仪山 | A kind of method for preparing 4 bromide |
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