CN100546970C - A kind of synthetic method of bromo benzoic ether - Google Patents
A kind of synthetic method of bromo benzoic ether Download PDFInfo
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- CN100546970C CN100546970C CNB2006100355108A CN200610035510A CN100546970C CN 100546970 C CN100546970 C CN 100546970C CN B2006100355108 A CNB2006100355108 A CN B2006100355108A CN 200610035510 A CN200610035510 A CN 200610035510A CN 100546970 C CN100546970 C CN 100546970C
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- bromo
- benzoic ether
- bromine
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Links
- -1 bromo benzoic ether Chemical compound 0.000 title claims abstract description 34
- 238000010189 synthetic method Methods 0.000 title claims abstract description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000003513 alkali Substances 0.000 claims abstract description 18
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical class [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 claims abstract description 18
- 239000000706 filtrate Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 7
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- XWNSFEAWWGGSKJ-UHFFFAOYSA-N 4-acetyl-4-methylheptanedinitrile Chemical group N#CCCC(C)(C(=O)C)CCC#N XWNSFEAWWGGSKJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004153 Potassium bromate Substances 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 229940094037 potassium bromate Drugs 0.000 claims description 5
- 235000019396 potassium bromate Nutrition 0.000 claims description 5
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 4
- 239000000047 product Substances 0.000 abstract description 18
- 239000002699 waste material Substances 0.000 abstract description 6
- 239000012065 filter cake Substances 0.000 abstract description 5
- 230000031709 bromination Effects 0.000 description 19
- 238000005893 bromination reaction Methods 0.000 description 19
- 235000010233 benzoic acid Nutrition 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000001246 bromo group Chemical group Br* 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 150000001559 benzoic acids Chemical class 0.000 description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 229940095102 methyl benzoate Drugs 0.000 description 3
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- WYJXFFFWDRMGRG-UHFFFAOYSA-M [Na+].BrN1C(=O)NC(=O)[N-]C1=O Chemical compound [Na+].BrN1C(=O)NC(=O)[N-]C1=O WYJXFFFWDRMGRG-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- ZTVIKZXZYLEVOL-DGKWVBSXSA-N 2-hydroxy-2-phenylacetic acid [(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] ester Chemical group C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-DGKWVBSXSA-N 0.000 description 1
- POVUENZMXWGMMC-UHFFFAOYSA-N 3-bromo-4-ethoxybenzonitrile Chemical compound CCOC1=CC=C(C#N)C=C1Br POVUENZMXWGMMC-UHFFFAOYSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- PJRLUGQMEZZDIY-UHFFFAOYSA-N 4-ethoxybenzonitrile Chemical compound CCOC1=CC=C(C#N)C=C1 PJRLUGQMEZZDIY-UHFFFAOYSA-N 0.000 description 1
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical group C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical class COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- MZJUGRUTVANEDW-UHFFFAOYSA-N bromine fluoride Chemical class BrF MZJUGRUTVANEDW-UHFFFAOYSA-N 0.000 description 1
- SOUPRKFYMHZDHZ-UHFFFAOYSA-N bromine(1+) Chemical compound [Br+] SOUPRKFYMHZDHZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-FTXFMUIASA-N bromine-75 Chemical compound [75BrH] CPELXLSAUQHCOX-FTXFMUIASA-N 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229940101209 mercuric oxide Drugs 0.000 description 1
- NCJZJVWOEXLSKA-UHFFFAOYSA-N methyl 3-bromo-4-ethoxybenzoate Chemical compound CCOC1=CC=C(C(=O)OC)C=C1Br NCJZJVWOEXLSKA-UHFFFAOYSA-N 0.000 description 1
- KMFJVYMFCAIRAN-UHFFFAOYSA-N methyl 3-bromobenzoate Chemical class COC(=O)C1=CC=CC(Br)=C1 KMFJVYMFCAIRAN-UHFFFAOYSA-N 0.000 description 1
- RNHXTCZZACTEMK-UHFFFAOYSA-N methyl 4-ethoxybenzoate Chemical compound CCOC1=CC=C(C(=O)OC)C=C1 RNHXTCZZACTEMK-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FQFKTKUFHWNTBN-UHFFFAOYSA-N trifluoro-$l^{3}-bromane Chemical compound FBr(F)F FQFKTKUFHWNTBN-UHFFFAOYSA-N 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of synthetic method of bromo benzoic ether, to mix in substituted benzene ring compound, bromo acid alkali metal-salt and the water adding reaction vessel, controlled temperature is 10～40 ℃ while stirring, splashes into bromine or bromine aqueous solution then, reacts after 1～4 hour, stopped reaction, decompress filter is removed filtrate, after residue washes with water, the oven dry filter cake makes bromo benzoic ether.Product fusing point of the present invention all can directly use near literature value, satisfies the requirement of quality products.Product purity height of the present invention need not to purify and directly uses pollution-free waste discharge; The reaction conditions gentleness, the reaction times is short, and is simple to operate; Product yield height is 65～95%.
Description
Technical field
The invention belongs to the preparing technical field of fine chemical product, be particularly related to a kind of benzoic ether between the method that replaces of the single bromine in position, the activating group of the contraposition of activation substituting group, the especially manthanoate of position replaced between the substituting group of raw material substituted benzoyl acid esters mainly was meant.
Background technology
The single bromo-derivative in position is a valuable chemical products between benzoic ether, is one of important intermediate of well phenyl ring intermediate stripping and slicing, fine chemistry industry and pharmaceutical industry in the organic synthesis.So far also many synthetic methods of practical application have been reported.Wherein Chang Yong method be with bromine under certain condition benzoic ether carry out bromination.For example: (S.A.Khan, M.A.Munawar, M.Siddiq such as S.A.Khan; Monobromination ofDeactivated Active Rings Using Bromine, Mercuric Oxide, and Strong Acid.J.Org.Chem.1988,53,1799-1800.) usefulness bromine bromination methyl benzoate under red precipitate and strong acid, obtain the m-bromobenzoic acid methyl esters of 78% productive rate, deficiency has been the by product m-bromobenzoic acid.(S.Rozen, M.Brand, R.Lidor such as Shlomo Rozen; Aromatic bromination using bromine fluoridewith no Friedel-Crafts catalyst.J.Org.Chem.; 1988; 53 (23); 5545-5547. and S.Rozen and M.Brand; Novel Aromatic Bromination Using BrF Prepared Directlyfrom the Corresponding Elements.J.Chem.Soc., Chem.Commun., 1987,752-753.) use fluorine and bromine-75 ℃ down generated in-situ bromine fluorides in low temperature-75～-45 ℃ following para Toluic Acid's ethyl ester bromination, obtain the mixture of a bromine replacement and dibromo substitution product (95: 5): (S.Rozen, O.Lerman such as Shlomo Rozen; Bromination of Deactivated Aromatics Using BrF
3Without a Catalyst.J.Org.Chem.1993,58,239-240) used the mixture para Toluic Acid methyl esters bromination of bromine trifluoride and bromine, used method deficiencies such as Shlomo Rozen are reaction needed low temperature, productive rate is not high, have severe corrosive hydrogen fluoride to generate, and there is the bromination that activates substituent compound the position between being not suitable for.(P.Basabe, A.Diego, S.Delgado, D.D í ez, I.S.Marcos, J.G.Urones such as Pilar Basabe; Short and efficient synthesis of (+)-subersic acids.Tetrahedron, 2003,59,9173-9177.).Come the bromination methyl p-hydroxybenzoate with bromine, react 24h in methylene dichloride, obtaining 3-bromo-4-methyl hydroxybenzoate productive rate is 95%, and deficiency is need be in the organochlorine solvent, long reaction time.
Other bromination process also has, (J.J.Harrison, J.P.Pellegrini, C.M.Selwitz such as J.J.Harrison; Bromination of deactivated aromatics using potassium bromate.J.Org.Chem.1981,46,2169-2171.) with Amiram Groweiss (A.Groweiss; Use of SodiumBromate for Aromatic Bromination:Research and Development.Org.Process Res.Dev.2000,4 (1), 30-33.) with the sulphuric acid soln (30～65%) of bromo acid alkali metal-salt (as sylvite or sodium salt) and the vitriol oil or high density as bromide reagent, deficiency need to be heating, and productive rate is not high, there is a small amount of many bromines product to generate, the oxidation of coal that also often responds in the reaction on the substrate becomes carbonic acid gas, or phenol is oxidized to quinone, or forms by product such as multinuclear aromatic compound.
Other bromination process also has, (D.H.Derbyshire, W.A.Water such as D.H.Derbyshire; The Significance of the Bromine Cation in Aronmatic Substitution.Part II.Preparative Applicability.J.Chem.Soc., 1950,573-577.) make bromide reagent with bromo acid alkali metal-salt and bromine, weak point is to need to use 50% sulfuric acid, easily produces the benzoic acids by product.Also have with hydrogen bromide and certain oxygenant, perhaps with the N-bromo-derivative as bromide reagent, as with NBS (T.Oberhauser; A New Bromination Method for Phenols and Anisoles:NBS/HBF
4Et
2O in CH
3CN.J.Org.Chem.1997,62,4504-4506), or with SMIB[Y.Okada, M.Yokozawa, M.Akiba, K.Oishi, K.O-kawa, T.Akeboshi, Y.Kawamura, S.Inokuma, Y.Nakamura, Jun Nishimura; Bromination by means of sodiummonobromoisocyanurate (SMBI)] etc. as bromide reagent, carrying out under the condition under sulfuric acid or the Lewis acid or with an organic solvent.
Above-mentioned bromo method is often with many brominated by products, in organic solvent, carry out or need high temperature or low temperature, or generate hydrogen bromide or hydrogen fluoride in the reaction, in industrial production, produce corrosive exhaust gases, the waste treatment difficulty, contaminate environment, and the strong acidic environment in the reaction makes reaction produce the benzoic acids by product.
Summary of the invention
In order to solve the weak point that above-mentioned prior art exists, the object of the present invention is to provide a kind of synthetic method of bromo benzoic ether.The method of the benzoic acid ester compounds that the single bromine in position replaces between the present invention's preparation, above-mentioned the deficiencies in the prior art have been overcome, in neutral or nearly neutral aqueous phase system, carry out, and mild condition, the reaction times is short, does not produce many bromo benzoic ethers or benzoic acids accessory substance, do not produce refuses such as hydrogen bromide, need not processing of waste, non-pollution discharge, cost reduces.
Purpose of the present invention is achieved through the following technical solutions: a kind of synthetic method of bromo benzoic ether comprises the steps:
(1) substituted benzene ring compound, bromo acid alkali metal-salt and water are mixed, controlled temperature is 10～40 ℃ while stirring, splashes into bromine or bromine aqueous solution then, reacts after 1～4 hour, and stopped reaction obtains reaction mixture; Described substituted benzene ring compound: bromine: bromo acid alkali metal-salt amount of substance ratio is 6: 2～3: 1～1.2; The consumption of described water is 20～40 times of bromo acid alkali metal-salt quality.
(2) with gained reaction mixture decompress filter, remove filtrate after, residue washes with water after clean, oven dry promptly makes single bromination product bromo benzoic ether.
Or as required, step (2) can also adopt extracted with diethyl ether with reaction mixture, drying, be spin-dried for the product bromo benzoic ether.
Reaction formula is as follows:
Efficiency of pcr product of the present invention is 65～95%, and after testing, its fusing point all can directly use near literature value, satisfies the requirement of quality products.
Described substituted benzene ring compound is a benzoic ether, and general formula is as follows:
R wherein
1Represent alkyl, as-CH
3, or-C
2H
5Deng; R
2Represent the phenyl ring activating group, as-OCH
3, or-OC
2H
5, or-OH, or-OCOCH
3, or-OCOC
2H
5, or-NH
2, or-N (CH
3)
2, or-NHCOCH
3Deng.
In order to realize the present invention better, the vacuum drying mode is adopted in described oven dry.Described bromo acid alkali metal-salt is bromo acid alkali metal-salts such as potassium bromate or sodium bromate.Preferred substituted benzene ring compound: bromine: the ratio of the amount of substance of bromo acid alkali metal-salt is 6: 3: 1.The amount of substance of described bromine and bromo acid alkali metal-salt is respectively 1/3～1/2 times and 1/5～1/6 times of amount of substance of substituted benzene ring compound; 1/2 times and 1/6 times of the special amount of substance that is preferably benzoic acid ester compounds respectively; The preferred reaction times is 2～3 hours.
The present invention has selected a kind ofly both to have had than highly selective, and non-pollutant discharge, and mild condition again is simple to operate, and the aqueous solution that meets the bromine of environment protection requirement and bromo acid alkali metal-salt is as brominated reagent.This is reflected in the water and carries out.The present invention with the single brominated reagent of the conduct of bromine and bromo acid alkali metal-salt, carries out single bromo to the phenyl ring of serial benzoic ether in the temperature (about 25 ℃) and water of gentleness, can obtain single bromination product of high yield in about 1～4 hour.The purity of product is higher, does not need purifying directly to use.Not detecting many bromination products or benzoic acids product in the reaction generates.
The present invention compared with prior art has following advantage and beneficial effect:
1, because the present invention has adopted the aqueous phase system of the bromine of selectivity height, pollution-free waste and bromo acid alkali metal-salt as single brominated reagent, in neutral aqueous solution, carry out single bromo-reaction of benzoic acid ester compounds, and reaction conditions gentleness, can obtain high productive rate 65～95%, can make direct use highly purified benzoic ether between the position single bromination product.
2, adopt gentle temperature because the present invention reacts, and reaction system be neutral or near neutrality, be applicable to wider reaction substrate type, comprise the reaction substrate that contains the acid labile group, especially the ester compound of hydrolysis under the strong acidic condition.
3, carry out at aqueous phase owing to technology of the present invention, and pollution-free waste discharge in the product, therefore compared with prior art, not only technology is simple, and meets environment protection requirement, need not processing of waste, and cost reduces greatly, and its application prospect is very wide.
Embodiment
The present invention is described in further detail below in conjunction with embodiment, but embodiments of the present invention are not limited thereto.
Embodiment 1
In the 250mL three-necked bottle, add the 4-methoxyl methyl benzoate (15.0g, 0.09mol) and potassium bromate (2.52g, 0.015mol), adding 100mL water stirs under 25 ℃ of conditions.Dripping bromine (2.4mL, 0.045mol).Reaction 4h finishes, after reaction finishes, (pressure: 10mmHg), remove filtrate, residue washes with water twice decompress filter, filter cake vacuum drying (pressure: 10mmHg, temperature: 70 ℃, time of drying: 8h), getting white solid is 3-bromo-4-methoxyl methyl benzoate (19.4g), productive rate 88%, 96～97 ℃ of fusing points (95.5～96 ℃ in document).
IR(KBr)：1709，1601，1500，1463，1431，1275，1119cm
-1；
1H?NMR(CDCl
3)：δ3.87(s，3H)，3.93(s，3H)，6.89(d，1H，J＝8.8Hz)，7.96(dd，1H，J＝8.8，2.0Hz)，8.21(d，1H，J＝2.0Hz)；
13C?NMR(CDCl
3)：δ165.3，159.1，134.4，1.30.3，123.4，111.1，110.8，56.1，51.8；MS?m/z：246and?244(1∶1，M
+)，169(100)。
Embodiment 2
Among the embodiment 1, the substituted benzoyl ester compound changes 4-nipagin A 15.0g (0.09mol) into, temperature of reaction changes 40 ℃ into, and the reaction times is 3h, extracted with diethyl ether (50mL * 3), merge organic phase, anhydrous magnesium sulfate drying is spin-dried under 50 ℃ of water-baths, and getting white solid is 3-bromo-4-nipagin A (23.2g), productive rate 95%, 102～103 ℃ of fusing points (103 ℃ in document).
Embodiment 3
In the 50mL three-necked bottle, add 4-subcutin 4.95g (0.03mol) and sodium bromate 0.76g (0.005mol), add 20mL water, stir under 10 ℃ of conditions.Dripping bromine 0.79mL (0.015mol).Reaction 1h finishes, after reaction finishes, (pressure: 10mmHg), remove filtrate, residue washes with water twice decompress filter, filter cake vacuum drying (pressure: 10mmHg, temperature: 70 ℃, time of drying: 8h), getting white solid is 3-bromo-4-subcutin (4.75g), productive rate 65%, 90～91 ℃ of fusing points (92 ℃ in document).
Embodiment 4
In the 50mL three-necked bottle, add 4-ethoxy benzonitrile acetoacetic ester 5.82g (0.03mol) and potassium bromate 1.00g (0.006mol), add 20mL water, stir under 30 ℃ of conditions.Dripping bromine 0.79mL (0.015mol).Reaction 4h finishes, after reaction finishes, (pressure: 10mmHg), remove filtrate, residue washes with water twice decompress filter, filter cake vacuum drying (pressure: 10mmHg, temperature: 70 ℃, time of drying: 8h), getting white solid is 3-bromo-4-ethoxy benzonitrile acetoacetic ester (5.49g), productive rate 67%, 58～59 ℃ of fusing points (60 ℃ in document).
Embodiment 5
In the 50mL three-necked bottle, add 4-ethoxy-benzoic acid methyl ester 5.40g (0.03mol) and sodium bromate 0.91g (0.006mol), add 20mL water, stir under 20 ℃ of conditions.Dripping bromine 0.52mL (0.01mol).Reaction 2h finishes, after reaction finishes, (pressure: 10mmHg), remove filtrate, residue washes with water twice decompress filter, filter cake vacuum drying (pressure: 10mmHg, temperature: 70 ℃, time of drying: 8h), getting white solid is 3-bromo-4-ethoxy-benzoic acid methyl ester (4.87g), productive rate 94%, 73～74 ℃ of fusing points (73.5～74 ℃ in document).
Claims (6)
1, a kind of synthetic method of bromo benzoic ether comprises the steps:
(1) substituted benzene ring compound, bromo acid alkali metal-salt and water are mixed, controlled temperature is 10～40 ℃ while stirring, splashes into bromine or bromine aqueous solution then, reacts after 1～4 hour, and stopped reaction obtains reaction mixture; Described substituted benzene ring compound: bromine: bromo acid alkali metal-salt amount of substance ratio is 6: 2～3: 1～1.2; The consumption of described water is 20～40 times of bromo acid alkali metal-salt quality;
(2) with gained reaction mixture decompress filter, remove filtrate after, residue washes with water after clean, oven dry promptly makes bromo benzoic ether;
Reaction formula is as follows:
Described substituted benzene ring compound is a benzoic ether, and general formula is as follows:
R wherein
1Representative-CH
3, or-C
2H
5R
2Represent the phenyl ring activating group;
Described phenyl ring activating group representative-OCH
3, or-OC
2H
5, or-OH, or-OCOCH
3, or-OCOC
2H
5, or-NH
2, or-N (CH
3)
2, or-NHCOCH
3
2, the synthetic method of a kind of bromo benzoic ether according to claim 1 is characterized in that: described step (2) replaces with following method: reaction mixture is adopted extracted with diethyl ether, drying, be spin-dried for bromo benzoic ether.
3, the synthetic method of a kind of bromo benzoic ether according to claim 1 is characterized in that: the vacuum drying mode is adopted in described oven dry.
4, the synthetic method of a kind of bromo benzoic ether according to claim 1 is characterized in that: described bromo acid alkali metal-salt is potassium bromate or sodium bromate.
5, the synthetic method of a kind of bromo benzoic ether according to claim 1 is characterized in that: described substituted benzene ring compound: bromine: the ratio of bromo acid alkali metal-salt amount of substance is 6: 3: 1.
6, the synthetic method of a kind of bromo benzoic ether according to claim 1 is characterized in that: the described reaction times is 2～3 hours.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0542671A1 (en) * | 1991-10-17 | 1993-05-19 | Ciba-Geigy Ag | Substituted hydroquinone derivatives as intermediates of benzofuran derivatives |
| EP0608714A1 (en) * | 1993-01-29 | 1994-08-03 | Hoechst Aktiengesellschaft | Process for preparing chlorinated 4,5-difluorobenzoic acids, -benzoic acid derivatives and -benzaldehyde |
| EP0968994A1 (en) * | 1996-08-19 | 2000-01-05 | Ube Industries, Ltd. | Substituted trifluorobenzoic acids, esters thereof, and process for producing the same |
| JP2000044501A (en) * | 1998-08-03 | 2000-02-15 | Tohkem Products:Kk | Production of fluorinated aromatic compound and apparatus therefor |
-
2006
- 2006-05-18 CN CNB2006100355108A patent/CN100546970C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0542671A1 (en) * | 1991-10-17 | 1993-05-19 | Ciba-Geigy Ag | Substituted hydroquinone derivatives as intermediates of benzofuran derivatives |
| EP0608714A1 (en) * | 1993-01-29 | 1994-08-03 | Hoechst Aktiengesellschaft | Process for preparing chlorinated 4,5-difluorobenzoic acids, -benzoic acid derivatives and -benzaldehyde |
| EP0968994A1 (en) * | 1996-08-19 | 2000-01-05 | Ube Industries, Ltd. | Substituted trifluorobenzoic acids, esters thereof, and process for producing the same |
| JP2000044501A (en) * | 1998-08-03 | 2000-02-15 | Tohkem Products:Kk | Production of fluorinated aromatic compound and apparatus therefor |
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