CN106278825B - A kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether - Google Patents
A kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether Download PDFInfo
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- CN106278825B CN106278825B CN201610664204.4A CN201610664204A CN106278825B CN 106278825 B CN106278825 B CN 106278825B CN 201610664204 A CN201610664204 A CN 201610664204A CN 106278825 B CN106278825 B CN 106278825B
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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Abstract
The invention discloses a kind of ether bond rupture methods of o-hydroxy-phenyl alkyl ether, include the following steps: in a solvent, under the conditions of existing for the alkali and catalyst aluminium triiodide, adjacent hydroxyaryl alkyl ether generates catechol and its derivative in -20 DEG C to the solvent refluxing of at a temperature of generation ether bond rupture reaction.This method is simple, and reaction condition is simple to operation, and yield is high, and applicable o-hydroxy-phenyl alkyl ether range is wide.
Description
Technical field
The present invention relates to the intermediate synthesis technical fields of drug and industrial chemicals, and in particular to a kind of o-hydroxy-phenyl alkane
The ether bond rupture method of base ether.
Background technique
Substituted catechol is intermediate common in drug and industrial chemicals, such as hydroxytyrosol
(J.Med.Chem.2015,58,9089), protocatechuic acid (CN 104072362) etc..Pass through the ehter bond of o-hydroxy-phenyl alkyl ether
Cleavage reaction removes alkyl, is a kind of synthetic method for commonly preparing catechol.The ehter bond of o-hydroxy-phenyl alkyl ether is disconnected
Splitting can carry out under the catalysis of Bronsted acid or Lewis acid.Common Bronsted acid has HCl, HBr, HI, pyridiniujm
Hydrochlorate (such as Org.Proc.Res.Dev.2004,8,670) etc..Common Lewis acid BBr3(CN 104072362) and
LiCl-DMF (Bioorg.Med.Chem.Lett.2011,21,2659) etc..These methods are cumbersome, when for containing to acid
The substrate of sensitive functional group, such as eugenol, yield are generally no more than 50%.
In order to solve this problem, Lange, which has developed, uses AlCl3The method of tertiary amine, and be applied successfully to vanillic aldehyde etc.
The demethylating reaction (US3256336) of compound.Due to AlCl3The reactivity of The Splitting of Ether Linkage is general, for removing eugenol
Deng the substrate of the functional group containing acid labile, yield is not high.For this purpose, Arifin et al. has developed AlCl3- DMS method
(Indon.J.Chem.2015,15,77), but the yield for eugenol demethylating reaction is still very low (30% or so).
In addition, AlCl3Tertiary amine can be used for removing methyl, and be not suitable for the bigger alkyl of steric hindrances such as removing ethyl
(J.Org.Chem.1962,27,2037), can significantly affect yield.
Summary of the invention
To solve the above-mentioned problems of the prior art, it is disconnected that the present invention provides a kind of ehter bonds of o-hydroxy-phenyl alkyl ether
Cracking method, this method is simple, and reaction condition is simple to operation, and yield is high, and applicable o-hydroxy-phenyl alkyl ether range is wide.
Realize technical solution used in above-mentioned purpose of the present invention are as follows:
A kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether, includes the following steps:
In a solvent, existing for the alkali and aluminium triiodide under the conditions of, o-hydroxy-phenyl alkyl ether is at -20 DEG C to the solvent
Ether bond rupture reaction occurs at a temperature of reflux, generates catechol and its derivative, the o-hydroxy-phenyl alkyl ether are as follows:
Wherein, R1For hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic, allyl, isopentene group,
The carbonyl containing-group of nitro, halogen atom, cyano, aryl or-O-R, hydroxyl ortho position can be competed with catalyst triiodide
Property coordination, therefore containing cannot be used with the o-hydroxy-phenyl alkyl ether of the carbonyl containing-group at hydroxyl ortho position；
R2、R3、R4It is respectively as follows: hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic, allyl, isoamyl
Alkenyl, nitro, halogen atom, cyano, formoxyl, acetyl group, trifluoroacetyl group, carboxyl, aryl, hydroxyl or-O-R；
The general formula of the aryl are as follows:
The R5、R6、R7、R8、R9Be respectively as follows: hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic,
Allyl, isopentene group, nitro, halogen atom, cyano, formoxyl, acetyl group, carboxyl, aryl, hydroxyl or-O-R；
The R is the common phenolic hydroxyl protecting group group other than alkyl or alkyl, and the alkyl is methyl, ethyl, just
Propyl, isopropyl, normal-butyl, isobutyl group, tert-butyl, n-hexyl, n-octyl, the phenolic hydroxyl protecting group group is benzyl, three
Benzyl, methoxy or ethoxy.
Preferably, the solvent is any one in alkane, aromatic hydrocarbons, halogenated hydrocarbons, carbon disulfide or nitrile solvents,
Or any several combination, the alkane are n-hexane, hexamethylene or heptane, aromatic hydrocarbons benzene, toluene or the dimethylbenzene,
The halogenated hydrocarbons is methylene chloride, chloroform, carbon tetrachloride or 1, and 2- dichloroethanes, the nitrile solvents are acetonitrile, the third two
Nitrile, succinonitrile, adiponitrile.
Preferably, the alkali is n,N-diisopropylethylamine, n,N-Dimethylaniline, quinoline, isoquinolin, adjacent Féraud
Quinoline, pyrimidine, pyridine, 2- picoline, 3- picoline, 4- picoline, 2,6- lutidines, 4-dimethylaminopyridine,
Any one of 2,2'- bipyridyls, 2,3'- bipyridyl, 3,3'- bipyridyl, or any several combination.
Preferably, the reaction time of ether bond rupture reaction is 0.5-48 hours.
Preferably, the reaction time of ether bond rupture reaction is 18 hours.
Preferably, when o-hydroxy-phenyl alkyl ether contains an ehter bond being urgently broken, aluminium triiodide, alkali and adjacent hydroxyl
The ratio of phenyl alkyl ether is 0.5~3:0.5~10:1, when o-hydroxy-phenyl alkyl ether contains multiple ehter bonds being urgently broken
When, the dosage of catalyst and alkali is multiplied by the number for the ehter bond being urgently broken, such as when the ehter bond wait be broken has 2, and three
The ratio of silver iodide, alkali and o-hydroxy-phenyl alkyl ether is 1-6:1-20:1.
Preferably, the molar ratio of aluminium triiodide, alkali and o-hydroxy-phenyl alkyl ether is 1.0~1.5:4~5:1.
Preferably, the reaction temperature of ether bond rupture reaction is 80 DEG C of reflux temperatures to the solvent.
Preferably, first aluminium triiodide is dissolved in solvent, sequentially adds alkali, o-hydroxy-phenyl alkyl ether；Or first will
Aluminium triiodide is dissolved in solvent, adds the mixture of alkali and o-hydroxy-phenyl alkyl ether；Or first by alkali and o-hydroxy-phenyl
Alkyl ether mixing, adds aluminium triiodide.If aluminium triiodide first touches o-hydroxy-phenyl alkyl ether, when o-hydroxy-phenyl alkane
When functional group in base ether containing acid labile, it is complicated to will lead to reaction, post-processes more troublesome.
Compared with prior art, advantages of the present invention is with beneficial effect:
1) catalyst aluminium triiodide of the invention it is more acid than the Lewis of alchlor acid it is stronger (Chem.Rev.1969,69,
251), the reactivity of The Splitting of Ether Linkage is also higher than alchlor (ARKIVOC2016, (vi), 446).
2) catalytic activity of The Splitting of Ether Linkage of the present invention is higher, and the yield of reaction can achieve medium to connecing with the difference of substrate
It is close quantitative.
3) the low polar solvent such as alkane, carbon disulfide or acetonitrile isopolarity solvent can be used in the present invention, to various
The o-hydroxy-phenyl alkyl ether of type can be dissolved and is applicable in.
4) present invention can be used for removing the alkyl bigger than methyl steric hindrance such as ethyl, isopropyl.
5) functional groups such as nitro, halogen, aldehyde radical, alkene, cyano, carbonyl or carboxyl etc. are not no in o-hydroxy-phenyl alkyl ether
It is influenced by reaction condition, it is applied widely.
Specific embodiment
The present invention is described in detail combined with specific embodiments below.
Embodiment 1 (eugenol demethylation)
It is separately added into iodine (12.727g), aluminium powder (1.902g) and acetonitrile (100ml) into a 250ml eggplant-shape bottle, heats
To reflux, 2 hours purplish red decolorations to iodine are stirred.Pyridine (12.183g) and eugenol (4.919g) are added, the reaction was continued
18 hours.Stop stirring, is cooled to dilute hydrochloric acid (50ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 4) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio) purifying is crossed, it is (white to obtain 4- allyl catechol
Color solid, 4.910g, yield 99%).
1H NMR (400MHz, CDCl3) δ 6.80 (d, J=8Hz, 1H), 6.72 (d, J=2Hz, 1H), 6.63 (dd, J1=
8Hz, J2=2Hz, 1H), 6.10 (brs, 2H), 5.92 (ddt, J1=17.2Hz, J2=10.4Hz, J2=6.8Hz, 1H),
5.05 (dq, J1=16.8Hz, J2=1.6Hz, 1H), 5.03 (dq, J1=10.0Hz, J2=1.6Hz, 1H), 3.26 (d, J=
6.4Hz,1H).
13C NMR(100MHz,CDCl3)δ143.35,141.54,137.65,133.60,121.33,116.09,
115.80,115.71,39.50.
Embodiment 2 (eugenol demethylation)
It is separately added into iodine (2.098g), aluminium powder (0.362g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.DMAP (2.750g) and eugenol (0.825g) are added, the reaction was continued 18
Hour.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio) purifying is crossed, it is (white to obtain 4- allyl catechol
Color solid, 0.362g, yield 48%), and recycle raw material (0.202g).
Embodiment 3 (eugenol demethylation)
It is separately added into iodine (2.107g), aluminium powder (0.409g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.2,6- lutidines (2.750g) and eugenol (0.823g) are added,
The reaction was continued 18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses second
Acetoacetic ester (50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, residual
Excess is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio), obtains 4- allyl neighbour's benzene
Diphenol (white solid, 0.692g, yield 92%).
Embodiment 4 (dehydrodimerization eugenol demethylation)
It is separately added into iodine (2.098g), aluminium powder (0.539g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.612g) and dehydrodimerization eugenol (0.819g) are added, after
Continuous reaction 18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses acetic acid
Ethyl ester (50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, remaining
Object is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio), obtains dehydrodimerization [(4- alkene
Propyl)-catechol] (pink solid, 0.747g, yield 96%).
1H NMR (400MHz, CD3OD) δ 6.65 (d, J=2.0Hz, 2H), 6.56 (d, J=2.4Hz, 2H), 5.95
(ddt, J1=16.8Hz, J2=10.0Hz, J3=6.4Hz, 2H), 5.06 (m, 2H), 5.01 (m, 2H), 3.27 (d, J=
6.8Hz,4H).
Embodiment 5 (vanillic aldehyde demethylation)
It is separately added into iodine (0.416g), aluminium powder (0.030g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (0.360g) and vanillic aldehyde (0.157g) are added, the reaction was continued 18
Hour.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, it is (white to obtain 3,4- 4-dihydroxy benzaldehyde
Color solid, 0.134g, yield 94%).
1H NMR(400MHz,d6-DMSO)δ10.11(brs,1H),9.70(s,1H),9.55(brs,1H),7.27(dd,
J1=8.0Hz, J2=2.0Hz, 1H), 7.23 (d, J=1.6Hz, 1H), 7.06 (s, 1H), 6.91 (d, J=8.0Hz, 1H)
Embodiment 6 (vanillic aldehyde demethylation)
It is separately added into iodine (2.107g), aluminium powder (0.574g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.180g) and vanillic aldehyde (0.761g) are added, the reaction was continued 18
Hour.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, it is (white to obtain 3,4- 4-dihydroxy benzaldehyde
Color solid, 0.498g, yield 72%).
Embodiment 7 (isovanillin demethylation)
It is separately added into iodine (2.099g), aluminium powder (0.497g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.586g) and isovanillin (0.761g) are added, the reaction was continued
18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, it is (white to obtain 3,4- 4-dihydroxy benzaldehyde
Color solid, 0.685g, yield 99%).
Embodiment 8 (Ethyl vanillin demethylation)
It is separately added into iodine (2.099g), aluminium powder (0.637g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.601g) and Ethyl vanillin (0.832g) are added, is continued anti-
It answers 18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, it is (white to obtain 3,4- 4-dihydroxy benzaldehyde
Color solid, 0.412g, yield 59%).
Embodiment 9 (o-isopropoxyphenol demethylation)
It is separately added into iodine (2.098g), aluminium powder (0.477g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.601g) and o-isopropoxyphenol (0.761g) are added, after
Continuous reaction 18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses acetic acid
Ethyl ester (50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, remaining
Object is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio), obtains catechol (colourless needle
Shape crystal, 0.779g, yield 64%), and recycle raw material (0.150g).
1H NMR(400MHz,CDCl3)δ6.90-6.85(m,2H),6.84-6.79(m,2H),5.23(brs,2H).
Embodiment 10 (4- hydroxy 3-methoxybenzene nitrile demethylation)
It is separately added into iodine (2.109g), aluminium powder (0.412g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Add pyridine (1.860g) and 4- hydroxy 3-methoxybenzene nitrile
(0.746g), the reaction was continued 18 hours.Stop stirring, is cooled to the dilute hydrochloric acid (10ml) that 2mol/L is added after room temperature into reaction solution
Acidification is extracted with ethyl acetate (50ml × 3).Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate rotary evaporation
Instrument is evaporated, and residue is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio), obtains 4- cyanogen
Base catechol (white solid, 0.598g, yield 88%).
1H NMR (400MHz, d6-DMSO) δ 9.96 (brs, 1H), 9.90 (brs, 1H), 7.11 (d, J=8.4Hz, 1H),
7.06 (s, 1H), 6.86 (d, J=8.4Hz, 1H)
13C NMR(100MHz,d6-DMSO)δ150.99,146.36,125.24,120.04,118.81,116.78,
101.36.
Embodiment 11 (3- hydroxyl -4- methoxy cyanophenyl demethylation)
It is separately added into iodine (2.115g), aluminium powder (0.431g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Add pyridine (1.814g) and 3- hydroxyl -4- methoxy cyanophenyl
(0.746g), the reaction was continued 18 hours.Stop stirring, is cooled to the dilute hydrochloric acid (10ml) that 2mol/L is added after room temperature into reaction solution
Acidification is extracted with ethyl acetate (50ml × 3).Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate rotary evaporation
Instrument is evaporated, and residue is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:4, volume ratio), obtains 4- cyanogen
Base catechol (white solid, 0.624g, yield 92%)
Embodiment 12 (vanillic acid demethylation)
It is separately added into iodine (2.100g), aluminium powder (0.464g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.622g) and vanillic acid (0.844g) are added, the reaction was continued 18
Hour.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Cross rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying, obtain protocatechuic acid (white solid,
0.510g, yield 65%).
1H NMR(400MHz,d6-DMSO)δ12.32(brs,1H),9.67(brs,1H),9.33(brs,1H),7.33
(d, J=2.0Hz, 1H), 7.06 (s, 1H), 7.28 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 6.78 (d, J=8.0Hz,
1H).
Embodiment 13 (vanillone demethylation)
It is separately added into iodine (2.101g), aluminium powder (0.417g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.622g) and vanillone (0.831g) are added, the reaction was continued 18
Hour.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, it is (white to obtain 3,4-Dihydroxyacetophenone
Color solid, 0.577g, yield 75%).
1H NMR (400MHz, d6-DMSO) δ 9.57 (brs, 2H), 7.34 (d, J=8.0Hz, 1H), 7.33 (s, 1H),
6.80 (d, J=8.0Hz, 1H), 2.43 (s, 3H)
Embodiment 14 (guaiacol demethylation)
It is separately added into iodine (2.098g), aluminium powder (0.467g) and acetonitrile (50ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.889g) and guaiacol (0.621g) are added, the reaction was continued
18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, uses ethyl acetate
(50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, and residue is logical
Rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:1, volume ratio) purifying is crossed, catechol (colourless needles are obtained
Crystal, 0.546g, yield 99%)
Embodiment 15 (5- nitro vanillin demethylation)
It is separately added into iodine (2.095g), aluminium powder (0.368g) and acetonitrile (40ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Pyridine (1.597g) and 5- nitro vanillin (0.986g) are added, is continued
Reaction 18 hours.Stop stirring, is cooled to dilute hydrochloric acid (10ml) acidification that 2mol/L is added after room temperature into reaction solution, with acetic acid second
Ester (50ml × 3) extraction.Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate are evaporated with Rotary Evaporators, residue
It is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:3, volume ratio), obtains 3,4- dihydroxy -5- nitro
Benzaldehyde (yellow solid, 0.650g, yield 71%).
1H NMR(400MHz,d6-DMSO)δ11.00(brs,2H),9.81(s,1H),7.98(s,H),7.46(s,1H).
Embodiment 16 (the bromo- 5- hydroxyl -4-methoxybenzaldehyde demethylation of 2-)
It is separately added into iodine (2.101g), aluminium powder (0.385g) and acetonitrile (40ml) into a 100ml eggplant-shape bottle, is heated to
2 hours purplish red decolorations to iodine are stirred in reflux.Add pyridine (1.787g) and the bromo- 5- hydroxyl -4-methoxybenzaldehyde of 2-
(1.161g), the reaction was continued 18 hours.Stop stirring, is cooled to the dilute hydrochloric acid (10ml) that 2mol/L is added after room temperature into reaction solution
Acidification is extracted with ethyl acetate (50ml × 3).Merge organic phase, it is dry with anhydrous sodium sulfate.Filtering, filtrate rotary evaporation
Instrument is evaporated, and residue is purified by rapid column chromatography (mobile phase is ethyl acetate: petroleum ether=1:3, volume ratio), obtains 2-
Bromo- 4,5- 4-dihydroxy benzaldehyde (yellow solid, 0.946g, yield 87%).
1H NMR(400MHz,d6-DMSO)δ10.21(brs,2H),9.95(s,1H),7.25(s,H),7.05(s,1H).
13C NMR(100MHz,d6-DMSO)δ190.44,153.55,146.14,125.27,120.02,117.45,
115.57.。
Claims (8)
1. a kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether, it is characterised in that include the following steps:
In a solvent, existing for the alkali and aluminium triiodide under the conditions of, o-hydroxy-phenyl alkyl ether is at -20 DEG C to the solvent refluxing
At a temperature of ether bond rupture reaction occurs, generate catechol and its derivative, the o-hydroxy-phenyl alkyl ether are as follows:
Wherein, R1For hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic, allyl, isopentene group, nitro,
Halogen atom, cyano, aryl or-O-R；
R2、R3、R4Be respectively as follows: hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic, allyl, isopentene group,
Nitro, halogen atom, cyano, formoxyl, acetyl group, trifluoroacetyl group, carboxyl, aryl, hydroxyl or-O-R；
The general formula of the aryl are as follows:
The R5、R6、R7、R8、R9It is respectively as follows: hydrogen atom, methyl, ethyl, propyl, isopropyl, vinyl, acrylic, allyl
Base, isopentene group, nitro, halogen atom, cyano, formoxyl, acetyl group, carboxyl or hydroxyl；
The R is alkyl, and the alkyl is methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, tert-butyl, just
Hexyl, n-octyl and benzyl or trityl；
The solvent be alkane, aromatic hydrocarbons, halogenated hydrocarbons, carbon disulfide perhaps in nitrile solvents any one or it is any several
The combination of kind, the alkane are n-hexane, hexamethylene or heptane, and the aromatic hydrocarbons is benzene, toluene or dimethylbenzene, the halogen
It is methylene chloride, chloroform, carbon tetrachloride or 1 for hydrocarbon, 2- dichloroethanes, the nitrile solvents are acetonitrile, malononitrile, succinonitrile
Or adiponitrile；
The alkali be N, N- diisopropylethylamine, N, accelerine, quinoline, isoquinolin, Phen, pyrimidine, pyridine,
2- picoline, 3- picoline, 4- picoline, 2,6- lutidines, 4-dimethylaminopyridine, 2,2'- bipyridyl, 2,
3'- bipyridyl, 3,3'- bipyridyl and 4,4'- bipyridyl any one, or any several combination.
2. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: the solvent
For nitrile solvents, the nitrile solvents are acetonitrile, malononitrile, succinonitrile or adiponitrile.
3. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: ether bond rupture is anti-
The reaction time answered is 0.5-48 hours.
4. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 3, it is characterised in that: ether bond rupture is anti-
The reaction time answered is 18 hours.
5. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: work as o-hydroxy
When base alkyl ether contains an ehter bond wait be broken, the ratio of aluminium triiodide, alkali and o-hydroxy-phenyl alkyl ether is 0.5~3:
0.5~10:1；When o-hydroxy-phenyl alkyl ether contains multiple ehter bonds being urgently broken, the dosage of aluminium triiodide and alkali is by urgently
The number of the ehter bond of fracture is multiplied.
6. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: aluminium triiodide,
The molar ratio of alkali and o-hydroxy-phenyl alkyl ether is 1.0~1.5:4~5:1.
7. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: ether bond rupture is anti-
The reaction temperature answered is 80 DEG C of reflux temperatures to the solvent.
8. the ether bond rupture method of o-hydroxy-phenyl alkyl ether according to claim 1, it is characterised in that: first by triiodide
Aluminium is dissolved in solvent, sequentially adds alkali, o-hydroxy-phenyl alkyl ether；Or first aluminium triiodide is dissolved in solvent, it adds
The mixture of alkali and o-hydroxy-phenyl alkyl ether；Or first mix alkali and o-hydroxy-phenyl alkyl ether, add aluminium triiodide.
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| CN101066912A (en) * | 2007-06-08 | 2007-11-07 | 中国科学院广州化学研究所 | Process of preparing trans-polyhydroxy diphenyl ethylene |
| WO2013111148A1 (en) * | 2011-12-13 | 2013-08-01 | Laurus Labs Private Limited | Process for preparation of luteolin |
| CN103833714A (en) * | 2014-02-23 | 2014-06-04 | 闻永举 | Semi-synthesis method of luteolin and galuteolin as well as luteolin rutinoside |
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| WO2013111148A1 (en) * | 2011-12-13 | 2013-08-01 | Laurus Labs Private Limited | Process for preparation of luteolin |
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