CN106278825A - 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 PDF

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CN106278825A
CN106278825A CN201610664204.4A CN201610664204A CN106278825A CN 106278825 A CN106278825 A CN 106278825A CN 201610664204 A CN201610664204 A CN 201610664204A CN 106278825 A CN106278825 A CN 106278825A
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hydroxy
alkyl ether
phenyl alkyl
ether
bond rupture
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CN106278825B (en
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桑大永
田娟
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Jingchu University of Technology
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
    • C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form

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Abstract

The invention discloses a kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether, comprise the steps: in a solvent, under conditions of alkali and catalyst aluminium triiodide exist, there is ether bond rupture reaction in adjacent hydroxyaryl alkyl ether at a temperature of 20 DEG C to described solvent refluxing, generates catechol and derivant thereof.The method is simple, and reaction condition is simple to operation, and productivity is high, and the o-hydroxy-phenyl alkyl ether scope being suitable for is wide.

Description

A kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether
Technical field
The present invention relates to the intermediate synthesis technical field of medicine and industrial chemicals, be specifically related to a kind of o-hydroxy-phenyl alkane The ether bond rupture method of base ether.
Background technology
Substituted catechol is intermediate common in medicine and industrial chemicals, such as hydroxytyrosol (J.Med.Chem.2015,58,9089), protocatechuic acid (CN 104072362) etc..By the ehter bond of o-hydroxy-phenyl alkyl ether Cleavage reaction removing alkyl, is a kind of conventional synthetic method preparing catechol.The ehter bond of o-hydroxy-phenyl alkyl ether breaks Split and can carry out under the catalysis of Bronsted acid or Lewis acid.Conventional Bronsted acid has HCl, HBr, HI, pyridiniujm Hydrochlorate (such as Org.Proc.Res.Dev.2004,8,670) etc..Conventional Lewis acid BBr3(CN 104072362) and LiCl-DMF (Bioorg.Med.Chem.Lett.2011,21,2659) etc..These method complex operations, when for containing to acid The substrate of sensitive functional group, such as eugenol, productivity typically no more than 50%.
In order to solve this problem, Lange has developed and has used AlCl3The method of-tertiary amine, and it is applied successfully to vanillin etc. The demethylating reaction (US3256336) of compound.Due to AlCl3The reactivity of The Splitting of Ether Linkage is general, is used for removing eugenol Deng the substrate of the functional group containing acid labile, yield is the highest.To this end, Arifin et al. has developed AlCl3-DMS method (Indon.J.Chem.2015,15,77), but for the productivity the lowest (about 30%) of eugenol demethylating reaction. Additionally, AlCl3-tertiary amine may be used for removing methyl, and is not suitable for removing the alkyl that the steric hindrances such as ethyl are bigger (J.Org.Chem.1962,27,2037), can appreciable impact yield.
Summary of the invention
For solving the problem that above-mentioned prior art exists, the ehter bond that the invention provides a kind of o-hydroxy-phenyl alkyl ether breaks Cracking method, the method is simple, and reaction condition is simple to operation, and productivity is high, and the o-hydroxy-phenyl alkyl ether scope being suitable for is wide.
Realizing the technical scheme that above-mentioned purpose of the present invention used is:
A kind of ether bond rupture method of o-hydroxy-phenyl alkyl ether, comprises the steps:
In a solvent, under conditions of alkali and aluminium triiodide exist, o-hydroxy-phenyl alkyl ether is at-20 DEG C to described solvent Ether bond rupture reaction occurring at a temperature of backflow, generates catechol and derivant thereof, described o-hydroxy-phenyl alkyl ether is:
Wherein, R1For hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, pi-allyl, isopentene group, Nitro, halogen atom, cyano group, aryl or-O-R, the carbonyl containing-group at hydroxyl ortho position can be competed with catalyst triiodide Property coordination, therefore can not use containing the o-hydroxy-phenyl alkyl ether with the carbonyl containing-group at hydroxyl ortho position；
R2、R3、R4It is respectively as follows: hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, pi-allyl, isoamyl Thiazolinyl, nitro, halogen atom, cyano group, formoxyl, acetyl group, trifluoroacetyl group, carboxyl, aryl, hydroxyl or-O-R；
The formula of described aryl is:
Described R5、R6、R7、R8、R9Be respectively as follows: hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, Pi-allyl, isopentene group, nitro, halogen atom, cyano group, formoxyl, acetyl group, carboxyl, aryl, hydroxyl or-O-R；
Described R is the conventional phenolic hydroxyl protecting group group beyond alkyl or alkyl, and described alkyl is methyl, ethyl, just Propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, n-hexyl, n-octyl, described phenolic hydroxyl protecting group group is benzyl, three Benzyl, methoxy or ethoxy.
Preferably, described solvent is any one in alkane, aromatic hydrocarbons, halogenated hydrocarbons, Carbon bisulfide or nitrile solvents, Or the most several combinations, described alkane is normal hexane, hexamethylene or heptane, described aromatic hydrocarbons benzene, toluene or dimethylbenzene, Described halogenated hydrocarbons is dichloromethane, chloroform, carbon tetrachloride or 1,2-dichloroethanes, described nitrile solvents be acetonitrile, the third two Nitrile, succinonitrile, adiponitrile.
Preferably, described alkali is DIPEA, DMA, quinoline, isoquinolin, adjacent Féraud Quinoline, pyrimidine, pyridine, 2-picoline, 3-picoline, 4-picoline, 2,6-lutidines, DMAP, 2,2'-bipyridyls, 2,3'-bipyridyl, 3, any one of 3'-bipyridyl, or the most several combinations.
Preferably, the response time of ether bond rupture reaction is 0.5-48 hour.
Preferably, the response time of ether bond rupture reaction is 18 hours.
Preferably, when o-hydroxy-phenyl alkyl ether contains the ehter bond that urgently ruptures, 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 bond urgently ruptured Time, the consumption of catalyst and alkali is multiplied by the number of the ehter bond urgently ruptured, such as when the ehter bond ruptured has 2, and three The ratio of silver iodide, alkali and o-hydroxy-phenyl alkyl ether is 1-6:1-20:1.
Preferably, the mol 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 described 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 mixes, and adds aluminium triiodide.If aluminium triiodide first touches o-hydroxy-phenyl alkyl ether, when o-hydroxy-phenyl alkane When containing the functional group of acid labile in base ether, can cause reaction complexity, post processing is cumbersome.
Compared with prior art, advantages of the present invention with have the beneficial effects that:
1) the catalyst aluminium triiodide of the present invention more higher than the Lewis acid acidity of aluminum chloride (Chem.Rev.1969,69, 251), the reactivity of The Splitting of Ether Linkage is also higher than aluminum chloride (ARKIVOC2016, (vi), 446).
2) the catalysis activity of The Splitting of Ether Linkage of the present invention is higher, and the productivity of reaction can reach medium to connecing with the difference of substrate Near quantitative.
3) present invention can use the solvent of the low polarity such as alkane, Carbon bisulfide, or acetonitrile polar solvent, to various The o-hydroxy-phenyl alkyl ether of type can dissolve and be suitable for.
4) present invention may be used for the alkyl removing ethyl, isopropyl geometric ratio methyl steric hindrance is big.
5) in o-hydroxy-phenyl alkyl ether, functional group such as nitro, halogen, aldehyde radical, alkene, cyano group, carbonyl or carboxyl etc. is not no Affected by reaction condition, applied widely.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1 (eugenol demethylation)
Iodine (12.727g), aluminium powder (1.902g) and acetonitrile (100ml) it is separately added into, heating in a 250ml eggplant-shape bottle To backflow, stir 2 hours aubergines to iodine and disappear.Add pyridine (12.183g) and eugenol (4.919g), continue reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (50ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 4) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Cross rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:4, volume ratio) purification, obtain 4-pi-allyl catechol (white Color solid, 4.910g, productivity 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)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.098g), aluminium powder (0.362g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add DMAP (2.750g) and eugenol (0.825g), continue reaction 18 Hour.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Cross rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:4, volume ratio) purification, obtain 4-pi-allyl catechol (white Color solid, 0.362g, productivity 48%), and reclaim raw material (0.202g).
Embodiment 3 (eugenol demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.107g), aluminium powder (0.409g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add 2,6-lutidines (2.750g) and eugenol (0.823g), Continue reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use second Acetoacetic ester (50ml × 3) extracts.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, residual Excess, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:4, volume ratio) purification, obtains 4-pi-allyl neighbour's benzene Diphenol (white solid, 0.692g, productivity 92%).
Embodiment 4 (dehydrodimerization eugenol demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.098g), aluminium powder (0.539g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.612g) and dehydrodimerization eugenol (0.819g), continue Continuous reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use acetic acid Ethyl ester (50ml × 3) extracts.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, remaining Thing, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:4, volume ratio) purification, obtains dehydrodimerization [(4-alkene Propyl group)-catechol] (pink solid, 0.747g, productivity 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 (vanillin demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (0.416g), aluminium powder (0.030g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (0.360g) and vanillin (0.157g), continue reaction 18 Hour.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Crossing rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain 3,4-4-dihydroxy benzaldehyde is (white Color solid, 0.134g, productivity 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 (vanillin demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.107g), aluminium powder (0.574g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.180g) and vanillin (0.761g), continue reaction 18 Hour.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Crossing rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain 3,4-4-dihydroxy benzaldehyde is (white Color solid, 0.498g, productivity 72%).
Embodiment 7 (isovanillin demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.099g), aluminium powder (0.497g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.586g) and isovanillin (0.761g), continue reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Crossing rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain 3,4-4-dihydroxy benzaldehyde is (white Color solid, 0.685g, productivity 99%).
Embodiment 8 (ethyl vanillin demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.099g), aluminium powder (0.637g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.601g) and ethyl vanillin (0.832g), continue anti- Answer 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Crossing rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain 3,4-4-dihydroxy benzaldehyde is (white Color solid, 0.412g, productivity 59%).
Embodiment 9 (o-isopropoxyphenol demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.098g), aluminium powder (0.477g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.601g) and o-isopropoxyphenol (0.761g), continue Continuous reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use acetic acid Ethyl ester (50ml × 3) extracts.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, remaining Thing, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:4, volume ratio) purification, obtains catechol (colourless pin Shape crystal, 0.779g, productivity 64%), and reclaim 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)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.109g), aluminium powder (0.412g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.860g) and 4-hydroxy 3-methoxybenzene nitrile (0.746g), reaction 18 hours is continued.Stop stirring, in reactant liquor, after being cooled to room temperature, add the dilute hydrochloric acid (10ml) of 2mol/L Acidifying, extracts by ethyl acetate (50ml × 3).Merge organic facies, be dried with anhydrous sodium sulfate.Filter, filtrate rotary evaporation Instrument is evaporated, and residue, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:4, volume ratio) purification, obtains 4-cyanogen Base catechol (white solid, 0.598g, productivity 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)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.115g), aluminium powder (0.431g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.814g) and 3-hydroxyl-4-methoxy cyanophenyl (0.746g), reaction 18 hours is continued.Stop stirring, in reactant liquor, after being cooled to room temperature, add the dilute hydrochloric acid (10ml) of 2mol/L Acidifying, extracts by ethyl acetate (50ml × 3).Merge organic facies, be dried with anhydrous sodium sulfate.Filter, filtrate rotary evaporation Instrument is evaporated, and residue, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:4, volume ratio) purification, obtains 4-cyanogen Base catechol (white solid, 0.624g, productivity 92%).
Embodiment 12 (vanillic acid demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.100g), aluminium powder (0.464g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.622g) and vanillic acid (0.844g), continue reaction 18 Hour.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Cross rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain protocatechuic acid (white solid, 0.510g, productivity 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)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.101g), aluminium powder (0.417g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.622g) and vanillone (0.831g), continue reaction 18 Hour.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Cross rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain DHAP (white Color solid, 0.577g, productivity 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)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.098g), aluminium powder (0.467g) and acetonitrile (50ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.889g) and guaiacol (0.621g), continue reaction 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use ethyl acetate (50ml × 3) extract.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, and residue leads to Cross rapid column chromatography (flowing is mutually for ethyl acetate: petroleum ether=1:1, volume ratio) purification, obtain catechol (colourless needles Crystal, 0.546g, productivity 99%).
Embodiment 15 (5-nitro vanillin demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.095g), aluminium powder (0.368g) and acetonitrile (40ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.597g) and 5-nitro vanillin (0.986g), continue React 18 hours.Stop stirring, in reactant liquor, add dilute hydrochloric acid (10ml) acidifying of 2mol/L after being cooled to room temperature, use acetic acid second Ester (50ml × 3) extracts.Merge organic facies, be dried with anhydrous sodium sulfate.Filtering, filtrate is evaporated with Rotary Evaporators, residue By rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:3, volume ratio) purification, obtain 3,4-dihydroxy-5-nitro Benzaldehyde (yellow solid, 0.650g, productivity 71%).
1H NMR(400MHz,d6-DMSO)δ11.00(brs,2H),9.81(s,1H),7.98(s,H),7.46(s,1H). Embodiment 16 (2-bromo-5-hydroxyl-4-methoxybenzaldehyde demethylation)
In a 100ml eggplant-shape bottle, it is separately added into iodine (2.101g), aluminium powder (0.385g) and acetonitrile (40ml), is heated to Backflow, stirs 2 hours aubergines to iodine and disappears.Add pyridine (1.787g) and 2-bromo-5-hydroxyl-4-methoxybenzaldehyde (1.161g), reaction 18 hours is continued.Stop stirring, in reactant liquor, after being cooled to room temperature, add the dilute hydrochloric acid (10ml) of 2mol/L Acidifying, extracts by ethyl acetate (50ml × 3).Merge organic facies, be dried with anhydrous sodium sulfate.Filter, filtrate rotary evaporation Instrument is evaporated, and residue, by rapid column chromatography (flowing is ethyl acetate mutually: petroleum ether=1:3, volume ratio) purification, obtains 2- Bromo-4,5-4-dihydroxy benzaldehyde (yellow solid, 0.946g, productivity 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 (9)

1. the ether bond rupture method of an o-hydroxy-phenyl alkyl ether, it is characterised in that comprise the steps:
In a solvent, under conditions of alkali and catalyst aluminium triiodide exist, o-hydroxy-phenyl alkyl ether is described the most molten at-20 DEG C There is ether bond rupture reaction at a temperature of agent backflow, generate catechol and derivant, described o-hydroxy-phenyl alkyl ether For:
Wherein, R1For hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, pi-allyl, isopentene group, nitro, Halogen atom, cyano group, aryl or-O-R；
R2、R3、R4Be respectively as follows: hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, pi-allyl, isopentene group, Nitro, halogen atom, cyano group, formoxyl, acetyl group, trifluoroacetyl group, carboxyl, aryl, hydroxyl or-O-R；
The formula of described aryl is:
Described R5、R6、R7、R8、R9It is respectively as follows: hydrogen atom, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, allyl Base, isopentene group, nitro, halogen atom, cyano group, formoxyl, acetyl group, carboxyl, aryl, hydroxyl or-O-R；
Described R is alkyl, and described alkyl is methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, just Hexyl, n-octyl and benzyl, trityl, methoxy or ethoxy.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 1, it is characterised in that: described solvent For any one in alkane, aromatic hydrocarbons, halogenated hydrocarbons, Carbon bisulfide or nitrile solvents, or the most several combinations, described Alkane is normal hexane, hexamethylene or heptane, and described aromatic hydrocarbons is benzene, toluene or dimethylbenzene, described halogenated hydrocarbons be dichloromethane, Chloroform, carbon tetrachloride or 1,2-dichloroethanes, described nitrile solvents is acetonitrile, Cyanoacetyl-Cyacetazid, succinonitrile, adiponitrile.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 1, it is characterised in that: described alkali is N, N-diisopropylethylamine, N, accelerine, quinoline, isoquinolin, Phen, pyrimidine, pyridine, 2-picoline, 3- Picoline, 4-picoline, 2,6-lutidines, DMAP, 2,2'-bipyridyl, 2,3'-bipyridyl, 3, 3'-bipyridyl and 4, any one of 4'-bipyridyl, or the most several combinations.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 1, it is characterised in that: ether bond rupture is anti- The response time answered is 0.5-48 hour.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 4, it is characterised in that: ether bond rupture is anti- The response time answered is 18 hours.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 1, it is characterised in that: work as o-hydroxy Base alkyl ether contain one when the ehter bond ruptured, 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 bond urgently ruptured, the consumption of catalyst and alkali is by urgently breaking The number of the ehter bond split is multiplied.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 7, it is characterised in that: aluminium triiodide, The mol ratio of alkali and o-hydroxy-phenyl alkyl ether is 1.0～1.5:4～5:1.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most 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 described solvent.
The ether bond rupture method of o-hydroxy-phenyl alkyl ether the most according to claim 1, it is characterised in that: first by triiodide Aluminum is dissolved in solvent, sequentially adds alkali, o-hydroxy-phenyl alkyl ether；Or first aluminium triiodide is dissolved in solvent, adds Alkali and the mixture of o-hydroxy-phenyl alkyl ether；Or first alkali and o-hydroxy-phenyl alkyl ether are mixed, add aluminium triiodide.
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CN106866377A (en) * 2017-02-13 2017-06-20 荆楚理工学院 A kind of ether bond rupture method of phenyl alkyl ether
CN106866377B (en) * 2017-02-13 2020-06-09 荆楚理工学院 Ether bond breaking method of phenyl alkyl ether
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