CN109912561A - A kind of preparation method of list benzo 21- crown- 7 and its derivative - Google Patents
A kind of preparation method of list benzo 21- crown- 7 and its derivative Download PDFInfo
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- CN109912561A CN109912561A CN201910288966.2A CN201910288966A CN109912561A CN 109912561 A CN109912561 A CN 109912561A CN 201910288966 A CN201910288966 A CN 201910288966A CN 109912561 A CN109912561 A CN 109912561A
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Abstract
The invention discloses the preparation methods of a kind of list benzo 21- crown- 7 and its derivative, under the conditions of the double p-methyl benzenesulfonic acid esters of catechol compound and hexaethylene glycol are existing for the organic solvent and alkali, 24-48 hours list benzo 21- crown- 7 and its derivatives to obtain the final product reacts under the conditions of 60-80 DEG C.KPF is not used in preparation process of the present invention6Or KBF4Equal template compounds, avoid the host-guest complexation of product and potassium ion, so that post-processing is very easy, the single benzo 21- crown- 7 and its derivative of high-purity is can be obtained in simple washing.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to the preparation of a kind of list benzo 21- crown- 7 and its derivative
Method.
Background technique
Single benzo 21- crown- 7 and its derivative are a kind of important crown compounds, can be coordinated with potassium ion, are formed steady
Fixed host-guest coordination compound.Single benzo 21- crown- 7 and its derivative be widely used in preparing supermolecule polymer, molecule machine,
Artificial ion channel.
The synthesis of current list benzo 21- crown- 7 and its derivative mainly uses template synthesis method: during the preparation process with
KPF6Or KBF4It, using potassium carbonate as acid binding agent, is prepared using acetonitrile as solvent by heating reflux reaction for template.Due to
KPF6Or KBF4There can be very strong host-guest interaction with single benzo 21- crown- 7 and its derivative, be prepared by template
The crude product arrived is the host-guest coordination compound that list benzo 21- crown- 7 and its derivative and potassium ion are formed, and is needed using water repeatedly
It washes and repeatedly column chromatography could remove the template in product, the synthesis of single benzo 21- crown- 7 and its derivative is caused to handle ten
Point cumbersome, yield is not high, while this kind of processing method can not remove template whole in product.In this way, limiting single benzo 21-
The large-scale application of crown- 7 and its derivative.
Such as Schalley (Beilstein Journal of Organic Chemistry, 2010,6, No.14) report
Utilize KBF4For templated synthesis list benzo 21- crown- 7 and its derivative, yield 62-70%, while needing cumbersome column
Chromatography is to remove KBF4。
Tomassen etc. (Tetrahedron Letters, 1979, No.22,2067-2070) is although using common
KPF6Or KBF4Template molecule, the yield of synthesis list benzo 21- crown- 7 are that 28% (using potassium fluoride) or 65% (use fluorine
Change caesium).
(Reports of graduate school of engineering, the University of such as Shibata
Hyogo, 2005, No.58) use KOH for alkali, list benzo 21- crown- 7 is prepared in tetrahydrofuran, yield only has 45%,
Need column chromatography to purify single benzo 21- crown- 7.
Summary of the invention
In order to solve defect existing in the prior art, the purpose of the invention is to provide a kind of simple, efficient
The preparation method of single benzo 21- crown- 7 and its derivative does not use KPF in preparation process6Or KBF4Equal template compounds, keep away
Exempted from the host-guest complexation of product and potassium ion, so that post-processing is very easy, simple washing can high yield
To single benzo 21- crown- 7 and its derivative.
In order to achieve the above technical purposes, the present invention adopts the following technical scheme:
The double p-methyl benzenesulfonic acid of the preparation method of a kind of list benzo 21- crown- 7 and its derivative, formula (1) compound and hexaethylene glycol
Under the conditions of ester is existing for the organic solvent and alkali, 24-48 hours are reacted under the conditions of 60-80 DEG C up to formula (2) compound,
Wherein, R is hydrogen, cyano, amino, nitro, aldehyde radical, ester group, carboxylic acid, the alkyl of C1~C4, halogen.
Preferably, the molar ratio of formula (1) compound and the double p-methyl benzenesulfonic acid esters of hexaethylene glycol is 1~1.5:1.
It is furthermore preferred that the molar ratio of formula (1) compound and the double p-methyl benzenesulfonic acid esters of hexaethylene glycol is 1:1.
Preferably, the organic solvent is acetonitrile, acetone.
It is furthermore preferred that the organic solvent is acetonitrile.
Preferably, the alkali is potassium carbonate, sodium carbonate, cesium carbonate and 1, in 11 carbon -7- alkene of 8- diazabicylo extremely
The molar ratio of few one kind, the double p-methyl benzenesulfonic acid esters of hexaethylene glycol and alkali is 1:2~20.
Preferably, after reaction, it filters while hot, removes organic solvent through revolving, gained residue is dissolved in methylene chloride
Or in chloroform, is rotated again after washing and remove dichloromethane or chloroform up to list benzo 21- crown- 7 and its derivative, institute
The yield for stating single benzo 21- crown- 7 and its derivative is 90~94%.
It is furthermore preferred that the list benzo 21- crown- 7 and its derivative are soluble in water, stir 12-24 hours, gained after filtering
Filtrate removes water, for example, by using conventional normal pressure or vacuum distillation to get purity be 98~99% single benzo 21- crown- 7 and
Its derivative.
Compared with prior art, advantage of the invention and the utility model has the advantages that
(1) present invention is not needed using KPF6Or KBF4Deng as template compound, it is entirely avoided single benzo 21- crown- 7
And its derivative and KPF6Or KBF4Form host-guest complex.The use of the highly basic such as KOH is avoided during simultaneous reactions.
(2) present invention post-processing is very easy, does not need cumbersome removing template step, and it is next pure not need multiple column chromatography yet
Change product, single benzo 21- crown- 7 and its derivative only can be obtained by simply washing.
(3) the single benzo 21- crown- 7 and its derivative yield that the present invention obtains are 90~94%.
(4) the characteristics of present invention is using list benzo 21- crown- 7 and its derivative good water solubility, by further simple pure
Change processing can obtain single benzo 21- crown- 7 and its derivative that purity is 98~99%.
Detailed description of the invention
Fig. 1 is the nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 1；
Fig. 2 is the nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 2；
Fig. 3 is the nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 3；
Fig. 4 is the nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 4；
Fig. 5 is the purified nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 1；
Fig. 6 is the purified nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 2；
Fig. 7 is the purified nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 3；
Fig. 8 is the purified nucleus magnetic hydrogen spectrum figure of sample made from the embodiment of the present invention 4.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It is worth explanation, these embodiments are merely to illustrate this hair
It is bright, rather than limit the scope of protection of the present invention.The improvement and tune that technical staff makes according to the present invention in practical applications
It is whole, still fall within protection scope of the present invention.
Embodiment 1
The synthesis of single benzo 21- crown- 7: 1.1 grams of catechol, double 5.91 grams of ester of the p-methyl benzenesulfonic acids of hexaethylene glycol, potassium carbonate
5.22 grams are reacted 48 hours in 350 milliliters of acetonitriles in 60 DEG C, after reaction, are filtered while hot, filtrate is removed with Rotary Evaporators
Remove acetonitrile, residue is dissolved with 250 milliliters of methylene chloride, is washed with water 2 times, then remove methylene chloride through Rotary Evaporators to obtain the final product
Single benzo 21- crown- 7 is 3.23 grams, yield 91%.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterated chloroform, room temperature): δ 6.90 (s, 4H), 4.16 (m, 4H), 3.92 (m, 4H), 3.81
(m,4H),3.73(m,4H),3.67(m,8H)。
Purifying: 1 gram of above-mentioned single benzo 21- crown- 7 being synthetically prepared is taken, is dissolved in 100 milliliters of water, is stirred at room temperature 12 hours
After filter, gained filtrate through vacuum distillation remove water, obtain purity be 98% single benzo 21- crown- 7.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterium-oxide, room temperature): δ 7.03 (d, J=4Hz, 4H), 4.20 (m, 4H), 3.91 (m, 4H),
3.74(m,4H),3.70(m,4H),3.66(m,8H)。
Embodiment 2
The synthesis of single 7 aldehyde of benzo 21- crown-: 3,4- 1.38 grams of 4-dihydroxy benzaldehydes, the double p-methyl benzenesulfonic acid esters of hexaethylene glycol
5.91 grams, 5.22 grams of potassium carbonate are reacted 48 hours in 350 milliliters of acetonitriles in 80 DEG C, after reaction, are filtered while hot, and filtrate is used
Rotary Evaporators remove acetonitrile, and residue is dissolved with 250 milliliters of methylene chloride, is washed with water 2 times, then remove through Rotary Evaporators
Methylene chloride is 3.46 grams up to 7 aldehyde of list benzo 21- crown-, yield 90%.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterated chloroform, room temperature): δ 9.87 (s, 1H), 7.47 (d, J=4Hz, 1H), 7.43 (s,
1H), 6.99 (d, J=4Hz, 1H), 4.26 (m, 4H), 3.97 (m, 4H), 3.84 (m, 4H), 3.78 (m, 4H), 3.71 (m, 8H).
Purifying: 1 gram of above-mentioned single 7 aldehyde of benzo 21- crown- being synthetically prepared is taken, is dissolved in 100 milliliters of water, it is small to be stirred at room temperature 12
When after filter, gained filtrate through vacuum distillation remove water, obtain purity be 98% single 7 aldehyde of benzo 21- crown-.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterium-oxide, room temperature): δ 9.67 (s, 1H), 7.56 (d, J=4Hz, 1H), 7.42 (s, 1H),
7.12 (d, J=4Hz, 1H), 4.28 (m, 2H), 4.21 (m, 2H), 3.91 (m, 4H), 3.73 (m, 4H), 3.68 (m, 4H), 3.64
(m,8H)。
Embodiment 3
The synthesis of single 7 nitrile of benzo 21- crown-: 3,4- 1.35 grams of dihydroxybenzonitriles, the double p-methyl benzenesulfonic acid esters of hexaethylene glycol
5.91 grams, 5.22 grams of potassium carbonate are reacted 48 hours in 350 milliliters of acetonitriles in 70 DEG C, after reaction, are filtered while hot, and filtrate is used
Rotary Evaporators remove acetonitrile, and residue is dissolved with 250 milliliters of methylene chloride, is washed with water 2 times, then remove through Rotary Evaporators
Methylene chloride is 3.58 grams up to 7 nitrile of list benzo 21- crown-, yield 94%.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterated chloroform,Room temperature): δ 7.27 (s, 1H) 7.10 (s, 1H) 6.99 (d, J=4Hz, 1H)
4.20(m,2H),4.17(m,2H),3.95(m,4H),3.80(m,4H),3.75(m,4H),3.68(m,8H)。
Purifying: 1 gram of above-mentioned single 7 nitrile of benzo 21- crown- being synthetically prepared is taken, is dissolved in 100 milliliters of water, it is small to be stirred at room temperature 24
When after filter, gained filtrate through vacuum distillation remove water, obtain purity be 99% single 7 nitrile of benzo 21- crown-.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterium-oxide, room temperature): δ 7.41 (d, J=4Hz, 1H), 7.35 (s, 1H), 7.10 (d, J=4Hz,
1H),4.27(m,2H),4.21(m,2H),3.93(m,4H),3.74(m,4H),3.71(m,4H),3.66(m,8H)。
Embodiment 4
The synthesis of single 7 methyl formate of benzo 21- crown-: 1.68 grams of 3,4-Dihydroxybenzoic acid methyl ester, hexaethylene glycol is double to methyl
5.91 grams of benzene sulfonate, 5.22 grams of potassium carbonate are reacted 48 hours, after reaction, mistake while hot in 80 DEG C in 350 milliliters of acetonitriles
Filter, filtrate remove acetonitrile with Rotary Evaporators, and residue is dissolved with 250 milliliters of methylene chloride, is washed with water 2 times, then through rotating
It is 3.80 grams that evaporimeter, which removes methylene chloride up to 7 methyl formate of list benzo 21- crown-, yield 92%.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterated chloroform, room temperature): δ 7.69 (d, J=4Hz, 1H), 7.58 (s, 1H), 6.91 (d, J=
4Hz,1H),4.25(m,4H),3.98(m,4H),3.92(s,3H),3.84(m,4H),3.79(m,4H),3.72(m,8H)。
Purifying: 1 gram of above-mentioned single 7 methyl formate of benzo 21- crown- being synthetically prepared is taken, is dissolved in 100 milliliters of water, room temperature is stirred
It is filtered after mixing 24 hours, gained filtrate removes water through vacuum distillation, obtains single 7 formic acid first of benzo 21- crown- that purity is 98%
Ester.
Hydrogen modal data is as follows:
1H NMR (400MHz, deuterium-oxide, room temperature): δ 7.60 (d, J=4Hz, 1H), 7.50 (s, 1H), 7.02 (d, J=4Hz,
1H),4.22(m,4H),3.91(m,4H),3.85(s,3H),3.73(m,4H),3.70(m,4H),3.65(m,8H)。
Claims (8)
1. the preparation method of a kind of list benzo 21- crown- 7 and its derivative, it is characterised in that: formula (1) compound and hexaethylene glycol are double
Under the conditions of p-methyl benzenesulfonic acid ester is existing for the organic solvent and alkali, 24-48 hours are reacted under the conditions of 60-80 DEG C up to formula (2)
Compound,
Wherein, R is hydrogen, cyano, amino, nitro, aldehyde radical, ester group, carboxylic acid, the alkyl of C1~C4, halogen.
2. preparation method according to claim 1, it is characterised in that: formula (1) compound and the double p-methyl benzenesulfonic acid of hexaethylene glycol
The molar ratio of ester is 1~1.5:1.
3. preparation method according to claim 2, it is characterised in that: formula (1) compound and the double p-methyl benzenesulfonic acid of hexaethylene glycol
The molar ratio of ester is 1:1.
4. preparation method according to claim 1, it is characterised in that: the organic solvent is acetonitrile, acetone.
5. the preparation method according to claim 4, it is characterised in that: the organic solvent is acetonitrile.
6. preparation method according to claim 1, it is characterised in that: the alkali be potassium carbonate, sodium carbonate, cesium carbonate and 1,
The molar ratio of at least one of 11 carbon -7- alkene of 8- diazabicylo, the double p-methyl benzenesulfonic acid ester of hexaethylene glycol and alkali be 1:2~
20。
7. preparation method according to claim 1, it is characterised in that: after reaction, filter while hot, removing through revolving has
Solvent, gained residue are dissolved in dichloromethane or chloroform, rotate removing dichloromethane or chloroform after washing again
Up to single benzo 21- crown- 7 and its derivative, the yield of the list benzo 21- crown- 7 and its derivative is 90~94%.
8. preparation method according to claim 7, it is characterised in that: the list benzo 21- crown- 7 and its derivative are dissolved in
In water, stir 12-24 hour, after filtering gained filtrate remove water to get purity for 98~99% single benzo 21- crown- 7 and its
Derivative.
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| TOBIAS S. FISCHER等: "Stepwise Unfolding of Single-Chain Nanoparticles by Chemically Triggered Gates", 《ANGEWANDTE CHEMIE-INTERNATIONAL EDITION》 * |
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Application publication date: 20190621 |