Asymmetric ring-opening cucurbiturils and preparation method thereof
阅读说明：本技术 一类不对称开环葫芦脲及其制备方法 (Asymmetric ring-opening cucurbiturils and preparation method thereof ) 是由 杨波 杨外祥 孔令广 洪浩玲 张东京 陈丽媛 杜刚 朱盼永 陈大蕾 施正斗 赵榆 于 2019-10-12 设计创作，主要内容包括：本发明公开了一类不对称开环葫芦脲及其制备方法；本发明不对称开环葫芦脲具有聚合甘脲和不对称对苯二酚衍生物、对萘二酚衍生物的分子砌块；该类分子具有C字形结构,空腔大小不同,可适应不同尺寸的客体分子,可作为超分子载体,与匹配客体物质形成多分子体系,应用于制药、食品、香精香料、烟草、化工催化等行业。(The invention discloses an asymmetric ring-opening cucurbituril and a preparation method thereof; the asymmetric ring-opening cucurbituril of the invention has molecular building blocks of polymerized glycoluril, asymmetric hydroquinone derivatives and hydroquinone derivatives; the molecules have C-shaped structures, have different cavity sizes, are suitable for guest molecules with different sizes, can be used as a supermolecular carrier to form a multi-molecule system with matched guest substances, and are applied to industries such as pharmacy, food, flavors and fragrances, tobacco, chemical industry catalysis and the like.)
1. Asymmetric ring-opening cucurbiturils having the structural formula shown in formula I, formula II, formula III:
formula III;
wherein R is1Is (CH)2)nX, n =1 ~ 5, X is Cl, Br, I, R2Is R1Or (CH)2)mCH3，m=0~4。
2. The method for producing an asymmetric ring-opened cucurbituril according to claim 1, wherein: reacting tetra-poly glycoluril, 3' - (1, 4-benzenedioxy) -di (1-propanesulfonic acid), hydroquinone derivative or p-naphthalenediol derivative serving as raw materials in a mixed solution of organic strong acid and an organic solvent, after the reaction is finished, adding cooled reaction liquid into the organic solvent, performing suction filtration after precipitation is completely separated out, recrystallizing the solid, and drying to obtain the asymmetric ring-opening cucurbituril.
3. The method for preparing the asymmetric ring-opening cucurbituril according to claim 2, wherein the molar ratio of the tetraglycoluril to the 3, 3' - (1, 4-benzenedioxy) -bis (1-propanesulfonic acid) to the hydroquinone derivative or the hydroquinone derivative to the naphthalenediol derivative is 5:6:6 ~ 5:8:8, and the volume ratio of the organic strong acid to the organic solvent is 1:1 ~ 3: 1.
4. The method for preparing an asymmetric ring-opened cucurbituril according to claim 3, wherein: organic strong acids include, but are not limited to, methanesulfonic acid, trifluoroacetic acid, trifluoromethanesulfonic acid; organic solvents include, but are not limited to, acetone, tetrahydrofuran, acetic anhydride, ethanol, methanol, N-dimethylformamide, dimethylsulfoxide.
5. The method for preparing asymmetric ring-opened cucurbituril according to claim 2, wherein the reaction temperature is 60 ~ 80 ℃ and the reaction time is 3 ~ 5 h.
6. The method for preparing an asymmetric ring-opened cucurbituril according to claim 2, wherein: the organic solvent used for separating out the reaction solution is acetone, tetrahydrofuran, ethanol, methanol, N-dimethylformamide or dimethyl sulfoxide.
7. The method for preparing an asymmetric ring-opened cucurbituril according to claim 2, wherein: the recrystallization adopts a method of dissolving in water and settling by an organic solvent.
8. The method for preparing an asymmetric ring-opened cucurbituril according to claim 7, wherein: the organic solvent used for sedimentation is tetrahydrofuran, ethanol, methanol, acetone, N-dimethylformamide or dimethyl sulfoxide.
9. Use of the asymmetric ring-opened cucurbituril of claim 1 as a supramolecular carrier.
Technical Field
The invention belongs to the field of new material preparation, and particularly relates to supramolecular carrier asymmetric ring-opening cucurbiturils and a preparation method thereof.
Background
Supramolecular chemistry is a leading discipline that has developed relatively rapidly in recent years. The recognition and self-assembly between supramolecular host molecules and other molecules is the main content of supramolecular research. Among these, macrocyclic compounds are the main supramolecular hosts. Most of the host molecules are provided with hydrophobic cavities which can be used for encapsulating small molecule substances to form a host-guest system. Common supramolecular bodies include crown ether, cyclodextrin, cucurbituril, pillared aromatic hydrocarbons, calixarenes, and the like.
The ring-opening cucurbituril is a novel supermolecule main body which develops rapidly in the last decade, and is characterized in that: the central glycoluril oligomer imparts curvature and has the ability to bind hydrophobic cations; the hydroquinone derivative at two ends can promote the pi-pi interaction between the container and the insoluble substance; sulfonic acid groups and the like on the side groups have solubilization; the cavity structure is similar to a C shape and can be flexibly adjusted to adapt to guest molecules with different sizes.
In 2009, professor Isaccs reported ring-opened cucurbituril molecules for the first time at 238 th annual meeting of organic chemistry in america. The following groups and others have studied such molecules in detail as synthesis and derivatization, molecular recognition, drug delivery, drug solubilization, and the like.
Regarding the ring-opened cucurbituril and the patent of the application thereof, the invention patent CN201711129478.4 discloses a ring-opened cucurbituril sensitive to alkali. The invention patent CN201810794331.5 discloses an inclusion compound of artemisinin drugs and ring-opened cucurbituril and a preparation method thereof. The invention patent CN201711129501.X discloses polyamine-derivatized ring-opening cucurbiturils and application thereof. The invention patent CN201711129505.8 discloses a D-galactose bonded ring-opened cucurbituril and application thereof.
The compounds prepared by the work are all symmetrical ring-opening cucurbiturils; and the asymmetric ring-opening cucurbiturils are not reported in patents.
Disclosure of Invention
The invention aims to provide an asymmetric ring-opening cucurbituril which is simple, convenient and quick and can be widely applied to industrial production, and the structural formula of the asymmetric ring-opening cucurbituril is shown as a formula I, a formula II and a formula III:
formula III;
wherein R is1Is (CH)2)nX, n =1 ~ 5, X is Cl, Br, I, R2Is R1Or (CH)2)mCH3，m=0~4。
The asymmetric ring-opening cucurbituril provided by the invention is a molecular building block of molecular building blocks of polymerized glycoluril, asymmetric hydroquinone derivatives and hydroquinone derivatives; the molecules have C-shaped structures, have different cavity sizes, are suitable for guest molecules with different sizes, can be used as a supermolecular carrier to form a multi-molecule system with matched guest substances, and are applied to industries such as pharmacy, food, flavors and fragrances, tobacco, chemical industry catalysis and the like.
The preparation method of the asymmetric ring-opening cucurbituril comprises the following steps:
(1) putting the quadripoly glycoluril, the 3,3 '- (1, 4-benzenedioxy) -di (1-propanesulfonic acid), the hydroquinone derivative or the paranaphthalenediol derivative (the molar ratio of the quadripoly glycoluril to the 3, 3' - (1, 4-benzenedioxy) -di (1-propanesulfonic acid) to the hydroquinone derivative or the paranaphthalenediol derivative is 5:6:6 ~ 5:8: 8) into a mixed solution of organic strong acid and an organic solvent, and reacting for 3 ~ 5h at the temperature of 60 ~ 80 ℃;
wherein the organic strong acid includes but is not limited to methane sulfonic acid, trifluoroacetic acid, trifluoromethane sulfonic acid;
organic solvents include, but are not limited to, acetone, tetrahydrofuran, acetic anhydride, ethanol, methanol, N-dimethylformamide, dimethylsulfoxide;
the volume ratio of the organic strong acid to the organic solvent is 1:1 ~ 3: 1;
The compound is synthesized according to the method described in Ma D, et al, Nature Chemistry, 2012, 4(6): 503: adding 1, 4-dioxane solution containing propane sultone into NaOH solution containing hydroquinone, stirring and reacting at room temperature, and filtering reaction liquid to obtain a precipitate which is a crude product; washing the crude product with acetone, vacuum filtering and drying to obtain the product;
(2) after the reaction is finished, cooling the reaction liquid to room temperature, pouring the reaction liquid into an organic solvent to separate out a precipitate, carrying out suction filtration, dissolving a solid with water, then carrying out sedimentation crystallization with the organic solvent, and drying crystals to obtain the asymmetric ring-opening cucurbituril;
the organic solvent used for precipitation comprises acetone, tetrahydrofuran, ethanol, methanol, N-dimethylformamide and dimethyl sulfoxide;
the organic solvent for crystallization is tetrahydrofuran, ethanol, methanol, acetone, N-dimethylformamide and dimethyl sulfoxide;
the reaction process of the invention is as follows:
r in hydroquinone derivative (1) or hydroquinone derivative (2, 3)1Is (CH)2)nX (n =1 ~ 5, X is Cl, Br, I), R2Is R1Or (CH)2)mCH3（m=0~4）；
The invention has the following advantages and effects:
the asymmetric ring-opening cucurbiturils provided by the invention have the advantages of few reaction synthesis steps, simpler, more convenient, safer and more efficient operation, easiness in operation and control, high purity of synthesized products, excellent quality and suitability for industrial production and application. The molecules can be used as a supermolecule carrier to form a multi-molecule system with a matched object substance, and are applied to the industries of pharmacy, food, flavors and fragrances, tobacco, chemical catalysis and the like.
Drawings
FIG. 1 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 1: (1H NMR) pattern;
FIG. 2 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 1: (13C NMR) pattern;
FIG. 3 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 2: (1H NMR) pattern;
FIG. 4 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 2: (13C NMR) pattern;
FIG. 5 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 3: (1H NMR) pattern;
FIG. 6 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 3: (13C NMR) pattern;
FIG. 7 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 4: (1H NMR) pattern;
FIG. 8 is the NMR spectrum of the asymmetric ring-opened cucurbituril of example 4: (13C NMR) graph.
Detailed Description
The present invention is further illustrated by the following examples, but the scope of the invention is not limited to the above-described examples.