CN109456332B - Stable aza [3.3.3] propellane carbene and preparation method thereof - Google Patents

Abstract

The invention relates to a stable aza [3.3.3] propellane carbene and a preparation method thereof, belonging to the field of organic chemistry. The carbene is 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellane carbene and is very stable. The carbene is prepared by preparing 2,4,6,8, 10-penta-substituted-3, 7,9, 11-penta aza [3.3.3] propeller alkane from 10-substituted-3, 7,9, 11-tetraoxo-2, 4, 8, 10-penta aza [3.3.3] propeller alkane and alkyl halide, reducing carbonyl, and finally adding palladium catalyst. Oxygen removal, dehumidification and inert gas protection are not needed in preparation and storage; the reaction precursor does not need to be made into salt. The preparation method is simple, the reaction condition is mild, the post-treatment is convenient, the yield is high, and the industrial production, storage and use are convenient.

Description

Stable aza [3.3.3] propellane carbene and preparation method thereof

Technical Field

The invention relates to a stable aza [3.3.3] propellane carbene and a preparation method thereof, in particular to a carbene which is a 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-penta aza [3.3.3] propellane carbene, belonging to the field of organic chemistry.

Background

Carbenes (carbenes), also known as carbenes and carbenes, are generally formed by elimination of a neutral molecule from a molecule containing a readily leaving group, and are abbreviated as H₂And substituted derivatives thereof. Carbene is a charge-neutral divalent carbon atom and is a highly reactive intermediate containing two unbound electrons. The lifetime of the carbene is much less than 1 second, and it can only be trapped at low temperature (below 77K), isolated and observed in the lattice.

For a long time, carbenes have been considered as reactive intermediates which cannot be stabilized at room temperature. Since heteroatoms such as nitrogen, phosphorus, silicon, boron and the like are introduced in the ortho position of the carbene carbon, the function of stabilizing the carbene carbon can be achieved, and therefore before and after the nineties of the last century, non-cyclic phosphorylsilyl carbene and 1, 3-diamantaldimidazole-2-carbene (J.Am.chem.Soc.,1988,110, 6463-; their remarkable work demonstrated that free carbenes are not always unstable intermediates, thus driving the explosive development of carbene chemistry. Today, carbene has become a very active research field in the field of synthetic chemistry, and the carbene and its metal complex are high-efficiency ligands (Angew Chem Int Ed.2012,51,6172-5; Angew Chem Int.Ed.Engl.1995,34, 2371-; efficient catalysts for organic reactions (Acc. chem. Res.2004,37, 534-541; Angew. chem. int. Ed.,2007,46, 2988-3000; chem. Rev.2007,107, 5606-5655; chem. Soc. Rev. 2012,41, 3511-3522; chem. Rev.2015,115, 4607-4692; chem. Rev.2015,115, 9307-9387; N-Heterocyclic Carbenes in organic catalysts, Wiley-VCH: Weinheim, Germany, 2019); and can be widely applied in the fields of medicines (J.Med.chem.2012,55, 5518-5525; Angew.chem.Int.Ed.2013,52, 11976-11984; chem.Rev.2009,109, 3859-3865; chem.Soc.Rev.2010,39, 1903-1912; Soc.Rev.2008,37,1998-2006) and functional materials (chem.Soc.Rev.2010,39, 1903-1912; Beilstein J.org.chem.2015,11,2584-2590) and the like.

The successful preparation, convenient isolation and convenient storage of carbenes are at the heart of carbene chemistry. To date, the major preparation of azacarbenes is as follows:

1. deprotonation of the imidazolium salt in an anhydrous solvent with a strong base (Angew. chem. Int. Ed.1968,7, 141-142; J.Am. chem. Soc,1997,119, 12742-12749; chem. Eur. J.1996,2, 772-776; Angew. chem. Int. Ed. Engl.1996,35, 1121-1126);

2. the imidazole-2-sulfur is generated by desulfurization reduction of metal potassium and sodium in dry tetrahydrofuran (Synthesis 1993, 561-;

3. carrying out pyrolysis on a precursor containing a leaving group at the 2-position under vacuum condition, and losing small molecules such as methanol, chloroform and the like (J.Am.chem.Soc.1995,117,11027-11028) to obtain the product;

the chemical reaction formulas of the above three main preparation methods are shown as follows:

of the three methods, route 1 is the predominant method of preparation. However, in this route, precursor salts and strong bases are essential; many times, the solubility of the precursor salt can be troublesome; the raw material thioketone in the route 2 is not easy to obtain, the preparation needs to be carried out under the vacuum condition, and metal potassium and the like are needed, so that the danger is high; the raw material of the route 3 is inconvenient to prepare, needs to be pyrolyzed under the ultra-vacuum condition, and has very limited application range. As highly sensitive active intermediates, the preparation methods all need special conditions, such as glove box, dehydration, dehumidification and inert gas protection, which is troublesome. Therefore, it is necessary to develop a new and convenient method for synthesizing carbene.

The stability of different structural carbenes is greatly different, for example, the carbene I synthesized by A.J. Arduengo III and the like needs to be stably existed for a certain time under the conditions of no oxygen and no humidity (J.Am.chem.Soc.1991,113, 361-363); the storage time of carbene II exposed to air is quite limited, solid samples need to be sealed and can only be stored for two days, and benzene solutions can only be used overnight (j.am. chem. soc.1997,119, 12742-12749); carbene III is relatively stable in an oxygen-free, dehumidified state (j.am. chem. soc.1995,117, 11027-11028); carbene IV is air sensitive, can only be stored in solid or solution for several days (Science,2009,326, 556-; carbene V is stable for several days at-38 ℃ and only for several hours at room temperature (angelw. chem. int. ed.2010,49, 4759-; carbene VI is relatively stable, solid without decomposition at room temperature for three days (angelw. chem. int. ed.2010,49, 4759-; the carbene VII can be stably stored for several days at-50 ℃ (Science,2001,292, 1901-; carbene VIII is very sensitive to air (as carbene VII)); a solid or solution of carbene X may be stored at room temperature for at least two weeks (Angew. chem. int. Ed.2005,117, 5851-5855). The structure of the carbenes I-X is as follows:

it follows that almost all known stable carbenes are "bottled" carbenes, i.e. require low temperature, dry solvent and inert gas shielding to be stored for a limited period of time.

Disclosure of Invention

In view of the above, it is an object of the present invention to provide a stable aza [3.3.3] propellane carbene; the second object of the present invention is to provide a process for the preparation of a stable aza [3.3.3] alane carbene.

In order to achieve the purpose of the invention, the following technical scheme is provided.

A stable aza [3.3.3] squalane carbene, which carbene is a 2,4,6,8, 10-pentasubstituted-2, 4,6,8, 10-pentaaza [3.3.3] squalane carbene, having the chemical structure as shown in the following formula (I):

wherein:

R₁and R₂Each independently is alkyl or aryl, R at different substituted positions₂Are the same group;

the alkyl is methyl, ethyl, propyl, cyclopropyl, isopropyl, n-butyl, isobutyl, tert-butyl, adamantyl, vinyl or allyl;

the aryl is a substituent of benzyl, naphthyl, pyridyl or benzyl;

the substitution position of the substituent of the benzyl is more than one of 2-position, 4-position and 6-position;

the substituent groups at the substitution positions are respectively and independently methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, methyl, ethyl, isopropyl, n-butyl, tert-butyl, amino or methylsulfonyl.

Preferably R₁Is benzyl, R₂Is a benzyl or a substituent of the benzyl, the substituent position of the substituent of the benzyl is 4-position, and the substituent is fluorine or methyl.

A preparation method of the stable aza [3.3.3] propellane carbene comprises the following steps:

preparation of 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellanes

The 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] spirostane is prepared by a modified Kim preparation method (Tetrahedron,2014,70, 1617-:

(1) dissolving 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane serving as a starting raw material in a first solvent, adding alkyl halide, adding alkali serving as a catalyst, and stirring for reaction; detecting the reaction progress by using a thin-layer chromatography, finishing the disappearance reaction of raw material points in the thin-layer chromatography, removing alkali after the reaction is finished, adding water, and extracting by using an organic solvent until a water phase does not contain substances developing under an ultraviolet lamp; combining the organic phases, drying the organic phases by using a drying agent, and removing the solvent to obtain a crude product; separating and purifying the crude product to obtain 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkyl;

wherein 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] spirostane is prepared according to the literature references Tetrahedron,2014,70, 1617-;

the first solvent is one or a mixture of two of N, N Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dichloromethane, trichloromethane, acetone, acetonitrile, methanol, ethanol, isopropanol, dioxane, benzene, toluene and xylene; preferably, the volume ratio of the two mixtures is 1: 1-10;

the base used as the catalyst is KOH, NaOH or Na₂CO₃、K₂CO₃、CH₃ONa、CH₃CH₂ONa, t-BuOK, t-BuONa, NaH, CaH or N (Et)₃；

HalogenatedThe alkyl is fluoro, chloro or bromo, and the substituent of the alkyl is R₂。

Preferably, the molar ratio of the 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the base is 1: 4-10.

Preferably, the molar ratio of the 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the alkyl halide is 1: 4-10.

The temperature of the catalyst during adding is 0-room temperature; preferably from 0 ℃ to 5 ℃.

Preferably, the reaction is carried out under nitrogen or argon.

The reaction temperature is preferably 0 ℃ to 80 ℃.

(2) Dissolving the 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane prepared in the step (1) in a second solvent, adding a reducing agent to reduce carbonyl, stirring for reaction, detecting the reaction progress by using thin-layer chromatography, completing the raw material point disappearance reaction in the thin-layer chromatography, and then cooling the reactant to 0-room temperature; slowly dripping ethyl acetate into the reactant to quench residual hydride, adding NaOH solution until a slurry phase disappears, stirring, extracting by using ethyl acetate, concentrating an organic phase to obtain a yellow oily substance, drying, and separating and purifying the yellow oily substance by silica gel column chromatography to obtain 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-penta aza [3.3.3] propellane;

wherein the second solvent is dichloromethane, trichloromethane or tetrahydrofuran;

the reducing agent is lithium aluminum hydride, sodium borohydride or red aluminum solution;

preferably, the molar ratio of the 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane to the reducing agent is 1: 4-1: 10;

the temperature of the reducing agent is 0-room temperature; preferably from 0 ℃ to 5 ℃.

The stirring reaction temperature is preferably 0 ℃ to 65 ℃.

The chemical structural formula of the 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane in the step (I) is shown as a formula (II); the chemical structural formula of the 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane is shown as a formula (III); the chemical structural formula of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellane is shown as the formula (IV):

wherein:

R₁and R₂Each independently is alkyl or aryl, R at different substituted positions₂Are the same group;

the alkyl is methyl, ethyl, propyl, cyclopropyl, isopropyl, n-butyl, isobutyl, tert-butyl, adamantyl, vinyl or allyl;

the aryl is a substituent of benzyl, naphthyl, pyridyl or benzyl;

the substitution position of the substituent of the benzyl is more than one of 2-position, 4-position and 6-position;

the substituent groups at the substitution positions are respectively and independently methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, methyl, ethyl, isopropyl, n-butyl, tert-butyl, amino or methylsulfonyl.

Preferably R₁Is benzyl, R₂Is a benzyl or a substituent of the benzyl, the substituent position of the substituent of the benzyl is 4-position, and the substituent is fluorine or methyl.

(II) preparation of 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] prop ane carbene

Dissolving the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane prepared in the step (I) into a reaction solvent, then adding a palladium catalyst, stirring and reacting at 0-65 ℃, detecting the reaction progress by using a thin-layer chromatography, finishing the disappearance reaction of raw material points in the thin-layer chromatography, then placing to room temperature, and extracting by using an organic solvent until a water phase does not contain substances developing under an ultraviolet lamp; combining the organic phases, drying the organic phases by using a drying agent, and removing the solvent to obtain a crude product; and (3) separating and purifying the crude product to obtain the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellane carbene which is the stable aza [3.3.3] propellane carbene.

The reaction solvent is one or two of ethyl acetate, petroleum ether, normal hexane, cyclohexane, methanol, ethanol, isopropanol, dichloromethane, trichloromethane, acetone, acetonitrile, benzene, toluene, xylene, acetic anhydride, formic acid, acetic acid, DMF and DMSO; preferably, the reaction solvent is a mixed solution of dichloromethane and isopropanol, and the volume of the dichloromethane and the isopropanol is 1: 2.

The palladium catalyst is Pd (OH)₂/C、Pd/C、Pd(CH₃COO)₂、PdCl₂、PdBr₂Or Pd (allyl) Cl₂(ii) a Preferably the palladium catalyst is Pd/C.

Preferably, the mass of the palladium catalyst is 10-100% of that of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane; more preferably, the palladium catalyst is present in an amount of 10 to 20% by mass based on the mass of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] alane.

In the step (I) and the step (II):

the developing agent of the thin-layer chromatography is as follows: two of ethyl acetate, petroleum ether, methanol, dichloromethane, chloroform, acetone, tetrahydrofuran and n-hexane; preferably, the developing solvent for thin-layer chromatography is ethyl acetate and methanol, and the volume ratio of the ethyl acetate to the methanol is 10: 1.

Preferably, the drying agent is anhydrous sodium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride or molecular sieve.

The solvent is preferably removed by distillation under reduced pressure.

Preferably, the separation and purification adopts column chromatography separation or/and solvent recrystallization.

When column chromatography separation and purification are preferred, the eluent is: two mixed liquids of ethyl acetate, petroleum ether, methanol, dichloromethane, chloroform, acetone, tetrahydrofuran and normal hexane;

preferably, in the solvent recrystallization purification, the recrystallization solvent is methanol, ethanol, isopropanol, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, dioxane, dichloromethane, chloroform, dichloroethane, benzene, toluene, xylene, dimethyl sulfoxide, N-dimethylformamide, water, hydrochloric acid, an aqueous solution of sulfuric acid, or an aqueous solution of sodium hydroxide.

Advantageous effects

1. The invention provides a stable aza [3.3.3] propellane carbene, wherein the beta-position of the carbene carbon has quaternary carbon, is three-dimensional and can form a novel propellane carbene of a protective cover at the tail part of the carbene carbon;

2. the invention provides a preparation method of stable aza [3.3.3] propellane carbene, which designs, synthesizes and represents a propeller type cage-shaped three-dimensional carbene which is prepared and stored without oxygen-free, dehumidification and inert gas protection (glove box), only needs conventional operation and is very stable, and the carbene is prepared without preparing a reaction precursor into salt.

Drawings

FIG. 1 shows nuclear magnetic carbon spectrum (100MHz, DMSO-d) of the product obtained in example 1₆)。

FIG. 2 shows nuclear magnetic hydrogen spectrum (400MHz, CDCl) of the product obtained in example 1₃)。

FIG. 3 is a high resolution mass spectrum of the product obtained in example 1.

FIG. 4 is an IR spectrum of the product obtained in example 1.

FIG. 5 shows nuclear magnetic carbon spectrum (100MHz, CDCl) of the product obtained in example 2₃)。

FIG. 6 shows nuclear magnetic hydrogen spectrum (400MHz, CDCl) of the product obtained in example 2₃)。

FIG. 7 is a high resolution mass spectrum of the product obtained in example 2.

FIG. 8 is an IR spectrum of the product obtained in example 2.

FIG. 9 shows nuclear magnetic carbon spectrum (100MHz, DMSO-d) of the product obtained in example 3₆)。

FIG. 10 shows nuclear magnetic hydrogen spectrum (400MHz, DMSO-d) of the product obtained in example 3₆)。

FIG. 11 is a high resolution mass spectrum of the product obtained in example 3.

FIG. 12 is an IR spectrum of the product obtained in example 3.

FIG. 13 shows nuclear magnetic carbon spectrum (100MHz, CDCl) of the product obtained in example 4₃)。

FIG. 14 shows nuclear magnetic hydrogen spectrum (700MHz, DMSO-d) of the product obtained in example 4₆)。

FIG. 15 is a high resolution mass spectrum of the product obtained in example 4.

FIG. 16 is an IR spectrum of the product obtained in example 4.

FIG. 17 is a diagram of a crystal thermal ellipsoid of the product obtained in example 4.

FIG. 18 is a thermogravimetric/differential thermal map of the product obtained in example 4.

FIG. 19 shows nuclear magnetic carbon spectrum (100MHz, CDCl) of the product obtained in example 5₃)。

FIG. 20 shows nuclear magnetic hydrogen spectrum (700MHz, CDCl) of the product obtained in example 5₃)。

FIG. 21 is a high resolution mass spectrum of the product obtained in example 5.

FIG. 22 is an IR spectrum of the product of example 5.

FIG. 23 shows nuclear magnetic carbon spectrum (100MHz, DMSO-d) of the product obtained in example 6₆)。

FIG. 24 shows nuclear magnetic hydrogen spectrum (700MHz, DMSO-d) of the product obtained in example 6₆)。

FIG. 25 is a high resolution mass spectrum of the product obtained in example 6.

FIG. 26 is an IR spectrum of the product of example 6.

FIG. 27 is a nuclear magnetic carbon spectrum (100MHz, CDCl) of the product obtained in example 7₃)。

FIG. 28 is a nuclear magnetic hydrogen spectrum (700MHz, CDCl) of the product obtained in example 7₃)。

FIG. 29 is a high resolution mass spectrum of the product obtained in example 7.

FIG. 30 is an IR spectrum of the product of example 7.

FIG. 31 is a diagram of a crystal thermal ellipsoid of the product obtained in example 7.

FIG. 32 is a thermogravimetric/differential thermal map of the product obtained in example 7.

FIG. 33 is a high resolution mass spectrum of the product obtained in example 8.

FIG. 34 is an IR spectrum of the product of example 8.

FIG. 35 is a high resolution mass spectrum of the product obtained in example 9.

FIG. 36 is a chemical structure of a stabilized aza [3.3.3] rotaxane carbene of the invention.

Detailed Description

In the following examples:

structural characterization correlation test of infrared, nuclear magnetic and mass spectra:

the infrared spectrum is measured by potassium bromide tabletting on a Shimadzu IR Affinity-1s infrared spectrometer;

the nuclear magnetic spectrum is CDCl₃Or DMSO-d₆Measured for solvent on a Bruker Ascend 400MHZ and Bruker Ascend 700MHZ nuclear magnetic spectrometer;

high resolution mass spectrum ESI using methanol or acetonitrile as solvent⁺The ion source was measured on a Q-TOF 6520 mass spectrometer.

Differential Thermal (DTA) and Thermogravimetric (TGA) stability test conditions: in the aluminum sample pool, the reference sample is empty, the temperature rise interval is 20-500 ℃, the temperature rise rate is 5 ℃/min, and the nitrogen flow rate is 20 ml/min.

X-ray measurement: placing the crystal on Bruker APEX DUO II type X-ray single crystal diffractometer with wavelength of

The MoK alpha ray of graphite monochromatization is used as a radiation light source, a diffraction point is collected at 296.15K, and the crystal structure is directly solved by a Shelxl program.

10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] spirostane reference (Tetrahedron,2014,70, 1617-.

Example 1

Preparation of 2,4,6,8, 10-pentabenzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane

Under an argon atmosphere, 3.01g (10mmol) of 10-benzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3]]Propylalane and 10.26g (60mmol) of benzyl bromideDissolving in 15ml of first solvent, cooling to 0 ℃ by using an ice bath, slowly adding 50mmol (1.20g) of sodium hydride solid, and continuously stirring for reacting for 1 h; after white bubbles in the reaction mixture disappear, heating the reaction system to room temperature; detecting the progress of the reaction by using thin-layer chromatography, and when the disappearance of the raw materials is detected by using the thin-layer chromatography, cooling the reaction mixture to 0 ℃ again by using an ice bath; diluting the reaction mixture with ethyl acetate, slowly adding dilute hydrochloric acid dropwise to quench unreacted hydride, and adjusting the pH of the solution to be neutral; adding water to the resulting mixture, and extracting three times with ethyl acetate; the organic phases were combined and over anhydrous MgSO₄Drying, concentrating the organic phase and recrystallising from 20ml of absolute ethanol gave the product as a white solid with a mass of 5.18g, a yield of 78% and a melting point of 151 ℃ -152 ℃.

The first solvent is a mixture of dimethyl sulfoxide (DMSO) and N, N Dimethylformamide (DMF), and the volume ratio of the dimethyl sulfoxide to the N, N dimethylformamide is 1: 4.

The developing solvent of the thin-layer chromatography is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 4: 1.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 1 to 4:

¹H NMR(400MHz,CDCl₃)δ7.84–6.43(m,25H),4.44(s,8H),4.26(s,2H)；¹³C NMR(100MHz,DMSO-d₆):166.80,156.65,137.02,134.41,128.66,128.37,128.03,127.13,126.42,74.72,44.87；IR(KBr)3032,2926,1718,1496,1446,1415,1359,1147,746,696cm^-1；HRMS(ESI⁺):calcd.for C₄₁H₃₆N₅O₄[M+H]⁺662.2762,found 662.2779.

the above data indicate that the product is 2,4,6,8, 10-pentabenzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane;

wherein, 10-benzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3]The chemical structural formula of the propellane is shown as a formula (II-a); 2,4,6,8, 10-Pentabenzyl-3, 7,9, 11-Tetraoxo-2, 4,6,8, 10-Pentaaza [3.3.3]]The chemical structural formula of the propellane is shown as a formula (III-a), wherein R₁And R₂Are all benzyl groups:

example 2

Preparation of 2,4,6, 8-tetrakis (4-methylbenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop-ane

The same procedure as in example 1 was repeated except for using 4-methylbenzyl bromide instead of the benzyl bromide in example 1 to give the product as a white solid with a mass of 2.66g, a yield of 37% and a melting point of 172.4 ℃ to 172.9 ℃.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 5 to 8:

¹H NMR(400MHz,CDCl₃)δ7.37–6.69(m,21H),4.41(s,8H),4.25(d,J＝14.7Hz,2H),2.22(s,12H)；¹³C NMR(100MHz,CDCl₃)δ166.13(s),156.07(s),136.04(s),132.69(d),128.26(s),127.65(d),127.17(s),125.97(s),74.32(s),44.38(s),41.52(s),20.09(d)；IR(KBr)3086,2962,2924,1716,1456,1386,1336,1244,1168,1139,1109,991,948,916,866,729,524cm^-1；HRMS(ESI⁺):calcd.for C₄₅H₄₃N₅O₄[M+H]⁺718.3388,found 718.3378.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-methylbenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3]The chemical structural formula of the propellane is shown as a formula (III-b), wherein R is₁Is benzyl, R₂Is 4-methylbenzyl:

example 3

Preparation of 2,4,6, 8-tetrakis (4-fluorobenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop-ane

The same procedure as in example 1 was repeated except for using 4-fluorobenzyl bromide instead of bromobenzyl in example 1 to give a white solid product having a mass of 3.52g, a yield of 48% and a melting point of 108.4 ℃ to 110.1 ℃.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 9 to 12:

¹H NMR(400MHz,DMSO)δ7.55–6.49(m,21H),5.06–4.11(m,10H).¹³C NMR(100MHz,DMSO)δ167.19(s),162.99(s),160.57(s),157.26(s),134.79(s),133.58(d),129.53–128.96(m),128.33(s),115.58(d),115.41–115.23(m),75.16(s),44.82(s)；IR(KBr)3068,2924,1720,1606,1510,1456,1411,1342,1232,1147,1099,947,844,815,736,698,665,526,491cm^-1；HRMS(ESI⁺):calcd.for C₄₁H₃₁F₄N₅O₄[M+H]⁺734.2385,found 734.2374.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-fluorobenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3]The chemical structural formula of the propellane is shown as a formula (III-c), wherein R₁Is benzyl, R₂Is 4-fluorobenzyl bromide:

example 4

Preparation of 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3] propellanes

The 2,4,6,8, 10-penta-benzyl-3, 7,9, 11-tetra-oxo-2, 4,6,8, 10-pentaaza [3.3.3] as obtained in example 1 was used]3.30g (5mmol) of spiroxane were dissolved in 50ml of anhydrous Tetrahydrofuran (THF), the solution was cooled to 0 ℃ with an ice bath, and 40mmol of lithium aluminum hydride (LiAlH) were added thereto under ice bath₄) Removing the ice bath when bubbles in the solution disappear; stirring for reaction, detecting the reaction progress by using thin-layer chromatography, finishing the disappearance reaction of the raw material points in the thin-layer chromatography, and then cooling the reaction mixture to 0 ℃ again; slowly dripping 6ml of ethyl acetate into the reaction mixture to quench residual hydride, adding 12ml of NaOH solution with the mass fraction of 10% until a slurry phase disappears, continuously stirring and stirring for 30min, extracting for three times by using ethyl acetate, concentrating an organic phase to obtain a yellow oily substance, and drying; passing through silica gel column chromatography, eluting with petroleum ether and ethyl acetate,the volume ratio of petroleum ether to ethyl acetate was 4:1, and the yellow oil was isolated and purified to give a white solid product with a mass of 2.57g, a yield of 85.10%, and a melting point of 142 ℃ -144 ℃.

The developing solvent of the thin-layer chromatography is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 4: 1.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 13 to 16:

¹H NMR(400MHz,CDCl₃)δ7.93–6.69(m,25H),3.92(d,J＝14.2Hz,6H),3.80–3.62(m,6H),3.30(d,J＝2.0Hz,2H),2.74(s,4H)；¹³C NMR(100MHz,DMSO)δ140.00(s),138.66(s),128.71(s),128.18(s),128.07(s),127.91(s),126.93(s),126.55(s),96.10(s),74.23(s),59.83(s),56.41(s),51.74(s)；IR(KBr)3061,3024,2900,2800,1602,1493,1453,773,698cm^-1；HRMS(ESI⁺):calcd.for C₄₁H₄₃N₅[M+H]⁺606.3591,found 606.3589.

the above data indicate that the product is 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]The chemical structural formula of the propellane is shown as a formula (IV-a), wherein R₁And R₂Are all benzyl groups:

2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]Propalane dissolved in CH₂Cl₂And CH₃In a mixed solvent of OH, CH₂Cl₂And CH₃OH volume ratio of 1:1, sealing the bottle mouth, slowly volatilizing at room temperature to obtain single crystal, and determining its structure by X-ray, as shown in FIG. 17. The X-ray measurement results show that the ring nitrogen atoms are all in a cone structure, N₁、N₃、N₅And N₇The sum of the bond angles of the atoms is 337 °, 342 °, 336 ° and 339 °, respectively. The three five-membered heterocycles are all arranged like a propeller in a signal-sealed configuration in a counterclockwise direction. The benzyl benzene rings on the two imidazolines are on the same side and have dihedral angles of 34.867 DEG and 62 DEG, respectively577. The sum of the internal angles of the two imidazolines is almost equal, and the degrees of their N-C-N angles are both 103.6 °. All C-N bonds of the heterocyclic ring in the molecule being

Belonging to the typical aza [3.3.3]Bond length range of the propeller alkane. The ring C-C bond length is in the range of 1.525 to

Middle, longest bond length

Is an axial C-C single bond, which is also in agreement with literature values (Tetrahedron 2014,70,1617-]The chemical structural formula of the propellane is shown as a formula (IV-a), wherein R₁And R₂Are both benzyl groups.

The thermogravimetric and differential thermal results for 2,4,6,8, 10-pentaaza [3.3.3] propellane-2, 4,6,8, 10-penta-aza [3.3.3] are shown in FIG. 18, showing: the substance showed a melting endothermic peak at 140 ℃ and a decomposition peak at 350 ℃ and thus it was found that 2,4,6,8, 10-penta-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] alane was stably present at 350 ℃ or lower.

Example 5

Preparation of 2,4,6, 8-tetrakis (4-methylbenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop-alane

Using the 2,4,6, 8-tetrakis (4-methylbenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] propeller obtained in example 2 instead of the 2,4,6,8, 10-pentabenzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller obtained in example 1, the procedure was otherwise as in example 4 to give a white solid product having a mass of 2.60g, a yield of 78% and a melting point of 122.0 ℃ to 123.2 ℃.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 19 to 22:

¹H NMR(400MHz,CDCl₃)δ7.52–6.77(m,21H),3.81(dd,J＝19.9,8.6Hz,6H),3.60(d,J＝13.2Hz,6H),3.19(d,J＝3.5Hz,2H),2.63(s,4H),2.17(d,J＝23.8Hz,12H)；¹³C NMR(100MHz,CDCl₃)δ135.87(s),135.12(s),127.85(s),127.26(s),126.93(s),126.00(s),95.09(s),73.46(s),58.94(s),55.52(s),50.51(s),20.04(s)；IR(KBr)3022,2916,2893,2819,2779,2696,1514,1452,1377,1359,1290,1261,1174,1101,1020,877,798,742,698,476cm^-1；HRMS(ESI⁺)calcd.for C₄₅H₅₁N₅[M+H]⁺662.4217,found 662.4220.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-methylbenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3 [ ] -penta]The chemical structural formula of the propellane is shown as a formula (IV-b), wherein R₁Is benzyl, R₂Is 4-methylbenzyl:

example 6

Preparation of 2,4,6, 8-tetrakis (4-fluorobenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop-alane

Using the 2,4,6, 8-tetrakis (4-fluorobenzyl) -3,7,9, 11-tetraoxo-10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] propeller obtained in example 3 in place of the 2,4,6,8, 10-pentabenzyl-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller obtained in example 1, the procedure was otherwise as in example 4 to give a white solid product having a mass of 2.06g, a yield of 61% and a melting point of 111.2 ℃ to 113.0 ℃.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 23 to 26:

¹H NMR(400MHz,CDCl₃)δ7.46–6.66(m,21H),3.75(d,J＝13.8Hz,6H),3.68–3.49(m,6H),3.15(d,J＝4.5Hz,2H),2.61(s,4H)；¹³C NMR(100MHz,CDCl₃)δ161.99(s),159.56(s),137.47(s),134.40(d),128.33(d),127.86(s),127.34(s),127.34–126.66(m),126.18(s),95.04(s),58.90(s),55.26(s),50.04(s).IR(KBr)3035,2912,2806,1602,1508,1452,1375,1220,1151,1091,1014,848,821,700cm^-1；HRMS(ESI⁺):calcd.for C₄₁H₃₉F₄N₅[M+H]⁺678.3214,found678.3225.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-fluorobenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The chemical structural formula of the propellane is shown as a formula (IV-c), wherein R₁Is benzyl, R₂Is 4-fluorobenzyl:

example 7

Preparation of 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3] propellane carbene

1.21g (2mmol) of 2,4,6,8, 10-penta-benzyl-2, 4,6,8, 10-penta-aza [3.3.3] propeller alkane prepared in example 4 was dissolved in 12ml of a reaction solvent, 0.10g of Pd/C catalyst was added thereto, and the reaction was stirred at room temperature; detecting the reaction progress by using a thin-layer chromatography, finishing the disappearance reaction of raw material points in the thin-layer chromatography, filtering out a catalyst, extracting for three times by using ethyl acetate until a water phase does not contain substances developing under an ultraviolet lamp, combining organic phases, drying the organic phases by using anhydrous magnesium sulfate, and then distilling under reduced pressure to remove the solvent to obtain a brownish black oily liquid crude product; performing column chromatography, wherein the eluent is ethyl acetate and methanol, and the volume ratio of the ethyl acetate to the methanol is 10: 1; the brownish black liquid was purified off and recrystallized from ethyl acetate to give the product as a white powder with a mass of 0.69g, a yield of 58% and a melting point of 192.0-193.0 ℃.

The reaction solvent is a mixed solution of dichloromethane and isopropanol, and the volume ratio of the dichloromethane to the isopropanol is 1: 2; the developing solvent of the thin layer chromatography is ethyl acetate and methanol, and the volume ratio of the ethyl acetate to the methanol is 10: 1.

The product was subjected to structural characterization correlation tests, and the test results are shown in fig. 27 to 30:

¹H NMR(700MHz,CDCl₃)δ10.58(s,1H),7.67–6.83(m,25H),5.29–4.98(m,2H),4.66–4.35(m,2H),3.98(t,J＝12.3Hz,2H),3.89(d,J＝14.0Hz,1H),3.75(dd,J＝47.8,9.6Hz,1H),3.32(s,1H),2.98(d,J＝11.1Hz,1H),2.04–1.70(m,4H),1.45–1.27(m,1H)；¹³C NMR(100MHz,CDCl₃)δ156.65(s),137.60(s),135.88(s),132.82(s),127.87(dd,J＝35.0,12.9Hz),127.54–127.34(m),127.20(s),126.75(d,J＝6.1Hz),98.46(s),75.05(s),57.79(s),57.33(s),52.86(s),48.64(s),45.00(s),7.78(s)；IR(KBr)3024,2926,2819,1618,1494,1454,1369,1274,1220,1105,1028,950,738,700,60cm^-1；HRMS(ESI⁺):calcd.for C₄₁H₄₁N₅[M+H]⁺604.3435,found 604.3430.

the above test results indicate that the product is 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The chemical structural formula of the spirostane carbene is shown as a formula (I-a), wherein R₁And R₂Are all benzyl groups:

2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]Dissolving Propylalkane carbene in CH₂Cl₂And THF in a mixed solvent of CH₂Cl₂And THF in a volume ratio of 1:1, sealing the bottle mouth, slowly volatilizing at room temperature to obtain crystals suitable for X-ray single crystal measurement, and determining the structure by X-ray single crystal measurement. As shown in fig. 31, the measurement results showed that: 2,4,6,8, 10-Pentabenzyl-2, 4,6,8, 10-Pentaaza [3.3.3]]The spiroalkane carbene is a triclinic system, and a single crystal cell contains two mutually independent propeller carbene molecules; the structure of the imidazoline carbene has significant difference with the reported structure of imidazoline carbene (J.Am.chem.Soc.1991,113, 361-363; J.Am.chem.Soc.1995,117, 11027-11208): first, 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The imidazoline ring of the spiroalkane carbene is a plane, and the sum of the internal angles of the planes is 539.9 degrees; secondly, the bond angle N-C-N ═ 113.8 ℃ at the carbon is significantly greater than that reported in the literature for saturated imidazoline-2-carbenes (104.7) (Nature 2001,412, 626-.

2,4,6,8, 10-Pentabenzyl-2, 4,6,8, 10-Pentaaza [3.3.3]]The bond angle of the carbon of the propeller alkane card is so large that it is due to aza [ alpha ], [ beta ], [ alpha ], [ beta ] is3.3.3]Due to an overlong-axis C-C single bond caused by a cage structure of the propellane, the carbene carbon is endowed with better electron donating property, stereoscopic effect and stability; the two nitrogen atoms in the carbon ring are in a planar state, and the sum of the bond angles of the atoms is 359.1 degrees and 360 degrees respectively; the C-N bond length in the ring is respectively

And

significantly shorter than the corresponding bond length of the saturated imidazoline-2-carbene in the literature (J.Am.chem.Soc.1995,117,11027-11208), which indicates 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3 [ ]]2p occupied orbitals of nitrogen atoms in the spirostane carbene molecules and unoccupied 2p orbitals of connected carbene carbon are tightly crosslinked; and N is₁-C₈And N₃-C₄Is still a distinct single bond characteristic. Furthermore, 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]Bond length of C-C single bond of Rapana carbene Ring

Is [3.3.3]Typical bond lengths for a propeller-shaft carbon single bond and 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The corresponding bond lengths of the spiroalkanes are comparable

(Tetrahedron 2003,59, 1961-; all other bond lengths are consistent with the starting material. 2,4,6,8, 10-Pentabenzyl-2, 4,6,8, 10-Pentaaza [3.3.3]]Benzene rings of two benzyl groups on a carbene ring of the propellane carbene are obviously twisted out of a carbene ring plane, and dihedral angles between the two benzyl groups and the carbene ring plane are 58.877 degrees and 66.221 degrees respectively; they are similarly clamped forward towards the crab thigh; the benzyl benzene rings on the other imidazoline ring are inclined forwards, and dihedral angles with the plane of the carbene ring are 63.333 degrees and 50.195 degrees respectively; the dihedral angle of the benzene ring of the last benzyl group with the plane of the carbene ring is 51.04 °。

Most surprisingly, the single 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3] s]The spirostane carbene molecule contains two molecules of water of crystallization, which is the first example found in carbene crystals. In the unit cell, two molecules of water of crystallization are located to the front left of the two benzyl phenyl rings of the non-carbene ring in the carbene molecule. Single crystal measurements show that: the carbene carbon is clamped by two benzyl benzene rings substituted by the ring nitrogen, the tail part of the carbene carbon is protected by two five-membered heterocyclic rings carrying benzyl substituents, and the head part of the carbene carbon is protected by a cover formed by three benzene rings of another molecule in a unit cell. They together form a lipophilic hydrophobic cavity which encloses 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The propeller alkane carbene carbon is not affected by water, which may be the distance from the carbene carbon to the nearest carbon atom of each benzene ring (from

To

) And (5) verification is obtained.

The 2,4,6,8, 10-penta benzyl-2, 4,6,8, 10-pentaaza [3.3.3] propelare carbene or its dichloromethane solution is simply stored in a laboratory vessel without any protection, and after several months, the compound is not changed or decomposed and can stably exist.

Thermal behavior studies were performed by DTA and TGA tests on 2,4,6,8, 10-penta-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] piperylene carbine. As shown in fig. 32, DTA and TGA results indicate: 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3] piperylene has an endothermic peak near 50 ℃, which is an endothermic peak of losing crystal water, a melting endothermic peak near 195 ℃ of melting point, and a decomposition peak above 200 ℃, and the results are also verified by TGA.

In conclusion, 2,4,6,8, 10-pentabenzyl-2, 4,6,8, 10-pentaaza [3.3.3] spirostane carbene is stable below 190 ℃.

Example 8

Preparation of 2,4,6, 8-tetra (4-methylbenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop-ane carbene

Using 2,4,6, 8-tetrakis (4-methylbenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] propellane obtained in example 5 in place of 2,4,6,8, 10-pentaaza [3.3.3] propellane obtained in example 4, the procedure was otherwise as in example 7 to give a white solid product.

The product was subjected to the relevant test for structural characterization, and the test results are shown in fig. 33 and 34:

3383，3024，2974，2937，2819，2738，2677，2492,1627,1514,1454,1435,1371,1276,1205,1101,1035,844,806,754,698,590,474；HRMS(ESI⁺)calcd.for C₄₅H₄₉N₅[M+H]⁺660.4061,found 660.4083.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-methylbenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3 [ ] -penta]The chemical structural formula of the spirostane carbene is shown as a formula (I-b), wherein R₁Is benzyl, R₂Is 4-methylbenzyl:

example 9

Preparation of 2,4,6, 8-tetra (4-fluorobenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] prop ane carbene

Using 2,4,6, 8-tetrakis (4-fluorobenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3] propellane obtained in example 6 in place of 2,4,6,8, 10-pentaaza [3.3.3] propellane obtained in example 4, the procedure was otherwise as in example 7 to obtain a white solid product.

The product was subjected to the relevant test for structural characterization, and the test results are shown in fig. 35:

HRMS(ESI⁺)calcd.for C₄₁H₃₇F₄N₅[M+H]⁺676.3058,found 676.3053.

the above data indicate that the product is 2,4,6, 8-tetrakis (4-fluorobenzyl) -10-benzyl-2, 4,6,8, 10-pentaaza [3.3.3]]The chemical structural formula of the spirostane carbene is shown as a formula (I-c), wherein R₁Is benzyl, R₂Is 4-fluorobenzyl:

Claims (9)

1. a stable aza [3.3.3] rotaxane carbene characterized by: the carbene is 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellane carbene, and the chemical structural formula is shown as the following formula (I):

wherein:

R₁and R₂Are independently aryl or R at different substituted positions₂Are the same group;

the aryl is benzyl or a substituent of the benzyl;

the substitution position of the substituent of the benzyl is more than one of 2-position, 4-position and 6-position;

and the substituent groups at the substitution positions are respectively and independently methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, methyl, ethyl, isopropyl, n-butyl or tert-butyl.

2. A stabilized aza [3.3.3] as defined in claim 1]The propellane carbene is characterized in that: r₁Is benzyl, R₂Is a benzyl or a substituent of the benzyl, the substituent position of the substituent of the benzyl is 4-position, and the substituent is fluorine or methyl.

3. A process for the preparation of a stable aza [3.3.3] propellane carbene according to claim 1 or 2, characterized in that: the method comprises the following steps:

preparation of 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellanes

(1) Dissolving 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane in a first solvent, adding alkyl halide, adding alkali as a catalyst, and then stirring for reaction; detecting the reaction progress by using a thin-layer chromatography, finishing the disappearance reaction of raw material points in the thin-layer chromatography, then removing alkali, adding water, and extracting by using an organic solvent until a water phase does not contain substances developing under an ultraviolet lamp; combining the organic phases, drying the organic phases by using a drying agent, and removing the solvent to obtain a crude product; separating and purifying the crude product to obtain 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkyl;

the alkyl halide is fluoro, chloro or bromo, and the alkyl is R₂；

(2) Dissolving 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane in a second solvent, adding a reducing agent to reduce carbonyl, stirring for reaction, detecting the reaction progress by using thin-layer chromatography, completing the raw material point disappearance reaction in the thin-layer chromatography, and then cooling the reactant to 0-room temperature; slowly dripping ethyl acetate into the reactant, adding NaOH solution until a slurry phase disappears, stirring, extracting by using ethyl acetate, concentrating an organic phase, drying, and separating and purifying by silica gel column chromatography to prepare 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane;

the chemical structural formula of the 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane in the step (I) is shown as a formula (II); the chemical structural formula of the 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane is shown as a formula (III); the chemical structural formula of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propellane is shown as the formula (IV):

(II) preparation of 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] prop ane carbene

Dissolving the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane prepared in the step (I) into a reaction solvent, then adding a palladium catalyst, stirring and reacting at 0-65 ℃, detecting the reaction progress by using a thin-layer chromatography, finishing the disappearance reaction of raw material points in the thin-layer chromatography, then placing to room temperature, and extracting by using an organic solvent until a water phase does not contain substances developing under an ultraviolet lamp; combining the organic phases, drying the organic phases by using a drying agent, and removing the solvent to obtain a crude product; separating and purifying the crude product to obtain the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] rotaxane carbene which is the stable aza [3.3.3] rotaxane carbene in the claim 1 or 2.

4. The process of claim 3, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene:

in the step (I) (1): the first solvent is one or two of N, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, trichloromethane, acetone, acetonitrile, methanol, ethanol, isopropanol, dioxane, benzene, toluene and xylene;

the base used as the catalyst is KOH, NaOH or Na₂CO₃、K₂CO₃、CH₃ONa、CH₃CH₂ONa, t-BuOK, t-BuONa, NaH, CaH or N (Et)₃；

The temperature of the alkali catalyst is 0-room temperature;

in the step (I) (2): the second solvent is dichloromethane, trichloromethane or tetrahydrofuran;

the reducing agent is lithium aluminum hydride, sodium borohydride or red aluminum solution;

the temperature of the reducing agent is 0-room temperature;

in the step (II): the reaction solvent is one or two of ethyl acetate, petroleum ether, normal hexane, cyclohexane, methanol, ethanol, isopropanol, dichloromethane, trichloromethane, acetone, acetonitrile, benzene, toluene, xylene, acetic anhydride, formic acid, acetic acid, N-dimethylformamide and dimethyl sulfoxide;

the palladium catalyst is Pd (OH)₂/C、Pd/C、Pd(CH₃COO)₂、PdCl₂、PdBr₂Or Pd (allyl) Cl₂；

In the step (I) and the step (II):

the developing agent of the thin-layer chromatography is as follows: two of ethyl acetate, petroleum ether, methanol, dichloromethane, chloroform, acetone, tetrahydrofuran and n-hexane.

5. The process of claim 4, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene:

in the step (I) (1):

the temperature of the alkali catalyst is 0-5 ℃;

the reaction temperature is 0-80 ℃;

in the step (I) (2):

the temperature of the reducing agent is 0-5 ℃;

the stirring reaction temperature is 0-65 ℃;

in the step (I) (1) and the step (II):

the separation and purification adopts column chromatography separation or/and solvent recrystallization.

6. The process of claim 5, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene:

in the step (I) (1):

the molar ratio of the 10-substituted 3,7,9, 11-pentasubstituted-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the base is 1: 4-10;

the molar ratio of the 10-substituted 3,7,9, 11-pentasubstituted-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the alkyl halide is 1: 4-10;

in the step (I) (2):

the molar ratio of the 2,4,6,8, 10-penta-substituted 3,7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane to the reducing agent is 1: 4-1: 10; in the step (II):

the mass of the palladium catalyst is 10-100% of that of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane;

in the step (I) (1) and the step (II):

when column chromatography separation and purification are carried out, the eluent is: two mixed liquids of ethyl acetate, petroleum ether, methanol, dichloromethane, chloroform, acetone, tetrahydrofuran and normal hexane;

when the solvent is recrystallized and purified, the recrystallization solvent is methanol, ethanol, isopropanol, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, dioxane, dichloromethane, chloroform, dichloroethane, benzene, toluene, xylene, dimethyl sulfoxide, N-dimethylformamide, water, hydrochloric acid, aqueous sulfuric acid solution or aqueous sodium hydroxide solution.

7. The process of claim 6, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene:

in the step (I) (1):

the first solvent is a mixture of two substances, and the volume ratio of the two substances is 1: 1-10;

in the step (II):

the reaction solvent is a mixed solution of dichloromethane and isopropanol, and the volume of the dichloromethane and the isopropanol is 1: 2;

the mass of the palladium catalyst is 10-20% of that of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane;

in the step (I) and the step (II):

the developing solvent of the thin layer chromatography is ethyl acetate and methanol, and the volume ratio of the ethyl acetate to the methanol is 10: 1.

8. The process of claim 7, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene:

in the step (I) (1):

the reaction is carried out under the protection of nitrogen or argon;

in the step (II):

the palladium catalyst is Pd/C;

in the step (I) and the step (II):

the drying agent is anhydrous sodium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride or molecular sieve;

the solvent was removed by distillation under reduced pressure.

9. The process of claim 4, wherein the reaction is carried out in the presence of a stable aza [3.3.3] propellane carbene: in the step (I) (1):

the temperature of the alkali catalyst is 0-5 ℃;

the reaction temperature is 0-80 ℃;

the molar ratio of the 10-substituted 3,7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the base is 1: 4-10; the molar ratio of the 10-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza- [3.3.3] propellane to the alkyl halide is 1: 4-10;

the first solvent is a mixture of two substances, and the volume ratio of the two substances is 1: 1-10;

the reaction is carried out under the protection of nitrogen or argon;

in the step (I) (2):

the temperature of the reducing agent is 0-5 ℃;

the stirring reaction temperature is 0-65 ℃;

the molar ratio of the 2,4,6,8, 10-penta-substituted-3, 7,9, 11-tetraoxo-2, 4,6,8, 10-pentaaza [3.3.3] propellane to the reducing agent is 1: 4-1: 10;

in the step (II):

the reaction solvent is a mixed solution of dichloromethane and isopropanol, and the volume of the dichloromethane and the isopropanol is 1: 2;

the mass of the palladium catalyst is 10-20% of that of the 2,4,6,8, 10-penta-substituted-2, 4,6,8, 10-pentaaza [3.3.3] propeller alkane;

the palladium catalyst is Pd/C;

in the step (I) (1) and the step (II):

the separation and purification adopts column chromatography separation or/and solvent recrystallization;

when column chromatography separation and purification are carried out, the eluent is: two mixed liquids of ethyl acetate, petroleum ether, methanol, dichloromethane, chloroform, acetone, tetrahydrofuran and normal hexane;

when the solvent is recrystallized and purified, the recrystallization solvent is methanol, ethanol, isopropanol, ethyl acetate, acetone, acetonitrile, tetrahydrofuran, dioxane, dichloromethane, chloroform, dichloroethane, benzene, toluene, xylene, dimethyl sulfoxide, N-dimethylformamide, water, hydrochloric acid, aqueous solution of sulfuric acid or aqueous solution of sodium hydroxide;

developing solvent of thin layer chromatography is ethyl acetate and methanol, volume ratio of ethyl acetate and methanol is 10: 1;

the drying agent is anhydrous sodium sulfate, anhydrous magnesium sulfate, anhydrous calcium chloride or molecular sieve;

the solvent was removed by distillation under reduced pressure.

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