CN104119267B - A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine - Google Patents
A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine Download PDFInfo
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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Abstract
The present invention relates to the preparation method of a kind of metal organic macrocycle crystalline material for resolving chiral amine, the method first synthesis of chiral part (1R, 2R) H2L, this chiral ligand (1R, 2R) H2L is (1R, 2R) N 2 hydroxyl 3 tert-butyl group 5 (4 pyridine) benzylidene N ' 2 hydroxyl 3 tert-butyl group 5 (4 pyridine) benzyl cyclohexanediamine, then prepares the metal organic macrocycle crystalline material for resolving chiral amine by solvent-thermal method.Compared with prior art, the present invention uses solvent-thermal method, reaction temperature is low, response time is short, and reaction raw materials cheaply and is easily prepared, and synthetic operation is simple, without complicated post processing, the structure of the chiral metal organic macrocycle crystalline material preparing gained is highly stable, and selective adsorption capacity is strong, and separation efficiency is high.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to a kind of metal organic macrocycle for resolving chiral amine brilliant
The preparation method of state material.
Background technology
In recent years, chiral metal organic material because of its changeable topological structure, chiral Recognition with separate, chirality fluorescence passes
The fields such as sense, Heterogeneous asymmetric catalysis show the prospect of being widely applied, and have become chiral chemistry and chiral material science etc.
One of hot research field.Show after deliberation, if the bore hole size of metal-organic framework material (MOFs) and form and object
Molecule matches, and the frame material with amphiphilic hole may demonstrate the strongest effect to those amphiphilic guest molecules
Power, this type of metal-organic framework material can carry out chiral Recognition to some chiral molecules and separate.Currently, divide for Chiral Amine
From the implant of Chiral gas chromatography post be mainly the derivant of cyclodextrin, the derivative type Chiral gas chromatography post of cyclodextrin
There are two deficiencies: one is that the synthesis ratio of derivant of cyclodextrin is cumbersome, the derivative type Chiral gas chromatography of cyclodextrin
The filling of post is more complicated；Another one deficiency is that the price comparison of the derivative type Chiral gas chromatography post of cyclodextrin is expensive.
More rare as the report of the gas chromatogram of fixing phase currently, with respect to the chiral material splitting better performances.Example
As, Xie, S.-M., Zhang, Z.-J., Wang, Z.-Y., Yuan, L.-M.J.AM.CHEM.SOC, 2011,133 (31),
11892-11895, article name is Chiral Metal-Organic Frameworks for high-resolution gas
(chirality organic framework materials is as the consolidating of chromatography of gases post of a kind of efficient separating for chromatographic separations
Determine phase), the document reports chirality MOF [{ Cu (salan) n}] the fixing phase as GC chromatographic isolation.[{Cu(salan)
N}] it is chosen as fixing phase due to its spiral chirality duct and excellent heat stability, and to a series of different racemizations
Compound chromatograph separates.Will [Cu (salan) n}] spread upon in capillary column, by racemic aldehyde, ketone, alcohol and aminoacid
Carrying out chiral separation, wherein, in addition to 2-methyl-1-butene alcohol and camphyl alcohol, remaining racemic compound can achieve preferably
Baseline separation.Document points out that the chiral Recognition between racemic compound and fixing phase occurs mainly in the surface of MOFs, its
Topmost active force is spatial match good between racemic compound and chiral helical duct.But, the most relevant tool
The unidextrality metal-organic framework material having Chiral Amine separation function rarely has report.
Summary of the invention
The purpose of the present invention is aiming at the deficiencies in the prior art and provides that a kind of raw material is cheap, step is relatively easy, behaviour
Make easy, the preparation method of Chiral Amine separating effect preferable chiral metal organic macrocycle crystalline material.
The purpose of the present invention can be achieved through the following technical solutions:
A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine, the method first synthesis of chiral
Part (1R, 2R)-H2L, this chiral ligand (1R, 2R)-H2L is R type, is specially (1R, the 2R)-N-2-hydroxyl-3-tert-butyl group-5-
(4-pyridine) benzylidene-the N '-2-hydroxyl-3-tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine, then passes through solvent thermal
Method prepares the metal organic macrocycle crystalline material for resolving chiral amine, specifically includes following steps:
(1) chiral ligand (1R, 2R)-H2The preparation of L:
1. (1R, 2R)-cyclohexanediamine one side hydrochlorate is joined in absolute methanol, dissolve, be configured to mixed solution, then
It is 1 according to the mol ratio of (1R, 2R)-cyclohexanediamine one side hydrochlorate Yu the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) benzaldehyde:
(1～1.2), are slowly added to the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) benzaldehyde absolute methanol solution, add at 70～80 DEG C
Hot reflux reaction 6～8h, rotation is evaporated off methanol solvate, and washs with absolute ether, filter, dries, obtain intermediate product 1b；
2. intermediate product 1b above-mentioned steps 1. prepared is dissolved in absolute methanol, at 0 DEG C, according to reducing agent and step
1. in, the mol ratio of (1R, 2R)-cyclohexanediamine one side hydrochlorate is (10～15): 1, is dividedly in some parts reducing agent, and is sufficiently stirred for 1
～3h, rotation is evaporated off methanol solvate, adds water stirring 10～20min, repeatedly extracts with ether, and organic facies anhydrous sodium sulfate is done
Dry, it is spin-dried for, prepares intermediate product 1c；
3. intermediate product 1c above-mentioned steps 2. prepared is dissolved in absolute methanol, dissolves, is configured to mixed solution, then adds
Enter the same step the most same amount of 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) benzaldehyde absolute methanol solution, add at 70～80 DEG C
Hot reflux reaction 6～8h, rotation is evaporated off methanol solvate, enters in water by residual reaction drop, i.e. has khaki solid to separate out, mistake
Filter, drying i.e. prepare chiral ligand (1R, 2R)-H2L；
(2) preparation of metal organic macrocycle crystalline material:
Chiral ligand (1R, the 2R)-H of gained is prepared by step (1)2L and zinc salt are 1 in molar ratio: (2～3) join
In the mixed solution of DMF and absolute methanol, it is sufficiently stirred for dissolving, under the conditions of 80～85 DEG C, isothermal reaction
10～12h, it is cooled to room temperature, filters, by gained crystal with after ether washing for several times, be placed in air and dry, i.e. prepare
There is the metal organic macrocycle crystalline material of chiral separation function.
In (1R, 2R)-cyclohexanediamine one side hydrochlorate absolute methanol mixed solution that step is 1. described, (1R, 2R)-hexamethylene
The mass concentration of diamidogen one side hydrochlorate is 7.2～8.5mg/ml；The described 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) benzene first
In aldehyde absolute methanol solution, the mass concentration of the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) benzaldehyde is 12.5～13.5mg/ml.
The 2. described reducing agent of step is sodium borohydride, adds in three batches.
DMF described in step (2) and the mixed solution of absolute methanol be DMF with
Absolute methanol is to mix at 1: 1 by volume.
Chiral ligand (1R, 2R)-H described in step (2)2L is molten in the mixing of DMF and absolute methanol
Molar concentration in liquid is 0.02～0.06mol/L.
Zinc salt described in step (2) is two acetate hydrate zinc.
The present invention prepares gained and has the metal organic macrocycle crystalline material of chiral separation function, the ee value of separating chiral amine
Assay method be: 80mg is had the metal organic macrocycle crystalline material of chiral separation function after solvent exchange, at 100 DEG C
Vacuum condition under, activate 4h, then at-10 DEG C, at 3mL dissolved with in the absolute methanol of racemic modification amine, selective absorption
Three days, filter, wash for several times with absolute ether；Then, soaking one day in absolute ether, filter, filtrate is spread out through Benzenecarbonyl chloride.
After biochemistry, with Chiralcel OD-H type liquid phase chiral separation post, being 25 DEG C in temperature, normal hexane with the mass ratio of isopropanol is
(90～95): (5～10), under the conditions of flow velocity is 0.5～0.8mL/min, measure the ee value of separating chiral amine.
Prepare the unidextrality metal organic macrocycle crystalline material of gained by chirality functional group and nitrogen-atoms in Chiral Amine
Hyarogen-bonding, can carry out chiral separation to little molecular chiral amine well.
Described Chiral Amine is 2-butylamine, 3-methyl-2-butylamine, 2-amylamine and 2-hexylamine.
Compared with prior art, the invention have the characteristics that:
(1) present invention uses solvent-thermal method, and reaction temperature is low, and the response time is comparatively short, about needs 12h, and reaction raw materials is just
Preferably and easily prepare, such as conventional zinc salt, absolute methanol, DMF, absolute ether etc., synthetic operation letter
Single；
(2) inside the metal organic macrocycle crystalline material that prepared by the present invention, there is chirality function functional group, can be with non-convention
Racemic modification amine is carried out with thinking chiral separation, such as, 2-butylamine, 3-methyl-2-butylamine, 2-amylamine and 2-hexylamine is selected
Property absorption ee value be up to 98.0%, 96.2%, 95.4% and 91.3% respectively, for preparing gained has chiral separation function
The structure of metal organic macrocycle crystalline material is highly stable, it is possible to very well selective absorption 2-butylamine, 3-methyl-2-fourth
The racemic modification amine such as amine, 2-amylamine and 2-hexylamine.
Accompanying drawing explanation
Fig. 1 is the molecular structure Zn that the present invention prepares gained metal organic macrocycle crystalline material6L6Schematic diagram；
Fig. 2 is the steric bulk schematic three dimensional views that the present invention prepares gained metal organic macrocycle crystalline material；
Fig. 3 and Fig. 4 is the liquid phase color that the present invention prepares gained metal organic macrocycle crystalline material selective absorption 2-butylamine
Spectrogram；
Fig. 5 and Fig. 6 is that the present invention prepares gained metal organic macrocycle crystalline material selective absorption 3-methyl-2-butylamine
Liquid chromatogram；
Fig. 7 and Fig. 8 is the liquid phase color that the present invention prepares gained metal organic macrocycle crystalline material selective absorption 2-amylamine
Spectrogram；
Fig. 9 and Figure 10 is the liquid phase color that the present invention prepares gained metal organic macrocycle crystalline material selective absorption 2-hexylamine
Spectrogram；
Figure 11 is the X ray diffracting spectrum that the present invention prepares gained metal organic macrocycle crystalline material.
Detailed description of the invention
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1:
A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine, the method first synthesis of chiral
Part (1R, 2R)-H2L, this chiral ligand (1R, 2R)-H2L is R type, is specially (1R, the 2R)-N-2-hydroxyl-3-tert-butyl group-5-
(4-pyridine) benzylidene-the N '-2-hydroxyl-3-tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine, then passes through solvent thermal
Method prepares the metal organic macrocycle crystalline material for resolving chiral amine, comprises the following steps:
(1) chiral ligand (1R, 2R)-H2The preparation of L:
1. 151mg (1R, 2R)-cyclohexanediamine one side hydrochlorate is joined in 20ml absolute methanol, dissolve, be configured to matter
Amount concentration is the solution of 7.55mg/ml, then is slowly added dropwise the 3-tert-butyl group-2-hydroxyl-5-(4-that mass concentration is 12.75mg/ml
Pyridine) benzaldehyde absolute methanol solution 20ml, at 70 DEG C, heating reflux reaction 6h, is spin-dried for, and washs with absolute ether, mistake
Filter, dries, obtains intermediate product 1b '；
2. the intermediate product 1b ' above-mentioned steps 1. prepared is dissolved in 150ml absolute methanol, adds in three batches at 0 DEG C
400mg sodium borohydride, is sufficiently stirred for 2h, is spin-dried for, and adds water stirring 10min, repeatedly extracts with ether, organic facies anhydrous slufuric acid
Sodium is dried, and is spin-dried for, and prepares intermediate product 1c '；
3. the intermediate product 1c ' above-mentioned steps 2. prepared is dissolved in 50ml absolute methanol, adds 20ml mass concentration
For the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) the benzaldehyde absolute methanol solution of 12.75mg/ml, it is heated to reflux anti-at 70 DEG C
Answer 6h, rotation that major part methanol solvate is evaporated off, residual reaction drop is entered in water, i.e. has khaki solid to separate out, filter, dry
I.e. prepare chiral ligand (1R, 2R)-H2L:(1R, 2R)-N-2-hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzylidene-N '-2-
Hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine；
Prepare chiral ligand (1R, 2R)-H2The reaction equation of L is:
(2) preparation of metal organic macrocycle crystalline material:
Chiral ligand (1R, the 2R)-H of gained is prepared by step (1)2L and two acetate hydrate zinc (Zn (OAC)2·2H2O) press
Mol ratio is 1: 2, joins and fills 2mlN, in the sample bottle of dinethylformamide and 2ml absolute methanol mixed solution, its
In, chiral ligand (1R, 2R)-H2The molar concentration of L is 0.05mol/L, screws bottle cap, be placed in by sample bottle after fully dissolving
In 80 DEG C of baking ovens, after isothermal reaction 12h, take out sample bottle, be cooled to room temperature, be filtered to remove reactant liquor, by gained crystal second
After ether washing for several times, it is placed in air and dries, i.e. prepare the metal organic macrocycle crystalline material with chiral separation function.
Chiral ligand (1R, the 2R)-H that in the present embodiment, step (1) prepares2L,1HNMR(CDCl3) δ: 8.62-8.60
(d, 2H, pyridy1H), 8.55-8.54 (d, 2H, pyridy1H), 8.51 (s, 1H, ArH), 7.61 (s, 1H, ArH), 7.44-
7.43 (d, 2H, pyridy1H), 7.43-7.38 (m, 4H, pyridy1H+ArH), 7.13 (s, 1H, ArH), 4.15-3.96 (dd,
2H, MethyleneH), 3.14-2.86 (m, 2H, cyclohexadecy1H), 2.29-2.26 (d, 1H,
Cyclohexadecy1H), 1.90-1.73 (m, 5H, eyclohexadecy1H), 1.49 (s, 9H, CMe3), 1.44-1.40 (m,
2H, cyclohexadecy1H), 1.33 (s, 9H, CMe3),13C NMR(CDCl3) δ: 166.07,161.63,158.80,
150.37,150.17,148.82,148.28,138.69,137.86,128.51,128.45,127.88,124.92,124.85,
124.17,121.17,119.10,74.13,61.35,50.88,35.31,35.03,34.25,30.88,29.59,24.84,
24.54,15.50.FTIR (KBr pellet, em-1): 3411 (w), 3205 (m), 2935 (s), 2860 (s), 1630 (s), 1565
(s), 1464 (s), 1443 (s), 1400 (m), 1360 (m), 1319 (m), 1257 (m), 1229 (m), 1171 (m), 1115 (m)
1078 (m), 992 (m), 890 (m), 821 (s), 710 (w), 622 (s), 512 (m) .ESI-MS:m/z591.37 (Calcd m/
z590.36for[L+H]+)。
The present embodiment prepares the crystal structure of gained metal organic macrocycle crystalline material as depicted in figs. 1 and 2, and metal is organic
Macro ring crystalline material crystallizes in tripartite chiral space group R3, and an asymmetric cell is contained within 1/3rd molecules, and presents
It it is a tubular structure.Zn takes at center a quadrangular pyramid coordination configuration, and transverse plane is by the N of a ligand L2O2Donor occupies,
Axial location is coordinated with another ligand L pyridine nitrogen atom.Each ZnL unit uses a terminal pyridine groups to be coordinated with Zn
And forming six aggressiveness, another pyridine is not coordinated.These ring-type six aggressiveness external diameters are 4.1nm, high 1.19nm, internal diameter
1.20nm.Adjacent Zn interatomic distance isWithThe interatomic distance of relative Zn isTwo
Individual independent Zn center is in N2O2Above the plane formedAnd point to pyridine groups.ZnN2O2The horizontal face formed with
Coordination pyridine interannular dihedral angle be 22.39 ° and 25.65 °, and be not coordinated pyridine interannular dihedral angle be 28.47 ° and
28.51 °, six pairs of tert-butyl groups of six L parts arrange in an orderly manner and cover in the both sides of ring-type six aggressiveness along crystallography triad,
And produce six hydrophobic cavities.
The present embodiment prepares such a object template effect in metal organic macrocycle crystalline material, can be from the first of part
The hydrophobic interaction that the methyl group of base group and solvent is formed embodies.Butyl group is conjugated pyridine ring with adjacent macro ring
Between strong CH ... π effect, cause macro ring along the parallel accumulation in crystallography c-axis direction, and formed duct size be 1.4 ×
The nanotube-shaped thing of 1.1nm.Such a structure passes through aspectant intermolecular π ... π effect is strengthened；Each Zn6L6
Unit is all by participating in six π ... in pi accumulation.It addition, between the pyridine groups that is not coordinated of ZnL unit and aromatic ring group
CH ... π and CH ... N effect further enhances the formation of nanotube-shaped thing.Metal organic macrocycle prepared by the present embodiment is brilliant
In state material, the noncovalent interaction power of highly directive can promote big interannular mutually to pile up, thus formed one homochiral
Three-dimensional porous nano structure.
The 80mg that the present embodiment is prepared gained has the metal organic macrocycle crystalline material of chiral separation function, through solvent
After exchange, under the vacuum of 100 DEG C, place 4h, then at-10 DEG C, anhydrous dissolved with 15mg racemic modification 2-butylamine of 3ml
In ether, selective absorption three days, filter, wash for several times with absolute ether, then, soak one day in absolute ether, filter,
Filtrate uses Chiralcel OD-H type liquid phase chiral separation post, at 25 DEG C, normal hexane and isopropanol after Benzenecarbonyl chloride. derivatization
Mass ratio is 93: 7, under conditions of flow velocity is 0.6ml/min, measure chirality 2-butylamine separate ee value be 98.0%, as Fig. 3 with
Shown in Fig. 4.
Wherein, Fig. 3 analysis result is as shown in Table 1.
Table one
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 18.9500 | 11533.9904 | BB | 148.0000 | 49.5373 |
| 2 | 24.5333 | 11749.4426 | FF | 182.0000 | 50.4627 |
| With | 23283.4330 |
Fig. 4 analysis result is as shown in Table 2.
Table two
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 18.7833 | 137.7251 | BB | 42.0000 | 0.9982 |
| 2 | 24.4833 | 13659.2243 | BB | 119.0000 | 99.0018 |
| With | 13796.9495 |
The 80mg that the present embodiment is prepared gained has the metal organic macrocycle crystalline material of chiral separation function, through solvent
After exchange, under the vacuum of 100 DEG C, place 4h, then at-10 DEG C, at 3ml dissolved with 15mg racemic modification 3-methyl-2-butylamine
Absolute ether in, selective absorption three days, filter, with absolute ether wash for several times, then, in absolute ether soak one
My god, to filter, filtrate uses Chiralcel OD-H type liquid phase chiral separation post, at 25 DEG C, normal hexane after Benzenecarbonyl chloride. derivatization
It is 95: 5 with isopropanol mass ratio, under conditions of flow velocity is 0.8ml/min, measures the ee value that chirality 3-methyl-2-butylamine separates
It is 96.2%, as shown in Figure 5 and Figure 6.
Wherein, Fig. 5 analysis result is as shown in Table 3.
Table three
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 13.0500 | 18811.6432 | BB | 117.0000 | 50.3613 |
| 2 | 22.1167 | 18541.7124 | BB | 143.0000 | 49.6387 |
| With | 37353.3556 |
Fig. 6 analysis result is as shown in Table 4.
Table four
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 13.3500 | 5927.1234 | BB | 91.0000 | 98.1017 |
| 2 | 22.7000 | 114.6915 | FF | 66.0000 | 1.8983 |
| With | 6041.8149 |
The 80mg that the present embodiment is prepared gained has the metal organic macrocycle crystalline material of chiral separation function, through solvent
After exchange, under the vacuum of 100 DEG C, place 4h, then at-10 DEG C, anhydrous dissolved with 15mg racemic modification 2-amylamine of 3ml
In ether, selective absorption three days, filter, wash for several times with absolute ether, then, soak one day in absolute ether, filter,
Filtrate uses Chiralcel OD-H type liquid phase chiral separation post, at 25 DEG C, normal hexane and isopropanol after Benzenecarbonyl chloride. derivatization
Mass ratio is 90: 10, and under conditions of flow velocity is 0.5ml/min, the ee value measuring the separation of chirality 2-amylamine is 95.4%, such as Fig. 7
Shown in Fig. 8.
Wherein, Fig. 7 analysis result is as shown in Table 5.
Table five
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 14.5333 | 20957.7579 | BB | 79.0000 | 51.4736 |
| 2 | 17.9000 | 19757.7949 | BB | 106.0000 | 48.5264 |
| With | 40715.5527 |
Fig. 8 analysis result is as shown in Table 6.
Table six
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 14.5000 | 8729.6652 | FF | 57.0000 | 97.7187 |
| 2 | 17.9000 | 203.8030 | FF | 46.0000 | 2.2813 |
| With | 8933.4682 |
The 80mg that the present embodiment is prepared gained has the metal organic macrocycle crystalline material of chiral separation function, through solvent
After exchange, under the vacuum of 100 DEG C, place 4h, then at-10 DEG C, anhydrous dissolved with 15mg racemic modification 2-hexylamine of 3ml
In ether, selective absorption three days, filter, wash for several times with absolute ether, then, soak one day in absolute ether, filter,
Filtrate uses Chiralcel OD-H type liquid phase chiral separation post, at 25 DEG C, normal hexane and isopropanol after Benzenecarbonyl chloride. derivatization
Mass ratio is 90: 10, and under conditions of flow velocity is 0.5ml/min, the ee value measuring the separation of chirality 2-hexylamine is 91.3%, such as Fig. 9
Shown in Figure 10.
Wherein, Fig. 9 analysis result is as shown in Table 5.
Table seven
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 15.9333 | 34634.2676 | BB | 144.0000 | 48.9792 |
| 2 | 19.9667 | 36077.9211 | BB | 160.0000 | 51.0208 |
| With | 70712.1886 |
Figure 10 analysis result is as shown in Table 6.
Table eight
| Numbering | RT [minute] | Area [mAbs*s] | Type | Peak width [second] | Area (%) |
| 1 | 15.9000 | 21237.1588 | BB | 137.0000 | 95.6661 |
| 2 | 20.1333 | 962.0971 | BB | 85.0000 | 4.3339 |
| With | 22199.2558 |
Figure 11 show the present embodiment and prepares the X ray diffracting spectrum of gained metal organic macrocycle crystalline material.
Embodiment 2:
A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine, the method first synthesis of chiral
Part (1R, 2R)-H2L, this chiral ligand (1R, 2R)-H2L is R type, is specially (1R, the 2R)-N-2-hydroxyl-3-tert-butyl group-5-
(4-pyridine) benzylidene-the N '-2-hydroxyl-3-tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine, then passes through solvent thermal
Method prepares the metal organic macrocycle crystalline material for resolving chiral amine, comprises the following steps:
(1) chiral ligand (1R, 2R)-H2The preparation of L:
1. (1R, 2R)-cyclohexanediamine one side hydrochlorate is joined in 20ml absolute methanol, dissolve, be configured to quality dense
Degree is the solution of 7.2mg/ml, then is slowly added dropwise the 3-tert-butyl group-2-hydroxyl-5-(the 4-pyrrole that 16ml mass concentration is 12.5mg/ml
Pyridine) benzaldehyde absolute methanol solution, at 75 DEG C, heating reflux reaction 7h, is spin-dried for, and washs with absolute ether, filters, and dries,
Obtain intermediate product 1b "；
2. the intermediate product 1b 1. above-mentioned steps prepared " it is dissolved in 150ml absolute methanol, add in three batches at 0 DEG C
380mg sodium borohydride, is sufficiently stirred for 1h, is spin-dried for, and adds water stirring 15mm, repeatedly extracts with ether, organic facies anhydrous slufuric acid
Sodium is dried, and is spin-dried for, and prepares intermediate product 1c "；
3. the intermediate product 1c 2. above-mentioned steps prepared " it is dissolved in 50ml absolute methanol, add 16ml mass concentration
For the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) the benzaldehyde absolute methanol solution of 12.5mg/ml, it is heated to reflux anti-at 75 DEG C
Answer 7h, rotation that major part methanol solvate is evaporated off, residual reaction drop is entered in water, i.e. has khaki solid to separate out, filter, dry
I.e. prepare chiral ligand (1R, 2R)-H2L:(1R, 2R)-N-2-hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzylidene-N '-2-
Hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine；
(2) preparation of metal organic macrocycle crystalline material:
Chiral ligand (1R, the 2R)-H of gained is prepared by step (1)2L and two acetate hydrate zinc (Zn (OAC)2·2H2O) press
Mol ratio is to join fill 2mlN at 1: 2.2, in the sample bottle of dinethylformamide and 2ml absolute methanol mixed solution, its
In, chiral ligand (1R, 2R)-H2The molar concentration of L is 0.02mol/L, screws bottle cap, be placed in by sample bottle after fully dissolving
In 80 DEG C of baking ovens, after isothermal reaction 10h, take out sample bottle, be cooled to room temperature, be filtered to remove reactant liquor, by gained crystal second
After ether washing for several times, it is placed in air and dries, i.e. prepare the metal organic macrocycle crystalline material with chiral separation function.
Embodiment 3:
A kind of preparation method of the metal organic macrocycle crystalline material for resolving chiral amine, the method first synthesis of chiral
Part (1R, 2R)-H2L, this chiral ligand (1R, 2R)-H2L is R type, is specially (1R, the 2R)-N-2-hydroxyl-3-tert-butyl group-5-
(4-pyridine) benzylidene-the N '-2-hydroxyl-3-tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine, then passes through solvent thermal
Method prepares the metal organic macrocycle crystalline material for resolving chiral amine, comprises the following steps:
(1) chiral ligand (1R, 2R)-H2The preparation of L:
1. (1R, 2R)-cyclohexanediamine one side hydrochlorate is joined in 18ml absolute methanol, dissolve, be configured to quality dense
Degree is the solution of 8.5mg/ml, then is slowly added dropwise the 3-tert-butyl group-2-hydroxyl-5-(the 4-pyrrole that 20ml mass concentration is 13.5mg/ml
Pyridine) benzaldehyde absolute methanol solution, at 80 DEG C, heating reflux reaction 8h, is spin-dried for, and washs with absolute ether, filters, and dries,
Obtain intermediate product 1b " '；
2. the intermediate product 1b 1. above-mentioned steps prepared " ' it is dissolved in 150ml absolute methanol, add in three batches at 0 DEG C
570mg sodium borohydride, is sufficiently stirred for 1h, is spin-dried for, and adds water stirring 20min, repeatedly extracts with ether, organic facies anhydrous slufuric acid
Sodium is dried, and is spin-dried for, and prepares intermediate product 1c " '；
3. the intermediate product 1c 2. above-mentioned steps prepared " ' it is dissolved in 50ml absolute methanol, add 50ml mass concentration
For the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine) the benzaldehyde absolute methanol solution of 13.5mg/ml, it is heated to reflux anti-at 80 DEG C
Answer 8h, rotation that major part methanol solvate is evaporated off, residual reaction drop is entered in water, i.e. has khaki solid to separate out, filter, dry
I.e. prepare chiral ligand (1R, 2R)-H2L:(1R, 2R)-N-2-hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzylidene-N '-2-
Hydroxyl-3-the tert-butyl group-5-(4-pyridine) benzyl-cyclohexanediamine；
(2) preparation of metal organic macrocycle crystalline material:
Chiral ligand (1R, the 2R)-H of gained is prepared by step (1)2L and two acetate hydrate zinc (Zn (OAC)2·2H2O) press
Mol ratio is to join fill 2mlN at 1: 3, in the sample bottle of dinethylformamide and 2ml absolute methanol mixed solution, wherein,
Chiral ligand (1R, 2R)-H2The molar concentration of L is 0.06mol/L, screws bottle cap, sample bottle is placed in 85 after fully dissolving
In DEG C baking oven, after isothermal reaction 12h, take out sample bottle, be cooled to room temperature, be filtered to remove reactant liquor, by gained crystal ether
After washing for several times, it is placed in air and dries, i.e. prepare the metal organic macrocycle crystalline material with chiral separation function.
Above the specific embodiment of the present invention is described.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make various deformation or amendment within the scope of the claims, this not shadow
Ring the flesh and blood of the present invention.
Claims (3)
1. the preparation method for the metal organic macrocycle crystalline material of resolving chiral amine, it is characterised in that described gold
Belonging to organic macrocycle crystalline material and crystallize in tripartite chiral space group R3, an asymmetric cell is contained within 1/3rd molecules,
And it being rendered as a tubular structure, Zn takes at center a quadrangular pyramid coordination configuration, and transverse plane is by the N of a ligand L2O2Supply
Body occupies, and axial location is coordinated with another ligand L pyridine nitrogen atom, and each ZnL unit uses a terminal pyridine groups
Being coordinated with Zn and form six aggressiveness, another pyridine is not coordinated, and these ring-type six aggressiveness external diameters are 4.1nm, high 1.19nm, interior
Footpath 1.20nm, adjacent Zn interatomic distance isWithThe interatomic distance of relative Zn is
Two independent Zn centers are in N2O2Above the plane formedAnd point to pyridine groups, ZnN2O2The horizontal face formed
With coordination pyridine interannular dihedral angle be 22.39 ° and 25.65 °, and be not coordinated pyridine interannular dihedral angle be 28.47 ° and
28.51 °, six pairs of tert-butyl groups of six L parts arrange in an orderly manner and cover in the both sides of ring-type six aggressiveness along crystallography triad,
And produce six hydrophobic cavities；
Described preparation method first synthesis of chiral part (1R, 2R)-H2L, this chiral ligand (1R, 2R)-H2L be (1R, 2R)-
N-2-hydroxyl-3-the tert-butyl group-5-(4-pyridine radicals) benzylidene-the N '-2-hydroxyl-3-tert-butyl group-5-(4-pyridine radicals) benzyl-
Cyclohexanediamine, then prepares the metal organic macrocycle crystalline material for resolving chiral amine by solvent-thermal method, and reaction equation is such as
Under:
Described preparation method specifically includes following steps:
(1) chiral ligand (1R, 2R)-H2The preparation of L:
1. (1R, 2R)-cyclohexanediamine one side hydrochlorate is joined in absolute methanol, dissolve, be configured to mixed solution, according still further to
(1R, 2R)-cyclohexanediamine one side hydrochlorate is 1:(1 with the mol ratio of the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine radicals) benzaldehyde
～1.2), it is slowly added to the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine radicals) benzaldehyde absolute methanol solution, adds at 70～80 DEG C
Hot reflux reaction 6～8h, rotation is evaporated off methanol solvate, and washs with absolute ether, filter, dries, obtain intermediate product 1b；
2. intermediate product 1b above-mentioned steps 1. prepared is dissolved in absolute methanol, at 0 DEG C, according to reducing agent and step 1. in
The mol ratio of (1R, 2R)-cyclohexanediamine one side hydrochlorate is (10～15): 1, is dividedly in some parts reducing agent, and be sufficiently stirred for 1～
3h, rotation is evaporated off methanol solvate, adds water stirring 10～20min, repeatedly extracts with ether, and organic facies anhydrous sodium sulfate is done
Dry, it is spin-dried for, prepares intermediate product 1c；
3. intermediate product 1c above-mentioned steps 2. prepared is dissolved in absolute methanol, dissolves, is configured to mixed solution, adds same
The step the most same amount of 3-tert-butyl group-2-hydroxyl-5-(4-pyridine radicals) benzaldehyde absolute methanol solution, heats at 70～80 DEG C
Back flow reaction 6～8h, rotation is evaporated off methanol solvate, enters in water by residual reaction drop, i.e. have khaki solid to separate out, filter,
Dry and i.e. prepare chiral ligand (1R, 2R)-H2L；
Wherein, in (1R, 2R)-cyclohexanediamine one side hydrochlorate absolute methanol mixed solution that step is 1. described, (1R, 2R)-ring
The mass concentration of hexamethylene diamine one side hydrochlorate is 7.2～8.5mg/ml；The described 3-tert-butyl group-2-hydroxyl-5-(4-pyridine radicals)
In benzaldehyde absolute methanol solution, the mass concentration of the 3-tert-butyl group-2-hydroxyl-5-(4-pyridine radicals) benzaldehyde be 12.5～
13.5mg/ml；
The 2. described reducing agent of step is sodium borohydride, adds in three batches；
(2) preparation of metal organic macrocycle crystalline material:
Chiral ligand (1R, the 2R)-H of gained is prepared by step (1)2L and zinc salt are in molar ratio for 1:(2～3) join N, N-bis-
In the mixed solution of methylformamide and absolute methanol, be sufficiently stirred for dissolve, under the conditions of 80～85 DEG C, isothermal reaction 10～
12h, is cooled to room temperature, filters, and by gained crystal with after ether washing for several times, is placed in air and dries, i.e. prepare and have
The metal organic macrocycle crystalline material of chiral separation function；
Zinc salt described in step (2) is two acetate hydrate zinc.
The preparation method of a kind of metal organic macrocycle crystalline material for resolving chiral amine the most according to claim 1,
It is characterized in that, DMF and the mixed solution of absolute methanol described in step (2) are N, N-dimethyl formyl
Amine mixes for 1:1 by volume with absolute methanol.
The preparation method of a kind of metal organic macrocycle crystalline material for resolving chiral amine the most according to claim 1,
It is characterized in that, chiral ligand (1R, the 2R)-H described in step (2)2L is in N,N-dimethylformamide and the mixing of absolute methanol
Molar concentration in solution is 0.02～0.06mol/L.
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