CN110652975B - (S) -BINOL derivative CSP filler and preparation method and application thereof - Google Patents
(S) -BINOL derivative CSP filler and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides (S) -BINOL derivative CSP filler and a preparation method and application thereof, belonging to the field of analytical chemistry. The (S) -BINOL derivative CSP filler provided by the invention can be used for separating chiral compounds with various structural types, has good stability and is suitable for being used as a high performance liquid chromatography filler. The data of the embodiment shows that the (S) -BINOL derivative CSP filler provided by the invention can be used for resolving 5 chiral compounds of 1,1'-binaphthol, 5-methoxy flavanone, 2' -hydroxy flavanone, thalidomide and N- (3,5-dinitrobenzoyl) -alpha-phenylethylamine under normal phase conditions, has stable chiral recognition capability in a normal phase chromatographic mode, and can meet the requirements of daily pharmaceutical analysis and production quality control.
Description
Technical Field
The invention relates to the technical field of analytical chemistry, in particular to (S) -BINOL derivative CSP filler and a preparation method and application thereof.
Background
Chirality is one of the essential attributes of the nature on which humans live, and biological macromolecules such as proteins, polysaccharides, nucleic acids and the like have chirality, and chiral substances with optical activity are widely present in the bodies of animals and plants. At present, about 57% of clinically used medicaments are chiral medicaments, but most of the medicaments are used as racemes, and the number of clinically used single enantiomer medicaments is less than 100. The absorption, distribution, metabolism, excretion and other pharmacokinetic processes of the chiral drug in vivo and the mutual recognition and interaction with biomolecules such as protein, nucleic acid, enzyme, receptor and the like have certain stereoselectivity, so that the concentration difference of different enantiomers in the blood of a human body is caused, and the difference of curative effect and adverse reaction is also caused. Two chiral compounds which are enantiomers of each other often have great differences in the aspects of biological activity, pharmacologic kinetics, potential toxic and side effects of medicaments and the like. Therefore, chiral recognition and enantiomer resolution research have important practical value and theoretical significance in the fields of biology, medicine and materials.
High performance liquid chromatography (HPLC method) has the advantages of high efficiency, rapidity and simplicity, and is the most widely used method for separating optical isomers and analyzing enantiomeric purity. The chiral stationary phase method (CSP method) in high performance liquid chromatography is the most attractive method for separating the enantiomers of drugs because of high efficiency and convenience, and can be used for analytical separation and preparation and semi-preparation of the enantiomers. Since the 70 s of the 20 th century, the development of CSP has been rapidly advanced, and more than 100 liquid chromatography chiral stationary phases have been commercialized. Common chiral stationary phases include brush-type CSP, cyclodextrin and derivatives CSP, crown ether and derivatives CSP, macrocyclic antibiotics CSP, polysaccharide derivatives CSP, and the like. However, so far, no CSP can adapt to the enantiomer separation of various structural types and higher enantiomer separation selectivity, so that continuous research and development of novel chiral stationary phases have important scientific significance and application value.
1,1'-binaphthol has a C2 symmetry axis and contains two identical naphthalene units, two naphthalene rings prevent free rotation of the 1,1' -bond, so that BINOL molecules have stable chiral configuration, but the problem that chiral compounds of various structural types cannot be separated still exists.
Disclosure of Invention
In view of the above, the present invention aims to provide a (S) -BINOL derivative CSP filler, and a preparation method and an application thereof. The (S) -BINOL derivative CSP filler provided by the invention has excellent separation performance on chiral compounds with various structural types.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides (S) -BINOL derivative CSP filler, the structural formula is shown as formula I;
in the formula I, the compound is shown in the specification,
represents a structural formula of the silica gel carrier after hydrogen is removed.
The invention also provides a preparation method of the (S) -BINOL derivative CSP filler, which comprises the following steps:
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
carrying out condensation reaction on a compound with a structure shown in a formula II and a silanization reagent to obtain a condensation product;
and bonding the condensation product to an acidified silica gel carrier, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
The invention also provides another preparation method of the (S) -BINOL derivative CSP filler, which comprises the following steps:
carrying out silanization reaction on a silanization reagent and an acidified silica gel carrier to obtain silanized silica gel;
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
and bonding a compound with a structure shown in a formula II to the silanized silica gel, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
Preferably, the silylating agent is 3-aminopropyltriethoxysilane.
Preferably, the acidified silica gel support is acidified with silica gel.
Preferably, the silica gel is spherical or amorphous silica gel for chromatography.
Preferably, the acidifying reagent used for acidifying is hydrochloric acid, the concentration of the hydrochloric acid is 4mol/L, and the using amount ratio of the silica gel to the hydrochloric acid is 10 g: 100 mL.
Preferably, the time of the condensation reaction is 3-4 h.
Preferably, the dehydroxylation protection is carried out in hydrochloric acid.
The invention also provides application of the (S) -BINOL derivative CSP filler in the technical scheme in the field of chiral resolution.
The invention provides the (S) -BINOL derivative CSP filler, which can be used for separating chiral compounds with various structural types, has good stability and is suitable for being used as a high performance liquid chromatography filler. The data of the embodiment shows that the (S) -BINOL derivative CSP filler provided by the invention can be used for resolving 5 chiral compounds of 1,1'-binaphthol, 5-methoxy flavanone, 2' -hydroxy flavanone, thalidomide and N- (3,5-dinitrobenzoyl) -alpha-phenylethylamine under normal phase conditions, has stable chiral recognition capability in a normal phase chromatographic mode, and can meet the requirements of daily pharmaceutical analysis and production quality control.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of a compound having a structure represented by formula II in example 1 and example 2;
FIG. 2 is a nuclear magnetic hydrogen spectrum of the condensation product of example 1;
FIG. 3 is a nuclear magnetic carbon spectrum of the condensation product of example 1;
FIG. 4 is an infrared spectrum of the S-6-A BINOL CSP of example 1;
FIG. 5 is a resolution chromatogram of 1,1'-Binaphthol (1,1' -Binaphthol) on S-6-A BINOL CSP;
FIG. 6 is a resolution chromatogram of 5-Methoxyflavanone (5-Methoxyflavanone) on S-6-A BINOL CSP;
FIG. 7 is a chromatogram of the resolution of 2'-Hydroxyflavanone (2' -Hydroxyflavanone) on S-6-A BINOL CSP;
FIG. 8 is a resolution chromatogram of Thalidomide (Thalidomide) on S-6-A BINOL CSP;
FIG. 9 shows a resolution chromatogram of N- (3,5-Dinitrobenzoyl) - α -phenylethylamine (N- (3,5-Dinitrobenzoyl) -1-phenylethyl-ylamine) on S-6-A BINOL CSP.
Detailed Description
The invention provides (S) -BINOL derivative CSP (abbreviated as S-6-A BINOL CSP) filler, which has a structural formula shown as a formula I;
in the formula I, the compound is shown in the specification,
represents a structural formula of the silica gel carrier after hydrogen is removed.
In the invention, the chemical bond on the benzene ring in the formula I is blackened, which represents that the structure of the stationary phase is S configuration.
The invention also provides a preparation method of the (S) -BINOL derivative CSP filler, which comprises the following steps:
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
carrying out condensation reaction on a compound with a structure shown in a formula II and a silanization reagent to obtain a condensation product;
and bonding the condensation product to an acidified silica gel carrier, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
The invention carries out hydroxyl protection on S-6-A BINOL to obtain a compound (called (S) -1 for short) with a structure shown in a formula II;
according to the invention, BINOL with S configuration is preferably subjected to structural modification, acrylic acid is substituted at 6-position of naphthalene ring to obtain S-6-acrylic acid BINOL (S-6-A BINOL), and then hydroxyl protection is carried out on 1 and 1' positions of S-6-A BINOL to obtain compound (S) -1. The hydroxyl group is protected in a specific manner without particular limitation, and a manner known to those skilled in the art may be used.
After the compound with the structure shown in the formula II is obtained, the compound with the structure shown in the formula II and a silanization reagent are subjected to condensation reaction to obtain a condensation product.
In the present invention, the silylating agent is preferably 3-aminopropyltriethoxysilane.
In the invention, the time of the condensation reaction is preferably 3-4 h.
In a specific embodiment of the present invention, it is preferable that: in a 50mL single neck flask, (S) -1(1.125mmol, 500mg) was dissolved in anhydrous dichloromethane (15mL), triethylamine (3.375mmol, 0.47mL) was added, after stirring for 5 minutes in ice bath, 2- (7-benzotriazole oxide) -N, N, N ', N' -tetramethylurea hexafluorophosphate (1.2375mmol, 470.25mg) was added, the ice bath was removed and stirring for 30 minutes at room temperature, 3-aminopropyltriethoxysilane (1.125mmol, 0.26mL) was added and the reaction was monitored by TLC at room temperature for 3 hours. After the reaction, the reaction mixture was extracted with ethyl acetate (3X 15mL), and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to give a condensation product (S) -2.
After the condensation product is obtained, the condensation product is bonded to an acidified silica gel carrier, and then dehydroxylation protection is carried out to obtain the (S) -BINOL derivative CSP filler.
In the present invention, the acidified silica gel support is preferably acidified with silica gel.
In the present invention, the silica gel preferably comprises a spherical or amorphous silica gel for chromatography.
In the invention, the acidifying reagent used for acidifying is preferably hydrochloric acid, the concentration of the hydrochloric acid is preferably 4mol/L, and the dosage ratio of the silica gel to the hydrochloric acid is preferably 10 g: 100 mL.
In the present invention, the dehydroxylation protection is preferably carried out in hydrochloric acid.
In a specific embodiment of the present invention, it is preferable that: silica gel (10g) was added to a 250mL single-neck flask, refluxed with 4M hydrochloric acid (100mL) for 5 hours, and after 5 hours, the silica gel was filtered through a sand-core funnel, washed to neutrality with water, and vacuum-dried at 150 ℃ for 24 hours. (S) -2(1.36g) was weighed into a 250mL single-neck flask, the silica gel (3.5g) was acidified and redistilled toluene (100mL) was added, and the reaction was refluxed for 12 hours under nitrogen. After the reaction is finished, cooling to room temperature, filtering silica gel by using a sand core funnel, washing with dichloromethane and methanol for multiple times, and drying for 4 hours in vacuum at 50 ℃ to obtain (S) -3; (S) -3 was dissolved in methanol (50mL) in a 100mL single-neck flask, hydrochloric acid (12M, 2mL) was added dropwise, the mixture was stirred at room temperature, and the end point of the reaction was checked by TLC. After the reaction is finished, filtering the silica gel by using a sand core funnel, washing the silica gel for multiple times by using methanol, and drying the silica gel for 4 hours in vacuum at 50 ℃ to obtain the S-6-A BINOL CSP.
The equation for preparing (S) -BINOL derivative CSP filler is shown below (starting with (S) -1) using 3-aminopropyltriethoxysilane as the silylating agent:
the invention also provides another preparation method of the (S) -BINOL derivative CSP filler, which comprises the following steps:
carrying out silanization reaction on a silanization reagent and an acidified silica gel carrier to obtain silanized silica gel;
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
and bonding a compound with a structure shown in a formula II on the silanized silica gel, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
The silanization reagent and the acidified silica gel carrier are subjected to silanization reaction to obtain the silanized silica gel.
In a specific embodiment of the present invention, it is preferable that: taking 10g of silica gel, 100mL of 4M hydrochloric acid, N2And (3) protective refluxing is carried out for 5h, the mixture is cooled to room temperature, the silica gel is washed to be neutral by using ultrapure water, vacuum drying is carried out for 24h at the temperature of 140 ℃, the acidified silica gel is obtained, and the acidified silica gel is sealed and stored in a shade place for later use. Acidified silica gel (3.5g) was added to a 250mL three-necked flask containing 100mL of dry toluene, which was cooled to room temperature with residual water being removed. 2 times of 3-aminopropyltriethoxysilane (per m) was added according to the specific surface area of silica gel2The silica gel contains about 8 to 10. mu. mol of OH), N2Protecting, heating in oil bath to 110 deg.C slowly, reflux reacting for 4h, naturally cooling to room temperature, filtering, washing with toluene and methanol respectively for three times, vacuum drying at 150 deg.C for 4h to obtain silanized silica gel.
The method carries out hydroxyl protection on S-6-A BINOL to obtain a compound with a structure shown in a formula II;
the specific mode for protecting the hydroxyl group is not particularly limited, and the method can be consistent with the scheme.
After obtaining the silanized silica gel and the compound with the structure shown in the formula II, the compound with the structure shown in the formula II is bonded to the silanized silica gel, and then dehydroxylation protection is carried out to obtain the (S) -BINOL derivative CSP filler.
In a specific embodiment of the present invention, it is preferable that: dissolving the compound (S) -1(1.0g) in 12mL of anhydrous dichloromethane, stirring at 0 ℃ for 5min, adding triethylamine (1.852g) and 2- (7-benzotriazole oxide) -N, N, N ', N' -tetramethylurea hexafluorophosphate (5.575g) to continue reacting for 2h, removing the ice bath, adding silanized silica gel (4.0g) to continue reacting for 24h to obtain (S) -3.
(S) -3 obtained in the above step was dissolved in methanol (50mL) in a 100mL single-neck flask, hydrochloric acid (12M, 2mL) was added dropwise, the mixture was stirred at room temperature, and the end point of the reaction was checked by TLC. After the reaction is finished, filtering silica gel by using a sand core funnel, washing the silica gel for multiple times by using methanol, and drying the silica gel for 4 hours in vacuum at 50 ℃ to obtain the S-6-A BINOL CSP.
The formula for preparing the (S) -BINOL derivative CSP filler is shown below, using 3-aminopropyltriethoxysilane as the silylating agent for example:
the invention also provides application of the (S) -BINOL derivative CSP filler in the technical scheme in the field of chiral resolution.
To further illustrate the present invention, the (S) -BINOL derivative CSP filler provided by the present invention, and the preparation method and use thereof, are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
In this example, BINOL with S configuration was structurally modified to substitute acrylic acid at the 6-position of the naphthalene ring to obtain BINOL S-6-acrylate (S-6-A BINOL), hydroxyl protection was performed at the 1 and 1' positions of S-6-A BINOL to obtain compound (S) -1, and the compound (S) -1 was silanized, then bonded to an acidified silica gel support, and then hydroxyl protection was removed to obtain BINOL S-6-acrylate chiral stationary filler (S-6-A BINOL CSP).
Derivative (S) -1(1.125mmol, 500mg) was dissolved in dry dichloromethane (15mL) in a 50mL single neck flask, followed by the addition of triethylamine (3.375mmol, 0.47mL), stirring for 5 minutes in an ice bath and the addition of 2- (7-oxabenzotriazol) -N, N, N ', N' -tetramethyluronium hexafluorophosphate (1.2375mmol, 470.25 mg). After the ice bath was removed and stirred at room temperature for 30 minutes, 3-aminopropyltriethoxysilane (1.125mmol, 0.26mL) was added and reacted at room temperature for 3 hours, followed by TLC. After completion of the reaction, the mixture was extracted with ethyl acetate (3X 15mL), and the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to give compound (S) -2.
Silica gel (10g) was placed in a 250mL single-neck flask and refluxed with 4M hydrochloric acid (100mL) for 5 hours. After 5 hours, the silica gel was filtered through a sand core funnel, washed to neutrality with water, and vacuum-dried at 150 ℃ for 24 hours. The product, compound (S) -2(1.36g) from the previous step was weighed into a 250mL single-neck flask, the silica gel (3.5g) was acidified and redistilled toluene (100mL) was added and the reaction was refluxed for 12 hours under nitrogen. After the reaction is finished, the reaction product is cooled to room temperature, silica gel is filtered by a sand core funnel, dichloromethane and methanol are used for multiple times of washing, and vacuum drying is carried out for 4 hours at the temperature of 50 ℃ to obtain (S) -3.
(S) -3 obtained in the above step was dissolved in methanol (50mL) in a 100mL single-neck flask, hydrochloric acid (12M, 2mL) was added dropwise, the mixture was stirred at room temperature, and the end point of the reaction was checked by TLC. After the reaction was complete, the silica gel was filtered through a sand-core funnel, washed with methanol several times, and vacuum-dried at 50 ℃ for 4 hours to give S-6-A BINOL CSP (3.64 g).
FIG. 1 is a nuclear magnetic hydrogen spectrum of a compound having the structure shown in formula II; FIG. 2 is a nuclear magnetic hydrogen spectrum of a condensation product; FIG. 3 is a nuclear magnetic carbon spectrum of a condensation product; FIG. 4 is an infrared spectrum of the S-6-A BINOL CSP, and it can be seen from FIGS. 1 to 4 that the S-6-A BINOL CSP prepared by the present invention.
The specific separation parameters of the S-6-A BINOL CSP in the normal phase chromatographic conditions described in this example are as follows:
1. the mobile phases used for resolving the compounds 1,1'-Binaphthol (1,1' -Binaphthol), 5-Methoxyflavanone (5-Methoxyflavanone) and 2'-Hydroxyflavanone (2' -Hydroxyflavanone) are: n-hexane/ethanol/trifluoroacetic acid 99/1/0.1 (v/v/v);
2. the compound Thalidomide (thalidoside) was resolved using a mobile phase of n-hexane/ethanol/trifluoroacetic acid (90/10/0.1 (v/v/v);
3. the compound N- (3,5-Dinitrobenzoyl) - α -phenylethylamine (N- (3,5-Dinitrobenzoyl) -1-phenylethylamine) was resolved using a mobile phase of N-hexane/ethanol/trifluoroacetic acid (97/3/0.1 (v/v/v).
4. The flow rates used were all 1mL/min, the detection wavelength: 220nm, temperature: at 20 ℃. The separation results are shown in Table 1 and FIGS. 5-9, FIG. 5 is a resolution chromatogram of 1,1'-Binaphthol (1,1' -Binaphthol) on S-6-A BINOL CSP, FIG. 6 is a resolution chromatogram of 5-Methoxyflavanone (5-Methoxyflavanone) on S-6-A BINOL CSP, FIG. 7 is a chromatogram of the resolution of 2'-Hydroxyflavanone (2' -Hydroxyflavanone) on S-6-A BINOL CSP, FIG. 8 is a chromatogram of the resolution of Thalidomide (Thalidomide) on S-6-A BINOL CSP, FIG. 9 shows a resolution chromatogram of N- (3,5-Dinitrobenzoyl) - α -phenylethylamine (N- (3,5-Dinitrobenzoyl) -1-phenylethyl-ylamine) on S-6-A BINOL CSP. As can be seen from table 1 and fig. 5 to 9, the S-6-a BINOL CSP prepared in this example can resolve 5 chiral compounds of 1,1'-binaphthol, 5-methoxyflavanone, 2' -hydroxyflavanone, thalidomide and N- (3,5-dinitrobenzoyl) - α -phenylethylamine under a normal phase condition, and the S-6-a BINOL CSP chiral column filled with the chiral column still has good chiral recognition capability after 2000 sample analyses, and can meet the needs of daily pharmaceutical analysis and production quality control.
TABLE 1 separation results of S-6-A BINOL CSP on 5 chiral compounds under normal phase chromatographic conditions
k1': retention factor for the first enantiomer, α: a separation factor. Mobile phase: 1,1'-binaphthol, 5-methoxyflavanone, and 2' -hydroxyflavanone is n-hexane/ethanol/trifluoroacetic acid-99/1/0.1 (v/v/v); thalidomide is n-hexane/ethanol/trifluoroacetic acid 90/10/0.1 (v/v/v); n- (3,5-dinitrobenzoyl) - α -phenylethylamine was N-hexane/ethanol/trifluoroacetic acid-97/3/0.1 (v/v/v). Flow rate: 1 mL/min; temperature: 20 ℃; detection wavelength: 220 nm.
Example 2
In this example, BINOL with S configuration was structurally modified, acrylic acid was substituted at the 6-position of the naphthalene ring to obtain S-6-acrylic acid BINOL (S-6-A BINOL), hydroxyl protection was performed at the 1 and 1' -positions of S-6-A BINOL to obtain compound (S) -1, compound (S) -1 was bonded to aminopropyl silica gel support, and finally dehydroxylation protection was performed to obtain S-6-A BINOL CSP.
Taking 10g of silica gel, 100mL of 4M hydrochloric acid, N2And (3) protective refluxing is carried out for 5h, the mixture is cooled to room temperature, the silica gel is washed to be neutral by using ultrapure water, vacuum drying is carried out for 24h at the temperature of 140 ℃, the acidified silica gel is obtained, and the acidified silica gel is sealed and stored in a shade place for later use. The silica gel (3.5g) was acidified and added to a 250mL three-necked flask containing 100mL of dry toluene, which carried away the residual waterAnd cooling to room temperature. 2 times of 3-aminopropyltriethoxysilane (per m) was added according to the specific surface area of silica gel2The silica gel contains about 8 to 10 mu mol of OH), N2Protecting, heating in oil bath to 110 deg.C slowly, reflux reacting for 4h, naturally cooling to room temperature, filtering, washing with toluene and methanol respectively for three times, vacuum drying at 150 deg.C for 4h to obtain silanized silica gel.
Dissolving the compound (S) -1(1.0g) in 12mL of anhydrous dichloromethane, stirring at 0 ℃ for 5min, adding triethylamine (1.852g) and 2- (7-benzotriazole oxide) -N, N, N ', N' -tetramethylurea hexafluorophosphate (5.575g) to continue reacting for 2h, removing the ice bath, adding silanized silica gel (4.0g) to continue reacting for 24h to obtain (S) -3.
(S) -3 obtained in the above step was dissolved in methanol (50mL) in a 100mL single-neck flask, hydrochloric acid (12M, 2mL) was added dropwise, the mixture was stirred at room temperature, and the end point of the reaction was checked by TLC. After the reaction was complete, the silica gel was filtered through a sand-core funnel, washed with methanol several times, and vacuum-dried at 50 ℃ for 4 hours to give S-6-A BINOL CSP (3.64 g).
FIG. 1 is a nuclear magnetic hydrogen spectrum of a compound (S) -1 having a structure represented by formula II; the S-6-A BINOL CSP obtained in this example was characterized by infrared ray, and the results were similar to those of example 1.
The foregoing is merely a preferred embodiment of the invention and is not intended to limit the invention in any manner. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can be made, and these improvements and modifications should also be construed as the protection scope of the present invention.
Claims (10)
1. The (S) -BINOL derivative CSP filler is characterized in that the structural formula is shown as a formula I;
in the formula I, the compound is shown in the specification,
represents a structural formula of the silica gel carrier after hydrogen is removed.
2. A process for the preparation of a (S) -BINOL derivative CSP filler according to claim 1, characterized by comprising the following steps:
carrying out structural modification on (S) -BINOL, and substituting acrylic acid at the 6-position of a naphthalene ring to obtain S-6-A BINOL;
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
carrying out condensation reaction on a compound with a structure shown in a formula II and a silanization reagent to obtain a condensation product;
and bonding the condensation product to an acidified silica gel carrier, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
3. The preparation method according to claim 2, wherein the condensation reaction time is 3-4 h.
4. A process for the preparation of a (S) -BINOL derivative CSP filler according to claim 1, characterized by comprising the following steps:
carrying out silanization reaction on a silanization reagent and an acidified silica gel carrier to obtain silanized silica gel;
carrying out structural modification on (S) -BINOL, and substituting acrylic acid at the 6-position of a naphthalene ring to obtain S-6-A BINOL;
carrying out hydroxyl protection on the S-6-A BINOL to obtain a compound with a structure shown in a formula II;
and bonding a compound with a structure shown in a formula II to the silanized silica gel, and then carrying out dehydroxylation protection to obtain the (S) -BINOL derivative CSP filler.
5. The method according to claim 4, wherein the silylating agent is 3-aminopropyltriethoxysilane.
6. The method of claim 4, wherein the acidified silica gel support is acidified with silica gel.
7. The method according to claim 6, wherein the silica gel is a spherical or amorphous silica gel for chromatography.
8. The preparation method according to claim 6, wherein the acidifying reagent used for the acidification is hydrochloric acid, the concentration of the hydrochloric acid is 4mol/L, and the dosage ratio of the silica gel to the hydrochloric acid is 10 g: 100 mL.
9. The method of claim 4, wherein the dehydroxylation protection is performed in hydrochloric acid.
10. Use of the (S) -BINOL derivative CSP filler according to claim 1 in the field of chiral resolution.
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