CN115385977A - Method for synthesizing bromo-cholesterol derivative - Google Patents
Method for synthesizing bromo-cholesterol derivative Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 29
- WGEHWCGDFFFRKA-UTLNTRLCSA-N (3S,8S,9S,10R,13S,14S,17R)-16-bromo-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol Chemical class C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(Br)[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 WGEHWCGDFFFRKA-UTLNTRLCSA-N 0.000 title claims abstract description 26
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 20
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000011324 bead Substances 0.000 claims abstract description 11
- 229910001868 water Inorganic materials 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 150000001841 cholesterols Chemical class 0.000 claims abstract description 6
- 239000007800 oxidant agent Substances 0.000 claims abstract description 6
- 238000007259 addition reaction Methods 0.000 claims abstract description 5
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910001928 zirconium oxide Inorganic materials 0.000 claims abstract description 5
- 238000000227 grinding Methods 0.000 claims abstract description 4
- 230000001590 oxidative effect Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract 2
- 239000000047 product Substances 0.000 claims description 28
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 18
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 claims description 18
- 239000007858 starting material Substances 0.000 claims description 13
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 10
- 239000012153 distilled water Substances 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 230000003197 catalytic effect Effects 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 239000012065 filter cake Substances 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 238000010907 mechanical stirring Methods 0.000 claims description 2
- MCPTUMJSKDUTAQ-UHFFFAOYSA-N vanadium;hydrate Chemical compound O.[V] MCPTUMJSKDUTAQ-UHFFFAOYSA-N 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 5
- 238000003912 environmental pollution Methods 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- 238000001514 detection method Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 235000012000 cholesterol Nutrition 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 150000003431 steroids Chemical class 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 3
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229960004544 cortisone Drugs 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- XUGISPSHIFXEHZ-UHFFFAOYSA-N 3beta-acetoxy-cholest-5-ene Natural products C1C=C2CC(OC(C)=O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 XUGISPSHIFXEHZ-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- LJGMGXXCKVFFIS-IATSNXCDSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] decanoate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCCCC)C1 LJGMGXXCKVFFIS-IATSNXCDSA-N 0.000 description 2
- XUGISPSHIFXEHZ-VEVYEIKRSA-N cholesteryl acetate Chemical compound C1C=C2C[C@@H](OC(C)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 XUGISPSHIFXEHZ-VEVYEIKRSA-N 0.000 description 2
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000005151 Cholesterol Decanoate Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229910001513 alkali metal bromide Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910000423 chromium oxide Inorganic materials 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960002089 ferrous chloride Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Abstract
The invention provides a method for synthesizing bromo-cholesterol derivative, which mainly comprises the following steps: cholesterol derivative is used as raw material, oxidant, catalyst and water are added, and then the mixture is subjected to addition reaction with sodium bromide in a zirconium oxide bead grinding medium. The method has the advantages of simple operation, mild reaction conditions, high yield, avoidance of toxicity and corrosivity of liquid bromine, reduction of environmental pollution and safe reaction.
Description
Technical Field
The invention relates to the technical field of synthesis of bromo-cholesterol derivatives, in particular to a method for synthesizing bromo-cholesterol derivatives.
Background
Cholesterol is a white or yellowish crystal that plays an important role in the vital activities of cells. The most widespread use of cholesterol and its derivatives is in the synthesis of other important steroids. However, during the synthesis of other steroids, the double bond at the 5,6 position of cholesterol may participate in the reaction, affecting the synthesis process.
Currently, to solve the above problems, a synthesis method is generally used in which an unsaturated steroid is converted into a 5,6 dihalo-compound, and then the double bond is regenerated using various reagents, such as zinc powder in boiling acetic acid, sodium iodide, ferrous chloride, or chromium oxide; in the preparation process of the dihalo-compound, chlorine needs to be treated, so that in practical use, unsaturated steroids are usually converted into corresponding dibromides, and the post-treatment difficulty and the waste hazard can be reduced while the stability of the synthesis of the cholesterol is improved.
Bromocholesterol is an important intermediate in the synthesis reaction of the steroid cholesterol and has wide application prospect. The existing method for synthesizing bromo-cholesterol uses cholesterol as raw material, organic acid and trace acetate as catalysts in an organic solvent, and the bromo-cholesterol is prepared by addition reaction of the raw material and liquid bromine at-20-50 ℃ and oxidation of hypochlorite/TEMPO/alkali metal bromide system. However, in this method, it is required to be carried out at-20 ℃ to 50 ℃ and liquid bromine has toxic and corrosive characteristics, resulting in limited application of the method.
Therefore, the method for synthesizing the bromo-cholesterol derivative, which is simple and safe to operate, mild in reaction conditions and high in yield, has important significance for synthesizing the cholesterol.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides a method for synthesizing bromo-cholesterol derivative, which comprises the step of carrying out addition reaction on the bromo-cholesterol derivative serving as a raw material and sodium bromide in a zirconium oxide bead grinding medium after adding an oxidant, a catalyst and water. The method has the advantages of simple operation, mild reaction conditions, high yield, avoidance of toxicity and corrosivity of liquid bromine, reduction of environmental pollution and safe reaction, and is suitable for wide popularization and application.
The technical scheme of the invention is as follows:
a method for synthesizing bromo-cholesterol derivative mainly comprises the following steps: the cholesterol derivative is used as a raw material, and after an oxidant, a catalyst and water are added, the cholesterol derivative and sodium bromide are subjected to addition reaction in a zirconium oxide bead grinding medium.
Further, the weight ratio (g/g) of the raw materials to the zirconia beads is 1: 35-60; the weight ratio (g/g) of the raw material to the sodium bromide is 1: 0.5-0.9; the weight volume ratio (g/m 1) of the raw material to the water is 1: 13-21.
Further, the oxidizing agent is hydrogen peroxide.
Further, the catalyst is concentrated sulfuric acid and vanadium pentoxide.
Further, the weight ratio (g/g) of the raw material to the hydrogen peroxide is 1: 0.9-1.5; the weight ratio (g/g) of the raw material to the concentrated sulfuric acid is 1: 1.6-2.5; the weight ratio (g/g) of the raw material to the vanadium pentoxide is 1: 0.04-0.07.
Further, the preparation method of the bromo-cholesterol comprises the following steps:
(1) Taking a cholesterol derivative as a starting material, adding sodium bromide as an addition reagent, then sequentially adding vanadium pentoxide, water and zirconia beads, and mechanically stirring to obtain a solution A;
(2) Dropwise adding concentrated sulfuric acid and hydrogen peroxide in the solution A in sequence for catalytic oxidation, and continuously mechanically stirring for 6-24h at room temperature to obtain a solution B;
(3) And filtering the solution B under reduced pressure, washing the solution B with distilled water for multiple times, and freeze-drying the obtained filter cake to obtain the product, namely the bromo-cholesterol derivative.
Further, in the step (1), the mechanical stirring speed is 500 to 1000 rpm.
Further, in step (3), washing with distilled water was performed 3 times.
Compared with the prior art, the invention has the beneficial effects that:
1. the method provided by the invention has the advantages of simple operation, mild reaction conditions, high yield, avoidance of toxicity and corrosivity of liquid bromine, reduction of environmental pollution and safe reaction. So that the method is suitable for wide popularization and application.
2. In the method provided by the invention, the yield is up to more than 75%.
Drawings
In order to more clearly illustrate the embodiments or technical solutions in the prior art of the present invention, the drawings used in the description of the embodiments or prior art will be briefly described below, and it is obvious for those skilled in the art that other drawings can be obtained based on these drawings without creative efforts.
FIG. 1 is a thin layer chromatogram of example 1.
FIG. 2 is a NMR hydrogen spectrum of the product provided in example 1.
FIG. 3 is a NMR carbon spectrum of the product provided in example 1.
FIG. 4 is a thin layer chromatogram of example 2.
FIG. 5 is a NMR spectrum of the product provided in example 2.
FIG. 6 is a NMR carbon spectrum of the product provided in example 2.
FIG. 7 is a thin layer chromatogram of example 3.
FIG. 8 is a NMR spectrum of the product provided in example 3.
FIG. 9 is a NMR carbon spectrum of the product provided in example 3.
Detailed Description
In order to make those skilled in the art better understand the technical solutions in the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In the following examples of the present invention, analytical methods referred to include thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry.
Example 1 starting material was cholesterol acetate
1. A method for synthesizing bromo-cholesterol derivatives comprises the following specific steps:
(1) Taking 1.7g of cholesterol acetate as a starting material, adding 1.2g of sodium bromide as an addition reagent, sequentially adding 0.09g of vanadium pentoxide, 30ml of water and 80g of zirconia beads, and mechanically stirring to obtain a solution A;
(2) Dropwise adding 3.6g of concentrated sulfuric acid and 2.1g of hydrogen peroxide into the solution A in sequence for catalytic oxidation, and continuously mechanically stirring for 6 hours at room temperature to obtain a solution B;
(3) The solution B was filtered under reduced pressure, washed 3 times with 60ml of distilled water, and the obtained cake was freeze-dried to obtain 2.59g of 5 α,6 β -dibromocholestane-3 β -acetate, which was a product with a yield of 86.6%.
2. Analysis and detection
1) Thin-layer chromatography: dissolving the raw materials and products with ethyl acetate, using petroleum ether as developing agent, using concentrated sulfuric acid and ethanol 1: 19 as developer, blowing to develop color with hot air gun, and finding the result in FIG. 1; in FIG. 1, a is the starting material and b is the product; from FIG. 1, it can be seen that the ratio shift of the raw material is 0.46, the ratio shift of the product is 0.20, 0.40, and the reaction is judged to be completed.
2) Nuclear magnetic resonance spectroscopy:
detecting the product by NMR spectroscopy, wherein the detection map is shown in figure 2 and figure 3, and the data obtained by detection are as follows:
1 H NMR(400MHz，CDCl 3 )δ5.48(m，1H)，4.83(t，1H)，2.04(s，3H)，1.46(s，3H)，0.70(s，3H).
13 C NMR(101MHz，CDCl 3 )δ169.42，87.04，70.99，55.09，54.07，46.17，41.63，40.88，40.79，38.51，38.45，36.13，35.42，35.06，34.72，29.75，27.13，26.98，25.13，23.00，22.75，21.80，21.54，20.34，19.11，17.61，11.16；
3) Mass spectrometry
From the mass spectrometric detection results, it can be seen that there is an excimer ion peak of the target product at m/z 609.1917, which coincides with the calculated molecular weight, indicating that the product molecular weight is correct.
Example 2 starting material is cortisone
1. A method for synthesizing bromo-cholesterol comprises the following specific steps:
(1) Taking 1.44g of cortisone as a starting material, adding 1.2g of sodium bromide as an addition reagent, sequentially adding 0.09g of vanadium pentoxide, 30ml of water and 80g of zirconia beads, and mechanically stirring to obtain a solution A;
(2) Dropwise adding 3.6g of concentrated sulfuric acid and 2.1g of hydrogen peroxide into the solution A in sequence for catalytic oxidation, and continuously mechanically stirring for 24 hours at room temperature to obtain a solution B;
(3) The solution B was filtered under reduced pressure and washed 3 times with 60ml of distilled water, and the resulting filter cake was freeze-dried to give 2.17g of 4 α,5 β -dibromocortisone at a yield of 79.5%. .
2. Analysis and detection
1) Thin-layer chromatography: preliminarily judging whether the product after freeze drying is reacted by thin layer chromatography, dissolving cortisone and 4 alpha, 5 beta-dibromocortisone by dichloromethane, taking dichloromethane and ethyl acetate with the ratio of 3: 1 as developing agent, and taking concentrated sulfuric acid and ethanol with the ratio of 1: 19 as color developing agent, wherein the result is shown in figure 4; in FIG. 4, a is the starting material and b is the product; as can be seen from FIG. 4, the ratio shift value of the starting material was 0.09, and the ratio shift value of the product was 0.24, and the reaction was judged to be complete.
2) Nuclear magnetic resonance spectroscopy:
performing NMR detection on the product after replacement with heavy water, wherein the chromatogram is shown in FIG. 5 and FIG. 6; the data obtained by detection are as follows:
1 H NMR(400MHz，CDCl 3 ，D 2 O change)δ4.90(s，1H)，4.62(d，1D)，4.27(m，1H)，1.98(m，3H)，0.61(d，3H).
13 C NMR(101MHz，CDCl 3 )δ 89.13，88.05，67.44，60.39，52.55，51.76，49.87，49.75，41.65，35.23，34.92，34.51，33.47，32.72，28.85，23.28，17.10，15.92.
3) Mass spectrometry
From the mass spectrum detection result, the excimer ion peak of the target product is present at the m/z of 530.6402, which is consistent with the calculated molecular weight, and the molecular weight of the product is correct.
Example 3 starting material is cholesteryl decanoate
1. A method for synthesizing bromo-cholesterol derivatives comprises the following specific steps:
(1) Taking 2.16g cholesterol decanoate as a starting material, adding 1.2g sodium bromide as an addition reagent, sequentially adding 0.09g vanadium pentoxide, 30ml water and 80g zirconium oxide beads, and mechanically stirring to obtain a solution A;
(2) Dropwise adding 3.6g of concentrated sulfuric acid and 2.1g of hydrogen peroxide into the solution A in sequence for catalytic oxidation, and continuously mechanically stirring for 20 hours at room temperature to obtain a solution B;
(3) The solution B was filtered under reduced pressure, washed 3 times with 60ml of distilled water, and the obtained cake was freeze-dried to obtain 2.62g of the product 5 α,6 β -dibromocholestane-3 β -decanoate with a yield of 75.9%.
2. Analysis and detection
1) Thin-layer chromatography: the raw materials and products were dissolved in dichloromethane, petroleum ether as developing agent, concentrated sulfuric acid and ethanol 1: 19 as color developing agent, and blown to color development by hot air gun, the result is shown in FIG. 7; in FIG. 7, a is the starting material and b is the product; as can be seen from FIG. 7, the ratio shift of the raw material is 0.50, the ratio shift of the product is 0.55, and the difference between the two values is significant, thus judging that the reaction is completed.
2) Nuclear magnetic resonance spectroscopy:
detecting the product by NMR spectroscopy, with the spectra shown in FIG. 8 and FIG. 9; the data obtained by detection are as follows:
1 H NMR(400MHz，CDCl 3 )δ5.48(m，1H)，4.83(t，1H)，2.28(s，3H)，1.46(s，3H)，0.70(s，3H).
13 C NMR(101MHz，CDCl 3 )δ173.27，88.15，71.75，56.15，56.07，55.14，47.24，42.68，41.95，41.86，39.58，39.51，37.21，36.51，36.13，35.78，34.59，31.90，30.81，29.46，29.30，29.15，28.20，28.04，26.23，25.04，24.07，23.81，22.86，22.72，22.60，21.29，20.18，18.68，14.18，12.22.
3) Mass spectrometry
From the mass spectrometric results, it can be seen that there is an excimer ion peak of the target product at m/z 721.3164, which corresponds to the calculated molecular weight, indicating that the product molecular weight is correct.
Although the present invention has been described in detail by referring to the preferred embodiments, the present invention is not limited thereto. Various equivalent modifications or substitutions can be made on the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and these modifications or substitutions are within the scope of the present invention/any person skilled in the art can easily conceive of the changes or substitutions within the technical scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (8)
1. A method for synthesizing bromo-cholesterol derivative is characterized by comprising the following main processes: cholesterol derivative is used as raw material, oxidant, catalyst and water are added, and then the mixture is subjected to addition reaction with sodium bromide in a zirconium oxide bead grinding medium.
2. The method of synthesizing bromocholesterol derivatives according to claim 1, wherein the weight ratio (g/g) of the raw material to zirconia beads is 1: 35-60; the weight ratio (g/g) of the raw materials to the sodium bromide is 1: 0.5-0.9; the weight volume ratio (g/m 1) of the raw material to the water is 1: 13-21.
3. The method of synthesizing the bromo-cholesterol derivative of claim 1 wherein said oxidizing agent is hydrogen peroxide.
4. The method of synthesizing bromo-cholesterol derivative according to claim 3 wherein said catalyst is concentrated sulfuric acid and vanadium pentoxide.
5. The method for synthesizing the bromo-cholesterol derivative according to claim 4, wherein the weight ratio (g/g) of said starting material to hydrogen peroxide is 1: 0.9-1.5; the weight ratio (g/g) of the raw material to the concentrated sulfuric acid is 1: 1.6-2.5; the weight ratio (g/g) of the raw material to the vanadium pentoxide is 1: 0.04-0.07.
6. The method of synthesizing bromo-cholesterol derivatives according to claim 5, wherein the process is as follows:
(1) Taking a cholesterol derivative as a starting material, adding sodium bromide as an addition reagent, then sequentially adding vanadium pentoxide, water and zirconia beads, and mechanically stirring to obtain a solution A;
(2) Dropwise adding concentrated sulfuric acid and hydrogen peroxide in the solution A in sequence for catalytic oxidation, and continuously mechanically stirring for 6-24h at room temperature to obtain a solution B;
(3) And filtering the solution B under reduced pressure, washing the solution B with distilled water for multiple times, and freeze-drying the obtained filter cake to obtain the product, namely the bromo-cholesterol derivative.
7. The process for synthesizing bromocholesterol derivatives according to claim 6, wherein in step (1), the mechanical stirring speed is 500 to 1000 rpm.
8. The method for synthesizing bromocholesterol according to claim 6, wherein in step (3), washing with distilled water is performed 3 times.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1835888A (en) * | 2003-05-30 | 2006-09-20 | 科学与工业研究委员会 | Process for prepn of non-hazardous brominating agent |
| US20170158729A1 (en) * | 2014-07-30 | 2017-06-08 | Zhejiang University Of Technology | Method of synthesizing 25-hydroxy cholesterol |
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- 2022-09-02 CN CN202211076881.6A patent/CN115385977A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1835888A (en) * | 2003-05-30 | 2006-09-20 | 科学与工业研究委员会 | Process for prepn of non-hazardous brominating agent |
| US20170158729A1 (en) * | 2014-07-30 | 2017-06-08 | Zhejiang University Of Technology | Method of synthesizing 25-hydroxy cholesterol |
Non-Patent Citations (2)
| Title |
|---|
| KAZUHIRO YONEHARA ET AL.: "An efficient H2O2-based oxidative bromination of alkenes, alkynes, and aromatics by a divanadium-substituted phosphotungstatew", 《CHEM. COMMUN.》, vol. 47, pages 1692 * |
| MACIEJ STODULSKI ET AL.: "Halocarbocyclization versus dihalogenation: substituent directed iodine(III) catalyzed halogenations", 《CHEM. COMMUN.》, vol. 50, pages 3455 * |
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