CN1197844C - Method for preparing cis-vitamin D or derivative thereof by sensitization of solid-phase photosensitizer with silica gel as carrier - Google Patents
Method for preparing cis-vitamin D or derivative thereof by sensitization of solid-phase photosensitizer with silica gel as carrier Download PDFInfo
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- CN1197844C CN1197844C CN 02117381 CN02117381A CN1197844C CN 1197844 C CN1197844 C CN 1197844C CN 02117381 CN02117381 CN 02117381 CN 02117381 A CN02117381 A CN 02117381A CN 1197844 C CN1197844 C CN 1197844C
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- silica gel
- vitamins
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- ether
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- 239000003504 photosensitizing agent Substances 0.000 title claims abstract description 60
- 239000011710 vitamin D Substances 0.000 title claims abstract description 57
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 239000000741 silica gel Substances 0.000 title claims abstract description 35
- 229910002027 silica gel Inorganic materials 0.000 title claims abstract description 35
- 239000007790 solid phase Substances 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 29
- 206010070834 Sensitisation Diseases 0.000 title claims abstract description 11
- 230000008313 sensitization Effects 0.000 title claims abstract description 11
- 229940046008 vitamin d Drugs 0.000 title abstract description 10
- 150000003722 vitamin derivatives Chemical class 0.000 title abstract 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 claims description 4
- 239000012188 paraffin wax Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N trimethylbenzene Natural products CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 claims description 3
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 150000004292 cyclic ethers Chemical class 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229920000570 polyether Polymers 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- -1 trimethylbenzene aromatic hydrocarbon Chemical class 0.000 claims 1
- 230000001235 sensitizing effect Effects 0.000 abstract description 9
- 239000000047 product Substances 0.000 abstract description 8
- 235000019166 vitamin D Nutrition 0.000 abstract description 6
- 238000005406 washing Methods 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 5
- 238000001914 filtration Methods 0.000 abstract description 4
- 229930003316 Vitamin D Natural products 0.000 abstract description 3
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 abstract description 3
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 1
- 230000001678 irradiating effect Effects 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 229960001866 silicon dioxide Drugs 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000005286 illumination Methods 0.000 description 10
- 208000017983 photosensitivity disease Diseases 0.000 description 10
- 231100000434 photosensitization Toxicity 0.000 description 10
- 238000012544 monitoring process Methods 0.000 description 6
- 238000001556 precipitation Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000004061 bleaching Methods 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000006392 deoxygenation reaction Methods 0.000 description 4
- 238000010812 external standard method Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 4
- 229910052753 mercury Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- XQFJZHAVTPYDIQ-LETJEVNCSA-N (1s)-3-[(e)-2-[(1r,3ar,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl]ethenyl]-4-methylcyclohex-3-en-1-ol Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)/C=C/[C@H](C)C(C)C)\C=C\C1=C(C)CC[C@H](O)C1 XQFJZHAVTPYDIQ-LETJEVNCSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- YUGCAAVRZWBXEQ-WHTXLNIXSA-N previtamin D3 Chemical compound C=1([C@@H]2CC[C@@H]([C@]2(CCC=1)C)[C@H](C)CCCC(C)C)\C=C/C1=C(C)CC[C@H](O)C1 YUGCAAVRZWBXEQ-WHTXLNIXSA-N 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- BUNBVCKYYMRTNS-UHFFFAOYSA-N tachysterol Natural products C=1CCC2(C)C(C(C)CCC(C)C(C)C)CCC2C=1C=CC1=C(C)CCC(O)C1 BUNBVCKYYMRTNS-UHFFFAOYSA-N 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001354 calcination Methods 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 230000003245 working effect Effects 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- JCJNNHDZTLRSGN-UHFFFAOYSA-N anthracen-9-ylmethanol Chemical compound C1=CC=C2C(CO)=C(C=CC=C3)C3=CC2=C1 JCJNNHDZTLRSGN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003837 high-temperature calcination Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of synthesizing vitamin D and derivatives thereof by a photochemical method, and particularly relates to a method for preparing cis-vitamin D or derivatives thereof by sensitizing a solid-phase photosensitizer taking silica gel as a carrier. Dissolving trans-vitamin D or derivatives thereof in a solvent, adding a solid phase photosensitizer mainly composed of a carrier and a photosensitive group, wherein the carrier is silica gel, the molar ratio of the photosensitive group of the solid phase photosensitizer to the trans-vitamin D or derivatives thereof is 1: 100 to 1000: 1, and performing sensitization reaction by irradiating with light of 300nm to 1000nm to obtain a sensitization reaction product cis-vitamin D or derivatives thereof. After the reaction is finished, the photosensitizer and the product can be completely separated by simple filtration and washing, the method can reduce the using amount of the sensitizer, simplifies the purification and separation process, is suitable for large-scale industrial production, and is favorable for environmental protection.
Description
Technical field
The invention belongs to photochemical method synthesis of vitamin d and the derivative field thereof of utilizing, particularly is the method that the solid phase photosensitizer sensitization of carrier prepares cis-vitamins D or derivatives thereof with silica gel.
Background technology
Trans-vitamins D and the reaction of derivative intramolecular photosensitization thereof are the important reactions of step during activated vitamin D synthesizes, and trans-vitamins D or derivatives thereof is converted into cis-vitamins D or derivatives thereof, for example activated vitamin D in the presence of photosensitizers
2And D
3
A large amount of researchs show, trans-vitamins D or derivatives thereof can be converted into cis-vitamins D or derivatives thereof by the intramolecular photosensitization reaction in the presence of suitable photosensitizers, and the toxic byproduct tachysterol that generates in the vitamins D production can be converted into Previtamin D.
The organic molecule photosensitizers is the simplest can directly use a kind of, because there is the intensive bleaching action in photosensitizers, usually need to use excessive greatly sensitizing agent (amount of sensitizing agent is times over reaction substrate) to finish this intramolecular photosensitization reaction (people such as J.W.J.Gielen, J.Rol.Netherlands Chem.Soc.1980,99,306), reaction back photosensitizers and photosensitizers bleaching product can only be finished by column chromatography for separation with separating of reaction product, this separation method cost height is unsuitable for scale operation.People such as K.H.Pfoertner have invented water-soluble photosensitizers (J.Chem.Soc., Perkin Trans.1991, (2), 523-530), reaction finishes back water method of extraction photosensitizers is removed from reaction system, though avoided column chromatography for separation to remove the trouble of photosensitizers, this can generate a large amount of waste water in scale operation, still can bring very big trouble in industrial production.
In order to improve this technology, Clarke E.Slemon (EP 0 252 740/1988) has invented the soluble high-molecular photosensitizers, and use it for the intramolecular photosensitization reaction that the toxic byproduct tachysterol that generates in the vitamins D production is converted into Previtamin D, polymer photosensitizer and reaction substrate are dissolved in the solvent, the intramolecular photosensitization reaction is carried out in illumination, after reaction finishes, add precipitation agent and make the polymer photosensitizer precipitation, with washing sensitizing agent is separated through filtering with product again, though this method has been saved the column chromatography for separation process, but can be in the polymer photosensitizer precipitation process with the product inclusion, portion of product and polymer photosensitizer co-precipitation, sensitizing agent need repeatedly dissolve with thoroughly separating of product, precipitation process, use a large amount of solvents, and the mixed solvent that reclaims must purified processing with they separated from one another could repeated uses, this has brought very big trouble for the production application process, and some solvent formation azeotrope can't separate at all, cause the waste of a large amount of solvents, and bring serious environmental issue.(US 5 035 783 for people such as Eric Goethals, US 5 175217) invented another kind of soluble high-molecular photosensitizers, use it for the toxic byproduct tachysterol that generates in the vitamins D production and be converted into Previtamin D, the intramolecular photosensitization that is converted into the cis-vitamins D with the trans-vitamins D reacts, reaction finishes the back makes the polymer photosensitizer precipitation by changing protonic acids such as temperature or adding hydrochloric acid, there is the problem of raw material and product and photosensitizers co-precipitation on the one hand in this method, on the other hand because vitamin d compounds is very responsive to acid, under acidic conditions multiple isomerization reaction can take place, can generate more by product when using acid as precipitation agent in system.The contriver also finds under study for action, and the bleaching speed of soluble high-molecular photosensitizers and corresponding small molecules photosensitizer-like seemingly are connected the stability that can not increase photosensitizers on the soluble high-molecular with the small molecules photosensitizers, prolong the work-ing life of photosensitizers.
Summary of the invention
The purpose of this invention is to provide a kind of economy, be the method that the solid phase photosensitizer sensitization of carrier prepares cis-vitamins D or derivatives thereof with silica gel easily.Utilize this type of solid phase photosensitizer can finish of the reaction of trans-vitamins D or derivatives thereof intramolecular photosensitization expeditiously for cis-vitamins D or derivatives thereof, this class can be separated with reaction system by filtration, washing process simply with the solid phase photosensitizer of silica gel as carrier, and can reclaim silica-gel carrier by high-temperature calcination.
Of the present invention is the solid phase photosensitizer of carrier with silica gel, prepares the method for cis-vitamins D or derivatives thereof by the sensitization isomerization reaction:
Trans-vitamins D or derivatives thereof is dissolved in the solvent, add the solid phase photosensitizer of mainly forming by carrier and photosensitive group, wherein carrier is a silica gel, the photosensitive group of solid phase photosensitizer and trans-vitamins D or derivatives thereof molecule mol ratio are 1: 100 to 1000: 1, with the rayed of about 300nm to 1000nm, carry out sensitized reaction, obtain sensitized reaction product cis-vitamins D or derivatives thereof.
Described is that the upload rate of photosensitive group on silica gel can be 1 * 10 in the solid phase photosensitizer of carrier with silica gel
-4Mmole/gram is to 1 mmole/gram scope; After sensitized reaction finishes, these with silica gel be the solid phase photosensitizer of carrier can be easily by filter, washing remove from reaction system, separate with sensitized reaction product cis-vitamins D or derivatives thereof.
Described sensitized reaction carries out in the presence of nitrogen or argon gas.
Described is that the photosensitive group of the solid phase photosensitizer of carrier links to each other with silica gel with covalent linkage with silica gel.
Described photosensitive group is the anthracene chromophoric group, and photosensitive group can not have substituting group or has substituting group.
Substituting group on the described photosensitive group is alkyl, ester group, acyl group, ether or the aldehyde radical of 1 to 6 carbon, and halogen, hydroxyl, carboxyl or amino etc.
Described is that anthracene chromophoric group in the solid phase photosensitizer of carrier links to each other with silica gel with covalent linkage by reaction with silica gel.
Described solvent is straight-chain paraffin, branched paraffin or the naphthenic hydrocarbon of five to 18 carbon, benzene,toluene,xylene, aromatic hydrocarbon such as trimethylbenzene; Lower alcohols such as methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, amylalcohol, hexanol; Ether solvents such as open chain ether, cyclic ether and polyethers such as ether, propyl ether, isopropyl ether, methyl tertiary butyl ether, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether; And these solvents mix the mixed solvent that obtains each other.
The present invention carries out the intramolecular photosensitization reaction in the presence of the solid phase photosensitizer that with silica gel is carrier, finish the back by simple filtering, washing in reaction, can finish thoroughly separating of photosensitizers and product, simplified sepn process greatly, and immobilized photosensitizers on silica gel, owing to can go up carrying capacity by control, avoided being in contact with one another between (removing) photosensitizers group, the mutual quencher between photosensitizers (removing) group and the generation of dimerization have been stoped, weaken the bleaching action of photosensitizers, prolonged the work-ing life of photosensitizers.This use with silica gel can be reduced the consumption of sensitizing agent as the method for the solid phase photosensitizer of carrier, simplified the purifies and separates process, is applicable to large-scale commercial production.Because silica gel is a kind of very stable inorganic materials, depleted is that the solid phase photosensitizer of carrier can reclaim silica gel by calcining with silica gel, help environmental protection, and silica gel is a kind of material very cheap and easy to get.
Embodiment
Embodiment 1.
With silica gel sensitizing agent synthetic of carrier
Take by weighing 1.8 grams and join in 10 milliliters of tetrahydrofuran (THF)s, add 2.6 gram propanedioic acid, 2.2 gram dicyclohexylcarbodiimide, 0.12 gram 4-Dimethylamino pyridine, stirring at room 3 days at 550 ℃ of silica gel of calcining 2 hours down.Filter, the solid water, ethanol, washing with acetone, vacuum-drying is weighed as 2.3 grams.Taking by weighing above-mentioned load has silica gel 2.2 grams of propanedioic acid to join in 20 milliliters of tetrahydrofuran (THF)s, adds 0.70 gram 9-anthryl carbinol and 2 gram dicyclohexylcarbodiimide, 0.5 gram 4-Dimethylamino pyridine, stirring at room 2 days.Stopped reaction filters, solid acetone, and ethanol, methyl alcohol, toluene wash no longer includes the uv-absorbing of anthracene until filtrate.Be weighed as 1.33 grams after the drying.
It is 5 * 10 that experiment records the upload rate of anthracene on silica gel
-5Moles per gram.Be labeled as Silica-AnI.
Replace propanedioic acid with hexanodioic acid, same method makes Silica-AnII, and the rate of uploading is 4 * 10
-4Moles per gram.
Embodiment 2.
With synthetic Silica-AnI among the embodiment 1 is photosensitizers, and ethanol is solvent sensitization trans-vitamins D
3To the cis-vitamins D
3Reaction
Preparation trans-vitamins D
35 milliliters of ethanolic solns, concentration is 8.0 * 10
-4Mol, add that synthetic is the solid phase photosensitizer Silica-AnI of carrier with silica gel among 20 milligrams of embodiment 1, logical nitrogen deoxygenation is after 20-30 minute, with the high voltage mercury lamp is light source, carry out illumination with 300nm to the light of 1000nm, keep logical nitrogen in the illumination process, nitrogen is saturated with solvent earlier, use the high performance liquid chromatography monitoring reaction, the cis-vitamins D
3With the trans-vitamins D
3Content determine that by external standard method anti-quick isomerization reaction the results are shown in table one.
Table one. intramolecular photosensitization reaction kinetics monitoring result
| Light application time/minute | The Cis-vitamins D 3％(w/w) | The trans-vitamins D 3％(w/w) |
| 0 | -- | 100 |
| 5 | 62.1 | 33.1 |
| 10 | 81.8 | 10.38 |
Embodiment 3.
With embodiment 1 synthetic solid phase sensitizing agent Silica-AnI is photosensitizers, is solvent sensitization trans-vitamins D with toluene
3To the cis-vitamins D
3Reaction
Preparation trans-vitamins D
35 milliliters of ethanolic solns, concentration is 8.0 * 10
-4Mol, add that synthetic is the solid phase photosensitizer Silica-AnI of carrier with silica gel among 20 milligrams of embodiment 1, logical nitrogen deoxygenation is after 20-30 minute, with the high voltage mercury lamp is that light source carries out illumination, filter light below the 300nm with spectral filter, keep logical nitrogen in the illumination process, nitrogen is saturated with solvent earlier, use the high performance liquid chromatography monitoring reaction, the cis-vitamins D
3With the trans-vitamins D
3Content determine by external standard method, the results are shown in table two.
Table two. intramolecular photosensitization reaction kinetics monitoring result
| Light application time/minute | The cis-vitamins D 3Amount % (w/w) | The trans-vitamins D 3Amount % (w/w) |
| 0 | -- | 100 |
| 5 | 31.8 | 71.6 |
| 10 | 55.5 | 47.9 |
| 15 | 76.3 | 21.4 |
| 25 | 86.8 | 7.5 |
Embodiment 4.
With embodiment 1 synthetic solid phase photosensitizer Silica-AnII sensitization trans-vitamins D
3To the cis-vitamins D
3Reaction
Preparing 5 ml concns is 8 * 10
-4The trans-vitamins D of mol
3Ethanolic soln, add 30 milligrams of synthetic solid phase sensitizing agent Silica-AnII in embodiment 1 therein, logical nitrogen deoxygenation is after 30 minutes, with the high voltage mercury lamp is that light source carries out illumination, filter light below the 300nm with spectral filter, keep logical nitrogen in the illumination process, nitrogen is saturated with solvent earlier, use the high performance liquid chromatography monitoring reaction, the cis-vitamins D
3With the trans-vitamins D
3Content determine by external standard method.After the illumination 15 minutes, the cis-vitamins D
3Productive rate be 33%.
Embodiment 5.
The reuse of synthetic solid phase photosensitizer Silica-AnI experiment among the embodiment 1
Compound concentration is 8.8 * 10
-4The trans-vitamins D of mol
3Ethanolic soln, get this solution of 5ml, and add synthetic solid phase photosensitizer Silica-AnI among 30 milligrams of embodiment 1 therein, logical nitrogen deoxygenation was that light source carries out illumination with the high voltage mercury lamp after 30 minutes, filtered light below the 300nm with spectral filter, keep logical nitrogen in the illumination process, nitrogen is saturated with solvent earlier, uses the high performance liquid chromatography monitoring reaction, the cis-vitamins D
3With the trans-vitamins D
3Content determine that by external standard method after each reaction finishes, photosensitizers Silica-AnI reclaimed reuse, photosensitizers Silica-AnI recycling the results are shown in table three.
The recycling situation of table three .Silica-AnI
| The reaction repeated circulation | The cis-vitamins D 3％(w/w) | The trans-vitamins D 3％(w/w) |
| 1 | 82.9 | 13.8 |
| 2 | 80.2 | 16.5 |
| 3 | 79.0 | 17.2 |
Claims (7)
1. one kind is the method that the solid phase photosensitizer sensitization of carrier prepares cis-vitamins D or derivatives thereof with silica gel, it is characterized in that:
Trans-vitamins D or derivatives thereof is dissolved in the solvent, add the solid phase photosensitizer of mainly forming by carrier and photosensitive group, wherein carrier is a silica gel, the photosensitive group of solid phase photosensitizer and trans-vitamins D or derivatives thereof molecule mol ratio are 1: 100 to 1000: 1, with the rayed of 300nm to 1000nm, carry out sensitized reaction, obtain sensitized reaction product cis-vitamins D or derivatives thereof;
The upload rate of described photosensitive group on silica gel is 1 * 10
-4Mmole/gram is to 1 mmole/gram scope.
2. the method for claim 1, it is characterized in that: described sensitized reaction carries out in the presence of nitrogen or argon gas.
3. the method for claim 1 is characterized in that: described is that the photosensitive group of the solid phase photosensitizer of carrier links to each other with silica gel with covalent linkage with silica gel.
4. the method for claim 1, it is characterized in that: described photosensitive group is the anthracene chromophoric group.
5. as claim 1 or 4 described methods, it is characterized in that: described photosensitive group has substituting group.
6. method as claimed in claim 4 is characterized in that: the substituting group on the described photosensitive group is alkyl, ester group, acyl group, ether or the aldehyde radical of 1 to 6 carbon, and halogen, hydroxyl, carboxyl or amino.
7. the method for claim 1, it is characterized in that: described solvent is straight-chain paraffin, branched paraffin or the naphthenic hydrocarbon of five to 18 carbon; Benzene,toluene,xylene, trimethylbenzene aromatic hydrocarbon; Methyl alcohol, ethanol, propyl alcohol, Virahol, butanols, amylalcohol, hexanol lower alcohol; Ether, propyl ether, isopropyl ether, methyl tertiary butyl ether, tetrahydrofuran (THF), dioxane, glycol dimethyl ether, ethylene glycol diethyl ether open chain ether, cyclic ether or polyethers; And these solvents mix the mixed solvent that obtains each other.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02117381 CN1197844C (en) | 2002-05-22 | 2002-05-22 | Method for preparing cis-vitamin D or derivative thereof by sensitization of solid-phase photosensitizer with silica gel as carrier |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02117381 CN1197844C (en) | 2002-05-22 | 2002-05-22 | Method for preparing cis-vitamin D or derivative thereof by sensitization of solid-phase photosensitizer with silica gel as carrier |
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| Publication Number | Publication Date |
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| CN1459446A CN1459446A (en) | 2003-12-03 |
| CN1197844C true CN1197844C (en) | 2005-04-20 |
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| CN 02117381 Expired - Fee Related CN1197844C (en) | 2002-05-22 | 2002-05-22 | Method for preparing cis-vitamin D or derivative thereof by sensitization of solid-phase photosensitizer with silica gel as carrier |
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