CN1257077A - 3 beta-hydroxy-5-cholenic acid ester derivant, synthesis process and use thereof - Google Patents

3 beta-hydroxy-5-cholenic acid ester derivant, synthesis process and use thereof Download PDF

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CN1257077A
CN1257077A CN 99119809 CN99119809A CN1257077A CN 1257077 A CN1257077 A CN 1257077A CN 99119809 CN99119809 CN 99119809 CN 99119809 A CN99119809 A CN 99119809A CN 1257077 A CN1257077 A CN 1257077A
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beta
hydroxies
cholenic acid
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CN1111167C (en
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闻建勋
沈悦海
陈锡敏
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention relates to a 3 beta-hydroxy-5-cholenic acid ester type fluorinated derivative, its synthesis method and application for making liquid crystal material. Said invention also provides its molecular formula.

Description

3 beta-hydroxy-5-cholenic acid ester derivant preparation method and uses
The present invention relates to a kind of fluorine-containing steroidal 3 beta-hydroxy-5-cholenic acid ester derivants, synthetic method and be used for the purposes of liquid crystal material.
Over more than 100 year, liquid crystal research has obtained significant progress, finds also that so far 12 kinds of smectic phases and 12 kinds of chiral smectic are mutually.The appearance of the seventies liquid-crystal display has produced a brand-new industrial colony, as portable computer, Die elektrische Zeituhr and notebook computer subsequently etc.The continuous development of lcd technology has proposed new requirement to liquid crystal material, as require liquid crystal material to have higher voltage conservation rate and bigger coefficient of elasticity to improve contrast gradient, bigger dielectric anisotropy, lower viscosity and higher degree of birefringence are to realize low voltage drive and to improve response speed etc., fluorinated liquid crystal can satisfy above-mentioned most of requirement, and chemical property is stable, has become the focus of present liquid crystal research.Aspect the structure and phase transition property of steroid liquid crystal, reported more in the past, but with rodlike molecule mesomorphic phase ratio, the research of steroid liquid crystal is also insufficient, and up to now, report at steroid class fluorinated liquid crystal is comparatively limited, Wen Jianxun etc. once reported " sterol polyfluoro aromatic ester, preparation method and use " (CN98110842.3), " ferroelectric type fluorine-containing steroid liquid crystal, preparation method and its usage " (CN99113424.9) etc., in order to satisfy people's needs growing, need constantly to explore novel liquid crystal compound to liquid-crystal display.
The object of the invention provides a kind of novel liquid crystalline cpd, specifically a kind of 3 beta-hydroxy-5-cholenic acid ester derivants.
Purpose of the present invention also provides a kind of method of synthetic above-mentioned 3 beta-hydroxy-5-cholenic acid ester derivants.
Another object of the present invention provides the purposes of this compounds.Specifically be used for liquid crystal material.
3 beta-hydroxy-5-cholenic acid ester derivants provided by the invention have following molecular formula:
Wherein
Figure A9911980900052
Or
Figure A9911980900054
Or R=CO 2R ' or CH 2O 2CC 6H 5, n=1-3, R '=C 1-10Alkyl.As 5-cholene-3 β, 24-glycol dibenzoate, 3 beta substitution benzoyloxy-5 α-cholic acid alkyl ester, 3 β-fluorine substituted benzoyl acyl-oxygen base-5-cholenic acid alkyl ester, 3 β-fluorine replaces cinnamoyloxy group-5 α-cholic acid alkyl ester, 3 β-(fluorine replacement-4-propoxy-) benzoyloxy-5-cholenic acid alkyl ester, 3 β-(fluorine replacement-4-propoxy-) benzoyloxy-5 α-cholic acid alkyl ester etc.
3 beta-hydroxy-5-cholenic acid ester derivants of the present invention, can be raw material from 3 beta-hydroxies-5-cholenic acid and hydride 3 beta-hydroxies-5 α-cholic acid thereof, through the esterification of side chain carboxyl group and synthetic the forming of esterification of 3 beta-hydroxies, but 3 beta-hydroxies-5-cholenic acid and ester thereof also direct hydrogenation become 3 beta-hydroxies-5 α-cholic acid and ester thereof, proceed the esterification of side chain carboxyl group and the esterification of 3 beta-hydroxies.Reaction formula is as follows:
Figure A9911980900061
In addition, adopt steroidal glycol (IV) and Benzoyl chloride condensation can obtain compound (V):
Figure A9911980900062
In the above-mentioned molecular formula
Figure A9911980900063
R, ph f, R ', n as previously mentioned, ph=C 6H 5
3 beta-hydroxies-5-cholenic acid or 3 beta-hydroxies-5 α-cholic acid can obtain Compound I I through the side chain esterification.3 beta-hydroxies-5-cholene acid esters can obtain Compound I I-2 through hydrogenation.
The side chain esterification of Compound I can be adopted two kinds of methods of nucleophilic reaction of the catalytic carboxyl esterification reaction of protonic acid or carboxyl negative ion and haloalkane.The catalytic reactive esterify hydroxy condition of protonic acid is that Compound I and pure R ' OH mol ratio are 1: during 1-500, and in the presence of protonic acid, room temperature reaction 5-30 hour.R ' OH can be used as solvent, and described protonic acid can be sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid etc.The carboxyl negative ion is that the oxyhydroxide of Compound I, haloalkane R ' X, monovalence metal or carbonate, crown compound mol ratio are 1 to the nucleophilic reaction condition of haloalkane: 1-5: 1-10: during 0.01-1, and in organic solvent room temperature reaction 10-50 hour.Described crown compound can be a hexaoxacyclooctadecane-6-6,15-crown ether-5 etc.X＝Cl、Br、I。
The esterification of 3 beta-hydroxies of Compound I I can be in the presence of dewatering agent and catalyzer fluorine-containing aromatic carboxylic acid and Compound I I react and realize Compound I I, fluorine-containing aromatic carboxylic acid ph fThe mol ratio of COOH, dewatering agent is 1: 0.5-2: 0.5-5, the weight ratio of dewatering agent and catalyzer is 1: 0.001-0.080, room temperature was reacted 1-48 hour to reflux temperature in organic solvent.Described dewatering agent is N, and N '-dicyclohexylcarbodiimide (being called for short DCC), catalyzer are [4-(N, N-dimethyl) amido pyridines (being called for short DMAP).Described organic solvent can be ethylene dichloride, trichloromethane, tetracol phenixin, sherwood oil, ether, pyridine, benzene, toluene etc.
3 beta-hydroxies-5-cholene acid esters (I-1), hydrogenation with the logical hydrogen of 10%Pd/C catalyzer in organic solvent can directly obtain 3 beta-hydroxies-5 α-cholate (II-2), Compound I-1 is 1 with the weight ratio of 10%Pd/C: 0.01-0.10, usually control pressure is 1-5MPa, reaction times 0.1-2 hour.
Steroidal glycol (IV) and Benzoyl chloride in organic solvent room temperature reaction 1-50 hour, can generate compound (V), mol ratio is 1: 0.8-3, adding the organic amine compound that lone-pair electron are arranged on the nitrogen-atoms such as triethylamine, Trimethylamine 99, dimethylamine in reaction will help to add fast response and carry out, the mol ratio of organic amine compound add-on and steroidal glycol is 0-10: 1, more the organic amine compound of volume has no adverse effect to reaction, and the recommendation mol ratio is 1-10.
3 beta-hydroxy-5-cholenic acid ester derivants of the present invention are measured through thermal induced phase transition and are shown all have liquid crystal liquid crystal property.Because simple synthetic method, this analog derivative is expected to be used for liquid crystal material.
By following embodiment, will help to understand the present invention, but can not limit content of the present invention.
Embodiment
Infrared absorption spectrum (IR) is with Shimatdzu IR440 or Bio-Rad FT IR determination of infrared spectroscopy, proton nmr spectra (1H NMR) and nucleus magnetic resonance fluorine spectrum ( 19F NMR) with Varian EM 360A, EM390L or Bruker AMX-300 type nuclear magnetic resonance spectrometer are measured, TMS and TFA are interior mark or external standard, and mass spectrum (MS) is measured by HP 5989A mass spectrograph, and high resolution mass spectrum (HP-MS) is measured with Finnigan mat 8401 mass spectrographs.
Transformation temperature and enthalpy change are measured with Shimadzu DSC 50 type differential scanning calorimeters, 5 ℃/min of temperature rate.Transformation temperature and phase are measured with polarizing microscope and Mettle FP 52 program control warm tables, and 2 ℃/min of temperature rate (suitably slowing down when undergoing phase transition) amplifies 100 times.
Rapid column chromatography is a stationary phase with silica gel H (10-40 μ) or silica gel (300-400 order), and eluent is sherwood oil (60-90)-acetate acetate except that indicating, and thin-layer chromatography adopts GF254 high-efficient silica gel plate, and with UV-light, iodine and potassium permanganate solution develop the color successively.
Shortenings: THF (tetrahydrofuran (THF)), DMF (N, dinethylformamide), DC (N, N-dicyclohexylcarbodiimide), DMAP[4-(N, N-dimethyl) amido pyridine], DMSO (dimethyl sulfoxide (DMSO)).
Embodiment 1
The preparation of 3 beta-hydroxies-5-cholenic acid alkyl ester
The preparation method one.
With 3 beta-hydroxies-5-cholenic acid methyl esters is example:
3 beta-hydroxies-5-cholenic acid 6.02mmol mixes with 10-80ml methyl alcohol and vitriol oil 1-10ml, stirring at room one day, and in the reaction solution impouring water, ethyl acetate extraction twice, organic layer merges, column chromatography after the conventional processing.Get product 2.292g, productive rate 98.0%.Ethyl alcohol recrystallization gets the flakey white crystal.MS(m/z)：388(M +)，370，355，303，277，255，213，145IR(KBr)υ(cm-1)：3364.7，2936.2，1739.6
3 beta-hydroxies-5-cholenic acid ethyl ester: 3 beta-hydroxy 5-cholenic acid 0.801mmol, ethanol 15ml, vitriol oil 0.5ml.Get product 258mg, productive rate 80.0%.MS(m/z)：402(M ++1)，384，369，317，291，255，213，145
3 beta-hydroxies-5-cholenic acid propyl ester: 3 beta-hydroxies-5-cholenic acid 0.801mmol, propyl alcohol 12ml, vitriol oil 1.0ml.Get product 235mg, productive rate 70.4%.MS(m/z)：416(M +)，397，382，305，255，213，145
3 beta-hydroxies-5-cholenic acid isopropyl ester: 3 beta-hydroxies-5-cholenic acid 300mg, Virahol 10-12ml, vitriol oil 1.0ml gets product 274mg, productive rate 82.1%.MS(m/z)：416(M +)，397，382，305，255，213，145 1HNMR(CDCl 3，TMS)δ(ppm)：5.30(d，1H，J＝4.5Hz)，4.95(m，1H)，3.45(m，1H)
The preparation method two
With 3 beta-hydroxies-5-cholenic acid monooctyl ester is example:
3 beta-hydroxies-5-cholenic acid 400mg is dissolved among the 1-3.0mlDMF, adds positive bromo spicy silane 0.45ml, sodium hydroxide or salt of wormwood 1-5mmol and hexaoxacyclooctadecane-6-6 or 15-crown ether-55mg, stirring at room 20-50 hour, in the reaction solution impouring water, ethyl acetate extraction, column chromatography after the conventional processing.Get white solid 473mg, productive rate 91.0%, MS (m/z): 486 (M +), 468,453,400,374,255,213,145
3 beta-hydroxies-5-cholenic acid butyl ester: 3 beta-hydroxy 5-cholenic acid 300mg, positive n-butyl bromide 0.1-0.20ml, salt of wormwood 250mg, hexaoxacyclooctadecane-6-65mg, DMF2.0ml.Get product 269mg, productive rate 78.0%.MS(m/z)：430(M +)，412，370，255，213，145
3 beta-hydroxies-5-cholenic acid pentyl ester: 3 beta-hydroxy 5-cholenic acid 400mg, positive bromine or iodine pentane.0.40ml, salt of wormwood 400mg, hexaoxacyclooctadecane-6-65mg, DMF3.0ml.Get product 355mg, productive rate 74.8%.MS(m/z)：444(M +)，426，411，358，332，255，213，145
3 beta-hydroxies-own the ester of 5-cholenic acid: 3 beta-hydroxy 5-cholenic acid 400mg, positive chlorine or bromine hexane.0.3-0.40ml, salt of wormwood 400mg, hexaoxacyclooctadecane-6-65mg, DMF 3.0ml.Get product 372mg, productive rate 75.9%.MS(m/z)：458(M +)，440，425，372，346，255，213，145
3 beta-hydroxies-5-cholenic acid heptyl ester: 3 beta-hydroxy 5-cholenic acid 1.07mmol, positive heptyl bromide 0.3-0.40ml, salt of wormwood 1-2.5mmol, hexaoxacyclooctadecane-6-6 3-5mg, DMF3.0ml.Get product 410mg, productive rate 81.2%.MS(m/z)：472(M +)，454，439，386，360，255，213，145
3 beta-hydroxies-5-cholenic acid ester in the ninth of the ten Heavenly Stems: 3 beta-hydroxy 5-cholenic acid 1.07mmol, positive heptyl bromide 0.50ml, salt of wormwood 1-5mmol, hexaoxacyclooctadecane-6-6 or 15-crown ether-5 and 1-5mg, DMF3.0ml.Get product 463mg, productive rate 86.6%.MS(m/z)：500(M +)，482，467，388，255，213，145
3 beta-hydroxies-5-cholenic acid ester in the last of the ten Heavenly stems: 3 beta-hydroxy 5-cholenic acid 1.07mmol, positive heptyl bromide 0.2-0.55ml (587mg, 2.66mmol), salt of wormwood 1-5mmol, hexaoxacyclooctadecane-6-6 1-5mg, DMF3.0ml.Get product 455mg, productive rate 82.8%.MS(m/z)：514(M +)，497，496，481，402，255，213，145
Synthesizing of embodiment 23 beta-hydroxies-5 α-Methyl cholate
3 beta-hydroxies-5-cholenic acid methyl esters 20.1mmol adds 10%Pd/C500-1000mg in the ethylene dichloride solvent, feed H 2Reaction is 0.1-2 hour during to 1-5MPa, and hydrogenation obtains 3 beta-hydroxies-5 α-Methyl cholate 7.83g, productive rate 99.9%.Ethyl alcohol recrystallization gets the flakey white crystal.MS(m/z)：390(M +)，372，357，233，215，165，147IR(KBr)υ(cm -1)：3431，1741
Embodiment 35-cholene-3 β, 24-glycol synthetic
3 beta-acetoxyl group-5s-cholenic acid methyl esters 0.511mmol is dissolved among the anhydrous THF of 3ml, adds lithium aluminium hydride 1.21mmol, and stirring at room adds the 0.5ml ethyl acetate after 3 hours.Add dilute hydrochloric acid, ethyl acetate extraction twice, organic layer merges, column chromatography after the conventional processing.Get white solid 110mg, productive rate 59.7%.MS (m/z): 360 (M+), 342,327,275,255,231,213,1455-cholene-3 β, 24-glycol dibenzoate synthetic
5-cholene-3 β, 24-glycol 110mg is dissolved in the 3ml pyridine, adds Benzoyl chloride 0.10ml, stirring at room 10-50 hour.In the ice-cold dilute hydrochloric acid of reaction solution impouring, column chromatography after the ethyl acetate extraction organic layer conventional processing.Get product 106mg, productive rate 61.1%.MZ (m/z): 446,431,323,255,147,105IR (KBr) υ (cm -1): 1717 1H NMR (CDCl 3, TMS) δ (ppm): 8.05 (m, 4H), 7.55 (m, 2H), 7.44 (m, 4H), 5.42 (d, 1H, J=4.09Hz), 4.86 (m, 1H), 4.30 (m, 2H) ultimate analysis, C 38H 48O 4: calculated value C80.24H8.51, measured value C80.36H8.61
Embodiment 4
3 β-(4-fluorine) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.901mmol, 4-fluorobenzoic acid 0.999mmol, DCC250mg, DMAP 2mg, THF7.0ml.Get product 307mg, productive rate 66.7%.MS (m/z): 370,355,255,249,213,149,123IR (KBr) υ (cm -1): 1706,1747 1H NMR (CDCl 3, TMS) δ (ppm): 8.07 (m, 2H), 7.10 (m, 2H), 5.44 (d, 1H, J=4.5Hz), 4.89 (m, 1H), 3.72 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 28.3 (m, 1F) ultimate analysis, C 32H 43FO 4: calculated value C75.26H8.49, measured value C75.37H8.51
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 1.00mmol, 3,4-difluoro-benzoic acid 170mg, 1.08mmol, DCC1.21mmol, DMAP2mg, THF or ethylene dichloride 8.0ml.Get product 425mg, productive rate 80.1%.MS (m/z): 370,355,255,249,213,149,141IR (KBr) υ (cm -1): 1715.6,1739.8 1H NMR (CDCl 3, TMS) δ (ppm): 7.87 (m, 2H), 7.15 (m, 1H), 5.44 (d, 1H, J=4.5Hz), 4.83 (m, 1H), 3.69 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.1 (m, 1F), 59.3 (m, 1F) ultimate analysis, C 32H 42F 2O 4: calculated value C72.70H8.01, measured value C72.61H8.01
3 β-(3, the 5-difluoro) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 50mg, 3,5-difluoro-benzoic acid 20-23mg, DCC32mg, DMAP2mg, THF2.0ml.Get product 61mg, productive rate 89.7%.MS (m/z): 529 (M ++ 1), 370,355,255,213,147IR (KBr) υ (cm -1): 1710,1745 1H NMR (CDCl 3, TSM) δ (ppm): 7.55 (m, 2H), 6.99 (m, 1H), 5.42 (d, 1H, J=4.23Hz), 4.85 (m, 1H), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 31.87 (m, 2F) ultimate analysis, C 32H 42F 2O 4: calculated value C72.70H8.01, measured value C72.70H8.04
3 β-(3,4, the 5-trifluoro) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.129mmol, 3,4,5-trifluoro-benzoic acid 0.159mmol, DCC0.155mmol, DMAP2mg, THF2.0ml.Get product 52mg, productive rate 73.9%.MS (m/z): 370,355,255,249,213,159,147IR (KBr) υ (cm -1): 1720,1742 1H NMR (CDCl 3, TMS) δ (ppm): 7.68 (m, 2H), 5.42 (d, 1H, J=4.42Hz), 4.84 (m, 1H), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 54.5 (m, 2F), 75.2 (m, 1F) ultimate analysis, C 32H 41F 3O 4: calculated value C70.307.56, measured value C70.20H7.65
3 β-(4-fluorine) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 190mg, 4-fluorobenzoic acid 70mg, DCC150mg, DMAP2mg, THF4.0ml.Get product 203mg, productive rate 81.4%.MS (m/z): 513 (M ++ 1), 372,357,230,215,147,123IR (KBr) υ (cm -1): 1707,1738 1H NMR (CDCl 3, TMS) δ (ppm): 8.05 (m, 2H), 7.09 (m, 2H), 4.92 (m, 1H), 3.70 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 28.4 (m, 1F) ultimate analysis, C 32H 45FO 4: calculated value C74.96H8.85, measured value C74.84H9.04
3 β-(3, the 4-difluoro) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.998mmol, 3,4-difluoro-benzoic acid 1.01mmol, DCC1-1.21mmol, DMAP 1-3mg, THF7.0ml.Get product 364mg, productive rate 68.7%.MS (m/z): 530 (M +), 371,356,255,230,215,147,141IR (KBr) υ (cm -1): 1715,1735 ultimate analyses, C 32H 44F 2O 4: calculated value C72.42H8.36, measured value C75.05H8.09 (to be purified)
3 β-(3, the 5-difluoro) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.998mmol, 3,5-difluoro-benzoic acid 1.01mmol, DCC1.21mmol, DMAP 2mg, THF7.0ml.Get product 249mg, productive rate 65.9%.MS (m/z): 513 (M +), 372,356,230,215,147,141IR (KBr) υ (cm -1): 1720,1745 1H NMR (CDCl 3, TMS) δ (ppm): 7.54 (m, 2H), 7.00 (m, 1H), 4.94 (m, 1H), 3.70 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 30.9 (m, 2F) ultimate analysis C 32H 44F 2O 4: calculated value C72.42H8.36, measured value C72.13H8.13
3 β-(3, the 4-difluoro) cinnamoyloxy group-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.299mmol, 3,4-cinnamic acid difluoride 0.272mmol, DCC0.388mmol, DMAP2mg, THF3.0ml.Get product 82mg, productive rate 54.4%.MS (m/z): 370,355,255,249,213,167,147IR (KBr) υ (cm -1): 1716,1737 1H NMR (CDCl 3, TMS) δ (ppm): 7.51 (d, 1H, J=16.2Hz), 7.16 (m, 3H), 6.35 (d, 1H, J=16.2Hz), 5.43 (d, 1H, J=4.5Hz), 4.74 (m, 1H), 3.68 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 57.7 (m, 1F), 59.9 (m, 1F) ultimate analysis C 32H 44F 2O 4: calculated value C73.61H8.00, measured value C73.60H8.11
3 β-(3, the 5-difluoro) cinnamoyloxy group-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.309mmol, 3,5-cinnamic acid difluoride 0.272mmol, DCC0.310mmol, DMAP2mg, THF3.0ml.Get product 95mg, productive rate 63.1%.MS(m/z)：369，354，255，249，213，167，147IR(KBr)υ(cm -1)：1712，1742 1H?NMR(CDCl 3，TMS)δ(ppm)：7.53(d，1H，J＝16.2Hz)，6.95(m，3H)，6.42(d，1H，J＝16.2Hz)，5.43(d，1H，J＝4.5Hz)，4.75(m，1H)，3.71(s，3H) 19F?NMR(CDCl 3，TFA)δ(ppm)：31.1(m，2F)
3 β-(3,4, the 5-difluoro) cinnamoyloxy group-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 120mg, 3,4,5-cinnamic acid difluoride 70mg, DCC90mg, DMAP2mg, THF3.0ml.Get product 107mg, productive rate 60.5%.MS (m/z): 370IR (KBr) υ (cm -1): 1717,1735 1H NMR (CDCl 3, TMS) δ (ppm): 7.58 (d, 1H, J=16.2Hz), 7.18 (m, 2H), 6.35 (d, 1H, J=16.2Hz), 5.43 (d, 1H, J=4.5Hz), 4.78 (m, 1H), 3.69 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 55.8 (m, 2F), 79.7 (m, 1F) ultimate analysis C 34H 43F 3O 4: calculated value C71.30H7.57, measured value C71.33H7.71
3 β-(3, the 4-difluoro) cinnamoyloxy group-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.998mmol, 3,4-cinnamic acid difluoride 1.03mmol, DCC1.21mmol, DMAP2mg, THF7.0ml.Get product 378mg, productive rate 68.0%.MS (m/z): 557 (M ++ 1), 372,357,257,230,215,167IR (KBr) υ (cm -1): 1705,1737 1H NMR (CDCl 3, TMS) δ (ppm): 7.55 (d, 1H, J=15.97Hz), 7.25 (m, 3H), 6.32 (d, 1H, J=15.96Hz), 4.81 (m, 1H), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 57.36 (m, 1F), 59.56 (m, 1F) ultimate analysis C 34H 46F 2O 4: calculated value C73.35H8.33, measured value C73.27H8.49
3 β-(3,4, the 5-trifluoro) cinnamoyloxy group-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.486mmol, 3,4,5-three fluoro cinnamic acid 0.495mmol, DCC0.727mmol, DMAP2mg, THF4.0ml.Get product 187mg, productive rate 66.9%.MS (m/z): 574 (M +), 372,257,230,215,185,147 ultimate analysis C 34H 45F 3O 4: calculated value C71.05H7.89, measured value C70.95H7.85
Embodiment 6
3 β-(2,3-two fluoro-4 propoxy-) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 80mg, 2,3-two fluoro-4-propoxy benzoic acid 43mg, DCC100mg, DMAP2mg, methylene dichloride 5.0ml gets product 108mg, productive rate 92.5%.MS (m/z): 370,369,354,255,249,199,147 1H NMR (CDCl 3, TMS) δ (ppm): 7.67 (m, 1H), 6.75 (m, 1H), 5.42 (d, 1H, J=4.09Hz), 4.84 (m, 1H), 4.06 (t, 2H, J=6.56Hz), 3.67 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 55.5 (m, 1F), 80.8 (m, 1F) ultimate analysis C 35H 48F 2O 5: calculated value C71.64H8.25, measured value C71.47H8.41
3 β-(2,3-two fluoro-4-butoxy) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.206mmol, 2,3-two fluoro-4-butyl phenyl ether formic acid 0.200-0.400mmol, DCC100mg 0.485mmol, DMAP2mg, methylene dichloride 5.0ml.Get product 103mg.Productive rate 85.5%.MS (m/z): 370,369,355,255,249,, 213,199,147 1H NMR (CDCl 3, TMS) δ (ppm): 7.66 (m, 1H), 6.73 (m, 1H), 5.43 (d, 1H, J=4.5Hz), 4.83 (m, 1H), 4.17 (t, 2H, J=6.3Hz), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.4 (m, 1F), 81.7 (m, 1F) ultimate analysis, C 36H 50F 2O 5: calculated value C71.97H8.39, measured value C71.91H8.54
3 β-(2,3-two fluoro-4-pentyloxys) benzoyloxy-5-cholenic acid methyl esters: 3 beta-hydroxies-5-cholenic acid methyl esters 0.206mmol, 2,3-two fluoro-4-amyl phenyl ether formic acid 0.197mmol, DCC0.485mmol, DMAP2mg, methylene dichloride 5.0ml.Get product 99mg, productive rate 81.9%.MS (m/z): 369,355,255,249,219,213,157,147 1H NMR (CDCl 3, TMS) δ (ppm): 7.66 (m, 1H), 6.75 (m, 1H), 5.42 (d, 1H, J=4.5Hz), 4.90 (m, 1H), 4.14 (t, 2H, J=6.3Hz), 3.71 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.3 (m, 1F), 81.6 (m, 1F) ultimate analysis, C 37H 52F 2O 5: calculated value C72.28H8.53 measured value C72.09H8.66.
3 β-(2,3-two fluoro-4-propoxy-) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.230mmol, 2,3-two fluoro-4-propoxy benzoic acid 0.231mmol, DCC0.485mmol, DMAP2mg, methylene dichloride 5.0ml.Get product 103mg, productive rate 75.9%.MS (m/z): 587 (M +-1), 372,357,230,257,215,147IR (KBr) υ (cm -1): 1725,1736 1H NMR (CDCl 3, TMS) δ (ppm): 7.68 (m, 1H), 4.94 (m, 1H), 4.08 (t, 2H, J=6.3Hz), 3.72 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.5 (m, 1F), 8.17 (m, 1F) ultimate analysis C 35H 50F 2O 5: calculated value C7140H8.56, measured value C71.54H8.37
3 β-(2,3-two fluoro-4-butoxy) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.230mmol, 2,3-two fluoro-4-butyl phenyl ether formic acid 0.217mmol, DCC100mg, 0.485mmol, DMAP2mg, methylene dichloride 5.0ml.Get product 113mg, productive rate 86.3%.MS (m/z): 603 (M +-1), 371,356,256,230,215,213,147IR (KBr) υ (cm -1): 1745,1721 1H NMR (CDCl 3, TMS) δ (ppm): 7.65 (m, 1H), 6.74 (m, 1H), 4.93 (m, 1H), 4.09 (t, 2H, J=6.49Hz), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.8 (m, 1F), 81.9 (m, 1F) ultimate analysis C 36H 52F 2O 5: calculated value C71.73H8.70, measured value C71.70H8.30
3 β-(2,3-two fluoro-4-pentyloxys) benzoyloxy-5 α-Methyl cholate: 3 beta-hydroxies-5 α-Methyl cholate 0.115mmol, 2,3-two fluoro-4-amyl phenyl ether formic acid 0.115mmol, DCC0.242mmol, DMAP2mg, methylene dichloride 3.0ml.Get product 63mg, productive rate 89.1%.MS (m/z): 618 (M +-1), 371,356,256,230,227,215,157 1H NMR (CDCl 3, TMS) δ (ppm): 7.67 (m, 1H), 6.75 (m, 1H), 4.93 (m, 1H), 4.08 (t, 2H, J=6.56Hz), 3.66 (s, 3H) 19F NMR (CDCl 3, TFA) δ (ppm): 56.2 (m, 1F), 81.4 (m, 1F) ultimate analysis C 37H 54F 2O 5: calculated value C72.04H8.82, measured value C71.89H9.07
Embodiment 7
3 β-(4-fluorine) benzoyloxy-5-cholenic acid butyl ester: 3 beta-hydroxies-5-cholenic acid butyl ester 0.186mmol, 4-fluorobenzoic acid 0.20-0.250mmol, DCC0.388mmol, DMAP2mg, methylene dichloride 4ml.Get product 95mg, productive rate 92.5%.MS (m/z): 551 (M +-1), 412,396,290,255,213,147,123 1H NMR (CDCl 3, TMS) δ (ppm): 8.06 (m, 2H), 7.09 (m, 2H), 5.43 (d, 1H, J=4.5Hz), 4.85 (m, 1H), 4.07 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 38.5 (m) ultimate analysis C 35H 49FO 4: calculated value C76.05H8.94, measured value C75.96H9.13
3 β-(3, the 5-difluoro) benzoyloxy-5-cholenic acid butyl ester: 3 beta-hydroxies-5-cholenic acid butyl ester 0.186mmol, 3,5-difluoro-benzoic acid 0.253mmol, DCC0.388mmol, DMAP2mg, methylene dichloride 4ml.Get product 96mg, productive rate 90.5%.MS (m/z): 571 (M ++ 1), 413,397,291,255,213,147,145 19F NMR (CDCl 3, TFA) δ (ppm): 31.4 (m) ultimate analysis C 35H 48F 2O 4: calculated value C73.65H8.48, measured value C73.60H8.62
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid butyl ester: 3 beta-hydroxies-5-cholenic acid butyl ester 0.186mmol, 3,4-difluoro-benzoic acid 0.253mmol, DCC0.388mmol, DMAP2mg, methylene dichloride 4ml.Get product 101mg, productive rate 95.3%. 1H?NMR(CDCl 3，TMS)δ(ppm)：7.85(m，2H)，7.15(m，1H)，5.44(d，1H，J＝4.5Hz)，4.85(m，1H)，4.08(t，，2H，J＝6.3Hz) 19F?NMR(CDCl 3，TFA)δ(ppm)：53.5(m，1F)，58.5(m，1F)
3 β-(3,4, the 5-trifluoro) benzoyloxy-5-cholenic acid butyl ester: 3 beta-hydroxies-5-cholenic acid butyl ester 80mg, 3,4,5-trifluoro-benzoic acid 30-40mg, DCC80mg, DMAP2mg, methylene dichloride 4ml.Get product 103mg, productive rate 81.0%.MS (m/z): 589 (M ++ 1), 414,413,396,291,255,213,159 1H NMR (CDCl 3, TMS) δ (ppm): 7.68 (m, 2H), 5.44 (d, 1H, J=4.5Hz), 4.84 (m, 1H), 4.08 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 55.7 (m, 2F), 76.0 (m, 1F) ultimate analysis C 35H 47F 3O 4: calculated value C71.40H8.05, measured value C71.36H8.16
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid pentyl ester: 3 beta-hydroxies-5-cholenic acid pentyl ester 100mg, 3,4-difluoro-benzoic acid 45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 120mg, productive rate 91.3%.MS (m/z): 585 (M ++ 1), 428,427,412,305,255,213,141 1H NMR (CDCl 3, TMS) δ (ppm): 7.86 (m, 2H), 7.16 (m, 1H), 5.44 (d, 1H, J=4.5Hz), 4.84 (m, 1H), 4.07 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 53.0 (m, 1F), 59.2 (m, 1F) ultimate analysis C 36H 50F 2O 4: calculated value C73.94H8.62, measured value C73.70H8.72
3 β-(3, the 4-difluoro) benzoyloxy-own ester of 5-cholenic acid: the own ester 100mg of 3 beta-hydroxies-5-cholenic acid, 3,4-difluoro-benzoic acid 45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 127mg, productive rate 97.3%.MS (m/z): 442,441,426,319,255,213,147,141 1HNMR (CDCl 3, TMS) δ (ppm): 7.84 (m, 2H), 7.18 (m, 1H), 5.44 (d, 1H, J=4.5Hz), 4.86 (m, 1H), 4.06 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 52.9 (m, 1F), 58.9 (m, 1F) ultimate analysis C 37H 52F 2O 4: calculated value C74.21H8.75, measured value C74.19H8.88
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid heptyl ester: 3 beta-hydroxies-5-cholenic acid heptyl ester 100mg, 3,4-difluoro-benzoic acid 40-45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 109mg, productive rate 84.1%.MS (m/z): 454,439,332,255,213,147,141 1H NMR (CDCl 3, TMS) δ (ppm): 7.85 (m, 2H), 7.19 (m, 1H), 5.45 (d, 1H, J=4.5Hz), 4.84 (m, 1H), 4.08 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 53.4 (m, 1F), 59.4 (m, 1F) ultimate analysis C 38H 54F 2O 4: calculated value C74.47H8.88, measured value C74.57H8.76
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid monooctyl ester: 3 beta-hydroxies-5-cholenic acid monooctyl ester 100mg, 3,4-difluoro-benzoic acid 45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 116mg, productive rate 90.1%.MS (m/z): 469,468,453,346,255,213,147,141 1H NMR (CDCl 3, TMS) δ (ppm): 7.85 (m, 2H), 7.17 (m, 1H), 5.43 (d, 1H, J=4.5Hz), 4.84 (m, 1H), 4.07 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 53.4 (m, 1F), 59.4 (m, 1F) ultimate analysis C 39H 56F 2O 4: calculated value C74.72H9.01, measured value C74.43H9.02
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid ester in the ninth of the ten Heavenly Stems: 3 beta-hydroxies-5-cholenic acid ester in ninth of the ten Heavenly Stems 100mg, 3,4-difluoro-benzoic acid 45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 107mg, productive rate 83.6%.MS (m/z): 641 (M ++ 1), 483,468,361,255,213,147,141 1H NMR (CDCl 3, TMS) δ (ppm): 7.84 (m, 2H), 7.18 (m, 1H), 5.44 (d, 1H, J=4.5Hz), 4.86 (m, 1H), 4.06 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 52.9 (m, 1F), 58.9 (m, 1F) ultimate analysis C 37H 52F 2O 4: calculated value C74.21H8.75, measured value C74.19H8.88
3 β-(3, the 4-difluoro) benzoyloxy-5-cholenic acid ester in the last of the ten Heavenly stems: 3 beta-hydroxies-5-cholenic acid ester in last of the ten Heavenly stems 100mg, 3,4-difluoro-benzoic acid 45mg, DCC100mg, DMAP2mg, methylene dichloride 4ml.Get product 103mg, productive rate 81.0%.MS (m/z): 498,497,482,375,255,213,147,145 1H NMR (CDCl 3, TMS) δ (ppm): 7.86 (m, 2H), 7.16 (m, 1H), 5.44 (d, 1H, J=4.5Hz), 4.84 (m, 1H), 4.07 (t, 2H, J=6.3Hz) 19F NMR (CDCl 3, TFA) δ (ppm): 52.9 (m, 1F), 59.0 (m, 1F) ultimate analysis C 41H 60F 2O 4: calculated value C75.19H9.24, measured value C75.27H9.17
Embodiment 8
The thermal induced phase transition measurement result of liquid crystal is listed in respectively in the following table:
Figure A9911980900191
Table 1
????X ????Ph f Phase transition property (℃)
??- ??- ??- ??- ????4-F ????3，4-F 2????3，5-F 2????3，4，5-F 3 ????Cr?157.5?Ch?232.0I?227.7?Ch?85.7?Recr ????Cr?189.8?Ch?216.1?I?212.4?Ch?136.0?Recr ????Cr?206.8?I?162.0?Ch?92.2?Recr ????Cr?194.8?I?188.2?Ch?149.3?Recr
??H ??H ????4-F ????3，5-F 2 ????Cr?160.4?Ch?215.8?I?210.5?Ch?106.8?Recr ????Cr?151.3?I?121.8?Ch?72.3?Recr
Table 2
??X ????Ph f Phase transition property (℃)
??- ??- ??- ????3，4-F 2????3，5-F 2????3，4，5-F 3 ????Cr?172.7?Ch?241.3?I?239.8?Ch?130.6?Recr ????Cr?161.8?Ch?180.2?I?175.2?Ch?102.8?Recr ????Cr?196.7?Ch?222.3?I?220.3?Ch?145.8?Recr
??H ??H ????3，4-F 2????3，4，5-F 3 ????Cr?158.7?Ch?224.6?I?222.6?Ch?105.6?Recr ????Cr?170.1?Ch?208.0?I?203.7?Ch?116.2?Recr
Table 3
??X ????n Phase transition property (℃)
??- ????3 ????Cr?105.3?Ch?238.9?I?236.0?Ch?50.0 +
??H ??H ??H ????3 ????4 ????5 ????Cr?131.3?Ch?225.4?I?222.8?Ch?87.8?Recr ????Cr?127.4?Ch?220.1?I?217.8?Ch?88.6?Recr ????Cr?119.2?Ch?211.5?I?209.4?Ch?92.8?Recr
+: temperature crystallization not yet so far.
Figure A9911980900202
Table 4
????R ????Ph f Phase transition property
????C 4H 9 n????C 4H 9 n ????4-F ????3，5-F 2 ????Cr?149.0?Ch?177.9?I??175.9+Ch?108.6?Recr ????Cr?122.2?I??99.2??Ch?87.8?Recr
????C 5H 11 n????C 6H 13 n????C 7H 14 n????C 8H 17 n????C 9H 19 n????C 10H 21 n ????3，4-F 2????3，4-F 2????3，4-F 2????3，4-F 2????3，4-F 2????3，4-F 2 ????Cr?158.0?I??152.2?Ch?138.0?Recr ????Cr?131.2?Ch?145.2?I?143.6?Ch?104.3?Recr ????Cr?106.4?Ch?137.4?I?135.9?Ch?74.8?Recr ????Cr?114.6?Ch?130.5?I?128?8?Ch?82.1?Recr ????Cr?117.4?Ch?125.3?I?122.5?Ch?89.1?Recr ????Cr?121.4?I??119.3?Ch?102.0?Recr
+: with determination of polarized light microscopy (5 ℃ of temperature rates/min)
The result of compound (V) is Cr163.0I143.9Ch67.8Recr.

Claims (4)

  1. 3 beta-hydroxies-3-cholenic acid ester derivant, it is characterized in that having following molecular formula:
    Figure A9911980900021
    Wherein
    Figure A9911980900022
    Or
    Figure A9911980900023
    Or
    Figure A9911980900025
    R=CO 2R ' or CH 2O 2Cph, n=1-3, R '=C 1-10Alkyl.
  2. 2. the synthetic method of 3 beta-hydroxies as claimed in claim 1-3-cholenic acid ester derivant is characterized in that with following method synthetic:
    (1) R ' OH mol ratio is 1: during 1-500, generated in room temperature reaction 5-30 hour in the presence of protonic acid
    (2)
    Figure A9911980900028
    The oxyhydroxide of haloalkane R ' X, monovalence metal or carbonate, crown compound mol ratio are 1: 1-5: 1-10: during 0.01-1, in organic solvent room temperature reaction 10-50 hour, generate
    (3)
    Figure A9911980900031
    With the 10%Pd/c weight ratio be 1: logical hydrogen during 0.01-0.10, reaction generated in 0.1-2 hour in 1-5MPa and organic solvent
    Figure A9911980900032
    (4)
    Figure A9911980900033
    Ph fThe mol ratio of COOH, dewatering agent is 1: 0.5-2: 0.5-5, dewatering agent and catalyst weight ratio are 1: 0.001-0.080, room temperature is reacted generation in 1-48 hour to reflux temperature in organic solvent Described dewatering agent is N, and N '-dicyclohexylcarbodiimide, catalyzer are [4-(N, N-dimethyl)] amido pyridines.
    (5)
    Figure A9911980900035
    Benzoyl chloride and triethylamine mol ratio are 1: 0.8-3: during 0-10, in organic solvent room temperature reaction 1-50 hour, generate
    Figure A9911980900036
    Wherein
    Figure A9911980900041
    Or
    Figure A9911980900042
    Figure A9911980900043
    Or R=CO 2R ' or CH 2O 2CPh, n=1-3, R '=C 1-10Alkyl, ph=C 6H 5, X=Cl, Br, I.
  3. 3. synthetic method as claimed in claim 1 is characterized in that described crown compound is hexaoxacyclooctadecane-6-6 or 15-crown ether-5.
  4. 4. the purposes of 3 beta-hydroxies as claimed in claim 1-3-cholenic acid ester derivant is characterized in that being used for liquid crystal material.
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