CN101591355A - A kind of chiral phosphonate and its synthesis method - Google Patents
A kind of chiral phosphonate and its synthesis method Download PDFInfo
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- CN101591355A CN101591355A CNA2009101171904A CN200910117190A CN101591355A CN 101591355 A CN101591355 A CN 101591355A CN A2009101171904 A CNA2009101171904 A CN A2009101171904A CN 200910117190 A CN200910117190 A CN 200910117190A CN 101591355 A CN101591355 A CN 101591355A
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 title claims abstract description 5
- 238000001308 synthesis method Methods 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 12
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000010189 synthetic method Methods 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract description 4
- 239000012046 mixed solvent Substances 0.000 claims abstract description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 10
- -1 phenol ester Chemical class 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 5
- VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical compound CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 claims description 3
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 2
- IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- NWYYWIJOWOLJNR-RXMQYKEDSA-N l-valinol Chemical compound CC(C)[C@H](N)CO NWYYWIJOWOLJNR-RXMQYKEDSA-N 0.000 claims 1
- 239000011592 zinc chloride Substances 0.000 claims 1
- 235000005074 zinc chloride Nutrition 0.000 claims 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 238000011914 asymmetric synthesis Methods 0.000 abstract description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract description 2
- 229960002510 mandelic acid Drugs 0.000 abstract description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 abstract 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 abstract 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 abstract 1
- 150000002902 organometallic compounds Chemical class 0.000 abstract 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 abstract 1
- 229940031826 phenolate Drugs 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 17
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 16
- 235000010290 biphenyl Nutrition 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- 125000006267 biphenyl group Chemical group 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000005499 phosphonyl group Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 3
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 3
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- QMXOFBXZEKTJIK-UHFFFAOYSA-N Glycinol Natural products C1=C(O)C=C2OCC3(O)C4=CC=C(O)C=C4OC3C2=C1 QMXOFBXZEKTJIK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Abstract
一种手性膦酸酯是二苯基膦酸－2－[(4S)－4，5－二氢化－4－R－2－噁唑啉基]苯酚酯，有以下化学式，式中R选自－CH2CH(CH3)2或－CH(CH3)2或－ph或－CH2ph。本化合物的合成方法是首先由2－氰基苯酚和L－氨基醇在无水无氧和催化剂ZnCl2存在时于氯苯溶剂中回流反应24小时制备中间体，然后中间体和二苯基膦酰氯在无水无氧条件下于甲苯和三乙胺混合溶剂中回流反应24小时合成目标产物。本化合物作为手性配体与金属有机化合物形成配合物在扁桃酸不对称合成中表现出良好的催化活性和高对映选择性。
A chiral phosphonate is diphenylphosphonic acid-2-[(4S)-4,5-dihydro-4-R-2-oxazolinyl]phenolate, which has the following chemical formula, where R is selected from From -CH 2 CH(CH 3 ) 2 or -CH(CH 3 ) 2 or -ph or -CH 2 ph. The synthetic method of this compound is at first by 2-cyano phenol and L-amino alcohol in anhydrous anaerobic and catalyst ZnCl 2 exist in chlorobenzene solvent back flow reaction 24 hours to prepare intermediate, then intermediate and diphenylphosphine The acid chloride was refluxed in a mixed solvent of toluene and triethylamine under anhydrous and oxygen-free conditions for 24 hours to synthesize the target product. The compound forms a complex with a metal organic compound as a chiral ligand and exhibits good catalytic activity and high enantioselectivity in the asymmetric synthesis of mandelic acid.
Description
One, technical field
The present invention relates to a kind of chipal compounds and preparation method thereof, specifically a kind of phosphonic acid ester and synthetic method thereof that contains the chiral oxazoline base.
Two, background technology
The title complex of chiral oxazoline and metal (shows the active and high enantioselectivity of good asymmetry catalysis, thereby is subjected to paying close attention to widely at Didls-Alder in the many reactions such as diene cycloaddition reaction, Michael (Mi Xieer) condensation reaction, Friedel-Crafts (Fu Ruide-carat Buddhist now) condensation reaction, Aldol (alcohol aldehyde) condensation reaction of Di Lesi-Ai Erte).
The applicant is engaged in the development of asymmetric compound for a long time, and patent of invention, ZL200610096004.X, CN101016311A, CN101099936A, 200810020198.4, CN101279954A, 200810022278.3,200910116614.5 have been applied for successively.
Three, summary of the invention
The present invention is intended to provide a kind of efficient chiral catalyst for the asymmetric synthesis field particularly prepares the chiral drug compound, technical problem to be solved be select and the synthesis of chiral part with the preparation composition catalyst.
The alleged chiral phosphine compound of the present invention is that chemical name is a phenylbenzene phosphonic acids-2-[(4S)-4,5-dihydro-4-R-2-oxazolinyl] phenol ester, following chemical structural formula is arranged:
R is selected from-CH in the formula
2CH (CH
3)
2(1 ', 1 '-dimethyl ethyl) or-CH (CH
3)
2(1 '-methylethyl) or-Ph (phenyl) or-CH
2Ph (benzyl).
This compound can form title complex with organometallics and show good catalytic activity and high enantioselectivity in the amygdalic acid asymmetric synthesis as chiral ligand.
The synthetic method of this chiral phosphine compound was two steps, the first step is with 2-4-hydroxy-benzonitrile (2-cyanophenol) and L-amino alcohol prepared in reaction intermediate 2-[(4S)-4,5-dihydro-4-R-2-oxazolinyl] phenol, above-mentioned intermediate of second step and diphenyl phosphonyl chloride are [(Ph)
2POCl] synthetic target product, flow process schematically as follows:
Described L-amino alcohol is selected from L-leucinol or L-valerian ammonia alcohol or L-benzene glycinol or L-phenylalaninol.Closed-loop shaped oxazoline base when above-mentioned each L-amino alcohol reacts with the 2-cyanophenol respectively, the R base that it carries is followed successively by-CH
2CH (CH
3)
2,-CH (CH
3)
2,-Ph and-CH
2Ph.
The synthetic method of this chiral phosphine compound is first synthetic target product behind the preparation intermediate, comprises reaction, separation and purifying, the reaction that it is characterized in that preparing intermediate by 2-cyanophenol and L-amino alcohol under the anhydrous and oxygen-free condition and the anhydrous ZnCl of catalyzer
2When existing in chlorobenzene solvent back flow reaction 24 hours, separate then, purifying, i.e. reaction is sloughed chlorobenzene after finishing, chloroform extraction is used in the back that is dissolved in water, and uses column chromatography purification behind the extraction phase precipitation; The reaction of synthetic target product be prepared intermediate with diphenyl phosphonyl chloride under the anhydrous and oxygen-free condition in toluene and triethylamine mixed solvent back flow reaction 24 hours, separate then, purifying, i.e. slough solvent after the reaction end, use column chromatography purification.
Four, description of drawings
Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 8, Figure 11, Figure 14 are respectively intermediate 1a, 1b, 1c, 1d and compound 2a, 2b, 2c, 2d
1HNMR figure.
Fig. 6, Fig. 9, Figure 12, Figure 15, be compound 2a, 2b, 2c, 2d respectively
13CNMR figure.
Fig. 7, Figure 10, Figure 13, Figure 16, be compound 2a, 2b, 2c, 2d respectively
31PNMR figure
Five, embodiment
(1) preparation of intermediate 1a～1d
1, intermediate 1a 2-[(4S)-4,5-dihydro-4-(1 ', 1 '-dimethyl ethyl)-the 2-oxazolinyl] preparation of phenol:
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl
260mg (0.37mmol), the 40mL chlorobenzene, 2-cyanophenol 1.0g (5.6mmol), L-leucinol 3g, temperature rising reflux reaction 24h, stopped reaction, decompression is desolvated to remove, and residuum is dissolved in water, and uses CHCl
3(30mL * 2) extraction, the organic phase anhydrous sodium sulfate drying, rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got colourless oil liquid 0.85g, productive rate 44%; [a]
5 D=-48.67 ° of (c=0.54, CHCl
3):
1HNMR (500MHz, CDCl
3, 27 ℃), and δ (ppm)=12.30 (s, 1H), 7.63～7.65 (d, J=8Hz, 1H), 7.36 (t, J=0.5Hz, 1H), 7.00～7.02 (d, J=8Hz, 1H), 6.86 (t, J=0Hz, 1H), 4.47 (t, J=0.5Hz, 1H), 4.37～4.3 (m, 1H), 3.93 (t, J=0.5Hz, 1H), 1.84～1.87 (m, 1H), 1.61～1.66 (m, 1H), 0.98～1.00 (m, J=11,6H).
2, intermediate 1b 2-[(4S)-4,5-dihydro-4-(1 '-methylethyl)-2-oxazolinyl] preparation of phenol:
Get 2-cyanophenol 1.0g (5.6mmol), L-valerian ammonia alcohol 3g, the preparation method is with example 1.Productive rate 56%.[a]
5 D＝-28.6°(c＝0.64，CHCl
3)：
1H?NMR(500MHz，CDCl
3，27℃)，δ(ppm)＝12.38(s，1H)，7.66～7.68(dd，J＝2.5，2.5Hz，1H)，7.38(t，1H)，7.06～7.03(d，J＝14Hz，1H)，6.89(t，1H)，4.39～4.42(m，1H)，4.12～4.13(m，2H)，1.78～1.82(m，1H)，0.96～1.06(dd，J＝11，11.5Hz，1H).
3, intermediate 1c 2-[(4S)-4,5-dihydro-4-(phenyl)-2-oxazolinyl] preparation of phenol:
Get 2-cyanophenol 1.0g, L-benzene glycinol 3g, reactions steps is with example 1, productive rate 55%; [a]
5 D=-23.4 ° of (c=0.35, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)，δ(ppm)＝12.36(s，1H)，7.87～7.88(d，J＝2.5Hz，1H)，7.34～7.49(m，6H)，7.17～7.20(d，J＝14Hz，1H)，7.00(t，1H)，5.44～5.50(m，1H)，4.78(t，J＝2Hz，1H)，4.26(t，1H).
4, intermediate 1d 2-[(4S)-4,5-dihydro-4-(benzyl)-2-oxazolinyl] preparation of phenol:
Get 2-cyanophenol 1.0g, L-phenylalaninol 3g, reactions steps is with example 1, productive rate 60%; [a]
5 D=-3.07 ° of (c=1.13, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)，δ(ppm)＝12.22(s，1H)，7.64(d，J＝8Hz，1H)，7.25～7.41(m，6H)，7.04～7.06(d，J＝8Hz，1H)，6.89(t，1H)，4.61～4.64(m，1H)，4.39(t，J＝0.5Hz，1H)，3.10～3.14(q，1H)，2.81～2.85(q，1H).
(2) compound 2a～2d's is synthetic
5, compound 2a phenylbenzene phosphonic acids-2-[(4S)-4,5-dihydro-4-(1 ', 1 '-dimethyl ethyl)-the 2-oxazolinyl] phenol ester synthetic:
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add 40mL toluene, 2-[(4S)-4,5-dihydro-4-(1 ', 1 '-dimethyl ethyl)-the 2-oxazolinyl] phenol (intermediate 1a) 2g (9.17mmol), triethylamine 20mL, phenylbenzene phosphono 1.0mL (6.96mmol) is with the mixture heating up 24h that refluxes, stopped reaction, decompression is desolvated to remove, thick product with sherwood oil/methylene dichloride (1: 9) column chromatography, is got weak yellow liquid 1.16g, productive rate 40%; [a]
5 D=-17.68 ° of (c=0.27, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)，δ(ppm)＝8.04～8.07(m，3H)，7.74～7.76(d，J＝8Hz，1H)，7.74(d，J＝8Hz，1H)，7.66(d，J＝8.5Hz，1H)，7.40～7.42(m，5H)，7.26～7.29(m，1H)，7.08(t，J＝0.5Hz，1H)，4.38～4.46(m，2H)，3.90(t，1H)，1.86～1.89(m，1H)，1.73～1.76(m，1H)，1.39～1.42(m，1H)，0.96～1.02(dd，J＝6.5Hz，6.5Hz，6H)，
13CNMR(125MHz，CDCl
3，27℃)160.98，149.95(x2)，132.34(x2)，132.12(x2)，131.25(x2)，128.46(x2)，128.34(x2)，124.16(x2)，121.64(x2)，120.18(x2)，56.63，45.79，39.72，25.22，22.45，22.32.
13PNMR：25.413，IR(KBr)：2970，2917，2849，2251，1679，1612，1588，1462，1440，1390，11313，1273，1221，1124，1063，1031，789，733，691，649，621，592，570，528；HRMS(EI)：m/z(％)：calcd?for?C
25H
26NO
3P：419.1650；found：419.1659.
6, compound 2b phenylbenzene phosphonic acids-2-[(4S)-4,5-dihydro-4-(1 '-methylethyl)-2-oxazolinyl] phenol ester synthetic:
Intermediate 2-[(4S)-4,5-dihydro-4-(1 '-methylethyl)-2-oxazolinyl] synthetic method of phenol (intermediate 1b) and diphenyl phosphonyl chloride is with example 5.
Weak yellow liquid, productive rate 38%; [a]
5 D=-20.27 ° of (c=0.28, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)δ(ppm)＝7.60～7.68(m，5H)，7.24～7.36(m，7H)，6.99(J＝8.5，1H)，6.84((t，1H)，4.28～4.43(m，1H)，4.08～4.14(m，2H)，1.76～1.82(m，1H)，0.92～1.00(dd，J＝7Hz，6.5Hz，6H).
13CNMR(125MHz，CDCl
3，27℃)165.16，160.05(x2)，133.32(x2)，131.37(x2)，131.27(x2)，128.28(x2)，128.14(x2)，128.05(x2)，118.62(x2)，116.78(x2)，71.62，69.94，33.10，18.78，18.66，
13PNMR(300MHz，CDCl
3，27℃)δ(ppm)＝23.18.IR(KBr)：3057，2959，2926，2872，1676，1644，1618，1583，1555，1492，1464，1438，1364，1438，1364，1309，1260，1233，1201，1155，1094，1069，1035，999，959，911，859，830，800，755，728；HRMS(EI)：m/z(％)：calcd?forC
24H
24NO
3P：405.1494；found：405.1502.
7, compound 2c phenylbenzene phosphonic acids-2-[(4S)-4,5-dihydro-4-(phenyl)-2-oxazolinyl] phenol ester synthetic:
Intermediate 2-[(4S)-4,5-dihydro-4-(phenyl)-2-oxazolinyl] synthetic method of phenol (intermediate 1c) and diphenyl phosphonyl chloride is with example 5.
Weak yellow liquid, productive rate 42%; [a]
5 D=19.38 ° of (c=0.05, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)δ(ppm)＝8.00～8.07(m，3H)，7.88(d，J＝7.5Hz，1H)，7.72(d，J＝8.5Hz，2H)，7.10～7.46(m，12H)，4.28(m，1H)，5.46(t，J＝1.5Hz，1H)，4.74～4.77(m，1H)，4.25(t，J＝0.5Hz，1H).
13CNMR(125MHz，CDCl
3，27℃)166.41，160.20，141.68，133.71，131.36，131.25，128.94，128.29，128.16(x2)，127.96(x2)，126.57，118.78，116.96，74.12，68.95.
13PNMR(300MHz，CDCl
3，27℃)，δ(ppm)＝25.56.IR(KBr)：3064，3033，2956，2924，2854，2250，1684，1643，1612，1590，1537，1495，1479，1461，1440，1378，1304，1274，1249，1221，1138，1156，1126，1070，1030，909，793，754，734，698，648，626，557，527.；HRMS(EI)：m/z(％)：calcd?forC
27H
23NO
3P：440.1416；found：440.1385.
8, compound 2d phenylbenzene phosphonic acids-2-[(4S)-4,5-dihydro-4-(benzyl)-2-oxazolinyl] phenol ester synthetic:
Intermediate 2-[(4S)-4,5-dihydro-4-(benzyl)-2-oxazolinyl] synthetic method of phenol (intermediate 1d) and diphenyl phosphonyl chloride is with example 5.
Weak yellow liquid, productive rate 45%; [a]
5 D=14.04 ° of (c=0.14, CHCl
3):
1HNMR(500MHz，CDCl
3，27℃)δ(ppm)＝7.61～7.70(m，5H)，7.23～7.38(m，11H)，7.00(d，J＝8Hz，1H)，6.86(t，J＝0.5Hz，2H)，4.60～4.64(m，1H)，4.39(t，J＝0.5Hz，1H)，4.14(t，J＝0.5Hz，2H)，3.09～3.13(m，1H)，2.79～2.84(m，.1H)，
13CNMR(125MHz，CDCl
3，27℃)165.55，160.01(x2)，137.64(x2)，133.48(x2)，131.34(x2)，131.24(x2)，129.30(x2)，128.72(x2)，128.27(x2)，128.11()x2)，126.78(x2)，118.70(x2)，116.84(x2)，71.28，66.82，42.00.
13PNMR(300MHz，CDCl
3，27℃)，δ(ppm)＝23.205.IR(KBr)：3061，3028，2955，2924，2854，1642，1617，1492，1438，1367，1311，1259，1234，1156，1129，1067，960，756，727，698.HRMS(EI)：m/z(％)：calcd?forC
28H
24NO
3P：453.1494；found：454.1522
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101962391A (en) * | 2010-03-17 | 2011-02-02 | 合肥工业大学 | A chiral phosphine compound |
| CN102127111A (en) * | 2010-11-30 | 2011-07-20 | 罗梅 | Chiral phosphonate compound |
| CN102351898A (en) * | 2011-08-29 | 2012-02-15 | 罗梅 | Synthesis method of diphenyl phosphonic acid |
| CN103965243A (en) * | 2014-06-02 | 2014-08-06 | 罗梅 | Chiral phosphonate crystal compound and use |
| CN105524092A (en) * | 2016-02-22 | 2016-04-27 | 合肥祥晨化工有限公司 | Synthesis method of chiral zinc complex crystal |
-
2009
- 2009-07-01 CN CNA2009101171904A patent/CN101591355A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101962391A (en) * | 2010-03-17 | 2011-02-02 | 合肥工业大学 | A chiral phosphine compound |
| CN101962391B (en) * | 2010-03-17 | 2012-09-26 | 合肥工业大学 | Chiral phosphorus compound |
| CN102127111A (en) * | 2010-11-30 | 2011-07-20 | 罗梅 | Chiral phosphonate compound |
| CN102127111B (en) * | 2010-11-30 | 2013-01-09 | 罗梅 | Chiral phosphonate compound |
| CN102351898A (en) * | 2011-08-29 | 2012-02-15 | 罗梅 | Synthesis method of diphenyl phosphonic acid |
| CN103965243A (en) * | 2014-06-02 | 2014-08-06 | 罗梅 | Chiral phosphonate crystal compound and use |
| CN105524092A (en) * | 2016-02-22 | 2016-04-27 | 合肥祥晨化工有限公司 | Synthesis method of chiral zinc complex crystal |
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