CN101787024B - Quinoline - Google Patents
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- CN101787024B CN101787024B CN2010101150205A CN201010115020A CN101787024B CN 101787024 B CN101787024 B CN 101787024B CN 2010101150205 A CN2010101150205 A CN 2010101150205A CN 201010115020 A CN201010115020 A CN 201010115020A CN 101787024 B CN101787024 B CN 101787024B
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Abstract
The invention relates to a quinoline, which is mainly obtained by introducing oxygen-containing groups into matrixes of glyoxalidine and [1,2-a] quinoline or [2,1-a] isoquinoline. The designed and synthesized quinoline can be used for asymmetric synthesis reaction of metallic catalysis. The quinoline has the main characteristics that: the glyoxalidine is used as a basic framework; catalytic activities (comprising enantioselectivitiy, regioselectivity, specific reaction type selectivity, catalytic efficiency and the like) of a formed catalyst are regulated through reversible balance of a coordinate bond and a covalent bond between a coordinate atom and a metal catalyst when the metal catalyst is used as an electrophilic reagent; and limitation that the conventional nitrogen-oxygen ligand catalytic reaction has fewer types is broken through.
Description
Technical field
The present invention relates to a kind of quinoline, specifically, relate to glyoxalidine also [1,2-a] quinoline or [2,1-a] isoquinoline compound
Background technology
Asymmetry catalysis is the very effective method of synthesizing chiral compound, and the design of chiral catalyst skeleton is the key factor of this method.
As everyone knows, chirality nitrogen phosphorus part and chirality nitrogen nitrogen ligand have obtained using very widely in asymmetry catalysis, and the range of application of nitrogen oxygen part is narrow and small relatively a lot.Tradition nitrogen oxygen part generally is by oxazole ring (Tetrahedron:Asymmetry, 1999,10,4689.; J.Org.Chem.2003,68,4322.), secondary amine and tertiary amine (Org.Lett.2006,8,4687; Angew.Chem.Int.Ed.2002,41,861; Angew.Chem., Int.Ed.2005,44,3881.) as basic framework, this type nitrogen oxygen part has needs the very high metal reagent of zinc alkyl(s), titan-alkoxide isoreactivity as source metal, and needing of having adds alkali and promotes reaction in the reaction system.In addition, these nitrogen oxygen parts are can catalytic reaction type less, mainly concentrate on the measured response type such as addition, Henry reaction of zinc alkyl(s).
Given this; We imagine: development is with the novel nitrogen oxygen part of glyoxalidine ring as basic framework;, so just might realize from the reversible balance of co-ordination bond between ligating atom and the metal catalyst and covalent linkage the catalytic activity of formed catalyzer is carried out (comprising enantioselectivity, regioselectivity as Electron Affinities reagent with metal catalyst; Specific reaction type selectivity and catalytic efficiency (etc.) regulate, break through the existing less limitation of nitrogen oxygen ligand catalysis reaction type.
Summary of the invention
The objective of the invention is to, a kind of quinoline that can be used for the metal catalytic asymmetric catalysis synthesis is provided, overcome the defective that exists in the prior art.
Quinoline of the present invention, it has compound shown in formula I or the formula II:
Among formula I and the formula II: R
1Be H or halogen (F, Cl, Br or I), R
2Be H or substituted C
1～C
3Alkyl, R
3Be H or substituted C
1～C
3Alkyl, R
4Be H or C
1～C
3Alkyl, R
5Be 5～6 yuan of aromatic ring yls or substituted C
1～C
3Alkyl, and R
2, R
3And R
5In at least one is substituted C
1～C
3Alkyl;
Wherein, said substituted C
1～C
3Substituting group is in the alkyl: hydroxyl (OH) with 5～6 yuan of aromatic ring yls or-OH and by C
1～C
3Substituted 5～6 yuan of aromatic ring yls of perfluoroalkyl.
In optimized technical scheme of the present invention, quinoline of the present invention is a compound shown in the formula I:
Wherein: R
1Be H, Cl, Br or I, R
2Be H or substituted C
1～C
3Alkyl, R
3Be H, R
4Be H or C
1～C
3Alkyl, R
5Be 5～6 yuan of aromatic ring yls or substituted C
1～C
3Alkyl, and R
2And R
5In at least one is substituted C
1～C
3Alkyl;
Said substituted C
1～C
3Substituting group is in the alkyl :-OH and 6 yuan of aromatic ring yls or-OH and by C
1～C
3Substituted 5～6 yuan of aromatic ring yls of perfluoroalkyl.
Preferred technical scheme is: R
1Be H or Br, R
2Be H or substituted methyl, R
3Be H, R
4Be H, methyl or ethyl, R
5Be phenyl or substituted methyl, and R
2And R
5In at least one is substituted methyl;
Substituting group is in the said substituted methyl :-OH and phenyl or-OH and by the substituted phenyl of perfluoro-methyl, like (but being not limited to): the group shown in formula III or the formula IV:
In another optimal technical scheme of the present invention, quinoline of the present invention is a compound shown in the formula II:
Wherein: R
1Be H, Cl, Br or I, R
2Be H or substituted C
1～C
3Alkyl, R
3Be H or substituted C
1～C
3Alkyl, R
5Be 5～6 yuan of aromatic ring yls, and R
2And R
3In at least one is substituted C
1～C
3Alkyl;
Said substituted C
1～C
3Substituting group is in the alkyl :-OH and 5～6 yuan of aromatic ring yls or-OH and by C
1～C
3Substituted 5～6 yuan of aromatic ring yls of perfluoroalkyl;
Preferred technical scheme is: R
1Be H or Br, R
2Be H or substituted methyl, R
3Be H or substituted methyl, R
5Be phenyl, and R
2And R
3In at least one is substituted methyl;
Substituting group is in the said substituted methyl :-OH and phenyl or-OH and by the substituted phenyl of perfluoro-methyl, like (but being not limited to): the group shown in formula III or the formula IV.
Embodiment
Quinoline of the present invention is to make by following synthesis strategy:
(1) works as R
2And R
3When being H:
Wherein: R
5-1Be substituted C
1～C
3Alkyl, said substituted C
1～C
3Substituting group is said identical with preamble in the alkyl, best R
5-1Be the group shown in formula III or the formula IV.
" replacement " described in the synthesis strategy (1); Its key step is: having under rare gas element (like nitrogen etc.) existence condition; Compound shown in compound shown in the formula V, the formula VI and organic amine (like diisopropyl ethyl amine) are placed reactor drum, and 130 ℃ of states kept 36 hours down at least, were cooled to room temperature (15 ℃～25 ℃); In this reactor drum, add an amount of polar organic solvent (as having polar haloalkane etc.) again, the gained reaction mixture gets compound shown in the formula VII through column chromatography;
" closed loop " described in the synthesis strategy (1); Its key step is: compound shown in the formula VII of gained is placed another reactor drum; Add an amount of polar organic solvent (like methylene dichloride etc.), under 0 ℃ of condition, add MsCl and triethylamine again; And under this state, kept at least one hour, be warming up to room temperature (15 ℃～25 ℃) back and add The addition of C
1～C
6Aliphatic monobasic alcohol (recommend use methyl alcohol), and under reflux state, keeping at least three hours, gained reaction mixture successively through washing, dry, concentrate and column chromatography gets compound shown in the formula Ia (one of target compound of the present invention).
(2) work as R
1And R
3When being H:
Wherein: R
2-1Be substituted C
1～C
3Alkyl, said substituted C
1～C
3Substituting group is said identical with preamble in the alkyl, best R
5-1Be the group shown in formula III or the formula IV.
" replacement " described in the synthesis strategy (2) similar with " closed loop " step with " replacement " described in the synthesis strategy (1) with " closed loop " (promptly remove reactant or claim raw material, other reaction conditions and institute add the reagent homogeneous phase together) is so repeat no more at this.
" displacement " described in the synthesis strategy (2), its key step is: have under rare gas element (like nitrogen etc.) existence condition, compound shown in the formula XI and organic aprotic polar solvent are placed reactor drum; Under-78 ℃ of conditions, in this reactor drum, add positive lithium alkylide (like n-Butyl Lithium etc.), and kept at least 15 minutes at this state; In this reactor drum, add UVNUL MS-40 again, after at least 5 minutes, be warming up to room temperature (15 ℃～25 ℃); The gained reaction solution is washed with saturated ammonium chloride with polar organic solvent (like methylene dichloride etc.) dilution again, and organic phase is used anhydrous sodium sulfate drying; Concentrate, column chromatography, compound shown in the formula Ib (target compound of the present invention two).
(3) work as R
2During for H:
Wherein: R
3-1Be substituted C
1～C
3Alkyl, said substituted C
1～C
3Substituting group is said identical with preamble in the alkyl, best R
3-1Be the group shown in formula III or the formula IV.
In synthesis strategy (3); Except that in raw materials used and synthesis strategy (1) and (2) used different; " replacement ", " closed loop " reach reaction conditions related in " displacement " step all to reach " displacement " step identical with " replacement ", " closed loop " of strategy described in (1) and (2), so can get compound shown in the formula IIa (target compound of the present invention three).
Through the instruction of above-mentioned three kinds of synthesis strategies, those of ordinary skills need not creative work, can obtain other target compound that is comprised among formula I and the formula II.
The quinoline that the present invention designs and synthesizes can be used for the catalysis asymmetric catalysis synthesis, like Mannich reaction and Henry reaction.Before the Mannich reaction among the present invention mainly is with chirality nitrogen nitrogen ligand, nitrogen phosphorus part (J.Org.Chem.2003,68,2583.; J.Am.Chem.Soc.2008,130,14362.) and phase-transfer catalysis (Org.Lett.2004; 6; 2397.) realize, but chirality nitrogen oxygen part also of no use is realized the catalysis of this reaction, in addition; The temperature of reaction that the catalystsystem reported needs lower (78 ℃ do not wait to 0 ℃), and the reaction system among the present invention at room temperature realizes the asymmetry catalysis of this reaction with nitrogen oxygen part.Henry among the present invention reaction, before in the successful catalystsystem of report, the very high zinc alkyl(s) of needs activity that has is made source metal and lower temperature (like Angew.Chem.Int.Ed.2002; 41; 861.), the needs that have add the generation that alkali promotes to react (like Angew.Chem., Int.Ed.2005; 44,3881.; J.Org.Chem.2005,70,3712.; J.Org.Chem.2008,73,4903.), and the catalystsystem among the present invention need not add alkali, and need not active very high metal as source metal.
Below by embodiment the present invention is further elaborated, its purpose only is better to understand content of the present invention.The example of therefore, being lifted does not limit protection scope of the present invention.
In the following example, except that special instruction was arranged, room temperature was meant 15 ℃～25 ℃.
Embodiment 1
(1) under the nitrogen protection, with 3.350g compounds X II-1 (compound shown in the formula XII, and R
1Be Br) and 1.710g L-benzene glycinol add respectively in the Schlenk pipe, add the 2.60mL diisopropyl ethyl amine again, reaction solution was 130 ℃ of following stirring reactions 36 hours～72 hours, reaction solution is scarlet.After reaction solution is cooled to room temperature,, directly go up an appearance column chromatography with an amount of methylene dichloride solubilizing reaction thing, 23.440g compounds X IV-1, productive rate is 78%.
1H?NMR(400MHz，CDCl
3)δ8.05(d，J＝4.6Hz，1H)，7.96(d，J＝6.0Hz，1H)，7.62(d，J＝8.2Hz，1H)，7.51(d，J＝8.2Hz，1H)，7.45(d，J＝7.3Hz，2H)，7.38(t，J＝7.5Hz，2H)，7.31(t，J＝5.7Hz，2H)，5.43(m，1H)，4.45(br，1H)，4.05(m，2H).
13C?NMR(100MHz，CDCl
3)δ154.62，142.75，139.96，139.16，133.70，132.39，128.94，127.80，126.92，122.18，117.35，117.28，110.32，68.77，59.73.
(2) in the single port flask, add 0.837g compounds X IV-1, add and after an amount of methylene dichloride dissolves it was stirred 5 minutes as for 0 ℃, add 0.24mL MsCl and 0.83mL triethylamine again and be allowed to condition at 0 ℃ of reaction 1-2 hour.Add an amount of methyl alcohol after rising to room temperature, be allowed to condition at 55 ℃ of refluxed 3-5 hours.Reaction finishes the back with an amount of washing, and organic phase is used anhydrous sodium sulfate drying, and organic phase concentrates, and column chromatography obtains 0.721g compounds X V-1 (yellow solid powder), productive rate 90%.
1H?NMR(400MHz，CDCl
3)δ7.34-7.49(m，6H)，7.28(d，J＝8.2Hz，1H)，6.84(d，J＝7.4Hz，1H)，6.33(d，J＝7.4Hz，1H)，5.54(dd，J＝11.2，8.2Hz，1H)，4.37(t，J＝10.7Hz，1H)，3.83(t，J＝9.1Hz，1H).
13C?NMR(100MHz，CDCl
3)δ154.71，144.21，138.34，135.19，133.40，130.94，128.65，127.20，126.52，123.01，121.51，119.80，101.74，67.57，56.67.
(3) under nitrogen protection, in Schlenk pipe, add 100.0mg compounds X V-1, and then add the 10mL THF, this Schlenk pipe is placed cryopump, be cooled to-78 ℃ after, drop into 0.19mL n-Butyl Lithium (the reaction solution color deepens immediately).After reacting about 15 minutes, under nitrogen protection, drop into the 90.0mg UVNUL MS-40 again, after 5 minutes, be warming up to room temperature (the reaction solution color shoals) naturally.Reaction solution dilutes with methylene dichloride, washes with saturated ammonium chloride again, and organic phase is used anhydrous sodium sulfate drying; Concentrate, column chromatography obtains ((S)-7-bromo-2-phenyl-2 of 76.6mg; 3-glyoxalidine thick [2,1-a] isoquinoline 99.9-10-yl) diphenyl-carbinol (count: compound I Ia-1) by letter.Productive rate 61%.
1H?NMR(400MHz，CDCl
3)δ11.67(s，1H)，7.54(d，J＝8.5Hz，1H)，7.28-7.13(m，13H)，6.86(d，J＝7.3Hz，1H)，6.70(d，J＝5.9Hz，2H)，6.63(d，J＝7.3Hz，1H)，6.53(d，J＝8.5Hz，1H)，5.13(t，J＝10.7Hz，1H)，4.30(t，J＝11.0Hz，1H)，3.71(t，J＝10.0Hz，1H).
13C?NMR(100MHz，CDCl
3)δ156.77，148.79，148.37，148.17，142.86，138.15，134.53，130.73，129.33，128.56，128.18，127.98，127.73，127.46，127.03，126.58，126.21，123.05，121.12，104.21，82.07，65.57，57.22。
Embodiment 2
(1) divided by compound VIII-1 (compound shown in the formula VIII, and R
1Be H) outside the compounds X II-1 in the step (1) of alternate embodiment 1, other condition is all identical, compounds X-1 (compound shown in the formula X, and R
4Be H, R
5Be phenyl), productive rate 62%.
1H?NMR(400MHz，CDCl
3)δ7.95(s，1H)，7.60(d，J＝8.4Hz，1H)，7.45(t，J＝7.7Hz，1H)，7.41-7.35(m，3H)，7.31(t，J＝7.5Hz，2H)，7.23(t，J＝7.2Hz，1H)，7.15(t，J＝7.4Hz，1H)，5.96(s，1H)，5.42(br，1H)，5.36-5.25(m，1H)，4.08-3.89(m，2H).
13C?NMR(100MHz，CDCl
3)δ152.43，145.85，140.20，139.37，130.12，128.99，127.90，126.82，126.58，125.91，124.32，123.20，108.16，68.28，59.29.
(2) divided by outside the compounds X IV-1 in the step (2) of compounds X-1 alternate embodiment 1, other condition is all identical, gets compounds X I-1, productive rate 73%.
(3) divided by outside the compounds X V-1 in the step (3) of compounds X I-1 alternate embodiment 1, other condition is all identical, ((S)-2-phenyl-1,2-glyoxalidine thick [1,2-a] quinolyl-4) diphenyl-carbinol (letter is counted: compound I b-1), productive rate 56%.
1H?NMR(400MHz，CDCl
3)δ7.50(dd，J＝7.8，1.5Hz，2H)，7.47-7.41(m，2H)，7.38-7.28(m，7H)，7.25-7.12(m，4H)，6.98-6.86(m，3H)，6.68(d，J＝8.2Hz，1H)，6.64(s，1H)，5.39(dd，J＝11.5，7.2Hz，1H)，4.33(dd，J＝11.3，10.3Hz，1H)，3.75(dd，J＝10.1，7.2Hz，1H).
13C?NMR(100MHz，CDCl
3)δ157.03，145.43，144.57，144.35，137.90，134.76，133.44，130.42，129.02，128.53，128.15，127.99，127.96，127.78，127.48，127.20，127.04，126.20，120.61，111.50，81.44，66.86，53.96。
Embodiment 3
(1) divided by compound V-1 (compound shown in the formula V, and R
1Be Br) compounds X II-1 in the step (1) of alternate embodiment 1, and with compound VI-1 (compound shown in the formula VI, and R
4Be H, R
5-1Be group shown in the formula III) outside the L-benzene glycinol in the step (1) of alternate embodiment 1, other condition is all identical, compound VI I-1, productive rate 45%.
(2) divided by outside the compounds X IV-1 in the step (2) of compound VI I-1 alternate embodiment 1, other condition is all identical, ((S)-6-bromo-1,2-glyoxalidine thick [1,2-a] quinoline-2-yl) diphenyl-carbinol (letter is counted: compound I a-1), productive rate 73%.
1H?NMR(400MHz，CDCl
3)δ7.68(dd，J＝8.5，5.7Hz，3H)，7.52(d，J＝7.8Hz，2H)，7.34(t，J＝7.6Hz，4H)，7.26-7.16(m，3H)，7.12(t，J＝8.0Hz，1H)，6.70(d，J＝10.0Hz，1H)，6.59(d，J＝8.1Hz，1H)，5.57(t，J＝10.2Hz，1H)，3.83-3.67(m，2H)，2.98(br，1H).
13C?NMR(100MHz，CDCl
3)δ158.36，146.21，144.28，139.79，135.90，130.96，128.41，128.39，126.98，126.75，126.51，125.66，124.49，123.24，119.92，118.20，111.47，78.72，71.36，48.18。
Embodiment 4
(1) divided by compound V-2 (compound shown in the formula V, and R
1Be H) compounds X II-1 in the step (1) of alternate embodiment 1, and with compound VI-1 (compound shown in the formula VI, and R
4Be H, R
5-1Be group shown in the formula III) outside the L-benzene glycinol in the step (1) of alternate embodiment 1, other condition is all identical, compound VI I-2, productive rate 17%.
(2) divided by outside the compounds X IV-1 in the step (2) of compound VI I-2 alternate embodiment 1, other condition is all identical, compound ((S)-1,2-glyoxalidine thick [1,2-a] quinoline-2-yl) diphenyl-carbinol (letter is counted: compound I a-2), productive rate 82%.
1H?NMR(400MHz，CDCl
3)δ7.68(d，J＝7.9Hz，2H)，7.51(d，J＝7.8Hz，2H)，7.37-7.26(m，6H)，7.25-7.15(m，3H)，6.94(t，J＝7.5Hz，1H)，6.62(t，J＝9.8Hz，2H)，5.54(t，J＝10.2Hz，1H)，3.90-3.66(m，2H)，3.01(br，1H).
13C?NMR(100MHz，CDCl
3)δ159.02，146.48，144.47，138.64，137.20，130.49，128.37，128.34，128.12，126.88，126.67，126.56，125.71，120.84，120.37，116.89，111.96，78.71，71.11，47.89。
Embodiment 5
(1) divided by compound V-1 (compound shown in the formula V, and R
1Be Br) compounds X II-1 in the step (1) of alternate embodiment 1, and with compound VI-2 (compound shown in the formula VI, and R
4Be H, R
5-1Be group shown in the formula IV) outside the L-benzene glycinol in the step (1) of alternate embodiment 1, other condition is all identical, compound VI I-3, productive rate 11%.
(2) divided by outside the compounds X IV-1 in the step (2) of compound VI I-3 alternate embodiment 1, other condition is all identical, gets ((S)-6-bromo-1; 2-glyoxalidine thick [1; 2-a] quinoline-2-yl) two (3, the 5-trifluoromethyl) methyl alcohol (letter is counted: compound I a-3), and productive rate 76%.
1H?NMR(400MHz，CDCl
3)δ8.12(s，2H)，7.98(s，2H)，7.85(s，1H)，7.82(t，J＝8.1Hz，1H)，7.81(d，J＝7.3Hz，1H)，7.80(s，1H)，7.55(d，J＝8.8Hz，1H)，6.68(d，J＝10.1Hz，1H)，6.55(d，J＝8.8Hz，1H)，5.60(dd，J＝10.6Hz，9.8Hz，1H)，3.83(d，J＝10.7Hz，1H)，3.68(d，J＝9.9Hz，1H)，3.57-3.31(brs，1H).
Embodiment 6
(1) divided by compound V-1 (compound shown in the formula V, and R
1Be Br) compounds X II-1 in the step (1) of alternate embodiment 1, and with compound VI-3 (compound shown in the formula VI, and R
4Be methyl, R
5-1Be group shown in the formula III) outside the L-benzene glycinol in the step (1) of alternate embodiment 1, other condition is all identical, compound VI I-4, productive rate 32%.
1H?NMR(400MHz，CDCl
3)δ7.97(d，J＝9.1Hz，1H)，7.71-7.51(m，5H)，7.44(d，J＝7.4Hz，1H)，7.39-7.29(m，3H)，7.25-7.17(m，1H)，7.07(t，J＝7.5Hz，2H)，7.00(t，J＝7.2Hz，1H)，6.44(d，J＝9.1Hz，1H)，5.64(d，J＝6.1Hz，1H)，5.48(d，J＝6.4Hz，1H)，5.39(br，1H)，4.10(q，J＝6.3Hz，1H)，2.78-2.17(br，1H)，1.14(d，J＝6.3Hz，3H).
13C?NMR(100MHz，CDCl
3)δ157.30，148.78，146.07，145.13，136.19，129.62，128.59，128.12，126.86，126.80，126.17，125.85，125.57，125.21，122.87，121.91，113.63，82.89，69.37，57.41，21.64。
(2) divided by outside the compounds X IV-1 in the step (2) of compound VI I-4 alternate embodiment 1, other condition is all identical, gets ((1S; 2S)-6-bromo-1-methyl isophthalic acid; 2-glyoxalidine thick [1,2-a] quinoline-2-yl) diphenyl-carbinol (letter is counted: compound I a-4), productive rate 78%.
1H?NMR(400MHz，CDCl
3)δ7.72-7.61(m，5H)，7.32(dt，J＝14.0，7.8Hz，4H)，7.24-7.09(m，4H)，6.74(d，J＝8.1Hz，1H)，6.68(d，J＝10.0Hz，1H)，5.50(d，J＝8.8Hz，1H)，4.67(dt，J＝13.1，6.5Hz，1H)，1.07(d，J＝6.5Hz，3H).
13C?NMR(100MHz，CDCl
3)δ157.47，148.26，145.33，139.04，135.49，130.82，128.48，128.47，126.69，126.59，125.50，124.89，124.50，123.70，120.73，118.66，112.34，77.33，73.44，59.82，12.94。
Embodiment 7
Quinoline according to the invention is in the application of asymmetry catalysis Mannich
In the Schlenk pipe, add two under the nitrogen protection
Molecular sieve is respectively with 4.7mg quinoline according to the invention (L) and 2.0mg one water Cu (OAc)
2, add 1mL exsiccant THF, reaction solution was at room temperature stirred 1 hour, add compound shown in the 25.3mg formula B again, add compound shown in the 31.1mg formula A at last, after reaction solution at room temperature stirs 6 hours, directly prepare plate separate product, concrete outcome is seen table 1,
Table 1
*Adopt high-efficient liquid phase color (HPLC) spectrum to detect, and HPLC (Chiral AD, hexane/2-propanol=90/10, Flow rate=0.6ml/min～1.0ml/min).
Embodiment 8
Nitrogen oxygen part is in the application of asymmetry catalysis Henry
4.8mg (0.013mmol) copper trifluoromethanesulfcomposite and 20mg molecular sieve are added in the Schlenk pipe, under vacuumizing, anhydrate to remove with fire is roasting.Under nitrogen protection, add 6.3mg (0.015mmol) compound I a-1 again, add the 1.0mL dissolve with ethanol again, at room temperature stirred 1 hour.Reaction moves to 0 ℃ then, under this temperature, adds paranitrobenzaldehyde and 70 μ L (1.3mmol) Nitromethane 99Min.s of 20.0mg (0.13mmol), and TLC follows the tracks of response situation.Directly revolve the dried appearance column chromatography of going up after reaction finishes and obtain product 27.8mg, productive rate 99%.
ee?22％HPLC(Chiral?AD，hexane/2-propanol＝65/35，Flow?rate＝0.7ml/min)，t
R＝11.77min，14.98min。
Claims (9)
1. quinoline, it has compound shown in formula I or the formula II:
In formula I and the formula II: R
1Be H or halogen, R
2Be H or substituted C
1～C
3Alkyl, R
3Be H or substituted C
1～C
3Alkyl, R
4Be H or C
1～C
3Alkyl, R
5Be 6 yuan of aromatic ring yls or substituted C
1～C
3Alkyl, and R
2, R
3And R
5In at least one is substituted C
1～C
3Alkyl;
Wherein, said substituted C
1～C
3Substituting group is in the alkyl: hydroxyl and 6 yuan of aromatic ring yls or hydroxyl and by C
1～C
3The substituted 6 yuan of aromatic ring yls of perfluoroalkyl.
2. quinoline as claimed in claim 1 is characterized in that, described quinoline is a compound shown in the formula I:
Wherein: R
1Be H, Cl, Br or I, R
2Be H or substituted C
1～C
3Alkyl, R
3Be H, R
4Be H or C
1～C
3Alkyl, R
5Be 6 yuan of aromatic ring yls or substituted C
1～C
3Alkyl, and R
2And R
5In at least one is substituted C
1～C
3Alkyl;
Said substituted C
1～C
3Substituting group is in the alkyl: hydroxyl and 6 yuan of aromatic ring yls or hydroxyl and by C
1～C
3The substituted 6 yuan of aromatic ring yls of perfluoroalkyl.
3. quinoline as claimed in claim 2 is characterized in that, wherein R
1Be H or Br, R
2Be H or substituted methyl, R
4Be H, methyl or ethyl, R
5Be phenyl or substituted methyl, and R
2And R
5In at least one is substituted methyl;
Substituting group is in the said substituted methyl: hydroxyl and phenyl or hydroxyl and by the substituted phenyl of perfluoro-methyl.
4. quinoline as claimed in claim 3 is characterized in that, wherein said substituted methyl is the group shown in formula III or the formula IV:
5. quinoline as claimed in claim 4 is characterized in that, described quinoline is: ((S)-2-phenyl-1; 2-glyoxalidine thick [1,2-a] quinolyl-4) diphenyl-carbinol, ((S)-6-bromo-1,2-glyoxalidine thick [1; 2-a] quinoline-2-yl) diphenyl-carbinol, ((S)-1,2-glyoxalidine thick [1,2-a] quinoline-2-yl) diphenyl-carbinol, ((S)-6-bromo-1; 2-glyoxalidine thick [1,2-a] quinoline-2-yl) two (3, the 5-trifluoromethyl) methyl alcohol or ((1S; 2S)-and 6-bromo-1-methyl isophthalic acid, 2-glyoxalidine thick [1,2-a] quinoline-2-yl) diphenyl-carbinol.
6. quinoline as claimed in claim 1 is characterized in that, described quinoline is a compound shown in the formula II:
Wherein: R
1Be H, Cl, Br or I, R
2Be H or substituted C
1～C
3Alkyl, R
3Be H or substituted C
1～C
3Alkyl, R
5Be 6 yuan of aromatic ring yls, and R
2And R
3In at least one is substituted C
1～C
3Alkyl;
Said substituted C
1～C
3Substituting group is in the alkyl: hydroxyl and 6 yuan of aromatic ring yls or hydroxyl and by C
1～C
3The substituted 6 yuan of aromatic ring yls of perfluoroalkyl.
7. quinoline as claimed in claim 6 is characterized in that, wherein R
1Be H or Br, R
2Be H or substituted methyl, R
3Be H or substituted methyl, R
5Be phenyl, and R
2And R
3In at least one is substituted methyl;
Substituting group is in the said substituted methyl: hydroxyl and phenyl or hydroxyl and by the substituted phenyl of perfluoro-methyl.
8. quinoline as claimed in claim 7 is characterized in that, wherein said substituted methyl is the group shown in formula III or the formula IV:
9. quinoline as claimed in claim 8 is characterized in that, described quinoline is: ((S)-7-bromo-2-phenyl-2,3-glyoxalidine thick [2,1-a] isoquinoline 99.9-10-yl) diphenyl-carbinol.
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|---|---|---|---|
| CN2010101150205A CN101787024B (en) | 2010-02-26 | 2010-02-26 | Quinoline |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101150205A CN101787024B (en) | 2010-02-26 | 2010-02-26 | Quinoline |
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| Publication Number | Publication Date |
|---|---|
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| CN101787024B true CN101787024B (en) | 2012-06-06 |
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|---|---|---|---|
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|---|---|---|---|---|
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