CN1053186C - Quinolinoxazole compound - Google Patents

Quinolinoxazole compound Download PDF

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CN1053186C
CN1053186C CN98110943A CN98110943A CN1053186C CN 1053186 C CN1053186 C CN 1053186C CN 98110943 A CN98110943 A CN 98110943A CN 98110943 A CN98110943 A CN 98110943A CN 1053186 C CN1053186 C CN 1053186C
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compound
quinolinoxazole
quinoline
oxazoline
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CN1201793A (en
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周其林
伍新燕
李向宏
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East China University of Science and Technology
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East China University of Science and Technology
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Abstract

The present invention belongs to the field of organic synthesis and relates to a quinolinoxazole compound. The present invention uses 8-quinoline carboxylic acid as a raw material to react with amino alcohol for generating the quinolinoxazole compound of the present invention. The quinolinoxazole compound has a chiral center on a bit 4. therefore, the compound has two optical isomers: a dextral quinolinoxazole compound and a sinistral quinolinoxazole compound; the isometric mixture of the two optical isomers becomes racemic quinolinoxazole. The quinolinoxazole compound of the present invention is a compound with wide purposes. For example, the quinolinoxazole compound can be used as a chiral ligand to react with asymmetrical cyclopropane, and has high stereo selectivity; an e. e. value can achieve more than 50%.

Description

Quinolinoxazole compound
The invention belongs to the organic synthesis field, relate to a class Quinolinoxazole compound.
Oxazoline and to have substituent compound be a kind of important organic intermediate all has in fields such as dyestuff, medicine, agricultural chemicals and materials very to use widely.In recent years, many patent disclosures have various substituting group De oxazoline compounds, for example:
(1) U.S.Patents 2,870, and 159,2,870,160,2,870,161,2,883,410 disclose 2 bit amino substituting group De oxazoline compounds respectively, and this compound has obtained important use in medicine is synthetic;
(2) U.S.Patents 2,865, and 856,2,911,419,2,964,471,2,924,571, disclose 2 heterocyclic substituent De oxazoline compounds respectively, this compound has obtained important use in the preparation of impregnating material;
(3) Henri Brunner is at " Catalyic Asymmetric Synthesis " Iwao Ojima Ed, VCH Publishers, reported the oxazoline compounds that 2-position pyridine replaces in 1993, this compounds has obtained important use in organic synthesis.
Along with industrial fast development, branch of industry needs the departments of science and technology constantly to research and develop Xin De oxazoline compounds, to satisfy the needs of organic synthesis industry.
The objective of the invention is to disclose a kind of Quinolinoxazole compounds.
Design of the present invention is such:
With the 8-Quinoline Carboxylic Acid is that raw material and amino alcohol react, and generates the said Quinolinoxazole compound of the present invention; When adopting the amino alcohol of different structure, can obtain the Quinolinoxazole compound of different structure.
The said Quinolinoxazole of the present invention is the compound with following chemical structure of general formula:
Figure C9811094300031
In the formula:
R 1Be H, Me, Et, i-Pr, i-Bu, t-Bu, Ph or PhCH 2In one;
R 2Be H, Me, Et, i-Pr, i-Bu, t-Bu, Ph or PhCH 2In one;
R 3Be one among H, Me, Et, i-Pr, i-Bu, the Ph;
X is among H, Me, t-Bu, Ph or the MeO;
n＝1～3；
R 1, R 2, R 3Can be identical, also can be different.
Said Quinolinoxazole compound, on 4, there is a chiral centre, so have two optically active isomers, one is the dextrorotation Quinolinoxazole compound---(4R)-Quinolinoxazoles, it two is left-handed Quinolinoxazole compound---(4S)-Quinolinoxazoles, and the equal amount of mixture of these two optically active isomers then becomes racemic modification---(±)-Quinolinoxazoles.Therefore, in fact the said Quinolinoxazole compound of the present invention comprises racemic modification, dextrorotatory form and levo form.Racemic modification, dextrorotatory form and levo form all have identical chemical structure of general formula, but have different three-dimensional arrangements and rotary light performance.
The said compound of the present invention can synthesize by following method:
With reaction raw materials 8-Quinoline Carboxylic Acid and thionyl chloride by 1: the weight ratio of (10～15) places reactor, reflux 10～20 hours, reaction solution is removed excessive thionyl chloride and is obtained quinoline formyl chlorine.The quinoline formyl chlorine of gained is dissolved in the chloroform, the amino alcohol that under-10 ℃ condition, adds 0.8～1.2 times (mol ratio), drip the trolamine of 3 times (weight ratios) again, reacted 20～30 hours down at 25 ℃, reaction solution obtains crude product through washing and drying except that after desolvating, obtain amide compound through silica gel column chromatography again, productive rate 60～85% (calculating) by 8-Quinoline Carboxylic Acid, amide compound is dissolved in the chloroform, 25 ℃ of thionyl chlorides that drip 2～3 times (weight ratios) down, refluxed 1 hour, through washing and drying remove desolvate after again through silica gel column chromatography, obtain pure chloro-product, chloro thing and sodium hydroxide refluxed in methyl alcohol 10～20 hours, the reaction solution chloroform extraction, extraction liquid is through washing, dry back is removed and is desolvated, and thick product obtains pure Quinolinoxazole compound with recrystallization or silica gel column chromatography.Reaction process is shown below:
Figure C9811094300051
R 1, R 2, R 3, X and n be same as above.
The said Quinolinoxazole compound of the present invention is a kind of purposes compound very widely, for example can be used as chiral ligand and is used for asymmetric cyclopropanization reaction, and its reaction formula is:
Figure C9811094300052
In the formula: L *=(4S)-2-(8 '-quinoline)-4-benzyl-2-oxazoline
Because the complex compound that said Quinolinoxazole compound of the present invention and copper form has suitable configuration, therefore this cyclopropanization reaction had higher stereoselectivity, e.e. value reaches more than 50%, and corresponding Bi Ding oxazoline chiral ligand does not then have stereoselectivity to this reaction.
To be further elaborated the said compound of the present invention by embodiment below.
Embodiment 1
(±)-2-(8 '-quinoline)-4-phenyl-2-oxazoline, its chemical structural formula is as follows:
This compound process is as follows:
3.46 gram 8-Quinoline Carboxylic Acids and 29ml thionyl chlorides are placed have stirring, in the reactor of heating and reflux, reflux 8 hours, excessive thionyl chloride is removed in distillation, resulting 8-quinoline formyl chlorine dissolves with the 50ml chloroform, add 2.88 gram (±)-2-phenyl-2-monoethanolamines down at-10 ℃, drip the 14ml triethylamine again, be warming up to 25 ℃, restir 24 hours, reaction solution is water respectively, 5% sodium hydrogen carbonate solution and saturated common salt water washing, anhydrous sodium sulfate drying, rotary evaporation removes the back resistates that desolvates through silica gel column chromatography (eluent is ethyl acetate/petroleum ether 1: 1), obtains white solid amide compound 4.30 grams, and productive rate is 69%; These compound 3.83 grams are dissolved in the 100ml chloroform, drip the 4.8ml thionyl chloride down at 25 ℃, adding the back refluxed 1 hour, be cooled to 25 ℃ and add 20ml water, tell organic phase, sodium hydrogen carbonate solution with 5% and saturated common salt water washing, anhydrous sodium sulfate drying, rotary evaporation removes desolvate back resistates and 1.16 gram sodium hydroxide and 150ml methanol mixed, and reflux boiled off methyl alcohol after 15 hours, the saturated common salt water washing of resistates chloroform extraction, extraction liquid, anhydrous sodium sulfate drying, rotatory evaporator removes and desolvates after silica gel column chromatography (eluent is ethyl acetate/petroleum ether 2: 1), obtain white solid (±)-2-(8 '-quinoline)-4-phenyl-2-oxazoline 1.46 grams, productive rate is 40%, and fusing point is 133 ℃.Spectral data is as follows: 1H NMR (CDCl 3): δ (ppm) 4.45 (m, 1H), 4.98 (dd, J=8.4,1.7Hz, 1H), 5.58 (dd, J=8.1,2.1Hz, 1H), 7.38 (m, 6H), 7.60 (dd, J=7.8,0.8Hz, 1H), 7.96 (dd, J=6.9,1.3Hz, 1H), 8.22 (m, 2H), 9.11 (dd, J=2.6,1.7 Hz, 1H) IR (KBr compressing tablet): (cm -1) 1649,1611,1592,1577,495,1472,1454,1387,1353,1320,1292,1277,1250,1191,1126,1011MS:m/e (%) 274 (M +) (16.7), 244 (57.8), 243 (67.1), 156 (100), 155 (27.5), 128 (22.6), 118 (16.8) ultimate analysis (C 18H 14N 2O): C:78.80, H:5.22, N:10.10
Embodiment 2
(4S)-2-(8 '-quinoline)-4-phenyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (S)-2-phenyl-2-monoethanolamine replacement embodiment 1, preparation method, chemical structural formula, spectral data and ultimate analysis are identical with embodiment 1,136 ℃ of fusing points, [α] 20 D=-50 (c0.8, EtOH).
Embodiment 3
(4R)-2-(8 '-quinoline)-4-phenyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (R)-2-phenyl-2-monoethanolamine replacement embodiment 1, preparation method, chemical structural formula, spectral data and ultimate analysis are identical with embodiment 1,132 ℃ of fusing points, [α] 20 D=+51 (c0.6, EtOH).
Embodiment 4
(4S)-and 2-(8 '-quinoline)-4-benzyl-2-oxazoline, its chemical structural formula is:
Figure C9811094300071
With (±)-2-phenyl-2-monoethanolamine among (S)-3-phenyl-2-amino-1-propyl alcohol replacement embodiment 1, other process is identical with embodiment 1.(4S)-and 2-(8 '-quinoline)-4-benzyl-2-oxazoline is a white solid, fusing point is 96 ℃, [α] 20 D=-8 (c0.8, EtOH); Spectral data is as follows: 1H NMR (CDCl 3): δ (ppm) 2.80 (dd, J=9.0,4.7Hz, 1H), 3.30 (dd, J=8.9,4.8Hz, 1H), 4.22 (dd, J=7.5,0.8Hz, 1H), 4.46 (dd, J=4.5,3.2Hz, 1H), 4.72 (m, 1H), 7.22 (m, 5H), 7.38 (dd, J=4.2,4.2Hz, 1H), 7.49 (dd, J=7.3,1.2Hz, 1H), 7.85 (dd, J=6.9,1.3Hz, 1H), 8.04 (dd, J=5.3,1.2Hz, 1H), 8.11 (dd, J=1.8,6.5Hz, 1H), 9.02 (dd, J=2.5,1.8 Hz, 1H) IR (KBr compressing tablet): (cm -1) 1656,1612,1602,1592,1578,1494,1471,1451,1389,1367,1356,1303,1286,1258,1194,1138,1072,1017,1005MS:m/e (%) 289 (M +) (37.8), 198 (88.6), 197 (89.0), 169 (62.7), 155 (70.6), 144 (27.1), 143 (100), 128 (60.8) ultimate analysis (C 19H 16N 2O): C:77.70, H:5.60, N:9.44
Embodiment 5
(4R)-2-(8 '-quinoline)-4-benzyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (R)-3-phenyl-2-amino-1-propyl alcohol replacement embodiment 1, other process is identical with embodiment 1.Chemical structural formula, spectral data and ultimate analysis are identical with embodiment 4, and white solid, fusing point are 97 ℃, [α] 20 D=+8.4 (c0.8, EtOH).
Embodiment 6
(±)-2-(8 '-quinoline)-4-methyl-2-oxazoline, its chemical structural formula is:
Figure C9811094300081
With (±)-2-phenyl-2-monoethanolamine among (±)-2-amino-1-propyl alcohol replacement embodiment 1, other process is identical with embodiment 1.(±)-2-(8 '-quinoline)-4-methyl-2-oxazoline is a white solid, and fusing point is 114 ℃; 1H NMR (CDCl 3): δ (ppm) 1.46 (dd, J=5.3Hz, 3H), 4.08 (t, J=7.6Hz, 1H), 4.61 (m, 2H), 7.43 (dd, J=4.2,4.1Hz, 1H), 7.56 (m, 1H), 7.91 (dd, J=6.8,1.4Hz, 1H), 8.16 (m, 2H), 9.077 (dd, J=1.8,1.2Hz, 1H), 7.85 (dd, J=6.9,1.3Hz, 1H), 8.04 (dd, J=5.3,1.2Hz, 1H), 8.11 (dd, J=1.8,1.4Hz, 1H) IR (coating): (cm -1) 1650,1594,1574,1546,1499,1473,1451,1388,1374,1355,1342,1296,1262,1258,1192,1142,1131,1061,1009MS:m/e (%) 212 (M +) (61.9), 197 (63.8), 181 (24.8), 171 (20.8), 156 (100), 155 (58.7), 154 (27.3), 142 (54.0), 129 (78.5), 128 (45.4) ultimate analysis (C 13H 12N 2O): C:71.77, H:5.96, N:13.24
Embodiment 7
(4S)-2-(8 '-quinoline)-4-methyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (S)-2-amino-1-propyl alcohol replacement embodiment 1, other process is identical with embodiment 1.Chemical structural formula, spectral data and ultimate analysis are identical with embodiment 6, and fusing point is 121 ℃, [α] 20 D=-42 (c0.6, EtOH).
Embodiment 8 (±)-2-(8 '-quinoline)-4-sec.-propyl-2-oxazoline, its chemical structural formula is:
With (±)-2-phenyl-2-monoethanolamine among (±)-2-amino-3-methyl isophthalic acid-butanols replacement embodiment 1, other process is identical with embodiment 1.(±)-2-(8 '-quinoline)-4-sec.-propyl-2-oxazoline is an oily matter; 1H NMR (CDCl 3): δ (ppm) 0.97 (dd, J=8.7Hz, 6H), 1.92 (m, 1H), 3.24 (m, 2H), 4.51 (m, 1H), 7.33 (dd, J=4.2,3.5Hz, 1H), 7.46 (m, 1H), 7.80 (dd, J=6.8,1.4Hz, 1H), 8.05 (m, 2H), 8.96 (dd, J=2.4,1.7Hz, 1H) IR (coating): (cm -1) 1657,1610,1594,1575,1498,1468,1387,13512,1298,1284,1256,1192,1140,1128,1066,1004MS:m/e (%) 197 (82.0), 198 (49.5), 168 (23.80,156 (63.6), 155 (42.1), 144 (15.1), 143 (100), 128 (48.8) ultimate analysis (C 15H 16N 2O): C:73.19, H:6.74, N:11.73
Embodiment 9
(4S)-2-(8 '-quinoline)-4-sec.-propyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (S)-2-amino-3-methyl isophthalic acid-butanols replacement embodiment 1, other process is identical with embodiment 1.Chemical structural formula, spectral data and ultimate analysis are identical with embodiment 8, oily matter, [α] 20 D=-59 (c0.9, EtOH).
Embodiment 10
(4R)-2-(8 '-quinoline)-4-sec.-propyl-2-oxazoline:
With (±)-2-phenyl-2-monoethanolamine among (R)-2-amino-3-methyl isophthalic acid-butanols replacement embodiment 1, other process is identical with embodiment 1.Chemical structural formula, spectral data and ultimate analysis are identical with embodiment 8, oily matter, [α] 20 D=+57.5 (c0.9, EtOH).
Embodiment 11 (4S)-2-(8 '-quinoline)-4-tertiary butyl-oxazolines, its chemical structural formula is:
Figure C9811094300101
With (S)-2-amino-3,3-dimethyl-1-butanols replaces (±)-2-phenyl-2-monoethanolamine among the embodiment 1, and other process is identical with embodiment 1.Oily matter, [α] 20 D=-72 (c1.0, EtOH). 1H NMR (CDCl 3): δ (ppm) 1.05 (s, 9H), 4.20 (m, 1H), 4.39 (t, J=8.3Hz, 1H), 4.61 (m, 1H), 7.42 (dd, J=4.2,4.1Hz, 1H), 7.66 (dd, J=7.2,1.0Hz, 1H), 7.90 (dd, J=6.7,1.5Hz, 1H), 8.08 (dd, J=5.6,1.5Hz, 1H), 8.16 (dd, J=6.5,1.8Hz, 1H), 9.03 (dd, J=2.4,1.8Hz, 1H) IR (coating): (cm -1) 1656,1610,1594,1574,1550,1499,1478,1393,1354,1399,1297,1260,1208,1192,1139,1129,1066,1046,1012MS:m/e (%) 256 (M + 2) (37.7), 254 (M +) (100), 197 (84.8), 196 (11.8), 169 (31.5), 156 (29.9), 14 (35.9) ultimate analysis (C 16H 18N 2O): C:78.33, H:7.83, N:12.01
Embodiment 12
(4R)-2-(8 '-quinoline)-4-tertiary butyl-2-oxazoline:
With (R)-2-amino-3,3-dimethyl-1-butanols replaces (±)-2-phenyl-2-monoethanolamine among the embodiment 1, and other process is identical with embodiment 1.Chemical structural formula, spectral data and ultimate analysis are identical with embodiment 11, oily matter, [α] 20 D=+73.8 (c1.0, EtOH).

Claims (4)

1. Quinolinoxazole compound is characterized in that having following chemical structure of general formula:
Figure C9811094300021
In the formula:
R 1Be H, Me, Et, i-Pr, i-Bu, t-Bu, Ph or PhCH 2In one;
R 2Be H, Me, Et, i-Pr, i-Bu, t-Bu, Ph or PhCH 2In one;
R 3Be one among H, Me, Et, i-Pr, i-Bu, the Ph;
X is among H, Me, t-Bu, Ph or the MeO;
n＝1～3；
R 1, R 2, R 3Can be identical, also can be different.
2. compound as claimed in claim 1 is characterized in that-Quinolinoxazoles for a kind of racemization Quinolinoxazole compound-(±).
3. compound as claimed in claim 1 is characterized in that being-Quinolinoxazoles of a kind of dextrorotation Quinolinoxazole compound-(4R).
4. compound as claimed in claim 1 is characterized in that being-Quinolinoxazoles of a kind of left-handed Quinolinoxazole compound-(4S).
CN98110943A 1998-07-09 1998-07-09 Quinolinoxazole compound Expired - Fee Related CN1053186C (en)

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CN108774216A (en) * 2018-02-11 2018-11-09 尚谷科技（天津）有限公司 A kind of list tooth Pei Wei oxazoline ligands and its preparation method and application

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6145169A (en) * 1984-08-06 1986-03-05 Aisin Warner Ltd Automatic speed change gear case for car
EP0612743A1 (en) * 1993-02-26 1994-08-31 Takeda Chemical Industries, Ltd. Oxazolidinedione derivatives, their production and use in lowering blood sugar and lipid levels

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6145169A (en) * 1984-08-06 1986-03-05 Aisin Warner Ltd Automatic speed change gear case for car
EP0612743A1 (en) * 1993-02-26 1994-08-31 Takeda Chemical Industries, Ltd. Oxazolidinedione derivatives, their production and use in lowering blood sugar and lipid levels

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