CN102206215B - Chiral compound - Google Patents
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- CN102206215B CN102206215B CN2010105490174A CN201010549017A CN102206215B CN 102206215 B CN102206215 B CN 102206215B CN 2010105490174 A CN2010105490174 A CN 2010105490174A CN 201010549017 A CN201010549017 A CN 201010549017A CN 102206215 B CN102206215 B CN 102206215B
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- 0 *[C@](CO)N(C[C@](*)N12)C1=Cc1ccccc1C2=O Chemical compound *[C@](CO)N(C[C@](*)N12)C1=Cc1ccccc1C2=O 0.000 description 1
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Abstract
The invention relates to a chiral compound, which is characterized by being shown by a chemical formulae in the specification, wherein R is selected from (-CH2CH(CH3)2) or (-CH(CH3)2) or (-Ph) or (-CH2Ph). The synthesis method for chiral compounds (I) and (II) comprises the following steps of: separately carrying out reflux reaction in chlorobenzene used as a solvent on 2-cyano phenyl acetonitrile, 1,2-bis(cyanomethyl)benzene and D-amino alcohol under a water-free oxygen-free condition in the presence of anhydrous ZnCl2 for 40-60 hours, and separating to obtain target products. The chiral compound presents excellent catalysis activity and high enantioselectivity in the asymmetric synthesis of mandel.
Description
One, technical field
The present invention relates to a kind of new compound and preparation method thereof, particularly a kind of chipal compounds and preparation method thereof exactly is a kind of chiral heterocycle compound and compound method thereof.
Two, background technology
Optically pure compound has special property and outstanding function because of it; Like the D-racemic melic acid; L-racemic melic acids etc. are rejected the composition of indusrial toxic spinoff through asymmetry catalysis, produce the homochiral medicine with single oriented structure; Thereby make pharmaceutical cpd purer, curative effect is faster when the treatment disease, the course of treatment is shorter.The research of chiral drug has become one of new direction of international new drug research at present, and national governments and each big pharmaceuticals drop into huge fund one after another, and the research and development of chiral catalyst are one of gordian techniquies of chiral drug exploitation, therefore extremely payes attention to.21 century is the century of chirality synthetic chemistry great development, calendar year 2001 Nobel chemistry Prize authorized three scientists that make significant contribution in the synthetic field of asymmetry catalysis, proved the importance of this research field.Although there are many asymmetric catalysis to be applied to industrial production, seek catalyzer cheap and easy to get, efficient, that selectivity is good and help producing and the process for catalytic synthesis of environment protection, remain the major issue that needs us to study and solve.
In recent years, both at home and abroad latest report miscellaneous bidentate, three teeth and Si Chi oxazoline part etc. and metal complex catalysts
[2]To hydrogenation
[3-5], Heck reaction
[6-8], allyl group alkylated reaction
[9-11], Diels-Alder reaction
[12-13], zinc ethyl is to aldehyde
[14-15]Addition reaction etc. have extraordinary catalytic activity, thereby receive widely and paying close attention to.[1-15]
1. open and give birth to bravely, Guo Jianquan, asymmetric catalysis, the .2002 of Science Press, 1.
2.Cozzi，P.G.；Menges，F.；Kaiser，S.Synlett.2003，833.
3.Tang，W.；Wang，W.；Zhang，X.Angew.Chem.，Int.Ed.Engl.2003，42，943.
4.Xu，G.；Gilbertson，S.R.Tetrahedron?Lett.2002，44，953.
5.Hilgraf，R.；Pfaltz，A.Synlett.1999，1814.
6.(a)Powell，M.T.；Hou，D.-R.；Perry，M.C.；Cui，X.；Burgess，K.J.Am.Chem.Soc.2001，123，8878.(b)Perry，M.C.；Cui，X.；Powell，M.T.；Hou，D.-R.；Reibenspies，J.H.；Burgess，K.J.Am.Chem.Soc.2003，125，113.
7.Gilbertson，S.R.；Xie，D.；Fu，Z.Tetrahedron?Lett.2001，42，368.
8.Hashimoto，Y.；Horie，Y.；Hayashi，M.；Saigo，K.Tetrahedron：Asymmetry?2000，11，2205.
9.Tu，T.；Deng，W.-P.；Hou，X.-L.；Dai，L.-X.；Dong，X.-C.Chem.Eur.J.2003，9，3073.
10.Gilbertson，S.R.；Xie，D.Angew.Chem.，Int.Ed.Engl.1999，38，2750.
11.Burgess，K.；Porte，A.M.Tetrahedron：Asymmetry?1998，9，2465.
12.Bolm，C.；Xiao，L.；Kesselgruber，M.Org.Biomol.Chem.2003，1，145.
13.Watanabe，K.；Hirasawa，T.；Hiroi，K.Chem.Pharm.Bull.2002，50，372.
14.Wipf，P.；Wang，X.Org.Lett.2002，4，1197.
15.Schinneri，M.；Seitz，M.；Kaiser，A.；Reiser，O.Org.Lett.2001，3，4259.
Application for a patent for invention 200910146269.X has put down in writing that 2-itrile group phenylacetonitrile and adjacent diethyl itrile group benzene and chirality L-amino alcohol are synthetic under the condition that catalyzer exists in organic solvent has developed a kind of chipal compounds; And I with the adjacent diethyl itrile group benzene of 2-itrile group phenylacetonitrile and chiral D-amino alcohol in organic solvent under the condition of catalyzer existence; Though only configuration is different; But they are two kinds of different materials; Have different purposes, for example the dextrorotatory form of propoxyphene is as anodyne, and levo form is as cough medicine; (S)-drug effect of Naproxen Base is 35 times of (R)-Naproxen Base drug effect, and (S)-Ibuprofen BP/EP is (R) 28 times.The present invention is raw material synthetic D-type chipal compounds in order to the D-amino alcohol respectively and is that raw material synthetic L-type chipal compounds is done catalyst phenyl aldehyde nitrile silicification reaction with the L-amino alcohol; Obtain two kinds of products that configuration is opposite; With the further hydrolysis of product; Acidifying; Can obtain two kinds of racemic melic acids that configuration is opposite, the R-racemic melic acid is used for the side chain modifier of Cephalosporins series microbiotic cefadole, and the S-racemic melic acid is the synthetic precursor raw material that is used to treat urgent urination, frequent micturition and urinary incontinence medicine S-Oxybutynin.
Three, summary of the invention
The present invention is intended to provide a kind of efficient chiral catalyst required chipal compounds part for the asymmetric synthesis field particularly prepares chiral drug, and technical problem to be solved is to select corresponding raw material and set up corresponding method synthesis of chiral catalyst ligand.
(1) the alleged chipal compounds of the present invention is the compound shown in the following chemical formula I:
R is selected from isobutyl-(CH in the formula
2CH (CH
3)
2) or sec.-propyl (CH (CH
3)
2) or phenyl is (Ph) or benzyl (CH
2Ph).Four kinds of chipal compounds by above group constitutes are claimed 1a, 1b, 1c and 1d, its chemical name successively: 1,2,3, and 10b-tetrahydro--β (R)-R base-4 (R)-R base-5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone.
(2) the present invention alleged second kind of chipal compounds be the compound shown in the following chemical formula II:
R is selected from isobutyl-(CH in the formula
2CH (CH
3)
2) or sec.-propyl (CH (CH
3)
2) or phenyl is (Ph) or benzyl (CH
2Ph).Four kinds of chipal compounds by above group constitutes are claimed 2a, 2b, 2c and 2d successively, its chemical name N-2-hydroxyethyl-β (R)-R base-3-[(4 (R)-R base-4,5-dihydro)]-amino indenes of oxazolinyl-2-.
The compound method of chipal compounds (I) and (II) respectively with 2-itrile group phenylacetonitrile and adjacent diethyl itrile group benzene and chiral D-amino alcohol in organic solvent under the catalyzer existence condition synthetic, reaction formula is following:
R is selected from isobutyl-(CH in the formula
2CH (CH
3)
2) or sec.-propyl (CH (CH
3)
2) or phenyl is (Ph) or benzyl (CH
2Ph).
That the compound method of this chipal compounds (I) and (II) comprises is synthetic, separate and purifying, described synthetic be exactly that 2-itrile group phenylacetonitrile and adjacent diethyl itrile group benzene and chiral D-amino alcohol have ZnCl in chlorobenzene
2Reacted 20～30 hours ZnCl when existing in anhydrous and oxygen-free condition refluxed
2Consumption is the 1～3wt% (weight percent, down together) of material quantity.
Preferred ZnCl
2Consumption is the 2wt% of material quantity.
The preparation of this chipal compounds, adopt simple and easy, methodology of organic synthesis efficiently, one-step synthesis chipal compounds ligand 1 a～1d and 2a～2d, they are warp respectively
1HNMR, IR characterizes, and it shows good catalytic activity and high enantioselectivity as catalyzer in the racemic melic acid asymmetric synthesis.
Four, description of drawings
Fig. 1, Fig. 3, Fig. 5, Fig. 7, Fig. 9, Figure 11, Figure 13, Figure 15 are respectively compound 1a, 1b, 1c, 1d and 2a, 2b, 2c, 2d
1HNMR figure.
Fig. 2, Fig. 4, Fig. 6, Fig. 8, Figure 10, Figure 12, Figure 14, Figure 16 are respectively compound 1a, 1b, 1c, 1d and 2a, 2b, 2c, 2d
13CNMR figure.
Five, embodiment
1,1a:1,2,3, being prepared in the 100mL two-mouth bottle of 10b-tetrahydro--β (R)-isobutyl--4 (R)-isobutyl--5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone under the anhydrous and oxygen-free condition, adds anhydrous ZnCl
2120mg (0.74mmol), the 40ml chlorobenzene, 2-itrile group phenylacetonitrile 2.0g (11.2mmol), D-leucinol 6g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove,, residuum is used water dissolution, and uses CHCl
3(20mLx2) extraction, organic phase is used anhydrous sodium sulfate drying, and rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got yellow oily liquid 1.379g, productive rate 72%; [a]
5 D=+91.3 ° of (c=0.49, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=8.08 (d, J=8Hz, 1H), 7.33 (d, J=0Hz, 1H); 7.13 (d, J=8Hz, 1H), 6.98 (t, J=0Hz, 1H), 4.64 (t, J=0.5Hz; 1H), 3.69～3.71 (m, 4H), 3.55～3.58 (t, J=0Hz, 1H), 3.32～3.34 (d, J=8.5Hz; 2H), 1.92～1.96 (d, J=0.5Hz, 1H), 1.36～1.48 (m, 5H), 0.85～0.98 (m, 12H).
13CNMR 21.48,22.51, and 22.83,23.52,24.83,25.23,36.54,40.52,47.84; 53.83,54.37,62.63,77.73,119.97,121.40,123.90,126.96,132.07; 140.65,147.02,160.91, IR:3404,3068,2962,2929,2874,1653; 1603,1530,1466,1370,1232,1159,1074,756.HRMS (EI): m/z (%): calcd for C
21H
30N
2O
2: 342.2307; Found:342.2302.
2,1b:1,2,3, the preparation of 10b-tetrahydro--β (R)-sec.-propyl-4 (R)-sec.-propyl-5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone feeds intake and operates with example 1.
Weak yellow liquid, productive rate 76%, [a]
5 D=+113.98 ° of (c=0.0896, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=7.81 (d, J=7.5Hz, 1H), 7.26～7.38 (m, 3H), 4.07～4.36 (m, 1H), 4.07～4.23 (m, 6H), 3.86～3.92 (m, 3H), 1.72～1.82 (m, 2H), 0.84～1.04 (m, 12H).
13CNMR 18.37,18.80, and 19.06,19.45,29.01,32.90,41.99,58.09,64.47; 69.86,73.17,127.62,129.99,131.38,131.48,132.94,136.57; 164.14,172.87.IR:3412,3269,3060,2926,2873,2853,1710; 1549,1359,1248,1162,1061,965,773,723.HRMS (EI): m/z (%): calcd for C
19H
28N
2O
2: 316.2151; Found:316.2152.2a:
3,1c 1,2,3, the preparation of 10b-tetrahydro--β (R)-phenyl-4 (R)-phenyl-5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone
Feed intake and operate with the example 1,
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl
2120mg (0.74mmol), the 40ml chlorobenzene, 2-itrile group phenylacetonitrile 2.0g (11.2mmol), D-benzene glycinol 6g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove,, residuum is used water dissolution, and uses CHCl
3(20mLx2) extraction, organic phase is used anhydrous sodium sulfate drying, and rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got yellow solid 3.251g, productive rate 76%; Fusing point: 88～90 ℃, [a]
5 D=217.39 ° of (c=0.03, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), and δ (ppm)=8.08 (d, J=8.1Hz, 1H), 7.25～7.45m, 12H), 7.11 (m; 1H), 5.65 (dd, J=4Hz, 3.5Hz, 2H), 5.05～5.07 (m, 1H), 4.08～4.11 (m; 3H), 3.89 (m, 1H) .3.62～3.65 (m, 1H), 2.83～2.96 (m, 3H)
13CNMR 52.49,57.86,60.08 (x2), 62.13 (x2), 120.95,122.41,124.42,125.92 (x2), 127.68; 127.73,128.27 (x2), 128.63 (x2), 129.10,129.17,132.57 (x2), 135.50,140.09,160.69 (x2) .IR:3290; 3031,2894,1650,1616,1593,1551,1486,1455,1432; 1269,1258,1151,1051,1026,770,753,699,691.HRMS (EI): m/z (%): calcd for C
25H
22N
2O
2: 382.1681; Found:382.1676.
4,1d:1,2,3, the preparation of 10b-tetrahydro--β (R)-benzyl-4-(R)-benzyl-5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone
Feed intake and operate with the example 1.
Productive rate 82% [a]
5 D=29.7 ° of (c=0.34, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=8.36 (d, J=13.5Hz, 1H), 7.21～7.58 (m, 13H), 5.50 (s, 1H), 5.07 (t, J=0.5Hz, 1H), 3.83～3.85 (m, 1H), 3.53～3.68 (m, 4H), 3.23～3.28 (m, 2H), 2.83～2.96 (m, 3H),
13CNMR:33.58,36.76,46.67,55.48,58.22,61.68,78.28,122.05 (x2), 124.30 (x2); 126.87,127.04,127.37 (x2), 128.71,128.87,129.72 (x2), 132.47 (x2), 136.62,137.52; 140.68,147.03,161.08 (x2) .IR:3380,3062,3027,2927,2874,2245,1652; 1617,1596,1552,1486,1455,1430,1361,1271,1151; 1173,1150,1026,910,771,733,701,531.HRMS (EI): m/z (%): calcd for C
27H
26N
2O
2: 410.1994; Found:410.1991.
5, the preparation of the amino indenes of 2a:N-2-hydroxyethyl-β (R)-isobutyl--3-[4 (R)-(isobutyl-)-4,5-dihydro]-oxazolinyls-2-
In the 100mL two-mouth bottle, under the anhydrous and oxygen-free condition, add anhydrous ZnCl
2120mg (0.74mmol), the 40ml chlorobenzene, 1,2-benzyl cyanide 2.0g (11.2mmol), D-leucinol 6g, with the mixture 24h that at high temperature refluxes, stopped reaction, decompression is desolvated to remove,, residuum is used water dissolution, and uses CHCl
3(20mLx2) extraction, organic phase is used anhydrous sodium sulfate drying, and rotation removes and desolvates, and thick product with sherwood oil/methylene dichloride (4: 1) column chromatography, is got white solid 1.754g, productive rate 88%; Fusing point: 36～38 ℃, [a]
5 D=+55.24 ° of (c=0.85, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=7.51～7.53 (d, J=7.5Hz, 1H), 7.18～7.19 (m, 2H); 6.89～6.91 (t, J=5.5Hz, 1H), 4.36～4.39 (t, J=0.5Hz, 1H), 4.18～4.21 (m; 1H), 3.86～3.89 (t, J=0Hz, 1H), 3.66～3.67 (m, 3H), 3.49～3.53 (m; 4H), 1.71～1.81 (m, 2H), 1.36～1.41 (m, 4H), 0.89～0.96 (m, 12H).
13CNMR 22.89,23.08, and 25.69,45.73,65.48,73.44,128.33,130.55; 162.92..IR:3062,3030,2956,2921,2850,2870,1720; 1659,1617,1604,1492,1463,1378,1290; 1205,1073,1027,909,759,700,505.HRMS (EI): m/z (%): calcd for C
22H
32N
2O
2: 356.2464; Found:356.2460.
6, the preparation of the amino indenes of 2b:N-2-hydroxyethyl-β (R)-sec.-propyl-3-[4 (R)-(sec.-propyl)-4,5-dihydro]-oxazolinyls-2-
Feed intake and operate with the example 5.
Blue oily liquids, productive rate 89%, [a]
5 D=+112.95 ° of (c=0.06, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), and δ (ppm)=7.52～7.54 (d, J=8Hz, 1H), 7.17～7.19 (t; J=0.5Hz, 2H), 6.89～6.92 (m, 1H), 4.30～4.34 (t, J=0Hz; 1H), 3.95～4.04 (m, 3H), 3.33～3.74 (m, 5H), 3.31～3.32 (m; 1H), 1.89～1.90 (m, 1H), 1.69～1.71 (m, 1H) .0.89～0.97 (m, 12H).
13CNMR 17.86,18.61,18.73,19.92,30.32,33.55,36.77 (x2), 63.25,64.34,69.25; 70.89,118.23,120.77,122.99,127.07,133.66,144.01,164.44 (x2) .IR:3062,2956,2921; 2870,2850,2249,1720,1659,1655,1617,1604,1492,1463; 1378,1290,1205,1073,1027,909,759,735,700,648; HRMS (EI): m/z (%): calcd for C
20H
28N
2O
2: 328.2151; Found:328.2149.
7, the preparation of the amino indenes of 2c:N-2-hydroxyethyl-β (R)-phenyl-3-[4 (R)-(phenyl)-4,5-dihydro]-oxazolinyls-2-
Feed intake and operate with the example 5.
Productive rate 76%; Light blue oily liquids [a]
5 D=+63.54 ° of (c=0.87, CHCl
3);
1HNMR (500MHz, CDCl
3, 27 ℃), δ (ppm)=7.59 (d, J=7.5MHz, 1H), 7.26～7.35 (m, 10H); 7.16～7.17 (m, 2H), 6.91 (t, 1H), 5.38-5.41 (m, 1H); 4.67～4.72 (m, 3H), 4.15～4.18 (m, 1H), 3.77～3.81 (m, 3H); 3.59～3.63 (d, J=21.5Hz, 1H), 3.28～3.32 (d, J=21.5Hz, 1H).
13CNMR 36.52,61.54,66.61,68.09,73.48,96.14,118.65 (x2), 121.06 (x2), 122.97 (x2); 126.36,126.41,126.90,127.22,127.59 (x2), 128.50,128.64,133.96,139.41; 143.41,143.72,163.91,165.25.IR:3411,3004,2957,2925,2855,2252; 1713,1605,1492,1463,1362,1221,1092,1073; 1027,939,912,760,734,701,648,531.HRMS (EI): m/z (%): calcd for C
26H
24N
2O
2: 396.1838; Found:396.1847.
8, the preparation of the amino indenes of 2d:N-2-hydroxyethyl-β (R)-benzyl-3-[4-(R) (benzyl)-4,5-dihydro]-oxazolinyls-2-feeds intake and operates with example 5.
Productive rate 82%; Light blue oily liquids, [a]
5 D=+118.29 ° of (c=0.072, CHCl
3);
1HNMR (300MHz, CDCl
3, 27 ℃), δ (ppm)=7.59～7.62 (d, J=13Hz, 1H), 7.27～7.32 (m, 12H); 6.95～6.99 (t, J=0Hz, 1H), 4.41～4.46 (m, 1H), 4.29～4.34 (t; J=0.3Hz, 1H), 4.13～4.18 (t, J=0.6Hz, 1H), 3.47～3.67 (m; 5H), 3.13～3.20 (d, J=6.9Hz, 1H), 2.81～3.00 (m, 5H).
13CNMR:36.35,38.92,42.78,59.29,64.62,66.17,70.68,95.10,118.19,120.83,122.91; 126.28,126.64,126.99,128.39,128.55,129.21,133.62,137.74,138.86,143.63,163.65; 164.52.IR:3373,3061,3026,2924,1717,1575,1494,1454,1463,1362,1308; 9,1205,1095,1074,1029,1006,952,760,701,509.HRMS (EI): m-1/z (%): calcd forC
28H
27N
2O
2: 423.2073; Found:423.2079.
2,2-phenyl-2-(three silyloxies) propionitrile
The preparation of 2-(4-phenyl)-2-(trimethylsilyloxy) acetonitrile
0.15mmol catalyzer 1a, 1b, 1c and 1d (1mmol), phenyl aldehyde 0.1mL, TMSCN 0.3ml (3.3mmol) add down at 20～30 ℃ in succession, behind the 19h, add shrend go out behind the post layer (sherwood oil/methylene dichloride: 5/1), colourless oil liquid.
1H?NMR(300MHz，CDCl3)7.56-7.59(m，0.9Hz，2H)，7.31-7.34(m，3H)，5.43(s，1H)，0.16(s，9H).13C?NMR(75MHz，CDCl3)136.1，128.8(x2)，126.2(x2)，119.1，63.5，-0.39(x3).
| Catalyzer | Solvent | Temperature (℃) | Reaction times (my god) | Transformation efficiency % | ee％ | Configuration |
| 1a-D | Anhydrous methanol | 30-40 | 3d | 99 | 85 | R |
| 1b-D | Anhydrous methanol | 30-40 | 3d | 99 | 90 | R |
| 1c-D | Anhydrous methanol | 30-40 | 3d | 99 | 82 | R |
| 1d-D | Anhydrous methanol | 30-40 | 3d | 99 | 80 | R |
| 2a-D | Anhydrous methanol | 30-40 | 3d | 99 | 75 | R |
| 2b-D | Anhydrous methanol | 30-40 | 3d | 99 | 85 | R |
| 2c-D | Anhydrous methanol | 30-40 | 3d | 99 | 88 | R |
| 2d-D | Anhydrous methanol | 30-40 | 3d | 99 | 78 | R |
Contrast experiment: with under the condition that catalyzer exists, synthesizing in organic solvent with chirality L-amino alcohol of patented claim 200910146269.X record having developed two all chipal compounds 1,2,3 by 2-itrile group phenylacetonitrile and adjacent diethyl itrile group benzene; 10b-tetrahydro--β (R)-R base-4 (R)-R base-5H-imidazoles [2,3-b] isoquinoline 99.9-1-ethanol-5-ketone, N-2-hydroxyethyl-β (R)-R base-3-[(4 (R)-R base-4; The 5-dihydro)] the amino indenes of-oxazolinyls-2-is abbreviated as catalyzer 1a-L, 1b-L; 1c-L, 1d-L, 2a-L; 2b-L, 2c-L, 2d-L.
Similarity condition is done the contrast experiment down, and the result is following:
| Catalyzer | Solvent | Temperature (℃) | Reaction times (my god) | Transformation efficiency % | ee％ | Configuration |
| 1a-L | Anhydrous methanol | 30-40 | 3d | 99 | 83 | S |
| 1b-L | Anhydrous methanol | 30-40 | 3d | 99 | 88 | S |
| 1c-L | Anhydrous methanol | 30-40 | 3d | 99 | 80 | S |
| 1d-L | Anhydrous methanol | 30-40 | 3d | 99 | 78 | S |
| 2a-L | Anhydrous methanol | 30-40 | 3d | 99 | 73 | S |
| 2b-L | Anhydrous methanol | 30-40 | 3d | 99 | 86 | S |
| 2c-L | Anhydrous methanol | 30-40 | 3d | 99 | 77 | S |
| 2d-L | Anhydrous methanol | 30-40 | 3d | 99 | 70 | S |
3, the preparation of (R)/(S)-racemic melic acid
37%HCl 10mL joins in the 0.2g trimethylammonium nitrile alcohol silicon ethereal solution, and mixture is at 80-100 ℃ of backflow 2h, and with extracted with diethyl ether (3x10mL) dried over sodium sulfate, rotation removes and desolvates, and gets racemic melic acid.
1HNMR(300MHz，CD
3OCD
3)7.49-7.52(m，2H)，7.28-7.38(m，3H)，5.22(s，1H).
13C?NMR(75MHz，CDCl
3)205.95，174.17，128.76，128.42，127.22，73.18。
Claims (2)
1. chipal compounds is characterized in that: by formula (I) expression,
R is selected from (CH in the formula
2CH (CH
3)
2) or (CH (CH
3)
2) or (Ph) or (CH
2Ph).
2. chipal compounds is characterized in that: by formula (II) expression,
R is selected from (CH in the formula
2CH (CH
3)
2) or (CH (CH
3)
2) or (Ph) or (CH
2Ph).
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|---|---|---|---|---|
| CN1939911A (en) * | 2006-09-09 | 2007-04-04 | 合肥工业大学 | Chiral oxazoline and its production |
| CN101279954A (en) * | 2008-05-14 | 2008-10-08 | 合肥工业大学 | Chiral oxazoline and synthetic method thereof |
| CN101613350A (en) * | 2008-06-30 | 2009-12-30 | 合肥工业大学 | A kind of chipal compounds and synthetic method thereof |
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| CN1939911A (en) * | 2006-09-09 | 2007-04-04 | 合肥工业大学 | Chiral oxazoline and its production |
| CN101279954A (en) * | 2008-05-14 | 2008-10-08 | 合肥工业大学 | Chiral oxazoline and synthetic method thereof |
| CN101613350A (en) * | 2008-06-30 | 2009-12-30 | 合肥工业大学 | A kind of chipal compounds and synthetic method thereof |
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