CN102766004A - Method for synthesizing aminoacyl arylamine - Google Patents
Method for synthesizing aminoacyl arylamine Download PDFInfo
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- CN102766004A CN102766004A CN2012102855715A CN201210285571A CN102766004A CN 102766004 A CN102766004 A CN 102766004A CN 2012102855715 A CN2012102855715 A CN 2012102855715A CN 201210285571 A CN201210285571 A CN 201210285571A CN 102766004 A CN102766004 A CN 102766004A
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- arylamine
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- phenylalanyl
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Abstract
Aminoacyl arylamine is widely used as medicine, chiral ligand, organic catalyst and intermediate. The conventional synthesizing method of aminoacyl arylamine is that amino acid is used first for synthesizing N-protection amino acid, then the N-protection amino acid and arylamine are blended to generate N-protection aminoacyl arylamine, and finally the N-protection aminoacyl arylamine is subjected to deprotection to obtain aminoacyl arylamine, and the conventional synthesizing method is many in synthesizing steps and high in cost. The invention discloses a method for synthesizing aminoacyl arylamine in one step, and the method is that copper salt catalysis amino acid amide and halogenated aromatics are subjected to C-N coupling to synthesize aminoacyl arylamine. By aid of C-N coupling reaction, chiral amino acid amide and halogenated aromatics are reacted to generate chiral aminoacyl arylamine.
Description
Technical field
This patent relates to that organic synthesis, medicine are synthetic, organic chemical industry's research field, concretely, is exactly to go on foot catalysis synthesizing amino acyl arylamine from amino acid amide and halogenated aryl hydrocarbon one.
Background technology
The aminoacyl arylamine extensively be present in medicine and the bioactive compound (
Eur. J. Med. Chem. 2011, 46,1331-1342;
J. Am. Chem. Soc. 2009, 131,11458-11470).Chiral amino acyl arylamine can also as chiral ligand and organic catalyst be used for asymmetric catalysis (
Tetrahedron Lett. 2001, 42,5045 – 5048;
Catal Lett. 2011, 141,872 – 876).In addition, the aminoacyl arylamine can also as the midbody of organic synthesis (
Org. Lett., 2008, 10,2905-2908).
The compound method of classical aminoacyl arylamine (
J. Chem. Soc.,
Perkin Trans. 1,
2001, 1767 – 1770;
Tetrahedron Lett. 200142; 5045 – 5048); Generally be made up of three reactions step: the acid anhydrides of (one) amino acid and tertbutyloxycarbonyl (Boc), carbobenzoxy-(Cbz) (Cbz) etc. or acyl chlorides synthesize amino such as N-Boc, N-Cbz and are protected amino acid, and the amino acid of protection such as (two) N-Boc, N-Cbz and aromatic amine condensation generate the aminoacyl arylamine of protections such as N-Boc, N-Cbz, and (three) remove protection bases such as Boc, Cbz and obtain the aminoacyl arylamine.This method is fit to aminoacyl arylamine synthetic of L configuration, D configuration and DL configuration, but synthesis step is more, and cost is high, and Atom economy is poor.In addition, recently bibliographical information the amination synthesizing amino acyl arylamine of ruthenium catalysis Alpha-hydroxy acid amides (
Angew. Chem. Int. Ed. 2011, 50,11197-11201), but product that can only synthesising racemation, and suitable product kind is fewer.The method that also has some synthesising racemation aminoacyl arylamine, and, the raw material mix more complicated (
Tetrahedron, 1996, 52,7585-7598), perhaps some other shortcoming.
Copper catalysis Ullmann type C-N coupling has had the history in more than 100 year, but does not see and the similar bibliographical information of this patent.
Summary of the invention
The present invention provides a kind of compound method of aminoacyl arylamine.
The compound method of aminoacyl arylamine disclosed by the invention was accomplished by a step, and promptly in the presence of alkali, C-N linked reaction one-step synthesis aminoacyl arylamine takes place for copper catalytic amino acid acid amides and halogenated aryl hydrocarbon.
Embodiment in conjunction with following sets forth the present invention in more detail, does not think that they limit the scope of the present invention.
Embodiment
Embodiment one
In the rub oral examination tube of drying belt magnetic stirring bar, add L-phenylalanyl amine (1.2 mmole), salt of wormwood (2.0 mmole) and cuprous iodide (0.05 mmole); Then, replace three times with high pure nitrogen or high-purity argon gas then with the sealing of turned welt soft rubber ball.Through syringe holder bromobenzene (1.0 mmole), N, N '-dimethyl-ethylenediamine (0.1 mmole) and toluene (6 milliliters) inject the test tube of turned welt soft rubber ball sealing.Then this test tube was put in the oil bath pan of 110 ° of C preheatings the heated and stirred reaction 24 hours.Let the reaction mixture cool to room temperature then, water cancellation reaction, with 20 milliliters of ethyl acetate extractions three times, the merging organic phase is used anhydrous sodium sulfate drying.The crude product that filtrating concentrates gained is with silica gel column chromatography, (volume ratio: 1/5 to 2/1) wash-out obtains light yellow solid L-phenylalanyl aniline, productive rate 86% with the mixed solvent of sherwood oil and ETHYLE ACETATE.Chiralcel OD-H high performance column (4.6 mm dias, 250 millimeters long, 5 the micron grain sizes) (moving phase: normal hexane/Virahol volume ratio 80/20) carry out the enantiomeric excess analysis that this L-phenylalanyl aniline product is produced with chirality liquid-phase chromatographic column Japan Daicel company on liquid chromatograph; The appearance time that at room temperature detects is 8.7 minutes (a L configuration) and 12.5 minutes (R configuration), and analytical results shows that the enantiomeric excess value of this product is 99%ee (a L configuration).
mp?59.6?~?60.8℃;?[α]
D 24?=?-83.3°?(c?=?0.20,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3)?δ?=?9.45?(s,?1H),?7.62?(d,?
J?=?7.7,?2H),?7.33?(m,?8H),?7.14?(t,?
J?=?7.4,?1H),?3.77?(dd,?
J?=?9.5,?3.9,?1H),?3.41?(dd,?
J?=?13.8,?3.9,?1H),?2.81?(dd,?
J?=?13.8,?9.6,?1H).?
13C?NMR?(CDCl
3):?40.74,?56.84,?119.48,?124.15,?126.97,?128.85,?129.00,?129.32,?137.71,?137.74,?172.37.?IR?(KBr),?v?(cm
-1):?3384.55,?3263.27,?3137.94,?3059.42,?3027.47,?2924.58,?2855.20,?2325.75,?1947.10,?1880.59,?1600.88,?1524.83,?1496.59,?1448.87,?1391.71,?1314.71,?1251.38,?1186.97,?1178.65,?1107.80,?1077.51,?1027.72,?1003.01,?963.82,?907.13,?882.24,?833.32,?752.82,?698.01,?617.13,?586.98,?509.40,?479.24.?Anal.?calcd.?for.?C
15H
16N
2O:?C,?74.97;?H,?6.71;?N,?11.66.?Found:?C,?74.89;?H,?6.63;?N,?11.56.
Embodiment two
Cuprous bromide replaces the cuprous iodide among the embodiment one, and the productive rate of L-phenylalanyl aniline is 83%.
Embodiment three
Cesium carbonate replaces the salt of wormwood among the embodiment one, and the productive rate of L-phenylalanyl aniline is 88%.
Embodiment four
Potassiumphosphate replaces the salt of wormwood among the embodiment one, and the productive rate of L-phenylalanyl aniline is 82%.
Embodiment five
Part N among the embodiment one, N '-dimethyl-ethylenediamine does not add fashionable, and the productive rate of L-phenylalanyl aniline is 68%.
Embodiment six
Iodobenzene replaces the bromobenzene among the embodiment one, and the productive rate of L-phenylalanyl aniline is 96%.
Embodiment seven
Chlorobenzene replaces the bromobenzene among the embodiment one, and the productive rate of L-phenylalanyl aniline is 21%.
Embodiment eight
The methyl bromobenzene is replaced the bromobenzene among the embodiment one, obtain yellow solid L-phenylalanyl para-totuidine, productive rate is 84%.
mp?84.1?~?85.0?℃;?[α]
D 24?=?-122.1°?(c?=?0.14,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3)?δ?=?8.46?(s,?1H),?6.62?(d,?
J?=?8.4,?2H),?6.44?(m,?6H),?6.28?(d,?
J?=?8.2,?2H),?2.87?(dd,?
J?=?9.5,?4.0,?1H),?2.51?(dd,?
J?=?13.8,?3.9,?1H),?1.93?(dd,?
J?=?13.8,?9.5,?1H),?1.45?(d,?
J?=?10.3,?3H),?0.75?(s,?3H),?0.41?(s,?1H).?
13C?NMR?(CDCl
3)?δ?=?166.98?(s),?132.55?(s),?129.93?(s),?128.48?(s),?124.15?(d,?J?=?16.1?Hz),?123.58?(s),?121.69?(s),?114.29?(s),?72.13?(s),?71.81?(s),?71.49?(s),?51.57?(s),?35.53?(s),?24.46?(s),?15.65?(s).?IR?(KBr),?v?(cm
-1):?3371.98,?3259.69,?3128.62,?3062,?38,?3030.28,?2920.96,?2861.67,?2348.98,?1671.40,?1645.92,?1605.35,?1453.63,?1408.02,?1340.39,?1315.96,?1260.28,?1242.72,?1178.34,?1106.59,?1074.24,?1019.52,?982.54,?972.71,?894.14,?820.35,?745.00,?716.42,?700.02,?668.58,?569.01,?548.58,?517.97,?486.30,?466.60.?Anal.?calcd.?for.?C
16H
18N
2O:?C,?75.56;?H,?7.13;?N,?11.01.?Found:?C,?75.46;?H,?7.08;?N,?10.92.
Embodiment nine
Between the methyl bromobenzene replace the bromobenzene among the embodiment one, obtain yellow liquid L-phenylalanyl meta-aminotoluene, productive rate is 76%.
[α]
D 24?=?-104.4°?(c?=?0.14,?CHCl
3):?
1H?NMR?(400?MHz,?CDCl
3)?δ?=?8.53?(s,?1H),?6.60?(s,?1H),?6.43?(ddt,?J?=?34.4,?17.1,?8.0,?8H),?6.08?(d,?J?=?7.5,?1H),?2.86?(dd,?J?=?9.2,?3.5,?1H),?2.51?(dd,?J?=?13.8,?3.9,?1H),?1.93?(dd,?J?=?13.8,?9.5,?1H),?1.50?(s,?3H).?
13C?NMR?(CDCl
3)?δ?=?167.19?,?133.63?,?132.46?(d,?J?=?10.2),?124.09?,?123.59?,?121.70?,?119.75?,?114.95?,?111.41,?51.60,?35.51,?26.71,?24.49,?24.15,?17.48,?16.28.?IR?(KBr),?v?(cm
-1):?3301.73,?3028.20,?2922.73,?2853.98,?1681.61,?1613.30,?1594.36,?1491.40,?1454.81,?1305.65,?1260.98,?1204.04,?1168.15,?1091.52,?1030.92,?872.57,?782.09,?748.30,?700.65,?662.67,?500.61.?Anal.?calcd.?for.?C
16H
18N
2O:?C,?75.56;?H,?7.13;?N,?11.01.?Found:?C,?75.46;?H,?7.07;?N,?10.02.
Embodiment ten
Adjacent methyl bromobenzene replaces the bromobenzene among the embodiment one, obtains yellow liquid L-phenylalanyl Ortho Toluidine, and productive rate is 55%.
[α]
D 24?=?-101.3°?(c?=?0.15,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3),?δ?(ppm):?7.21?(d,?
J?=?8.1?Hz,?1H),?6.43?(m,?2H),?6.35?(dt,?
J?=?18.2,?5.8,?4H),?6.27?(d,?
J?=?7.4?Hz,?1H),?6.15?(t,?
J?=?7.4?Hz,?1H),?2.87?(dd,?
J?=?9.2,?3.8?Hz,?1H),?2.47?(dd,?
J?=?13.8,?3.9?Hz,?1H),?1.93?(dd,?
J?=?13.8,?9.3?Hz,?1H),?1.32?(s,?3H),?0.76?(s,?2H),?0.39?(d,?
J?=10.0?Hz,?1H).?
13C?NMR?(CDCl
3),?δ?(ppm):?167.06?(s),?132.47?(s),?130.63?(s),?125.09?(s),?124.12?(s),?123.58?(s),?122.61?(s),?121.64?(d,?
J?=?15.7),?119.19?(s),?116.01?(s),?72.21?(s),?71.89?(s),?71.57?(s),?51.76?(s),?35.55?(s),?26.71?(s),?24.48?(s),?24.15?(s),?17.48?(s),?12.39?(s),?8.93?(s).?IR?(KBr),?v?(cm
-1):?3301.33,?3061.31,?3027.58,?2921.43,?2852.36,?1680.87,?1587.84,?1496.01,?1455.95,?1381.47,?1291.18,?1251.83,?1157.17,?1116.22,?1046.66,?1031.52,?896.72,?841.26,?754.17,?701.39,?618.64,?539.05,?493.90.?Anal.?calcd.?for.?C
16H
18N
2O:?C,?75.56;?H,?7.13;?N,?11.01.?Found:?C,?75.49;?H,?7.08;?N,?10.91.
Embodiment 11
The meta-methoxy bromobenzene replaces the bromobenzene among the embodiment one, obtains yellow oily liquid L-phenylalanyl m-anisidine, and productive rate is 77%.
[α]
D 24?=?-97.0°?(c?=?0.27,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3),?δ?(ppm):?8.57?(s,?1H),?6.48?(d,?
J?=?1.7,?1H),?6.32?(m,?7H),?6.16?(d,?
J?=?7.8?Hz,?1H),?5.74?(dd,?
J?=?8.1,?2.1?Hz,?1H),?2.79?(m,?4H),?2.39?(dd,?
J?=?13.6,?3.2?Hz,?1H),?1.84?(dd,?
J?=?13.6,?9.4?Hz,?1H),?0.97?(d,?
J?=?26.1?Hz,?2H),?0.37?(d,?
J?=?18.3?Hz,?1H).?
13C?NMR?(CDCl
3)?δ?=?168.03?(s),?155.43?(s),?134.31?(s),?133.01?(s),?124.95?(s),?124.60?(s),?124.06?(s),?122.18?(s),?107.18?(s),?105.28?(s),?100.63?(s),?73.00?(s),?72.68?(s),?72.36?(s),?52.15?(s),?50.51?(s),?36.01?(s),?27.24?(s),?24.85?(d,?
J?=?33.8),?18.02?(s),?9.50?(s).?IR?(KBr),?v?(cm
-1):?3298.38,?3061.55,?3027.87,?3002.95,?2932.87,?2839.93,?1953.40,?1682.44,?1528.24,?1494.90,?1454.92,?1429.29,?1315.40,?1286.99,?1264.14,?1209.39,?1157.09,?1079.40,?1048.00,?995.24,?957.51,?855.89,?771.05,?701.39,?663.62,?586.22,?501.85,?458.69.?Anal.?calcd.?for.?C
16H
18N
2O
2:?C,?71.09;?H,?6.71;?N,?10.36.?Found:?C,?70.00;?H,?6.65;?N,?10.28.
Embodiment 12
M-bromoxynil replaces the bromobenzene among the embodiment one, obtains cyano-aniline between yellow oily liquid L-phenylalanyl, and productive rate is 81%.
[α]
D 24?=?-16.9°?(c?=?0.24,?CHCl
3).?
1H?NMR?(300?MHz,?CDCl
3)?δ?=?9.67?(s,?1H),?7.98?(d,?J?=?16.6,?1H),?7.67?(d,?J?=?7.8,?1H),?7.26?(ddd,?J?=?22.9,?15.7,?7.7,?7H),?3.70?(s,?1H),?3.26?(dd,?J?=?13.7,?3.4,?1H),?2.78?(dd,?J?=?13.7,?9.2,?1H),?1.79?(s,?2H).?
13C?NMR?(75?MHz,?CDCl
3)?δ?=?172.82?(s),?138.24?(s),?136.96?(s),?129.34?(d,?J?=?14.1),?128.09?(m),?126.66?(s),?126.66?(s),?122.75?(m),?122.19?(s),?122.19?(s),?118.31?(s),?112.29?(s),?56.33?(s),?40.17?(s).?IR?(KBr),?v?(cm
-1):?3315.23,?3063.47,?3029.96,?2957.27,?2851.17,?2231.35,?1688.23,?1588.27,?1552.65,?1485.47,?1455.09,?1432.10,?1378.34,?1289.25,?1260.65,?1171.15,?1096.42,?1026.50,?889.89,?796.01,?748.86,?700.54,?682.77,?663.73,?614.64,?473.53.?Anal.?calcd.?for.?C
16H
15N
3O:?C,?72.43;?H,?5.70;?N,?15.84.?Found:?C,?72.33;?H,?5.61;?N,?15.76.
Embodiment 13
The nitro bromobenzene is replaced the bromobenzene among the embodiment one, obtain yellow solid L-phenylalanyl p-Nitroaniline, productive rate is 94%.
mp?155.4?~?156.2℃;?[α]
D 24?=?-156.6°?(c?=?0.14,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3),?δ?(ppm):?9.05?(s,?1H),?7.36?(m,?2H),?6.91?(m,?2H),?6.43?(m,?6H),?2.92?(dd,?
J?=?9.4,?3.9?Hz,?1H),?2.51?(dd,?
J?=?13.9,?3.9?Hz,?1H),?1.97?(dd,?
J?=?13.9,?9.4?Hz,?1H),?0.80?(s,?3H),?0.41?(m,?1H).?
13C?NMR?(CDCl
3),?δ?(ppm):?167.80?(s),?138.23?(d,?
J?=?4.5),?131.88?(s),?124.02?(s),?123.72?(s),?121.95?(s),?119.87?(s),?113.64?(s),?72.11?(s),?71.79?(s),?71.48?(s),?51.50?(s),?35.20?(s).?IR?(KBr),?v?(cm
-1):?3400.26,?3235.29,?3087.13,?3030.47,?2925.81,?2853.57,?2446.79,?1928.18,?1688.544,?1599.09,?1525.98,?1488.65,?1458.87,?1442.13,?1406.96,?1375.29,?1345.51,?1301.42,?1261.68,?1200.95,?1175.07,?1114.05,?1075.07,?1101.45,?1029.88,?1002.50,?960.78,?918.19,?882.45,?846.58,?809.84,?749.53,?701.43,?686.45,?663.56,?628.96,?612.21,?548.18,?529.42,?495.56,?486.03.?Anal.?calcd.?for.?C
15H
15N
3O
3:?C,?63.15;?H,?5.30;?N,?14.73.?Found:?C,?63.03;?H,?5.20;?N,?14.61.
Embodiment 14
P-bromobenzaldehyde replaces the bromobenzene among the embodiment one, obtains yellow oily liquid L-phenylalanyl to formyl radical aniline, and productive rate is 54%.
[α]
D 24?=?-2.9°?(c?=?0.17,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3),?δ?(ppm):?9.09?(s,?1H),?6.96?(s,?1H),?6.58?(m,?3H),?6.45?(m,?3H),?6.23?(m,?2H),?6.01?(s,?1H),?5.31?(s,?1H),?3.07?(m,?1H),?2.56?(dd,?J?=?13.4,?3.0,?1H),?2.09?(m,?1H).
13C?NMR?(CDCl
3),?δ?(ppm):185.53,?170.02,?156.03,?137,92,?132.07,?131.98,?129.69,?128.90,?127.13,?126.79,?125.39,?124.44,?119.50,?54.02,?35.77.?IR?(KBr),?v?(cm
-1):?3442.05,?3061.43,?3028.62,?2923.83,?2853.02,?1600.99,?1562.94,?1495.52,?1454.65,?1376.40,?1262.23,?1069.98,?1028.62,?872.44,?789.23,?751.08,?699.89,?663.72.?Anal.?calcd.?for.?C
16H
16N
2O
2:?C,?71.62;?H,?6.01;?N,?10.44.?Found:?C,?71.54;?H,?5.93;?N,?10.36.
Embodiment 15
P-Fluoro bromo benzene replace among the embodiment one bromobenzene, obtain yellow solid L-phenylalanyl para-fluoroaniline, productive rate is 56%.
mp?86.6?~?87.2℃;?[α]
D 24?=?+110.6°?(c?=?0.15,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3),?δ?(ppm):?8.55?(s,?1H),?6.69?(dd,?
J?=?8.8,?4.8?Hz,?2H),?6.44?(m,?6H),?6.16?(t,?
J?=?8.6?Hz,?2H),?2.88?(dd,?
J?=?9.3?Hz,?3.7,?1H),?2.51?(dd,?
J?=?13.8,?3.8?Hz,?1H),?1.93?(dd,?
J?=?13.8,?9.5?Hz,?1H),?0.77?(s,?3H),?0.42?(d,?
J?=?10.6?Hz,?1H).?
13C?NMR?(CDCl
3),?δ?(ppm):?167.08?(s),?155.24?(s),?152.82?(s),?132.37?(s),?128.55?(d,?
J?=?2.7?Hz),?124.06?(s),?123.61?(s),?121.76?(s),?115.91?(d,?
J?=?7.9?Hz),?110.47?(s),?110.24?(s),?72.12?(s),?71.80?(s),?71.49?(s),?51.46?(s),?35.44?(s),?24.46?(s).?IR?(KBr),?v?(cm
-1):?3384.74,?3266.19,?3064.73,?3028.47,?2923.36,?2853.76,?2112.03,?1953.11,?1886.82,?1660.37,?1607.38,?1454.34,?1409.70,?1327.53,?1300.03,?1245.06,?1214.12,?1156.44,?1110.19,?1097.76,?1028.95,?1012.96,?934.32,?915.58,?893.93,?869.89,?825.58,?772.25,?744.37,?697.02,?638.09,?616,33,?571.80,?513.16,?480.06,?469.16.?Anal.?calcd.?for.?C
15H
15FN
2O:?C,?69.75;?H,?5.85;?N,?10.85.?Found:?C,?69.67;?H,?5.73;?N,?10.77.
Embodiment 16
To toluene iodide replace among the embodiment one bromobenzene, obtain yellow solid L-phenylalanyl para-totuidine, productive rate is 93%.
Embodiment 17
Between ioxynil replace the bromobenzene among the embodiment one, obtain cyano-aniline between yellow oily liquid L-phenylalanyl, productive rate is 93%.
Embodiment 18
To the fluorine iodobenzene replace among the embodiment one bromobenzene, obtain yellow solid L-phenylalanyl para-fluoroaniline, productive rate is 76%.
Embodiment 19
P-Nitrophenyl chloride replace among the embodiment one bromobenzene, obtain yellow solid L-phenylalanyl p-Nitroaniline, productive rate is 47%.
Embodiment 20
DL-phenylalanyl amine replaces the L-phenylalanyl amine among the embodiment one, obtains light yellow solid DL-phenylalanyl aniline, productive rate 84%.
Embodiment 21
L-alanimamides hydrochloride replaces the L-phenylalanyl amine among the embodiment one, and the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-alanyl aniline, productive rate 62%.
[α]
D 24?=?-4.8°?(c?=?0.13,?CHCl
3):?
1H?NMR(400?MHz,?CDCl
3)?δ?=?9.41?(s,?1H),?7.51?(d,?J?=?7.8,?2H),?7.25?(q,?J?=?8.4,?2H),?7.02?(m,?1H),?3.52?(d,?J?=?6.3,?1H),?1.74?(s,?2H),?1.33?(m,?3H).
13C?NMR?(CDCl
3):?20.54,?50.13,123.00,?123.70,?127.55,?128.20,?128.55,?136.79,?172.81.?IR?(KBr),?v?(cm
-1):?3301.58,?3060.12,?2950.17,?2853.50,?1682.76,?1601.00,?1531.17,?1499.78,?1443.74,?1377.39,?1312.97,?1253.10,?1177.36,?1127.75,?1078.79,?1029.70,?905.92,?802.06,?756.51,?693.74,?662.55,?510.98.?Anal.?calcd.?for.?C
9H
12N
2O:?C,?65.83;?H,?7.37;?N,?17.06.?Found:?C,?65.75;?H,?7.29;?N,?16.96.
Embodiment 22
L-alanimamides hydrochloride replaces the L-phenylalanyl amine among the embodiment one, iodobenzene replace among the embodiment one bromobenzene, the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-alanyl aniline, productive rate 79%.
Embodiment 23
L-valine amide hydrochloride replaces the L-phenylalanyl amine among the embodiment one, and the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-valyl aniline, productive rate 68%.
[α]
D 24?=?-64.0°?(c?=?0.15,?CHCl
3):?
1H?NMR?(400?MHz,?CDCl
3):?δ?=?9.42?(s,?1H),?7.53?(d,?
J?=?7.9,?3H),?7.26?(t,?
J?=?7.9,?3H),?7.03?(t,?
J?=?7.4?Hz,?1H),?4.04?(m,?1H),?3.32?(d,?
J?=?3.3?Hz,?1H),?2.38?(dtd,?
J?=?13.8,?6.9,?3.7?Hz,?1H),?0.79?(m,?6H).?
13C?NMR?(CDCl
3):?13.10,?15.04,?18.69,?21.63,?29.87,?59.41,?118.77,?122.62,?127.98,?136.79,?171.89.?IR?(KBr),?v?(cm
-1):?3302.45,?3136.45,?3060.10,?2981.06,?2962.07,?2872.73,?1668.18,?1601.24,?1446.43,?1443.73,?1389.13,?1370.98,?1313.11,?1249.40,?1176.16,?1072.61,?1029.71,?985.83,?901.55,?802.54,?755.25,?693.07,?663.36,?530.00,?508.96.?Anal.?calcd.?for.?C
11H
16N
2O:?C,?68.72;?H,?8.39;?N,?14.57.?Found:?C,?68.66;?H,?8.31;?N,?14.48.
Embodiment 24
L-valine amide hydrochloride replaces the L-phenylalanyl amine among the embodiment one, iodobenzene replace among the embodiment one bromobenzene, the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-valyl aniline, productive rate 82%.
Embodiment 25
L-leucyl amine hydrochloride replaces the L-phenylalanyl amine among the embodiment one, and the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-leucyl aniline, productive rate 73%.
[α]
D 24?=?-24.4°?(c?=?0.13,?CHCl
3):?
1H?NMR?(400?MHz,?CDCl
3):?δ?=?9.54?(s,?1H),?7.62?(d,?
J?=?7.7?Hz,?2H),?7.34?(t,?
J?=?7.9?Hz,?2H),?7.11?(t,?
J?=?7.4?Hz,?1H),?5.31?(s,?1H),?3.53?(dd,?
J?=?9.9,?3.4?Hz,?1H),?1.80?(m,?3H),?0.99?(dd,?
J?=?11.0,?6.3,?6H).?
13C?NMR?(CDCl
3):?21.36,?23.42,?29.37,?31.93,?43.87,?53.93,?58.21,?119.43,?123.99,?128.95,?137.91,?173.85.?IR?(KBr),?v?(cm
-1):?3302.86,?3060.63,?2957.64,?2976.99,?2870.43,?1682.85,?1601.70,?1600,32,?1443.76,?1407.10,?1386,55,?1368.46,?1312.14,?1259.34,?1174.75,?1103.42,?1079.35,?1030.27,?903.57,?803.14,?755.53,?693.80,?616.57,?511.75.?Anal.?calcd.?for.?C
12H
18N
2O:?C,?69.87;?H,?8.80;?N,?13.58.?Found:?C,?69.75;?H,?8.72;?N,?13.49.
Embodiment 26
L-valine amide hydrochloride replaces the L-phenylalanyl amine among the embodiment one, iodobenzene replace among the embodiment one bromobenzene, the amount of salt of wormwood changes 3 mmoles into, obtains yellow liquid L-leucyl aniline, productive rate 86%.
Embodiment 27
L-benzene G-NH2 replaces the L-phenylalanyl amine among the embodiment one, obtains yellow liquid L-benzene glycyl aniline, productive rate 72%.
[α]
D 24=?-6.8°?(c?=?2.3,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3):?δ?=?9.31?(s,?1H),?7.52?(d,?
J?=?7.9,?2H),?7.36?(d,?
J?=?7.1?Hz,?2H),?7.26?(dt,?
J?=?6.6,?5.4?Hz,?5H),?7.02?(t,?
J?=?7.4?Hz,?1H),?4.56?(s,?1H),?3.63?(d,?
J?=?7.0?Hz,?1H).?
13C?NMR?(CDCl
3):?39.84,?39.98,?119.48,?124.00,?126.85,?127.95,?128.76,?128.82,?129.00,?129.32,?137.71,?137.74,?172.37.?IR?(KBr),?v?(cm
-1):?3268.56,?3061.34,?2961.16,?2924.42,?2853.13,?1599.65,?1538.85,?1490.08,?1444.47,?1384.63,?1313.70,?1261.10,?1106.92,?1025.54,?803.41,?755.34,?694.64,?617.30,?495.16.?Anal.?calcd.?for.?C
14H
14N
2O:?C,?74.31;?H,?6.24;?N,?12.38.?Found:?C,?74.23;?H,?6.19;?N,?12.28.
Embodiment 28
L-benzene G-NH2 replaces the L-phenylalanyl amine among the embodiment one, obtains yellow liquid L-benzene glycyl aniline, productive rate 90%.
Embodiment 29
The L-prolineamide replaces the L-phenylalanyl amine among the embodiment one, obtains yellow liquid L-prolyl aniline, productive rate 54%.
mp?68.6?~?70.2℃;?[α]
D 24?=?-50.8°?(c?=?0.13,?CHCl
3).?
1H?NMR?(400?MHz,?CDCl
3)?δ?=?9.45?(s,?1H),?7.62?(d,?
J?=?7.7,?2H),?7.33?(m,?8H),?7.14?(t,?
J?=?7.4,?1H),?3.77?(dd,?
J?=?9.5,?3.9,?1H),?3.41?(dd,?
J?=?13.8,?3.9,?1H),?2.81?(dd,?
J?=?13.8,?9.6,?1H).?
13C?NMR?(CDCl
3):?26.32,?30.77,?47.36,?61.04,?119.26,?123.89,?124.14,?128.95,?129.22,?137.88,?173.46.?IR?(KBr),?v?(cm
-1):?3050.85,?3231.63,?3056,93,?2966.29,?2873.16,?1947.58,?1872.76,?1669.12,?1600.49,?1442.72,?1410.71,?1313.90,?1300.05,?1246.62,?1213.09,?1180.46,?1148.72,?1103.05,?1080.07,?1000.97,?980.93,?926.83,?910.08,?884.19,?847.80,?755.53,?692.01,?653.21,?630.75,?577.94,?515.68,?488.72,?468.95.?Anal.?calcd.?for.?C
11H
14N
2O:?C,?69.45;?H,?7.42;?N,?14.73.?Found:?C,?69.33;?H,?7.37;?N,?14.68.
Embodiment 30
L-benzene G-NH2 replaces the L-phenylalanyl amine among the embodiment one, obtains yellow liquid L-prolyl aniline, productive rate 76%.
Claims (4)
1. the compound method of an aminoacyl arylamine is characterized in that: in the presence of alkali, and copper catalytic amino acid acid amides and halogenated aryl hydrocarbon C-N coupling one-step synthesis aminoacyl arylamine.
2. the compound method of claims 1 described a kind of aminoacyl arylamine is characterized in that said amino acid amide comprises phenylalanyl amine, alanimamides, valine amide, leucyl amine, benzene G-NH2, prolineamide; Their configuration comprises L configuration, D configuration and DL configuration; And the configuration of product is by the configuration decision of amino acid amide, and promptly L-phenylalanyl amine and bromobenzene or iodobenzene obtain L-phenylalanyl aniline through the C-N linked reaction.
3. the compound method of claims 1 described a kind of aminoacyl arylamine is characterized in that said copper catalyst by mantoquita and N, and N '-dimethyl-ethylenediamine part is formed; Mantoquita is cuprous iodide or cuprous bromide.
4. the compound method of claims 1 described a kind of aminoacyl arylamine is characterized in that said alkali is salt of wormwood, cesium carbonate or potassiumphosphate.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102976966A (en) * | 2012-11-27 | 2013-03-20 | 浙江大学 | Synthetic method for high-steric-hindrance tertiary amides |
| CN104610090A (en) * | 2015-03-04 | 2015-05-13 | 成都理工大学 | Synthetic process of chiral aryl lactyl aromatic amine |
| CN104672100A (en) * | 2015-02-27 | 2015-06-03 | 成都理工大学 | Synthetic process of alpha-hydroxy aryl acetyl arylamine |
| CN105732413A (en) * | 2016-03-25 | 2016-07-06 | 成都理工大学 | Synthetic process of chiral N-aromatic amino acid amide |
| CN110407830A (en) * | 2019-08-21 | 2019-11-05 | 河南师范大学 | A method of synthesis N- aryl phenothiazine compound |
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| CN102516103A (en) * | 2011-11-18 | 2012-06-27 | 成都理工大学 | Method for synthesizing N-o-nitrophenyl amino acid from o-chloronitrobenzene |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976966A (en) * | 2012-11-27 | 2013-03-20 | 浙江大学 | Synthetic method for high-steric-hindrance tertiary amides |
| CN102976966B (en) * | 2012-11-27 | 2015-01-28 | 浙江大学 | Synthetic method for high-steric-hindrance tertiary amides |
| CN104672100A (en) * | 2015-02-27 | 2015-06-03 | 成都理工大学 | Synthetic process of alpha-hydroxy aryl acetyl arylamine |
| CN104610090A (en) * | 2015-03-04 | 2015-05-13 | 成都理工大学 | Synthetic process of chiral aryl lactyl aromatic amine |
| CN105732413A (en) * | 2016-03-25 | 2016-07-06 | 成都理工大学 | Synthetic process of chiral N-aromatic amino acid amide |
| CN105732413B (en) * | 2016-03-25 | 2017-08-25 | 成都理工大学 | The synthesis technique of chiral N aryl amino acids acid amides |
| CN110407830A (en) * | 2019-08-21 | 2019-11-05 | 河南师范大学 | A method of synthesis N- aryl phenothiazine compound |
| CN110407830B (en) * | 2019-08-21 | 2020-08-04 | 河南师范大学 | Method for synthesizing N-arylphenothiazine compound |
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