(1R,2R) or (1S,2S)-1-(4'-substitute-1'8'-naphthoyl imdo group)-2-amino cyclohexane, preparation and application
A technology based on aminocyclohexane and naphthalimide, which is applied in the direction of organic chemistry methods, chemical instruments and methods, and organic racemization, can solve the problems of small inequalities in chemical shifts and application limitations, and achieve easy operation, Inexpensive and easy to synthesize effects
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Embodiment 1
[0023] Example 1: Preparation of (1R, 2R)-1-(1', 8'-naphthoimide)-2-aminocyclohexane 1
[0024] Add 240ml of cyclohexanediamine into 400ml of distilled water, heat to 75°C, and then control the temperature at 80-90°C while stirring, first add 150g (1mol) of (+)-tartaric acid in batches, and divide Add 100ml (1.7mol) of glacial acetic acid in batches to adjust the pH value to approximately equal to 6. Continue to stir, cool in an ice bath for 2 hours, filter with suction, wash with 80ml of ice water, then wash with 250×4ml of methanol, and dry in air to obtain white crystal {(-)chxnH 2}{(+)tart}144g, [α] D 20 =12.6° (c=2, H 2 O) [Document Value: [α] D 20 =12.2° (c=1, H 2 O) (Acta Chem. Scand. 1972, 26, 3605-3611)].
[0025] Heat the above mother liquor to 80°C, add 375g (2.5mol) of (+)-tartaric acid under stirring, stir overnight at room temperature, precipitate precipitate, filter, wash with 40ml of ice water, wash with 250×4ml of methanol, and dry in air to obtain whi...
Embodiment 2
[0028] Example 2: Preparation of (1R, 2R)-1-(4'-bromo-1', 8'-naphthalimide)-2-aminocyclohexane 2 Resolution of optically pure cyclohexanediamine Ditto.
[0029] Add the solution of 2.77g (0.01mol) 4-bromo-1,8-naphthalene dicarboxylic anhydride and 90mlDMF / ethanol (2: 1) in a 250ml three-neck round-bottomed flask, under nitrogen protection conditions, heating under reflux makes 4 -Bromo-1,8-naphthalene dicarboxylic anhydride was dissolved, and then 1.37g (0.012mol) (1R,2R)-cyclohexanediamine in 30ml DMF / ethanol (2:1 volume ratio) solution was added, and the solution was refluxed for half an hour. It becomes clear, then reflux for 4-5 hours, pour it into 1000ml of ice water while it is hot, and a large amount of solids precipitate out, filter with suction, wash with water, dry in a vacuum oven, and recrystallize twice with ethanol or acetonitrile to obtain a light yellow solid , is the target compound 2, yield: 95.0%; m.p.: 211-214°C; [α] D 20 =-12.8° (c=0.0625, CHCl 3 ); 1...
Embodiment 3
[0030] Example 3: Preparation of (1R, 2R)-1-(4'-(N, N-dimethylamino)-1', 8'-naphthalimide)-2-aminocyclohexane 3
[0031] The resolution of optically pure cyclohexanediamine is the same as above.
[0032] Add 1.2g (0.005mol) 4-(N,N-dimethylamino)-1,8-naphthalene dicarboxylic anhydride and 100ml ethanol solution in a 250ml three-necked round-bottomed flask, under nitrogen protection conditions, heat to reflux to make 4-(N,N-dimethylamino)-1,8-naphthalene dicarboxylic anhydride was dissolved, and then 0.68g (0.006mol) (1R,2R)-cyclohexanediamine in 30ml ethanol solution was added, and the solution was refluxed for half an hour. It becomes clear, then reflux for 4-5 hours, pour it into 500ml of ice water while it is hot, and a large amount of solids precipitate out, filter with suction, wash with water, dry in a vacuum oven, and recrystallize twice with ethanol or acetonitrile to obtain bright yellow needles. like crystals, the target compound 3, yield: 92.5%; m.p.: 183-184°C; [α]...
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