CN1296360C - (1R,2R) or (1S,2S)-1-(4'-substitute-1'8'-naphthoyl imdo group)-2-amino cyclohexane, preparation and application - Google Patents
(1R,2R) or (1S,2S)-1-(4'-substitute-1'8'-naphthoyl imdo group)-2-amino cyclohexane, preparation and application Download PDFInfo
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- CN1296360C CN1296360C CNB2004100613558A CN200410061355A CN1296360C CN 1296360 C CN1296360 C CN 1296360C CN B2004100613558 A CNB2004100613558 A CN B2004100613558A CN 200410061355 A CN200410061355 A CN 200410061355A CN 1296360 C CN1296360 C CN 1296360C
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Abstract
The present invention discloses novel chiral dissolving agent (1R, 2R)-or (1S, 2S)-1-(4'-substitute-1'8'-naphthoyl imdo group)-2-amino cyclohexane, which has a structural formula disclosed in the right formula. The preparation method comprises the steps that: firstly, two kinds of optically pure trans (1R, 2R) or(1S, 2S)-cyclohexyldiamine are respectively prepared from dl-cyclohexyldiamine by resolution; then, the optically pure trans (1R, 2R) or (1S, 2S)-cyclohexyldiamine and 4-substituted-1, 8 naphthalic anhydride are treated by reflux in alcohol and N, N-dimethylformamide(DMF) or alcohol/DMF solutions under the condition of nitrogen protection for 4 to 5 hours and poured in ice water to separate a large quantity of solids; finally, the solids are recrystallized twice by alcohol or acetonitrile to prepare a target compound. When used as an NMR chiral dissolving agent, the compound shows good enantiomer recognition effect on some chiral carboxylic acid containing aryl. The compound has the characteristics of simple synthesis, simple and convenient operation, low cost, good enantiomer recognition effect, wide application range, etc.
Description
Technical field
The invention discloses the novel chirality solvating agent (1R of a class, 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane and preparation method thereof, the preparing technical field that belongs to the chirality solvating agent, this chirality solvating agent is used for the Enantiomeric Purity of chipal compounds, relates to separation, the analysis field of chiral compound enantiomer.
Background technology
Chiral drug only is the difference of opticity between the enantiomorph with regard to physicochemical property, other equal indistinctions.In many cases, but there is significant difference in a pair of enantiomorph of chipal compounds aspects such as pharmacologically active, metabolic process, accretion rate and toxicity in vivo.Therefore,, be badly in need of development and set up chiral drug Separation of Enantiomers analytical procedure simply fast, be used for the control of clinical study and medicine quality in order to understand drug effect and safe medication exactly.Chiral carboxylic acids is the important structure unit of many natural products and drug molecule, be the chipal compounds that a class has substantial economics and scientific meaning, measure its enantiomeric purity apace, identify its absolute configuration, for medicine, the development in fields such as asymmetry catalysis has important effect.
In many chiral recognition research methods, nucleus magnetic resonance (NMR) technology is so that it is quick, accurate, easy, consumption is few, can determine the space conformation of compound and the advantages such as dynamic information of molecular interaction are provided, and becomes rapidly that a kind of quilt is extensively approved and the instrument of the chiral recognition research of using.Wherein select for use suitable NMR chirality solvating agent can measure the purity and the content of enantiomorph quickly and accurately, exploitation for medicine, the rapid screening of chiral catalyst particularly with the quantity of product and the combinatorial chemistry coupling of structure diversity, has its unique advantage.
Many bibliographical informations about chirality solvating agent (CSAs) are arranged at present, but it is still less to be suitable for the CSAs of chiral carboxylic acids compounds enantiomorph identification.Optically active amine is often used as the chirality solvating agent of measuring chiral carboxylic acids, wherein be most widely used (the modern study method of chipal compounds,, the press of China Science ﹠ Technology University in 1993) of 1-aryl amine compounds.This compounds all has solubility property preferably in the more weak aprotic solvent of polarity, and all has an aryl that directly is connected on the asymmetric center.When CSAs and a pair of enantiomorph interaction of molecules, form a pair of diastereomer associated complex, this probe group to diastereomer is gone up the different selectivity antimagnetic shields that cause aryl to the probe group with mean distance of orientation of aryl with CSAs, thereby makes the probe group produce chemical shift non-equivalence (Δ Δ δ).But because of the chemical shift non-equivalence (Δ Δ δ) of analyte is less its application is restricted sometimes.This just needs us to remove to research and develop the novel chirality solvating agent that the chirality carboxylic acid compound is had better chiral recognition effect.
Summary of the invention
It is simple that problem solved by the invention provides class preparation, chirality solvating agent (1R with better chiral recognition effect with low cost, 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-2-aminocyclohexane compound and its production and use.
Technical scheme provided by the invention is: (1R, 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane, its structural formula is:
1R＝H 4R＝H
2R＝Br 5R＝Br
3R＝N(CH
3)
2 6R＝N(CH
3)
2
(1R, 2R)-or (1S, 2S)-1-(4 '-replace-1 '; 8 '-naphthalimide)-preparation method of 2-aminocyclohexane: will (1R, 2R)-or (1S, 2S)-cyclohexanediamine and 4-replacement-1; 8 naphthalic anhydrides are at ethanol; N, in dinethylformamide (DMF) or ethanol/DMF (1: the 2) solution, backflow 4-5 is individual hour under the nitrogen protection condition; pour in the frozen water; promptly there are a large amount of solids to separate out, with ethanol or acetonitrile recrystallization twice, obtain target compound at last.It is 1,8 naphthalic anhydride, 4-bromo-1,8 naphthalic anhydride or 4-(N, N-dimethylamino)-1,8 naphthalic anhydride that above-mentioned 4-replaces-1,8 naphthalic anhydrides.
(1R, 2R)-or (1S, 2S)-cyclohexanediamine can according to document (Acta Chem.Scand.1972,26, the cyclohexanediamine of method resolution of racemic 3605-3611) obtains.
Below be the reaction mechanism of preparation compound of the present invention:
Optically pure trans cyclohexanediamine can be split with (+)-tartrate by racemic cyclohexanediamine and obtain, and its fractured operation is simple, and raw material is cheap and easy to get.For target compound, the existence of cyclohexane structure makes very stable of substituent space conformation on two chiral centres of hexanaphthene, and this point is very favorable for the enantio-selectivity identification of chirality solvating agent.Important role is also being played the part of in the amino simultaneously salification with carboxyl when host-guest interaction.We in conjunction with these characteristics designs synthesized the novel chirality solvating agent of this class (1R, 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-2-aminocyclohexane, by
1H NMR,
13C NMR, MS, IR and ultimate analysis have been carried out structural characterization to it.This compounds has solubility property preferably.The novel chirality solvating agent of this class disclosed in this invention is for tens kinds of chirality organic carboxyl acids, as some chiral drug molecule (isobutyl-Ibuprofen BP/EPs, Ketoprofen BP 93, naphthalene is general gloomy), amino acid whose derivative, α-methoxyphenylacetic acid, dibenzoyl tartaric acid etc. have all showed enantio-selectivity recognition effect (maximum chemical shift non-equivalence value (Δ Δ δ) has reached more than the 100Hz) preferably.For example discern (mol ratio of Subjective and Objective is 1: 1) for the enantiomorph of α-methoxyphenylacetic acid, alpha-chiral hydrogen is as the probe group, compound 1-3 is as the chirality solvating agent, and chemical shift non-equivalence value (Δ Δ δ) equals 15.3Hz, 16.5Hz and 47.1Hz respectively; And the chirality solvating agent of city pin, 5-amino-4-phenyl-2,2-dimethyl-1,3-dioxane but can not to the selective identification of chirality hydrogen of α-methoxyphenylacetic acid (Tetrahedron:Asymmetry, 1999,10,323-326); Several sulfonyl-derivatives for L-Ala; the optically pure phenylethylamine of chirality solvating agent of city's pin does not just have recognition effect preferably to them; and we the synthetic compound 1-6 of institute shows enantiomorph recognition effect preferably; make the chirality hydrogen signal of guest molecule all realize the separation of baseline, and then can carry out the mensuration of enantiomeric purity.Therefore this compounds of the present invention might become the NMR chirality solvating agent and the chirality derivatization reagent of the chiral carboxylic acids compounds of a new generation, mensuration for chiral compound enantiomer purity, the compartment analysis of chipal compounds, the development in fields such as the screening of chiral catalyst and combinatorial chemistry has good promoter action.
The novel chirality solvating agent of this class of the present invention's preparation has following characteristics:
1. be connected with naphthalimide amino and that replace on the chiral centre of this compounds respectively, wherein amino can interact by salify with carboxyl, is an important action site; The naphthalimide that replaces has bigger aroma system, can combine with guest molecule by π-π effect, simultaneously, also can produce the effect of selectivity antimagnetic shield to the probe group of guest molecule, become the Another important function site, therefore, this compounds is particularly suitable for as the chirality solvating agent that contains the chiral carboxylic acids compounds of aryl.
2. this compounds is because the existence of cyclohexane structure makes the amino that connects on adjacent two chiral centres and the naphthalimide of replacement spatially have highly stable conformation, and this point helps the enantio-selectivity identification of this compounds.
3. this compounds has solvability preferably in the more weak aprotic solvent of polarity, as CDCl
3, CD
2Cl
2, CCl
4, C
6D
6Or the like, make it be very suitable for chirality solvating agent as nucleus magnetic resonance.
4. (1R, 2R)-or (1S, 2S)-1-(4 '-(N, the N-dimethylamino)-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane is to some chiral carboxylic acids such as dibenzoyl tartaric acid, amino acid whose derivative shows the enantio-selectivity recognition effect on fluorescence spectrum, make it can be used as the fluorescent probe of some chiral carboxylic acids compound enantiomorph identifications.
5. this compounds is synthetic simple, easy and simple to handle, with low cost.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is further described:
Embodiment 1:(1R, 2R)-preparation of 1-(1 ', 8 '-naphthalimide)-2-aminocyclohexane 1
The cyclohexanediamine of 240ml is added in the distilled water of 400ml, be heated to 75 ℃, then under stirring condition, controlled temperature is at 80-90 ℃, elder generation adds (+)-tartrate of 150g (1mol) in batches, adds the Glacial acetic acid of 100ml (1.7mol) more in batches, transfers to the pH value and approximates 6.Continue to stir, with ice bath cooling 2 hours, suction filtration was washed with the 80ml frozen water, uses 250 * 4ml methyl alcohol to wash again, at air drying, got white crystal { (-) chxnH
2{ (+) tart}144g, [α]
D 20=12.6 ° of (c=2, H
2O) [literature value: [α]
D 20=12.2 ° of (c=1, H
2O) (Acta Chem.Scand.1972,26,3605-3611)].
Above-mentioned mother liquor is heated to 80 ℃, and stirring adds (+)-tartrate of 375g (2.5mol) down, stirs under the room temperature and spends the night, and separates out precipitation, filters, and the 40ml frozen water is washed, and 250 * 4ml methyl alcohol is washed, and at air drying, gets white crystal { (+) chxnH
2{ H (+) tart}
2H
2O 179g, [α]
D 20=25.4 ° of (c=2, H
2O) [literature value: [α]
D 20=25.8 ° of (c=1, H
2O) (Acta Chem.Scand.1972,26,3605-3611)].
Take by weighing { (-) chxnH
2{ (+) tart}115g puts into the separating funnel of 500ml, adds the 70ml aqueous solution that contains 100g KOH (1.8mol), shakes up, separate while hot, tell organic layer, place the round-bottomed flask of 500ml, connect a reflux condensing tube that has the KOH drying tube, add the 250ml anhydrous diethyl ether.Add excessive sodium, backflow is spent the night, and pours out the amine phase, adds excessive sodium again, and backflow is spent the night, and pours out the amine phase again, uses activated carbon treatment, filters under nitrogen protection.With the water-bath that this filtrate places room temperature, use the water pump concentrating under reduced pressure, seeing has solid to separate out, stop to concentrate, put into refrigerator and cooled and freeze, promptly have a large amount of white solids to separate out, take advantage of cold filtration, wash 2 times with the ice ether, optically pure (1R, 2R)-cyclohexanediamine 30g, mother liquor can concentrate once more, freezing another part product 5g, [α] of getting
D 20=-25.2 ° of (c=5,1NHCl) [literature values: [α]
D 20=-25 ° (c=5, and 1N HCl (Aldrich, 2001, p505)].
In three mouthfuls of round-bottomed flasks of a 250ml, add 3.96g (0.02mol) 1, the DMF solution of 8-naphthalic anhydride and 150ml, under the nitrogen protection condition, reflux makes 1, the dissolving of 8-naphthalic anhydride, add 2.74g (0.024mol) (1R, 2R)-and the 50ml DMF solution of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 1400ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets light yellow needle-like crystal, be target compound 1, productive rate: 93.5%; M.p.:230-233 ℃; [α]
D 20=2.28 ° of (c=2.5, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.75-8.55 (m, 6H, 6ArH), 4.72-4.81 (td, 1H,
3J
Ae=3.3Hz,
3J
Aa=10.8Hz, CHN), 3.71-3.80 (td, 1H,
3J
Ae=3.6Hz,
3J
Aa=11.1Hz, CHNH
2), 1.19-2.54 (m, 10H, 4CH
2, 2NHH);
13C NMR (75MHz, CDCl
3): δ=165.7,164.6,133.8,131.7,131.0,128.5,127.1,123.5,122.8,61.2,50.7,37.6,29.0,26.5,25.8; IR (KBr/cm
-1): 3436,2933,2859,1690,1657,1625,1588,1342,1238,777; MS (FAB) m/z:295[M+1]
+Ultimate analysis C
18H
18N
2O
2, theoretical value (%): C, 73.45; N, 6.16; H, 9.52; Measured value (%): C, 73.04; N, 6.21; H, 10.23.
Embodiment 2:(1R, 2R)-fractionation of the optically pure cyclohexanediamine of preparation of 1-(4 '-bromo-, 1 ', 8 '-naphthalimide)-2-aminocyclohexane 2 is the same.
In three mouthfuls of round-bottomed flasks of a 250ml, add 2.77g (0.01mol) 4-bromo-1, the solution of 8-naphthalic anhydride and 90mlDMF/ ethanol (2: 1), under the nitrogen protection condition, reflux makes 4-bromo-1, the dissolving of 8-naphthalic anhydride, add 1.37g (0.012mol) (1R again, 2R)-and 30ml DMF/ ethanol (2: the 1 volume ratios) solution of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 1000ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets light yellow solid, be target compound 2, productive rate: 95.0%; M.p.:211-214 ℃; [α]
D 20=-12.8 ° of (c=0.0625, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.78-8.59 (m, 5H, 5ArH), 4.69-4.77 (td, 1H,
3J
Ae=3.3Hz,
3J
Aa=11.1Hz, CHN), 3.68-3.77 (td, 1H,
3J
Ae=3.9Hz,
3J
Aa=10.8Hz, CHNH
2), 1.20-2.53 (m, 10H, 4CH
2, 2NHH);
13C NMR (75MHz, CDCl
3): δ=165.1,164.0,133.1,132.6,131.9,131.2,130.6,130.1,129.3,128.3,123.3,122.8,61.3,50.7,37.8,29.0,26.5,25.8; IR (KBr/cm
-1): 3436,3089,3070,2932,2854,1700,1661,1587,1405,1344,1237,1186,780; MS (FAB) m/z:375[M+1]
+Ultimate analysis C
18H
17BrN
2O
2, calculated value (%): C, 57.92; N, 4.59; H, 7.51; Measured value (%): C, 58.37; N, 4.61; H, 7.66.
Embodiment 3:(1R, 2R)-preparation of 1-(4 '-(N, N-dimethylamino)-1 ', 8 '-naphthalimide)-2-aminocyclohexane 3
The fractionation of optically pure cyclohexanediamine is the same.
In three mouthfuls of round-bottomed flasks of a 250ml, add 1.2g (0.005mol) 4-(N, N-dimethylamino)-1,8-naphthalic anhydride and 100ml ethanolic soln, under the nitrogen protection condition, reflux makes 4-(N, N-dimethylamino)-1, the dissolving of 8-naphthalic anhydride, add 0.68g (0.006mol) (1R again, 2R)-and the 30ml ethanolic soln of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 500ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets the glassy yellow needle-like crystal, be target compound 3, productive rate: 92.5%; M.p.:183-184 ℃; [α]
D 20=-16.0 ° of (c=0.025, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.10-8.55 (m, 5H, 5ArH), 4.73-4.80 (t, 1H,
3J=9.9Hz, CHN), 3.73-3.82 (td, 1H,
3J
Ae=3.9Hz,
3J
Aa=10.2Hz, CHNH
2), 3.098 (s, 6H, 2CH
3) 1.19-2.54 (m, 10H, 4CH
2, 2NHH);
13C NMR (75MHz, CDCl
3): δ=166.2,165.5,133.3,132.5,131.6,131.2,130.9,130.6,125.3,125.1,113.5,60.9,50.7,45.1,37.3,29.0,26.5,25.8; IR (KBr/cm
-1): 3381,2926,2852,2798,1690,1643,1587,1389,1359,1241,1132,1082,1002,784,760; MS (FAB) m/z:338[M+1]
+Ultimate analysis C
20H
23N
3O
2, calculated value (%): C, 71.19; N, 6.87; H, 12.45; Measured value (%): C, 70.73; N, 7.15; H, 12.41.
Embodiment 4:(1S, 2S)-preparation of 1-(1 ', 8 '-naphthalimide)-2-aminocyclohexane 4
Take by weighing { (+) chxnH
2{ H (+) tart}
2H
2O 177g puts into the separating funnel of 500ml, adds the 50ml aqueous solution that contains 100g KOH (1.8mol), shakes up, separate while hot, tell organic layer, place the round-bottomed flask of 500ml, connect a reflux condensing tube that has the KOH drying tube, add the 250ml anhydrous diethyl ether.Add excessive sodium, backflow is spent the night, and pours out the amine phase, adds excessive sodium again, and backflow is spent the night, and pours out the amine phase again, uses activated carbon treatment, filters under nitrogen protection.With the water-bath that this filtrate places room temperature, use the water pump concentrating under reduced pressure, seeing has solid to separate out, stop to concentrate, put into refrigerator and cooled and freeze, promptly have a large amount of white solids to separate out, take advantage of cold filtration, wash 2 times with the ice ether, optically pure (1S, 2S)-cyclohexanediamine 29g, mother liquor can concentrate once more, freezing another part product 8g, [α] of getting
D 20=+25.2 ° of (c=5,1N HCl) [literature values: [α]
D 20=+25 ° (c=5, and 1NHCl) (Aldrich, 2001, p505)].
In three mouthfuls of round-bottomed flasks of a 250ml, add 3.96g (0.02mol) 1, the DMF solution of 8-naphthalic anhydride and 150ml, under the nitrogen protection condition, reflux makes 1, the dissolving of 8-naphthalic anhydride, add 2.74g (0.024mol) (1S, 2S)-and the 50ml DMF solution of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 1400ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets light yellow needle-like crystal, be target compound 1, productive rate: 90.5%; M.p.:230-233 ℃; [α]
D 20=-2.28 ° of (c=2.5, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.75-8.55 (m, 6H, 6ArH), 4.72-4.81 (td, 1H,
3J
Ae=3.3Hz,
3J
Aa=10.8Hz, CHN), 3.71-3.80 (td, 1H,
3J
Ae=3.6Hz,
3J
Aa=11.1Hz, CHNH
2), 1.19-2.54 (m, 10H, 4CH
2, 2NHH);
13C NMR (75MHz, CDCl
3): δ=165.7,164.6,133.8,131.7,131.0,128.5,127.1,123.5,122.8,61.2,50.7,37.6,29.0,26.5,25.8; IR (KBr/cm
-1): 3436,2933,2859,1690,1657,1625,1588,1342,1238,777; MS (FAB) m/z:295[M+1]
+Ultimate analysis C
18H
18N
2O
2, theoretical value (%): C, 73.45; N, 6.16; H, 9.52; Measured value (%): C, 73.15; N, 6.30; H, 9.83.
Embodiment 5:(1S, 2S)-preparation of 1-(4 '-bromo-, 1 ', 8 '-naphthalimide)-2-aminocyclohexane 5
The fractionation of optically pure cyclohexanediamine is the same.
In three mouthfuls of round-bottomed flasks of a 250ml, add 2.77g (0.01mol) 4-bromo-1, the solution of 8-naphthalic anhydride and 90mlDMF/ ethanol (2: 1), under the nitrogen protection condition, reflux makes 4-bromo-1, the dissolving of 8-naphthalic anhydride, add 1.37g (0.012mol) (1S again, 2S)-and the 30ml ethanolic soln of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 1000ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets light yellow solid, be target compound 5, productive rate: 933%; M.p.:211-214 ℃; [α]
D 20=+12.8 ° of (c=0.0625, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.78-8.59 (m, 5H, 5ArH), 4.69-4.77 (td, 1H,
3J
Ae=3.3Hz,
3J
Aa=11.1Hz, CHN), 3.68-3.77 (td, 1H,
3J
Ae=3.9Hz,
3J
Aa=10.8Hz, CHNH
2), 1.20-2.53 (m, 10H, 4CH
2, 2NHH);
13C NMR (75MHz, CDCl
3): δ=165.1,164.0,133.1,132.6,131.9,131.2,130.6,130.1,129.3,128.3,123.3,122.8,61.3,50.7,37.8,29.0,26.5,25.8; IR (KBr/cm
-1): 3436,3089,3070,2932,2854,1700,1661,1587,1405,1344,1237,1186,780; MS (FAB) m/z:375[M+1]
+Ultimate analysis C
18H
17BrN
2O
2, calculated value (%): C, 57.92; N, 4.59; H, 7.51; Measured value (%): C, 58.09; N, 4.78; H, 7.34.
Embodiment 6:(1S, 2S)-preparation of 1-(4 '-(N, N-dimethylamino)-1 ', 8 '-naphthalimide)-2-aminocyclohexane 6
The fractionation of optically pure cyclohexanediamine is the same.
In three mouthfuls of round-bottomed flasks of a 100ml, add 1.2g (0.005mol) 4-(N, N-dimethylamino)-1,8-naphthalic anhydride and 50ml DMF solution, under the nitrogen protection condition, reflux makes 4-(N, N-dimethylamino)-1, the dissolving of 8-naphthalic anhydride, add 0.68g (0.006mol) (1S again, 2S)-and the 30ml DMF solution of cyclohexanediamine, reflux half an hour the solution becomes clarification, back flow reaction 4-5 hour again, pour into while hot in the frozen water of 500ml, promptly have a large amount of solids to separate out suction filtration, washing, the vacuum drying oven drying with ethanol or acetonitrile recrystallization twice, gets the glassy yellow needle-like crystal, be target compound 6, productive rate: 90.8%; M.p.:183-184 ℃; [α]
D 20=+16.0 ° of (c=0.025, CHCl
3);
1H NMR (300MHz, CDCl
3): δ=7.10-8.55 (m, 5H, 5ArH), 4.73-4.80 (t, 1H,
3J=9.9Hz, CHN), 3.73-3.82 (td, 1H,
3J
Ae=3.9Hz,
3J
Aa=10.2Hz, CHNH
2), 3.098 (s, 6H, 2CH
3) 1.19-2.54 (m, 10H, 4CH
2, 2NHH);
13CNMR (75MHz, CDCl
3): δ=166.2,165.5,133.3,132.5,131.6,131.2,130.9,130.6,125.3,125.1,113.5,60.9,50.7,45.1,37.3,29.0,26.5,25.8; IR (KBr/cm
-1): 3381,2926,2852,2798,1690,1643,1587,1389,1359,1241,1132,1082,1002,784,760; MS (FAB) m/z:338[M+1]
+Ultimate analysis C
20H
23N
3O
2, calculated value (%): C, 71.19; N, 6.87; H, 12.45; Measured value (%): C, 70.94; N, 7.03; H, 11.89.
Application Example:
CDCl is all adopted in all NMR experiments
3Being solvent, testing on Varian Mercury VX300FT-NMR, is interior mark with TMS.Master, object (product 1,2,3,4,5 of the present invention or 6 is a main body) etc. mol ratio add the nuclear-magnetism pipe, add 0.5ml CDCl
3Be made into the solution that concentration is 20mM, under 25 ℃ of conditions, place on the nuclear magnetic resonance spectrometer and test.The chemical shift non-equivalence value of the alpha-chiral hydrogen of guest molecule and Alpha-Methyl (Δ Δ δ) is listed in table 1.
The chemical shift non-equivalence value of the α-hydrogen of table 1. guest molecule and Alpha-Methyl (Δ Δ δ)
| CSAs | Object | ΔΔδ(Hz) | ||
| α-H | -CH 3 | |||
| 1 | 1 | To Methyl benzenesulfonyl base L-Ala | 58.8 | 14.7 |
| 2 | 2 | P-oil of mirbane alkylsulfonyl L-Ala | 36.6 | 3.7 |
| 3 | 3 | α-anisole ethamine | 47.1 | |
| 4 | 4 | P-oil of mirbane alkylsulfonyl L-Ala | 30.0 | 17.7 |
| 5 | 5 | To Methyl benzenesulfonyl base L-Ala | 102.0 | 40.8 |
| 6 | 6 | Ketoprofen | 7.2 | 25.2 |
Claims (3)
1. (1R, 2R)-1-(4 '-replace-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane, structural formula is:
In the formula: R=Br or N (CH
3)
2Or
(1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane, structural formula is:
In the formula: R=H, Br or N (CH
3)
2
2. described (the 1R of claim 1; 2R)-or (1S; 2S)-1-(4 '-replace-1 '; 8 '-naphthalimide)-preparation method of 2-aminocyclohexane, it is characterized in that: with optically pure (1R, 2R)-or (1S; 2S)-cyclohexanediamine and 4-replacement-1; 8 naphthalic anhydrides are at ethanol; N, dinethylformamide or ethanol/N are in the N-dimethyl formyl solution; backflow 4-5 is individual hour under the nitrogen protection condition; pour in the frozen water, promptly have solid to separate out, with ethanol or acetonitrile recrystallization; promptly get (1R; 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-the 2-aminocyclohexane.
Claim 1 described (1R, 2R)-or (1S, 2S)-1-(4 '-replace-1 ', 8 '-naphthalimide)-2-aminocyclohexane is as the chirality solvating agent of nucleus magnetic resonance, chirality derivatization reagent or be used for separation, the analysis of chipal compounds.
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| CN102329241A (en) * | 2011-09-09 | 2012-01-25 | 诚达药业股份有限公司 | Chemical resolution method for 1,2-diamino cyclohexane |
| JP6287836B2 (en) * | 2013-03-19 | 2018-03-07 | 東レ・ファインケミカル株式会社 | Process for producing optically active trans 1,2-diaminocyclohexane |
| CN111099995B (en) * | 2018-10-25 | 2023-04-07 | 中国石油化工股份有限公司 | Method for recovering and purifying 2, 6-naphthalenedicarboxylic acid |
| CN109400587B (en) * | 2018-11-12 | 2021-06-08 | 中国科学院化学研究所 | Red thermal activation delayed fluorescence material with circular polarization luminescence property and preparation method and application thereof |
| CN110790645B (en) * | 2019-11-14 | 2023-01-31 | 陕西师范大学 | Amphipathic binaphthyl derivative containing dihydroxy, preparation method thereof and application of derivative in distinguishing chiral cyclohexanediamine gas |
| CN113999204B (en) * | 2021-11-08 | 2023-09-05 | 常州大学 | Achiral imidazole type ionic compound and preparation method and application thereof |
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| CN1403458A (en) * | 2002-10-09 | 2003-03-19 | 武汉大学 | (8S,18S)-1,4,10,13,16-pentazatricyclo [16.3.0.0 4.8] heneicosane-9,17-diketone and its prepn process |
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