CN105061225B - A kind of both hands alkamine compound and its preparation method and application - Google Patents
A kind of both hands alkamine compound and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of both hands alkamine compound and its preparation method and application, selects and synthesis of chiral part is to prepare chiral catalyst.The chemical name of the compound is：Double [1 aryl ethyl of (1S) 2 hydroxyl] the Isosorbide-5-Nitrae benzene dimethylamine of N, N', its structural formula is：Or chemical name is：Double [1 aryl ethyl of (1S) 2 hydroxyl] 1,3 benzene dimethylamines of N, N', structural formula is：The method prepares double [1 aryl ethyl of (1S) 2 hydroxyl] the Isosorbide-5-Nitrae benzene dimethyleneimines of intermediate product N, N' with phthalaldehyde and L amino alcohol reaction, and intermediate product synthesizes both hands alkamine compound under the reduction of sodium borohydride.The application of the compound, both hands alkamine compound are combined with copper ion coordination, are added in the reaction system of aromatic aldehyde and nitromethane, using silica gel column chromatography separating-purifying.Catalyst system and catalyzing reaction condition of the present invention is gentle, and chiral selectivity is good, and yield is higher.
Description
Technical field
The present invention relates to a kind of pair of chipal compounds and its preparation method and application, particularly a kind of pair chiral amino alcohol
Compound and its preparation method and application.
Background technology
Chiral β-amino alcohols derivative can conveniently be obtained through series reaction by natural chiral amino acid (Xiao Rong etc.,
Chemical Engineering Technology and exploitation, 2009,38,10-14；Gan Chunfang etc., chemistry world, 2007,538-540；Zhang Chunhua etc., organises
Learn, 2004,24：343-345), as which is cheap and easy to get, it is widely used in asymmetry catalysis.Nitro aldehyde alcohol (Henry) reacts,
It is a classical name reaction.Henry reaction refers to that the nitroparaffins with α-H are carried out to carbonyls under base catalysis
Electrophilic addition generates the class reaction of β-nitroalcohol.1895, Henry be found that first this reaction (L.C.R.Henry,
Hebd.Seances.Acad.Sci., 1895,120,1265-1268.), the reaction is that the effective carbon-carbon bond of a class builds reaction,
Its product β-nitroalcohol is the important organic intermediate of a class (V.Farina et al., Chem.Rev.2006,106:2734-
2793；D.J.Ager et al.,Chem.Rev.,1996,96:835-976；E.J.Corey et al.,1999,38:1931-
1934；B.M.Trost et al.,Org.Lett.,2002,4:2621-2623；A.Cochi et al.,Org.Lett.,
2010,12:3693-3695), beta-alkamine can be reduced to, is oxidized to carbonyls etc..Carbonyl carbon is located in the reaction
Position can form a chiral centre, therefore when such reaction is catalyzed, chiral control just seems critically important (N.Ono, The
Nitro Group in Organic Synthesis,Wiley-VCH,New York,2001；M.Watanabe,et al.,
J.Org.Chem.2002,67:1712-1715；H.Chikashita et al.,Synth.Commun.1987,17:677-
683.).Henle reaction asymmetric chiral catalysis research start from 1992 (H.Sasai et al., J.Am.Chem.Soc,
1992,114:4418-4420), through the development of recent two decades, multiple different catalyst system and catalyzings are had been developed over now
(A.Bulut et al.,J.Org.Chem,2008,73:7373-7375；C.Palomo,et al.,
Angew.Chem.Int.Ed.,2005,44:3881-3884；C.S.Gan,Can.J.Chem,2008,86:261-263；W.Jin
et al.,J.Org.Chem,2011,76:484-491；T.Arai et al.,J.Org.Chem,2008,73:4903-4906；
A.Gualandi et al.,J.Org.Chem,2011,76:3399-3408；Y.R.Zhou et al.,J.Org.Chem.,
2011,76:588-600；N.H.Khan et al.,Catal.Lett.,2010,140:189-196).
Content of the invention
The invention provides a kind of both hands alkamine compound and its preparation method and application, selects and synthesis of chiral is joined
Body is to prepare chiral catalyst.
The chemical name of a kind of both hands alkamine compound that the present invention is provided is：Double [(the 1S) -2- hydroxyl -1- of N, N'-
Aryl ethyl]-Isosorbide-5-Nitrae-benzene dimethylamine, its structural formula is：Or chemical name is：N,N'-
Double [(1S) -2- hydroxyl -1- aryl ethyl] -1,3- benzene dimethylamines, structural formula is：In formula
Ar is selected from-Ph, referred to as phenyl, or-CH2Ph, referred to as benzyl, four kinds of double chiral amino alcohols that above group is constituted are referred to as changing successively
Compound 1a, 1b, 1c, 1d.
A kind of preparation method of both hands alkamine compound, the method are two steps, and the first step is with phthalaldehyde and L- ammonia
Base alcohol reaction prepares double [(1S) -2- hydroxyl -1- aryl ethyl] -1,4- benzene dimethyleneimines of intermediate product N, N'- or N, N'- are double
[(1S) -2- hydroxyl -1- aryl ethyl] -1,3- benzene dimethyleneimine, the above-mentioned intermediate product of second step go back original work in sodium borohydride
With lower synthesis both hands alkamine compound.
Described phthalaldehyde is terephthalaldehyde or m-terephthal aldehyde, and L- amino alcohol is L- benzene glycinol or L- phenylpropyl alcohol ammonia
Alcohol, above-mentioned each L- amino alcohol are reacted with phthalaldehyde respectively and generate Schiff base intermediate, and the Ar base entrained by which is followed successively by-Ph
With-CH2Ph.
The described reaction for preparing intermediate product be by phthalaldehyde and L- amino alcohol in the presence of catalyst acetic acid, in second
Back flow reaction 8 hours in alcoholic solvent, product is not separated；Add methanol solution in above-mentioned reactant liquor, cooling, gradation add boron hydrogen
Change sodium, stir under room temperature to gas generation is there is no longer, then concentrated hydrochloric acid adjusts pH value, and cooling separates out crystal, and suction filtration obtains both hands
Property alkamine compound.
A kind of application of both hands alkamine compound, first both hands alkamine compound are combined with copper ion coordination
Afterwards, it is then added in the reaction system of aromatic aldehyde and nitromethane, stirs at normal temperature or 10 DEG C, after reaction, rotary evaporation is removed
Organic solvent, using silica gel column chromatography separating-purifying.
Compared with existing similar technique, which significantly has the beneficial effect that the present invention：
This compound can be used for nitro aldehyde alcohol (Henry) reaction, and can obtain preferable catalysis as chiral catalyst
Effect.Henle reaction is the C-C bond formation reaction between the nitroparaffin hydrocarbon compound based on carbonyl and containing α-active hydrogen.
In Henle reaction, the nitro compound containing α-active hydrogen is taken by force under proton reagent effect in alkali etc. and becomes carbanion, then attack
Carbonyl forms new carbon-carbon bond, and obtains difunctional β-nitro alcoholic compound.Compared with existing similar technique, this compound
Synthetic method, is raw material using cheap fragrant dialdehyde and amino alcohol, by simple two steps successive reaction, preparation method is simple,
With low cost.Catalyst system and catalyzing reaction condition of the present invention is gentle, and chiral selectivity is good, and yield is higher.
Specific embodiment
1. a kind of both hands alkamine compound, the chemical name of the compound is：Double [(the 1S) -2- hydroxyl -1- of N, N'-
Aryl ethyl]-Isosorbide-5-Nitrae-benzene dimethylamine, its structural formula is：Or chemical name is：N,N'-
Double [(1S) -2- hydroxyl -1- aryl ethyl] -1,3- benzene dimethylamines, structural formula is：In formula
Ar is selected from-Ph, referred to as phenyl, or-CH2Ph, referred to as benzyl, four kinds of double chiral amino alcohols that above group is constituted are referred to as joining successively
Body compound 1a, 1b, 1c, 1d.
2. a kind of preparation method embodiment of both hands alkamine compound.
Embodiment 1
Double [(1S) -2- hydroxyl -1- phenethyl] -1,4- benzene dimethylamine 1a's of a kind of both hands alkamine compound N, N'-
Preparation method is as follows the step of the method：
In two mouthfuls of flasks of 50mL, L- benzene glycinol 1.37g (10mmol), terephthalaldehyde 0.67g (5mmol) is added,
25ml absolute ethyl alcohol, instills one and drips glacial acetic acid, be heated to reflux 8 hours, stops reaction, TLC monitoring reaction.React after reaction completely
Liquid is cooled to less than 0 DEG C, adds 5ml methyl alcohol, then weighs sodium borohydride 0.95g (25mmol), keep reactant liquor 0 DEG C with
Under, divide and be added in flask for 4 times, after adding sodium borohydride, stir under room temperature to no longer generation gas.Dense salt is dripped into flask
Acid adjusts PH to alkalescent (PH=8-9), adjusts and finishes rear stir about 10min, is eventually adding about 15ml deionized water, by flask
Be put into ice-water bath cooling 0.5h, suction filtration, washing, be dried to obtain white powder 1.71g, yield 91.4%.
The structural characterization data of 1 products therefrom of embodiment are：
White powder；Fusing point：114.0-117.0℃；IR(cm-1, KBr)：3384,3259,3018,2929,1599,
1549,1481,1078,1043；1H NMR (500MHz, DMSO-d6,ppm)δ:7.38 (d, J=7.5Hz, 4H), 7.33 (m,
4H), 7.25 (t, J=8.0Hz, 2H), 7.21 (s, 4H), 4.89 (dd, J=5.5 × 5.0Hz, 1H), 3.68 (m, 2H), 3.57
(m, 2H), 3.44 (s, 4H)；13C NMR (500MHz, DMSO-d6,ppm)δ:142.29,139.54,128.63,128.19,
127.98,127.37,67.07,64.45,50.92；HRMS(ESI)for C24H28N2O2Na：calcd 399.2048([M+Na
]+),found399.2056.
Embodiment 2
Double [(1S) -2- hydroxyl -1- benzyl ethyl] -1,4- benzene dimethylamine 1b's of a kind of both hands alkamine compound N, N'-
Preparation method is as follows the step of the method：
L- phenylalaninol 1.51g (10mmol) is taken, terephthalaldehyde 0.67g (5mmol), preparation method are obtained with embodiment 1
To white powder 1.46g, yield：72.3%.
The structural characterization data of 2 products therefrom of embodiment are：
150.9-151.8 DEG C of fusing point；IR(cm-1, KBr)：3472,3232,3029,2922,1602,1591,1491,
1383；1H-NMR (500MHz, DMSO-d6,ppm)δ:7.26 (t, J=7.5Hz, 4H) 7.18 (m, 6H), 7.14 (s, 4H), 4.53
(t, J=5.5Hz, 2H), 3.70 (s, 4H), 3.25 (m, 2H), 2.61-2.71 (m, 6H), 1.83 (s, 2H)；13C NMR
(500MHz, DMSO-d6,ppm)δ:139.69,139.23,129.17,127.95,127.48,125.63,62.29,59.92,
50.25,37.38；HRMS(ESI)for C26H32N2O2Na：calcd 427.2361([M+Na]+),found 427.2353.
Embodiment 3
Double [(1S) -2- hydroxyl -1- phenethyl] -1,3- benzene dimethylamine 1c's of a kind of both hands alkamine compound N, N'-
Preparation method is as follows the step of the method：
L- benzene glycinol 1.37g (10mmol) is taken, m-terephthal aldehyde 0.67g (5mmol), preparation method are obtained with embodiment 1
To white powder 1.89g, yield：93.6%.
The structural characterization data of 3 products therefrom of embodiment are：
120.2-121.8 DEG C of fusing point；IR(cm-1, KBr)：3462,3223,3019,2932,1602,1551,1472,
1061,1032；1H-NMR (500MHz, DMSO-d6,ppm)δ:7.27 (d, J=6.0Hz, 4H) 7.21 (m, 3H), 7.15 (d, J=
5.5Hz, 4H), 7.05 (m, 3H), 3.78 (br, 2H), 3.66-3.72 (m, 4H), 3.53-3.56 (m, 4H), 2.67 (br, 4H)
；13C NMR (500MHz, DMSO-d6,ppm)δ:139.80,138.38,129.24,128.65,128.60,128.01,
127.18,126.50,66.75,63.88,50.91,37.38；HRMS(ESI)for C24H28N2O2Na：calcd399.2048
([M+Na]+),found 399.2056.
Embodiment 4
Double [(1S) -2- hydroxyl -1- benzyl ethyl] -1,3- benzene dimethylamine 1d's of a kind of both hands alkamine compound N, N'-
Preparation method is as follows the step of the method：
L- benzene glycinol 1.51g (10mmol) is taken, m-terephthal aldehyde 0.67g (5mmol), preparation method are obtained with embodiment 1
To white powder 1.94g, yield：93.6%.
The structural characterization data of 4 products therefrom of embodiment are：
110.9-120.0 DEG C of fusing point；IR(cm-1)：3454,3302,3024,2937,2925,1604,1491,1460,
1059,1032；1H NMR (500MHz, DMSO-d6,ppm)δ:7.25 (t, J=7.5Hz, 2H), 7.18 (m, 7H), 7.12 (s,
1H), 7.08 (d, J=7.5Hz, 2H), 4.60 (t, J=5.0Hz, 2H) 3.69 (s, 4H), 2.63-2.72 (m, 6H), 1.82 (s,
21H)；13C-NMR(500MHz,DMSO-d6, ppm) and δ:141.39,140.25,129.73,128.51,128.26,127.82,
126.46,126.19,62.80,60.54,51.06,37.96；HRMS(ESI)for C26H32N2O2Na：calcd427.2361
([M+Na]+),found 427.2353.
3. catalytic applications embodiment of the ligand 1 a-1d in paranitrobenzaldehyde Henle reaction.
Embodiment 1-6
Applying step of the ligand 1 a-1d in 2- nitro -1- p-nitrophenyl ethanol is prepared is as follows：
Take 0.1mmol ligand 1 a-1d (part consumption be 10%), mono- water acetic acid copper of 0.2mmol in the little flask of 25mL,
5ml absolute ethyl alcohol is added, reaction 2h obtains navy blue solution.Then, the p-nitrophenyl first of 1mmol is added in above-mentioned solution
Aldehyde and the nitromethane of 10mmol, normal temperature or 10 DEG C of stirrings, after reacting 24 hours, rotary evaporation removes organic solvent, crude product
Through silica gel column chromatography separating-purifying, eluant, eluent is petrol ether/ethyl acetate=5/1 (v/v), obtains faint yellow solid, and vacuum is done
Dry, weigh, calculate separation yield, analysis chiral selectivity (e.e. value).The results are shown in Table 1.
The Henle reaction catalytic effect of 1 catalyst 1a-1d of table
The structural characterization data of 6 products therefrom of embodiment are：
Faint yellow solid；Fusing point:70.6-71.7℃；1H NMR(500MHz,CDCl3,ppm)δ：8.30 (d, J=8.5Hz,
2H), 7.65 (d, J=8.5Hz, 2H), 5.63 (dd, J=8.7 × 3.7Hz, 1H), 4.67 4.55 (m, 2H), 3.08 (s, 1H)
；13C-NMR(126MHz,CDCl3)δ：148.22,144.83,126.94,124.23,80.57,69.97.HPLC analyses
(Chiralcel OD-H chromatographic column, 1.0mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr(major)=
17.88min, tr(minor)=22.05min；[α]D 25=-35.8 (c=1.78, CH2Cl2).
4. catalytic applications embodiment of the ligand 1 b in different aromatic formaldehyde Henle reactions
Embodiment 1-10
Ligand 1 b is as follows in different aromatic formaldehyde Henle reaction catalytic applications reactions steps：
Take 0.1mmol ligand 1 b (part consumption be 10%), mono- water acetic acid copper of 0.2mmol in the little flask of 25mL, plus
Enter 5ml absolute ethyl alcohol, reaction 2h obtains navy blue solution.Then, in above-mentioned solution add 1mmol aromatic formaldehyde and
The nitromethane of 10mmol, stirs at 10 DEG C, and after reaction 45-48 hour, rotary evaporation removes organic solvent, and crude product is through silica gel
Column chromatography separating-purifying, eluant, eluent are petrol ether/ethyl acetate=5/1 (v/v), obtain faint yellow solid, vacuum drying, claim
Weight, calculates separation yield, analysis chiral selectivity (e.e. value).The results are shown in Table 2.
Henle reaction catalytic effect of the 2 catalyst 1b of table to different aromatic aldehydes
| Embodiment | Aldehyde | Time (h) | Yield (%) | E.e.% |
| 1 | Benzaldehyde | 48 | 82 | 91.9 |
| 2 | 3- nitrobenzaldehyde | 45 | 88 | 90.6 |
| 3 | 2- nitrobenzaldehyde | 45 | 67 | 94.5 |
| 4 | 4- cyanobenzaldehyde | 48 | 85 | 93.0 |
| 5 | 4- trifluoromethyl benzaldehyde | 48 | 91 | 91.9 |
| 6 | 3- fluorobenzaldehyde | 48 | 80 | 93.5 |
| 7 | 4- bromobenzaldehyde | 48 | 86 | 92.4 |
| 8 | 4- chlorobenzaldehyde | 48 | 71 | 93.0 |
| 9 | 4-methoxybenzaldehyde | 48 | 75 | 85.2 |
| 10 | 2,4 dichloro benzene formaldehyde | 48 | 82 | 93.2 |
The structural characterization data of 1 products therefrom of embodiment are：
Colourless liquid；1H NMR(500MHz,CDCl3,ppm)δ：7.36-7.20(m,5H),5.33-5.26(m,1H),
4.46-4.40 (dd, J=13.1 × 9.9Hz, 1H), 4.36-4.32 (dd, J=13.1 × 3.1Hz, 1H), 3.07 (d, J=
3.6Hz,1H)；13C NMR(500MHz,CDCl3,ppm):δ：138.33,128.92,128.81,125.87,81.20,
70.92；HPLC analyzes (Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV
215nm),tr(major)=11.76min, tr(minor)=14.36min；[α]D 25=-40.5 (c=1.22, CH2Cl2).
The structural characterization data of 2 products therefrom of embodiment are：
Yellow solid；Fusing point：62.4-64.8℃；1H NMR (500MHz, CDCl3,ppm)δ：8.33(s,1H),8.23(d,
J=8.0Hz, 1H), 7.78 (d, J=8Hz, 1H), 7.62 (dd, J=8.0 × 8.0Hz, 1H), 5.62 (d, J=7.5Hz, 1H),
4.58-4.66(m,2H),3.22(br,1H)；13C-NMR (500MHz, CDCl3,ppm)δ：149.57,141.12,132.86,
131.04,124.75,122.06,81.57,70.78；HPLC analysis (Chiralcel OD-H chromatographic column, 0.8mL/min, just oneself
Alkane/isopropanol=85:15v/v, UV 215nm), tr(major)=19.74min, tr(minor)=24.05min；[α]D 25=-
36.4 (c=1.05, CH2Cl2).
The structural characterization data of 3 products therefrom of embodiment are：
Colorless solid；Fusing point：68.6-69.7℃；1H NMR (500MHz, CDCl3,ppm)δ:8.09 (d, J=7.5Hz,
1H), 7.96 (d, J=8Hz, 1H), 7.76 (m, 1H), 7.57 (m, 1H), 6.06 (dd, J=2.0 × 9.0Hz, 1H), 4.89
(dd, J=2.0 × 13.5Hz, 1H), 4.57 (dd, J=9 × 13.5Hz, 1H), 3.155 (br, 1H)；13C NMR (500MHz,
CDCl3,ppm)δ:135.24,134.84,129.60,125.94,80.95,67.72；HPLC analyzes (Chiralcel OD-H color
Spectrum post, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr(major)=25.74min, tr(minor)
=31.05min；[α]D 25=-36.4 (c=1.07, CH2Cl2).
The structural characterization data of 4 products therefrom of embodiment are：
Colorless solid；Fusing point：88.2-90.6℃；1H-NMR(500MHz,CDCl3, ppm) δ 7.73 (d, J=8.0Hz,
2H), 7.57 (d, J=8.0Hz, 2H), 5.57 (m, 1H), 4.58 (dd, J=9.0 × 5.0Hz, 2H), 3.03 (d, J=4.0Hz,
1H)；13C-NMR(500MHz,CDCl3, ppm) and δ 143.01,132.80,126.71,118.12,113.00,86.60,70.14；
HPLC analyzes (Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr
(major)=17.50min, tr(minor)=19.62min；[α]D 25=-33.9 (c=1.16, CH2Cl2).
The structural characterization data of 5 products therefrom of embodiment are：
Colourless oil liquid；1H-NMR(500MHz,CDCl3,ppm)：δ 7.70 (d, J=8.1Hz, 2H), 7.58 (d, J=
8.0Hz, 2H), 5.57 (dd, J=9.3 × 3.1Hz, 1H), 4.66 4.52 (m, 2H), 2.88 (s, 1H)；13C NMR(500MHz,
CDCl3,ppm)：δ 142.03,131.49,131.10,125.88,80.86,70.22.HPLC analyzes (Chiralcel OD-H color
Spectrum post, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr(major)=12.64min, tr(minor)
=15.57min；[α]D 25=-49.8 (c=1.30, CH2Cl2).
The structural characterization data of 6 products therefrom of embodiment are：
Colourless oil liquid；1H-NMR(500MHz,CDCl3,ppm)：δ 7.38 (m, 1H), 7.16 (dd, J=2 × 7.5HZ,
2H), 7.06 (m, 1H), 5.48 (dd, J=3.0 × 9.5H, 1H), 4.55 (m, 2H)；；13C-NMR(500MHz,CDCl3,ppm)：
δ 163.12,140.61,130.69,121.47,115.91,113.10,80.95,70.30；HPLC analyzes (Chiralcel OD-
H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr(major)=8.74min, tr
(minor)=9.27min；[α]D 25=-27.5 (c=0.98, CH2Cl2).
The structural characterization data of 7 products therefrom of embodiment are：
Yellow oily liquid；1H NMR(500MHz,CDCl3,ppm)：δ 7.53 (d, J=8.5Hz, 2H), 7.27 (d, J=
8.5Hz, 2H), 5.44 (m, 1H), 4.58 (dd, J=9.5 × 13.5Hz, 1H), 4.50 (dd, J=3.0 × 13.5Hz, 1H),
2.99 (d, J=3.0Hz, 1H)；13C NMR(500MHz,CDCl3,ppm)：δ137.11,132.19,127.60,123.03,
80.89,70.35；HPLC analyzes (Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v,
UV 215nm),tr(major)=13.82min, tr(minor)=17.12min；[α]D 25=-71.12 (c=1.11,
CH2Cl2).
The structural characterization data of 8 products therefrom of embodiment are：
Colourless oil liquid；1H-NMR(500MHz,CDCl3,ppm)：δ 7.32-7.41 (m, 4H), 5.45 (d, J=
8.0Hz,1H),4.47-4.60(m,2H),2.96(s,1H)；13C-NMR(500MHz,CDCl3,ppm)：δ 136.62,134.85,
129.26,127.47,82.34,71.67；HPLC analyzes (Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropyl
Alcohol=85:15v/v, UV 215nm), tr(major)=13.03min, tr(minor)=16.42min；[α]D 25=-37.5 (c
=1.14, CH2Cl2).
The structural characterization data of 9 products therefrom of embodiment are：
Yellow oily liquid；1H-NMR(500MHz,CDCl3,ppm)：δ 7.27 (d, J=8.0Hz, 2H), 6.90 (d, J=
8.0Hz, 2H), 5.45 (m, 1H), 4.72 4.60 (m, 1H), 4.29 4.54 (m, 1H), 3.81 (s, 3H), 2.92 (brs, 1H)
；13C-NMR(500MHz,CDCl3,ppm)：δ159.98,130.21,127.26,114.39,81.22,70.57,55.21；HPLC
Analysis (Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr
(major)=19.73min, tr(minor)=15.72min；[α]D 25=-40.7 (c=1.21, CH2Cl2).
The structural characterization data of 10 products therefrom of embodiment are：
Clear crystal；Fusing point:73.3-74.3℃；1H-NMR(500MHz,CDCl3,ppm)：δ 7.63 (d, J=8.5Hz,
1H), 7.43 (d, J=2.0Hz, 1H), 7.36 (dd, J=8.5 × 2.0Hz, 1H), 5.82 (m, 1H), 4.67 (dd, J=13.5
× 2.0Hz, 1H), 4.44 (dd, J=13.5 × 4.0Hz, 1H), 3.04 (d, J=4.0Hz, 1H)；13C-NMR(500MHz,
CDCl3,ppm)：δ 135.30,134.11,132.11,129.53,128.59,127.99,79.05,67.44；HPLC is analyzed
(Chiralcel OD-H chromatographic column, 0.8mL/min, n-hexane/isopropanol=85:15v/v, UV 215nm), tr(major)=
9.86min, tr(minor)=11.81min；[α]D 25=-52.3 (c=1.01, CH2Cl2).
Claims (5)
1. a kind of both hands alkamine compound, is characterized in that the chemical name of the compound is：Double [(the 1S) -2- hydroxyls of N, N'-
Base -1- aryl ethyl]-Isosorbide-5-Nitrae-benzene dimethylamine, its structural formula is：Or chemical name is：
Double [(1S) -2- hydroxyl -1- aryl ethyl] -1, the 3- benzene dimethylamine of N, N'-, structural formula is：In formula, Ar is selected from-Ph, referred to as phenyl, or-CH2Ph, referred to as benzyl, above group are constituted
Four kinds of double chiral amino alcohols be referred to as compound 1a, 1b, 1c, 1d successively.
2. a kind of preparation method of both hands alkamine compound described in claim 1, is characterized in that the method for two steps, first
Step prepares double [(1S) -2- hydroxyl -1- aryl ethyl] -1,4- benzene of intermediate product N, N'- with phthalaldehyde and L- amino alcohol reaction
Dimethyleneimine or double [(1S) -2- hydroxyl -1- aryl ethyl] -1, the 3- benzene dimethyleneimines of N, N'-, the above-mentioned intermediate product of second step exist
Synthesize both hands alkamine compound under the reduction of sodium borohydride.
3. a kind of preparation method of both hands alkamine compound according to claim 2, is characterized in that described benzene two
Formaldehyde is terephthalaldehyde or m-terephthal aldehyde, and L- amino alcohol is L- benzene glycinol or L- phenylalaninol, above-mentioned each L- amino alcohol
React with phthalaldehyde respectively and Schiff base intermediate is generated, the Ar base entrained by which is followed successively by-Ph and-CH2Ph.
4. a kind of preparation method of both hands alkamine compound according to claim 2, is characterized in that described preparation
The reaction of intermediate product is back flow reaction 8 in alcohol solvent by phthalaldehyde and L- amino alcohol in the presence of catalyst acetic acid
Hour, product is not separated；Add methanol solution in above-mentioned reactant liquor, cooling, by several times add sodium borohydride, stir under room temperature to
Gas generation is there is no longer, then concentrated hydrochloric acid adjusts pH value, cooling separates out crystal, and suction filtration obtains both hands alkamine compound.
5. a kind of application of both hands alkamine compound described in claim 1, first both hands alkamine compound and copper from
After son coordination is combined, it is then added in the reaction system of aromatic aldehyde and nitromethane, stirs at normal temperature or 10 DEG C, after reaction, rotation
Turn evaporating organic solvent, using silica gel column chromatography separating-purifying.
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