CN106866610B - A kind of 2- amino chromene derivative N- alkylation that Lewis/Bronsted acid promotes lower alcohol to participate in - Google Patents
A kind of 2- amino chromene derivative N- alkylation that Lewis/Bronsted acid promotes lower alcohol to participate in Download PDFInfo
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Abstract
The present invention relates to the N- alkylations for the 2- amino chromene derivative that a kind of collaboration of Lewis/Bronsted acid promotes lower alcohol to participate in.It is characterized by: respectively by 10 mmol R1Substituted 2- Amino 3 cyano -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative, 10 ~ 100 mmol R2OH alcohol, 1 ~ 2 mmol Lewis acid and 1.0 ~ 10.0 mL Bronsted acid are added in reaction vessel, and mixture reacts 0.5 ~ 30 h at 25 ~ 100 DEG C, is cooled to room temperature.100 ~ 200 mL water are added into reaction system, with 5% Na2CO3Aqueous solution adjusts pH value and three times with organic solvent extraction merges organic phase to neutrality, dry, and crude product is obtained after concentration.Crude product is obtained by pillar layer separationNAlkylated 3- cyano -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative.The present invention has many advantages, such as that raw material is cheap and easy to get, experimental implementation is simple, reaction condition is mild, wide application range of substrates is general, Atom economy is high, meets the development and practical application in commercial synthesis field.
Description
Technical field
The invention belongs to technical field of organic synthetic chemistry, and in particular under a kind of collaboration of Lewis/Bronsted acid promotes
The 2- amino chromene derivative that alcohol participates inNAlkylation.
Background technique
NAlkylated reaction refers to that the alkyl various saturations, unsaturated substituent group is introduced into organic compound molecule
Reaction on nitrogen-atoms.CommonlyNAlkylating reagent has halogenated hydrocarbons, ester, alcohol, ether and alkenes compounds.NAlkylated reaction
It is widely used in and prepares drug, surfactant and the important intermediate of textile auxiliary, especially have in pharmaceutical synthesis
Special application value.
Alcohol as it is a kind of it is from a wealth of sources, at a low price be easy to get, small toxicity, stability it is highNAlkylating reagent occurs with amineN-
The by-product of alkylated reaction is only water, is had an enormous advantage from Atom economy and the angle of environmental protection tool.So closely
Chemists are to using alcohol as electrophilic reagent over yearNAlkylated reaction conducts extensive research.2009, Kempe seminar
Report a kind of [IrCl (cod)]2With P, N- ligand in-situ preparation complex catalysis alcohol and the highly selective life of (heterocycle) aromatic amine
At the system [Chem. Eur. J., 2009,15,3790-3799] of monoalkylated product；2013, Hidemasa etc.
People reports unprotected ortho-aminobenzoic acid and secondary alcohol in aqueous solutionNAlkylated reaction uses in reaction
AuCl4Na·2H2O catalyst and ligand TPPMS realize [J. Org. Chem., 2013,78 (13): 6714-6720].
Currently, what the alcohol that document is reported participated inNAlkylated reaction mostly use transition metal (rhodium, ruthenium, iridium, palladium etc.) " borrow hydrogen " or
The method of " hydrogen shifts certainly " needs the noble metal and complicated ligand of inert gas shielding and valuableness, and severe reaction conditions, operation is again
It is miscellaneous, certain pollution is caused to environment, thus limit the development and application of this method.
Summary of the invention
It is an object of the invention to overcome drawbacks described above, provide a kind of using a kind of simple Lewis/Bronsted acid association
With the 2- amino chromene derivative for promoting lower alcohol to participate inNAlkylation.The present invention is cheap and easy to get with raw material, experiment is grasped
Make the advantages that simple, reaction condition is mild, wide application range of substrates is general, Atom economy is high, meets the hair in commercial synthesis field
Exhibition and practical application.
In order to solve the above technical problems, the present invention is achieved by the following technical solutions.
The 2- amino chromene derivative that a kind of Lewis/Bronsted acid collaboration according to the invention promotes lower alcohol to participate inNAlkylation, comprising the following steps: respectively by 10 mmol R1Substituted 2- Amino 3 cyano -5- oxo -5,6,7,8-
Tetrahydro -4HChromene derivative, 10 ~ 100 mmol R2OH alcohol, 1 ~ 2 mmol Lewis acid and 1.0 ~ 10.0 mL
Bronsted acid is added in reaction vessel, and mixture reacts 0.5 ~ 30 h at 25 ~ 100 DEG C, is cooled to room temperature.To anti-
100 ~ 200 mL water of addition in system are answered, with 5% Na2CO3Aqueous solution adjusts pH value to neutrality, with organic solvent extraction three
It is secondary, merge organic phase, it is dry, crude product is obtained after concentration.Crude product is obtained by pillar layer separationNAlkylated 3- cyano -5-
Oxo -5,6,7,8- tetrahydro -4HChromene derivative.Reaction equation are as follows:
Wherein, R1For phenyl, substituted phenyl or heterocyclic substituent, substituted phenyl includes 4- aminomethyl phenyl, 4- methoxy
Base phenyl, 4- chlorophenyl, 4- nitrobenzophenone, 2- nitrobenzophenone, 2- aminomethyl phenyl, trifluoromethyl, 4- hydroxy phenyl, it is miscellaneous
Ring substituents include 2- furyl, 2- pyridyl group；R2For the alkyl (C of linear chain or branched chain1~C8), cyclohexyl, benzyl, to methyl benzyl
Base, to bromobenzyl, benzhydryl.
Lewis acid involved in the present invention is AlCl3、MgCl2、FeCl3、InCl3、ZnCl2、TiCl4、SnCl4One
Kind.
Bronsted acid involved in the present invention is the concentrated sulfuric acid, formic acid, acetic acid, benzoic acid, p-methyl benzenesulfonic acid, fluoroform
One kind of base benzene sulfonic acid, perchloric acid.
In the reaction, R1Substituted 2- Amino 3 cyano -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative with
R2The amount of substance ratio of OH alcohol is 1:1 ~ 1:10.The Lewis acid and Bronsted acid of use can be optionally combined, and amount of substance ratio is 1:
5 ~ 1:50.25 ~ 100 DEG C of reaction temperature, 0.5 ~ 30 h of reaction time.The extractant used is ethyl acetate, acetonitrile, second
One kind of ether, methylene chloride and chloroform.
Specific embodiment
Synthetic method of the invention is described further below by specific implementation example.
Example 1:2- methylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), methanol (100 mmol, 4.0 mL), anhydrous AlCl3(1 mmol, 0.13 g) is added to three-necked flask with acetic acid (1.0 mL)
In, mixture reacts 2.0 h at 25 DEG C, is cooled to room temperature.100 mL water are added into reaction system, with 5% Na2CO3Water
Solution adjusts pH value to 7.0, is extracted with ethyl acetate three times, merges organic phase, drying obtains crude product after concentration.It is chromatographed through column
Isolated 2- methylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, white solid, yield
262.4 DEG C of 95%, m.p. 261.2-.1H NMR (600 MHz, DMSO): δ(ppm) 9.76 (s, 1H, NH), 7.27
(t, J = 7.8 Hz, 2H, ArH), 7.17-7.19 (m, 3H, ArH), 4.48 (s, 1H, CH), 3.92 (s,
3H, CH3N), 2.48-2.56 (m, 2H, CH2), 2.17-2.27 (m,2H, CH2), 1.82-1.94 (m, 2H,
CH2); 13C NMR (150 MHz, DMSO):δ(ppm) 195.1, 158.4, 152.0, 146.2, 128.9, 127.5,
127.1, 119.4, 110.3, 68.6, 59.8, 39.1, 37.1, 26.7, 21.1; IR (KBr, cm-1): 3436,
3166, 3029, 2949, 2205, 1665, 1603, 1497, 1255. Anal. Calcd. for C17H16N2O2: C,
72.84; H, 5.75; N, 9.99; Found: C, 72.98; H, 5.63 N, 9.97.
Example 2:2- ethylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), ethyl alcohol (80 mmol, 4.7 mL), anhydrous ZnCl2(1 mmol, 0.14 g) is added to three-necked flask with formic acid (0.7 mL)
In, mixture reacts 2.0 h at 60 DEG C, is cooled to room temperature.100 mL water are added into reaction system, with 5% Na2CO3Water
Solution adjusts pH value to 7.0, three times with acetonitrile extraction, merges organic phase, drying obtains crude product after concentration.Through column chromatography for separation
Obtain 2- ethylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, light tan solid, yield 94%,
m. p. 237.8- 238.6℃。1H NMR (600 MHz, DMSO): δ(ppm) 9.76(s, 1H, NH), 7.28 (t,J = 7.8 Hz, 2H, ArH), 7.17-7.18 (m, 3H, ArH), 4.48 (s, 1H, CH), 4.26-4.30 (m,
1H, CH2N), 4.16-4.20 (m, 1H, CH2N), 2.50-2.56 (m, 2H, CH2), 2.16-2.27 (m, 2H,
CH2), 1.82-1.94 (m, 2H, CH2), 1.2 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (150 MHz,
DMSO):δ(ppm) 195.0, 157.3, 152.1, 142.3, 128.9, 127.4, 127.0, 119.5, 110.2,
70.3, 68.7, 39.1, 37.1, 26.6, 21.1, 15.2; IR (KBr, cm-1): 3442, 3170, 3061,
2949, 2193, 1604, 1487, 1250; Anal. Calcd. for C18H18N2O2: C, 73.45; H, 6.16;
N, 9.52; Found: C, 73.33; H, 6.25 N, 9.50.
Example 3:2- propylcarbamic -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), propyl alcohol (40 mmol, 3.0 mL), anhydrous SnCl4(1 mmol, 0.1 g) is added to three-necked flask with perchloric acid (0.3 mL)
In, mixture reacts 3.5 h at 80 DEG C, is cooled to room temperature.200 mL water are added into reaction system, with 5% Na2CO3Water
Solution adjusts pH value to 7.0, three times with chloroform extraction, merges organic phase, drying obtains crude product after concentration.It is chromatographed through column
Isolated 2- propylcarbamic -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, beige solid, yield
91%, m. p. 218.0-219.5 DEG C.H NMR (600 MHz, DMSO):δ(ppm) 9.74 (s, 1H, NH), 7.28
(d, J = 7.8 Hz, 2H, ArH), 7.18 (t, J = 7.8 Hz, 3H, ArH), 4.48 (s, 1H, CH),
4.19-4.22 (m, 1H, CH2N), 4.05-4.08 (m, 1H, CH2N), 2.49-2.54 (m, 2H, CH2),
2.20-2.24 (m, 2H, CH2), 1.63-1.66 (m, 2H, CH2), 0.94 (t, J = 7.4 Hz, 3H, CH3);13C NMR (150 MHz, DMSO):δ(ppm) 195.0, 157.6, 152.1, 146.3, 128.8, 127.4,
127.0, 119.4, 110.3, 74.2, 69.8, 39.1, 37.1, 26.6, 22.7, 21.1, 10.5; IR (KBr,
cm-1): 3435, 3173, 3062, 2952, 2190, 1648, 1626, 1606, 1485, 1249; Anal.
Calcd. for C19H20N2O2: C,74.00; H, 6.54; N, 9.08; Found: C, 74.16; H, 6.44; N,
9.05.
Example 4:2- butylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), butanol (50 mmol, 4.6 mL), anhydrous FeCl3(1 mmol, 0.2 g) is added to trifluoromethyl benzene sulfonic acid (1.0 mL)
In three-necked flask, mixture reacts 3.5 h at 100 DEG C, is cooled to room temperature.120 mL water are added into reaction system, with 5%
Na2CO3Aqueous solution adjusts pH value to 7.0, is extracted with dichloromethane three times, merges organic phase, drying obtains crude product after concentration.
2- butylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4 is obtained through column chromatography for separationHChromene, it is cream-coloured solid
Body, yield 87%, m.p. 184.4-185.2 DEG C.1H NMR (600 MHz, DMSO): δ(ppm) 9.74 (s, 1H,
NH), 7.29 (t, J = 7.8 Hz, 2H, ArH), 7.18 (m, 3H, ArH), 4.48 (s, 1H, CH),
4.24-4.27 (m, 1H, CH2N), 4.10-4.13 (m, 1H, CH2N), 2.51-2.57 (m, 2H, CH2),
2.18-2.28 (m, 2H, CH2), 1.81-1.94 (m, 2H, CH2), 1.60-1.64 (m, 2H, CH2), 1.38-
1.43 (m, 2H, CH2), 0.90 (t, J =7.4Hz , 3H, CH3); 13C NMR (150 MHz, DMSO):δ
(ppm) 195.0, 157.6, 152.1, 146.3, 128.8, 127.4, 127.0, 119.4, 110.2, 72.4,
69.8, 39.1, 37.1, 31.3, 26.6, 21.1, 18.7, 14.0; IR (KBr, cm-1): 3436, 3246,
3198, 2960, 2190, 1625, 1488, 1249; Anal. Calcd. for C20H22N2O2: C, 74.51; H,
6.88; N, 8.69; Found: C, 74.48; H, 6.92; N, 8.64.
Example 5:2- isopropylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), isopropanol (30 mmol, 2.3 mL), anhydrous InCl3(1 mmol, 0.22 g) is added to three mouthfuls of burnings with acetic acid (1.5 mL)
In bottle, mixture reacts 6.0 h at 90 DEG C, is cooled to room temperature.100 mL water are added into reaction system, with 5% Na2CO3
Aqueous solution adjusts pH value to 7.0, three times with ether extraction, merges organic phase, drying obtains crude product after concentration.Through column chromatography point
From obtaining 2- isopropylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, white solid, yield
84%, m. p. 171.2-172.4 DEG C.1H NMR (600 MHz, DMSO): δ(ppm) 9.72 (s, 1H, NH),
7.27-7.30 (t, J =7.8Hz, 2H, ArH), 7.17-7.19 (m, 3H, ArH), 4.67-4.71 (m, 1H,
CHN), 4.48 (s, 1H, CH), 2.50-2.55(m, 2H, CH2), 2.16-2.27 (m, 2H, CH2), 1.91-
1.99 (m, 2H, CH2), 1.26-1.27 (d, J =6.1 Hz, 3H, CH3), 1.21-1.22 (t, J =6.0 Hz,
3H, CH3); 13C NMR (150 MHz, DMSO):δ(ppm) 195.0, 156.3, 152.2, 146.3, 128.8,
127.4, 127.1, 119.4, 110.1, 76.3, 72.8, 39.2, 37.1, 26.6, 22.4, 21.9, 21.1;
IR (KBr, cm-1): 3437, 3170, 3059, 2953, 2188, 1627, 1484, 1247; Anal. Calcd.
for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08; Found: C, 69.87; H, 6.62; N, 9.13.
Example 6:2- benzylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol, 2.66
G), benzylalcohol (20 mmol, 2.1 mL), anhydrous MgCl2(1 mmol, 0.20 g) is added to three mouthfuls of burnings with the concentrated sulfuric acid (0.5 mL)
In bottle, mixture reacts 7.0 h at 100 DEG C, is cooled to room temperature.150 mL water are added into reaction system, with 5% Na2CO3
Aqueous solution adjusts pH value to 7.0, three times with acetonitrile extraction, merges organic phase, drying obtains crude product after concentration.Through column chromatography point
From obtaining 2- benzylamino -3- cyano -4- phenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, white solid, yield 88%,
m. p. 225.2-226.9℃。1H NMR (600 MHz, DMSO): δ(ppm) 9.89 (s, 1H, NH), 7.39-
7.44 (m, 5H, ArH), 7.24 (t, J =7.8Hz, 2H, ArH), 7.15-7.18 (m, 1H, ArH), 7.08
(t, J = 7.8 Hz, 2H, ArH), 5.31 (d, J = 11.4Hz, 1H, CH2N), 5.23 (d, J = 12.0
Hz, 1H, CH2N), 4.47 (s, 1H, CH), 2.50-2.57 (m, 2H, CH2), 2.17-2.24 (m, 2H,
CH2), 1.78-1.94 (m, 2H, CH2); 13C NMR (150 MHz, DMSO):δ(ppm) 195.0, 157.1,
151.9, 146.0, 135.4, 129.2, 129.0, 128.9, 128.8, 127.5, 127.0, 119.4, 110.4,
73.8, 71.0, 39.1, 37.1, 26.6, 21.1; IR (KBr, cm-1): 3436, 3155, 3040, 2947,
2198, 1656, 1607, 1491, 1255; Anal. Calcd. for C23H20N2O2: C, 77.51; H, 5.66;
N, 7.86; Found: C, 77.48; H, 5.69; N, 7.79.
Example 7:2- benzylamino -3- cyano -4- p-methylphenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- p-methylphenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10
Mmol, 2.80 g), benzylalcohol (15 mmol, 1.6 mL), anhydrous TiCl4(1 mmol, 0.1 mL) and acetic acid (1.0 mL) are added
Into three-necked flask, mixture reacts 5.0 h at 80 DEG C, is cooled to room temperature.150 mL water are added into reaction system, with 5%
Na2CO3Aqueous solution adjusts pH value to 7.0, three times with acetonitrile extraction, merges organic phase, drying obtains crude product after concentration.Through column
Chromatography obtains 2- benzylamino -3- cyano -4- p-methylphenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene, it is cream-coloured solid
Body, yield 85%, m. p. 187.6-188.8 DEG C.1H NMR (600 MHz, DMSO): δ(ppm) 9.85 (s, 1H,
NH), 7.38-7.44 (m,5H, ArH ), 7.03 (d, J = 7.8 Hz, 2H, ArH), 6.95 (d, J = 7.8
Hz, 2H, ArH), 5.30 (d, J = 11.4 Hz, 1H, CH2N), 5.21 (d, J = 11.4 Hz, 1H,
CH2N), 4.42 (s, 1H, CH), 2.50-2.55 (m, 2H, CH2), 2.24 (s, 3H, CH3), 2.15-2.22
(m, 2H, CH2), 1.89-1.93 (m, 1H, CH2), 1.75-1.79 (m, 1H, CH2); 13C NMR (150 MHz,
DMSO):δ(ppm) 195.0, 157.0, 151.6, 143.1, 136.0, 135.4, 129.3, 129.2, 129.0,
128.9, 127.4, 119.4, 110.5, 73.8, 71.1, 38.7, 37.1, 26.6, 21.1, 21.0; IR
(KBr, cm-1): 3436, 3159, 3050, 2948, 2198, 1653, 1492, 1253; Anal. Calcd. for
C24H22N2O2: C, 77.81; H, 5.99; N, 7.56; Found: C, 77.87; H, 5.90; N, 7.53.
Example 8:2- benzylamino -3- cyano -4- rubigan -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- rubigan -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10 mmol,
3.00 g), benzylalcohol (20 mmol, 2.1 mL), anhydrous InCl3(1 mmol, 0.22 g) is added to three with the concentrated sulfuric acid (0.5 mL)
In mouth flask, mixture reacts 5.0 h at 80 DEG C, is cooled to room temperature.150 mL water are added into reaction system, with 5%
Na2CO3Aqueous solution adjusts pH value to 7.0, three times with ether extraction, merges organic phase, drying obtains crude product after concentration.Through column layer
Analyse isolated 2- benzylamino -3- cyano -4- rubigan -5- oxo -5,6,7,8- tetrahydro -4HChromene, beige solid,
Yield 84%, m. p. 179.7-181.2 DEG C.1H NMR (600 MHz, DMSO): δ(ppm) 9.93 (s, 1H, NH),
7.39-7.44 (m, 5H, ArH ), 7.28 (t, J = 8.4 Hz, 2H, ArH), 7.07 (d, J = 8.4 Hz,
2H, ArH), 5.31 (d, J = 11.4 Hz, 1H, CH2N), 5.23 (d, J = 12.0 Hz, 1H, CH2N),
4.47 (s, 1H, CH), 2.50-2.56 (m, 2H, CH2), 2.15-2.26 (m, 2H, CH2), 1.89-1.93
(m, 1H, CH2), 1.76-1.81 (m, 1H, CH2); 13C NMR (150 MHz, DMSO):δ(ppm) 195.0,
157.2, 152.1, 144.9, 135.3, 131.6, 129.4, 129.2, 129.0, 129.0, 128.7, 119.2,
110.0, 73.8, 70.1, 38.7, 37.0, 26.6, 21.1；IR (KBr, cm-1): 3433, 3148, 3034,
2948, 2195, 1655, 1490, 1255; Anal. Calcd. for C23H19N2O2Cl: C, 70.68; H, 4.90;
N, 7.17; Found: C, 70.64; H, 4.97; N, 7.25.
Example 9:2- benzylamino -3- cyano -4- p-nitrophenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene
By 2- Amino 3 cyano -4- p-nitrophenyl -5- oxo -5,6,7,8- tetrahydro -4HChromene derivative (10
Mmol, 3.11 g), benzylalcohol (25 mmol, 2.6 mL), anhydrous FeCl3(1 mmol, 0.16 g) adds with benzoic acid (1.4 mL)
Enter into three-necked flask, mixture reacts 8.0 h at 100 DEG C, is cooled to room temperature.150 mL water are added into reaction system,
With 5% Na2CO3Aqueous solution adjusts pH value to 7.0, three times with chloroform extraction, merges organic phase, drying obtains slightly after concentration
Product.2- benzylamino -3- cyano -4- p-nitrophenyl -5- oxo -5,6,7,8- tetrahydro -4 is obtained through column chromatography for separationHColor
Alkene, yellow solid, yield 85%, m.p. 120.8-122.4 DEG C.1H NMR (600 MHz, DMSO): δ(ppm) 10.04
(s, 1H, NH), 8.11 (d, J =8.4Hz, 2H, ArH), 7.39-7.44 (m, 5H, ArH), 7.34 (d, J
= 9.0 Hz, 2H, ArH), 5.33-5.35 (d, J = 11.4 Hz, 1H, CH2N), 5.26 (d, J =11.4Hz,
1H, CH2N), 4.64 (s, 1H, CH), 2.50-2.60 (m, 2H, CH2), 2.16-2.28 (m, 2H, CH2),
1.90-1.96 (m, 1H, CH2), 1.77-1.85 (m, 1H, CH2); 13C NMR (150 MHz, DMSO):δ(ppm)
195.0, 157.5, 153.1, 152.7, 146.7, 135.2, 129.2, 129.0, 129.0, 128.9, 124.1,
118.9, 109.4, 73.9, 70.0, 39.4, 36.9, 26.7, 21.1; IR (KBr, cm-1): 3176, 3063,
2951, 2196, 1660, 1517, 1490, 1347, 1249; Anal. Calcd. for C23H19N3O4: C,
68.82; H, 4.77; N, 10.47; Found: C, 68.75; H, 4.51; N, 10.42.
Claims (3)
1. a kind of N- alkylation for the 2- amino chromene derivative that Lewis/Bronsted acid collaboration promotes lower alcohol to participate in,
It is characterized in that: respectively by 10mmol R1Substituted 2- Amino 3 cyano -5- oxo -5,6,7,8- tetrahydro -4H- chromene is derivative
Object, 10~100mmol R2OH alcohol, 1~2mmol Lewis acid and 1~10mL Bronsted acid are added in reaction vessel, are mixed
It closes object and reacts 0.5~30h at 25~100 DEG C, be cooled to room temperature；100~200mL water is added into reaction system, with 5%
Na2CO3Aqueous solution adjusts pH value and three times with organic solvent extraction merges organic phase to neutrality, dry, and crude product is obtained after concentration；
Crude product obtains the alkylated 3- cyano -5- oxo -5,6,7,8- tetrahydro -4H- chromene derivative of N- by pillar layer separation；Instead
Answer formula are as follows:
Wherein, R1For phenyl, substituted phenyl or heterocyclic substituent, substituted phenyl includes 4- aminomethyl phenyl, 4- methoxybenzene
Base, 4- chlorophenyl, 4- nitrobenzophenone, 2- nitrobenzophenone, 2- aminomethyl phenyl, trifluoromethyl, 4- hydroxy phenyl, heterocycle take
Dai Ji includes 2- furyl, 2- pyridyl group；R2For C1~C8 alkyl of linear chain or branched chain, cyclohexyl, benzyl, to methylbenzyl,
To bromobenzyl, benzhydryl；The Lewis acid is AlCl3、MgCl2、FeCl3、InCl3、ZnCl2、TiCl4、SnCl4One
Kind；The Bronsted is the concentrated sulfuric acid, formic acid, acetic acid, benzoic acid, p-methyl benzenesulfonic acid, trifluoromethyl benzene sulfonic acid, perchloric acid
It is a kind of.
2. the 2- amino chromene that a kind of Lewis/Bronsted acid collaboration according to claim 1 promotes lower alcohol to participate in is derivative
The N- alkylation of object, which is characterized in that the mass ratio of the material of the lewis acid and bronsted acid is 1:5~1:
50。
3. the 2- amino chromene that a kind of Lewis/Bronsted acid collaboration according to claim 1 promotes lower alcohol to participate in is derivative
The N- alkylation of object, which is characterized in that the extractant is ethyl acetate, acetonitrile, ether, methylene chloride and trichlorine
One kind of methane.
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Citations (2)
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| WO2005077863A1 (en) * | 2004-02-11 | 2005-08-25 | Saltigo Gmbh | METHOD FOR ESTABLISHING CC BONDS BETWEEN ELECTROPHILIC SUBSTRATES AND π - NUCLEOPHILES IN NEUTRAL TO ALKALINE AQUEOUS OR ALCOHOLIC SOLVENTS WITHOUT USING A LEWIS OR BRONSTED ACID |
| CN104822683A (en) * | 2012-08-06 | 2015-08-05 | 罗盖特公司 | Method for preparing dialkyloxydianhyrohexitol by etherification of dianhydrohexitol using light alcohol, in presence of acidic catalyst |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2005077863A1 (en) * | 2004-02-11 | 2005-08-25 | Saltigo Gmbh | METHOD FOR ESTABLISHING CC BONDS BETWEEN ELECTROPHILIC SUBSTRATES AND π - NUCLEOPHILES IN NEUTRAL TO ALKALINE AQUEOUS OR ALCOHOLIC SOLVENTS WITHOUT USING A LEWIS OR BRONSTED ACID |
| CN104822683A (en) * | 2012-08-06 | 2015-08-05 | 罗盖特公司 | Method for preparing dialkyloxydianhyrohexitol by etherification of dianhydrohexitol using light alcohol, in presence of acidic catalyst |
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