CN100478333C - Chiral and non-chiral diimidazolinylbenzene compounds and synthesis method - Google Patents
Chiral and non-chiral diimidazolinylbenzene compounds and synthesis method Download PDFInfo
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Abstract
The invention discloses a chirality and non-chirality diimidazoline benzene compound and synthesizing method with general formula as right formula (R1 is H, i-Pr or Bn; R2 is p-phenylmethyl, p-tolyloxy, cyclohexyl or isopropyl; R3 is H, OH, NO2, NH2 or CH3COO), which comprises the following steps: refluxing bishydralkamine in the thionyl chloride; evaporating excessive thionyl chloride; dissolving in the ether; filtering; adding trimethylamine and different substituted ammonia; stirring under indoor temperature; adding sodium hydroxide solution; extracting; drying; condensing; proceeding film chromatographic separation; obtaining the product.
Description
Technical field
The invention belongs to the synthetic and applied technical field of organic compound, relate to chirality and non-chiral diimidazolinylbenzencompounds compounds and synthetic method.
Background technology
Asymmetric catalytic technology is all to have obtained immense success in the fundamental research field or in the applied research field, especially the ten years since nineteen nineties, the part of novel texture, new asymmetric catalysis and new asymmetry catalysis notion and method emerge in an endless stream especially, and asymmetry catalysis research is in the flourishing as never before stage.
At numerous P that have, N is in the single, double and multiple tooth chiral ligand of O and other ligating atom; bisoxazoline is one of part type that attracts most attention, such part is easy to preparation, and chiral source is easy to get and Adjustable structure, mainly is to close ring by amidation, halogenation, the alkalescence of chiral amino alcohol.The bisoxazoline part can with the metallic ion coordination of a large amount of different valence state, form to determine in a series of asymmetric catalysis, to have a wide range of applications the metal complex catalysts of structure, have advantages such as the high and reaction conditions gentleness of enantioselectivity.For example 1, (the ee value of trans product is up to 96% for the effective catalyzing propone acid esters of rhodium complex energy of 3-bisoxazoline base benzene or the asymmetric reduction Aldol reaction of aldehyde and silane, J.Am.Chem.Soc.2005,127,6972), and α, (the ee value is up to 98% for β unsaturated ester and the conjugation reduction reaction under the silane effect, Synlett 2004,14, and 2493); Its palladium complex also has good application (reference (a) Tetrahedron Lett.1997,38,5881, (b) Organometallics2000,19,1282) in Diels-Alder reaction and Michael reaction; Its platinum complex successfully is used for the Aldol type condensation reaction (Organometallics 2002,21,3408) of isocyanide compound and aldehyde.On the other hand, have research group report to replace corresponding chiral oxazoline part in recent years with the chiral imidazole quinoline after, owing to the NR group electronic effect that increases newly and the influence of steric effect, make its cis-selectivity in asymmetric catalysis have raising (reference (a) Org.Lett.2002,4,4713 in various degree, (b) Synlett 2003,1, and 102, (c) Org.Lett.2003,5,595, (d) Tetrahedron:Asymmetry 2004,15,3365, (e) Org.Biomol.Chem.2004,2,1995, (f) Org.Lett.2005,7,3393, (g) Org.Lett.2005,7,4137).
In the numerous imidazolines of synthetic, mostly be non-chiral compound greatly, and it is less to the imidazolines research of chirality, chirality bi-imidazoline compounds only have a few example reports (as 2,6-bi-imidazoline yl pyridines Org.Lett.2005,7,3393, bi-imidazoline base alkane Org.Biomol.Chem.2004,2,1995); On the Study of synthesis method of imidazolines, be mainly acid or ester and diamine reactant dehydration ring closure and the synthetic method in addition,, limited the application of this method in the synthesis of chiral tetrahydroglyoxaline because the difficulty and the price of chiral diamine preparation are higher.This seminar in the exploration of long-term organic synthesis, found one simple and easy to do, utilize amino alcohol cheap and easy to get to prepare the synthetic method of chirality and non-chiral diimidazolinylbenzencompounds compounds, utilize this method to synthesize a series of chirality and non-chiral diimidazolinylbenzencompounds compounds simultaneously.
Summary of the invention
In order to reduce the production cost of chirality and non-chiral diimidazolinylbenzencompounds compounds, increase the kind of this compounds, enlarge such application of compound field, the purpose of this invention is to provide a class chirality and non-chiral diimidazolinylbenzencompounds compounds and synthetic method, this synthetic method goes out to send the chirality and the non-chiral diimidazolinylbenzencompounds compounds of preparation broad variety and function from the raw material that simply is easy to get.
The present invention realizes above-mentioned purpose by the following technical solutions: chirality and non-chiral diimidazolinylbenzencompounds compounds are following general formula:
R wherein
1Be H, i-Pr (sec.-propyl), Bn (benzyl);
R
2Be p-methylphenyl, p-methoxyphenyl, cyclohexyl, sec.-propyl;
R
3Be H, OH, NO
2, NH
2, CH
3COO
Bi-imidazoline base benzene-like compounds is synthetic by the following method: two amido alcohol are refluxed in thionyl chloride, boil off excessive thionyl chloride then, it is dissolved in ether, crosses the elimination insolubles, add triethylamine and aromatic amine or aliphatic amide again, stirring at room, the aqueous solution that adds sodium hydroxide then, extraction, drying, concentrate, the thin-layer chromatography separation promptly gets bi-imidazoline base benzene-like compounds.
The mol ratio of the pure and mild thionyl chloride of two amidos is two amido alcohol: thionyl chloride=1: 8-20, return time are 4-10 hour; The mole dosage of triethylamine is 4-8 a times of two amido alcohol, aromatic amine is that para-totuidine or P-nethoxyaniline, aliphatic amide are hexahydroaniline or Isopropylamine, the mole dosage of aromatic amine or aliphatic amide is 2-3 a times of two amido alcohol, and the stirring at room time was at least 5 hours; Separation method adopts thin-layer chromatography to separate, and the thin-layer chromatography developping agent is methyl alcohol or acetone.
Positively effect of the present invention is:
The present invention relates to a class chirality and a non-chiral diimidazolinylbenzencompounds compounds, at first, this type of bi-imidazoline base benzene-like compounds is compared NR with corresponding bisoxazoline base benzene compound
2The introducing of group will change its electronic effect and steric effect, be expected to improve its cis-selectivity in asymmetric catalysis.Secondly, R in this compounds
3Can be active function groups such as hydroxyl, amino etc., for next step immobilized providing may, the advantage of this compounds of immobilized back is conspicuous, no matter carrier is the polymkeric substance or the insoluble carrier of solubility, can realize separating of part or catalyzer and reaction system by simple filtering, for the recycling of catalyzer provides convenience, estimate that this type of part has good application prospects.In addition, in building-up process, utilize amino alcohol cheap and easy to get to replace diamine compounds, the method of easy, an easy row is provided for synthetic bi-imidazoline compounds, more synthesis of chiral bi-imidazoline compounds provides a valid approach, and this method will facilitate for the research and the widespread use of chirality bi-imidazoline compounds.
Embodiment
Further describe the present invention below in conjunction with example:
Used pair of amido alcohol of the present invention is according to document (J.Org.Chem.1998,63,2961-2967) the two amido alcohol of described method preparation.Concrete grammar is: in the tetrahydrofuran solution of chirality or achirality amino alcohol and triethylamine, between adding Benzoyl chloride or have active function groups between the tetrahydrofuran solution of Benzoyl chloride, stirred 16 hours under the room temperature, remove by filter insolubles, boil off tetrahydrofuran (THF), use acetone solution, column chromatography for separation gets the two amido alcohol of product.
Example 1,1,3-two (4,5-dihydro-1-p-methylphenyl-1H-imidazoles-2-yl) preparation of benzene: N, N '-two (2-hydroxyethyl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 4 hours down, revolves to steam to remove excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (565mg again to add dry good triethylamine, 5.28mmol), stirred 5 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, utilize or methyl alcohol as developping agent cross plate separate pure product, yield 68.5%.M.p.:169-170 ℃, IR (KBr): v 3030,2923,2866,1618,1587,1513,1486,1420,1383,1322,1300,1250,1150,1029,996,895,814,706,550cm
-1.
1H NMR (400MHz) is (DMSO): δ 7.53 (s, 1H, H2,1,3-disubstituted benzene ring), 7.30 (d, J=7.7Hz, 2H, H4 and H6,1,3-disubstituted benzene ring), 7.24 (t, J=7.6Hz, 1H, H5,1,3-disubstituted benzene ring), 7.00 (d, J=8.2Hz, 4H, H3 and H5,1,4-disubstituted benzene ring), 6.62 (d, J=8.3Hz, 4H, H2 and H6,1,4-disubstituted benzene ring), 3.88 (s, 8H, CH
2), 2.20 (s, 6H, CH
3).
13C NMR (100MHz) is (DMSO): δ 161.4 (C2imidazoline), 140.9 (C1,1,4-disubstituted benzene ring), 132.7 (C4,1,4-disubstituted benzene ring), 131.9 (C1 and C3,1,3-disubstituted benzene ring), 129.4 (C4 and C6,1,3-disubstituted benzene ring, C3 and C5,1,4-disubstituted benzene ring), 128.2 (C2 and C5,1,3-disubstituted benzene ring), 122.9 (C2 and C6,1,4-disubstituted benzene ring), 54.1 and 53.0 (C4 and C5 imidazoline), 20.5 (CH
3) .MS (m/z, ES
+): 395 (M+H), high-resolution MS (m/z, ES
+), found for M+H=395.2228, C
26H
27N
4Requires395.2236.
Example 2,1, two ((the S)-4-sec.-propyls-4 of 3-, 5-dihydro-1-p-methylphenyl-1H-imidazoles-2-yl) preparation of benzene: N, N '-two ((S)-1-hydroxy-3-methyl butyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 6 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (565mg again to add dry good triethylamine, 5.28mmol), stirred 6 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone as developping agent cross plate separate product, yield 44.5%.Light yellow oil, IR (KBr): v 3032,2961,2928,2873,1693,1612,1571,1514,1481,1440,1383,1305,1155,1023,914,816,703cm
-1.
1H NMR (400MHz) (CH
3COCH
3-d
6): δ 7.75 (t, J=1.6Hz, 1H, H2,1,3-disubstituted benzene ring), 7.39 (dd, J=1.6,7.7Hz, 2H, H4and H6,1,3-disubstituted benzene ring), 7.18 (t, J=7.8Hz, 1H, H5,1,3-disubstituted benzene ring), 7.02 (d, J=8.0Hz, 4H, H3 and H5,1,4-disubstituted benzene ring), 6.68 (d, J=8.3Hz, 4H, H2 and H6,1,4-disubstituted benzene ring), 4.08 (dd, J=9.2,10.6Hz, 2H, CHH), 4.00 (m, 2H, NCH), 3.57 (dd, J=7.6,9.0Hz, 2H, CHH), 2.23 (s, 6H, CH
3), 1.83-1.80 (m, 2H, (CH
3)
2CH), 0.97 (d, J=6.8Hz, 6H, CH
3CH), 0.91 (d, J=6.8Hz, 6H, CHCH
3).
13C NMR (100MHz) (CH
3COCH
3-d
6): δ 161.6 (C2 imidazoline), 141.7 (C1,1,4-disubstituted benzene rings), 133.8 (C4,1,4-disubstituted benzene ring), 132.3 (C1 and C3,1,3-disubstituted benzene rings), (130.3 C4 andC6,1,3-disubstituted benzene ring), 130.1 (C2,1,3-disubstituted benzene ring), 129.9 (C3 and C5,1,4-disubstituted benzene rings), (128.3 C5,1,3-disubstituted benzene ring), 124.0 (C2 and C6,1,4-disubstituted benzene ring), 70.6 (NCH), 57.1 (CH
2), 33.6 ((CH
3)
2CH), 20.6 (CH
3), 18.6 (CH
3CH), 18.1 (CHCH
3) .MS (m/z, ES
+): 479 (M+H), high-resolution MS (m/z, ES
+), found for M+H=479.3176, C
32H
39N
4Requires 479.3175.
Example 3,1, two ((the S)-4-benzyls-4 of 3-, 5-dihydro-1-p-methylphenyl-1H-imidazoles-2-yl) preparation of benzene: N, N '-two ((S)-1-hydroxyl-3-phenyl propyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 8 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (565mg again to add dry good triethylamine, 5.28mmol), stirred 7 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone as developping agent cross plate separate product, yield 53.7%.Light yellow oil, IR (KBr): v 3060,3027,2922,2867,1605,1570,1513,1495,1476,1452,1438,1383,1304,1154,1111,1084,1031,911,816,747,702cm
-1.
1H NMR (400MHz) (CH
3COCH
3-d
6): δ 7.79 (s, 1H, H2,1,3-disubstituted benzene ring), 7.34-7.28 (m, 6H, H4 andH6,1,3-disubstituted benzene ring and H2 and H6, single-substituted ring), 7.23 (t, J=7.2Hz, 4H, H3and H5, single-substituted ring), 7.19-7.13 (m, 3H, H5,1,3-disubstituted benzene ring and H4, single-substituted ring), 6.95 (d, J=8.1Hz, 4H, H3 and H5,1,4-disubstituted benzene ring), 6.48 (d, J=8.2Hz, 4H, H2 and H6,1,4-disubstituted benzene ring), 4.52-4.44 (m, 2H, NCH), 4.08 (apt, J=9.8Hz, 2H, NCHH), 3.60 (dd, J=6.9,9.5Hz, 2H, NCHH), 3.02 (dd, J=5.2,13.5Hz, 2H, CHHPh), 2.86 (dd, J=7.0,13.5Hz, 2H, CHHPh), 2.21 (s, 6H, CH
3).
13C NMR (100MHz) (CH
3COCH
3-d
6): δ 162.0 (C=N), 141.5 (C1,1,4-disubstituted benzene rings), (139.1 C1, single-substituted ring), 134.1 (C4,1,4-disubstituted benzene ring), 132.5 (C1 and C3,1,3-disubstituted benzene rings), (130.7 C4 and C6,1,3-disubstituted benzene ring), 130.6 (C2 and C6, single-substituted ring), 130.1 (C3 and C5,1,4-disubstituted benzene rings), (130.0 C2,1,3-disubstituted benzene ring), (128.9 C3 and C5, single-substituted ring), 128.5 (C5,1,3-disubstituted benzene ring), 127.0 (C4, single-substituted ring), 124.0 (C2 andC6,1,4-disubstituted benzene ring), 65.8 (NCH), 58.9 (NCH
2), 42.5 (CH
2Ph), 20.8 (CH
3) .MS (m/z, ES
+): 575 (M+H), high-resolution MS (m/z, ES
+), found for M+H=575.3168, C
40H
39N
4Requires 575.3175.
Example 4,1,3-two (4,5-dihydro-1-p-methoxyphenyl-1H-imidazoles-2-yl) preparation of benzene: N, N '-two (2-hydroxyethyl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 5 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds P-nethoxyaniline (651mg again to add dry good triethylamine, 5.28mmol), stirred 5 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, utilize acetone recrystallization to get pure product, yield 60.8%.M.p.:181-182 ℃, IR (KBr): v 3011,2927,2878,1612,1577,1512,1473,1389,1324,1283,1244,1176,1108,1029,901,832,700,611,566cm
-1.
1H NMR (400MHz) is (DMSO): δ 7.55 (s, 1H, H2,1,3-disubstituted benzene ring), 7.28 (d, J=8.3Hz, 2H, H4 and H6,1,3-disubstituted benzene ring), 7.18 (t, J=7.7Hz, 1H, H5,1,3-disubstituted benzene ring), 6.78 (d, J=9.0Hz, 4H, CH, 1,4-disubstituted benzene ring), 6.72 (d, J=9.0Hz, 4H, CH, 1,4-disubstituted benzene ring), 3.86-3.81 (m, 8H, CH
2), 3.68 (s, 6H, OCH
3).
13C NMR (100MHz) is (DMSO): δ 162.0 (C2 imidazoline), 156.1 (C), 136.9 (C), 131.6 (C), (129.3 C4 and C6,1,3-disubstituted benzene ring), 128.4 (C2,1,3-disubstituted benzene ring), 128.0 (C5,1,3-disubstituted benzene ring), 125.3 (CH, 1,4-disubstituted benzene ring), 114.3 (CH, 1,4-disubstituted benzene ring), 55.3 (OCH
3), 55.0 and 53.1 (C4and C5imidazoline) .MS (m/z, ES
+): 427 (M+H) .high-resolution MS (m/z, ES
+), found for M+H=427.2140, C
26H
27N
4Requires 427.2134.
Example 5,1, two ((the S)-4-sec.-propyls-4 of 3-, 5-dihydro-1-p-methoxyphenyl-1H-imidazoles 2-yl) preparation of benzene: N, N '-two ((S)-1-hydroxy-3-methyl butyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 7 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds P-nethoxyaniline (651mg again to add dry good triethylamine, 5.28mmol), stirred 6 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone as developping agent cross plate separate product, yield 52.3%.Light yellow oil, IR (KBr): v 3040,2956,2871,2836,1617,1575,1511,1465,1441,1382,1281,1245,1179,1107,1040,917,832,807,703cm
-1.
1H NMR (400MHz) is (DMSO): δ 7.55 (s, 1H, H2,1,3-disubstituted benzene ring), 7.32 (dd, J=1.6,7.2Hz, 2H, H4and H6,1,3-disubstituted benzene ring), 7.20 (t, J=7.2Hz, 1H, H5,1,3-disubstituted benzene ring), 6.79 (d, J=8.8Hz, 4H, CH, 1,4-disubstituted benzene ring), 6.71 (d, J=8.8Hz, 4H, CH, 1,4-disubstituted benzene ring), 4.02 (apt, J=10.4Hz, 2H, CHH), 3.93 (ddd, J=6.0,7.2,10.8Hz, 2H, NCH), 3.67 (s, 6H, OCH
3), 3.45 (apt, J=8.8Hz, 2H, CHH), 1.78-1.73 (m, 2H, (CH
3)
2CH), 0.92 (d, J=6.8Hz, 6H, CH
3CH), 0.86 (d, J=6.8Hz, 6H, CHCH
3).
13C NMR (100MHz) is (DMSO): δ 160.8 (C2 imidazoline), 156.3 (C), 136.2 (C), 130.9 (C), (129.7 C4 and C6,1,3-disubstituted benzene ring), 129.1 (C2,1,3-disubstituted benzene ring), 128.1 (C5,1,3-disubstituted benzene ring), 125.3 (CH, 1,4-disubstituted benzene ring), 114.3 (CH, 1,4-disubstituted benzene ring), 69.3 (NCH), 57.1 (CH
2), 55.3 (OCH
3), 32.8 ((CH
3)
2CH), 18.5 (CH
3CH), 18.1 (CHCH
3) .MS (m/z, ES
+): 511 (M+H), high-resolution MS (m/z, ES
+), foundfor M+H=511.3062, C
32H
39N
4O
2Requires 511.3073.
Example 6,1, two ((the S)-4-benzyls-4 of 3-, 5-dihydro-1-p-methoxyphenyl-1H-imidazoles-2-yl) preparation of benzene: N, N '-two ((S)-1-hydroxyl-3-phenyl propyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 9 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (651mg again to add dry good triethylamine, 5.28mmol), stirred 7 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone as developping agent cross plate separate product, yield 89.5%.Light yellow oil, IR (KBr): v 3028,2928,1615,1572,1511,1442,1384,1286,1245,1177,1038,831,804,703cm
-1.
1H NMR (400MHz) (CH
3COCH
3-d
6): δ 7.77 (s, 1H, H2,1,3-disubstituted benzene ring), 7.33-7.29 (m, 6H, H4 and H6,1,3-disubstituted benzene ring and H2 and H6, single-substituted ring), 7.25 (t, J=7.2Hz, 4H, H3 and H5, single-substituted ring), 7.19 (t, J=7.1Hz, 2H, H4, single-substituted ring), 7.12 (t, J=7.7Hz, 1H, H5,1,3-disubstituted benzene ring), 6.73 (d, J=8.2Hz, 4H, CH, 1,4-disubstituted benzene ring), 6.56 (d, J=8.9Hz, 4H, CH, 1,4-disubstituted benzene ring), 4.51-4.44 (m, 2H, CH), 4.03 (apt, J=9.9Hz, 2H, NCHH), 3.71 (s, 6H, OCH
3), 3.51 (dd, J=7.2,9.4Hz, 2H, NCHH), 3.03 (dd, J=5.2,13.5Hz, 2H, CHHPh), 2.88 (dd, J=6.9,13.5Hz, 2H, CHHPh).
13C NMR (100MHz) (CH
3COCH
3-d
6): δ 162.6 (C=N), 157.5 (C), 139.2 (C), 137.5 (C), 132.4 (C), (130.7 C4 and C6,1,3-disubstituted benzene ring), 130.6 (C2 and C6, single-substituted rings), (130.2 C2,1,3-disubstituted benzene ring), 128.9 (C3 and C5, single-substituted rings), (128.3 C5,1,3-disubstituted benzene ring), 127.0 (C4, single-substituted rings), (126.4 CH, 1,4-disubstituted benzene ring), 114.8 (CH, 1,4-disubstituted benzene ring), 66.0 (CH), 59.6 (NCH
2), 55.7 (OCH
3), 42.5 (CH
2Ph) .MS (m/z, ES
+): 607 (M+H), high-resolutionMS (m/z, ES
+), found for M+H=607.3098, C
40H
39N
4O
2Requires 607.3073.
Example 7,5-hydroxyl-1, two ((the S)-4-sec.-propyls-4 of 3-, 5-dihydro-1-p-methylphenyl-1H-imidazoles-2-yl) preparation of benzene: 5-hydroxy-n, N '-two ((S)-1-hydroxy-3-methyl butyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 10 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (565mg again to add dry good triethylamine, 5.28mmol), stirred 8 hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone as developping agent cross plate separate product, yield 43.6%.M.p.:116-118 ℃, IR (KBr): v 3327.2,2963.8,2876.6,1644.1,1592.9,1542.1,1468.9,1430.3,1367.1,1228.4,1145.5,1072.1,1019.2,980.1,881.9,754.4,711.0,685.8cm
-1.
1H NMR (400MHz) is (DMSO): and δ 9.76 (s, Ar-OH), 7.02 (d, J=8.0Hz, 4H, CH, 1,4-disubstituted benzene ring), 6.94 (s, 1H, H4,1,3,5-trisubstituted benzene rings), (6.76 s, 2H, H2,1,3,5-trisubstituted benzene ring), 6.64 (d, J=7.9Hz, 4H, CH, 1,4-disubstituted benzene ring), 4.04 (apt, J=9.9Hz, 2H, CHH), 3.93 (m, 2H, NCH), 3.53 (apt, J=8.1Hz, 2H, CHH), 2.11 (s, 6H, CH
3), 1.71～1.75 (m, 2H, (CH
3)
2CH), 0.89 (d, J=6.8Hz, 6H, CH
3CH), 0.83 (d, J=6.8Hz, 6H, CHCH
3).
13C NMR (100MHz) is (DMSO): δ 160.5 (C=N), 156.8 (C), 140.3 (C), 133.1 (C), 132.2 (C), 129.5 (CH), 122.9 (CH), 119.9 (CH), 116.9 (CH), 69.0 (CH), 56.4 (NCH
2), 32.8 ((CH
3)
2CH), 20.6 (PhCH
3), 18.4 (CH
3CH), 18.0 (CHCH
3) .MS (m/z, ES
+): 495 (M+H).
Example 8,5-nitro-1, two ((the S)-4-sec.-propyls-4 of 3-, 5-dihydro-1-p-methylphenyl-1H-imidazoles-2-yl) preparation of benzene: 5-nitro-N, N '-two ((S)-1-hydroxy-3-methyl butyl-2-yl)-1, thionyl chloride (the 3mL of 3-dibenzamide (2.4mmol), 41.3mmol) solution refluxes and to stir 4 hours down, revolves to boil off excessive thionyl chloride and get light yellow oil, and it is dissolved in (10mL) in the dried ether, remove by filter insolubles, (2mL 14.3mmol), adds para-totuidine (565mg again to add dry good triethylamine, 5.28mmol), stirred three hours under the reaction solution room temperature.The reaction back adds the NaOH aqueous solution of 20mL 10%, with dichloromethane extraction (3 times, 20mL is each), merges organic phase, with saturated common salt washing, anhydrous MgSO
4Boil off solvent under the drying, vacuum, acetone/methylene dichloride=1: 2 as developping agent cross plate separate product, yield 61.0%.Light yellow oil, IR:3031,2958,2872,1607,1572,1539,1477,1346,1023,907,818,740,717;
1H NMR (400MHz) (CH
3COCH
3-d
6): δ 8.25 (d, J=1.3Hz, 2H, H2,1,3,5-trisubstituted benzene ring), (7.98 s, 1H, H4,1,3,5-trisubstituted benzene ring), 7.07 (d, J=8.1Hz, 4H, CH, 1,4-disubstituted benzene ring), 6.75 (d, J=8.3Hz, 4H, CH, 1,4-disubstituted benzene ring), 4.13 (apt, J=10.4Hz, 2H, CHH), 4.07-4.01 (m, 2H, NCH), 3.60 (apt, J=8.9Hz, 2H, CHH), 2.24 (s, 6H, CH
3), 1.86-1.81 (m, 2H, (CH
3)
2CH), 0.98 (d, J=6.8,6H, CH
3CH), 0.93 (d, J=6.7Hz, 6H, CHCH
3);
13C NMR (100MHz) (CH
3COCH
3-d
6): δ 159.8 (C=N), 148.1 (C), 141.2 (C), 135.5 (C), 134.8 (C), 133.9 (CH benzene), 130.3 (CH benzene), 124.8 (CH benzene), 124.5 (CH benzene), 71.1 (NCH), 57.7 (NCH
2), 33.7 ((CH
3)
2CH), 20.6 (PhCH
3), 18.6 (CH
3CH), 18.2 (CHCH
3) .MS (m/z, ES
+): 524 (M+H), high-resolution MS (m/z, ES
+), found for M+H=524.3045, C
32H
38N
5O
2Requires 524.3025.
Claims (10)
1, chirality and non-chiral diimidazolinylbenzencompounds compounds is characterized in that: be the compound of following general formula:
R wherein
1Be H, i-Pr or Bn;
R
2Be p-methylphenyl, p-methoxyphenyl, cyclohexyl or sec.-propyl;
R
3Be H, OH, NO
2, NH
2Or CH
3COO.
2, chirality as claimed in claim 1 and non-chiral diimidazolinylbenzencompounds compounds is characterized in that: work as R
3During for H, R
1Be H, R
2Be p-methylphenyl, p-methoxyphenyl, cyclohexyl or sec.-propyl.
3, a kind of method of synthetic bi-imidazoline base benzene-like compounds, it is characterized in that, two amido alcohol are refluxed in thionyl chloride, boil off excessive thionyl chloride then, add ether solvent, add triethylamine and aromatic amine or aliphatic amide again, stirring at room adds the aqueous solution of sodium hydroxide then, extraction, drying concentrates, and the thin-layer chromatography separation promptly gets product.
4, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 3 is characterized in that, two amido alcohol: thionyl chloride=1: 8-20 (mol ratio).
5, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 4 is characterized in that, two amido alcohol return time in thionyl chloride is 4-10 hour.
6, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 5 is characterized in that, the mole dosage of triethylamine is 4-8 a times of two amido alcohol.
7, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 6 is characterized in that, aromatic amine is para-totuidine or P-nethoxyaniline, and aliphatic amide is hexahydroaniline or Isopropylamine.
8, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 7 is characterized in that, the mole dosage of aromatic amine or aliphatic amide is 2-3 a times of two amido alcohol.
9, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 8 is characterized in that, at least 5 hours stirring at room time behind adding aromatic amine or the aliphatic amide.
10, the method for synthetic bi-imidazoline base benzene-like compounds as claimed in claim 9 is characterized in that, developping agent was methyl alcohol or acetone when thin-layer chromatography separated.
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Non-Patent Citations (12)
| Title |
|---|
| An efficient method for the synthesis of enantiopurephosphine-imidazoline ligands: application to theIr-catalyzed hydrogenation of imines. Eater Guiu et al..Tetrahedron:Asymmetry,Vol.15 . 2004 |
| An efficient method for the synthesis of enantiopurephosphine-imidazoline ligands: application to theIr-catalyzed hydrogenation of imines. Eater Guiu et al.Tetrahedron:Asymmetry,Vol.15. 2004 * |
| Ligand Electronic Effect in Enantioselective DiethylzincAdditions. Mike Casey et al..Synlett,Vol.1 . 2003 |
| Ligand Electronic Effect in Enantioselective DiethylzincAdditions. Mike Casey et al.Synlett,Vol.1. 2003 * |
| Preparation and DiastereoselectiveOrtho-Metalation of Chiral FerrocenylImidazolines: Remarkable Influence ofLDA as Metalation Additive. Rene Peters et al..ORGANIC LETTERS,Vol.7 No.19. 2005 |
| Preparation and DiastereoselectiveOrtho-Metalation of Chiral FerrocenylImidazolines:Remarkable Influence ofLDA as Metalation Additive. Rene Peters et al.ORGANIC LETTERS,Vol.7 No.19. 2005 * |
| Preparation of enantiopure biimidazoline ligands and their usein asymmetric catalysis. Nicola A.Org.Biomol.Chem.,,Vol.2 . 2004 |
| Preparation of enantiopure biimidazoline ligands and their usein asymmetric catalysis. Nicola A.Org.Biomol.Chem.,Vol.2. 2004 * |
| Probing Electronic Effects in theAsymmetric Heck Reaction with the BIPILigands. Carl A.ORGANIC LETTERS,Vol.5 No.4. 2003 |
| Probing Electronic Effects in theAsymmetric Heck Reaction with the BIPILigands. Carl A.ORGANIC LETTERS,Vol.5 No.4. 2003 * |
| Synthesis and Application of ChiralPhosphino-Imidazoline Ligands:Ir-Catalyzed EnantioselectiveHydrogenation. Frederik Menges et al..ORGANIC LETTERS,Vol.4 No.26. 2002 |
| Synthesis and Application of ChiralPhosphino-Imidazoline Ligands:Ir-Catalyzed EnantioselectiveHydrogenation. Frederik Menges et al.ORGANIC LETTERS,Vol.4 No.26. 2002 * |
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