CN101585812B - Preparation method of (S) type thioic imidazolone compound - Google Patents
Preparation method of (S) type thioic imidazolone compound Download PDFInfo
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- CN101585812B CN101585812B CN2009100998657A CN200910099865A CN101585812B CN 101585812 B CN101585812 B CN 101585812B CN 2009100998657 A CN2009100998657 A CN 2009100998657A CN 200910099865 A CN200910099865 A CN 200910099865A CN 101585812 B CN101585812 B CN 101585812B
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- imidazolone compound
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- -1 imidazolone compound Chemical class 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 69
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims abstract description 40
- 239000003960 organic solvent Substances 0.000 claims abstract description 38
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 144
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 35
- 239000000126 substance Substances 0.000 claims description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000000706 filtrate Substances 0.000 claims description 13
- 230000035484 reaction time Effects 0.000 claims description 13
- GNTDGMZSJNCJKK-UHFFFAOYSA-N divanadium pentaoxide Chemical compound O=[V](=O)O[V](=O)=O GNTDGMZSJNCJKK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 239000012065 filter cake Substances 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 8
- 238000004821 distillation Methods 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000008096 xylene Substances 0.000 claims description 7
- 229960001701 chloroform Drugs 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- NHOWDZOIZKMVAI-UHFFFAOYSA-N (2-chlorophenyl)(4-chlorophenyl)pyrimidin-5-ylmethanol Chemical group C=1N=CN=CC=1C(C=1C(=CC=CC=1)Cl)(O)C1=CC=C(Cl)C=C1 NHOWDZOIZKMVAI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 4
- 230000008034 disappearance Effects 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 125000006289 hydroxybenzyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 238000012805 post-processing Methods 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 abstract 3
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 69
- 239000001301 oxygen Substances 0.000 description 46
- 229910052760 oxygen Inorganic materials 0.000 description 46
- 239000007788 liquid Substances 0.000 description 24
- 239000005864 Sulphur Substances 0.000 description 23
- 238000005987 sulfurization reaction Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 5
- 239000004570 mortar (masonry) Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- SARRRAKOHPKFBW-UHFFFAOYSA-N 2-chloro-3-phenylprop-2-enal Chemical compound O=CC(Cl)=CC1=CC=CC=C1 SARRRAKOHPKFBW-UHFFFAOYSA-N 0.000 description 1
- CAAMSDWKXXPUJR-UHFFFAOYSA-N 3,5-dihydro-4H-imidazol-4-one Chemical compound O=C1CNC=N1 CAAMSDWKXXPUJR-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005575 aldol reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003556 thioamides Chemical class 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a preparation method of (S) type thioic imidazolone compound represented by formula (II). The method includes: making the (S) type imidazolone compound and the thioic reagent react for 4 to 8 hours in the temperature of 70 to 110 degrees centigrade in an organic solvent; processing the reaction liquid after the reaction is finished so as to obtain (S) type thioic imidazolone compound represented by formula (II); the thioic reagent is the phosphorus pentasulfide which uses the aluminium oxide as carrier and which is prepared by evenly mixing the aluminum oxide with the phosphorus pentasulfide based on the mass ratio of 1: 0.4 to 0.8; the mass ratio of the (S) type imidazolone compound to the phosphorus pentasulfide in the thioic reagent is 1: 0.4 to 1.2. The invention successfully synthesizes a new organic functional chiral catalyst, which has wide application prospect in synthesis of natural product or chiral medicine.
Description
(1) technical field
The present invention relates to the preparation method of a kind of new catalyst (S) type thioic imidazolone compound.
(2) background technology
Suc as formula (S) type thioic imidazolone compound shown in (II) is the novel organic functions type catalyzer of a class, has the catalytic activity of potential asymmetric reaction.Before the present invention provides, its analogue (S) type imidazolone compound, shown in (I), reactions such as the alpha-fluoro of intermolecular Aldol reaction, Michael addition, Diels-Alder reaction, [3+2] cycloaddition, Friedel-Crafts reaction, aldehyde and asymmetric hydrogenation reduction have been widely used in.(S) the catalytic reaction conditions gentleness of type imidazolone compound is even also can reach productive rate and higher ee value preferably in room temperature, air, under the aqueous condition.In addition, Gryko (Adv.Synh.Catal., 2005,347,1948; J.Org.Chem., 2007,72,964) group is incorporated into sulphur atom in the amide group in the structural modification to the proline(Pro) acid amides, thereby has developed performance and active better thioamides organic micromolecule catalyst.
(3) summary of the invention
According to above-mentioned achievement in research, this project is carried out secondary development to the chiral imidazolinone catalyzer of having developed, be about to (S) type imidazolone compound and be transformed into (S) type thioic imidazolone compound, employing is that the thiophosphoric anhydride of carrier is a sulfo-reagent with the aluminum oxide, thereby develop the novel organic catalyst of a class, and the raising catalytic efficiency, reduce catalyst levels.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A kind of preparation method suc as formula (S) type thioic imidazolone compound shown in (II), described method is: suc as formula (S) type imidazolone compound and the sulfo-reagent shown in (I), in organic solvent, under 70～110 ℃ of temperature, reacted 4～8 hours, after reaction finished, reaction solution obtained suc as formula (S) type thioic imidazolone compound shown in (II) through aftertreatment; Described sulfo-reagent is to be the thiophosphoric anhydride of carrier with the aluminum oxide, is mixed according to mass ratio 1: 0.4～0.8 by aluminum oxide and thiophosphoric anhydride to make; Described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.4～1.2; Described organic solvent is one of following: benzene,toluene,xylene, chlorobenzene, trichloromethane, 1,2-ethylene dichloride, acetonitrile, tetrahydrofuran (THF) or Nitromethane 99Min..The reaction equation of described reaction is as follows:
In formula (I) or the formula (II), R
1For phenyl, benzyl, to hydroxybenzyl, propyl group or p-chlorobenzyl; R
2, R
3Independent separately is methyl, ethyl, hydrogen, sec.-propyl, the tertiary butyl, phenyl, rubigan, m-nitro base or p-methoxyphenyl; Perhaps R
2, R
3Connect into ring, R
2, R
3Constitute cyclopentyl, cyclohexyl or suberyl with the C on the imidazole ring.
Preferred described R
1Be phenyl or benzyl; Preferred R
2, R
3Independent separately is methyl, ethyl, sec.-propyl, phenyl, rubigan, the tertiary butyl or p-methoxyphenyl.
Sulfo-reagent of the present invention is to be the thiophosphoric anhydride of carrier with the aluminum oxide, is designated as P usually
2S
5/ Al
2O
3, mix according to mass ratio 1: 0.4～0.8 by aluminum oxide and thiophosphoric anhydride and to make.Common preparation method takes by weighing aluminum oxide and thiophosphoric anhydride according to mass ratio, puts into mortar and grinds 10～15min, gets final product up to the pale yellow powder that becomes homogeneous.Preferred described sulfo-reagent is mixed according to mass ratio by aluminum oxide and thiophosphoric anhydride and makes at 1: 0.6.
Described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.4～1.2, be preferably 1: 0.6～and 0.8.
Described organic solvent is one of following: benzene,toluene,xylene, chlorobenzene, trichloromethane, 1,2-ethylene dichloride, acetonitrile, tetrahydrofuran (THF) or Nitromethane 99Min., be preferably benzene,toluene,xylene, 1,2-ethylene dichloride or chlorobenzene most preferably are benzene or toluene.The quality of described organic solvent is 20～40 times of the imidazolone compound of (S) type shown in the formula (I) quality, is preferably 30～35 times.
Further, temperature of reaction of the present invention is preferably 80～90 ℃, and the reaction times is preferably 5～6 hours.
The present invention is usually with TLC tracking monitor reaction, and developping agent is that sherwood oil, ethyl acetate, methylene chloride volume ratio are 4: 1: 1 mixed solvent, judges reaction end by the disappearance that detects the raw material imidazolone compound.It is 4～8 hours that the required time is finished in general reaction.
Reaction postprocessing method of the present invention is: after reaction finishes, reaction solution leaves standstill, filter, get filter cake and filtrate, the filtrate distillation removes desolvates, residuum uses column chromatography purification, and developping agent is that sherwood oil, ethyl acetate, methylene chloride volume ratio are 4: 1: 1 mixed solvent, obtains suc as formula (S) type thioic imidazolone compound product shown in (II).Described filter cake can be used washed with dichloromethane, and washings and filtrate merge, and distillation removes and desolvates, and residuum uses column chromatography purification again.
Comparatively concrete, recommend the preparation method of (S) of the present invention type thioic imidazolone compound to carry out: to add in the organic solvent suc as formula (S) type imidazolone compound and the sulfo-reagent shown in (I) according to following steps, under 80～90 ℃ of temperature, reacted 5～6 hours, the reaction of TLC tracking monitor, judge reaction end by the disappearance that detects imidazolone compound, after reaction finishes, reaction solution leaves standstill, filter, get filter cake and filtrate, the filter cake washed with dichloromethane, washings and filtrate merge, and distillation removes and desolvates, and residuum uses column chromatography purification, developping agent is a sherwood oil, ethyl acetate, the methylene chloride volume ratio is 4: 1: 1 a mixing solutions, obtains suc as formula (S) type thioic imidazolone compound product shown in (II); Described sulfo-reagent is mixed according to mass ratio 1: 0.4～0.8 by aluminum oxide and thiophosphoric anhydride and makes; Described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.6～0.8; Described organic solvent is a benzene,toluene,xylene, 1,2-ethylene dichloride or chlorobenzene; The quality of described organic solvent is 30～35 times of (S) type imidazolone compound quality.
Beneficial effect of the present invention is: successfully synthesize the novel organic functions chiral catalyst of a class, synthetic method is simple, and cost of material is cheap.Product can be applicable to catalysis pyrrole derivatives and the Friedel-Crafts alkylated reaction that replaces phenylacrolein, has broad application prospects in natural product or chiral drug synthetic.
(4) embodiment
Below with specific examples technical scheme of the present invention is described, but protection scope of the present invention is not limited thereto:
Embodiment 1
The preparation of sulfo-reagent: accurately take by weighing aluminum oxide (10g), thiophosphoric anhydride (6g) is put into mortar and is ground 10～15min, up to the pale yellow powder that becomes homogeneous.
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.4 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
In the 100mL there-necked flask of mechanical stirring, reflux condensing tube and thermometer is housed, add (S)-5-benzyl-2,2,3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(1.18g), open and stir, slowly be warming up to 70 ℃, keep leaving standstill after 4 hours, filter, get filter cake and filtrate, the filter cake washed with dichloromethane, washings and filtrate merge, distillation removes desolvates, and residuum uses column chromatography purification, and developping agent is that sherwood oil, ethyl acetate, methylene chloride volume ratio are 4: 1: 1 mixing solutions, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.78g, productive rate 67%.
Embodiment 2
Change feed ratio, (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.5 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(1.48g), other are operated with embodiment 1, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.81g, productive rate 69%.
Embodiment 3
Change feed ratio, (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.6 (mol ratio) in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(1.78g), other are operated with embodiment 1, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.84g, productive rate 72%.
Embodiment 4
Change feed ratio, (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), other are operated with embodiment 1, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.91g, productive rate 78%.
Embodiment 5
Change feed ratio, (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.9 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.67g), other are operated with embodiment 1, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.87g, productive rate 75%.
Embodiment 6
Change feed ratio, (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 1.2 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(3.55g), other are operated with embodiment 1, get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.85g, productive rate 73%.
Embodiment 7
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 90 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.96g, productive rate 82% with embodiment 1.
Embodiment 8
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 110 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.94g, productive rate 80% with embodiment 1.
Embodiment 9
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 90 ℃, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-tri-methylimidazolium-4-ketone 1.01g, productive rate 86% with embodiment 1.
Embodiment 10
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 90 ℃, 8 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.94g, productive rate 80% with embodiment 1.
Embodiment 11
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, acetonitrile is an organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), acetonitrile 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.73g, productive rate 62% with embodiment 1.
Embodiment 12
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, chloroform is an organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), chloroform 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.54g, productive rate 46% with embodiment 1.
Embodiment 13
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, 1, the 2-ethylene dichloride is an organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), 1,2-ethylene dichloride 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.76g, productive rate 65% with embodiment 1.
Embodiment 14
Feed ratio (S)-5-benzyl-2-ethyl-2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-dimethyl-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2-ethyl-2, and 3-dimethyl-4-oxygen imidazolidone (5mmol, 1.16g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operate same EXAMPLE l, get pale yellow oily liquid body (S)-5-benzyl-2-ethyl-2,3-dimethyl-4-sulphur imidazolidone 0.99g, productive rate 80%.
Embodiment 15
Feed ratio (S)-5-benzyl-2-sec.-propyl-2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-dimethyl-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2-sec.-propyl-2, and 3-dimethyl-4-oxygen imidazolidone (5mmol, 1.23g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2-sec.-propyl-2,3-dimethyl-4-sulphur imidazolidone 1.02g, productive rate 78% with embodiment 1.
Embodiment 16
Feed ratio (S)-5-benzyl-2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-dimethyl-2-phenyl-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2, and 3-dimethyl-2-phenyl-4-oxygen imidazolidone (5mmol, 1.4g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,3-dimethyl-2-phenyl-4-sulphur imidazolidone 1.17g, productive rate 79% with embodiment 1.
Embodiment 17
Feed ratio (S)-5-phenyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-phenyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.02g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-phenyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.92g, productive rate 84% with embodiment 1.
Embodiment 18
Feed ratio (S)-5-benzyl-2-(4-chloro-phenyl-)-2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-dimethyl-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2-(4-chloro-phenyl-)-2, and 3-dimethyl-4-oxygen imidazolidone (5mmol, 1.57g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2-(4-chloro-phenyl-)-2,3-dimethyl-4-sulphur imidazolidone 1.34g, productive rate 81% with embodiment 1.
Embodiment 19
The amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in feed ratio (the S)-5-benzyl-2-tertiary butyl-3-methyl-4-oxygen imidazolidone and the sulfo-reagent, and toluene is organic solvent.
Actual feed intake into (S)-5-benzyl-2-tertiary butyl-3-methyl-4-oxygen imidazolidone (5mmol, 1.23g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), 90 ℃ of temperature of reaction, 6 hours reaction times.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2-tertiary butyl-3-methyl-4-sulphur imidazolidone 0.98g, productive rate 75% with embodiment 1.
Embodiment 20
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 25mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 90 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.92g, productive rate 79% with embodiment 1.
Embodiment 21
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 50mL, sulfuration reagent P
2S
5/ Al
2O
3(2.07g), temperature of reaction is 90 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.90g, productive rate 77% with embodiment 1.
Embodiment 22
The preparation of sulfo-reagent: accurately take by weighing aluminum oxide (10g), thiophosphoric anhydride (4g) is put into mortar and is ground 10～15min, up to the pale yellow powder that becomes homogeneous.
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(2.72g), temperature of reaction is 90 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.84g, productive rate 72% with embodiment 1.
Embodiment 23
The preparation of sulfo-reagent: accurately take by weighing aluminum oxide (10g), thiophosphoric anhydride (8g) is put into mortar and is ground 10～15min, up to the pale yellow powder that becomes homogeneous.
Feed ratio (S)-5-benzyl-2,2, the amount of substance ratio of thiophosphoric anhydride is 1: 0.7 in 3-trimethylammonium-4-oxygen imidazolidone and the sulfo-reagent, toluene is organic solvent.
Actual feeding intake is (S)-5-benzyl-2,2, and 3-trimethylammonium-4-oxygen imidazolidone (5mmol, 1.09g), toluene 40mL, sulfuration reagent P
2S
5/ Al
2O
3(1.75g), temperature of reaction is 90 ℃.
Other operations get pale yellow oily liquid body (S)-5-benzyl-2,2,3-trimethylammonium-4-sulphur imidazolidone 0.88g, productive rate 75% with embodiment 1.
Embodiment 24
(S)-5-benzyl-2 that embodiment 7 is made, 2,3-trimethylammonium-4-sulphur imidazolidone (0.047g, 0.2mmol) be dissolved in tetrahydrofuran (THF) and the water (3ml+0.5ml), trifluoroacetic acid (the 0.023g of amount of substances such as interpolation, 0.2mmol), stir 5min in 0 ℃, adding is to chlorocinnamaldehyde (0.33g, 2mmol), restir 15min, add N-methylpyrrole (0.24g at last, 3mmol), slow stirring reaction is 6 hours under 0 ℃, after the TLC demonstration reacts completely, the ethanol that in reaction solution, adds 3.5ml, add sodium borohydride (0.09g again, 2.4mmol), stir 30min, add saturated sodium bicarbonate solution, regulating the pH value is 7.5, continue to stir 15min, use methylene dichloride (30ml*2) extraction at last, standing demix, getting organic phase washs with saturated sodium bicarbonate solution, standing demix is got the organic phase anhydrous sodium sulfate drying, filters, the filtrate distillation removes desolvates, residuum uses column chromatography purification, is that 1: 2 mixing solutions is a developping agent with the volume ratio of ethyl acetate and sherwood oil, obtains Friedel-Crafts alkylate (S)-3-(4-chloro-phenyl-)-3-(1-methyl isophthalic acid H-pyrroles-2-yl) propyl alcohol 0.39g of N-methylpyrrole, productive rate 78%, ee value are 87%.
Liquid phase chromatogram condition is: moving phase Virahol/normal hexane=10: 90, and flow velocity 1ml/min detects wavelength 226nm, and chromatographic column AS-H chiral column detects on Agilent 1100 liquid chromatographs.
Claims (9)
1. preparation method suc as formula (S) type thioic imidazolone compound shown in (II), it is characterized in that described method is: suc as formula (S) type imidazolone compound and the sulfo-reagent shown in (I), in organic solvent, under 70～110 ℃ of temperature, reacted 4～8 hours, after reaction finished, reaction solution obtained suc as formula (S) type thioic imidazolone compound shown in (II) through aftertreatment; Described sulfo-reagent is to be the thiophosphoric anhydride of carrier with the aluminum oxide, is mixed according to mass ratio 1: 0.4～0.8 by aluminum oxide and thiophosphoric anhydride to make; Described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.4～1.2; Described organic solvent is one of following: benzene,toluene,xylene, chlorobenzene, trichloromethane, 1,2-ethylene dichloride, acetonitrile, tetrahydrofuran (THF) or Nitromethane 99Min.;
In formula (I) or the formula (II), R
1For phenyl, benzyl, to hydroxybenzyl, propyl group or p-chlorobenzyl; R
2, R
3Independent separately is methyl, ethyl, hydrogen, sec.-propyl, the tertiary butyl, phenyl, rubigan, m-nitro base or p-methoxyphenyl; Perhaps R
2, R
3Constitute cyclopentyl, cyclohexyl or suberyl with the carbon on the imidazole ring.
2. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound is characterized in that described R
1Be phenyl or benzyl; R
2, R
3Independent separately is methyl, ethyl, sec.-propyl, phenyl, rubigan, the tertiary butyl or p-methoxyphenyl.
3. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound, the quality that it is characterized in that described organic solvent are 20～40 times of (S) type imidazolone compound quality shown in the formula (I).
4. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound is characterized in that described organic solvent is a benzene,toluene,xylene, 1,2-ethylene dichloride or chlorobenzene.
5. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound is characterized in that described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.6～0.8.
6. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound is characterized in that described temperature of reaction is 80～90 ℃, and the reaction times is 5～6 hours.
7. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound, it is characterized in that described reaction postprocessing method is: after reaction finishes, reaction solution leaves standstill, filter, get filter cake and filtrate, the filtrate distillation removes desolvates, and residuum uses column chromatography purification, developping agent is that sherwood oil, ethyl acetate, methylene chloride volume ratio are 4: 1: 1 mixing solutions, obtains suc as formula (S) type thioic imidazolone compound product shown in (II).
8. the preparation method of (S) as claimed in claim 7 type thioic imidazolone compound is characterized in that described filter cake washed with dichloromethane, and washings and filtrate merge, and distillation removes and desolvates, and residuum uses column chromatography purification.
9. the preparation method of (S) as claimed in claim 1 type thioic imidazolone compound, it is characterized in that described method carries out according to following steps: add in the organic solvent suc as formula (S) type imidazolone compound and the sulfo-reagent shown in (I), under 80～90 ℃ of temperature, reacted 5～6 hours, the reaction of TLC tracking monitor, judge reaction end by the disappearance that detects (S) type imidazolone compound, after reaction finishes, reaction solution leaves standstill, filter, get filter cake and filtrate, the filter cake washed with dichloromethane, washings and filtrate merge, and distillation removes and desolvates, and residuum uses column chromatography purification, developping agent is a sherwood oil, ethyl acetate, the methylene chloride volume ratio is 4: 1: 1 a mixing solutions, obtains suc as formula (S) type thioic imidazolone compound product shown in (II); Described sulfo-reagent is mixed according to mass ratio 1: 0.4～0.8 by aluminum oxide and thiophosphoric anhydride and makes; Described amount of substance ratio suc as formula Vanadium Pentoxide in FLAKES in (S) type imidazolone compound shown in (I) and the sulfo-reagent is 1: 0.6～0.8; Described organic solvent is a benzene,toluene,xylene, 1,2-ethylene dichloride or chlorobenzene; The quality of described organic solvent is 30～35 times of (S) type imidazolone compound quality.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4090025A (en) * | 1976-04-26 | 1978-05-16 | American Cyanamid Company | Intermediates for synthesis of tetramisole, levamisole and their derivatives |
| US4370482A (en) * | 1978-02-15 | 1983-01-25 | American Cyanamid Co. | Synthesis of tetramisole, levamisole and their derivatives |
| US6307057B1 (en) * | 2000-01-18 | 2001-10-23 | The Regents Of The University Of California | Acid addition salts of imidazolidinones as reaction catalysts |
| EP1204728B1 (en) * | 1999-07-22 | 2004-09-01 | UNIROYAL CHEMICAL COMPANY, Inc. | Imidazole thione additives for lubricants |
-
2009
- 2009-06-17 CN CN2009100998657A patent/CN101585812B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4090025A (en) * | 1976-04-26 | 1978-05-16 | American Cyanamid Company | Intermediates for synthesis of tetramisole, levamisole and their derivatives |
| US4370482A (en) * | 1978-02-15 | 1983-01-25 | American Cyanamid Co. | Synthesis of tetramisole, levamisole and their derivatives |
| EP1204728B1 (en) * | 1999-07-22 | 2004-09-01 | UNIROYAL CHEMICAL COMPANY, Inc. | Imidazole thione additives for lubricants |
| US6307057B1 (en) * | 2000-01-18 | 2001-10-23 | The Regents Of The University Of California | Acid addition salts of imidazolidinones as reaction catalysts |
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