CN108148054B - Pyridyl bridged chiral oxazoline compound and synthetic method thereof - Google Patents
Pyridyl bridged chiral oxazoline compound and synthetic method thereof Download PDFInfo
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- -1 oxazoline compound Chemical class 0.000 title claims abstract description 20
- 125000004076 pyridyl group Chemical group 0.000 title claims abstract description 7
- 238000010189 synthetic method Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- QWFHFNGMCPMOCD-UHFFFAOYSA-N 6-bromopyridine-2-carbaldehyde Chemical compound BrC1=CC=CC(C=O)=N1 QWFHFNGMCPMOCD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000000276 potassium ferrocyanide Substances 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 10
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001414 amino alcohols Chemical class 0.000 claims abstract description 9
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 8
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- 150000004987 o-phenylenediamines Chemical class 0.000 claims abstract description 5
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 9
- 238000006555 catalytic reaction Methods 0.000 claims description 8
- 229940125898 compound 5 Drugs 0.000 claims description 8
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 7
- 229940126214 compound 3 Drugs 0.000 claims description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 6
- 239000007810 chemical reaction solvent Substances 0.000 claims description 6
- 239000012362 glacial acetic acid Substances 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 5
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 3
- 229940125904 compound 1 Drugs 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- ZMLPZCGHASSGEA-UHFFFAOYSA-M zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F ZMLPZCGHASSGEA-UHFFFAOYSA-M 0.000 claims description 2
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical group CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims 2
- 239000003054 catalyst Substances 0.000 abstract description 10
- 150000004696 coordination complex Chemical class 0.000 abstract description 4
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 239000003446 ligand Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- ASQOQJYHIYYTEJ-GBESFXJTSA-N (1r,7s,9as)-7-decyl-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-1-ol Chemical compound O[C@@H]1CCCN2C[C@@H](CCCCCCCCCC)CC[C@H]21 ASQOQJYHIYYTEJ-GBESFXJTSA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000012327 Ruthenium complex Substances 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a pyridyl bridged chiral oxazoline compound and a simple synthesis method thereof. 6-bromopyridine-2-formaldehyde and o-phenylenediamine compounds are used as initial raw materials, a bromo compound is obtained through condensation reaction, the bromo compound is reacted with potassium ferrocyanide to obtain a cyano-substituted compound, and the cyano-substituted compound is reacted with chiral amino alcohol to generate a pyridyl-bridged chiral oxazoline compound. The compound can be used for synthesizing high-efficiency metal complex catalysts. The method has the advantages of cheap and easily obtained raw materials, simple and convenient operation, mild synthesis reaction conditions, high efficiency and the like.
Description
Technical Field
The invention relates to a pyridyl bridged chiral oxazoline compound and a synthesis method thereof. 6-bromopyridine-2-formaldehyde and o-phenylenediamine compounds are used as initial raw materials, a bromo compound is obtained through condensation reaction, the bromo compound is reacted with potassium ferrocyanide to obtain a cyano-substituted compound, and the cyano-substituted compound is reacted with chiral amino alcohol to generate a pyridyl-bridged chiral oxazoline compound. The compound can be used for synthesizing high-efficiency metal complex catalysts. The method has the advantages of cheap and easily obtained raw materials, simple and convenient operation, mild synthesis reaction conditions, high efficiency and the like.
Background
The tridentate NNN compound is used as an N-heterocyclic compound with wide application, has potential biological activity, and can be used for preparing a complex luminescent material or a high-activity complex catalyst. The 2006 patent (PCT int.appl., WO2006098505) reports the potential use of such substances in organic electroluminescent materials. In 2008, 2009, the research group on the Yun Zhengkun reported that a metal ruthenium complex with NNN as a ligand has higher catalytic activity in catalyzing hydrogen transfer reaction of ketone (Yu, Z.K. et al. Organometallics 2008,27, 2898; Organometallics 2009,28, 1855.).
It is known that chirality is an essential attribute of nature, and most of the organic molecules constituting a living body are chiral molecules, and the configuration of these chiral molecules determines their physiological activity. Meanwhile, the research on chiral drugs has very important significance, and the sales of chiral drugs worldwide each year exceeds 3000 billion dollars at present and is still increasing year by year. It is known that racemate resolution, substrate induction and chiral catalysis are 3 main ways to obtain a single chiral compound. Wherein the obtaining of a single isomer by asymmetric catalysis is a more commonly applied method. Wherein the asymmetric catalysis comprises metal complex catalysis, enzyme catalysis and organic small molecule catalysis. In recent years, catalysis using metal complexes has achieved good results, and for example, some metal complex catalysts have been used in industrial production. How to design and synthesize a catalyst with high selectivity and high activity is a key point, wherein a chiral ligand plays a very important role (Linzhou Qiang et al. chiral synthesis-asymmetric reaction and application thereof [ M ]. Beijing: scientific Press, Beijing, 2013.). Among a plurality of chiral ligands, the nitrogen-containing ligand is an important chiral ligand, has the advantages of easy obtaining, stability and the like, and can form a complex with transition metal so as to efficiently catalyze the reaction. Of the nitrogen-containing chiral ligands, oxazolines are a relatively excellent class of chiral ligands (Lu, z.et al.angelw.chem.int.ed.2015, 54,4661; Gade, l.h.et al.j.am.chem.soc.2015,137, 2456.). The invention adds chiral elements (chiral oxazoline) on the basis of the tridentate NNN compound, and successfully designs a chiral ligand with higher activity and enantioselectivity.
According to the invention, 6-bromopyridine-2-formaldehyde and o-phenylenediamine compounds are used as initial raw materials, a bromo compound is obtained through a condensation reaction, the bromo compound is reacted with potassium ferrocyanide to obtain a cyano-substituted compound, and the cyano-substituted compound is reacted with chiral amino alcohol to generate a pyridyl bridged chiral oxazoline compound. The method has the advantages of cheap and easily obtained raw materials, simple and convenient operation, few synthesis steps, mild synthesis reaction conditions, high efficiency and the like.
Disclosure of Invention
The invention aims to provide a method for efficiently synthesizing a pyridine-based bridged chiral oxazoline compound, which has the advantages of readily available raw materials, mild reaction conditions and wide adaptability.
In order to achieve the purpose, the technical scheme of the invention is as follows:
taking 6-bromopyridine-2-formaldehyde 2 and an o-phenylenediamine compound 3 as initial raw materials, carrying out condensation reaction to obtain a bromo compound 4 (reaction formula 1), reacting the bromo compound 4 with potassium ferrocyanide to obtain a cyano-substituted compound 5 (reaction formula 2), and reacting the cyano-substituted compound 5 with chiral amino alcohol to generate a pyridyl bridged chiral oxazoline compound 1 (reaction formula 3).
The technical scheme is characterized in that:
1. 6-bromopyridine-2-formaldehyde 2 is a synthon.
2. The o-phenylenediamine compound 3 is a known compound and can be prepared by a reference method.
3. 6-bromopyridine-2-formaldehyde 2 and o-phenylenediamine compounds 3 are subjected to condensation reaction to prepare compounds 4, wherein the reaction solvent is one or two of glacial acetic acid, methanol, n-butyl alcohol, toluene and 1, 4-dioxane, and is preferably carried out in glacial acetic acid or methanol.
4. The mol ratio of the 6-bromopyridine-2-formaldehyde 2 to the o-phenylenediamine compound 3 is 1:1-1: 4; the reaction temperature is 20-150 ℃; the reaction time is 1-24 hours.
5. Reacting the compound 4 with potassium ferrocyanide and cuprous iodide in one or two of N, N-dimethylformamide, N-dimethylacetamide and N-methylimidazole as a reaction solvent; the molar ratio of the compound 4 to the potassium ferrocyanide and the cuprous iodide is 1:1:0.2-1:10: 1; the reaction temperature is 50-200 ℃; the reaction time is 2-24 hours.
6. Reacting the compound 5 with chiral amino alcohol, wherein the reaction solvent is one or two of glacial acetic acid, methanol, n-butanol, toluene and tetrahydrofuran; the molar ratio of the compound 5 to the chiral amino alcohol and the zinc trifluoromethanesulfonate is 1:1:1-1:10: 1; the reaction temperature is 50-150 ℃; the reaction time is 12-28 hours. The ligand can be used for synthesizing high-efficiency chiral metal catalysts.
The invention has the following advantages:
1) the raw materials are wide in source, cheap and easy to obtain or easy to prepare.
2) The pyridine-based bridged chiral oxazoline compound 1 has the advantages of simple synthesis method, high preparation efficiency, wide product application and easy derivatization.
Detailed Description
The starting materials 6-bromopyridine-2-carbaldehyde 2(Hicks, r.g.et al.org.lett.,2004,6,1887.) and orthophenylenediamine compound 3(Cheeseman, g.w.h.j.chem.soc. (Resummed),1962,1170.) were prepared according to literature procedures.
Example 1
A mixture of 6-bromopyridine-2-carbaldehyde 2(186mg,1.0mmol), p-toluenesulfonamide phenylenediamine 3a (447mg,1.0mmol), sodium bisulfite (109mg, 1.1mmol), and 15mL of formic acid was stirred at 120 ℃ for 12 hours. After cooling to room temperature, the carboxylic acid was neutralized by adding concentrated aqueous ammonia, filtered under suction, and the solid was washed with 3X 5mL of water to give 4a as a pale yellow solid (500mg, yield 82%) as the objective product. The target product is confirmed by the measurement of nuclear magnetic resonance spectrum and high-resolution mass spectrum.
Example 2
A mixture of compound 4a (613mg,1.0mmol), potassium ferrocyanide (368mg, 1.0mmol), cuprous iodide (38mg, 0.2mmol) and 5mL of N-methylimidazole was stirred at 100 ℃ for 12 hours. After cooling to room temperature, part of the solvent was removed under reduced pressure and column chromatography was performed to give 5a (500mg, yield 90%) as a pale yellow solid. The target product is confirmed by the measurement of nuclear magnetic resonance spectrum and high-resolution mass spectrum.
Example 3
Compound 5a (250.0mg,0.45mmol), S-valinol (50.8mg, 0.49mmol), Zn (OTf)2(178.9mg, 0.49mmol) was reacted with 5mL of toluene at 110 ℃ with stirring for 12 hours. After cooling to room temperature, part of the solvent was removed under reduced pressure and column chromatography was performed to give 1a (150.8mg, yield 52%) as a pale yellow solid. The target product is confirmed by the measurement of nuclear magnetic resonance spectrum and high-resolution mass spectrum.
Application example 1
Ligand 1a (48mg,0.07mmol), RuCl were added sequentially to a 25mL Schlenk reaction flask under nitrogen protection2(PPh3)3(72mg,0.07mmol) and 5mL of toluene were refluxed for 1 h. After cooling to room temperature, filtration was carried out and the solid was washed with diethyl ether (3X 20 mL). After drying in vacuo, brick red solid product 6a was obtained (83mg, 85% yield). The target product is confirmed by nuclear magnetic resonance spectrum and element analysis and measurement.
Under the protection of nitrogen, catalyst 6a (10.79mg,0.01mmol) was dissolved in 50.0mL of isopropanol to prepare a catalyst solution. Acetophenone (2.0mmol), 10.0mL of the catalyst solution and 9.8mL of isopropanol were stirred at 28 ℃ for 5 minutes under nitrogen. Then 0.2mL of iPrOK in isopropanol (0.1M) was injected into the reaction system, and 0.1mL of the reaction solution was withdrawn at a specified time and immediately diluted with 0.5mL of isopropanol for gas chromatography. Under the conditions, acetophenone is reduced into an s-type alcohol product at the conversion rate of 97% and the ee value of 98% at 3min, which shows that the pyridine-based bridged chiral oxazoline compound can be used as a potential ketone reduction catalyst.
Claims (6)
1. A pyridyl-bridged chiral oxazoline compound, the structural formula of which is shown in the following formula 1,
the substituent R is isopropyl, tert-butyl, phenyl or benzyl, and the substituent R' is p-toluenesulfonamide.
2. A method for synthesizing a pyridyl-bridged chiral oxazoline compound according to claim 1, which comprises the steps of: taking 6-bromopyridine-2-formaldehyde 2 and o-phenylenediamine compound 3 as initial raw materials in NaHSO3Under the action, a bromo-compound 4 is obtained through condensation reaction, the bromo-compound 4 is reacted with potassium ferrocyanide and CuI to obtain a cyano-substituted compound 5, the cyano-substituted compound 5 is reacted with chiral amino alcohol, Zn (OTf)2Reacting under catalysis to generate a pyridyl bridged chiral oxazoline compound 1;
the synthetic route is shown as the following reaction formula and is divided into three steps,
the substituent R is isopropyl, tert-butyl, phenyl or benzyl, and the substituent R' is p-toluenesulfonamide.
3. A method of synthesis according to claim 2, characterized in that:
wherein: carrying out condensation reaction on 6-bromopyridine-2-formaldehyde 2 and an o-phenylenediamine compound 3 to prepare a brominated compound 4, wherein the reaction solvent is one or more than two of glacial acetic acid, methanol, n-butanol, toluene and 1, 4-dioxane; in the reaction process, the molar ratio of the 6-bromopyridine-2-formaldehyde 2 to the o-phenylenediamine compound 3 is 1:1-1: 4; the reaction temperature is 20-150 ℃; the reaction time is 1-24 hours.
4. A method of synthesis according to claim 3, characterized in that: the reaction of 6-bromopyridine-2-formaldehyde 2 and o-phenylenediamine compounds 3 is carried out in one or two of glacial acetic acid or methanol which are protonic solvents.
5. A method of synthesis according to claim 2, characterized in that: reacting the compound 4 with potassium ferrocyanide and cuprous iodide in one or more of N, N-dimethylformamide, N-dimethylacetamide and N-methylimidazole as a reaction solvent; the molar ratio of the compound 4 to the potassium ferrocyanide and the cuprous iodide is 1:1:0.2-1:10: 1; the reaction temperature is 50-200 ℃; the reaction time is 2-24 hours.
6. A method of synthesis according to claim 2, characterized in that: reacting the compound 5 with chiral amino alcohol, wherein the reaction solvent is one or more than two of glacial acetic acid, methanol, n-butanol, toluene and tetrahydrofuran; the molar ratio of the compound 5 to the chiral amino alcohol and the zinc trifluoromethanesulfonate is 1:1:1-1:10: 1; the reaction temperature is 50-150 ℃; the reaction time is 12-28 hours.
Priority Applications (1)
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| Highly Active Ruthenium(II) Complex Catalysts Bearing an Unsymmetrical NNN Ligand in the (Asymmetric) Transfer Hydrogenation of Ketones;Wenjing Ye,et al.;《Chem. Eur. J.》;20110314;第17卷;第4737-4741页 * |
| Ru(II) pyridyl‐based NNN complex catalysts for (asymmetric) transfer hydrogenation of ketones at room temperature;DU Wangming,et al.;《Chinese Journal of Catalysis》;20130720;第34卷;第1373-1377页 * |
| Synthesis and properties of a novel Cu(II)-pyridineoxazoline containing polymeric catalyst for asymmetric Diels-Alder reaction;Wang, Heng,et al.;《RSC Advances》;20151231;第5卷(第4期);第2882-2890页 * |
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