CN111675629A - Synthesis method and application of 4, 5-diphenyl imidazoline - Google Patents

Synthesis method and application of 4, 5-diphenyl imidazoline Download PDF

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CN111675629A
CN111675629A CN202010614324.XA CN202010614324A CN111675629A CN 111675629 A CN111675629 A CN 111675629A CN 202010614324 A CN202010614324 A CN 202010614324A CN 111675629 A CN111675629 A CN 111675629A
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chiral compound
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罗梅
李国雄
谢蓝
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Hefei University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
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    • C07C253/00—Preparation of carboxylic acid nitriles
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
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Abstract

A method for synthesizing chiral compound with the following structural formula: the method comprises the steps of synthesizing, separating and purifying, wherein in the synthesis process, 1 mol% of catalyst palladium complex is used as a catalyst under the anhydrous and anaerobic conditions, 0.5mmol of benzil and 5.0g of ammonium formate are weighed and put into a 250mL two-neck flask, 100mL of chlorobenzene is added as a solvent, after reflux reaction is carried out for 30 hours, column chromatography separation is carried out, petroleum ether/dichloromethane (1/100) is used for elution, and the collected final component is naturally volatilized to obtain single crystal 4, 5-diphenyl imidazoline:
Figure DDA0002563241760000011
the application of the chiral compound (I) in the reaction of benzophenone imine and trimethylsilyl cyanideA certain catalytic effect is shown, and the conversion rate reaches 66%.

Description

Synthesis method and application of 4, 5-diphenyl imidazoline
One, the technical field
The invention relates to a preparation method and application of a compound, in particular to a nitrogen-containing compound and a preparation method thereof, and specifically relates to a synthesis method and application of 4, 5-diphenyl imidazoline.
Second, background Art
4, 5-diphenyl imidazoline is an important medical intermediate, and the synthetic method and the application thereof are reported in the literature [ 1-3 ]
Reference documents:
1.Green synthesis of biologically active 2,4,5-trisubstitutedimidazoles catalyzed by large pore zeolite H-BEA through lophine MCRs，Gabla,Jenifer J.et al，Journal of Catalyst&Catalysis,4(3),20-36；2017.
2.Functionalized Diphenyl-Imidazolo-Pyrimidines,Lyubashov,Pavel P.etal,Journal of Heterocyclic Chemistry,55(1),276-281；2018.
3.A mechanistic study of carbonyl activation under solvent-freeconditions:evidence drawn from the synthesis of imidazoles,Pradhan,Kiran etal,RSC Advances,6(13),10743-10749；2016。
third, the invention
The invention aims to provide an amino-protected synthesis method for the field of organic synthesis, in particular for preparing a drug intermediate, and aims to solve the technical problems of selecting corresponding raw materials and establishing a corresponding method for synthesizing a chiral drug intermediate.
The compound of the invention is a compound shown in the following chemical formula (I):
Figure BDA0002563241740000011
the chemical name is as follows: 4, 5-diphenyl imidazoline.
The synthesis method of the compound (I) comprises the steps of carrying out reflux reaction on benzil and ammonium formate in a chlorobenzene solvent for 30 hours,
the chemical reaction formula is as follows:
Figure BDA0002563241740000012
the synthesis method of the chiral compound 4, 5-diphenyl imidazoline comprises synthesis, separation and purification, wherein in the synthesis, under the anhydrous and anaerobic conditions, 1% mol of a catalyst palladium complex is used as a catalyst, 0.5mmol of benzil and 5.0g of ammonium formate are weighed and placed in a 250mL two-neck flask, 100mL of chlorobenzene is added as a solvent, after reflux reaction is carried out for 30 hours, column chromatography separation is carried out, petroleum ether/dichloromethane (3/7) is used for elution, and the collected final component is naturally volatilized to obtain the single crystal 4, 5-diphenyl imidazoline.
The reaction mechanism of this reaction can be presumed as follows:
the benzil reacts with ammonium formate under the catalysis of the synthesized palladium catalyst to generate an intermediate
Figure BDA0002563241740000021
With CO produced from ammonium formate2Acting and further condensing to form the target compound.
Similar reactions were reported by j.o.c in 2017 for the target compound (j.o.c.2017,82,1768-1774), but different structures of the product were caused due to different catalysts.
The catalyst shows a certain catalytic effect in the reaction of benzophenone imine and trimethylsilonitrile, and the conversion rate of the catalyst reaches 66 percent.
Description of the drawings
FIG. 1 is a single crystal diffractogram of 4, 5-diphenylimidazoline compound (I).
Fifth, detailed description of the invention
1.4, 5-Diphenylimidazoline Compounds
Under the anhydrous and anaerobic conditions, taking 1% mol of catalyst palladium complex as a catalyst, weighing 0.5mmol of benzil and 5.0g of ammonium formate, putting the benzil and the ammonium formate into a 250mL two-neck flask, adding 100mL of chlorobenzene as a solvent, performing reflux reaction for 30 hours, performing column chromatography separation, eluting with petroleum ether/dichloromethane (1/100), and naturally volatilizing the collected final component to obtain single-crystal 4, 5-diphenyl imidazoline; elemental analysis data C15H12N2, theoretical value: c: 81.79 percent; h: 5.49 percent; n: 12.72 percent; measured value: c81.56%; h: 5.38 percent; n: 12.49 percent; EI (C15H13N2) HRMS [ m +1/e]: theoretical value: 221.1079, respectively; measured value: 221.0905;1HNMR(600MHz,CDCl327 ℃ C.), yield 75%;1HNMR(400MHz,CDCl3,27℃),(ppm)＝8.0(br,1H),7.64-7.50(m,1H),7.48-7.50(m，4H),7.23-7.30(m，6H),13CNMR(100MHz,CDCl3,27℃)135.1,133.4(x2)，128.2(x4)，127.6(x4),126.8(x4)；IR(KBr):3273,3060，2820，2639，1666，1603，1514，1498，1464，1442，1376，1294，1248，1194，1176，1156，1135，1070，1028，984，955，931，913，877，845，833，778，760，722，673，649，617，567，530；
compound crystal data are as follows:
Figure BDA0002563241740000022
Figure BDA0002563241740000031
typical bond length data for crystals:
Figure BDA0002563241740000032
Figure BDA0002563241740000041
typical bond angle data for crystals:
Figure BDA0002563241740000042
Figure BDA0002563241740000051
2. preparation of palladium complexes
Preparation of [1,4- (4R) -diisopropyl-2-oxazolinyl ] benzene
Adding anhydrous ZnCl21.4054g (mmol),40mL chlorobenzene, 1, 4-dicyanobenzene 5.0236g (50.75mmol) and L-valinol 16.2075g into a 100mL two-mouth bottle under anhydrous and oxygen-free conditions, refluxing the mixture at high temperature for 60h, stopping the reaction, reducing the pressure to remove the solvent, dissolving the residue with water, extracting with CHCl3(20mLx2), drying the organic phase with anhydrous sodium sulfate, rotating to remove the solvent, and performing column chromatography on the crude product with petroleum ether/dichloromethane (4:1) to obtain a light green viscous liquid, wherein the yield is 52%; white crystals with a melting point of 48-50 ℃ and [ a ]5D +111.9 ° (c 0.429, CHCl 3); 1HNMR (500MHz, CDCl3,27 ℃), (ppm) — 7.97(s,4H), (4.39-4.43 (t,3.18Hz,1H), (4.09-4.15 (m,2H), 1.85-1.86 (m,1H), (d, J) ═ 6.24Hz,6H), 0.86-0.96 (d, J ═ 6.24Hz,6H), CN13 MR 18.13,19.03,32.85,70.26,72.76,128.10,128.16,130.32,162.82.IR:3273,2976,2960,2932,2889,2869,1643,1512,1469,1408,1382,1366,1350, EI, 1296,1276,1214,1180, 1077,1047, 900, 971, 891, 1320, 6978 (%/75H), 3639/27H, (75H), (75, 35, 67, 35, 3, 35, 150, 150,67, 150,67,67,67,67,67, 75,540; 300.1833 for found;
2.2 preparation of bis { [1,4- (4S) -diisopropyl-2-oxazolinylphenyl ] palladium chloride } complex
In a 100mL two-mouth bottle, under the anhydrous and oxygen-free conditions, 1.5603g (4.92mmol) of palladium chloride, 1.0435g (3.48mmol) of 1,4- (4R) -diisopropyl-2-oxazolinylbenzene and 30mL of chlorobenzene are added, the mixture is refluxed for 48 hours at high temperature, the reaction is stopped, the solvent is removed by decompression, the residual chloroform and ethanol are dissolved, and natural volatilization is carried out to obtain a red-brown complex, namely crystals, wherein the yield is as follows: 82%; m.p.:>200℃,[a]5 D＝+514.2°(c＝0.0564,CH3OH)：1HNMR(600MHz,CDCl3,27℃),(ppm)＝8.86(s,4H),4.56-4.64(m，4H),7.10-7.35(m,6H),5.57(t,J＝0.6Hz,1H)，5.22(t,J＝0.6Hz,1H),4.97(t,J＝0.3Hz,1H),4.46-4.48(m,2H),2.96-2.98(m,2H),1.06-1.12(dd,J＝6.6,7.2Hz,12H)；13CNMR: 168.7,132.8,75.2,72.5,33.5,21.5, 18.7; elemental analysis found in C36H50N4Cl4O5Pd 2: 44.42% of C, 5.18% of H and 5.76% of N; calculated values: 44.31% of C, 5.14% of H and 5.55% of N; IR 3487,3049,2957,2929, 2872,1642,1609,1572,1509,1480,1464,1416,1379,1331,1288,1246,1178,1141,1123,1099,1045,1018,959,933,899,854,804,770,722,693, 438;
3. condensation reaction application of benzophenone imine and trimethylsilonitrile
Figure BDA0002563241740000061
Weighing 1mmol of benzophenone imine and trimethylPutting 0.2mL of cyanosilane into a 25mL small flask, adding 2mL of dichloromethane 0.1mmol of compound I, stirring at normal temperature for 5h, taking a small amount of sample for nuclear magnetic detection, and enabling the conversion rate to reach 65%;1H NMR(600MHz,CDCl3,27℃)7.23–7.59(m,10H),4.10(s,2H)；
in addition, the inventors carried out the parallel reaction without a catalyst, and after 5 hours, the conversion was 30%.

Claims (2)

1. A method for synthesizing chiral compounds with the following structural formula and unit cell parameters: the method comprises the steps of synthesizing, separating and purifying, wherein in the synthesis process, 1% mol of catalyst palladium complex is used as a catalyst under the anhydrous and anaerobic conditions, 0.5mmol of benzil and 5.0g of ammonium formate are weighed and put into a 250mL two-neck flask, 100mL of chlorobenzene is added as a solvent, after reflux reaction is carried out for 30 hours, column chromatography separation is carried out, petroleum ether/dichloromethane (1/100) is used for elution, and the collected final component is naturally volatilized to obtain single crystal 4, 5-diphenyl imidazoline:
Figure FDA0002563241730000011
the chiral compound crystal (I) is prepared by using MoK α rays monochromatized by a graphite monochromator on an Oxford X-ray single crystal diffractometer at the temperature of 296(2) K
Figure FDA0002563241730000012
Diffraction data were collected by ω - θ scanning, characterized by the fact that the crystals belong to the monoclinic system, P21/C, unit cell parameters:
Figure FDA0002563241730000013
α＝90°；
Figure FDA0002563241730000014
β＝93.645(2)°；
Figure FDA0002563241730000015
γ＝90°。
2. the chiral compound (I) has a certain catalytic effect in the reaction of benzophenone imine and trimethylsilonitrile, and the conversion rate of the chiral compound (I) reaches 66%.
CN202010614324.XA 2020-06-30 2020-06-30 Synthesis method and application of 4, 5-diphenyl imidazoline Withdrawn CN111675629A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112174893A (en) * 2020-10-15 2021-01-05 合肥工业大学 Synthetic method and application of 2,4, 5-trimethyl-1H-imidazoline formate
CN112225652A (en) * 2020-11-10 2021-01-15 合肥工业大学 Preparation and application of tetracarbonylcyclobutane dihydrate compound
CN112480126A (en) * 2020-12-11 2021-03-12 合肥工业大学 Preparation and application of 5-alkyl quinazoline derivative

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CN1326839C (en) * 2004-09-03 2007-07-18 首都医科大学 2-substituted-4,4,5,5-tetramethyl-1-hydroxyimidazoline, and its synthesis and use
US8455661B2 (en) * 2007-02-18 2013-06-04 University Of Florida Research Foundation, Inc. Catalysts containing N-heterocyclic carbenes for enantioselective synthesis
CN102875416B (en) * 2012-10-31 2014-04-16 罗梅 Chiral compound
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CN106810533A (en) * 2016-12-20 2017-06-09 浙江大学 A kind of chiral compound and preparation method and metal complex containing '-imine pyridinyl imidazoline
CN108658869A (en) * 2017-03-29 2018-10-16 复旦大学 Compound with anti-tumor activity and preparation method thereof and the purposes in pharmacy
CN108997242B (en) * 2018-07-28 2020-10-20 浙江大学 Substituted phenyl pyrazolone derivative, preparation and application

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112174893A (en) * 2020-10-15 2021-01-05 合肥工业大学 Synthetic method and application of 2,4, 5-trimethyl-1H-imidazoline formate
CN112174893B (en) * 2020-10-15 2023-09-22 合肥工业大学 Synthesis method and application of 2,4, 5-trimethyl-1H-imidazoline formate
CN112225652A (en) * 2020-11-10 2021-01-15 合肥工业大学 Preparation and application of tetracarbonylcyclobutane dihydrate compound
CN112225652B (en) * 2020-11-10 2023-07-25 合肥工业大学 Preparation and application of tetracarbonyl cyclobutane compound dihydrate
CN112480126A (en) * 2020-12-11 2021-03-12 合肥工业大学 Preparation and application of 5-alkyl quinazoline derivative

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Application publication date: 20200918