CN107353221B - A kind of Preparation method and use of chipal compounds - Google Patents

A kind of Preparation method and use of chipal compounds Download PDF

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CN107353221B
CN107353221B CN201710571934.4A CN201710571934A CN107353221B CN 107353221 B CN107353221 B CN 107353221B CN 201710571934 A CN201710571934 A CN 201710571934A CN 107353221 B CN107353221 B CN 107353221B
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chipal compounds
catalyst
phenyl
benzamide
reaction
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CN107353221A (en
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罗梅
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Hefei Xiangchen Chemical Engineering Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
    • 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
    • B01J31/02—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/22—Separation; Purification; Stabilisation; Use of additives
    • C07C231/24—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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Abstract

A kind of synthetic method of chipal compounds (I); catalyst 1- (Cyanoacetyl) pyrrolidines 3.4382g is with palladium chloride 33mol%; 60ml chlorobenzene; D- benzene glycinol 4.8075g; mixture is flowed back 60h at high temperature, stops reaction, is depressurized to remove solvent; residue is dissolved with water, and uses CHCl3(20mLx2) extraction, organic phase is dry with anhydrous sodium sulfate, rotation removes solvent, upper silica gel column chromatography column separating purification, with petroleum ether/methylene chloride (volume ratio 1:9) mixed liquor elution, the first component point is collected, eluant, eluent is sloughed and obtains target product (R)-(+)-α-chloro- phenyl ethylamine of phenyl -2-, chemical formula is as follows:

Description

A kind of Preparation method and use of chipal compounds
One, technical field
The present invention relates to a kind of preparation method of chipal compounds, in particular to nitrogenous chipal compounds preparation method, It is exactly a kind of synthetic method of (R)-(+)-α-chloro- benzamide of phenyl -2- and purposes.
Two, background technique
The chloro- benzamide compounds of phenyl -2- are widely used in biological medicine and organic synthesis is anti-by chirality (R)-(+)-α - Ying Zhong, synthetic method have document report.[1-2]
Bibliography:
1.Enantioselective synthesis of 1,2-diarylaziridines by the Organocatalytic reductive amination of α-chloroketones, Malkov, Andrei V.et al, Angewandte Chemie, International Edition, 2007,46 (20), 3722-3724.
α 2.-Phenyl-2-chloroethylamine, C6H3CH (NH2) CH2Cl, Gabriel, S.；Colman, J., Berichte der Deutschen Chemischen Gesellschaft, 1914,47,866-73.
This experiment has unexpectedly obtained another chipal compounds in the experiment of synthesis oxazoline palladium complex
Three, summary of the invention
The present invention is intended to provide a kind of synthetic method of chirality hydroxyl amide compound, the technical problem to be solved is that a steps Synthesizing chiral compound (R)-(+)-α-chloro- benzamide of phenyl -2-.
It is 1- (Cyanoacetyl) pyrrolidines and D- benzene glycinol in chlorine that the so-called chipal compounds of the present invention, which are by synthesizing, Have in benzene solvent 33mol% catalyst palladium chloride reaction preparation by following below formula compound represented:
Chemical name: (R)-(+)-α-chloro- benzamide of phenyl -2-, abbreviation compound (I).
The synthetic method of this chiral amides compound includes synthesis and separation, and the synthesis is made of palladium chloride 33mol% Catalyst 1- (Cyanoacetyl) pyrrolidines 3.4382g, 60ml chlorobenzene, D- benzene glycinol 4.8075g, at high temperature by mixture Flow back 60h, stops reaction, depressurizes to remove solvent, residue is dissolved with water, and use CHCl3(20mLx2) extraction, it is organic Mutually dry with anhydrous sodium sulfate, rotation removes solvent, upper silica gel column chromatography column separating purification, with petroleum ether/methylene chloride (volume ratio 1:9) mixed liquor elutes, and collects the first component point, sloughs eluant, eluent and obtain the chloro- benzene first of target product (R)-(+)-α-phenyl -2- Amide.
Synthetic reaction is as follows:
The reaction mechanism of the reaction can be speculated as 1- (Cyanoacetyl) pyrrolidines and divide under the effect of 33mol% palladium chloride Solution, and reacted with (R)-benzene glycinol, obtain a kind of chipal compounds.
Four, Detailed description of the invention
Fig. 1 is chipal compounds (R)-(+)-α-chloro- benzamide of phenyl -2- (I) single crystal diffraction figure.
Five, specific embodiment
(1) chipal compounds α-phenyl -2- chloro- benzamide preparation
In 100mL two-mouth bottle, under the conditions of anhydrous and oxygen-free, it is added palladium chloride 1.4442g (mmol), 1- (Cyanoacetyl) Pyrrolidines 3.4382g, 60ml chlorobenzene, D- benzene glycinol 4.8075g flow back mixture 60h at high temperature, stop reaction, subtract It presses to remove solvent, residue is dissolved with water, and use CHCl3(20mLx2) extraction, organic phase is dry with anhydrous sodium sulfate, Rotation removes solvent, and upper silica gel column chromatography column separating purification is eluted with petroleum ether/methylene chloride (volume ratio 1:9) mixed liquor, collects First component point sloughs eluant, eluent and obtains target product (R)-(+)-α-chloro- phenyl ethylamine of phenyl -2-；[a]5 D=+12.5 ° of (c= 0.0764, CH3OH):1HNMR(500MHz,CDCl3, 27 DEG C), δ (ppm)=8.09 (d, J=7.52Hz, 2H), 7.32-7.52 (m, 9H), 5.39-5.42 (m, 1H), 4.78-4.81 (m, 1H)；4.27-4.30(m,1H)；13CNMR(500MHz,CDCl3,27 ℃),164.7,142.6(x2),131.4(x2),128.6(x2),128.5,128.3,127.9,127.5,120.7(x2), 74.8,70.3；IR (ν, KBr) 3328,3060,1642,1579,1532,1491,1465,1359,1332,1306,1208, 1176,1027,764,723,698,633,521；HRMS (EI): m/z (%): calcd for C15H14NOCl:259.0764； found:259.068；
Match crystal volume data is as follows:
The typical bond distance's data of crystal:
The typical bond angle data of crystal:
Henle reaction application
0.0675g compound (I), is placed in 25mL flask, sequentially add 1mL tetrahydrofuran, 0.3mL nitromethane and 0.5mmol ethyl pyruvate, stirring at normal temperature react 48h, separately sampled progress1HNMR detection, conversion ratio 41%；1H NMR (CDCl 3): δ) 4.86 (d, J=13.8Hz, 1H), 4.58 (d, J=13.8Hz, 1H), 4.34 (m, 2H), 3.85 (s, 1H), 1.46 (s, 3H), 1.33 (t, J=7.2Hz, 3H)13C NMR (CDCl 3): δ=173.4,80.9,72.4,63.0,23.8, 13.9。
The preparation of N, N '-(phenylmethylene) dibenzamide
In 25mL two-mouth bottle, be added 0.0659g compound I, 2mLTHF and chlorobenzene 2mL, 0.05mL benzaldehyde and 0.1302g benzamide has crystal appearance: being detected with nuclear-magnetism after back flow reaction 96 hours, conversion ratio: 94%；1HNMR (500MHz,CDCl3, 27 DEG C), δ (ppm)=9.02 (d, J=7.77Hz, 2H), 7.91 (d, J=7.42Hz, 4H), 7.54 (t, J=7.4Hz, 2H), 7.47 (t, J=7.7Hz, 6H), 7.37 (t, J=7.7Hz, 2H), 7.30 (t, J=7.3Hz, 1H), 7.03 (t, J=7.9Hz, 1H).

Claims (2)

1. one kind has the synthetic method of following cell parameter chipal compounds (I), including synthesizes and separate, the synthesis is used Palladium chloride 33mol% does catalyst 1- (Cyanoacetyl) pyrrolidines 3.4382g, 60ml chlorobenzene, D- benzene glycinol 4.8075g, Mixture is flowed back 60h at high temperature, stops reaction, is depressurized to remove solvent, residue is dissolved with water, and use CHCl3 20mLx2 extraction, organic phase is dry with anhydrous sodium sulfate, and rotation removes solvent, upper silica gel column chromatography column separating purification, with petroleum ether/ 1:9 mixed liquor elutes methylene chloride by volume, collects the first component point, sloughs eluant, eluent and obtain target product (R)-(+)-α- The chloro- benzamide of phenyl -2-,
Its chemical formula is as follows:
The chipal compounds (I), at a temperature of 293 (2) k, on the X-ray single crystal diffractometer of Oxford, with through graphite monochromator list The MoK alpha ray of colorDiffraction data is collected with ω-θ scanning mode, it is characterised in that crystal anorthic system, P2(1)；Cell parameterα=90 °；β=101.777 (5) °；γ=90 °.
2. being the Henle reaction as catalyst in ethyl pyruvate by the purposes of chipal compounds described in claim 1 (I) And applied in the reacting of benzaldehyde and benzamide, conversion ratio is respectively up to 41 and 94%.
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CN109912427A (en) * 2019-04-06 2019-06-21 合肥祥晨化工有限公司 A kind of preparation and purposes of ammonium salt
CN111662236A (en) * 2020-07-29 2020-09-15 合肥工业大学 Synthesis method and application of 2-hydroxyphenyl-5-pyrazinyl ketone
CN112480126B (en) * 2020-12-11 2022-03-11 合肥工业大学 Preparation and application of 5-alkyl quinazoline derivative

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Enantioselective synthesis of 1,2- diarylaziridines by the organocatalytic reductive amination of α-chloroketones;Malkov, Andrei V.等;《Angewandte Chemie, International Edition》;20071231;第46卷(第20期);第3722-3724页
EPC-synthesis of functionalized amides via chiral β-nitrogenated organolithium compounds;Foubelo, Francisco等;《Tetrahedron: Asymmetry》;19961231;第7卷(第10期);第2911-2922页
Synthesis of enantiomerically pure functionalized amides (EPC-synthesis) from chiral β-aminated organolithium intermediates;Foubelo, Francisco等;《Tetrahedron Letters》;19941231;第35卷(第27期);第4831-4834页

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