CN107353221A - 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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CN107353221A
CN107353221A CN201710571934.4A CN201710571934A CN107353221A CN 107353221 A CN107353221 A CN 107353221A CN 201710571934 A CN201710571934 A CN 201710571934A CN 107353221 A CN107353221 A CN 107353221A
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reaction
chipal compounds
phenyl
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benzene
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CN107353221B (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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  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A kind of synthetic method of chipal compounds (I); (Cyanoacetyl) pyrrolidines of catalyst 1 3.4382g is with palladium bichloride 33mol%; 60ml chlorobenzenes; D benzene glycinols 4.8075g; mixture is flowed back 60h at high temperature, stops reaction, depressurizes to remove solvent; residue is dissolved with water, and uses CHCl3(20mLx2) is extracted, organic phase anhydrous sodium sulfate drying, and rotation removes solvent, upper silica gel column chromatography column separating purification, with petroleum ether/dichloromethane (volume ratio 1：9) mixed liquor elutes, and collects the first component point, sloughs eluant, eluent and obtain the chlorophenethylamine of target product (R) (+) α phenyl 2, its chemical formula is as follows：

Description

A kind of Preparation method and use of chipal compounds
First, technical field
The present invention relates to a kind of preparation method of chipal compounds, more particularly to nitrogenous chipal compounds preparation method, definitely Ground, which is said, is（R）A kind of synthetic method and purposes of-(+)-α-chloro- phenyl ethylamines of phenyl -2-.
2nd, background technology
Chiral alpha-phenyl -2- chlorophenethylamine compounds are widely used in biological medicine and organic synthesis, its synthetic method Existing 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.
In the experiment of this experiment He oxazoline palladium complexes, another chipal compounds have unexpectedly been obtained（R）-(+)-α- The chloro- phenyl ethylamines of phenyl -2-.
3rd, the content of the invention
The present invention is intended to provide a kind of synthetic method of chiral hydroxyl amide compound, technical problem to be solved is one-step synthesis Chipal compounds.
It by synthesizing is 1- (Cyanoacetyl) pyrrolidines with D- benzene glycinols in chlorine that chipal compounds alleged by the present invention, which are, Have in benzene solvent 33mol% catalyst palladium bichloride reaction prepare as the compound shown in below formula：
Chemical name：(R)-(+)-α-chloro- phenyl ethylamines of phenyl -2-, abbreviation compound (I).
The synthetic method of this chiral amides compound includes synthesis and separation, and described synthesis is urged with palladium bichloride 33mol% Agent 1- (Cyanoacetyl) pyrrolidines 3.4382g, 60ml chlorobenzenes, D- benzene glycinol 4.8075g, by mixture in high temperature Lower backflow 60h, stop reaction, depressurize to remove solvent, residue is dissolved with water, and use CHCl3 20mLx2 is extracted, and is had Machine mutually uses anhydrous sodium sulfate drying, and rotation removes solvent, upper silica gel column chromatography column separating purification, body pressed with petroleum ether/dichloromethane Product ratio 1：9 mixed liquors elute, and collect the first component point, and sloughing eluant, eluent, to obtain target product (R)-(+)-α-phenyl -2- chloro- Phenyl ethylamine.
Synthetic reaction is as follows：
The reaction mechanism of the reaction can be speculated as 1- (Cyanoacetyl) pyrrolidines and be decomposed under the effect of 33mol% palladium bichlorides, and with （R）- benzene glycinol reacts, and obtains a kind of chipal compounds.
4th, illustrate
Fig. 1 is the single crystal diffraction figure of chipal compounds (R)-(+)-α-chloro- phenyl ethylamines of phenyl -2- (I).
5th, embodiment
（One）The preparation of chipal compounds α-chloro- phenyl ethylamines of phenyl -2-
In 100mL two-mouth bottles, under the conditions of anhydrous and oxygen-free, palladium bichloride 1.4442g (mmol), 1- (Cyanoacetyl) pyrrole are added Cough up alkane 3.4382g, 60ml chlorobenzene, D- benzene glycinol 4.8075g, mixture is flowed back 60h at high temperature, stops reaction, subtracts Press to remove solvent, residue is dissolved with water, and use CHCl3(20mLx2) is extracted, organic phase anhydrous sodium sulfate drying, Rotation removes solvent, upper silica gel column chromatography column separating purification, with petroleum ether/dichloromethane（Volume ratio 1：9）Mixed liquor elutes, and collects First component point, slough eluant, eluent and obtain target product (R)-(+)-α-chloro- phenyl ethylamines of phenyl -2-；[ a]5 D=+12.5º (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：
Empirical formula C1514NOCl
Molecular weight 259.72
Temperature 293 (2) K
Wavelength 0.71073
Crystallographic system, space group anorthic system, P2（1）
Cell parameter a=8.6108 (19) α=90 °
b = 5.1845(12) Å β = 101.777（5）°.
c = 14.778(3) Å γ= 90 °.
Volume 645.8（2）Å^3
Charge density 2,1.336Mg/m^3
The mm^-1 of absorption correction parameter 0.282
Number of electrons 272 in unit cell
The mm of 0.200 x 0.140x of crystal size 0.070
The to 25.998 of scope 2.416 at Theta angles
HKL index capture range -8<=h<=10, -6<=k<6, -18<=l<=16
Collection/independent diffraction data 3824/ 2380 [R (int)=0.0327]
The % of data integrity degree 99.7 of theta=30.5
The method Multi Slice Mode of absorption correction
The and 0.6299 of transmitance 0.7456 of minimax
The Matrix least square method for the method F^2 that refine uses
Number/number of parameters 2380/1/167 of data number/use limitation
The method 0.988 that refine uses
The uniformity factor R 1=0.0464 of point diffraction, ω R2=0.1106
The identical factor R 1=0.0544 of observable diffraction, ω R2=0.1149
Absolute configuration parameter 0.06（6）
Maximum summit and peak valley 0.344and -0.217e. ^-3 on difference Fourier figure
The typical bond distance's data of crystal：
Cl(1)-C(15) 1.769(4)
N(1)-C(1) 1.334(4)
N(1)-C(8) 1.457(4)
N(1)-H(1) 0.88(5)
O(1)-C(1) 1.216(4)
C(1)-C(2) 1.500(4)
C(2)-C(7) 1.374(5)
C(2)-C(3) 1.385(5)
C(3)-C(4) 1.372(5)
C(3)-H(3) 0.9300
C(4)-C(5) 1.371(6)
C(4)-H(4) 0.9300
C(5)-C(6) 1.374(5)
C(5)-H(5) 0.9300
C(6)-C(7) 1.384(4)
C(6)-H(6) 0.9300
C(7)-H(7) 0.9300
C(8)-C(15) 1.513(5)
C(8)-C(9) 1.519(5)
C(8)-H(8) 0.9800
C(9)-C(10) 1.371(5)
C(9)-C(14) 1.377(5)
C(10)-C(11) 1.374(5)
C(10)-H(10) 0.9300
C(11)-C(12) 1.363(6)
C(11)-H(11) 0.9300
C(12)-C(13) 1.349(7)
C(12)-H(12) 0.9300
C(13)-C(14) 1.372(6)
C(13)-H(13) 0.9300
C(14)-H(14) 0.9300
C(15)-H(15A) 0.9700
C(15)-H(15B) 0.9700
The typical bond angle data of crystal：
C(1)-N(1)-C(8) 121.3(3)
C(1)-N(1)-H(1) 120(2)
C(8)-N(1)-H(1) 119(2)
O(1)-C(1)-N(1) 122.1(3)
O(1)-C(1)-C(2) 121.7(3)
N(1)-C(1)-C(2) 116.2(3)
C(7)-C(2)-C(3) 119.7(3)
C(7)-C(2)-C(1) 122.3(3)
C(3)-C(2)-C(1) 117.9(3)
C(4)-C(3)-C(2) 119.8(3)
C(4)-C(3)-H(3) 120.1
C(2)-C(3)-H(3) 120.1
C(3)-C(4)-C(5) 120.7(3)
C(3)-C(4)-H(4) 119.6
C(5)-C(4)-H(4) 119.6
C(4)-C(5)-C(6) 119.7(3)
C(4)-C(5)-H(5) 120.2
C(6)-C(5)-H(5) 120.2
C(5)-C(6)-C(7) 120.1(3)
C(5)-C(6)-H(6) 119.9
C(7)-C(6)-H(6) 119.9
C(2)-C(7)-C(6) 120.0(3)
C(2)-C(7)-H(7) 120.0
C(6)-C(7)-H(7) 120.0
N(1)-C(8)-C(15) 109.2(3)
N(1)-C(8)-C(9) 112.7(3)
C(15)-C(8)-C(9) 109.7(3)
N(1)-C(8)-H(8) 108.4
C(15)-C(8)-H(8) 108.4
C(9)-C(8)-H(8) 108.4
C(10)-C(9)-C(14) 117.7(3)
C(10)-C(9)-C(8) 120.8(3)
C(14)-C(9)-C(8) 121.5(3)
C(9)-C(10)-C(11) 121.0(4)
C(9)-C(10)-H(10) 119.5
C(11)-C(10)-H(10) 119.5
C(12)-C(11)-C(10) 120.2(4)
C(12)-C(11)-H(11) 119.9
C(10)-C(11)-H(11) 119.9
C(13)-C(12)-C(11) 119.5(4)
C(13)-C(12)-H(12) 120.2
C(11)-C(12)-H(12) 120.2
C(12)-C(13)-C(14) 120.7(4)
C(12)-C(13)-H(13) 119.7
C(14)-C(13)-H(13) 119.7
C(13)-C(14)-C(9) 120.8(4)
C(13)-C(14)-H(14) 119.6
C(9)-C(14)-H(14) 119.6
C(8)-C(15)-Cl(1) 111.8(2)
C(8)-C(15)-H(15A) 109.3
Cl(1)-C(15)-H(15A) 109.3
C(8)-C(15)-H(15B) 109.3
Cl(1)-C(15)-H(15B) 109.3
H(15A)-C(15)-H(15B) 107.9
Henle reaction application
0.0675g compounds（I）, be placed in 25mL flasks, sequentially add 1mL tetrahydrofurans, 0.3 mL nitromethanes and 0.5mmol ethyl pyruvates, stirring at normal temperature reaction 48h, sampling are carried out1HNMR is detected, and its conversion ratio is 41%;1 H NMR (CDCl 3 ): δ ) 4.86 (d,J =13.8 Hz, 1H), 4.58 (d, J =13.8 Hz, 1H), 4.34 (m, 2H), 3.85(s, 1H), 1.46 (s, 3H), 1.33 (t, J =7.2 Hz, 3H).13 C NMR (CDCl 3 ):δ= 173.4, 80.9, 72.4, 63.0, 23.8, 13.9。
N, N '-（Phenylmethylene）The preparation of dibenzamide
In 25mL two-mouth bottles, add 0.0659g compounds I, 2mLTHF and chlorobenzene 2mL, 0.05mL benzaldehyde and 0.1302g benzamides, back flow reaction have crystal appearance after 96 hours：Detected with nuclear-magnetism, 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, described synthesis is used Catalyst 1- (Cyanoacetyl) pyrrolidines 3.4382g, 60ml chlorobenzenes, D- benzene glycinols are done with palladium bichloride 33mol% 4.8075g, mixture is flowed back 60h at high temperature, stops reaction, depressurize to remove solvent, residue is dissolved with water, And use CHCl3 (20mLx2) is extracted, organic phase anhydrous sodium sulfate drying, and rotation removes solvent, and upper silica gel column chromatography post separation is pure Change, with petroleum ether/dichloromethane（Volume ratio 1：9）Mixed liquor elutes, and collects the first component point, sloughs eluant, eluent and obtains target production Thing (R)-(+)-α-chloro- phenyl ethylamines of phenyl -2-,
Its chemical formula is as follows：
The chipal compounds (I), 293（2）At a temperature of k, on the X-ray single crystal diffractometer of Oxford, with through graphite monochromator The MoK alpha rays of monochromatization（λ=0.71073 Å）Diffraction data is collected with ω-θ scan modes, it is characterised in that crystal three is tiltedly brilliant System, P2（1）；Cell parameter a=8.6108 (19) α=90 °；b = 5.1845(12) Å β = 101.777（5）°；c = 14.778(3) Å γ= 90 °。
2. the purposes of the chipal compounds (I), it is Henle reaction and benzaldehyde and benzene first as catalyst in ethyl pyruvate Applied in the reaction of acid amides, its conversion ratio is respectively up to 41 and 94%.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CN112047891A (en) * 2020-07-29 2020-12-08 合肥工业大学 Synthesis method and application of 2-hydroxyphenyl-5-pyrazinyl ketone
CN112480126A (en) * 2020-12-11 2021-03-12 合肥工业大学 Preparation and application of 5-alkyl quinazoline derivative

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO2020207129A1 (en) * 2019-04-06 2020-10-15 合肥祥晨化工有限公司 Preparation and use of an ammonium salt
CN112047891A (en) * 2020-07-29 2020-12-08 合肥工业大学 Synthesis method and application of 2-hydroxyphenyl-5-pyrazinyl ketone
CN112047891B (en) * 2020-07-29 2021-11-30 合肥工业大学 Synthesis method and application of 2-hydroxyphenyl-5-pyrazinyl ketone
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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