CN107652205A - A kind of synthetic method and purposes of imines crystalline compounds - Google Patents

A kind of synthetic method and purposes of imines crystalline compounds Download PDF

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Publication number
CN107652205A
CN107652205A CN201711003299.6A CN201711003299A CN107652205A CN 107652205 A CN107652205 A CN 107652205A CN 201711003299 A CN201711003299 A CN 201711003299A CN 107652205 A CN107652205 A CN 107652205A
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reaction
crystalline compounds
imines
benzophenonehydrazones
zncl
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罗梅
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Hefei Xiangchen Chemical Engineering Co Ltd
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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
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/14—Separation; Purification; Stabilisation; Use of additives
    • 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
    • B01J31/0241—Imines or enamines
    • 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
    • C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
    • C07C249/12—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
    • 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
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • 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

Abstract

A kind of synthetic method for the imines crystalline compounds for having a following cell parameter, including synthesizing, separating and purify, described synthesis is that 2.1168g Benzophenonehydrazones have ZnCl with 1.6473g acetylureas with 1.4101g ureas element or 1.2110g Benzophenonehydrazones in chlorobenzene solvent2In the presence of under the conditions of anhydrous and oxygen-free back flow reaction 48 hours, ZnCl2Dosage is 15 20mol% of material quantity（Molar percentage, similarly hereinafter）After reaction stops, i.e. reaction sloughs chlorobenzene after terminating, and is extracted with chloroform after being dissolved in water, is purified after extraction phase precipitation with column chromatography；It is 1 by volume by crude product petroleum ether/dichloromethane:1 column chromatography, obtains white crystal compound, and the structural formula of the compound is as follows：

Description

A kind of synthetic method and purposes of imines crystalline compounds
First, technical field
The present invention relates to a kind of compound and preparation method thereof, more particularly to（E）The synthesis side of -1,2- di- Benzophenone imines Method.
2nd, background technology
（E）- 1,2- di- Benzophenone imines are important medicines, and the existing lot of documents of its synthetic method is reported【1-4】:
Bibliography：
1. Realized C-H Functionalization of Aryldiazo Compounds via Rhodium Relay Catalysis, Qiu, Lin et al, Organic Letters, 17(7), 1810-1813; 2015;
2.Cobalt(II) Complex of a Diazoalkane Radical Anion, Bonyhady, Simon J. et al, Inorganic Chemistry, 54(11), 5148-5150; 2015;
3. Rhodium(III)-catalyzed coupling of aromatic ketazines or oximes with 2-vinyloxirane via C-H activation, Wen, Jing et al, Tetrahedron Letters, 56 (41), 5512-5516; 2015;
4. Copper(II) acetylacetonate, Parish, Edward J. and Li, Shengrong, e- EROS Encyclopedia of Reagents for Organic Synthesis, 1-4; 2007;
5. Cs2CO3-mediated decomposition of N-tosylhydrazones for the synthesis of azines under mild conditionsLuo, Zai-Gang et al, Research on Chemical Intermediates, 43(2), 1139-1148; 2017。
3rd, the content of the invention
It is contemplated that medicine is particularly prepared for organic synthesis field provides a kind of chipal compounds, technology to be solved is asked Topic is to select corresponding raw material and establish corresponding method to synthesize compound.
（One）Compound alleged by the present invention is below formula (I) institute compound：
（Ⅰ）.
Its chemical name：（E）- 1,2- di- Benzophenone imines, abbreviation compound（I）.
Compound（Ⅰ）Synthetic method be urea element with benzophenone track in organic solvent chlorobenzene in catalyst zinc chloride Synthesized under 5mol% existence conditions, chemical equation is as follows：
The synthetic method of this compound (I) includes synthesis, separation and purifying, and described synthesis is 2.1168g Benzophenonehydrazones There is ZnCl in chlorobenzene solvent with 1.6473g acetylureas with 1.4101g ureas element or 1.2110g Benzophenonehydrazones2In the presence of in nothing Back flow reaction 48 hours, ZnCl under water oxygen free condition2Dosage is the 15-20mol% of material quantity（Molar percentage, similarly hereinafter）Reaction After stopping, i.e. reaction sloughs chlorobenzene after terminating, and is extracted with chloroform after being dissolved in water, is purified after extraction phase precipitation with column chromatography；Will Crude product petroleum ether/dichloromethane is 1 by volume:1 column chromatography, obtain white crystal compound.
The reaction mechanism of the reaction can be presumed as follows：
With urea element in the presence of lewis acid zinc chloride, the Benzophenonehydrazones of 2 molecules are condensed to form targeted Benzophenonehydrazones Compound I.
The preparation of this compound, using simple, efficient methodology of organic synthesis, one-step synthesis compound, through X- diffraction, NMR, IR and elementary analysis determine its structure.
4th, illustrate
Fig. 1 is the single crystal diffraction figure of crystalline compounds (I).
5th, embodiment
1.(E）- 1,2- hexichol join the preparation of imines
In 100mL two-mouth bottles, under the conditions of anhydrous and oxygen-free, 2.1168g Benzophenonehydrazones and 1.4101g ureas element or 1.2110g bis- Benzophenone hydrazone has ZnCl with 1.6473g acetylureas in chlorobenzene solvent2In the presence of under the conditions of anhydrous and oxygen-free back flow reaction 48 it is small When, ZnCl2Dosage is the 15-20mol% of material quantity（Molar percentage, similarly hereinafter）After reaction stops, i.e. reaction is sloughed after terminating Chlorobenzene, extracted with chloroform after being dissolved in water, purified after extraction phase precipitation with column chromatography；By crude product petroleum ether/dichloromethane It is 1 by volume:1 column chromatography, obtain white crystal compound；Yield：62%, 68%; m.p.145--147°C：1HNMR (500MHz, CDCl3, 27℃), 1 H NMR (400 MHz, CDCl3) δ 7.50 – 7.44 (m, 4H), 7.43 – 7.36 (m, 6H), 7.36 – 7.25 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 158.93, 138.20, 135.56, 129.60, 129.34, 128.68, 128.66, 128.04, 127.88.; IR : 3422, 3057, 1664, 1622, 1491, 1444, 1321, 1278, 1176, 1076, 1028, 956, 914, 767, 694, 655; HRMS(EI): m+1/z (%): calcd for C26H20N2: 360.1626 ; found:360.4600 the cooperation Thing crystal data is as follows：
Empirical formula C26H20N2
Molecular weight 360.44
Temperature 296 (2) K
The A of wavelength 0.71073
Crystallographic system, space group orthorhombic system, C2/c
The deg. of cell parameter a=21.9863 (8) alpha=90
b = 5.4974(2)Å beta = 94.4730(10) deg
c = 16.3053(6) Å gamma = 90 deg.
Volume 1964.78.79 (12) ^3
Charge density 4,1.219Mg/m^3
The mm^-1 of absorption correction parameter 0.071
Number of electrons 760 in unit cell
Crystal size 0.170x 0.110x 0.050mm
The to 24.994 of scope 2.506 at Theta angles
HKL index capture range -26<=h<=26, -6<=k<=6, -19<=l<=19
Collection/independent diffraction data 19437/1732 [R (7int)=0.0559]
The data integrity degree 96.7% of theta=25.242
The method Multi Slice Mode of absorption correction
The transmitance 0.75and 0.34 of minimax
The Matrix least square method for the method F^2 that refine uses
Number/number of parameters 1732/0/128 of data number/use limitation
The method 1.051 that refine uses
The uniformity factor R 1=0.0447 of point diffraction, wR2=0.1063
The identical factor R 1=0.640 of observable diffraction, wR2=0.1203
Absolute configuration parameter 0.0084（16）
And -0.135 e.A^-3 of maximum summit and peak valley 0.123 on difference Fourier figure
The typical bond distance's data of crystal
N(1)-C(1) 1.289(2)
N(1)-N(1)#1 1.394(3)
C(1)-C(8) 1.486(2)
C(1)-C(2) 1.486(2)
C(2)-C(7) 1.385(2)
C(2)-C(3) 1.385(3)
C(3)-C(4) 1.381(3)
C(3)-H(3) 0.9300
C(4)-C(5) 1.370(3)
C(4)-H(4) 0.9300
C(5)-C(6) 1.364(3)
C(5)-H(5) 0.9300
C(6)-C(7) 1.384(3)
C(6)-H(6) 0.9300
C(7)-H(7) 0.9300
C(8)-C(9) 1.384(2)
C(8)-C(13) 1.386(3)
C(9)-C(10) 1.405(3)
C(9)-H(9) 0.9300
C(10)-C(11) 1.360(3)
C(10)-H(10) 0.9300
C(11)-C(12) 1.357(3)
C(11)-H(11) 0.9300
C(12)-C(13) 1.374(3)
C(12)-H(12) 0.9300
C(13)-H(13) 0.9300
The typical bond angle data of crystal：
C(1)-N(1)-N(1)#1 116.29(16)
N(1)-C(1)-C(8) 125.29(15)
N(1)-C(1)-C(2) 116.43(15)
C(8)-C(1)-C(2) 118.24(14)
C(7)-C(2)-C(3) 118.24(17)
C(7)-C(2)-C(1) 120.21(16)
C(3)-C(2)-C(1) 121.54(16)
C(4)-C(3)-C(2) 120.3(2)
C(4)-C(3)-H(3) 119.8
C(2)-C(3)-H(3) 119.8
C(5)-C(4)-C(3) 120.7(2)
C(5)-C(4)-H(4) 119.6
C(3)-C(4)-H(4) 119.6
C(6)-C(5)-C(4) 119.6(2)
C(6)-C(5)-H(5) 120.2
C(4)-C(5)-H(5) 120.2
C(5)-C(6)-C(7) 120.2(2)
C(5)-C(6)-H(6) 119.9
C(7)-C(6)-H(6) 119.9
C(6)-C(7)-C(2) 120.8(2)
C(6)-C(7)-H(7) 119.6
C(2)-C(7)-H(7) 119.6
C(9)-C(8)-C(13) 117.94(18)
C(9)-C(8)-C(1) 120.46(17)
C(13)-C(8)-C(1) 121.57(16)
C(8)-C(9)-C(10) 119.6(2)
C(8)-C(9)-H(9) 120.2
C(10)-C(9)-H(9) 120.2
C(11)-C(10)-C(9) 120.7(2)
C(11)-C(10)-H(10) 119.6
C(9)-C(10)-H(10) 119.6
C(12)-C(11)-C(10) 119.8(2)
C(12)-C(11)-H(11) 120.1
C(10)-C(11)-H(11) 120.1
C(11)-C(12)-C(13) 120.3(2)
C(11)-C(12)-H(12) 119.8
C(13)-C(12)-H(12) 119.8
C(12)-C(13)-C(8) 121.5(2)
C(12)-C(13)-H(13) 119.2
C(8)-C(13)-H(13) 119.2
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 60h, separately sampled progress1HNMR is detected, and its conversion ratio is 53%;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。

Claims (2)

1. a kind of synthetic method for the imines crystalline compounds for having a following cell parameter, including synthesize, separate and purify, it is described Synthesis is 2.1168g Benzophenonehydrazones and 1.4101g ureas element or 1.2110g Benzophenonehydrazones and 1.6473g acetylureas in chlorobenzene There is ZnCl in solvent2In the presence of under the conditions of anhydrous and oxygen-free back flow reaction 48 hours, ZnCl2Dosage is the 15-20mol% of material quantity （Molar percentage, similarly hereinafter）After reaction stops, i.e. reaction sloughs chlorobenzene after terminating, and is extracted after being dissolved in water with chloroform, extraction phase Purified after precipitation with column chromatography；It is 1 by volume by crude product petroleum ether/dichloromethane:1 column chromatography, obtain white crystal conjunction Thing, the structural formula of the compound are as follows：
（Ⅰ）
The crystalline compounds（I）Cell parameter：273（2）At a temperature of k, on the X-ray single crystal diffractometer of Oxford, with warp The orthorhombic system of graphite monochromator monochromatization, C2/c, cell parameter： a = 21.9863(8) Å α = 90°；b = 5.4974(2) Å β = 94.4730(10)°.；c = 16.3053(6) Å γ = 90 °.
2. the purposes of the acetylurea dimer crystalline compounds (I) described in claim 1, is in phenylpyruvic acid second as catalyst Applied in the Henle reaction of ester, its conversion ratio is up to 53%.
CN201711003299.6A 2017-10-24 2017-10-24 A kind of synthetic method and purposes of imines crystalline compounds Pending CN107652205A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110256284A (en) * 2019-06-05 2019-09-20 合肥工业大学 A kind of synthetic method and purposes of benzophenone 9 oxime derivate

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102659707A (en) * 2012-04-26 2012-09-12 罗梅 Preparation and application of chiral compound
CN103319428A (en) * 2013-07-07 2013-09-25 罗梅 Chiral oxazoline and synthesis method thereof
CN107163085A (en) * 2017-06-09 2017-09-15 合肥祥晨化工有限公司 A kind of preparation of chiral platinum complex crystal and purposes
CN107253923A (en) * 2017-08-07 2017-10-17 合肥祥晨化工有限公司 A kind of synthetic method and purposes of acetylurea dimer crystalline compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102659707A (en) * 2012-04-26 2012-09-12 罗梅 Preparation and application of chiral compound
CN103319428A (en) * 2013-07-07 2013-09-25 罗梅 Chiral oxazoline and synthesis method thereof
CN107163085A (en) * 2017-06-09 2017-09-15 合肥祥晨化工有限公司 A kind of preparation of chiral platinum complex crystal and purposes
CN107253923A (en) * 2017-08-07 2017-10-17 合肥祥晨化工有限公司 A kind of synthetic method and purposes of acetylurea dimer crystalline compounds

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110256284A (en) * 2019-06-05 2019-09-20 合肥工业大学 A kind of synthetic method and purposes of benzophenone 9 oxime derivate

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