CN106565518A

CN106565518A - Synthesis method of amide crystal compound

Info

Publication number: CN106565518A
Application number: CN201610994422.4A
Authority: CN
Inventors: 罗梅
Original assignee: Hefei Xiangchen Chemical Engineering Co Ltd
Current assignee: Hefei Xiangchen Chemical Engineering Co Ltd
Priority date: 2016-11-11
Filing date: 2016-11-11
Publication date: 2017-04-19
Also published as: CN107286039A

Abstract

The invention discloses an amide crystal compound as shown in the chemical formula (I). The formula (I) is defined in the specification. The synthesis method of the amide crystal compound (I) comprises synthesis and separation. The synthesis is to carry out reflux reaction on 1.0 ml benzaldehyde and 1.6516 g benzamide under an anhydrous anaerobic condition for 24 hours when PdC12 exists in a chlorobenzene and tetrahydrofuran solvent; and crystal appears after the reaction is stopped when the dosage of the PdC12 is 5 mol% of the amount of the raw materials.

Description

A kind of synthetic method of amide crystalline compounds

First, technical field

The present invention relates to a kind of compound and preparation method thereof, more particularly to N, N '-（Phenylmethylene）The conjunction of dibenzamide Into method.

2nd, background technology

N, N '-（Phenylmethylene）Dibenzamide is important medicine, can be used as insecticide and cancer therapy drug, its synthesis side The existing lot of documents report of method【1-4】:

List of references：

1. An efficient synthesis of symmetrical N,N-alkylidine bis-amides catalysed by nano copper ferrite Organic Chemistry: An Indian Journal (2015), 11, (9), 323-327.

2. N-Boc-aminals as easily accessible precursors for less accessible N- Boc-imines: facile synthesis of optically active propargylamine derivatives using Mannich-type reactions Tetrahedron (2016).

3.Efficient synthesis of symmetrical N,N'-alkylidene bisamides catalysed by acetyl chloride Journal of Chemical Research (2013), 37, (12), 751-753.

4. A convenient synthesis of bisamides with BF3 etherate as catalyst Tetrahedron (2013), 69, (52), 11080-11083。

3rd, the content of the invention

It is contemplated that for organic synthesis field, particularly preparing medicine provides a kind of chipal compounds, and technology to be solved is asked Topic is to select corresponding raw material and set up corresponding method synthesis compound.

（One）Compound alleged by the present invention is below formula (I) institute compound：

（Ⅰ）.

Its chemical name：N, N '-（Phenylmethylene）Dibenzamide, abbreviation compound（I）.

Compound（Ⅰ）Synthetic method be benzaldehyde with benzene carbon amide in organic solvent tetrahydrofuran with chlorobenzene in catalyst Synthesize under Palladous chloride. 5mol% existence conditions, chemical equation is as follows：

The synthetic method of this compound (I) includes synthesizing, separates and purification, described synthesis be 1.0ml benzaldehydes with 1.6516g Benzoylamides have PdCl in chlorobenzene and tetrahydrofuran solvent₂In the presence of under the conditions of anhydrous and oxygen-free back flow reaction 24 Hour, PdCl₂5mol% of the consumption for material quantity（Molar percentage, similarly hereinafter）After reaction stops, there is crystal to occur.

The reaction mechanism of the reaction can be presumed as follows：

The Benzoylamide of benzaldehyde and 2 molecules is condensed in the presence of lewis acid sloughs a molecular water, forms target compound I。

The preparation of this compound, adopts simple, efficient methodology of organic synthesis, one-step synthesis compound, Jing X- diffraction, NMR, IR and elementary analysiss determine its structure.

4th, illustrate

Fig. 1 is the single crystal diffraction figure of compound (I).

5th, specific embodiment

1.N, N '-（Phenylmethylene）The preparation of dibenzamide

In 100mL two-mouth bottles, under the conditions of anhydrous and oxygen-free, 0.0080g Palladous chloride .s, 20mL chlorobenzenes and 20mLTHF are added, 1.0mL benzaldehydes and 1.6516g Benzoylamides backflow 24h, after stopped reaction, have crystal to occur：Yield 96%; m.p.232- 234°C：¹HNMR (500MHz, CDCl₃, 27 DEG C), δ (ppm)=9.02 (d, J=7.77Hz, 2H), 7.91 (d, J= 7.42Hz, 4H), 7.55 (t, J=7.4Hz, 2H), 7.47 (t, J=7.7Hz, 6H), 7.37 (t, J=7.7Hz, 6H), 7.30 (t, J=7.3Hz, 1H), 7.03(t, J=7.9Hz, 1H);¹³CNMR(125MHz, CDCl₃, 27℃), 165.5(x2), 140.3,133.8,131.5,

128.3(x3),128.1(x3),127.6(x3),127.4(x3),126.4(x3),58.7;IR :3283,3086, 3061,3031,2774,1602,1581,1507,1483,1448,1350,1337,1309,1271,1199, 1180, 1139, 1088, 1077, 1062, 1048, 1030, 1001, 937, 874, 847, 780, 749, 696, 666, 610, 589, 566, 486; HRMS(EI): m/z (%): calcd for C₁₂H₁₅NO₃: 330.1368; found:330.1362, the match crystal volume data is as follows：

Empirical formula C21H18N2O2

Molecular weight 330.37

100.01 (10) K of temperature

0.71073 A of wavelength

Crystallographic system, space group orthorhombic system, P3 (1)

Cell parameter a=17.0645 (7) alpha=90 deg.

b = 17.0645Å beta = 90 deg

c = 4.9440(2) Å gamma = 120 deg.

1246.79 (11) ^3 of volume

Charge density 4,1.203Mg/m^3

Absorption correction parameter 0.087mm^-1

Number of electrons 472 in unit cell

Crystal size 0.25x 0.08x 0.05mm

10.368 to 14 of scope at Theta angles

The index capture range -19 of HKL<=h<=21, -16<=k<9, -5<=l<=5

Collection/independent diffraction data 2723/2098 [R (7int)=0.0406]

The data integrity degree 1.133% of theta=30.5

The method Multi Slice Mode of absorption correction

Transmitance 0.75and 0.34 of minimax

The Matrix least square method of method F^2 that refine is used

Number/number of parameters 2098/1/227 that data number/use is limited

The method 1.133 that refine is used

The concordance factor R 1=0.0579 of point diffraction, wR2=0.1505

The identical factor R 1=0.6190 of observable diffraction, wR2=0.1535

Absolute configuration parameter 0.2（8）

0.27 and -0.26e.A^-3 of maximum summit and peak valley on difference Fourier figure

The typical bond distance's data of crystal

Atom

Length/Å

Atom

Length/Å

O(1)

C(1)

1.224(9)

C(9)

C(10)

1.382(10)

O(2)

C(15)

1.230(9)

C(9)

C(14)

1.392(10)

N(1)

C(1)

1.358(9)

C(10)

C(11)

1.378(10)

N(1)

C(8)

1.460(8)

C(11)

C(12)

1.389(12)

N(2)

C(8)

1.463(8)

C(12)

C(13)

1.367(11)

N(2)

C(15)

1.350(8)

C(13)

C(14)

1.389(10)

C(1)

C(2)

1.487(10)

C(15)

C(16)

1.486(9)

C(2)

C(3)

1.387(12)

C(16)

C(17)

1.402(11)

C(2)

C(7)

1.381(11)

C(16)

C(21)

1.381(12)

C(3)

C(4)

1.379(12)

C(17)

C(18)

1.370(13)

C(4)

C(5)

1.393(17)

C(18)

C(19)

1.358(17)

C(5)

C(6)

1.343(16)

C(19)

C(20)

1.359(18)

C(6)

C(7)

1.415(14)

C(20)

C(21)

1.378(13)

C(8)

C(9)

1.529(9)

The typical bond angle data of crystal：

Atom

Angle/˚

Atom

Angle/˚

C(1)

N(1)

C(8)

119.9(6)

C(14)

C(9)

C(8)

123.5(6)

C(15)

N(2)

C(8)

122.6(6)

C(11)

C(10)

C(9)

121.3(7)

O(1)

C(1)

N(1)

122.7(7)

C(10)

C(11)

C(12)

120.0(7)

O(1)

C(1)

C(2)

121.7(7)

C(13)

C(12)

C(11)

119.3(7)

N(1)

C(1)

C(2)

115.6(6)

C(12)

C(13)

C(14)

120.8(7)

C(3)

C(2)

C(1)

121.6(7)

C(13)

C(14)

C(9)

120.2(6)

C(7)

C(2)

C(1)

119.9(7)

O(2)

C(15)

N(2)

123.1(6)

C(7)

C(2)

C(3)

118.5(8)

O(2)

C(15)

C(16)

121.6(6)

C(4)

C(3)

C(2)

121.4(9)

N(2)

C(15)

C(16)

115.3(6)

C(3)

C(4)

C(5)

119.6(10)

C(17)

C(16)

C(15)

122.6(7)

C(6)

C(5)

C(4)

120.0(8)

C(21)

C(16)

C(15)

120.1(7)

C(5)

C(6)

C(7)

120.7(9)

C(21)

C(16)

C(17)

117.3(7)

C(2)

C(7)

C(6)

119.8(9)

C(18)

C(17)

C(16)

120.7(9)

N(1)

C(8)

N(2)

109.5(5)

C(19)

C(18)

C(17)

121.1(11)

N(1)

C(8)

C(9)

112.9(5)

C(18)

C(19)

C(20)

118.9(9)

N(2)

C(8)

C(9)

109.5(5)

C(19)

C(20)

C(21)

121.5(10)

C(10)

C(9)

C(8)

118.2(6)

C(20)

C(21)

C(16)

120.5(10)

C(10)

C(9)

C(14)

118.4(7)

Claims

1. one kind has following chemical formula（I）Shown amide crystalline compounds:

（Ⅰ）

Amide crystalline compounds (I) described in claim 1, at a temperature of 100.01 (10) K, in Oxford, X-ray monocrystalline spreads out Penetrate on instrument, with the CuK of Jing graphite monochromator monochromatizations a rays（λ=1.54184Å）Diffraction number is collected with ω-θ scan modes According to, it is characterised in that crystal belongs to orthorhombic system, orthorhombic system, P3 (1), cell parameter:a = 17.0645(7)Å alpha = 90 deg; b = 17.0645Å beta = 90 deg; c = 4.9440(2) Å gamma = 120 deg。

2. amide crystalline compounds described in claim 1（I）Synthetic method, including synthesis and separate, described synthesis is 1.0ml benzaldehydes have PdCl with 1.6516g Benzoylamides in chlorobenzene and tetrahydrofuran solvent₂In the presence of in anhydrous and oxygen-free condition Lower back flow reaction 24 hours, PdCl₂After consumption is for the 5mol% reaction stoppings of material quantity, there is crystal to occur.