CN102850281B

CN102850281B - Synthesis method for 2,5-diphenylpyrazine

Info

Publication number: CN102850281B
Application number: CN201210320978.7A
Authority: CN
Inventors: 罗梅
Original assignee: 罗梅
Current assignee: Haining Economic Development Industrial Park Development and Construction Co., Ltd
Priority date: 2012-04-29
Filing date: 2012-09-03
Publication date: 2014-04-09
Anticipated expiration: 2032-09-03
Also published as: CN102643239A; CN102850281A

Abstract

The invention relates to a synthesis method for 2,5-diphenylpyrazine. The synthesis method comprises that: 3-(N-ethyl-N-phenyl)-propanenitrile and D-phenylglycinol are subjected to a reflux reaction for 60-70 hours in a chlorobenzene solvent in the presence of a catalyst anhydrous ZnCl2 under an anhydrous and anaerobic condition, wherein a use amount of ZnCl2 is 75-85 mol% of the amount of the raw materials; after the reaction is completed, the chlorobenzene is removed, and water is added to stir and dissolve; chloroform is adopted to extract; the extraction phase is subjected to drying and precipitation, and then is loaded on a silica gel chromatography column to separate; petroleum ether/dichloromethane ( a volume ratio of 7:3) is adopted to carry out elution, and the first component is collected; the eluant is removed to obtain the target product 2,5-diphenylpyrazine.

Description

A kind of 2, the synthetic method of 5-diphenyl pyrazine

One, technical field

The present invention relates to a kind of preparation method of organic fine chemical, is exactly a kind of 2, the synthetic method of 5-diphenyl pyrazine.

Two, background technology

The existing many bibliographical informations of synthetic method of 2,5-diphenyl pyrazine.As far back as 1975, J.Am.Chem.Soc. reported the synthetic method of this compound, 1993, synthesising communication again reported this material synthetic method (1, Alper, Howard; Wollowitz, Susan, j.Am.Chem.Soc.1975,97,3541-3543.2、Joseph Daniel ; D. N. Dhar, Synthetic Communications, 1993, 23, 2151-2157）。

Applicant, in the experiment of He oxazoline, has unexpectedly obtained another kind of compound 2,5-diphenyl pyrazine.

Three, summary of the invention

The present invention aims to provide compound 2,5-diphenyl pyrazine, and technical problem to be solved is that one-step synthesis obtains target product.

This synthetic method comprises synthetic with separated, and the described synthetic 3-of being exactly (N-ethyl-N-phenyl)-propionitrile and D-benzene glycinol have the anhydrous ZnCl of catalyzer in chlorobenzene solvent ₂while existing under anhydrous and oxygen-free condition back flow reaction 60 ~ 70 hours, ZnCl ₂consumption 75 ~ 85 mol % that are material quantity.

After reaction finishes, slough chlorobenzene, add water stirring and dissolving, then use chloroform extraction, after extraction phase drying, precipitation, upper silica gel column chromatography is separated, with sherwood oil/methylene dichloride (volume ratio 7:3) wash-out, collect the first component point, obtain target product 2,5-diphenyl pyrazine after sloughing eluent.

Building-up reactions is as follows:

Figure 2012103209787100002DEST_PATH_IMAGE002

This synthetic method one step obtains target product, and technique is simple, easy to operate.

This reaction mechanism can be speculated as 3-(N-ethyl-N-phenyl)-propionitrile and decompose under the strong lewis acid zinc dichloride effect of 83.1%mol, C-N bond rupture, generate small molecules group cyano group and cyanoethyl, then attack phenyl ring intermediate benzyne, generate adjacent cyano benzyl cyanide, the adjacent cyano benzyl cyanide of two molecules carries out condensation reaction, sloughs a part CH ₂n ₂, form 2,5-diphenyl pyrazine.

Figure 2012103209787100002DEST_PATH_IMAGE004

Four, accompanying drawing explanation

Fig. 1 is the X-diffraction analysis figure of 2,5-diphenyl pyrazine.

Five, embodiment

In 100mL two-mouth bottle, under anhydrous and oxygen-free condition, add anhydrous ZnCl ₂0.6728g (4.947mmol), 40ml chlorobenzene, 3-(N-ethyl-N-phenyl)-propionitrile 1.0367g (5.95mmol), D-benzene glycinol 4.2 g, by the mixture 72h that at high temperature refluxes, stopped reaction, decompression is with except desolventizing,, by residuum water dissolution, and use CHCl ₃(20mLx2) extraction, organic phase anhydrous sodium sulfate drying, rotation is except desolventizing, upper silica gel column chromatography column separating purification, with sherwood oil/methylene dichloride (volume ratio 7:3) mixed solution wash-out, collects the first component point, slough eluent and obtain target product 2,5-diphenyl pyrazine.Productive rate: 15%, ultimate analysis: Anal.Calc. for C ₆h ₁₆n ₂o ₄: C%:82.73; H:5.21; N:12.06; Found:C%:82.54; H%:5.04; N%:15.50; HRMS (EI): m/z (%): calcd for C ₈h ₁₂nO:232.1000; Found:232.1008;

The crystal structure determination of compound:

The monocrystalline of choosing under the microscope suitable size at room temperature carries out the experiment of X-ray single crystal diffraction, at 293k temperature, on Oxford X-ray single crystal diffractometer, use through the MoKa of graphite monochromator monochromatization ray (λ=0.71073 A) and collect diffraction data with w-Theta scan mode.The data obtained is carried out to the Lp factor and experience absorption correction, and crystalline structure is solved by direct method, and diffraction data reduction and structure elucidation work are used respectively SAINT-5.0 and SHELXS-97 program to complete.Crystal data is as follows:

Empirical formula C16 H12 N2

Formula weight 232.28

Temperature 293(2) K

Wavelength 0.71073 A

Crystal system, space group Monoclinic, P2(1)/c

Unit cell dimensions a = 13.422(3) A alpha = 90 deg.

b = 5.7453(12) A beta = 92.800(4) deg.

c = 7.6781(16) A gamma = 90 deg.

Volume 591.4(2) A^3

Z, Calculated density 2, 1.304 Mg/m^3

Absorption coefficient 0.078 mm^-1

F(000) 244

Crystal size 0.257 x 0.123 x 0.078 mm

Theta range for data collection 1.52 to 25.49 deg.

Limiting indices -15<=h<=16, -6<=k<=5, -9<=l<=9

Reflections collected / unique 3211 / 1097 [R(int) = 0.0235]

Completeness to theta = 25.49 100.0 %

Absorption correction Empirical

Max. and min. transmission 1.00000 and 0.56771

Refinement method Full-matrix least-squares on F^2

Data / restraints / parameters 1097 / 0 / 82

Goodness-of-fit on F^2 1.124

Final R indices [I>2sigma(I)] R1 = 0.0523, wR2 = 0.1304

R indices (all data) R1 = 0.0643, wR2 = 0.1381

Largest diff. peak and hole 0.194 and -0.175 e.A^-3;

bond distance's data of crystal:

N(1)-C(8) 1.329(2)

N(1)-C(7) 1.337(2)

C(1)-C(2) 1.392(2)

C(1)-C(6) 1.393(2)

C(1)-C(7) 1.477(2)

C(2)-C(3) 1.375(2)

C(2)-H(2) 0.9300

C(3)-C(4) 1.378(3)

C(3)-H(3) 0.9300

C(4)-C(5) 1.371(3)

C(4)-H(4) 0.9300

C(5)-C(6) 1.378(2)

C(5)-H(5) 0.9300

C(6)-H(6) 0.9300

C(7)-C(8)#1 1.381(2)

C(8)-C(7)#1 1.381(2)

C(8)-H(8) 0.9300

the bond angle data of crystal:

C(8)-N(1)-C(7) 117.26(15)

C(2)-C(1)-C(6) 118.22(16)

C(2)-C(1)-C(7) 119.84(15)

C(6)-C(1)-C(7) 121.93(15)

C(3)-C(2)-C(1) 120.85(17)

C(3)-C(2)-H(2) 119.6

C(1)-C(2)-H(2) 119.6

C(2)-C(3)-C(4) 120.16(18)

C(2)-C(3)-H(3) 119.9

C(4)-C(3)-H(3) 119.9

C(5)-C(4)-C(3) 119.75(16)

C(5)-C(4)-H(4) 120.1

C(3)-C(4)-H(4) 120.1

C(4)-C(5)-C(6) 120.60(18)

C(4)-C(5)-H(5) 119.7

C(6)-C(5)-H(5) 119.7

C(5)-C(6)-C(1) 120.41(17)

C(5)-C(6)-H(6) 119.8

C(1)-C(6)-H(6) 119.8

N(1)-C(7)-C(8)#1 119.41(16)

N(1)-C(7)-C(1) 117.47(15)

C(8)#1-C(7)-C(1) 123.13(15)

N(1)-C(8)-C(7)#1 123.33(17)

N(1)-C(8)-H(8) 118.3

C(7)#1-C(8)-H(8) 118.3

Claims

1. one kind 2, the synthetic method of 5-diphenyl pyrazine, comprises and synthesizing with separated, it is characterized in that: the described synthetic 3-of being (N-ethyl-N-phenyl)-propionitrile and D-benzene glycinol have the anhydrous ZnCl of catalyzer in chlorobenzene solvent ₂while existing under anhydrous and oxygen-free condition back flow reaction 60～70 hours, ZnCl ₂the consumption 75～85mol% that is material quantity, after reaction finishes, slough chlorobenzene, add water stirring and dissolving, use again chloroform extraction, after extraction phase drying, precipitation, upper silica gel column chromatography is separated, by its volume ratio of sherwood oil/methylene dichloride, it is 7:3 wash-out, collect the first component point, obtain target product 2,5-diphenyl pyrazine after sloughing eluent.