CN104926776A - Green synthesis method for 4-phenacylidene flavane derivatives - Google Patents
Green synthesis method for 4-phenacylidene flavane derivatives Download PDFInfo
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Abstract
The invention discloses a green synthesis method for 4-phenacylidene flavane derivatives, and belongs to the field of organic chemistry. Under the catalysis of boric acid, 2,4-dihydroxy benzaldehyde and an acetophenone derivative react for 6 hours at a temperature of 120 DEG C by taking polyethylene glycol 400 as a solvent so as to greenly synthesize 4-phenacylidene flavane derivatives through a one-step process. The synthesis method provided by the invention is simple and convenient to operate, simple in aftertreatment, and environmentally-fiendly and low-toxic, and has a good industrial application prospect; and the raw materials are easily available.
Description
Technical field
The present invention relates to the green synthesis method of 4-phenacylidene flavanoid derivative, belong to organic chemistry filed.
Background technology
Chalcones is a class of flavonoid compound, has tyrosinase inhibitory activity, in addition antibacterial, anticancer, anti-inflammatory and anti-oxidant isoreactivity.Natural cinnamophenone is extensively present in fruit, vegetables, spices, tea, soybean food and some herbal medicine.The main method of current cinnamophenone synthesis is that aromatic aldehyde and methyl phenyl ketone are in the basic conditions by Clasein-Schmidt condensation reaction.In the past few decades, the method for many synthesizing chalcones is developed from researchist all over the world.But these methods have a lot of defect, as the reaction conditions of harshness, toxic reagent and metal catalyst, strong acid and strong base, oil product, long reaction times, low-yield, low selectivity and loaded down with trivial details finishing sequence.In addition, in most cases, synthesis of hydroxy chalcone derivative needs protection and goes to protect hydroxyl, not only increases reaction step number and time, also increases the chance using poisonous or harmful reagent simultaneously.Although also have some green synthesis methods at present, as used calcium hydroxide to make catalyzer, spent glycol is as reaction solvent etc., and these green synthesis methods also exist the problems such as low-yield, oil product and loaded down with trivial details aftertreatment equally.4-phenacylidene flavanoid derivative is obtained, the synthetic method of 4-phenacylidene flavanoid derivative by the further Michael addition of cinnamophenone and dehydration, exists and synthesizes same problem with cinnamophenone.
Green synthesis method because of its environmental friendliness, subtract the characteristics such as dirty reduction of discharging, in scientific research and industrial application, there is far-reaching Research Significance and important using value.Along with the raising day by day of environmental protection, economy and social desirability, with the focus adopting green synthetic chemistry that nontoxic raw material, solid acid/alkaline catalysts and green solvent are representative to become research both at home and abroad.The present invention, by using gentle method, selects innoxious solvent as reaction solvent, and selects non-toxic catalyst, single stage method green syt 4-phenacylidene flavanoid derivative.
Summary of the invention
The object of the invention is to by single stage method green syt 4-phenacylidene flavanoid derivative, there is provided a kind of simple to operate, the novel method of gentle synthesis 4-phenacylidene flavanoid derivative, under the catalysis of boric acid, acetophenone derivs and 2, 4-Dihydroxy benzaldehyde passes through aldol reaction in poly(oxyethylene glycol) 400, first chalcone derivative is generated, the chalcone derivative generated generates 1 through Michael addition (Michael addition reaction) further, 5-diketone derivative, dewater further again and obtain, products therefrom is further by extraction, silica gel column chromatography, after gel filtration chromatography is separated, obtain 4-phenacylidene flavanoid derivative.The general formula of described 4-phenacylidene flavanoid derivative is such as formula shown in I:
R in formula
1=R
2=H, OH, OCH
3, CH
3, NO
2, Br, Cl, F.4-phenacylidene flavanoid derivative is synthesized by acetophenone derivs and 2,4-Dihydroxy benzaldehyde and obtains, known R
1, R
2the position of substitution on two rings is corresponding, and substituting group is identical.When the structure of acetophenone derivs determines, R
1, R
2the position of substitution and substituting group kind also just determine.
Described 4-phenacylidene flavanoid derivative comprises structural formula such as formula the compound shown in II, III, IV, V, VI, VII, VIII, IX, X, XI.
In one embodiment of the invention, the preparation method of Compound II per is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and methyl phenyl ketone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, carries out wash-out with methylene dichloride;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the above-mentioned dry product of dissolve with methanol, there is Precipitation, collected by filtration thing, obtain Compound II per: 2-(7-hydroxyl-2-phenyl-chromen-4-subunit)-1-methyl phenyl ketone, i.e. 2-(7-hydroxy-2-phenyl-chromen-4-ylidene)-1-phenyl-ethanone.
In one embodiment of the invention, the preparation method of compound III is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, with dichloromethane eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, be separated through Sephadex LH-20 gel filtration chromatography again, using the methanol-water of 7:3 mixing by volume as eluent, obtain compound III: 2-[7-hydroxyl-2-(2-hydroxy-pheny)-chromene-4-subunit]-1-(2-hydroxy-pheny)-ethyl ketone, i.e. 2-[7-hydroxy-2-(2-hydroxy-phenyl)-chromen-4-ylidene]-1-(2-hydroxy-phenyl)-ethanone.
In one embodiment of the invention, the preparation method of compound IV is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 3-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, uses isopyknic methylene dichloride respectively, with the methylene chloride-methanol of volume ratio 25:1 mixing, collects the wash-out position using the methylene chloride-methanol of volume ratio 25:1 mixing as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, again through Sephadex LH-20 gel filtration chromatography, wash-out is carried out as eluent using the methanol-water of 7:3 mixing by volume, obtain compound IV: 2-[7-hydroxyl-2-(3-hydroxy-pheny)-chromene-4-subunit]-1-(3-hydroxy-pheny)-ethyl ketone, i.e. 2-[7-hydroxy-2-(3-hydroxy-phenyl)-chromen-4-ylidene]-1-(3-hydroxy-phenyl)-ethanone.
In one embodiment of the invention, the preparation method of compound V is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-hydroxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, uses isopyknic methylene dichloride respectively, the methylene chloride-methanol wash-out of 20:1 mixing by volume, collects the wash-out position of the methylene chloride-methanol eluent of 20:1 mixing by volume;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, dissolve with methanol, again through Sephadex LH-20 gel filtration chromatography, using the methanol-water of 7:3 mixing by volume as eluent, collect elutriant recycling design, obtain compound V:2-[7-hydroxyl-2-(4-hydroxy-pheny)-chromene-4-subunit]-1-(4-hydroxy-pheny)-ethyl ketone, i.e. 2-[7-hydroxy-2-(4-hydroxy-phenyl)-chromen-4-ylidene]-1-(4-hydroxy-phenyl)-ethanone.
In one embodiment of the invention, the preparation method of compound VI is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-methoxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, insolubles methyl alcohol repeatedly washs, obtain compound VI: 2-[7-hydroxyl-2-(4-methoxyl group-phenyl)-chromene-4-subunit]-1-(4-methoxyl group-phenyl)-ethyl ketone, i.e. 2-[7-hydroxy-2-(4-methoxy-phenyl)-chromen-4-ylidene]-1-(4-methoxy-phenyl)-ethanone.
In one embodiment of the invention, the preparation method of compound VI I is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-methyl acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, insolubles methyl alcohol repeatedly washs, obtain compound VI I:2-(7-hydroxyl-2-p-methylphenyl-chromene-4-subunit)-1-p-methylphenyl-ethyl ketone, i.e. 2-(7-hydroxy-2-p-tolyl-chromen-4-ylidene)-1-p-tolyl-ethanone.
In one embodiment of the invention, the preparation method of compound VI II is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-nitro-acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, using the methylene chloride-methanol of 30:1 mixing by volume as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, obtain compound VI II:2-[7-hydroxyl-2-(4-nitro-phenyl)-chromene-4-subunit]-1-(4-nitro-phenyl)-ethyl ketone, i.e. 2-[7-hydroxy-2-(4-nitro-phenyl)-chromen-4-ylidene]-1-(4-nitro-phenyl)-ethanone.
In one embodiment of the invention, the preparation method of Compound I X is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-fluoro acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, obtain Compound I X:1-(the fluoro-phenyl of 4-)-2-[2-(the fluoro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone, i.e. 1-(4-fluoro-phenyl)-2-[2-(4-fluoro-phenyl)-7-hydroxy-chromen-4-ylidene]-ethanone.
In one embodiment of the invention, the preparation method of compounds X is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-chloro-acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, obtain compounds X: 1-(the chloro-phenyl of 4-)-2-[2-(the chloro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone, i.e. 1-(4-chloro-phenyl)-2-[2-(4-chloro-phenyl)-7-hydroxy-chromen-4-ylidene]-ethanone.
In one embodiment of the invention, the preparation method of compounds X I is as follows:
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-bromoacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, obtain compounds X I:1-(the bromo-phenyl of 4-)-2-[2-(the bromo-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone, i.e. 1-(4-bromo-phenyl)-2-[2-(4-bromo-phenyl)-7-hydroxy-chromen-4-ylidene]-ethanone.
Usefulness of the present invention is: a kind of method providing single stage method green syt 4-phenacylidene flavanoid derivative, has the advantages such as simple to operate, gentle environmental protection.The a series of new 4-phenacylidene flavanoid derivative of first passage single stage method green syt.
Embodiment
The preparation method of embodiment 1 2-(7-hydroxyl-2-phenyl-chromen-4-subunit)-1-methyl phenyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol methyl phenyl ketone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles part methyl alcohol repeatedly washs, and obtains 2-(7-hydroxyl-2-phenyl-chromen-4-subunit)-1-methyl phenyl ketone.
2-(7-hydroxyl-2-phenyl-chromen-4-subunit)-1-methyl phenyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
23h
16o
3.
1h NMR (DMSO-d
6, 400MHz) δ: 10.578 (1H, s, OH-4 "), 8.876 (1H, s, H-10), 8.236 (1H, d, J=9.6Hz, H-6 "), 8.102 (2H, d, J=7.6Hz, H-2,6), 7.947 (2H, d, J=7.2Hz, H-2', 6'), 7.576 (2H, d, J=Hz, H-3', 5'), 7.575 (1H, s, H-8), 7.559 (1H, m, H-4), 7.528 (2H, d, J=7.6Hz, H-3,5), 7.194 (1H, s, H-4'), 6.897 (2H, overlapping, H-3 ", 5 "),
13c NMR (DMSO-d
6, 100MHz) δ: 188.509 (C=O, C-7), 161.299 (C, C-4 "), 155.065 (C, C-11), 153.861 (C, C-2 "), 142.103 (C, C-1 "), 140.679 (C, C-1'), 131.965 (C, C-1), 131.532 (CH, C-4), 130.739 (CH, C-4'), 129.108 (CH, C-2, 6), 128.373 (CH, C-2', 6'), 127.562 (CH, C-3, 5), 125.617 (CH, C-6 "), 125.445 (CH, C-3', 5'), 114.788 (CH, C-10), 111.510 (C, C-9), 103.018 (CH, C-5 "), 101.813 (CH, C-3 "), 100.960 (CH, C-8).
ESI-MS:m/z 339.1[M-H]
-(C
23H
15O
3)。
The preparation method of embodiment 2 2-[7-hydroxyl-2-(2-hydroxy-pheny)-chromene-4-subunit]-1-(2-hydroxy-pheny)-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 2-hydroxy acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, then gel filtration chromatography (Sephadex LH-20) is separated further, methanol-water (7:3, v/v) wash-out, flow point is received with automatic receptor, TLC detects, and the same stream containing object divides and merges rear recycling design, obtains 2-[7-hydroxyl-2-(2-hydroxy-pheny)-chromene-4-subunit]-1-(2-hydroxy-pheny)-ethyl ketone.
-1-(2-hydroxy-pheny)-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows for 2-[7-hydroxyl-2-(2-hydroxy-pheny)-chromene-4-subunit]:
Molecular formula is C
23h
16o
5.
1H NMR(Acetone-d
6,400MHz)δ:13.819(1H,s,OH-2),10.651(2H,s,OH-2',4”),9.204(1H,s,H-10),8.320(1H,d,J＝9.2Hz,H-6”),8.263(1H,d,J＝8.0Hz,H-6),7.838(2H,d,J＝7.6Hz,H-6'),7.455(1H,t,J＝7.6Hz,H-4),7.353(1H,t,J＝8.0Hz,H-4'),7.206(1H,s,H-8),7.018(1H,d,J＝8.8Hz,H-3'),6.977(1H,d,J＝7.6Hz,H-3),6.930(1H,overlapped,H-5'),6.915(1H,overlapped,H-5),6.900(1H,overlapped,H-3”),6.883(1H,overlapped,H-5”)；
13C NMR(Acetone-d
6,100MHz)δ:192.305(C＝O,C-7),162.306(C,C-2),161.603(C,C-4”),156.230(C,C-2'),154.418(C,C-11),154.304(C,C-2”),144.963(C,C-1”),134.555(CH,C-4),131.713(CH,C-4'),129.433(CH,C-6),128.309(CH,C-6'),126.016(CH,C-6”),121.776(C,C-1),119.284(CH,C-3),118.553(C,C-1'),118.400(CH,C-5'),117.678(CH,C-5),116.828(CH,C-3'),114.966(CH,C-5”),111.634(C,C-9),106.590(CH,C-10),102.808(CH,C-3”),98.637(CH,C-8)。
ESI-MS:m/z 371.1[M-H]
-(C
23H
15O
5)。
The preparation method of embodiment 3 2-[7-hydroxyl-2-(3-hydroxy-pheny)-chromene-4-subunit]-1-(3-hydroxy-pheny)-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 3-hydroxy acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying, dry sample silica gel column chromatography, use isopyknic methylene dichloride respectively, methylene chloride-methanol (25:1), methylene chloride-methanol (10:1) wash-out, collect methylene chloride-methanol (25:1) wash-out position, recycling design, solid part dissolve with methanol, then gel filtration chromatography (SephadexLH-20) is separated further, methanol-water (v/v, 7:3) wash-out, TLC detects, containing the flow point recycling design of object, obtain 2-[7-hydroxyl-2-(3-hydroxy-pheny)-chromene-4-subunit]-1-(3-hydroxy-pheny)-ethyl ketone.
-1-(3-hydroxy-pheny)-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows for 2-[7-hydroxyl-2-(3-hydroxy-pheny)-chromene-4-subunit]:
Molecular formula is C
23h
16o
5.
1H NMR(DMSO-d
6,400MHz)δ:10.558(1H,s,OH-4”),9.817(1H,s,OH-3),9.619(1H,s,OH-3'),8.792(1H,s,H-10),8.175(1H,d,J＝9.2Hz,H-6”),7.550(1H,d,J＝8.0Hz,H-6),7.412(1H,H-4),7.378(2H,overlapped,H-5',6'),7.347(1H,H-4'),7.306(1H,t,J＝8.0Hz,H-5),7.095(1H,s,H-8),6.968(1H,H-2),6.949(1H,H-2'),6.881(1H,dd,J＝8.8,2.4Hz,H-5”),6.849(1H,d,J＝2.4Hz,H-3”)；
13C NMR(DMSO-d
6,100MHz)δ:188.484(C＝O,C-7),161.232(C,C-4”),157.807(C,C-3'),157.444(C,C-3),155.006(C,C-11),153.792(C,C-2”),142.240(C,C-1),141.857(C,C-1”),133.186(C,C-1'),130.207(CH,C-5'),129.338(CH,C-5),125.459(CH,C-6”),118.609(CH,C-6),118.449(CH,C-2),117.907(CH,C-2'),116.229(CH,C-6'),114.753(CH,C-5”),114.032(CH,C-4),111.881(CH,C-4'),111.494(C,C-9),102.935(CH,C-3”),101.694(CH,C-10),101.006(CH,C-8)。
ESI-MS:m/z 371.1[M-H]
-(C
23H
15O
5).
The preparation method of embodiment 4 2-[7-hydroxyl-2-(4-hydroxy-pheny)-chromene-4-subunit]-1-(4-hydroxy-pheny)-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-hydroxyacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add the PEG400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel column chromatography, use isopyknic methylene dichloride respectively, methylene chloride-methanol (20:1) wash-out, collect methylene chloride-methanol (20:1) wash-out position, recycling design, solid part dissolve with methanol, then gel filtration chromatography (Sephadex LH-20) is separated further, methanol-water (v/v, 7:3) wash-out, TLC detects, and containing the flow point recycling design of object, obtains 2-[7-hydroxyl-2-(4-hydroxy-pheny)-chromene-4-subunit]-1-(4-hydroxy-pheny)-ethyl ketone.
-1-(4-hydroxy-pheny)-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows for 2-[7-hydroxyl-2-(4-hydroxy-pheny)-chromene-4-subunit]:
Molecular formula is C
23h
16o
5.
1H NMR(DMSO-d
6,400MHz)δ:10.147(3H,br s,OH-4,4',4”),8.738(1H,s,H-10),8.171(1H,d,J＝8.8Hz,H-6”),8.003(2H,d,J＝8.8Hz,H-2,6),7.785(2H,d,J＝8.4Hz,H-2',6'),7.087(1H,s,H-8),6.957(2H,d,J＝8.8Hz,H-3',5'),6.860(2H,d,J＝8.8Hz,H-3,5),6.849(2H,overlapped,H-3”,5”)；
13C NMR(DMSO-d
6,100MHz)δ:187.153(C＝O,C-7),160.871(C,C-4”),160.667(C,C-4),159.872(C,C-4'),154.973(C,C-11),153.685(C,C-2”),141.365(C,C-1”),132.198(C,C-1),129.871(CH,C-2,6),127.232,127.118(CH,C-2',6'),125.401(CH,C-6”),122.726(C,C-1'),116.044,115.780(CH,C-3',5'),115.023,114.772(CH,C-3,5),111.684(C,C-9),103.073,102.820(CH,C-3”,5”),99.808(CH,C-8,10)。
ESI-MS:m/z 371.1[M-H]
-(C
23H
15O
5)。
The preparation method of embodiment 5 2-[7-hydroxyl-2-(4-methoxyl group-phenyl)-chromene-4-subunit]-1-(4-methoxyl group-phenyl)-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-methoxyacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 2-[7-hydroxyl-2-(4-methoxyl group-phenyl)-chromene-4-subunit]-1-(4-methoxyl group-phenyl)-ethyl ketone.
2-[7-hydroxyl-2-(4-methoxyl group-phenyl)-chromene-4-subunit]-1-(4-methoxyl group-phenyl)-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
25h
20o
5.
1H NMR(DMSO-d
6,400MHz)δ:8.777(1H,s,H-10),8.196(1H,d,J＝9.6Hz,H-6”),8.093(2H,d,J＝8.8Hz,H-2,6),7.880(2H,d,J＝8.4Hz,H-2',6'),7.132(2H,d,J＝8.8Hz,H-3',5'),7.121(1H,s,H-8),7.029(2H,d,J＝8.8Hz,H-3,5),6.866(1H,overlapped,H-3”),6.857(1H,overlapped,H-5”)；
13C NMR(DMSO-d
6,100MHz)δ:187.267(C＝O,C-7),162.024(C,C-4”),161.314(C,C-4),161.075(C,C-4'),154.855(C,C-11),153.784(C,C-2”),141.725(C,C-1”),133.566(C,C-1),129.751(CH,C-2,6),127.153(CH,C-2',6'),125.545(CH,C-6”),124.344(C,C-1'),114.620(CH,C-3',5'),114.578(CH,C-10),113.602(CH,C-3,5),111.656(C,C-9),103.038(CH,CH-5”),100.377(CH,C-3”),100.221(CH,C-8),55.466(CH
3O-4),55.404(CH
3O-4')。
ESI-MS:m/z 399.1[M-H]
-(C
25H
19O
5)。
The preparation method of embodiment 6 2-(7-hydroxyl-2-p-methylphenyl-chromene-4-subunit)-1-p-methylphenyl-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol methyl phenyl ketone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 2-(7-hydroxyl-2-p-methylphenyl-chromene-4-subunit)-1-p-methylphenyl-ethyl ketone.
2-(7-hydroxyl-2-p-methylphenyl-chromene-4-subunit)-1-p-methylphenyl-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
25h
20o
3.
1H NMR(DMSO-d
6,400MHz)δ:10.519(1H,s,OH-4”),8.835(1H,s,H-10),8.198(1H,d,J＝8.8Hz,H-6”),8.004(2H,d,J＝8.0Hz,H-2,6),7.821(2H,d,J＝8.4Hz,H-2',6'),7.374(2H,d,J＝8.4Hz,H-3',5'),7.308(2H,d,J＝8.0Hz,H-3,5),7.147(1H,s,H-8),6.880(1H,dd,J＝8.0,2.4Hz,H-5”),6.865(1H,d,J＝2.4Hz,H-3”)；
13C NMR(DMSO-d
6,100MHz)δ:188.703(C＝O,C-7),161.188(C,C-4”),155.008(C,C-11),153.810(C,C-2”),141.931(C,C-1”),141.595(C,C-4),140.718(C,C-4'),138.147(C,C-1),129.683(CH,C-2,6),129.200(C,C-1'),128.951(CH,C-2',6'),127.700(CH,C-3,5),125.555(CH,C-6”),125.343(CH,C-3',5'),114.658(CH,C-10),111.600(C,C-9),103.019(CH,CH-5”),101.165(CH,C-3”),100.607(CH,C-8),21.033(CH
3-4),20.969(CH
3-4')。
ESI-MS:m/z 367.1[M-H]
-(C
25H
19O
3)。
The preparation method of embodiment 7 2-[7-hydroxyl-2-(4-nitro-phenyl)-chromene-4-subunit]-1-(4-nitro-phenyl)-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-nitro-acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, methylene chloride-methanol (30:1) wash-out, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 2-[7-hydroxyl-2-(4-nitro-phenyl)-chromene-4-subunit]-1-(4-nitro-phenyl)-ethyl ketone.
-1-(4-nitro-phenyl)-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows for 2-[7-hydroxyl-2-(4-nitro-phenyl)-chromene-4-subunit]:
Molecular formula is C
23h
14n
2o
7.
13C NMR(DMSO-d
6,100MHz)δ:186.481(C＝O,C-7),161.712(C,C-4”),153.718(C,C-11),153.255(C,C-2”),148.864(C,C-4),148.228(C,C-4'),142.675(C,C-1”),141.667(C,C-1),137.495(C,C-1'),128.713(CH,C-2,6),126.544(CH,C-2',6'),125.619(CH,C-6”),123.968(CH,C-3',5'),123.237(CH,C-3,5),115.130(CH,C-10),111.036(C,C-9),104.316(CH,CH-5”),102.855(CH,C-3”),101.797(CH,C-8)。
ESI-MS:m/z 429.1[M-H]
-(C
23H
13N
2O
7)。
The preparation method of embodiment 8 1-(the fluoro-phenyl of 4-)-2-[2-(the fluoro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-fluoro acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 1-(the fluoro-phenyl of 4-)-2-[2-(the fluoro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone.
1-(the fluoro-phenyl of 4-)-2-[2-(the fluoro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
23h
14f
2o
3.
1H NMR(DMSO-d
6,400MHz)δ:8.765(1H,s,H-10),8.166(1H,d,J＝8.8Hz,H-6”),8.152(2H,d,J＝8.8Hz,H-2,6),7.977(2H,d,J＝8.8Hz,H-2',6'),7.391(2H,d,J＝8.4Hz,H-3',5'),7.279(2H,d,J＝8.8Hz,H-3,5),7.132(1H,s,H-8),6.892(1H,dd,J＝8.8,2.4Hz,H-5”),6.867(1H,d,J＝2.0Hz,H-3”)；
13C NMR(DMSO-d
6,100MHz)δ:186.835(C＝O,C-7),161.117(C,C-4”),154.028(C,C-11),153.621(C,C-2”),141.940(C,C-1”),137.142(C,C-1),137.114(C,C-4),133.099(C,C-4'),128.440(C,C-1'),130.081(CH,C-2,6),129.991(CH,C-2',6'),127.746(CH,C-3',5'),127.658(CH,C-3,5),125.269(CH,C-6”),114.768(CH,C-10),111.285(C,C-9),102.831(CH,CH-5”),102.041(CH,C-3”),100.680(CH,C-8)。
ESI-MS:m/z 375.1[M-H]
-(C
23H
13F
2O
3)。
The preparation method of embodiment 9 1-(the chloro-phenyl of 4-)-2-[2-(the chloro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-chloro-acetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 1-(the chloro-phenyl of 4-)-2-[2-(the chloro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone.
1-(the chloro-phenyl of 4-)-2-[2-(the chloro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
23h
14cl
2o
3.
1H NMR(DMSO-d
6,400MHz)δ:8.791(1H,s,H-10),8.163(1H,d,J＝8.8Hz,H-6”),8.083(2H,d,J＝8.4Hz,H-2,6),7.917(2H,d,J＝8.4Hz,H-2',6'),7.604(2H,d,J＝8.4Hz,H-3',5'),7.533(2H,d,J＝8.4Hz,H-3,5),7.117(1H,s,H-8),6.890(1H,dd,J＝8.8,2.0Hz,H-5”),6.861(1H,d,J＝2.4Hz,H-3”)；
13C NMR(DMSO-d
6,100MHz)δ:187.017(C＝O,C-7),161.277(C,C-4”),153.578(C,C-11),153.665(C,C-2”),142.169(C,C-1”),139.193(C,C-1),136.265(C,C-4),135.285(C,C-4'),130.680(C,C-1'),129.240(CH,C-2,6),128.169(CH,C-2',6'),127.008(CH,C-3,5),125.340(CH,C-6”),114.769(CH,C-10),111.290(C,C-9),102.880(CH,CH-5”),102.094(CH,C-3”),100.849(CH,C-8)。
ESI-MS:m/z 407.1[M-H]
-(C
23H
13Cl
2O
3)。
The preparation method of embodiment 10 1-(the bromo-phenyl of 4-)-2-[2-(the bromo-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone
Take 0.036mol 2,4-Dihydroxy benzaldehyde, 0.018mol 4-bromoacetophenone, 2.1g boric acid in 50mL round-bottomed flask, add PEG 400 stirring and dissolving of 25mL, be placed in 120 DEG C of oil bath stirring and refluxing 6h, TLC follows the tracks of reaction process.Reaction solution is extracted with ethyl acetate three times, and organic phase is evaporated to drying; Dry sample silica gel (200-300 order) column chromatography, dichloromethane eluent, TLC detects, same stream divides and merges rear recycling design, containing the solid part dissolve with methanol of object, there is Precipitation, filter, insolubles methyl alcohol repeatedly washs, and obtains 1-(the bromo-phenyl of 4-)-2-[2-(the bromo-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone.
1-(the bromo-phenyl of 4-)-2-[2-(the bromo-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone spectroscopic data of the nuclear magnetic resonance is as follows:
Molecular formula is C
23h
14br
2o
3.
1H NMR(DMSO-d
6,400MHz)δ:8.843(1H,s,H-10),8.218(1H,d,J＝8.8Hz,H-6”),8.033(2H,d,J＝8.8Hz,H-2,6),7.857(2H,d,J＝8.8Hz,H-2',6'),7.759(2H,d,J＝8.8Hz,H-3',5'),7.692(2H,d,J＝8.4Hz,H-3,5),7.146(1H,s,H-8),6.886(1H,dd,J＝8.8,2.4Hz,H-5”),6.866(1H,d,J＝2.4Hz,H-3”)；
13C NMR(DMSO-d
6,100MHz)δ:187.282(C＝O,C-7),161.473(C,C-4”),154.207(C,C-11),153.796(C,C-2”),142.448(C,C-1”),139.564(C,C-1),132.110(CH,C-2,6),131.349(C,C-1'),131.075(CH,C-2',6'),129.691(CH,C-3',5'),127.384(CH,C-3,5),125.702(C,C-4),125.532(CH,C-6”),124.300(C,C-4'),114.918(CH,C-10),111.390(C,C-9),103.007(CH,CH-5”),102.152(CH,C-3”),100.794(CH,C-8)。
ESI-MS:m/z 497.0[M-H]
-(C
23H
13Br
2O
3)。
Although the present invention with preferred embodiment openly as above; but it is also not used to limit the present invention, any person skilled in the art, without departing from the spirit and scope of the present invention; all can do various changes and modification, what therefore protection scope of the present invention should define with claims is as the criterion.
Claims (10)
1. one kind is synthesized the method for 4-phenacylidene flavanoid derivative, it is characterized in that, under the catalysis of boric acid, acetophenone derivs and 2,4-Dihydroxy benzaldehyde by aldol reaction, first generates chalcone derivative in poly(oxyethylene glycol) 400, and the further Michael reaction of chalcone derivative of generation generates 1,5-diketone derivative, and then dehydration obtains 4-phenacylidene flavanoid derivative further; The general structure of described 4-phenacylidene flavanoid derivative is such as formula shown in I:
R in formula
1=R
2=H, OH, OCH
3, CH
3, NO
2, Br, Cl, F.
2. method according to claim 1, is characterized in that, described 4-phenacylidene flavanoid derivative comprises structural formula such as formula the compound shown in II, III, IV, V, VI, VII, VIII, IX, X or XI:
3. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and methyl phenyl ketone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, carries out wash-out with methylene dichloride;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, and the above-mentioned dry product of dissolve with methanol, has Precipitation, collected by filtration thing, obtains 2-(7-hydroxyl-2-phenyl-chromen-4-subunit)-1-methyl phenyl ketone.
4. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 2-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, with dichloromethane eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, be separated through Sephadex LH-20 gel filtration chromatography again, using the methanol-water of 7:3 mixing by volume as eluent, wash-out obtains 2-[7-hydroxyl-2-(2-hydroxy-pheny)-chromene-4-subunit]-1-(2-hydroxy-pheny)-ethyl ketone.
5. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 3-hydroxy acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, respectively with isopyknic methylene dichloride, carry out wash-out with the methylene chloride-methanol of volume ratio 25:1 mixing, collects using the methylene chloride-methanol of volume ratio 25:1 mixing as the wash-out position of eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, again through Sephadex LH-20 gel filtration chromatography, carry out wash-out using the methanol-water of 7:3 mixing by volume as eluent, obtain 2-[7-hydroxyl-2-(3-hydroxy-pheny)-chromene-4-subunit]-1-(3-hydroxy-pheny)-ethyl ketone.
6. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-hydroxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, carries out wash-out with the methylene chloride-methanol of isopyknic methylene dichloride, by volume 20:1 mixing respectively, collects the wash-out position of the methylene chloride-methanol eluent of 20:1 mixing by volume;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, dissolve with methanol, again through Sephadex LH-20 gel filtration chromatography, using the methanol-water of 7:3 mixing by volume as eluent, collect elutriant recycling design, obtain 2-[7-hydroxyl-2-(4-hydroxy-pheny)-chromene-4-subunit]-1-(4-hydroxy-pheny)-ethyl ketone.
7. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-methoxyacetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, and obtains 2-[7-hydroxyl-2-(4-methoxyl group-phenyl)-chromene-4-subunit]-1-(4-methoxyl group-phenyl)-ethyl ketone.
8. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-methyl acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, has throw out to separate out, filters, insolubles methyl alcohol repeatedly washs, and obtains 2-(7-hydroxyl-2-p-methylphenyl-chromene-4-subunit)-1-p-methylphenyl-ethyl ketone.
9. method according to claim 1, is characterized in that,
(1) take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-nitro-acetophenone being raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, using the methylene chloride-methanol of 30:1 mixing by volume as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out methyl alcohol repeatedly washs, and obtains 2-[7-hydroxyl-2-(4-nitro-phenyl)-chromene-4-subunit]-1-(4-nitro-phenyl)-ethyl ketone.
10. method according to claim 1, is characterized in that, comprises the following steps:
(1) take mol ratio as 2 of 2:1,4-Dihydroxy benzaldehyde and 4-fluoro acetophenone are raw material, or be 2 of 2:1 with mol ratio, 4-Dihydroxy benzaldehyde and 4-chloro-acetophenone are raw material, or take mol ratio as 2, the 4-Dihydroxy benzaldehydes of 2:1 and 4-bromoacetophenone be raw material, under the catalysis of boric acid, take poly(oxyethylene glycol) 400 as solvent, in 130 DEG C of reactions 6 hours;
(2) reaction solution ethyl acetate or methylene dichloride or chloroform extraction 3 times, organic phase is concentrated to obtain dry sample;
(3) silicagel column on dry sample, methylene dichloride is as eluent;
(4) eluate sample that step (3) is collected concentrates to obtain dry sample, the dry thing of dissolve with methanol, throw out is had to separate out, filter, throw out with methanol wash repeatedly, obtain 1-(the fluoro-phenyl of 4-)-2-[2-(the fluoro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone, or 1-(the chloro-phenyl of 4-)-2-[2-(the chloro-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone, or 1-(the bromo-phenyl of 4-)-2-[2-(the bromo-phenyl of 4-)-7-HYDROXY-CHROMEN-4-subunit]-ethyl ketone.
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