CN109867593A - A kind of γ-hydroxyl ketone derivatives and its synthetic method - Google Patents
A kind of γ-hydroxyl ketone derivatives and its synthetic method Download PDFInfo
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Abstract
The invention discloses a kind of γ-hydroxyl ketone derivatives and its synthetic methods.Using styrene as raw material, under ruthenium complex and illumination effect, coupling reaction occurs with alpha-brominated acetophenone, has synthesized a series of γ-hydroxyl ketone derivatives of different structures, product can be further converted into functionalization product.This method raw material is easy to get, is easy to operate, reaction condition is mild, and functional group has diversity.
Description
Technical field
The present invention relates to a kind of methods that visible light catalytic prepares a kind of γ-hydroxyl ketone derivatives.Easily to prepare, source it is wide
And cheap styrene is raw material, under ruthenium complex effect and under illumination condition, realizes that the hydroxyalkylation of alkene is anti-
It answers, a step generates γ-hydroxy-ketone 1.Compared with the synthetic method of existing γ-hydroxy-ketone, raw material of the present invention is easy to get, operates letter
Just, reaction condition is mild, environmental-friendly；And the conversion that organic matter is realized using luminous energy, do not need to be added any oxidant or
Reducing agent has the characteristics that Atom economy is high.
Background technique
Visible light is a kind of cheap natural resources abundant.Chemists favor in how to efficiently use visible extensively at present
Light realizes the conversion of organic compound.2008, Macmillan and Yoon reported the fatty aldehyde α of visible light catalytic respectively
[2+2] cycloaddition reaction of position enantioselective alkylation (Science 2008,322,77) and unsaturated ketenes
(J.Am.Soc.Chem.2008,130,12886).Later, it is seen that application of the photocatalysis in organic synthesis is by chemists
Extensive concern.
The bifunctional dough of alkene is to construct the important method of complicated molecule.Research before is concentrated mainly on transition metal
The disadvantages of bifunctional dough of catalyzed alkene, but often reaction condition is harsher, substrate narrow scope of application, limits it
Using (Eur.J.Org.Chem.2017,2017,5821).However, in recent years, visible light catalytic can overcome transition metal
These disadvantages of catalysis.The bifunctional dough of visible light catalytic alkene has caused chemists' extensive concern at present.However it is sharp
Halides are used as generating free radicals under free based precursor photocatalysis to carry out addition reaction to alkene and have relevant report
(Chem.Eur.J.2016,22,13794；J.Org.Chem.2016,81,7148；Adv.Synth. Catal.2016,358,
1219).But use halides as free based precursor generate free radicals realize it is few at present to the O-alkylation of alkene
Report.Currently, mainly there is two reports, one is using visible light catalytic, and an another piece is but to be all using transition metal-catalyzed
Using α-bromoacetonitrile as alkylating reagent (Chem.Asian.J.2015,10,96；Adv.Catal.Synth.2014,356,
2873) it, uses alpha-brominated acetophenone to react as alkylating reagent with alkene generation hydroxyalkyl to be not yet reported that.
The styrene that the present invention utilizes easily preparation, source wide and cheap is raw material, in ruthenium complex and in illumination item
It is reacted under part with alpha-brominated acetophenone, realizes the hydroxyalkylation reaction of alkene, a step generates γ-hydroxyl ketone derivatives.
Summary of the invention
It is an object of the invention to easily to prepare, source is wide and cheap styrene is raw material 2, by a step be coupled
It realizes the building of C-C key and C-O key, synthesizes γ-hydroxyl ketone derivatives.
To achieve the goals above, technical scheme is as follows:
Using ruthenium complex as catalyst, styrene 2 is carried out in the presence of illumination and the cross-coupling of alpha-brominated acetophenone 3 is anti-
It answers, generates γ-hydroxyl ketone derivatives 1 (reaction equation 1).Routinely isolation and purification method carries out product separation and table after reaction
Sign, obtains target product.
Technical solution is characterized in that:
1. the substituent group of styrene 2: R2For methyl, methoxyl group, fluorine, chlorine, bromine, hydroxyl, cyclopropyl, trifluoromethyl, cyano,
Hydroxyl, carbethoxyl group or acetyl group.
2. the substituent group of alpha-brominated acetophenone 3: methyl, methoxyl group, fluorine, chlorine, bromine, cyclopropyl, trifluoromethyl, cyano, hydroxyl
Base, carbethoxyl group or acetyl group.
3. catalyst is Ru (bpy)3Cl2·6H2O、Ru(bpy)3(PF6)2Or Ru (phen)3Cl2；Wherein, reaction is with Ru
(bpy)3Cl2·6H2O is that catalyst effect is best, and the optimum molar ratio of styrene 2 and catalyst is 1:0.02.
4. reaction effect is best when alkali is sodium bicarbonate.
5. reaction effect is best when reaction dissolvent is acetonitrile.
6. the reaction time is 6-48 hours.Wherein, optimum reacting time is 24-48 hours.
7. reaction temperature is 0-50 DEG C, peak optimization reaction temperature is at 20-40 DEG C.
8. reaction lamp source color is that white, green and blue LED light and white CFL lamp, peak optimization reaction lamp source color are
White CFL lamp, peak optimization reaction lamp source power are 26W.
9. the preferred molar ratio of styrene 2 and alpha-brominated acetophenone 3 is 1:2.
The invention has the following advantages that
1) Materials Styrene 2 has the characteristics that source is wide and cheap, can be used to synthesize the γ-of different type and structure
Hydroxyl ketone derivatives 1.
2) alkene hydroxyalkyl reaction can realize cross-coupling by visible light catalytic, and reaction condition is mild, operation letter
The characteristics of list, wide application range of substrates, Atom economy height and large-scale production.
3) any oxidant of outer addition or reducing agent are not needed in the reaction of alkene hydroxyalkyl.
In short, the present invention is using the source of styrene 2 is wide and cheap feature efficiently synthesizes different type and structure
γ-hydroxyl ketone derivatives 1, raw material is easy to get, easy to operate, and target product yield is high, and can further derivatization.
Specific embodiment
The present invention is raw material with simple styrene 2 and alpha-brominated acetophenone 3, is carried out under ruthenium complex and illumination condition
Cross-coupling reaction (reaction equation 1).
Detailed process are as follows: weighed in glove box styrene 2 (0.3mmol), ruthenium complex (0.006 mmol) is alpha-brominated
Acetophenone 3 (0.6mmol), sodium bicarbonate (0.3mmol) are added to 25mL in branch mouth pipe, second are added under nitrogen atmosphere
Nitrile (3mL) and water (0.3mmol), react for 24 hours under 26W CFL illumination.After fully reacting, vacuum rotary steam removes solvent, later
With silica gel column chromatography (eluent is petroleum ether (60-90 DEG C)/ethyl acetate: 20:1, v/v), target product 1 is obtained.Target produces
Object is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Facilitate to further understand the present invention by following embodiments, but the contents of the present invention are not limited to that.
Embodiment 1
Detailed process are as follows: weighed in glove box p-methylstyrene 2a (35mg, 0.3mmol), Ru (bpy)3Cl2·
6H2O (4mg, 0.006mmol), alpha-brominated acetophenone 3a (120mg, 0.6mmol), NaHCO3(25mg, 0.3mmol) is added to
25mL is in branch mouth pipe, and addition acetonitrile (3mL) and water (18mg, 0.3mmol) shine in 26W white CFL lamp under nitrogen atmosphere
Penetrate lower room temperature reaction for 24 hours.After fully reacting, vacuum rotary steam, remove solvent, rear pillar chromatograph (petroleum ether (60-90 DEG C)/acetic acid
Ethyl ester: 20:1, v/v) obtain weak yellow liquid product 1a (53mg, yield 70%).Target product passes through nuclear magnetic resoance spectrum and height
Resolution Mass Spectrometry measurement is confirmed.
Embodiment 2
Detailed process are as follows: weighed in glove box 1a (76mg, 0.3mmol), sodium azide (20mg, 0.3mmol) is added
In the reaction tube for having branch mouth to 25mL, in N2Protection is lower be added 3mL Isosorbide-5-Nitrae-dioxane and boron trifluoride ether (55mg,
0.39mmol), 4h is reacted at 90 DEG C.Solvent, column chromatography: PE (60-90 DEG C)/EA=10/1, v/v are removed in rotation.Obtain light yellow liquid
Body 4a (17mg, yield 20%).Target product is confirmed by nuclear magnetic resoance spectrum and high resolution mass spectrum measurement.
Typical compound characterize data
4- hydroxyl-Isosorbide-5-Nitrae-diphenyl -1- butanone derivative (1a), weak yellow liquid1H NMR(400MHz, CDCl3)δ
8.02-7.85 (m, 2H), 7.58-7.48 (m, 1H), 7.42 (dd, J=10.6,4.7Hz, 2H), 7.25 (d, J=8.0Hz,
2H), 7.14 (d, J=7.9Hz, 2H), 4.77 (t, J=6.3Hz, 1 H), 3.08 (t, J=7.0Hz, 2H), 2.56 (s, 1H),
2.33(s,3H),2.24–2.09(m,2H). 13C NMR(100MHz,CDCl3)δ200.7(s),141.5(s),137.3(s),
136.9(s),133.2 (s),129.3(s),128.7(s),128.2(s),125.8(s),73.5(s),34.9(s),33.1
(s),21.2(s). C17H18O2HRMS theoretical value: [M]+:254.1307；Measured value: 254.1307.
Claims (9)
1. a kind of γ-hydroxyl ketone derivatives, molecular structural formula 1 are as follows:
R1Selected from following group: methyl, methoxyl group, fluorine, chlorine, bromine, cyclopropyl, trifluoromethyl, cyano, hydroxyl, carbethoxyl group or second
1-5 kind in acyl group, the number of substituent group are 1-5；
R2For in methyl, methoxyl group, fluorine, chlorine, bromine, hydroxyl, cyclopropyl, trifluoromethyl, cyano, hydroxyl, carbethoxyl group or acetyl group
1-5 kind, the number of substituent group is 1-5.
2. a kind of γ described in claim 1-hydroxyl ketone derivatives synthetic method, it is characterised in that: former for starting with styrene 2
Material, ruthenium salt are photosensitizer, and alpha-brominated acetophenone 3 is that alkylating reagent realizes that the hydroxyalkylation of alkene is anti-under illumination condition
It answers, a step generates γ-hydroxy-ketone 1；
The molecular structural formula of styrene 2 is as follows,
R2For in methyl, methoxyl group, fluorine, chlorine, bromine, hydroxyl, cyclopropyl, trifluoromethyl, cyano, hydroxyl, carbethoxyl group or acetyl group
1-5 kind, the number of substituent group is 1-5；
Synthetic route as shown in following reaction equations,
Wherein, R1Selected from following group: methyl, methoxyl group, fluorine, chlorine, bromine, cyclopropyl, trifluoromethyl, cyano, hydroxyl, ethoxy carbonyl
1-5 kind in base or acetyl group, the number of substituent group are 1-5；R2For methyl, methoxyl group, fluorine, chlorine, bromine, hydroxyl, cyclopropyl,
1-5 kind in trifluoromethyl, cyano, hydroxyl, carbethoxyl group or acetyl group, the number of substituent group are 1-5.
3. synthetic method according to claim 2, it is characterised in that:
Wherein, catalyst is Ru (bpy)3Cl2·6H2O、Ru(bpy)3(PF6)2, Eosin Y or Ru (phen)3Cl2One of
Or it is two or more, the molar ratio of styrene 2 and catalyst is 1:0.005-1:0.05；Styrene 2 rubs with alpha-brominated acetophenone 3
You are than being 1:1-1:3；Alkali is sodium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, one or more of potassium phosphate；Reaction
Solvent is one in 1,4- dioxane, dimethyl sulfoxide, acetonitrile, toluene, methanol, N,N-dimethylformamide or tetrahydrofuran
Kind is two or more；Reaction temperature is 0-50 DEG C；Reaction time is 6-48 hours；The color for reacting institute's light requirement is white light, blue light
Or one or more of green light, lamp source power are 3-26W, adaptation reaction system volume is 2mL-100mL.
4. synthetic method described in accordance with the claim 3, it is characterised in that: optimal catalyst is in the reaction of the generation of styrene 21
Ru(bpy)3Cl2·6H2O, styrene 2 and Ru (bpy)3Cl2Preferred molar ratio be 1:0.02.
5. synthetic method described in accordance with the claim 3, it is characterised in that: optimal alkali is carbonic acid in the reaction of the generation of styrene 21
Hydrogen sodium.
6. synthetic method described in accordance with the claim 3, it is characterised in that: optimum solvent is second in the reaction of the generation of styrene 21
Nitrile.
7. synthetic method described in accordance with the claim 3, it is characterised in that: optimum reacting time in the reaction of the generation of styrene 21
It is 24-48 hours, optimal reaction temperature is 20-40 DEG C.
8. synthetic method described in accordance with the claim 3, it is characterised in that: best lamp source is white in the reaction of the generation of styrene 21
Color CFL lamp, optimal lamp source power are 26W.
9. synthetic method described in accordance with the claim 3, it is characterised in that: the molar ratio of styrene 2 and bromoacetophenone 3 is 1:
The preferred molar ratio of 1-1:3, styrene 2 and bromoacetophenone 3 is 1:2.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114345370A (en) * | 2021-12-03 | 2022-04-15 | 陕西师范大学 | Method for reducing and cross-coupling aromatic olefin and halogenated hydrocarbon through photocatalysis |
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|---|---|---|---|---|
| EP0592881A2 (en) * | 1992-10-05 | 1994-04-20 | Takasago International Corporation | Process for producing optically active gamma-hydroxyketones |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0592881A2 (en) * | 1992-10-05 | 1994-04-20 | Takasago International Corporation | Process for producing optically active gamma-hydroxyketones |
Non-Patent Citations (4)
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| CHEN DAOQIAN等: "A metal-free transformation of alkynes to carbonyls directed by remote OH group", 《GREEN CHEMISTRY》 * |
| LI LUN等: "2,2,2-Trifluoroethylation of Styrenes with Concomitant Introduction of a Hydroxyl Group from Molecular Oxygen by Photoredox Catalysis Activated by Visible Light", 《ORGANIC LETTERS》 * |
| MURPHY WILLIAM S.等: "Reactions of aryl cyclopropyl ketones. A new synthesis of aryl tetralones", 《JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1: ORGANIC AND BIO-ORGANIC CHEMISTRY》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114345370A (en) * | 2021-12-03 | 2022-04-15 | 陕西师范大学 | Method for reducing and cross-coupling aromatic olefin and halogenated hydrocarbon through photocatalysis |
| CN114345370B (en) * | 2021-12-03 | 2023-07-21 | 陕西师范大学 | Method for reduction cross coupling of photocatalytic aromatic olefin and halogenated hydrocarbon |
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