CN105585554B - A kind of method of copper catalysis water phase end alkene and sulphur powder reaction generation thiphene ring - Google Patents
A kind of method of copper catalysis water phase end alkene and sulphur powder reaction generation thiphene ring Download PDFInfo
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- CN105585554B CN105585554B CN201510180179.8A CN201510180179A CN105585554B CN 105585554 B CN105585554 B CN 105585554B CN 201510180179 A CN201510180179 A CN 201510180179A CN 105585554 B CN105585554 B CN 105585554B
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- styrene
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/08—Hydrogen atoms or radicals containing only hydrogen and carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/12—Radicals substituted by halogen atoms or nitro or nitroso radicals
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses catalysis end alkene in a kind of pure water phase, and the method for preparing thiophene derivant is reacted with sulphur powder, using water-soluble complexes as catalyst, one pot reaction prepares the reaction of thiophenes in pure water phase, has invented a kind of novel method environmental-friendly, easy to operate, safety is cheap, raw material simply prepares substituted thiophene class compound.Compared with prior art, the method can be applied not only to many functional groups, and starting material is simple, is simple to operate and friendly to environment.
Description
Technical field
The invention belongs to synthesis methodology technical fields, are related to the formation field of the coupling of C-S key, thiphene ring, are that one kind is urged
The method for being combined to thiphene ring.
Background technique
Thiophene substance in pharmaceutical chemistry and materials chemistry using very extensive.For example, thiophene is such as Evista
(reloxifen), Duloxetine (Cymbalta), Tiotropium Bromide (Spiriva), cosopt (dorzolamide) etc. are several
The backbone structure of important drug.Said medicine is synthesized usually using simple thiophene as raw material.[ M. D.
Dhanaraju, Y. R. Rani, G. Thirumurugan, Pharmacia Lettre. 2009, 1, 219-226;
J. L. Pilgrim, Dimitri. Gerostamoulos, O. H. Drummer, Forensic Science
International, 2014, 234, 165-173;G. M. Keating, Drugs, 2012, 72,273-300; C.
Plummer, E. MacKay, K. Gelatt, Vet Ophthalmol, 2006,9,245-249.] it can be effective
It synthesizes the organic compound containing thiphene ring and meets the simple method of Atom economy, Green Chemistry, method by chemist
Extensive concern.Since application of the compound containing thiphene ring in terms of material is also very extensive.For example it can be used for light-emitting diodes
Tube material, field effect transistor, solar battery.[ R. Jin, S.Tang, D. Luo, Journal of Molecular
Modeling, 2014, 20, 1-10; A. Hoppe, T. Balster, T. Muck, V. Wagner, Organic
Electronics, 2009,469-497；S. Venkatesan, E. C. Ngo, Q. Chen, A. Dubey, L.
Mohammad, N. Adhikari, A. Mitul, Q. Qiao, Nanoscale, 2014, 6, 7093-7100.]
The method of synthesizing thiofuran class compound has much at present, mainly includes that Gewald reacts, Willgerodt-Kindle
Reaction, Paul-Knorr reaction, fluorine synthesize agreement, sulfur auxiliary reaction, electricity-hydrophiling and direct arylation method etc..
[K.Gewald,E. Schinke, H.Böttcher, Ber. 1966, 99, 94-100；K.Willgerodt, Ber
Dtsch Chem Ges, 1888, 431, 534–536; G.Minetto , L. F. Raveglia , A. Sega, M.
Taddei, Eur J Org Chem, 2005, 24,5277–5288; Z. Kaleta , B. T. Makowski , T.
Soos, R. Dembinski, Org Lett, 2006, 8, 1625–1628; H. F. Guo , H. Y. Shao , Z.
Y. Yang, J Med Chem, 2010, 53, 1819–1829; B. Godoi , R. F. Schumacher , G.
Zeni, Chem Rev, 2011, 111, 2937–2980; A. Ohta , T. Akia, T. Ohkuwa, M. Chiba,
Heterocycles, 1990,31,1951-1958.] but the starting material preparation that has of these methods is complicated, some atoms
Less economical, some is complicated harsh using poisonous and hazardous organic solvent, the reaction condition having.
Summary of the invention
The purpose invented herein is to have developed an aqueous phase reactions system, with one pot process thiophenes.With it is existing
There is synthesizing thiofuran substance to compare, the feature of this system maximum be it is environmental-friendly, starting material is simple and easy to get, furthermore avoid using
Noble metal, equipment requirement be not high.The operation is simple, cheap, pollution is small, and substrate extension is also very extensive, is attained by good
Good yield.
Technical solution of the present invention is specific as follows:
The purpose is in water phase middle-end alkene and sulphur powder one pot process thiophenes under the action of catalyst, reaction
When it is as follows:
Its middle-end alkene can be aliphatic end alkene, be also it is non-substituted or with chlorine, bromine, methyl, ethyl aromatic series end alkene,
Substituent group can be located at o-, m- and p- position.
Reaction system is implemented in the presence of inorganic base or organic base, and inorganic base can be sodium hydroxide, potassium hydroxide, carbonic acid
Potassium, sodium carbonate, sodium bicarbonate, saleratus, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, potassium dihydrogen phosphate etc., organic base can be
Triethylamine, tripropyl amine (TPA), pyridine, DBU, DBN, DMAP etc..It is preferred that sodium hydroxide, potassium hydroxide.
Reaction system is implemented in the presence of inorganic additives, and inorganic salts can be potassium fluoride, sodium fluoride, potassium chloride, chlorination
Sodium, potassium bromide, sodium bromide, potassium iodide, sodium iodide, preferably potassium iodide, sodium iodide.
It in a preferred embodiment of the invention, is standard based on 2 moles of styrene, the dosage of sulphur powder is 1 to 5 mole, more excellent
It is selected as 1.2 to 3.0 moles.
In a preferred embodiment of the invention, based on the dosage that 2 moles of styrene are alkali potassium hydroxide described in standard be 0.5 to
5, preferably 1 to 3 mole.
It in a preferred embodiment of the invention, is standard based on 2 moles of styrene, the usage amount of hydroquinone of polymerization retarder is
0.001 to 0.2 mole, preferably 0.02-0.1 moles.
It in a preferred embodiment of the invention, is standard, Cu (acac) based on 2 moles of styrene2The usage amount of catalyst is
0.001 to 1 mole, preferably 0.01 to 0.5 mole.
It in a preferred embodiment of the invention, is standard based on 2 moles of styrene, phase transfer catalyst tetrabutylammonium bromide
Usage amount is 0 to 3 mole, preferably 0.1 to 2 mole.
It in a preferred embodiment of the invention, is standard, the usage amount of inorganic additives potassium iodide based on 2 moles of styrene
It is 0 to 6 mole, preferably 1 to 4 mole.
The amount ranges of water as solvent are wider, and the concentration of reaction substrate styrene is preferably 0.2 to 2 mole/L,
More preferably 0.2 to 0.5 mole/L.
In the preferred solution of the invention, reaction temperature be 30 to 160 DEG C, preferably 50-140 DEG C, and more preferably 80-120 DEG C
Under the conditions of implement.
In the preferred solution of the invention, the reaction time is 1-60 hours, preferably 5-48 hours.
The present invention is beneficial to be had the technical effect that
1, the present invention provides a kind of method of completely new synthesizing thiofuran ring, the characteristics of this method, is starting material letter
It is singly easy to get and does not need complicated preparation process.
2, the present invention does not need special reaction kit.
3, the present invention carries out environmentally friendly in water phase, and post-processing is simple.
The copper catalyst that the present invention is easy to get using business, good economy performance.
Detailed description of the invention:
Fig. 1: the preparation of compound diphenyl thiophene1H NMR
Fig. 2: the preparation of compound diphenyl thiophene13C NMR
Fig. 3: the preparation of compound two (p-methylphenyl) thiophene1H NMR
Fig. 4: the preparation of compound two (p-methylphenyl) thiophene13C NMR
Fig. 5: the preparation of compound two (rubigan) thiophene1H NMR
Fig. 6: the preparation of compound two (rubigan) thiophene13C NMR
Specific embodiment
Embodiment 1: the preparation of diphenyl thiophene: styrene 2mmol (208mg) is added in the reaction vessel, Cu (acac)20.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinone 0.02mmol (2mg), potassium iodide 2mmol (332mg),
8ml water is added in tetrabutylammonium bromide 1mmol (322mg), sulphur powder 3mmol (96mg).It is reacted 24 hours in 120 DEG C of oil baths, it is cold
But it to room temperature, after being extracted with ethyl acetate, is concentrated under reduced pressure.Product passes through column separating purification, obtains white solid, yield 72%
(GC:2,4- diphenyl thiophene: 2,5- diphenyl thiophene=3:1).1H NMR (400MHz, CDCl3) δ 7.82-7.58 (m,
5H, ArH), 7.57-7.38 (m, 5H, ArH), 7.35-7.28 (m, 2H, ArH); 13C NMR (100MHz,
CDCl3) δ 145.12, 143.19, 135.93, 134.39, 128.99, 127.65, 127.32, 126.38,
125.59, 122.39, 119.78; GC-MS m/z 236 .
The preparation of embodiment 2: two (p-methylphenyl) thiophene: 4- methyl styrene 2mmol is added in the reaction vessel
(236mg), Cu (acac) 20.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinone 0.02mmol (2mg), iodine
Change potassium 2mmol (332mg), tetrabutylammonium bromide 1mmol (322mg), sulphur powder 3mmol (96mg), 8ml water is added.In 120 DEG C of oil
It reacts 24 hours, is cooled to room temperature in bath, after being extracted with ethyl acetate, be concentrated under reduced pressure.Product passes through column separating purification, obtains white
Color solid, yield 78%(GC:2,4- bis- (p-methylphenyl) thiophene: 2,5- bis- (p-methylphenyl) thiophene=6:1).1H NMR
(400 MHz, CDCl3) δ = 7.61 – 7.53 (m, 5H), 7.39 (ddd, J=8.6, 5.7, 3.0, 5H),
2.20 (s, 6H).；13C NMR (100 MHz, CDCl3) δ = 145.09 , 143.28, 143.07, 137.56,
137.32, 136.99, 133.21, 131.69, 129.74 – 129.41, 126.24, 125.80, 125.54,
123.48, 121.87, 118.66, 21.25. GC-MS m/z 264.
The preparation of embodiment 3: two (rubigan) thiophene: 4- chlorostyrene 2mmol is added in the reaction vessel
(278mg),Cu(acac)2 0.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinone 0.02mmol (2mg), iodine
Change potassium 2mmol (332mg), tetrabutylammonium bromide 1mmol (322mg), sulphur powder 3mmol (96mg), 8ml water is added.In 120 DEG C of oil
It reacts 24 hours, is cooled to room temperature in bath, after being extracted with ethyl acetate, be concentrated under reduced pressure.Product passes through column separating purification, obtains white
Color solid, yield 83%(GC:2,4- bis- (rubigan) thiophene: 2,5- bis- (rubigan) thiophene=8:1).1H NMR
(400MHz, CDCl3) δ 7.62-7.53 (m, 5H, ArH), 7.44-7.36 (m, 5H, ArH); 13C NMR (100
MHz, CDCl3) δ = 144.06 , 142.62 , 142.02 , 134.10 , 133.61 , 133.40 , 133.19
, 132.61 , 129.28 – 128.92 , 127.53 , 127.03 , 126.79 , 124.44 , 122.40 ,
120.28.
Claims (10)
1. a kind of method that copper catalysis water phase end alkene and sulphur powder reaction generate thiphene ring comprising the following steps:
The method that water-soluble copper complex catalysis end alkene and sulphur powder one pot reaction prepare thiophenes in pure water phase, such as
Chemical equation (1), the specific steps of synthesis are as follows: end alkene, Cu (acac) are added in the reaction vessel2, potassium hydroxide, to benzene
Diphenol, potassium iodide, tetrabutylammonium bromide, sulphur powder and water are cooled to room temperature after heating reaction in oil bath, are extracted with ethyl acetate
Product out is concentrated under reduced pressure, and then carries out the column chromatographic purifying of product,
(1)
Wherein the end alkene is styrene.
2. method described according to claim 1, is standard based on 2 moles of styrene, the dosage of sulphur powder is 60% to 150%.
Be standard based on 2 moles of styrene 3. method described according to claim 1, the dosage of potassium hydroxide be 50% to
150%。
4. method described according to claim 1, is standard based on 2 moles of styrene, the usage amount of hydroquinone of polymerization retarder is
1% to 5%.
5. method described according to claim 1 is standard, Cu (acac) based on 2 moles of styrene2The usage amount of catalyst is
5% to 25%.
6. method described according to claim 1 is standard, the use of inorganic salts potassium iodide additive based on 2 moles of styrene
Amount is 1 to 4 mole.
7. method described according to claim 1 is standard, phase transfer catalyst tetrabutylammonium bromide based on 2 moles of styrene
Usage amount be 5% to 100%.
8. method described according to claim 1, the concentration of reaction substrate styrene is 0.2 to 0.5 mole/L.
9. method described according to claim 1, the temperature that reaction is heated in oil bath is 80-120 DEG C.
10. method described according to claim 1, the time that reaction is heated in oil bath is 5-48 hours.
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| CN201510180179.8A CN105585554B (en) | 2015-08-26 | 2015-08-26 | A kind of method of copper catalysis water phase end alkene and sulphur powder reaction generation thiphene ring |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1583741A (en) * | 2003-08-21 | 2005-02-23 | 淄博洁鑫化工有限公司 | Preparation of 3-alkylthiophene |
| CN102010282A (en) * | 2010-10-18 | 2011-04-13 | 四川大学 | Method for preparing diaryl disulfide and diaryl diselenide under catalysis of aqueous phase |
| CN102702053A (en) * | 2012-06-25 | 2012-10-03 | 四川大学 | Method for preparing thioacid amide derivatives in aqueous phases |
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2015
- 2015-08-26 CN CN201510180179.8A patent/CN105585554B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1583741A (en) * | 2003-08-21 | 2005-02-23 | 淄博洁鑫化工有限公司 | Preparation of 3-alkylthiophene |
| CN102010282A (en) * | 2010-10-18 | 2011-04-13 | 四川大学 | Method for preparing diaryl disulfide and diaryl diselenide under catalysis of aqueous phase |
| CN102702053A (en) * | 2012-06-25 | 2012-10-03 | 四川大学 | Method for preparing thioacid amide derivatives in aqueous phases |
Non-Patent Citations (2)
| Title |
|---|
| A Practical,One-Pot Synthesis of Highly Substituted Thiophenes and Benzo[b]thiophenes from Bromoenynes and o-Alkynylbromobenzenes;Veronica Guilarte et al.;《Organic Letters》;20110901;第13卷(第19期);第8-10页 |
| 噻吩合成工艺技术进展;徐晓宁;《宁波化工》;20131231(第2期);第5100-5103页 |
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