CN105585554A - Method for catalyzing terminal alkene and powdered sulfur with copper to react in water phase to generate thiophene ring - Google Patents
Method for catalyzing terminal alkene and powdered sulfur with copper to react in water phase to generate thiophene ring Download PDFInfo
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- CN105585554A CN105585554A CN201510180179.8A CN201510180179A CN105585554A CN 105585554 A CN105585554 A CN 105585554A CN 201510180179 A CN201510180179 A CN 201510180179A CN 105585554 A CN105585554 A CN 105585554A
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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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- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a method for catalyzing terminal alkene and powdered sulfur to react in a pure water phase to prepare a thiophene derivative. A water-soluble complex is used as a catalyst, and a one-pot reaction is conducted in the pure water phase to prepare the thiophene compound. The novel method for preparing the substituent thiophene compound is environmentally friendly, convenient to operate, safe and cheap, and raw materials are simple. Compared with the prior art, the method can be suitable for multiple functional groups, the initial raw materials are simple, and the method is easy to operate and environmentally friendly. The formula is shown in the description.
Description
Technical field
The invention belongs to the synthetic method field that learns a skill, relate to the formation field of the coupling of C-S key, thiphene ring, is that one is urgedBe combined to the method for thiphene ring.
Background technology
The application of thiophene-based material in pharmaceutical chemistry and materials chemistry is very extensive. For example, thiophene is as Evista(reloxifen), Duloxetine (Cymbalta), Tiotropium Bromide (Spiriva), cosopts (dorzolamide) etc. are severalThe backbone structure of important medicine. Synthetic said medicine is used simple thiophene as raw material conventionally. [M.D.Dhanaraju,Y.R.Rani,G.Thirumurugan,PharmaciaLettre.2009,1,219-226;J.L.Pilgrim,Dimitri.Gerostamoulos,O.H.Drummer,ForensicScienceInternational,2014,234,165-173;G.M.Keating,Drugs,2012,72,273-300;C.Plummer, E.MacKay, K.Gelatt, VetOphthalmol, 2006,9,245 – 249.] can haveEffect the synthetic organic compound that contains thiphene ring and meet Atom economy, Green Chemistry, the simple method of methodScholar's extensive concern. Because the compound containing thiphene ring is also very extensive in the application aspect material. Luminous such as can be used forDiode material, field-effect transistor, solar cell. [R.Jin, S.Tang, D.Luo, JournalofMolecularModeling,2014,20,1-10;A.Hoppe,T.Balster,T.Muck,V.Wagner,OrganicElectronics,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 compounds has much at present, mainly comprises Gewald reaction, and Willgerodt – Kindle is anti-Should, Paul-Knorr reaction, fluorine synthesizes agreement, sulfur auxiliary reaction, electricity-hydrophiling and directly arylation method etc.[K.Gewald,E.Schinke,H.B?ttcher,Ber.1966,99,94-100；K.Willgerodt,BerDtschChemGes,1888,431,534–536;G.Minetto,L.F.Raveglia,A.Sega,M.Taddei,EurJOrgChem,2005,24,5277–5288;Z.Kaleta,B.T.Makowski,T.Soos,R.Dembinski,OrgLett,2006,8,1625–1628;H.F.Guo,H.Y.Shao,Z.Y.Yang,JMedChem,2010,53,1819–1829;B.Godoi,R.F.Schumacher,G.Zeni,ChemRev,2011,111,2937–2980;A.Ohta,T.Akia,T.Ohkuwa,M.Chiba,Heterocycles, 1990,31,1951 – 1958.] but the initiation material that these methods have preparation is complicated, some atomsLess economical, the poisonous and hazardous organic solvent of some uses, the complicated harshness of the reaction condition having.
Summary of the invention
The object of invention is to have developed an aqueous phase reactions system herein, with one kettle way synthesizing thiofuran compounds. With existingHave synthesizing thiofuran class material to compare, the feature of this system maximum is environmental friendliness, and initiation material is simple and easy to get, avoids in addition usingNoble metal, equipment requirement are not high. This operation is simple, cheap, it is little to pollute, and substrate expansion is also very extensive, can reach goodGood productive rate.
Technical scheme of the present invention is specific as follows:
Described object is one kettle way synthesizing thiofuran compounds under catalyst action at water middle-end alkene and sulphur powder, when reaction asUnder:
Its middle-end alkene can be aliphatic end alkene, also can be non-substitutedly or with the aromatic series end alkene of chlorine, bromine, methyl, ethyl, replacesBase can be positioned at neighbour, and contraposition.
Reaction system is implemented under inorganic base or organic base existence, and inorganic base can be NaOH, potassium hydroxide, carbonic acidPotassium, sodium carbonate, sodium acid carbonate, saleratus, sodium tert-butoxide, potassium tert-butoxide, potassium phosphate, potassium dihydrogen phosphate etc., organic base can beTriethylamine, tripropyl amine (TPA), pyridine, DBU, DBN, DMAP etc. Preferably NaOH, potassium hydroxide.
Reaction system is implemented under inorganic additives exists, and inorganic salts can be potassium fluoride, sodium fluoride, potassium chloride, chlorinationSodium, KBr, sodium bromide, KI, sodium iodide, preferably KI, sodium iodide.
In preferred version of the present invention, be standard based on 2 moles of styrene, the consumption of sulphur powder is 1 to 5 mole, more excellentElect 1.2 to 3.0 moles as.
In preferred version of the present invention, be that the consumption of alkali is 0.5 to 5 described in standard based on 2 moles of styrene, be preferably1 to 3 mole.
In preferred version of the present invention, be standard based on 2 moles of styrene, the use amount of polymerization inhibitor is 0.001 to 0.2Mole, preferably 0.02-0.1 mole.
In preferred version of the present invention, be standard based on 2 moles of styrene, the use amount of copper catalyst is 0.001 to 1Mole, preferably 0.01 to 0.5 mole.
In preferred version of the present invention, be standard based on 2 moles of styrene, the use amount of nitrogen ligand is 0.001 to 1 to rubYou, preferably 0.01 to 0.5 mole.
In preferred version of the present invention, be standard based on 2 moles of styrene, the use amount of phase transfer catalyst is 0 to 3Mole, be preferably 0.1 to 2 mole.
In preferred version of the present invention, be standard based on 2 moles of styrene, the use amount of inorganic additives is 0 to 6Mole, be preferably 1 to 4 mole.
Amount ranges as the water of solvent is wider, the concentration of reaction substrate (styrene) be preferably 0.2 to 2 mole/L, more preferably 0.2 to 0.5 mole/L.
In preferred version of the present invention, reaction temperature is 30 to 160 DEG C, preferably 50-140 DEG C, and more preferably 80-120 DEG CUnder condition, implement.
In preferred version of the present invention, the reaction time is 1-60 hour, is preferably 5-48 hour.
The technique effect that the present invention is useful is:
1, the invention provides a kind of method of brand-new synthesizing thiofuran ring, the feature of this method is that initiation material is simpleBe easy to get and do 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, and post processing is simple.
4, copper catalyst and nitrogen ligand that the present invention adopts business to be easy to get, good economy performance.
Brief description of the drawings
Fig. 1: the preparation of compound diphenyl thiophene1HNMR
Fig. 2: the preparation of compound diphenyl thiophene13CNMR
Fig. 3: the preparation of compound two (p-methylphenyl) thiophene1HNMR
Fig. 4: the preparation of compound two (p-methylphenyl) thiophene13CNMR
Fig. 5: the preparation of compound two (rubigan) thiophene1HNMR
Fig. 6: the preparation of compound two (rubigan) thiophene13CNMR。
Detailed description of the invention
Embodiment 1: the preparation of diphenyl thiophene: add styrene 2mmol (208mg) in reaction vessel, Cu (acac)20.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinones 0.02mmol (2mg), KI 2mmol (332mg),TBAB 1mmol (322mg), sulphur powder 3mmol (96mg), adds 8ml water. In 120 DEG C of oil baths, react 24 hours, coldBut to room temperature, after being extracted with ethyl acetate, reduced pressure concentration. Product, through column separating purification, obtains white solid, productive rate 72%(GC:2,4-diphenyl thiophene: 2,5-diphenyl thiophene=3:1).1HNMR(400MHz,CDCl3)δ7.82-7.58(m,5H,ArH),7.57-7.38(m,5H,ArH),7.35-7.28(m,2H,ArH);13CNMR(100MHz,CDCl3)δ145.12,143.19,135.93,134.39,128.99,127.65,127.32,126.38,125.59,122.39,119.78;GC-MSm/z236.
The preparation of 2: two (p-methylphenyl) thiophene of embodiment: add 4-methyl styrene 2mmol in reaction vessel(236mg), Cu (acac) 20.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinones 0.02mmol (2mg), iodineChange potassium 2mmol (332mg), TBAB 1mmol (322mg), sulphur powder 3mmol (96mg), adds 8ml water. At 120 DEG C of oilIn bath, react 24 hours, be cooled to room temperature, after being extracted with ethyl acetate, reduced pressure concentration. Product, through column separating purification, obtains whiteLook solid, productive rate 78%(GC:2,4-bis-(p-methylphenyl) thiophene: 2,5-bis-(p-methylphenyl) thiophene=6:1).1HNMR(400MHz,CDCl3)δ=7.61–7.53(m,5H),7.39(ddd,J=8.6,5.7,3.0,5H),2.20(s,6H).；13CNMR(100MHz,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-MSm/z264.
The preparation of 3: two (rubigan) thiophene of embodiment: add 4-chlorostyrene 2mmol (278mg) in reaction vessel, Cu(acac)20.2mmol (53mg), potassium hydroxide 2mmol (112mg), hydroquinones 0.02mmol (2mg), KI 2mmol(332mg), TBAB 1mmol (322mg), sulphur powder 3mmol (96mg), adds 8ml water. In 120 DEG C of oil baths, react24 hours, be cooled to room temperature, after being extracted with ethyl acetate, reduced pressure concentration. Product, through column separating purification, obtains white solid,Productive rate 83%(GC:2,4-bis-(rubigan) thiophene: 2,5-bis-(rubigan) thiophene=8:1).1HNMR(400MHz,CDCl3)δ7.62-7.53(m,5H,ArH),7.44-7.36(m,5H,ArH);13CNMR(100MHz,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. copper catalysis water end alkene and the reaction of sulphur powder generate a method for thiphene ring, and it comprises the following steps: pure water middle water mutuallyDissolubility cupric coordination compound for catalysis end alkene and sulphur powder one pot reaction are prepared the method for thiophenes, as figure below chemical reactionFormula, its synthetic concrete steps are: in reaction vessel, add end alkene, sulphur powder, the water-soluble complex of catalytic amount, inorganicAlkali, phase transfer catalyst, water, is cooled to room temperature after adding thermal response in oil bath, is extracted with ethyl acetate out product, reduces pressure denseContracting, then carries out the column chromatography purification of product, wherein alkene can be aliphatic end alkene, also can be non-substituted or with chlorine, bromine, firstThe aromatic series end alkene of base, ethyl, substituting group can be positioned at neighbour, and contraposition
。
2. according to method described in claim (1), be standard based on 2 moles of styrene, the consumption of sulphur powder more preferably 60% to150% mole.
3. according to method described in claim (1), be that the consumption of alkali is 50% to 150% described in standard based on 2 moles of styrene.
4. according to method described in claim (1), be standard based on 2 moles of styrene, the use amount of polymerization inhibitor is 1% to 5%Mole.
5. according to method described in claim (1), be standard based on 2 moles of styrene, the use amount of copper catalyst be 5% to25% mole.
6. according to method described in claim (1), be standard based on 2 moles of styrene, the use amount of nitrogen ligand be 10% to50% mole.
7. according to method described in claim (1), be standard based on 2 moles of styrene, the use amount of phase transfer catalyst is5% to 100% mole.
8. according to method described in claim (1), wider as the amount ranges of the water of solvent, reaction substrate (styrene)Concentration be preferably 0.2 to 0.5 mole/L.
9. according to method described in claim (1), reaction temperature is to implement under 80-120 DEG C of condition.
10. according to method described in claim (1), be preferably 5-48 hour.
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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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| CN105585554B CN105585554B (en) | 2019-03-05 |
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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 |
|---|
| VERONICA GUILARTE ET AL.: "A Practical,One-Pot Synthesis of Highly Substituted Thiophenes and Benzo[b]thiophenes from Bromoenynes and o-Alkynylbromobenzenes", 《ORGANIC LETTERS》 * |
| 徐晓宁: "噻吩合成工艺技术进展", 《宁波化工》 * |
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Granted publication date: 20190305 Termination date: 20190826 |