CN102030602A - Method for synthesizing terminal alkyne by using bromoacetylene compound - Google Patents
Method for synthesizing terminal alkyne by using bromoacetylene compound Download PDFInfo
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- CN102030602A CN102030602A CN2010105451269A CN201010545126A CN102030602A CN 102030602 A CN102030602 A CN 102030602A CN 2010105451269 A CN2010105451269 A CN 2010105451269A CN 201010545126 A CN201010545126 A CN 201010545126A CN 102030602 A CN102030602 A CN 102030602A
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- bromo
- acetylide
- terminal alkyne
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Abstract
The invention belongs to the technical field of organic synthesis intermediates, and in particular relates to a method for synthesizing terminal alkyne by using a bromoacetylene compound. In the method, the terminal alkyne compound is synthesized under an alkaline condition by using the bromoacetylene compound as a raw material. The terminal alkyne is an important organic synthesis intermediate which can be widely applied to synthesis of medicaments, pesticides, materials and functional molecules. The method has the advantages of low cost, easiness of operation, high yield and the like and has broad application prospect.
Description
Technical field
The invention belongs to the organic synthesis intermediate technical field, be specifically related to a kind of method of utilizing the synthetic Terminal Acetylenes of bromo acetylide.
Background technology
Terminal Acetylenes is important organic synthesis intermediate, at aspect extensive application (Barry M. Trost, et al. such as medicine, agricultural chemicals and functional materialss
Angew. Chem. Int. Ed. 2009,
48, 5478-5481.).Terminal Acetylenes participates in 1, and the 3-Dipolar Cycloaddition claims again " click chemistry ", and is synthetic polytype easily 1,2, the 3-triazole compound, and the latter has been widely used in research and development (Franck Amblard, the et al. of newtype drug, agricultural chemicals etc.
Chem. Rev. 2009,
109, 4207-4220.).In addition, Terminal Acetylenes participates in the polyyne based compound of polyreaction preparation, also is widely used in production (Chang-Min XING, the et al. of liquid crystal material etc.
J. Polym. Sci., Part A:Polym. Chem. 2008,
46, 2960-2974.).
From 1, it also is a kind of comparatively common method that 1-two bromo vinyl compounds set out with synthetic terminal alkyne compound.Early stage Corey-Fuchs reaction (E. J. Corey, the et al. that occurs
Tetrahedron Lett. 1972,
13, be to be raw material 3769-3772.), at highly basic with the sym-dibromoethane based compound
nThe BuLi effect is following, reacts to prepare alkynes under-78 ℃.This reaction because
nBuLi alkalescence is extremely strong, and the reaction pair substrate functional group limits more, so have significant limitation on the preparation Terminal Acetylenes.Other similar reactions adopt Grignard reagent as reaction reagent, and the reaction operability is still not good.
The reaction for preparing Terminal Acetylenes from the bromo acetylide is rarely found, and this type of reaction all uses organic super base or Grignard reagent as reaction reagent, has limited the application of this type of reaction to a certain extent.
The present invention from be easy to prepare 1,1-two bromo vinyl compounds set out, and use cheap organic amine to eliminate and obtain the bromo acetylide, and then use the mineral alkali effect, make acetylenebromide protonated, thereby obtain the Terminal Acetylenes product.Entire reaction course is simple to operate, and raw material economics is easy to get, the reaction yield height.
Summary of the invention
The object of the present invention is to provide a kind of method of utilizing the synthetic Terminal Acetylenes of bromo acetylide.
A kind of method of utilizing the synthetic Terminal Acetylenes of bromo acetylide that the present invention proposes, its reaction principle is as follows:
Wherein: R is aryl or alkyl etc.
Concrete synthesis step is as follows:
In closed reactor, add the bromo acetylide
1, alkali and solvent, under greater than 25 ℃ temperature of reaction stirring reaction 1-24 hour, use extracted with diethyl ether after reaction is finished.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out the column chromatography for separation purification with the ethyl acetate/petroleum ether, promptly gets desired product.Wherein, bromo acetylide
1With the mol ratio of alkali be 0.5:1-1:1.
Among the present invention, described bromo acetylide is to toluene acetylenebromide, 1,4-two (2-bromo ethynyl) benzene, 1-bromo-4-phenyl-3-alkene-ethyl acetylene, to chlorobenzene acetylenebromide, 3, in 7-dimethyl-6-alkene-1-octyne base bromine or the phenylacetylene base bromine etc. any.
Among the present invention, described alkali is mineral alkali MxAy, and wherein M is Li
+, Na
+, K
+, Cs
+, Mg
2+, Ca
2+, Sr
2+Or Ba
2+Deng in any; A is CO
3 2-, HCO
3-, SiO
3 2-, Si
2O
5 2-, SiF
2-, B
4O
7 2-, SO
3 2-, HSO
3 -, PO
4 3-, HPO
4 2-, HCOO
-, CH
3COO
-, C
2H
5COO
-, C
3H
7COO
-, C
6H
5O
-, C
6H
5COO
-Or CH
2(COO
-)
2CO
3 2-, HCO
3-, SiO
3 2-, Si
2O
5 2-, SiF
2-, B
4O
7 2-, SO
3 2-, HSO
3 -, PO
4 3-, HPO
4 2-, HCOO
-, CH
3COO
-, C
2H
5COO
-, C
3H
7COO
-, C
6H
5O
-, C
6H
5COO
-Or CH
2(COO
-)
2Preferred alkali is Cs
2CO
3, CsF or K
2CO
3
Among the present invention, described solvent is dimethyl sulfoxide (DMSO), N, dinethylformamide, N,N-dimethylacetamide, N-methyl pyrrole one to multiple kind in alkane ketone, C2-C11 alcohol, C1-C7 halohydrocarbon, C3-C7 ester, C3-C6 ether, C3-C7 ketone, C2-C5 nitrile, benzene or the toluene.Preferred solvent is dimethyl sulfoxide (DMSO) or N, dinethylformamide.
The bromo acetylide that the present invention is easy to get with economy is a raw material, uses the stable mineral alkali of chemical property to do reaction reagent, compares with existing synthetic method, and the inventive method operation is simple and easy, economy, good substrate applicability.
Embodiment
Further specify the present invention below by embodiment, but can not limit content of the present invention.
Embodiment 1: to synthesizing of methylbenzene acetylene
In 60mL tube sealing reaction device, add toluene acetylenebromide 98mg(0.5mmol), cesium carbonate 163mg(0.5mmol), dimethyl sulfoxide (DMSO) 5mL, finish at 15 hours afterreactions of 95 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the sherwood oil, is colourless liquid, 54mg, yield 93%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR(500MHz,?CDCl
3):?
δ?2.34(s,?3H),?3.02(s,?1H),?7.11(d,?
J?=?7.85?Hz,?2H),?7.37(d,?
J?=?8.10?Hz,?2H)。
Embodiment 2:1,4-diacetylene-benzene synthetic
In reactor, add 1,4-two (2-bromo ethynyl) benzene 142mg(0.5mmol), dimethyl sulfoxide (DMSO) 6mL salt of wormwood 207mg(1.5mmol),, finish at 12 hours afterreactions of 135 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the normal hexane, is white crystal, 61mg, yield 90%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR (500MHz, CDCl
3):
δ3.17 (s, 2H), 7.44 (s, 4H).
Embodiment 3: phenyl-1-alkene-3-butine synthetic
In reactor, add 1-bromo-4-phenyl-3-alkene-ethyl acetylene 103mg(0.5mmol), cesium fluoride 304mg(1.0mmol), dimethyl sulfoxide (DMSO) 5mL, finish at 12 hours afterreactions of 105 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the sherwood oil, is light yellow liquid, 63mg, yield 92%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR (500MHz, CDCl
3):
δ3.05 (dd,
J=2.5Hz, 0.5Hz, 1H), 6.11 (d,
J=16.0Hz, 1H), 7.02 (d,
J=16.5Hz, 1H), 7.29-7.39 (m, 5H).
Embodiment 4: to synthesizing of chlorobenzene acetylene
In 60mL tube sealing reaction device, add chlorobenzene acetylenebromide 108mg(0.5mmol), cesium carbonate 163mg(1.25mmol), N, dinethylformamide 5mL, finish at 12 hours afterreactions of 110 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the sherwood oil, is light yellow liquid, 58mg, yield 85%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR(500MHz,?CDCl
3):?
δ?3.10(s,?1H),?7.28(d,?
J?=?8.90?Hz,?2H),?7.40(d,?
J?=?8.90?Hz,?2H)。
Embodiment 5: phenylacetylene synthetic
In 60mL tube sealing reaction device, add phenylacetylene base bromine 91mg(0.5mmol), cesium fluoride 152mg(1mmol), dimethyl sulfoxide (DMSO) 5mL, finish at 10 hours afterreactions of 120 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the sherwood oil, is colourless liquid, 44mg, yield 87%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR(500MHz,?CDCl
3):?
δ?3.06(s,?1H),?7.28-7.34(m,?3H),?7.48-7.50(m,?2H)。
Embodiment 6:3,7-dimethyl-6-alkene-1-octyne synthetic
In 60mL tube sealing reaction device, add 3,7-dimethyl-6-alkene-1-octyne base bromine 108mg(0.5mmol), dimethyl sulfoxide (DMSO) 5mL cesium carbonate 244mg(0.75mmol),, finish at 12 hours afterreactions of 110 ℃ of following stirring reactions, add deionized water to system, with extracted with diethyl ether.Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out column chromatography and purifies and promptly get desired product again with the sherwood oil, is colourless liquid, 60mg, yield 88%.
Its nucleus magnetic hydrogen spectrum data are as follows:
1H-NMR (500MHz, CDCl
3):
δ0.99 (d,
J=6.5Hz, 3H), 1.42-1.49 (m, 1H), 1.61 (s, 3H), 1.68 (s, 3H), 1.94-2.02 (m, 3H), 2.05-2.10 (m, 1H), 2.15-2.20 (m, 1H), 5.08-5.11 (m, 1H).
Claims (4)
1. method of utilizing the synthetic terminal alkyne compound of bromo acetylide is characterized in that the synthetic route of described terminal alkyne compound is as follows:
Wherein: R is aryl or alkyl;
Concrete steps are as follows:
In reactor, add bromo acetylide, alkali and solvent, under greater than 25 ℃ temperature of reaction stirring reaction 1-24 hour, use extracted with diethyl ether after reaction is finished; Organic layer is behind saturated common salt water washing, anhydrous sodium sulfate drying, and the pressure reducing and steaming solvent promptly gets thick product, and thick product is that leacheate carries out the column chromatography for separation purification with the ethyl acetate/petroleum ether, promptly gets desired product; Wherein, the mol ratio of bromo acetylide and alkali is 0.5:1-1:1.
2. the method for utilizing the synthetic terminal alkyne compound of bromo acetylide according to claim 1, it is characterized in that described bromo acetylide is to toluene acetylenebromide, 1,4-two (2-bromo ethynyl) benzene, 1-bromo-4-phenyl-3-alkene-ethyl acetylene, to chlorobenzene acetylenebromide, 3, in 7-dimethyl-6-alkene-1-octyne base bromine or the phenylacetylene base bromine any.
3. the method for utilizing the synthetic terminal alkyne compound of bromo acetylide according to claim 1 is characterized in that described alkali is mineral alkali MxAy; Wherein M is Li
+, Na
+, K
+, Cs
+, Mg
2+, Ca
2+, Sr
2+Or Ba
2+In any; A is CO
3 2-, HCO
3-, SiO
3 2-, Si
2O
5 2-, SiF
2-, B
4O
7 2-, SO
3 2-, HSO
3 -, PO
4 3-, HPO
4 2-, HCOO
-, CH
3COO
-, C
2H
5COO
-, C
3H
7COO
-, C
6H
5O
-, C
6H
5COO
-Or CH
2(COO
-)
2In any.
4. the method for utilizing the synthetic terminal alkyne compound of bromo acetylide according to claim 1, it is characterized in that described solvent dimethyl sulfoxide (DMSO), N, dinethylformamide, N,N-dimethylacetamide, N-methyl pyrrole one to multiple kind in alkane ketone, C2-C11 alcohol, C1-C7 halohydrocarbon, C3-C7 ester, C3-C6 ether, C3-C7 ketone, C2-C5 nitrile, benzene or the toluene.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104003827A (en) * | 2014-06-16 | 2014-08-27 | 厦门大学 | Terminal alkyne synthesizing method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245040A (en) * | 2008-03-20 | 2008-08-20 | 同济大学 | Process for producing 4-ethynyl benzene sulfonamide (I) |
-
2010
- 2010-11-16 CN CN2010105451269A patent/CN102030602A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245040A (en) * | 2008-03-20 | 2008-08-20 | 同济大学 | Process for producing 4-ethynyl benzene sulfonamide (I) |
Non-Patent Citations (3)
| Title |
|---|
| 《J. CHEM. soc. PERKIN TRANS. I》 1989 Derek R. Buckle and Ashley E. Fenwick Synthesis of Analogues of Arachidonic Acid as Potential Inhibitors of Leukotriene Biosynthesis 477-482 3 , * |
| DEREK R. BUCKLE AND ASHLEY E. FENWICK: "Synthesis of Analogues of Arachidonic Acid as Potential Inhibitors of Leukotriene Biosynthesis", 《J. CHEM. SOC. PERKIN TRANS. I》, 1989, pages 477 - 482 * |
| WILLIAM H. OKAMURA,ET AL.: "Synthesis and NMR Studies of 13C-Labeled Vitamin D Metabolites", 《J. ORG. CHEM.》, vol. 67, no. 5, 2002, pages 1637 - 1650, XP008156634, DOI: 10.1021/jo011096y * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104003827A (en) * | 2014-06-16 | 2014-08-27 | 厦门大学 | Terminal alkyne synthesizing method |
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Application publication date: 20110427 |