CN103554094B - One prepares 2, the method for 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) - Google Patents
One prepares 2, the method for 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) Download PDFInfo
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- CN103554094B CN103554094B CN201310580687.6A CN201310580687A CN103554094B CN 103554094 B CN103554094 B CN 103554094B CN 201310580687 A CN201310580687 A CN 201310580687A CN 103554094 B CN103554094 B CN 103554094B
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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Abstract
The invention discloses one and prepare 2, the method for 2 ˊ-dipyridyl-4,4 ˊ-(5-hexyl-2-thiophene), belongs to organic synthesis field.Comprise the steps: 1. zinc chloride, tetrahydrofuran (THF) and form reagent react to be prepared zincon stand-by; 2. under nitrogen protection environment; by 4; 4 ˊ-two bromo-2; 2 ˊ-dipyridyl and zincon are at catalyst system 1; react under 2-two (diphenylphosphine) ethane chlorination nickel, triphenylphosphine and dimethyl formamide; product obtains 2,2 ˊ-dipyridyl-4,4 ˊ-(5-hexyl-2-thiophene) product after the steps such as cooling, filtration, washing, recrystallization are refining.The method raw materials cost is low, and the intermediate of generation is nontoxic, and reaction process is easy to control, and environmental pollution is little, has good industrial value.
Description
Technical field
The invention belongs to organic synthesis field, be specifically related to one and prepare 2, the method for 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene).
Background technology
2,2 '-dipyridyl and derivative thereof are the important chemical industry of a class and medicinal intermediates, there is unique sequestering action, can react with many metal ions and generate metal complex, be widely used in the part of metal catalyst, luminescent material, medicine intermediate, and the numerous areas such as photosensitizer.2,2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) is 2 of a kind of 4,4 ' position replacement, and 2 '-dipyridyl derivatives, can be used as various metals catalyst ligand and use, cause the concern of people's height.
Dipyridyl derivatives synthetic method is the earliest Ullmann reactions, and Suzuki reported Sunuki-Miyaura reaction in 1979 subsequently, and this reaction makes catalyzer with palladium, under triphenylphosphine participates in, and halogenated aromatic coupling.But existing synthetic method exists, and productive rate is large compared with low, expensive catalyst, intermediate toxicity, product is difficult to the problems such as separating-purifying, is unfavorable for suitability for industrialized production.For this reason, be badly in need of at present improving its preparation technology.
Summary of the invention
For the deficiency of existing technique, the object of the invention is to provide that a kind of reaction is mild, toxicity is low, yield is high, and with low cost, there is improving one's methods of higher industrial using value.
For achieving the above object, the present invention with Grignard reagent, 4,4 '-two bromo-2,2 '-dipyridyl is that main raw material prepares 2,2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene).The following technical scheme of concrete employing:
Realized by following two steps:
1. the preparation of zincon: add zinc chloride (ZnCl successively under nitrogen protection in reaction flask
2), tetrahydrofuran (THF) (THF), drip grignard reagent under stirring, 60 ~ 65 DEG C of obtained structures of reaction are stand-by such as formula the zincon of 1.
formula 1)
2. 2, the synthesis of 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene): add 4 successively in reaction flask, 4 '-two bromo-2,2 '-dipyridyl, 1,2-two (diphenylphosphine) ethane chlorination nickel, triphenylphosphine (P (Ph)
3), dimethyl formamide (DMF), slowly drips above-mentioned zincon under nitrogen protection environment; react at 80 ~ 85 DEG C; react complete, by product cooled and filtered, filter cake add after petroleum ether and stirring filter, dry; add methylene dichloride again to dissolve; add activated carbon decolorizing to filter, filter cake washed with dichloromethane, after filtrate evaporate to dryness, recrystallization obtains 2; 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) product.
formula 2)
Above-mentioned steps 1. in the synthesis reference literature Synthesis1993 (11) of Grignard reagent: the method for 1099-1103.
Above-mentioned steps 1. in ZnCl
2should make of anhydrous magnesium sulfate in advance and use except after water treatment.
Above-mentioned steps 2. in 4,4 '-two bromo-2, the synthesis reference literature InorganicChemistry2011 of 2 '-dipyridyl, the method for 50 (8), 3271 – 3280.
Above-mentioned steps 2. in 4,4 '-two bromo-2,2 '-dipyridyl, 1,2-two (diphenylphosphine) ethane chlorination nickel, P (Ph)
3, DMF mass ratio be: 1:0.01 ~ 0.1:2 ~ 5:5 ~ 20.
Above-mentioned steps 2. in zincon add-on be 4,4 '-two bromo-2,2 ~ 5 times of 2 '-dipyridyl quality.
The consumption of above-mentioned steps 2. PetroChina Company Limited.'s ether is 3 ~ 8 times of solid masses.
Above-mentioned steps 2. in add methylene dichloride amount be 4 ~ 10 times of solid masses, the amount of gac is 0.03 ~ 0.1 times of solid masses;
Above-mentioned steps 2. middle recrystallization is that wherein the volume ratio of ethyl acetate and sherwood oil is 1:2 ~ 5 with ethyl acetate, a certain proportion of mixed solution crystallization of sherwood oil.
The present invention, on the basis of existing preparation method, makes further research its synthesis condition and technique and improves, make reaction pollute little, toxicity is low, yield is high, the cheap and excellent catalytic effect of the catalyzer of use.Such as, in (1) existing document conventional tin reagent toxicity is large, and easily makes people produce anaphylaxis, and step of the present invention 1. middle zincon toxicity of synthesizing is little, excellent catalytic effect, safe preparation process.(2) step of the present invention 2. in use cheap 1, two (diphenylphosphine) ethane chlorination nickel of 2-replaces expensive Palladous chloride to make catalyzer, greatly reduce cost, and total yield of products is increased to more than 80% by 58% after improving, catalytic effect is obvious and product separation method of the present invention is effectively simple and easy, is different from the column chromatography process for purification in document.Cost of the present invention reduces, environmental friendliness, has better effect to industrial amplification production.
Accompanying drawing explanation
Fig. 1 is the nuclear magnetic resonance map of the compounds of this invention that embodiment 1 obtains.
Embodiment
Below by way of several preferred embodiment, synthetic method of the present invention is described in further detail, but protection scope of the present invention is not limited thereto.
Embodiment 1
1. the preparation of zincon: add zinc chloride (ZnCl successively under nitrogen protection in reaction flask
2) 100g, tetrahydrofuran (THF) (THF) 400g, stir lower dropping grignard reagent 200g, after 65 DEG C of reaction 1h, obtained zincon 229g is stand-by.
2. 2, the synthesis of 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene): add 4 successively in reaction flask, 4 '-two bromo-2,2 '-dipyridyl 57g, 1,2-two (diphenylphosphine) ethane chlorination nickel 1.1g, triphenylphosphine (P (Ph)
3) 170g; dimethyl formamide (DMF) 570g; slowly zincon 229g is dripped under nitrogen protection environment; react complete after reacting 1h at 80 DEG C; by product cooled and filtered; filter cake adds sherwood oil 580g and stirs rear filtration, drying; add methylene dichloride 585g again to dissolve; add gac 5.85g decolorization filtering; filter cake methylene dichloride 117g washs; after filtrate evaporate to dryness, recrystallization (ethyl acetate: sherwood oil=1:4) obtains 2,2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) product 100.6g(yield 86%).Nuclear magnetic resonance map: 1HNMR (CDCl3): δ=8.62(d, 2H), 8.58(s, 2H), 7.48(d, 2H), 7.45(d, 2H), 6.82(d, 2H), 2.85(m, 4H), 1.72(m, 4H), 1.41-1.32(m, 12H), 0.90(m, 6H).
Embodiment 2
1. the preparation of zincon: add zinc chloride (ZnCl successively under nitrogen protection in reaction flask
2) 200g, tetrahydrofuran (THF) (THF) 800g, stir lower dropping grignard reagent 400g, after 60 DEG C of reaction 1.5h, obtained zincon 450g is stand-by.
2. 2, the synthesis of 2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene): add 4 successively in reaction flask, 4 '-two bromo-2,2 '-dipyridyl 114g, 1,2-two (diphenylphosphine) ethane chlorination nickel 6.8g, triphenylphosphine (P (Ph)
3) 342g; dimethyl formamide (DMF) 1710g; slowly zincon 450g is dripped under nitrogen protection environment; react complete after reacting 1h at 80 DEG C; by product cooled and filtered; filter cake adds sherwood oil 1170g and stirs rear filtration, drying; add methylene dichloride 1170g again to dissolve; add gac 11.7g decolorization filtering; filter cake methylene dichloride 250g washs; after filtrate evaporate to dryness, recrystallization (ethyl acetate: sherwood oil=1:5) obtains 2,2 '-dipyridyl-4,4 '-(5-hexyl-2-thiophene) product 206g(yield 88%).
Claims (3)
1. the preparation method of a dipyridyl-4,4'-(5-hexyl-2-thiophene), be is characterized in that, realized by following steps:
1. the preparation of zincon: add zinc chloride, tetrahydrofuran (THF) successively under nitrogen protection in reaction flask, drips grignard reagent under stirring, 60 ~ 65 DEG C of reactions, and obtained structure is stand-by such as formula the zincon of 1;
Formula 1
2. 2, 2'-dipyridyl-4, the synthesis of 4'-(5-hexyl-2-thiophene): add 4 successively in reaction flask, 4'-bis-bromo-2, 2'-dipyridyl, 1, two (diphenylphosphine) ethane chlorination nickel of 2-, triphenylphosphine, dimethyl formamide, slowly above-mentioned zincon is dripped under nitrogen protection environment, react at 80 ~ 85 DEG C, react complete, by product cooled and filtered, filter cake filters after adding petroleum ether and stirring, dry, add methylene dichloride again to dissolve, add activated carbon decolorizing to filter, filter cake washed with dichloromethane, after filtrate evaporate to dryness, recrystallization obtains 2, 2'-dipyridyl-4, 4'-(5-hexyl-2-thiophene) product.
2. as claimed in claim 12,2'-dipyridyl-4, the preparation method of 4'-(5-hexyl-2-thiophene), it is characterized in that, step 2. in 4, the mass ratio of bromo-2, the 2'-dipyridyls of 4'-bis-, 1,2-two (diphenylphosphine) ethane chlorination nickel, triphenylphosphine, dimethyl formamide is: 1:0.01 ~ 0.1:2 ~ 5:5 ~ 20.
3. the preparation method of 2,2'-dipyridyls-4,4'-(5-hexyl-2-thiophene) as claimed in claim 1, is characterized in that, step 2. middle zincon add-on is 2 ~ 5 times of bromo-2, the 2'-dipyridyl quality of 4,4'-bis-.
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| WO2012155247A1 (en) * | 2011-05-13 | 2012-11-22 | Uti Limited Partnership | Cyclometalated transition metal dyes |
| CN103275052A (en) * | 2013-05-24 | 2013-09-04 | 陕西师范大学 | Method for synthesizing isoflavone by nickel-catalyzed Negishi cross coupling reaction at room temperature |
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| CN101514196A (en) * | 2009-04-02 | 2009-08-26 | 长兴化学工业股份有限公司 | Thiophene derivative and application thereof |
| WO2012085170A2 (en) * | 2010-12-22 | 2012-06-28 | Haag Benjamin | Process for making organoboron compounds, products obtainable thereby, and their use |
| CN102643284A (en) * | 2011-02-17 | 2012-08-22 | 兰州大成科技股份有限公司 | Preparation method and application of 4,9-bisalkylene indene thieno[3,2-b]thiophene derivative and conjugated polymer thereof |
| WO2012155247A1 (en) * | 2011-05-13 | 2012-11-22 | Uti Limited Partnership | Cyclometalated transition metal dyes |
| CN103275052A (en) * | 2013-05-24 | 2013-09-04 | 陕西师范大学 | Method for synthesizing isoflavone by nickel-catalyzed Negishi cross coupling reaction at room temperature |
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Address after: No. 6, No. 4, No. 52, No. 4, Huang Yang Street, high tech Zone, Zhengzhou, Henan Province, 41 Patentee after: Zhengzhou principle Biological Technology Co., Ltd. Address before: 450001 Henan Zhengzhou hi tech Zone Ruida road science and technology venture square 2 building B918 Patentee before: Zhengzhou Sigma Chemical Co., Ltd. |
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Effective date of registration: 20200615 Address after: 476000 east section, south side of Gongye Road, Xiayi County, Shangqiu City, Henan Province Patentee after: Shanghai Huiren Pharmaceutical Co.,Ltd. (Xia Yi) Address before: No. 6, No. 4, No. 52, No. 4, Huang Yang Street, high tech Zone, Zhengzhou, Henan Province, 41 Patentee before: ZHENGZHOU YUANLI BIOLOGICAL TECHNOLOGY Co.,Ltd. |