CN102898343B - Method for preparing poly-substituted pyrrole derivatives - Google Patents

Method for preparing poly-substituted pyrrole derivatives Download PDF

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CN102898343B
CN102898343B CN201210390160.2A CN201210390160A CN102898343B CN 102898343 B CN102898343 B CN 102898343B CN 201210390160 A CN201210390160 A CN 201210390160A CN 102898343 B CN102898343 B CN 102898343B
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benzyl
cuprous
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CN102898343A (en
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席婵娟
周逸清
陈超
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Tsinghua University
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Abstract

The invention discloses a method for preparing poly-substituted pyrrole derivatives, which comprises the following steps of: reacting zirconocene prepared in situ with cuprous salts for 5 to 15 minutes, adding azide compounds, reacting at 45 to 60 DEG C for 3h-24h, quenching the reaction, extracting the reaction solution, washing the product of the reaction, drying the product, concentrating the product and purifying the product to obtain finished product. The synthesis method of the poly-substituted pyrrole derivative prepared by the invention is scientific and reasonable, and can synthesize poly-substituted pyrrole derivatives with various substituents, which cannot be synthesized by other methods. And the method has high yield and high selectivity, and products are easy to purify.

Description

The preparation method of polysubstituted pyrrole derivative
Technical field
The present invention relates to a kind of preparation method of polysubstituted pyrrole derivative.
Background technology
Pyrrole derivative is the important penta azacyclo compound of a class, it is widely used in medicine and Materials science research field, as the important intermediate of pyrrole derivative as fine chemical product, in household chemicals, food, agricultural chemicals, coating, weaving, papermaking, macromolecular material, sensitive materials, there is purposes widely.In the complete synthesis process of some natural product, synthesizing of pyrroles's segment is also most important in addition.Therefore, one of synthetic priority research areas that always is chemist research of pyrroles.
Laboratory pyrroles's preparation method has: 1) Isosorbide-5-Nitrae-dicarbonyl compound reacts and produces with ammonia or amine; 2) keto-amine and alpha-methylene ketone carry out condensation reaction; 3) 'beta '-ketoester reacts synthetic substituted azole with ammonia (primary amine) and α-halogenatedketone; 4) Isosorbide-5-Nitrae dihalo-1,3-butadiene and amine reacts.Although above preparation method is widely used in the preparation of pyrrole derivative, because raw material obtains relatively difficulty, practical application prepared by pyrrole derivative, the particularly preparation of some polysubstituted pyrrole derivatives and application have been limited.
Summary of the invention
The object of this invention is to provide a kind of easy and simple to handle, method of preparing polysubstituted pyrrole derivative that efficiency is higher.
The method of preparing polysubstituted pyrrole derivative (structural formula is suc as formula shown in I or formula II) provided by the present invention, comprise the steps: the compound shown in formula III or formula IV first to turn metal reaction with cuprous salt, and then add the triazo-compound shown in formula V to react, reaction finishes rear cancellation reaction, obtains described polysubstituted pyrrole derivative.Above-mentioned reaction completes at one pot.
Figure BDA00002256497600011
(formula I) (formula II) (formula III) (formula IV) (formula V)
In above-mentioned formula I, R 1straight chained alkyl, tolyl or benzyl for C1-C6; R 2, R 3, R 4, R 5all independently selected from any one in following radicals: the straight chained alkyl of H, C1-C6, phenyl, tolyl and TMS base (trimethyl silicon based).
In above-mentioned formula II, R 1, R 2, R 5definition cotype I.
In above-mentioned formula III, R 2, R 3, R 4, R 5definition cotype I.
In above-mentioned formula IV, R 2, R 5definition cotype I.
In above-mentioned formula V, R 1definition cotype I.
Zirconium heterocyclic pentylene shown in above-mentioned formula III or formula IV is synthetic in tetrahydrofuran solution by low price zirconium and two molecule alkynes or diine.Reference is as follows: T.Takahashi, D.R.Swanson, E.Negishi, Chem.Lett., 1987,623; E.Negishi, D.R.Swanson, F.E.Cederbaum, T.Takahashi, Tetrahedron Lett., 1986,27,2829.
Described solvents tetrahydrofurane needs to process through anhydrous and oxygen-free before use.Anhydrous and oxygen-free treating processes is the general method that adopts anhydrous and oxygen-free solvent, under high pure nitrogen, to being furnished with in three mouthfuls of round-bottomed flasks of reflux condensing tube and vent piston, add commodity tetrahydrofuran (THF), sodium Metal 99.5, after reflux 4-5 hour, distillation is then preserved under nitrogen.
Described cuprous salt can be selected from following any one: cuprous chloride, cuprous bromide, cuprous iodide or cuprous cyanide.
The described reaction times that turns metal reaction is 5-15 minute.
The described temperature of reaction that adds the triazo-compound shown in formula V to react can be 45-60 ℃, and the reaction times can be 3-24 hour.
In described method, material molar ratio is followed successively by: zirconium heterocyclic pentylene: cuprous salt: triazo-compound=1.0: 2.0-2.2: 1.1-1.3.
Described reaction can be by adding sodium hydrogen carbonate solution or water to carry out cancellation in reaction solution.
After reaction terminating, generally also need to obtain product through purge processes such as extraction, washing, dry, concentrated and column chromatographies.Described extraction be take ether and is carried out as extraction agent; Washing comprises twice of washing and saturated common salt washing once; Dry is that to take anhydrous magnesium sulfate or anhydrous sodium sulphate be siccative, dry about 30 minutes; Filter, concentrate employing air distillation, underpressure distillation or rotary evaporation method etc. by solvent evaporate to dryness; It is separation resin that column chromatography be take 200-300 order silica gel, and eluent can be selected the saturated alkanes such as sherwood oil, hexane, pentane.
The synthetic method of polysubstituted pyrrole derivative provided by the present invention is scientific and reasonable, can synthesize and obtain various substituent polysubstituted pyrrole derivative that has that other method can not synthesize, but also have, synthetic yield is high, product is easy to the features such as purifying.
Accompanying drawing explanation
Fig. 1 is the compound of embodiment 1 preparation 1hNMR collection of illustrative plates.
Fig. 2 is the compound of embodiment 2 preparation 1hNMR collection of illustrative plates.
Fig. 3 is the compound of embodiment 8 preparation 1hNMR collection of illustrative plates.
Fig. 4 is the compound of embodiment 12 preparation 1hNMR collection of illustrative plates.
Embodiment
Below by specific embodiment, method of the present invention is described, but the present invention is not limited thereto.
Experimental technique described in following embodiment, if no special instructions, is ordinary method; Described reagent and material, if no special instructions, all can obtain from commercial channels.
The alkyl diazoimide compounds using in the following example is made according to literature method in acetone by alkyl bromide compound and sodiumazide.The aryl azide compounds using by the synthetic diazonium salt of aniline and Sodium Nitrite after, add after sodiumazide and react and prepare gained.Two compounds are all to make according to following document: S.W.Kwok, J.R.Fotsing, R.J.Fraser, V.O.Rodionov, V.V.Fokin, Org.Lett.2010,12,4217; A.R.Katrizky, K.Widyan, K.Kirichenko, J.Org.Chem.2007,72,5802.Alkyl bromide compound, sodiumazide, aniline and Sodium Nitrite all can obtain from commercial channels
In following embodiment, tetrahydrofuran (THF) used is all processed through anhydrous and oxygen-free before using.
Embodiment 1,1-benzyl-2,3,4,5-tetraethyl-pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=ethyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 3-hexin (1mmol, 114 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetraethyl-pyrroles 87.5mg, isolated yield 65%.
1-benzyl-2,3,4,5-tetraethyl-pyrroles's Structural Identification
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.16-7.29 (m, 3H), 6.83 (d, J=6.9Hz, 2H), 5.00 (s, 2H), 2.40-2.47 (m, 8H), 1.31 (t, J=7.5Hz, 6H), 0.97 (t, J=7.5Hz, 6H); 13cNMR (CDCl 3, 75MHz) δ 140.2,128.8,128.6,126.8,125.8,119.6,46.6,18.0,17.9,17.4,16.0.
GC-MS data: m/z=269
Analytical results shows, the object product of acquisition is correct.
Embodiment 2,1-benzyl-2,3,4,5-tetrapropyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 100.3mg, isolated yield 62%.
1-benzyl-2,3,4,5-tetrapropyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.19-7.27 (m, 3H), 6.79 (d, J=6.9Hz, 2H), 4.98 (s, 2H), 2.32-2.37 (m, 8H), 1.48 (q, J=8.8Hz, 4H), 1.32 (q, J=7.8Hz, 4H), 0.96 (t, J=6.9Hz, 6H), 0.84 (t, J=7.3Hz, 6H); 13c NMR (CDCl 3, 75MHz) δ 140.3,128.5,127.8,126.7,125.6,118.5,46.7,27.4,27.1,25.5,24.5,14.6,14.3.
GC-MS data: m/z=325
Analytical results shows, the object product of acquisition is correct.
Embodiment 3,1-benzyl-2,3,4,5-tetrabutyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=butyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 5-decine (1mmol, 180 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 114.6mg, isolated yield 60%.
1-benzyl-2,3,4,5-tetrabutyl pyrroles's Structural Identification: nuclear magnetic resonance data 1h NMR (CDCl 3, 300MHz) δ 7.19-7.27 (m, 3H), 6.80 (d, J=7.3Hz, 2H), 4.98 (s, 2H), 2.34-2.38 (m, 8H), 1.36-1.50 (m, 8H), 1.23-1.33 (m, 8H), 0.95 (t, J=7.3Hz, 6H), 0.82 (t, J=7.3Hz, 6H; 13c NMR (CDCl 3, 75MHz) δ 140.3,128.5,127.7,126.7,125.6,118.5,46.7,34.7,33.4,24.8,24.6,23.2,22.8,14.2,13.9.
GC-MS data: m/z=381
Analytical results shows, the object product of acquisition is correct.
Embodiment 4,1-benzyl-2,3,4,5-tetraphenyl pyrroles's preparation (R in structural formula I in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=phenyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add tolane (1mmol, 178mg), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains yellow solid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetraphenyl pyrroles 94.6mg, isolated yield 41%.
1-benzyl-2,3,4,5-tetraphenyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 6.87-7.21 (m, 25H), 5.10 (s, 2H). 13cNMR (CDCl 3, 75MHz) δ 139.2,135.6,132.8,132.0,131.6,130.9,128.2,128.0,127.4,127.3,126.7,126.0,125.1,122.6,48.2.
ESI data: m/z=461
Analytical results shows, the object product of acquisition is correct.
Embodiment 5,1-benzyl-2,3,4,5-tetramethylphenyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=tolyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add xylyl acetylene (1mmol, 206mg), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains faint yellow solid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetramethylphenyl pyrroles 131.8mg, isolated yield 51%.
1-benzyl-2,3,4,5-tetramethylphenyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 6.76-7.17 (m, 21H), 5.05 (s, 2H), 2.28 (s, 6H), 2.23 (s, 6H). 13c NMR (CDCl 3, 75MHz) δ 139.7,136.9,134.3,133.0,131.8,131.5,130.8,130.1,128.8,128.3,128.2,126.7,126.2,122.4,48.2,21.4,21.3.
ESI data: m/z=517
Analytical results shows, the object product of acquisition is correct.
Embodiment 6,1-benzyl-2,3-dibutyl-4,5-dipropyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=butyl, R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently ethylmagnesium chloride tetrahydrofuran solution (2M, 1.2mmol, 0.60mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (0.5mmol, 71 μ L), at room temperature react one hour, then add 5-decine (0.5mmol, 90 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3-dibutyl-4,5-dipropyl pyrroles 93.4mg, isolated yield 53%.
1-benzyl-2,3-dibutyl-4,5-dipropyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.18-7.27 (m, 3H), 6.79 (d, J=6.9Hz, 2H), 4.97 (s, 2H), 2.32-2.37 (m, 8H), 1.25-1.50 (m, 12H), 0.92-0.97 (m, 6H), 0.78-0.86 (m, 6H); 13c NMR (CDCl 3, 75MHz) δ 140.3,128.5,127.7,127.6,126.7,125.6,118.6,118.4,46.7,34.7,33.4,27.4,27.1,25.5,24.8,24.6,24.5,23.2,22.8,14.6,14.3,14.2,13.9.
GC-MS data: m/z=353
Analytical results shows, the object product of acquisition is correct.
Embodiment 7,1-benzyl-2,3-diethyl-4, the preparation of 5-Diphenyl Pyrrole (R in structural formula I 1=benzyl, R 2=R 3=ethyl, R 4=R 5=phenyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently ethylmagnesium chloride tetrahydrofuran solution (1.2mmol, 0.60mL), remain on-78 ℃ of reactions after one hour, add tolane (0.5mmol, 89mg), at 0 ℃, react three hours, then add 3-hexin (0.5mmol, 57 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mgg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3-diethyl-4,5-Diphenyl Pyrrole 113.2mg, isolated yield 62%.
1-benzyl-2,3-diethyl-4, the Structural Identification of 5-Diphenyl Pyrrole:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.06-7.28 (m, 13H), 6.88 (d, J=6.9Hz, 2H), 5.07 (s, 2H), 2.54 (t, J=7.6Hz, 4H), 1.02-1.11 (m, 6H); 13c NMR (CDCl 3, 76MHz) δ 139.8,137.0,133.1,131.4,131.1,130.4,130.3,128.5,127.9,127.7,126.8,126.6,125.8,125.1,122.7,121.0,47.6,18.1,17.9,16.8,15.5.
GC-MS data: m/z=365
Embodiment 8,2-benzyl-1,3-diethyl-4, the preparation (R in formula II of 5,6,7-tetrahydrochysene isoindole 1=benzyl, R 2=R 5=ethyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 3, 9-12 carbon diine (0.5mmol, 98 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 2-benzyl-1 that purity is greater than 99%, 3-diethyl-4,5,6,7-tetrahydrochysene isoindole 85.5mg, isolated yield 64%.
2-benzyl-1,3-diethyl-4, the Structural Identification of 5,6,7-tetrahydrochysene isoindole:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.18-7.29 (m, 3H), 6.90 (d, J=7.3Hz, 2H), 5.01 (s, 2H), 2.51 (br, 4H), 2.43 (q, J=7.3Hz, 4H), 1.73-1.78 (m, 4H), 0.97 (t, J=7.8Hz, 6H). 13c NMR (CDCl 3, 75MHz) δ 139.9,128.5,127.2,126.8,125.8,114.8,46.4,24.4,21.8,18.0,14.8.
GC-MS data: m/z=267
Analytical results shows, the object product of acquisition is correct.
Embodiment 9,1-benzyl-2,3-phenylbenzene-5-butyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=phenyl, R 4=hydrogen, R 5=butyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently ethylmagnesium chloride tetrahydrofuran solution (2M, 1.2mmol, 0.60mL), remain on-78 ℃ of reactions after one hour, add tolane (0.5mmol, 89mg), at 0 ℃, react one hour, then add 1-hexin (0.5mmol, 57 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3-phenylbenzene-5-butyl pyrroles 87.7mg, isolated yield 48%.
1-benzyl-2,3-phenylbenzene-5-butyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 6.91-7.28 (m, 15H), 6.31 (s, 1H), 5.01 (s, 2H), 2.47 (t, J=7.9Hz, 2H), 1.67 (q, J=7.6Hz, 2H), 1.41 (q, J=7.6Hz, 2H), 0.91 (t, J=7.2Hz, 3H); 13c NMR (CDCl 3, 75MHz) δ 139.2,136.8,134.3,133.5,131.4,130.3,128.7,128.5,128.1,127.7,127.6,127.0,125.8,124.9.121.9.106.1,47.5,30.7,26.4,22.7,14.1.
GC-MS data: m/z=365
Analytical results shows, the object product of acquisition is correct.
Embodiment 10,1-benzyl-2, the trimethyl silicon based pyrroles's of 3-phenylbenzene-5-preparation (R in structural formula I 1=benzyl, R 2=R 3=phenyl, R 4=hydrogen, R 5=trimethyl silicon based)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently ethylmagnesium chloride tetrahydrofuran solution (2M, 1.2mmol, 0.60mL), remain on-78 ℃ of reactions after one hour, add tolane (0.5mmol, 89mg), at 0 ℃, react one hour, then add trimethyl silicane ethyl-acetylene (0.5mmol, 69 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3-phenylbenzene-5-butyl pyrroles 76.3mg, isolated yield 40%.
1-benzyl-2, the trimethyl silicon based pyrroles's of 3-phenylbenzene-5-Structural Identification:
Nuclear magnetic resonance data 1h NMR (CDCl 3, 300MHz) δ 7.06-7.26 (m, 13H), 6.80 (d, J=6.4Hz, 2H), 6.76 (s, 1H), 5.14 (s, 2H), 0.16 (s, 9H); 13c NMR (CDCl 3, 75MHz) δ 139.7,136.4,136.0,133.2,131.1,128.8,128.4,128.1,128.0,127.8,127.5,127.0,125.8,125.1,123.6,119.4,50.7,0.0.
GC-MS data: m/z=381
Analytical results shows, the object product of acquisition is correct.
Embodiment 11,1-hexyl-2,3,4,5-tetrapropyl pyrroles prepares (R in structural formula I 1=hexyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and after ten minutes, add n-hexyl nitrine (0.6mmol, 80mg), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-hexyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 90.7mg, isolated yield 57%.
1-hexyl-2,3,4,5-tetrapropyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 3.61-3.67 (m, 2H), 2.41-2.47 (m, 4H), 2.27-2.33 (m, 4H), 1.31-1.55 (m, 16H), 0.88-0.99 (m, 15H); 13c NMR (CDCl 3, 75MHz) δ 127.1,118.1,43.8,32.3,31.6,27.6,27.3,27.0,25.7,24.8,22.7,14.9,14.6,14.1.
GC-MS data: m/z=319
Analytical results shows, the object product of acquisition is correct.
Embodiment 12,1-tolyl-2,3,4,5-tetrapropyl pyrroles prepares (R in structural formula I 1=tolyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and after ten minutes, add p-methylphenyl nitrine (0.6mmol, 96 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-tolyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 131.2mg, isolated yield 81%.
1-tolyl-2,3,4,5-tetrapropyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.07-7.21 (m, 4H), 2.41 (s, 3H), 2.26-2.40 (m, 8H), 1.50-1.59 (m, 4H), 1.14-1.27 (m, 4H), 0.99 (t, J=7.2Hz, 6H), 0.71 (t, J=7.2Hz, 6H); 13c NMR (CDCl 3, 75MHz) δ 137.2,137.0,129.3,129.0,128.8,118.3,27.5,27.2,25.5,24.1,21.2,14.8,14.3.
GC-MS data: m/z=325
Analytical results shows, the object product of acquisition is correct.
Embodiment 13,1-tolyl-2,3,4,5-tetraphenyl pyrroles prepares (R in structural formula I 1=tolyl, R 2=R 3=R 4=R 5=phenyl)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add tolane (1mmol, 178mg), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous chloride (1mmol, 99mg), react and after ten minutes, add p-methylphenyl nitrine (0.6mmol, 96 μ L), temperature of reaction system is risen to 50 ℃ of reactions to spend the night.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-tolyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 133.7mg, isolated yield 58%.
1-tolyl-2,3,4,5-tetrapropyl pyrroles's Structural Identification:
Nuclear magnetic resonance data: 1h NMR (CDCl 3, 300MHz) δ 7.82-7.31 (m, 24H), 2.28 (s, 3H); 13cNMR (CDCl 3, 75MHz) δ 136.6,136.1,135.5,132.5,131.8,131.6,131.3,129.1,129.0,127.7,127.6,126.5,125.5,122.9,21.2.
ESI data: m/z=461
Analytical results shows, the object product of acquisition is correct.
Embodiment 14,1-benzyl-2,3,4,5-tetrapropyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous bromide (1mmol, 144mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 92.5mg, isolated yield 57%.Analytical results shows, the object product of acquisition is correct.
Embodiment 15,1-benzyl-2,3,4,5-tetrapropyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous iodide (1mmol, 191mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 85.6mg, isolated yield 53%.Analytical results shows, the object product of acquisition is correct.
Embodiment 16,1-benzyl-2,3,4,5-tetrapropyl pyrroles's preparation (R in structural formula I 1=benzyl, R 2=R 3=R 4=R 5=propyl group)
In the reactor of 25mL, add bis cyclopentadienyl zirconium dichloride (0.6mmol, 176mg), substitute after nitrogen three times, add tetrahydrofuran (THF) (3mL), cooling temperature of reaction is to-78 ℃, add subsequently n-Butyl Lithium hexane solution (1.6M, 1.2mmol, 0.75mL), remain on-78 ℃ of reactions after one hour, add 4-octyne (1mmol, 142 μ L), temperature of reaction is risen to 50 ℃, react, after one hour, reaction system is cooled to 0 ℃, add cuprous cyanide (1mmol, 89mg), react and add benzyl azide (0.6mmol after ten minutes, 78 μ L), temperature of reaction system is risen to 50 ℃ of reactions three hours.After question response system is cooling, adds the 5mL shrend reaction of going out, and divide and extract for three times with 15mL ether, filtrate merges, and washes twice with water, and saturated common salt water washing once.Add dried over mgso 30 minutes, filter, the concentrated crude product that obtains of filtrate rotary evaporation.Crude product is done eluent post separated (200-300 order silica gel) with sherwood oil, obtains weak yellow liquid product 1-benzyl-2 that purity is greater than 99%, 3,4,5-tetrapropyl pyrroles 77.6mg, isolated yield 48%.Analytical results shows, the object product of acquisition is correct.

Claims (5)

1. the method for compound shown in a preparation formula I or formula II, comprise the steps: compound shown in formula III or formula IV first to turn metal reaction with cuprous salt, and then add the triazo-compound shown in formula V to react, reaction finishes rear cancellation reaction, obtains compound shown in described formula I or formula II;
Figure FDA0000394552730000011
In described formula I, R 1straight chained alkyl, tolyl or benzyl for C1-C6; R 2, R 3, R 4, R 5all independently selected from any one in following radicals: the straight chained alkyl of H, C1-C6, phenyl, tolyl and trimethyl silicon based;
In described formula II, R 1, R 2, R 5definition cotype I;
In described formula III, R 2, R 3, R 4, R 5definition cotype I;
In described formula IV, R 2, R 5definition cotype I;
In described formula V, R 1definition cotype I;
Described cuprous salt be selected from following any one: cuprous chloride, cuprous bromide, cuprous iodide or cuprous cyanide;
The described reaction times that turns metal reaction is 5-15 minute;
Described to add the temperature of reaction that the triazo-compound shown in formula V reacts be 45-60 ℃, and the reaction times is 3-24 hour.
2. method according to claim 1, is characterized in that: in described method, shown in formula III or formula IV, the mol ratio of the triazo-compound shown in compound, cuprous salt and formula V is followed successively by 1.0:2.0-2.2:1.2-1.3.
3. method according to claim 1, is characterized in that: the method for described cancellation reaction is: in reaction solution, add sodium hydrogen carbonate solution or water to carry out cancellation.
4. according to the method described in any one in claim 1-3, it is characterized in that: described method also comprises that shown in formula I to obtaining or formula II, compound carries out the step of following purifying successively: extraction, washing, dry, concentrated and column chromatography.
5. method according to claim 4, is characterized in that: described extraction be take sherwood oil, normal hexane or Skellysolve A and carried out as extraction agent; Described washing comprises twice of washing and saturated common salt washing once; Describedly dry take anhydrous magnesium sulfate or anhydrous sodium sulphate and carry out as siccative; Described column chromatography is that to take 200-300 order silica gel be separator column, and eluent is sherwood oil, hexane or pentane.
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* Cited by examiner, † Cited by third party
Title
1,1-Cycloaddition of Oxalyl Dichloride with Dialkenylmetal Compounds:Formation of Cyclopentadienone Derivatives by the Reaction of 1,4,-Dilithio-1,3-dienes or Zirconacyclopentadienes with Oxalyl Chloride in the Presence of CuCl;Chao Chen,et al.;《J. AM. CHEM. SOC.》;20050512;第127卷(第22期);第8024页式（2）-（5） *
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