CN102887851B - Compound 3,5-dimethyl-1H-pyrrole-2,4-diformaldehyde and preparation method thereof - Google Patents

Abstract

The invention relates to a compound 3,5-dimethyl-1H-pyrrole-2,4-diformaldehyde and a preparation method thereof. According to the invention, the 3,5-dimethyl-1H-pyrrole-2,4-diformaldehyde with a complicated structure is synthesized by use of the raw materials such as ethyl acetoacetate and acetic acid for the first time, and the yield of the final product is as high as 38%; and moreover, the crystallization effect is good, the purity is high, and a high-purity master standard or sample is provided for the subsequent chemical and biological experiments. The invention also provides a detailed synthesis and purification method of the 3,5-dimethyl-1H-pyrrole-2,4-diformaldehyde; and the production method is scientific and reasonable, and elaborate theoretical and practical guide is provided for the subsequent expanded production.

Description

Compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde and preparation method thereof

Technical field

The invention belongs to compound preparation field, especially compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde and preparation method thereof.

Background technology

At present, because Bioexperiment makes new breakthroughs, make us in treatment and find in the process of the cause of disease, means are mistake more, result is more accurate, so for treating various diseases property pharmaceutical requirements is also increased gradually, therefore, the various compounds with new function are in a large amount of being developed, the whole world all has the new compound of the various difficult and complicated cases of opposing in searching, so in the process of these new compound exploitations, can produce the compound of numerous new textures and new configuration, and then in these numerous new compounds, find useful, the molecule that has treatment use, therefore developing new compound is one and important process.

Summary of the invention

The object of the present invention is to provide a kind of brand-new compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde and preparation method thereof, the present invention is synthetic and this compound of purifying first, make its purity arrive certain requirement, can further test or application it.

The technical scheme that the present invention realizes object is as follows:

Compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde, structural formula is as follows:

Compound 3,5-dimethyl-1H-pyrroles-2, the preparation method of 4-dicarbaldehyde, step is as follows:

(1) compound 2,4-dimethyl pyrrole-3, and 5-diethyl dicarboxylate's is synthetic

When 5-15 spends, to in the acetum of methyl aceto acetate, drip the aqueous solution of Sodium Nitrite, continue reaction 1 hour, reaction solution is heated to room temperature and under violent stirring, adds zinc powder, reaction solution is refluxed one hour, TLC detection reaction finishes, and reaction solution is poured into water, and stirring was filtered after half an hour, filter cake washes with water three times, at room temperature being dried and within 10-14 hour, obtaining faint yellow solid powder is 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate;

Described methyl aceto acetate: Sodium Nitrite: the mol ratio of zinc powder is: 1.3: 0.7: 1.31;

(2) compound 2,4-dimethyl pyrrole synthetic

By 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate is suspended in the aqueous solution of potassium hydroxide, backflow is spent the night, and TLC detects, and after reaction finishes, reaction solution is cooled under the stirring of room temperature ice bath and adds concentrated hydrochloric acid, regulate pH to stir one hour to acid, with saturated potassium carbonate regulator solution, to neutral, be extracted with ethyl acetate three times, merge organic phase dried over sodium sulfate, filter, be spin-dried for and obtain dark-brown oily liquids, 80 ℃ of underpressure distillation obtain white transparent liquid 2,4-dimethyl pyrrole;

Described 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate: the mol ratio of potassium hydroxide is: 0.3:2;

(3) compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde synthetic

2,4-dimethyl pyrrole is dissolved in DMF, and slowly the slow phosphorus oxychloride that drips, then at room temperature stirs and spends the night, and reaction solution is slowly poured in frozen water, with saturated potassium carbonate, regulates pH=8, and ethyl acetate extraction three times merges organic relevant dry filtration and is spin-dried for and obtains thick product.

Described 2,4-dimethyl pyrrole: the mol ratio of phosphorus oxychloride is 40:90.

And the concentration of the acetum of described methyl aceto acetate is: every 1.3 moles of methyl aceto acetates adopt 500ml acetate dissolution.

Advantage of the present invention and beneficial effect are:

1, the present invention uses the raw materials such as methyl aceto acetate, acetic acid to synthesize first to have 3 of complex construction, 5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde, prepare the productive rate of end product up to 38%, and crystallization effect is good, purity is high, for follow-up chemistry and Bioexperiment provide highly purified standard specimen or sample.

2, the present invention also provides 3,5-dimethyl-1H-pyrroles-2, the detailed synthetic and purification process of 4-dicarbaldehyde, and production method science, reasonable, instructs for follow-up expanding production provides detailed theory and practice.

3, the invention provides 3,5-dimethyl-1H-pyrroles-2, synthesis condition, the raw material of each step in 4-dicarbaldehyde building-up process, and the nuclear-magnetism figure of synthetic after product, for the analysis and identification of intermediate product in building-up process provides detailed support.

Accompanying drawing explanation

Fig. 1 is the compounds of this invention 3(2,4-dimethyl pyrrole) nuclear magnetic spectrogram, ¹h NMR:(300MHz, CDCl3);

Fig. 2 is the compounds of this invention 4(3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde) nuclear magnetic spectrogram, ¹h NMR:(300MHz, CDCl3).

Embodiment

Below in conjunction with embodiment, technical scheme of the present invention is further illustrated, following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.

The present invention prepare 3,5-dimethyl-1H-pyrroles-2, the structural formula of 4-dicarbaldehyde (3,5-dimethyl-1H-pyrrole-2,4-dicarbaldehyde) is:

The synthetic route of this compound

Raw material

The raw materials such as methyl aceto acetate are market and buy, without particular requirement.

The synthetic method step of this chemical combination is as follows:

The present invention 3,5-dimethyl-1H-pyrroles-2, and the synthetic method of 4-dicarbaldehyde, step is as follows:

(1) compound 2 (2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate) is synthetic

When 10 spend, will in the acetic acid of methyl aceto acetate (1.3mol) (500mL) solution, drip the aqueous solution of Sodium Nitrite (0.7mol), continue reaction 1 hour, reaction solution is heated to room temperature and under violent stirring, adds zinc powder (1.31mol).Reaction solution is refluxed one hour, and TLC detection reaction finishes.Reaction solution is poured into water, and stirring was filtered after half an hour.Filter cake washes with water three times, at room temperature the dry faint yellow solid powder 80g that obtains for 12 hours.

(2) compound 3(2,4-dimethyl pyrrole) synthetic

By 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate (0.3mol) is suspended in the aqueous solution of potassium hydroxide (2mol), and backflow is spent the night.TLC detects, and after reaction finishes, reaction solution is cooled under the stirring of room temperature ice bath and adds concentrated hydrochloric acid, regulates pH to stir one hour to acid.With saturated potassium carbonate regulator solution, to neutral, be extracted with ethyl acetate three times, merge organic phase dried over sodium sulfate, filter, be spin-dried for and obtain dark-brown oily liquids.80 ℃ of underpressure distillation obtain white transparent liquid 2,4-dimethyl pyrrole (11.5g, 36.2%).

(3) compound 4(3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde) synthetic

2,4-dimethyl pyrrole (40mmol) is dissolved in DMF (25mL), and slowly the slow phosphorus oxychloride (90mmol) that drips, then at room temperature stirs and spends the night.Reaction solution is slowly poured in frozen water, with saturated potassium carbonate, regulates pH=8, and ethyl acetate extraction three times merges organic relevant dry filtration and is spin-dried for and obtains thick product.With PE:EA recrystallization, obtain product 2.7g, productive rate 38%.

Claims (2)

1. compound 3,5-dimethyl-1H-pyrroles-2, and the preparation method of 4-dicarbaldehyde, is characterized in that: structural formula is as follows:

Step is as follows:

(1) compound 2,4-dimethyl pyrrole-3, and 5-diethyl dicarboxylate's is synthetic

When 5-15 spends, to in the acetum of methyl aceto acetate, drip the aqueous solution of Sodium Nitrite, continue reaction 1 hour, reaction solution is heated to room temperature and under violent stirring, adds zinc powder, reaction solution is refluxed one hour, TLC detection reaction finishes, and reaction solution is poured into water, and stirring was filtered after half an hour, filter cake washes with water three times, at room temperature being dried and within 10-14 hour, obtaining faint yellow solid powder is 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate;

Described methyl aceto acetate: Sodium Nitrite: the mol ratio of zinc powder is: 1.3:0.7:1.31;

(2) compound 2,4-dimethyl pyrrole synthetic

By 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate is suspended in the aqueous solution of potassium hydroxide, backflow is spent the night, and TLC detects, and after reaction finishes, reaction solution is cooled under the stirring of room temperature ice bath and adds concentrated hydrochloric acid, regulate pH to stir one hour to acid, with saturated potassium carbonate regulator solution, to neutral, be extracted with ethyl acetate three times, merge organic phase dried over sodium sulfate, filter, be spin-dried for and obtain dark-brown oily liquids, 80 ℃ of underpressure distillation obtain white transparent liquid 2,4-dimethyl pyrrole;

Described 2,4-dimethyl pyrrole-3,5-diethyl dicarboxylate: the mol ratio of potassium hydroxide is: 0.3:2;

(3) compound 3,5-dimethyl-1H-pyrroles-2,4-dicarbaldehyde synthetic

2,4-dimethyl pyrrole is dissolved in DMF, slowly drips phosphorus oxychloride, then at room temperature stir and spend the night, reaction solution is slowly poured in frozen water, with saturated potassium carbonate, regulates pH=8, and ethyl acetate extraction three times merges organic relevant dry filtration and is spin-dried for and obtains thick product.

Described 2,4-dimethyl pyrrole: the mol ratio of phosphorus oxychloride is 40:90.

2. compound 3 according to claim 1,5-dimethyl-1H-pyrroles-2, the preparation method of 4-dicarbaldehyde, is characterized in that: the concentration of the acetum of described methyl aceto acetate is: every 1.3 moles of methyl aceto acetates adopt 500ml acetate dissolution.

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