A kind of α,β-unsaturated nitrile with strong π electron delocalization and preparation method thereof

Abstract

The present invention discloses a strong π Electron delocalized α,β-unsaturated nitrile and preparation method thereof, which is a compound ( Z )-3-amino-2-nitroacrylonitrile. The present invention also discloses ( Z )-3-amino-2-nitroacrylonitrile, comprising: using 5-amino-4-nitro-3-azido-1 H ‑pyrazole as the starting material, 1,4‑dioxane as the solvent, thermal denitrification reaction, and then purification by silica gel column chromatography to obtain ( Z )-3-amino-2-nitroacrylonitrile. Due to its high thermal stability, π With its electron delocalization characteristics and excellent reactivity, it is a very important synthon and intermediate in organic synthesis. Its preparation method is simple, with high yield and conversion rate, and it is green and pollution-free. It has broad application prospects in biochemistry, medicinal chemistry, and material chemistry.

Description

Technical Field

[0001] The invention belongs to the field of synthetic chemistry, and specifically relates to (Z)-3-amino-2-nitro-acrylonitrile and a synthesis method thereof. Background Art

[0002] Nitriles occur naturally in a wide variety of plants and animals, and more than 120 natural products of the nitrile class have been isolated from land and sea. Historically, there are currently more than 30 nitrile-containing drugs used for a variety of different medical indications, and many more are in clinical development. Nitriles are a wide variety of drugs with different functions. From the recently released antidiabetic drug Vildagliptin to the standard drug anazolol for the treatment of breast cancer. In many cases, nitriles mimic the function of natural enzyme substrates, while in other cases, nitriles increase water solubility or reduce the sensitivity of oxidative metabolism in the liver.

[0003] Alkenyl nitriles are one of the most widely used reagents in organic chemistry. They have been used as precursors for the production of nucleotides and the synthesis of various heterocyclic compounds. These include purines, pyrimidines, pyrazines (some of which are widely used in the fluorescent dye industry), imidazoles, biphenyls, porphyrins (which have great potential in optical sensor technology), and diimines used as catalysts. Alkenyl nitriles, such as α,β-unsaturated nitriles, are a typical stable organic molecule, and their stability is mainly due to the delocalized π electron system of the molecule. Therefore, highly active alkenyl nitrile compounds are very important synthons and intermediates in organic synthesis. They can be used as an effective substance to efficiently build quite complex structures from relatively simple raw materials. So far, a large number of researchers have reported the application of these compounds in heterocyclic synthesis, because researchers have found that among various possible synthetic methods, the use of alkenyl nitrile analogs may be the most direct way to introduce heterocycles into a certain structure. α,β-Unsaturated nitriles can undergo cyclization reactions with thiol derivatives, amine compounds, active methylene groups, etc. to increase the ring size and synthesize different single heterocycles such as four-membered rings, five-membered rings and six-membered rings or polyheterocycles and fusion compounds.

[0004] How to directly convert simple, known carbon, hydrogen and nitrogen compounds into complex, high value-added compounds is a long-standing issue in organic synthesis. As an important class of α,β-unsaturated carbonyl compounds, alkenyl nitriles are not only useful cornerstones in synthetic chemistry, but also important structures commonly found in medicinal chemistry research, with important chemical and biological significance. How to prepare alkenyl nitriles efficiently and practically is extremely attractive, and the search for greener and more efficient synthetic strategies remains an urgent scientific research topic. Summary of the invention

[0005] The purpose of the present invention is to provide an α,β-unsaturated nitrile with strong π electron delocalization and a preparation method thereof.

[0006] The object of the present invention is achieved in that:

[0007] A strong π-electron delocalized α,β-unsaturated nitrile named (Z)-3-amino-2-nitroacrylonitrile, with the structural formula:

[0008]

[0009] The present invention also provides a method for preparing an α,β-unsaturated nitrile with high reactivity, high thermal stability and strong π electron delocalization, which uses 5-amino-4-nitro-3-azido-1H-pyrazole as a starting material and 1,4-dioxane as a solvent, performs a thermal cracking denitrogenation reaction, and obtains (Z)-3-amino-2-nitroacrylonitrile through post-treatment.

[0010] Furthermore, the reaction temperature may be 90° C. to 110° C.; and the reaction time may be 16 to 48 hours.

[0011] Furthermore, the ratio of 5-amino-4-nitro-3-azido-1H-pyrazole to solvent is 0.05 g·mL -1 .

[0012] Further, the mobile phase reagent is used for purification and separation through silica gel column chromatography, and (Z)-3-amino-2-nitroacrylonitrile is obtained after rotary evaporation and drying. The mobile phase reagent can be any one or more mixtures of acetonitrile, dichloromethane, ethyl acetate, acetone, methanol, ethanol, petroleum ether, etc.

[0013] Compared with the prior art, the present invention has the following significant advantages: the present invention uses 5-amino-4-nitro-3-azido-1H-pyrazole as a raw material, initiates a denitrogenation reaction by thermal cracking, and synthesizes (Z)-3-amino-2-nitroacrylonitrile, thereby developing a method for preparing (Z)-3-amino-2-nitropropene with strong π electron delocalization, which is simple to operate, green and efficient, mild in reaction, and does not require metal catalysis. It is expected that the reaction strategy and the compound (Z)-3-amino-2-nitropropene will be widely used in the fields of organic chemistry, biochemistry, pharmaceutical intermediates, and material chemistry. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is the single crystal structure diagram of (Z)-3-amino-2-nitropropene.

[0015] Figure 2 This is the H NMR spectrum of (Z)-3-amino-2-nitropropene.

[0016] Figure 3 This is the C NMR spectrum of (Z)-3-amino-2-nitropropene.

[0017] Figure 4This is the infrared spectrum of (Z)-3-amino-2-nitropropene.

[0018] Figure 5 This is the mass spectrum of (Z)-3-amino-2-nitropropene. DETAILED DESCRIPTION

[0019] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments.

[0020] The present invention provides a novel α,β-unsaturated nitrile (Z)-3-amino-2-nitro-acrylonitrile with high thermal stability and high reactivity. Compared with common α,β-unsaturated nitriles such as acrylonitrile, β-aminoacrylonitrile, and 2-benzoyl-3-phenyl-acrylonitrile, the compound has a green and efficient preparation method and a novel and simple strategy. It has high thermal stability and high reactivity. Based on the compound, a series of novel cyclization reactions and Michael addition reaction strategies can be studied and developed to further expand the application of α,β-unsaturated nitriles in the fields of chemistry and biology.

[0021] The present invention provides a method for preparing the α,β-unsaturated nitrile, which specifically comprises the following steps:

[0022] At a certain temperature, 5-amino-4-nitro-3-azido-1H-pyrazole is dispersed in 1,4-dioxane solvent, stirred and ultrasonicated to completely dissolve, and then continued to react at a certain temperature for a certain time, and then purified and separated by silica gel column chromatography with a certain mobile phase ratio, and a yellow solid can be obtained after rotary evaporation and drying. The reaction formula is as follows:

[0023]

[0024] Example 1

[0025] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL 1,4-dioxane, stirred until completely dissolved, then reacted at 90°C for 24 h, cooled to room temperature, filtered, and the filtrate was collected and separated and purified by silica gel column chromatography with a mobile phase ratio of (petroleum ether: ethyl acetate = 4:1). A yellow solid was obtained after rotary evaporation and drying.

[0026] Example 2

[0027] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of 1,4-dioxane (0.05 g mL -1), stirred until completely dissolved, then reacted at 100°C for 24h, cooled to room temperature, filtered and collected the filtrate, separated and purified by silica gel column chromatography with a mobile phase ratio of (petroleum ether: ethyl acetate = 4:1). After rotary evaporation and drying, a yellow solid was obtained.

[0028] Example 3

[0029] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of 1,4-dioxane (0.05 g mL -1 ), stirred until completely dissolved, then reacted at 110°C for 24h, cooled to room temperature, filtered and collected the filtrate, separated and purified by silica gel column chromatography with a mobile phase ratio of (petroleum ether: ethyl acetate = 4:1). After rotary evaporation and drying, a yellow solid was obtained.

[0030] Example 4

[0031] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of 1,4-dioxane (0.05 g mL -1 ), stirred until completely dissolved, then reacted at 100°C for 12h, cooled to room temperature, filtered and collected the filtrate, separated and purified by silica gel column chromatography with a mobile phase ratio of (petroleum ether: ethyl acetate = 4:1). After rotary evaporation and drying, a yellow solid was obtained.

[0032] Example 5

[0033] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of 1,4-dioxane (0.05 g mL -1 ), stirred until completely dissolved, then reacted at 100°C for 36h, cooled to room temperature, filtered and collected the filtrate, separated and purified by silica gel column chromatography with a mobile phase ratio of (petroleum ether: ethyl acetate = 4:1). After rotary evaporation and drying, a yellow solid was obtained.

[0034] Comparative Example 1

[0035] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of toluene (0.05 g mL -1 ), stirred until completely dissolved, then reacted at 100°C for 24h, cooled to room temperature, and no reaction occurred as detected by thin layer chromatography.

[0036] Comparative Example 2

[0037] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of water (0.05 g mL-1 ), stirred until completely dissolved, then reacted at 100°C for 24h, cooled to room temperature, and no reaction occurred as detected by thin layer chromatography.

[0038] Comparative Example 3

[0039] At room temperature, 5-amino-4-nitro-3-azido-1H-pyrazole (2.0 g) was dispersed in 20 mL of chloroform (0.05 g mL -1 ), stirred until completely dissolved, then reacted at 100°C for 24h, cooled to room temperature, and no reaction occurred as detected by thin layer chromatography.

[0040]

[0041] By analyzing the effects of reaction time, reaction temperature, and reaction reagents on the reaction yield of Examples 1-5 and Comparative Examples 1-3, it can be concluded that compared with Comparative Examples 1-3, the thermal cracking denitrogenation reaction of Examples 1-5 can only be achieved in 1,4-dioxane solvent. This is a method for preparing (Z)-3-amino-2-nitropropene with strong π electron delocalization, which is simple to operate, green and efficient, mild in reaction, and does not require metal catalysis.

[0042] The crystal structure of the target product (yellow powder solid) of Example 1-5 is as follows Figure 1 As shown, Figure 2 to Figure 5 is the spectrum of the target product, and the analysis and test data results are as follows:

[0043] DSC (148℃, 40℃–400℃, 5℃·min -1 ). 1 H NMR (500MHz, CD3CN, 25℃) δ: 9.01 (s, NH), 8.56 (dd, J = 16.75, 9.15Hz, 1H), 7.87 (s, NH), 7.64 (dd, J = 16.51, 9.55Hz, 1H), 7.23 (d, J = 43.45Hz, 2H) ppm. 13C NMR (126MHz, CD3CN, 25℃)δ:156.50,153.09,114.20,111.88,102.78,99.14ppm.HRMS (ESI, m / z) calculated value: C3H3N3O2[MH]-:112.0152; found value:112.013940, IR (KBr):ν~=3393.27,3268.19,2228. 59,2155.02,1652.49,1574.94,1528.57,1490.02,1435.65,1373.27,1309.11,1254.79,1231.89,1189.66,796.80,761.10,699.18,635.31,517.11. Elemental analysis C3H3N3O2 (113.0225): calculated: C 31.87, H 2.67, N 37.16, O 28.30%. Found: C 31.81H 2.60N 37.11O28.25%.

[0044] (Z)-3-Amino-2-nitroacrylonitrile is a yellow powder solid. The pure substance precipitated by recrystallization is a white block crystal. The crystal density is 1.6g·cm -3 .

[0045] Although the present invention is described herein with reference to illustrative implementations of the present invention, the above-mentioned embodiments are merely preferred implementations of the present invention, and the implementation methods of the present invention are not limited to the above-mentioned embodiments. It should be understood that those skilled in the art can design many other modifications and implementations, which will fall within the scope and spirit of the principles disclosed in this application.

Claims

1. A method for preparing a strongly π-electron delocalized α,β-unsaturated nitrile, using 5-amino-4-nitro-3-azido-1H-pyrazole as a starting material and 1,4-dioxane as a solvent, and performing a thermal cracking and denitrogenation reaction at 90°C to 110°C for 16-48h, and then post-treating to obtain (Z)-3-amino-2-nitroacrylonitrile, the structural formula of which is:

2. The method according to claim 1, characterized in that The ratio of 5-amino-4-nitro-3-azido-1H-pyrazole to solvent is 0.05 g·mL -1 .

3. The method according to claim 1, characterized in that The product was purified and separated by silica gel column chromatography using a mobile phase reagent, and then dried by rotary evaporation to obtain (Z)-3-amino-2-nitroacrylonitrile.

4. The method according to claim 3, characterized in that The mobile phase reagents were petroleum ether and ethyl acetate in a ratio of 4:1.

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