CN110746278B - Nonmetal-catalyzed method for preparing 1, 3-diketone compound based on alkynone - Google Patents

Nonmetal-catalyzed method for preparing 1, 3-diketone compound based on alkynone Download PDF

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CN110746278B
CN110746278B CN201911048852.7A CN201911048852A CN110746278B CN 110746278 B CN110746278 B CN 110746278B CN 201911048852 A CN201911048852 A CN 201911048852A CN 110746278 B CN110746278 B CN 110746278B
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蔡显荣
万峻钊
白雨欣
覃聪
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Sichuan University of Science and Engineering
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Abstract

The invention discloses a nonmetal-catalyzed method for preparing 1, 3-diketone compounds based on alkynone, which is a step method or a one-pot method. The fractional step method is that the alkynone compound I, the nitrogen-containing aromatic compound II and a first class of alkali are mixed and reacted, then separated and purified to obtain an intermediate product, then the intermediate product is mixed and reacted with a second class of alkali, and finally separated and purified to obtain a product; the one-pot method is that the alkynone compound I and the nitrogen-containing aromatic compound II are mixed and then added with the first class alkali for reaction for a period of time, then added with the second class alkali for continuous reaction for a period of time, and finally separated and purified to obtain the product. The method has the advantages of mild reaction conditions, simple and convenient operation, high yield which is generally over 80 percent, and great practical application value in the aspect of medicine synthesis.

Description

Nonmetal catalysis method for preparing 1, 3-diketone compounds based on alkynone
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing 1, 3-diketone compounds based on alkynone under nonmetal catalysis.
Background
The 1, 3-diketone compound has the characteristics of stability and innocuity, is easy to store and use, is often used for synthesizing heterocyclic compounds such as imidazole, pyrazole, pyrrole, pyrimidine, quinoline and the like, can quickly construct a medicine skeleton containing the heterocyclic compounds, and is also widely used for the synthesis of metal complexes, polymers and other related technical fields.
Many methods are currently used for synthesizing 1, 3-diketones, such as acetylene ketone hydrolysis, Claisen condensation of ketones and esters, coupling of ketones and amides or esters, ruthenium-catalyzed coupling of aldehydes and ketenes, oxidation of beta-hydroxy ketones, palladium-catalyzed carbonylation of ketones and aryl iodides, and the like. Among these, the process for the hydrolytic conversion of alkynones into 1, 3-diketones presents various problems, such as the direct addition of sulfuric acid, PtCl4High-temperature catalysis, severe reaction conditions such as sodium methoxide and the like, and poor substrate universality; further, since the alkynone is easily decomposed into the alkyne and the carboxylic acid under an alkaline condition, the yield of the method of directly hydrolyzing with an alkali such as potassium hydroxide is very low.
Glotova et al, 2009, reported that acetylenic ketones reacted with amines to form beta-enaminones, which were hydrolyzed by hydrochloric acid to 1, 3-dione compounds at room temperature, but only in 20% yield; in 2013, Nordmann et al reported that β -enaminone under p-toluenesulfonic acid condition produced pyrrole compound (yield 53%), by-product of which was hydrolyzed 1, 3-dione compound; tarigopula et al report in 2016 on the use of the metal reagents IPrAuCl and AgSbF6Hydrolyzing alkynone into a 1, 3-diketone compound under a catalytic condition; in 2019 Kuang et al also by the Metal reagent PPh3AuCl and AgOTf are used for catalyzing the reaction to obtain a 1, 3-diketone compound; the same year university of Wenzhou, summer polygala et al patented a method of catalyzing acetylenic ketones with gold and silver to produce 1, 3-dione compounds. Although they all achieve high yields, the reaction requires the use of expensive metal reagents.
In summary, the yield of 1, 3-diketone compounds produced by acid or base hydrolysis of alkynones is generally low, and the current mainstream method is catalyzed by gold complexes and silver reagents, but the cost is obviously increased.
Disclosure of Invention
Aiming at the prior art, the invention provides a method for preparing 1, 3-diketone compounds based on alkynone under non-metal catalysis, which aims to solve the problems of low yield and high cost of the synthesized 1, 3-diketone compounds.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: providing a nonmetal-catalyzed method for preparing 1, 3-diketone compounds based on alkynone, wherein the preparation method is a fractional step method or a one-pot method; wherein, the step-by-step method comprises the following steps:
s1: putting the alkynone compound I, the nitrogen-containing aromatic compound II and a base into a reactor filled with a solvent according to a molar ratio of 1: 1-4: 1-4.5, uniformly stirring, reacting at 20-80 ℃ for 12-24 h, and then separating and purifying to obtain a compound III; the reaction equation is shown in formula (1-1):
Figure BDA0002254813390000021
s2: putting the compound III and a second-class alkali into a reactor filled with a solvent according to a molar ratio of 1: 1-5, uniformly stirring, reacting at 20-50 ℃ for 2-12 h, and then separating and purifying to obtain a 1, 3-diketone compound IV; the reaction equation is shown in formula (1-2):
Figure BDA0002254813390000022
the one-pot method comprises the following steps:
firstly, putting an alkynone compound I, a nitrogen-containing aromatic compound II and a base into a reactor according to a molar ratio of 1: 1-4: 1-4.5, and reacting at 20-80 ℃ for 12-24 h; adding a second class of alkali into the reactor, reacting for 2-12 h at 20-50 ℃ at a molar ratio of the added second class of alkali to the alkynone compound I of 1-5: 1, and separating and purifying to obtain a 1, 3-diketone compound IV; the reaction equation is shown in the formulas (1-3):
Figure BDA0002254813390000031
wherein R is1、R2Are respectively and independently selected from phenyl, alkylphenyl of C1-C6, alkoxyphenyl of C1-C6, halogenated alkylphenyl of C1-C6, naphthyl, heteroaryl, cycloalkyl of C3-C6 or alkyl of C1-C6;
a is nitrogen atom or carbon atom, D is carbon atom or nitrogen atom; r3、R4、R5And R6Are respectively and independently selected from hydrogen, alkyl of C1-C6, halogenated alkyl of C1-C6, cyclane or halogen of C3-C6, or R5And R6Connected to form a benzene ring or a substituted benzene ring;
the first base and the second base are respectively and independently selected from at least one of 4-dimethylamino pyridine, triethylamine, N-diisopropylethylamine, hydroxide of alkali metal and carbonate of alkali metal;
compound IV can be written as an isomeric form with the structure:
Figure BDA0002254813390000032
on the basis of the technical scheme, the invention can be further improved as follows.
Further, R1And R2Each independently selected from phenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, methoxyphenyl, dimethoxyphenyl, halophenyl, thienyl, furyl, pyridyl, naphthyl, cyclopropyl, methyl, or butyl; r3、R4、R5And R6Each independently selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, fluoro, bromo or iodo, or R5And R6Connected to form benzene ring or substituted benzene ring.
Further, the compound II is pyrrole, imidazole, pyrazole, benzimidazole, indole, indazole, 2-methylimidazole, 2-isopropylimidazole, 2-ethylimidazole or 2-methyl-5-nitroimidazole.
Further, the reaction temperature of S1 in the fractional step method is between room temperature and 50 ℃, and the reaction time is 16 h; the reaction temperature of S2 was room temperature, and the reaction time was 8 h.
Further, the reaction temperature of the front section in the one-pot method is room temperature to 50 ℃, and the reaction time is 16 h; the latter stage reaction temperature is room temperature and the time is 8 h.
Further, the alkali is 4-dimethylamino pyridine, and the molar ratio of the alkali to the alkynone compound I is 1-1.5: 1; or the alkali is a mixture of 4-dimethylamino pyridine and triethylamine according to a molar ratio of 1: 5-10, and the molar ratio of the mixture to the alkynone compound I is 1-1.5: 1; or the alkali is potassium carbonate, sodium carbonate, cesium carbonate or sodium bicarbonate, and the molar ratio of the alkali to the alkynone compound I is 2-4.5: 1.
Further, the second type of alkali is sodium hydroxide, potassium hydroxide or lithium hydroxide, and the molar ratio of the second type of alkali to the alkynone compound I is 2-4: 1.
Further, the solvent is dimethyl sulfoxide, 1, 4-dioxane, tetrahydrofuran, acetone, acetonitrile, ethanol or methanol.
Further, the separation and purification treatment comprises the following steps: pouring the reaction solution after the reaction into cold water, extracting with ethyl acetate for three times, and combining organic layers; then, the organic layer was washed with water and saturated brine in this order, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure; then separating by a chromatographic silica gel column to obtain the corresponding compound.
The invention has the beneficial effects that: compared with the prior art, the alkaline hydrolysis method does not need special ligand and high temperature, has mild reaction conditions, simple and convenient operation and higher yield which is generally more than 80 percent, and has larger practical application value in the aspect of drug synthesis.
Detailed Description
The present invention will be described in further detail with reference to the following examples, which are provided for illustration only and are not intended to limit the scope of the present invention, and any equivalent replacement in the field made in the light of the present disclosure is included in the scope of the present invention. The structure of the compound was determined by Nuclear Magnetic Resonance (NMR). Nuclear magnetic resonance apparatus (1H NMR is Bruker AVANCE-600, nuclear magnetic resonance: (1H NMR) shifts (δ) are given in parts per million (ppm) and the solvent is determined to be CDCl3Internal standard is Tetramethylsilane (TMS), and chemical shift is 10-6(ppm) is given as a unit. The term "room temperature" in the present invention means a temperature of 20 to 30 ℃.
The first embodiment is as follows: preparation of 1, 3-diphenyl-1, 3-propanedione
Figure BDA0002254813390000051
A step-by-step method:
step 1:1, 3-Diphenyl-2-propiophenone (41.2mg, 0.20mmol) was added to 2mL of dimethylsulfoxide as a solvent, followed by imidazole (16.3mg, 0.24mmol), triethylamine (24.2mg, 0.24mmol) and 4-Dimethylaminopyridine (DMAP) (4.88mg, 0.04mmol) in that order, stirred overnight at room temperature (about 16 h), and the reaction was monitored by TLC to complete the reaction. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 54.2mg of cis-trans isomeric mixture 3-imidazolyl-1, 3-diphenyl-2-propenone, wherein the yield is as follows: the content of the waste water is 98.9%,1H NMR(600MHz,CDCl3)δ7.91–7.88(m,4H),7.72(s,1H),7.63(s,1H),7.57–7.51(m,3H),7.47–7.41(m,7H),7.37(t,J＝8.6Hz,4H),7.31(d,J＝7.8Hz,2H),7.20(s,1H),7.14(s,1H),7.08(s,1H),6.99(s,1H),6.98(s,1H),6.91(s,1H)。
step 2: 3-imidazolyl-1, 3-diphenyl-2-propenone (27.4mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, potassium hydroxide (16.8mg, 0.30mmol) was added, stirred at room temperature for 8h, and the reaction was monitored by TLC until the starting material was reacted completely. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 19.2mg of 1, 3-diphenyl-1, 3-propanedione, wherein the yield is as follows: 85.7 percent of the total weight of the mixture,1H NMR(600MHz,CDCl3)δ16.85(s,1H),7.99(dd,J＝5.2,3.3Hz,4H),7.58–7.53(m,2H),7.53–7.45(m,4H),6.86(s,1H)。
a one-pot method:
1, 3-Diphenyl-2-propiophenone (20.6mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in this order, and the mixture was stirred at room temperature overnight (about 16 h) byThe reaction was monitored by TLC, after the starting material had reacted completely, potassium hydroxide (16.8mg, 0.30mmol) was added and stirred at room temperature for 8h, and the reaction was monitored by TLC and the starting material was reacted completely. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, collecting under reduced pressure, and performing vacuum drying to obtain 18.6mg of yellow oily 1, 3-diphenyl-1, 3-propanedione, wherein the yield is as follows: the content of the active carbon is 83.0 percent,1H NMR(600MHz,CDCl3)δ16.85(s,1H),7.99(dd,J＝5.2,3.3Hz,4H),7.58–7.53(m,2H),7.53–7.45(m,4H),6.86(s,1H)。
example two: preparation of 1-phenyl-3-o-methylphenyl-1, 3-propanedione
Figure BDA0002254813390000061
A step-by-step method:
step 1: 3-phenyl-1-o-methylphenyl-2-propiophenone (44.0mg, 0.20mmol) was added to 2mL of dimethylsulfoxide solvent, followed by the addition of imidazole (27.2mg, 0.4mmol), triethylamine (80.1mg, 0.8mmol) and DMAP (12.2mg, 0.1mmol) in that order, the reaction was stirred at room temperature for 24h, and the reaction was monitored by TLC until the starting material was completely reacted. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 57.2mg of cis-trans isomeric mixture 3-imidazolyl-3-phenyl-1-o-methylphenyl-2-propynone, wherein the yield is as follows: 99.3 percent.
Step 2: 3-Imidazoyl-3-phenyl-1-o-methylphenyl-2-propenone (28.8mg, 0.10mol) was added to 1mL dimethylsulfoxide solvent, sodium hydroxide (8.0mg, 0.20mmol) was added, the reaction was stirred at room temperature for 2h, and the reaction was monitored by TLC until the starting material was completely reacted. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed with water, saturated brine in that order, dried over sodium sulfate, filtered, and reduced pressureRotary evaporating, purifying by chromatography silica gel column, collecting under reduced pressure, and vacuum drying to obtain 20.9mg of 1-phenyl-3-o-methylphenyl-1, 3-propanedione, with yield: the mass ratio of the mixture to the mixed solution is 87.8%,1H NMR(600MHz,CDCl3)δ16.62(s,1H),7.95(dd,J＝5.2,3.4Hz,2H),7.59–7.52(m,2H),7.47(dd,J＝10.5,4.7Hz,2H),7.37(td,J＝7.5,1.3Hz,1H),6.53(s,1H),2.56(s,3H)。
a one-pot method:
3-phenyl-1-o-methylphenyl-2-propargyl ketone (22.0mg, 0.10mmol) is added into 1mL of dimethyl sulfoxide solvent, imidazole (13.6mg, 0.2mmol) and DMAP (12.1mg, 0.12mmol) are sequentially added, the mixture is stirred at room temperature overnight, the reaction is monitored by TLC, after the raw materials completely react, sodium hydroxide (12mg, 0.30mmol) is added, the mixture is stirred at room temperature for 4h, the reaction is monitored by TLC, and the raw materials completely react. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, collecting under reduced pressure, and performing vacuum drying to obtain 22.0mg of yellow oily 1-phenyl-3-o-methylphenyl-1, 3-propanedione, wherein the yield is as follows: the content of the active carbon is 92.4%,1H NMR(600MHz,CDCl3)δ16.62(s,1H),7.95(dd,J＝5.2,3.4Hz,2H),7.59–7.52(m,2H),7.47(dd,J＝10.5,4.7Hz,2H),7.37(td,J＝7.5,1.3Hz,1H),6.53(s,1H),2.56(s,3H)。
example three: preparation of 1-p-ethylphenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000081
A step-by-step method:
step 1: 3-p-ethylphenyl-1-phenyl-2-propenone (46.8mg, 0.20mmol) was added to 2mL of dimethylsulfoxide solvent, followed by imidazole (20.5mg, 0.3mmol), triethylamine (50.5mg, 0.5mmol) and DMAP (12.2mg, 0.1mmol) in that order, and the reaction was stirred at 80 ℃ for 12h, followed by TLC to monitor the completion of the reaction of the starting materials. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 59.8mg of yellow oily cis-trans isomeric mixture 3-imidazolyl-3-p-ethylphenyl-1-phenyl-2-propiophenone, wherein the yield is as follows: 99.0 percent.
Step 2: 3-imidazolyl-3-p-ethylphenyl-1-phenyl-2-propenone (30.2mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, lithium hydroxide (9.6mg, 0.4mmol) was added thereto, the reaction was stirred at 30 ℃ for 12 hours, and the reaction was monitored by TLC to complete the reaction of the starting materials. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 23.6mg of yellow oily 1-p-ethylphenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: the content of the active carbon is 93.2%,1H NMR(600MHz,CDCl3)δ16.92(s,1H),7.98(dd,J＝5.2,3.4Hz,2H),7.92(d,J＝8.3Hz,2H),7.57–7.53(m,1H),7.49(dd,J＝10.4,4.7Hz,2H),7.32(d,J＝8.3Hz,2H),6.84(s,1H),4.61(s,1H),2.73(q,J＝7.6Hz,2H),1.28(d,J＝7.6Hz,3H)。
a one-pot method:
3-p-ethylphenyl-1-phenyl-2-propiophenone (23.4mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (10.2mg, 0.15mmol) and DMAP (12.1mg, 0.12mmol) in that order, followed by stirring at room temperature overnight, followed by TLC to monitor the reaction, and after completion of the reaction of the starting material, lithium hydroxide (9.6g, 0.4mmol) was added thereto, followed by stirring at room temperature for 4 hours, followed by TLC to monitor the reaction, whereby the completion of the reaction of the starting material was monitored. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, collecting under reduced pressure, and performing vacuum drying to obtain 22.8mg of yellow oily 1-p-ethylphenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: 90.4%, 1H NMR (600MHz, CDCl3) δ 16.92(s,1H),7.98(dd, J ═ 5.2,3.4Hz,2H),7.92(d, J ═ 8.3Hz,2H), 7.57-7.53 (m,1H),7.49(dd, J ═ 10.4,4.7Hz,2H),7.32(d, J ═ 8.3Hz,2H),6.84(s,1H),4.61(s,1H),2.73(q, J ═ 7.6Hz,2H),1.28(d, J ═ 7.6Hz, 3H).
Example four: preparation of 1-p-methoxyphenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000091
A one-pot method:
1-p-methoxyphenyl-3-phenyl-2-propiophenone (23.6mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ and monitored by TLC for reaction, after completion of the reaction of the starting material, potassium hydroxide (28.0mg, 0.5mmol) was added, stirred at room temperature for 2h, and monitored by TLC for completion of the reaction of the starting material. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, collecting under reduced pressure, and performing vacuum drying to obtain 20.5mg of yellow oily 1-p-methoxyphenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: 80.7 percent of the total weight of the steel,1H NMR(600MHz,CDCl3)δ16.97(s,1H),8.00–7.93(m,4H),7.54(t,J＝7.3Hz,1H),7.48(t,J＝7.5Hz,2H),6.98(d,J＝8.8Hz,2H),6.79(s,1H),3.88(s,3H)。
example five: preparation of 1-o-bromophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000101
A one-pot method:
1-o-bromophenyl-3-phenyl-2-propiophenone (28.5mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ and monitored for reaction by TLC, and after completion of the reaction of the starting material, potassium hydroxide (28.0mg, 0.50mmol) was added and stirred at room temperature for 2 hours, and the reaction was monitored by TLC until completion of the reaction of the starting material. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combinedWashing with water and saturated saline in sequence, then drying with sodium sulfate, filtering, performing rotary evaporation under reduced pressure, purifying by a chromatographic silica gel column, collecting under reduced pressure, and performing vacuum drying to obtain 25.2mg of yellow oily 1-o-bromophenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: the content of the active carbon is 83.2%,1H NMR(600MHz,CDCl3)δ16.23(s,1H),7.96(d,J＝7.6Hz,2H),7.67(d,J＝8.0Hz,1H),7.60(dd,J＝7.7,1.5Hz,1H),7.56(t,J＝7.4Hz,1H),7.48(t,J＝7.7Hz,2H),7.41(t,J＝7.5Hz,1H),7.32(td,J＝7.8,1.6Hz,1H),6.67(s,1H)。
example six: preparation of 1-p-fluorophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000102
A one-pot method:
1-p-fluorophenyl-3-phenyl-2-propiophenone (22.4mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, followed by stirring overnight at 50 deg.C, followed by TLC to monitor the reaction, followed by the addition of potassium hydroxide (11.2mg, 0.20mmol) after completion of the reaction of the starting material, followed by stirring at room temperature for 2h, followed by TLC to monitor the reaction and completion of the reaction of the starting material. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed sequentially with water and saturated brine, then dried over sodium sulfate, filtered, rotary evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 19.7mg of 1-p-fluorophenyl-3-phenyl-1, 3-propanedione as a yellow oil, yield: the content of the waste water is 81.4%,1H NMR(600MHz,CDCl3)δ16.83(s,1H),8.06–7.96(m,4H),7.58–7.53(m,1H),7.52–7.46(m,2H),7.20–7.14(m,2H),6.80(s,1H)。
example seven: preparation of 1-m-fluorophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000111
A one-pot method:
1-m-fluoroPhenyl-3-phenyl-2-propiophenone (22.4mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, stirring overnight at 50 deg.C, monitoring the reaction by TLC, after completion of the reaction of the starting material, addition of potassium hydroxide (16.8mg, 0.30mmol), stirring at room temperature for 2h, monitoring the reaction by TLC, and completion of the reaction of the starting material. The reaction solution was poured into 10mL of water, then extracted with ethyl acetate (three times 10mL each), the organic phases were combined, washed sequentially with water and saturated brine, then dried over sodium sulfate, filtered, rotary evaporated under reduced pressure, purified by a chromatographic silica gel column, collected under reduced pressure, and dried under vacuum to give 20.6mg of 1-m-fluorophenyl-3-phenyl-1, 3-propanedione as a yellow oil, yield: 85.1 percent of the total weight of the mixture,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example eight: preparation of 1- (3, 4-dimethoxyphenyl) -3-phenyl-1, 3-propanedione
Figure BDA0002254813390000121
A one-pot method:
1- (3, 4-Dimethoxyphenyl) -3-phenyl-2-propiophenone (26.6mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ with monitoring by TLC, and after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added thereto and stirred at room temperature for 2 hours, and the reaction was monitored by TLC to complete the reaction of the starting material. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed successively with water and saturated brine, then dried over sodium sulfate, filtered, rotary-evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 25.3mg of 1- (3, 4-dimethoxyphenyl) -3-phenyl-1, 3-propanedione as a yellow oil in yield: 89.1 percent of the total weight of the mixture,1H NMR(600MHz,CDCl3)δ16.95(s,1H),8.00–7.95(m,2H),7.62(dd,J＝8.4,2.0Hz,1H),7.57(d,J＝2.0Hz,1H),7.54(t,J＝7.3Hz,1H),7.48(t,J＝7.5Hz,2H),6.93(d,J＝8.4Hz,1H),6.80(s,1H),3.97(d,J＝10.3Hz,6H)。
example nine: preparation of 1-phenyl-3- (thien-2-yl) -1, 3-propanedione
Figure BDA0002254813390000122
A one-pot method:
3-phenyl-1- (thiophen-2-yl) -2-propiophenone (21.2mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at room temperature, followed by TLC to monitor the reaction, and after completion of the reaction, potassium hydroxide (16.8mg, 0.30mmol) was added, followed by stirring for 2 hours at room temperature, followed by TLC to monitor the reaction, and the reaction was completed. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed with water and saturated brine in this order, dried over sodium sulfate, filtered, rotary-evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 19.2mg of 1-phenyl-3- (thiophen-2-yl) -1, 3-propanedione as a yellow oil, yield: the content of the waste water is 83.4%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example ten: preparation of 1-phenyl-3-m-trifluoromethylphenyl-1, 3-propanedione
Figure BDA0002254813390000131
A one-pot method:
3-phenyl-1-m-trifluoromethylphenyl-2-propiophenone (27.4mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) were sequentially added thereto, the mixture was stirred overnight at 50 ℃ and the reaction was monitored by TLC, potassium hydroxide (16.8mg, 0.30mmol) was added after the reaction of the starting materials was completed,stir at rt for 2h, monitor the reaction by TLC and the starting material is reacted completely. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed with water and saturated brine in this order, dried over sodium sulfate, filtered, rotary-evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 26.6mg of 1-phenyl-3-m-trifluoromethylphenyl-1, 3-propanedione as a yellow oil, yield: 91.1 percent of the total weight of the steel,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example eleven: preparation of 1-phenyl-3- (furan-2-yl) -1, 3-propanedione
Figure BDA0002254813390000141
A one-pot method:
adding 3-phenyl-1- (furan-2-yl) -2-propiophenone ((19.6mg, 0.10mmol) to 1mL of dimethylsulfoxide solvent, sequentially adding imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol), stirring overnight at room temperature, monitoring the reaction by TLC, after the reaction of the raw materials is completed, adding potassium hydroxide (16.8mg, 0.30mmol), stirring for 2h at room temperature, monitoring the reaction by TLC, after the reaction of the raw materials is completed, pouring the reaction solution into 10mL of water, extracting with ethyl acetate (three times per 10mL), combining the organic phases, washing with water and saturated saline sequentially, drying with sodium sulfate, filtering, rotary evaporating under reduced pressure, purifying with a chromatographic silica gel column, collecting under reduced pressure, vacuum drying to obtain 17.5mg of 1-phenyl-3- (furan-2-yl) -1 as a yellow oily substance, 3-propanedione, yield: the content of the active carbon is 81.8%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example twelve: preparation of 1- (naphthalen-1-yl) -3-phenyl-1, 3-propanedione
Figure BDA0002254813390000142
A one-pot method:
1- (Naphthalen-1-yl) -3-phenyl-2-propiophenone (25.6mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ with monitoring by TLC, and after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added and stirred at room temperature for 2h with monitoring by TLC, and the reaction of the starting material was completed. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed with water and saturated brine in this order, dried over sodium sulfate, filtered, rotary-evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 23.5mg of 1- (naphthalen-1-yl) -3-phenyl-1, 3-propanedione as a yellow oil in yield: the content of the waste water is 85.8%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example thirteen: preparation of 1-cyclopropyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000151
A one-pot method:
3-cyclopropyl-1-phenyl-2-propiophenone (17.0mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, followed by stirring overnight at room temperature, followed by TLC to monitor the completion of the reaction, followed by the addition of potassium hydroxide (16.8mg, 0.30mmol), stirring at room temperature for 2h, followed by TLC to monitor the completion of the reaction. The reaction solution was poured into 10mL of water, followed by extraction with ethyl acetate (three times 10mL each), and the organic phases were combined, washed with water and saturated brine in this order, dried over sodium sulfate, filtered, rotary-evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 15.1mg of 1-cyclopropyl-3-phenyl-1, 3-propanedione as a yellow oil, yield: 80.3 percent，1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
Example fourteen: preparation of 1-p-bromophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000152
A one-pot method:
3-p-bromophenyl-1-phenyl-2-propenone (28.5mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ and monitored for reaction by TLC, and after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added and stirred at room temperature for 2 hours, and the reaction was monitored by TLC until completion of the reaction of the starting material. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 25.6mg of yellow oily 1-p-bromophenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: the content of the waste water is 84.4%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example fifteen: preparation of 1-p-bromophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000161
A one-pot method:
adding 3-p-bromophenyl-1-phenyl-2-propiophenone (28.5mg, 0.10mmol) to 1mL of dimethyl sulfoxide solvent, sequentially adding pyrazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol), stirring at 50 ℃ overnight, monitoring the reaction by TLC, adding potassium hydroxide (1.1 mmol) after the reaction of the raw materials is completed6.8mg, 0.30mmol), stirred at room temperature for 2h, the reaction was monitored by TLC and the starting material reacted completely. The reaction solution was poured into 10mL of water, then extracted with ethyl acetate (10 mL each time after three extractions), the organic phases were combined, washed sequentially with water and saturated brine, then dried over sodium sulfate, filtered, rotary evaporated under reduced pressure, purified by a silica gel column chromatography, collected under reduced pressure, and dried under vacuum to give 25.0mg of 1-p-bromophenyl-3-phenyl-1, 3-propanedione as a yellow oil, yield: the content of the waste water is 82.5%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example sixteen: preparation of 1-p-bromophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000171
A one-pot method:
1-p-bromophenyl-3-phenyl-2-propiophenone (28.5mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of imidazole (8.16mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ and monitored for reaction by TLC, and after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added and stirred at room temperature for 2 hours, and the reaction was monitored by TLC until completion of the reaction of the starting material. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 24.5mg of yellow oily 1-p-bromophenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: 85.8 percent of the total weight of the steel,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example seventeen: preparation of 1-p-bromophenyl-3-phenyl-1, 3-propanedione
Figure BDA0002254813390000172
A one-pot method:
1-p-bromophenyl-3-phenyl-2-propiophenone (28.5mg, 0.10mmol) was added to 1mL of dimethylsulfoxide solvent, followed by the addition of 2-methylimidazole (9.84mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and DMAP (2.44mg, 0.02mmol) in that order, and the mixture was stirred overnight at 50 ℃ with monitoring by TLC, and after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added, and the mixture was stirred at room temperature for 2 hours with monitoring by TLC, whereupon the reaction of the starting material was completed. Pouring the reaction solution into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, performing reduced pressure collection, and performing vacuum drying to obtain 24.8mg of yellow oily 1-p-bromophenyl-3-phenyl-1, 3-propanedione, wherein the yield is as follows: the content of the active carbon is 81.8%,1H NMR(600MHz,CDCl3)δ16.80(s,1H),7.98(dd,J＝8.3,1.2Hz,2H),7.89–7.83(m,2H),7.65–7.61(m,2H),7.59–7.54(m,1H),7.53–7.48(m,2H),6.82(s,1H)。
example eighteen: preparation of 1, 3-diphenyl-1, 3-propanedione
Figure BDA0002254813390000181
A one-pot method:
1, 3-Diphenyl-2-propiophenone (20.6mg, 0.10mmol) was added to 1mL of dimethylsulfoxide as a solvent, followed by the addition of pyrrole (80.4mg, 0.12mmol), triethylamine (12.1mg, 0.12mmol) and NaCO3(37.3mg, 0.45mmol), stirred overnight at 50 deg.C (about 16 h), monitored by TLC for reaction, after completion of the reaction of the starting material, potassium hydroxide (16.8mg, 0.30mmol) was added, stirred at room temperature for 8h, and monitored by TLC for completion of the reaction of the starting material. Pouring the reaction liquid into 10mL of water, extracting with ethyl acetate (extracting for three times, 10mL each time), combining organic phases, washing with water and saturated saline in sequence, drying with sodium sulfate, filtering, performing reduced pressure rotary evaporation, purifying by a chromatographic silica gel column, collecting under reduced pressure, performing vacuum drying to obtain 18.0mg of yellow oily 1, 3-diphenyl-1, 3-propanedione, and collectingRate: 80.3 percent of the total weight of the mixture,1H NMR(600MHz,CDCl3)δ16.85(s,1H),7.99(dd,J＝5.2,3.3Hz,4H),7.58–7.53(m,2H),7.53–7.45(m,4H),6.86(s,1H)。
while the present invention has been described in detail with reference to the embodiments, it should not be construed as limited to the scope of the patent. Various modifications and changes may be made by those skilled in the art without inventive step within the scope of the appended claims.

Claims (7)

1. The nonmetal-catalyzed method for preparing the 1, 3-diketone compound based on the alkynone is characterized in that the method for preparing the 1, 3-diketone compound is a fractional step method or a one-pot method; wherein, the step-by-step method comprises the following steps:
s1: putting the alkynone compound I, the nitrogen-containing aromatic compound II and a base into a reactor filled with a solvent according to a molar ratio of 1: 1-4: 1-4.5, uniformly stirring, reacting at 20-80 ℃ for 12-24 h, and then separating and purifying to obtain a compound III; the reaction equation is shown in formula (1-1):
Figure FDA0003679920300000011
s2: putting the compound III and a second-class alkali into a reactor filled with a solvent according to a molar ratio of 1: 1-5, uniformly stirring, reacting at 20-50 ℃ for 2-12 h, and then separating and purifying to obtain a 1, 3-diketone compound IV; the reaction equation is shown in formula (1-2):
Figure FDA0003679920300000012
the one-pot method comprises the following steps:
firstly putting an alkynone compound I, a nitrogen-containing aromatic compound II and a base into a reactor according to a molar ratio of 1: 1-4: 1-4.5, and reacting at 20-80 ℃ for 12-24 h; adding a second class of alkali into the reactor, reacting for 2-12 h at 20-50 ℃ at a molar ratio of the added second class of alkali to the alkynone compound I of 1-5: 1, and separating and purifying to obtain a 1, 3-diketone compound IV; the reaction equation is shown in the formulas (1-3):
Figure FDA0003679920300000021
wherein R is1、R2Are respectively and independently selected from phenyl, alkylphenyl of C1-C6, alkoxyphenyl of C1-C6, halogenated alkylphenyl of C1-C6, naphthyl, heteroaryl, cycloalkyl of C3-C6 or alkyl of C1-C6;
a is nitrogen atom or carbon atom, D is carbon atom or nitrogen atom; r3、R4、R5And R6Each independently selected from hydrogen, alkyl of C1-C6, halogenated alkyl of C1-C6, naphthene or halogen of C3-C6, or R5And R6Connected to form a benzene ring or a substituted benzene ring;
the alkali is 4-dimethylamino pyridine, and the molar ratio of the alkali to the alkynone compound I is 1-1.5: 1; or the alkali is a mixture of 4-dimethylaminopyridine and triethylamine according to a molar ratio of 1: 5-10, wherein the molar ratio of the mixture to the alkynone compound I is 1-1.5: 1; the second alkali is sodium hydroxide, potassium hydroxide or lithium hydroxide.
2. The non-metal catalyzed acetylenic ketone based process for the preparation of 1, 3-diketones according to claim 1 wherein: the R is1And R2Each independently selected from phenyl, methylphenyl, ethylphenyl, trifluoromethylphenyl, methoxyphenyl, dimethoxyphenyl, halophenyl, thienyl, furyl, pyridyl, naphthyl, cyclopropyl, methyl or butyl; the R is3、R4、R5And R6Each independently selected from hydrogen, methyl, ethyl, isopropyl, cyclopropyl, trifluoromethyl, fluoro, bromo or iodo, or R5And R6Connected to form benzene rings or substituted benzene rings.
3. The non-metal catalyzed acetylenic ketone based process for the preparation of 1, 3-diketones according to claim 1 wherein: the compound II is pyrrole, imidazole, pyrazole, benzimidazole, indole, indazole, 2-methylimidazole, 2-isopropylimidazole, 2-ethylimidazole or 2-methyl-5-nitro imidazole.
4. The non-metal catalyzed acetylenic ketone based process for the preparation of 1, 3-diketones according to claim 1 wherein: the reaction temperature of S1 in the step method is room temperature-50 ℃, and the reaction time is 16 h; the reaction temperature of S2 was room temperature, and the reaction time was 8 h.
5. The non-metal catalyzed acetylenic ketone based process for the preparation of 1, 3-diketones according to claim 1 wherein: the reaction temperature of the front section in the one-pot method is between room temperature and 50 ℃, and the reaction time is 16 h; the latter stage reaction temperature is room temperature and the time is 8 h.
6. The non-metal catalyzed acetylenic ketone based process for the preparation of 1, 3-diketones according to claim 1 wherein: the solvent is dimethyl sulfoxide, 1, 4-dioxane, tetrahydrofuran, acetone, acetonitrile, ethanol or methanol.
7. The non-metal catalyzed acetylenic ketone based process for preparing 1, 3-diketones according to claim 1 wherein said separation purification process comprises the steps of: pouring the reaction solution after the reaction into cold water, extracting with ethyl acetate for three times, and combining organic layers; then, the organic layer was washed with water and saturated brine in this order, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure; then separating by a chromatographic silica gel column to obtain the corresponding compound.
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