A 1,4-dicarbonyl compound, its preparation method and application

Abstract

The present invention discloses a 1,4-dicarbonyl compound, its preparation method and application. The 1,4-dicarbonyl compound has the structure shown in Formula I. The preparation method includes the following steps: S1. Compound a reacts with thionyl chloride and dimethylamine hydrochloride to form compound b; S2. Compound b reacts with iodine, magnesium chips and 4-bromo-1-butene to form compound c; S3. Compound c reacts with dimethyl sulfide to obtain the compound with the structure shown in Formula I. Among them, the preparation method of the 1,4-dicarbonyl compound of the present invention is simple in operation and relatively mild in reaction conditions, and has broad application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and particularly relates to a 1,4-dicarbonyl compound, a preparation method thereof, and an application thereof. Background Art

[0002] 1,4-Dicarbonyl compounds are important organic compounds, widely present in natural products and bioactive pharmaceutical molecules, and are also common intermediates in organic synthesis reactions. They are applied to organic synthesis and polymer fields in agriculture, medicine, petrochemical industries, and are often used to prepare heterocyclic compounds such as furan, pyrrole, indole, and non-heterocyclic compounds such as cyclopentenone. Therefore, developing simple, green, and efficient synthesis methods for 1,4-dicarbonyl compounds is a hot topic in modern organic chemistry research.

[0003] Currently, the main methods for synthesizing 1,4-dicarbonyl compounds include the synthesis of 1,4-dicarbonyl compounds by the Stetter reaction of aldehydes with α,β-unsaturated aldehydes and ketones, the hydroalkylation acylation of aldehydes with α,β-unsaturated ketones under the action of metal catalysts to synthesize 1,4-dicarbonyl compounds, and the base-catalyzed synthesis of 1,4-dicarbonyl compounds, etc.

[0004] Among them, the preparation of 1,4-dicarbonyl compounds by the Stetter and metal-catalyzed reactions is relatively mature, but the above preparation methods have more or less some limiting factors. For example, the raw material sources are complex. Most of the starting materials of these methods are derivatives of two carbonyl compounds, and the substrate range is narrow; and the reaction conditions are relatively harsh. Some methods require the use of a large amount of base, the catalyst is expensive, and the catalytic system is complex. Summary of the Invention

[0005] In view of the above-mentioned defects of the prior art, the present invention provides a preparation method of a 1,4-dicarbonyl compound. This preparation method uses a benzoic acid compound a as a raw material, reacts with thionyl chloride and dimethylamine hydrochloride to obtain an N,N-dimethylbenzamide compound b, the compound b reacts with iodine, magnesium chips, and 4-bromo-1-butene to prepare a 1-phenyl-4-penten-1-one compound c, and the compound c reacts with ozone and dimethyl sulfide to obtain the target product. This preparation method is simple to operate, the reaction conditions are relatively mild, and it has a wide application prospect.

[0006] To solve the above technical problems, in the first aspect of the present invention, a 1,4-dicarbonyl compound is provided, and its structural general formula is as follows:

[0007] Wherein R is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, alkoxy, fluoroalkyl, ester group, thioether, sulfone, sulfoxide, and tertiary amine group.

[0008] The second aspect of the present invention provides a method for preparing the above-mentioned 1,4-dicarbonyl compound, which comprises the following steps:

[0009] S1. Compound a reacts with thionyl chloride, triethylamine, and dimethylamine hydrochloride to form compound b;

[0010] S2. Compound b reacts with iodine, magnesium chips, and 4-bromo-1-butene to form compound c;

[0011] S3. Compound c reacts with ozone and dimethyl sulfide to obtain the compound shown in Formula I; wherein the structural formulas of compounds a, b, and c are as follows:

[0012] R is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, alkoxy, fluoroalkyl, ester group, thioether, sulfone, sulfoxide, and tertiary amino group.

[0013] As a preferred embodiment, the step S1 includes:

[0014] S11. Compound a reacts with thionyl chloride to form an acyl chloride compound;

[0015] S12. The acyl chloride compound reacts with triethylamine and dimethylamine hydrochloride to form compound b.

[0016] As a preferred embodiment, the molar ratio of compound a, thionyl chloride, dimethylamine hydrochloride, and triethylamine in the step S1 is 1:(2-6):(1-2):(2-3).

[0017] As a preferred embodiment, the reaction solvent in the step S2 is any one of THF, ethylene glycol dimethyl ether, and 2-methyltetrahydrofuran.

[0018] As a preferred embodiment, the molar ratio of compound b, 4-bromo-1-butene, magnesium chips, and iodine in the step S2 is 1:(1-1.5):(1.1-1.5):(0.001-0.1).

[0019] As a preferred embodiment, the reaction solvent in the step S3 is methanol, dichloromethane, or a mixed solvent of the two.

[0020] As a preferred embodiment, the molar ratio of compound c, oxygen, and dimethyl sulfide in the step S3 is 1:(2-10):(1-2), and the amount of oxygen used is the amount introduced into the ozone generator.

[0021] The third aspect of the present invention provides a method for preparing a 2-phenylfuran compound, which is prepared by reacting the compound shown in Formula I with p-toluenesulfonic acid.

[0022] In a fourth aspect of the present invention, there is provided a method for preparing a 2-phenylpyrrole compound, which is prepared by reacting a compound represented by Formula I with p-toluenesulfonic acid and an amino compound.

[0023] As a preferred embodiment, the amino compound is selected from any one of aniline, benzylamine, methylamine, and p-chloroaniline.

[0024] Advantages of the present invention:

[0025] (1) The method for preparing the 1,4-dicarbonyl compound of the present invention uses a benzoic acid compound as a starting material, and the raw material source is rich.

[0026] (2) The method for preparing the 1,4-dicarbonyl compound of the present invention is simple in operation, the reaction conditions are relatively mild, and it has a wide application prospect.

[0027] (3) The method for preparing the 1,4-dicarbonyl compound of the present invention does not require a complex catalytic system and the use of expensive catalysts, and the cost is relatively low.

[0028] The concept, specific structure and technical effects of the present invention will be further described below to fully understand the purpose, features and effects of the present invention. Detailed Embodiments

[0029] In order to make the technical means, creative features, achieved purposes and effects of the invention easy to understand, the present invention will be further described below. However, the present invention is not limited to the following embodiments.

[0030] A 1,4-dicarbonyl compound has the following general structural formula:

[0031]

[0032] Wherein R is selected from any one of hydrogen, fluorine, chlorine, bromine, iodine, alkyl, alkoxy, fluoroalkyl, ester group, thioether, sulfone, sulfoxide, and tertiary amino group.

[0033] Alkyl includes both alkyl without substituents (unsubstituted alkyl) and alkyl with substituents (substituted alkyl).

[0034] The preferred number of carbon atoms for alkyl and alkoxy is 1-4.

[0035] Fluoroalkyl has one or more fluorine atoms connected to its carbon atom, and preferably one fluorine atom is connected to the carbon atom.

[0036] The ester group is selected from any one of ethyl acetate group, n-butyl acetate group, amyl formate group, isobutyl acetate group, butyl propionate group, isopropyl acetate group, ethyl butyrate group, and butyl butyrate group.

[0037] The preparation method of the above-mentioned 1,4-dicarbonyl compound has the following reaction mechanism:

[0038]

[0039] Specifically, it includes the following steps:

[0040] S1. Compound a reacts with thionyl chloride and dimethylamine hydrochloride to form compound b. The structural formulas of compound a and compound b are as follows:

[0041]

[0042] Compound a is a benzoic acid compound. Compound a reacts with thionyl chloride to form an acyl chloride compound, and the acyl chloride compound reacts with triethylamine and dimethylamine hydrochloride to obtain an N,N-dimethylbenzamide compound b. After that, through the steps of washing with water and concentration, a purified product is obtained.

[0043] In step S1, the benzoic acid compound is used as the starting material, and the raw material source is rich; at the same time, the purification step is simple and easy to implement.

[0044] Among them, the molar ratio of compound a, thionyl chloride, dimethylamine hydrochloride, and triethylamine is 1:(2 - 6):(1 - 2):(2 - 3). In this reaction, thionyl chloride is in excess, so that compound a can react fully and is thus completely converted into compound b.

[0045] S2. In a THF environment, compound b is mixed with iodine and magnesium chips, and then 4-bromo-1-butene is added to obtain compound c. The structural formula of compound c is as follows:

[0046]

[0047] After compound b, THF, iodine, and magnesium chips are added to the reaction flask, 4-bromo-1-butene needs to be added dropwise under nitrogen protection, and the temperature is controlled at 5 - 15 °C (in this process, the dropping amount needs to be controlled, and it should be noted that too much cannot be added at the beginning. After the reaction is initiated, the remaining raw materials can be added dropwise). After the dropping is completed, the temperature is raised to 20 - 30 °C, stirred, and then dilute hydrochloric acid is added. After phase separation, washing and concentration are carried out to obtain compound c.

[0048] Taking 1-phenyl-4-penten-1-pentanone as an example, the reaction mechanism corresponding to step S2 is as follows:

[0049]

[0050] The above reaction can be initiated under the temperature condition of 0-30°C. However, generally, the lower the temperature, the slower the initiation rate. To initiate the reaction faster, the reaction temperature can be increased. However, a higher temperature will lead to more side reactions. Therefore, on the one hand, the initiation temperature should be appropriately increased, and on the other hand, the initiation temperature should be strictly controlled to avoid the occurrence of side reactions. Considering various factors and experimental exploration, the temperature for dropping 4-bromo-1-butene is controlled at 5-15°C, and the reaction temperature after dropping is controlled at 20-30°C.

[0051] Among them, the molar ratio of compound b, 4-bromo-1-butene, magnesium shavings, and iodine is 1:(1-1.5):(1.1-1.5):(0.001-0.1).

[0052] S3. Compound c reacts with ozone and dimethyl sulfide to obtain the target product.

[0053] First, add methanol as a solvent to the reaction flask and protect it by replacing with nitrogen. Pass ozone as an oxidant, control the temperature at -10°C - 0°C, and the reaction time is 3-5 h. Then, add dimethyl sulfide as a reducing agent and react for 2-3 h to obtain the target product.

[0054] Taking 1-phenyl-4-penten-1-one as an example, the reaction mechanism of the above reaction is as follows:

[0055]

[0056] After the reaction is completed, add water to the reaction product, extract with ethyl acetate, wash the organic phase with saturated brine, dry with anhydrous sodium sulfate, and concentrate the organic phase to dryness to obtain the purified product.

[0057] Among them, the molar ratio of compound c, oxygen, and dimethyl sulfide is 1:(2-10):(1-2), and the amount of oxygen used is the amount introduced into the ozone generator.

[0058] 1,4-Dicarbonyl compounds are widely used and are common intermediates in organic synthesis reactions. The inventors of this application used 1,4-dicarbonyl compounds as raw materials to synthesize furan compounds or pyrrole compounds. Specifically:

[0059] A method for preparing a 2-phenylfuran compound is prepared by reacting a compound represented by formula I with p-toluenesulfonic acid.

[0060] Specifically: Add the compound represented by formula I and toluene to the reaction flask, heat up to 60-70°C, add p-toluenesulfonic acid, and react for 2-3 h. After the reaction is completed, wash, separate the phases, and concentrate the organic phase to dryness to obtain the 2-phenylfuran compound. The molar ratio of the compound represented by formula I to p-toluenesulfonic acid is 1:1.

[0061] A preparation method of 2-phenylpyrrole compounds is prepared by reacting the compound shown in Formula I with p-toluenesulfonic acid and an amine group-containing compound. Specifically: Add the compound shown in Formula I and toluene into a reaction flask, heat up to 30-40 °C, add p-toluenesulfonic acid, dropwise add the THF solution of the amine group compound, react for 2-3 h. After the reaction is completed, wash, separate the phases, and concentrate the organic phase to dryness to obtain 2-phenylpyrrole compounds.

[0062] The molar ratio of the compound shown in Formula I to p-toluenesulfonic acid and the amine group compound is 1:1:1.2.

[0063] The amine group compound selected at this time is any one of aniline, benzylamine, methylamine, and p-chloroaniline.

[0064] In order to obtain better reaction conditions, the inventors of this application screened the reaction raw materials, solvents, etc. during the reaction process. Taking the preparation of 1-phenyl-4-pentanal-1-one as an example, the specific screening process is as follows:

[0065] 1. Benzoic acid reacts with thionyl chloride and dimethylamine hydrochloride to form N,N-dimethylbenzamide

[0066]

[0067] By changing the equivalent ratio of benzoic acid, thionyl chloride, dimethylamine hydrochloride, and triethylamine, compare the yields of the reaction products under different equivalent ratios. The specific dosages are shown in Table 1.

[0068] The equivalent ratio here is the multiple ratio of the molar equivalents of different raw materials. Taking the reaction of hydrochloric acid and sodium hydroxide as an example, when both hydrochloric acid and sodium hydroxide are 1 mol, the equivalent ratio of hydrochloric acid to sodium hydroxide is 1. If the dosage of hydrochloric acid is 3 mol and the dosage of sodium hydroxide is 5 mol, it is equivalent to the dosage of hydrochloric acid being 1 molar equivalent, while the dosage of sodium hydroxide is 5 / 3 molar equivalents, and the equivalent ratio of hydrochloric acid to sodium hydroxide is 3:5.

[0069] Table 1

[0070]

[0071] It can be seen from Table 1 that when thionyl chloride is in excess, further increasing the dosage of triethylamine to make triethylamine fully in excess can increase the yield of the reaction product, but the effect is very small, only increasing from 70% to 73%. This shows that triethylamine is not the key factor determining the reaction yield. The inventors continued to explore, changed the dosage of thionyl chloride, and increased the equivalent ratio of thionyl chloride to benzoic acid from 2:1 to 5:1, while other conditions remained basically unchanged. At this time, it was unexpectedly found that the reaction yield increased from 73% to 95%. Regarding the influence of dimethylamine hydrochloride on the reaction yield, the inventors also conducted relevant investigations and found that the influence is relatively small and can be almost ignored for the reaction yield.

[0072] Thionyl chloride, dimethylamine hydrochloride, and triethylamine are all used as reaction raw materials to convert benzoic acid into N,N-dimethylbenzamide. However, their effects on the reaction process are different. Therefore, in the specific experimental process, in order to obtain a higher reaction yield, there are obvious differences in their dosages. Thionyl chloride needs to be in sufficient excess (equivalent ratio ≥ 5), triethylamine needs to be in excess (equivalent ratio 2 - 3), and dimethylamine hydrochloride only needs to be slightly higher than 1 molar equivalent.

[0073] 2、 N,N-dimethylbenzamide reacts with iodine, magnesium chips, and 4-bromo-1-butene to form 1-phenyl-4-penten-1-pentanone

[0074]

[0075] By changing the equivalent ratios of N,N-dimethylbenzamide with iodine, magnesium chips, and 4-bromo-1-butene under different solvent conditions, the yields of the reaction products under different equivalent ratios were compared. The specific screening conditions are shown in Table 2.

[0076] Table 2

[0077]

[0078] As can be seen from Table 2, when other dosages remain basically unchanged, When the equivalent ratio of iodine to N,N-dimethylbenzamide is increased from 0.001:1 to 0.01:1, the reaction yield increases by 13%. However, when the amount of iodine is further increased such that the equivalent ratio of iodine to N,N-dimethylbenzamide is 0.1:1, the reaction yield decreases instead. Therefore, the amount of iodine used is very critical for the reaction yield, and the amount of iodine needs to be strictly controlled. Keeping other conditions unchanged, when the solvent is changed from THF to 2-MeTHF or ethylene glycol dimethyl ether, the reaction yield decreases significantly, even from 90% to 76%. Although THF, 2-MeTHF, and ethylene glycol dimethyl ether are all commonly used reaction solvents in organic reaction processes, in this reaction process, THF is obviously the better choice. In addition, the inventors of this application also investigated the effect of 4-bromo-1-butene on the reaction yield and found that when the amount of 4-bromo-1-butene is slightly increased, the reaction yield decreases significantly.

[0079] 3. 1-Phenyl-4-penten-1-pentanone reacts with ozone and dimethyl sulfide to obtain the target product.

[0080]

[0081] By changing the equivalent ratios of 1-phenyl-4-penten-1-pentanone with oxygen and dimethyl sulfide under different solvent conditions, the yields of the reaction products under different equivalent ratios were compared. The specific conditions are shown in Table 3.

[0082] Table 3

[0083]

[0084]

[0085] Since ozone is produced by the ozone generator itself, an oxygen cylinder is connected to the ozone machine, and then air is introduced to generate ozone. Therefore, the amount of ozone used is controlled by controlling the amount of oxygen introduced. Under the condition that other conditions are basically unchanged, when the molar equivalent ratio of oxygen to 1-phenyl-4-penten-1-one is increased from 2:1 to 5:1, the yield increases by 15%, indicating that oxygen is the key factor controlling the progress of the whole reaction. However, when the amount of oxygen used continues to increase, the change in yield is small. In addition, by changing the type of solvent, when the solvent is changed from dichloromethane to methanol or dichloromethane / methanol (1 / 1), the reaction yield decreases.

[0086] Synthesis of Compound b

[0087] Example 1

[0088] Add benzoic acid (10 g) and thionyl chloride (48.7 g) to a 250 mL reaction flask, close the reaction kettle, heat up to reflux, and react for 2 - 4 h; stop the reaction and concentrate to dryness; then add dichloromethane to dissolve, control the temperature at 0 - 10 °C, add 24.8 g of triethylamine, stir for 30 min, add 8.0 g of dimethylamine hydrochloride, react for 2 - 3 h, end the reaction, wash with water, concentrate the organic phase, and purify by column chromatography to obtain 11.6 g of the intermediate N,N-dimethylbenzamide with a yield of 95%.

[0089] Example 2

[0090] Add benzoic acid (50 g) and thionyl chloride (146.0 g) to a 1500 mL reaction flask, close the reaction kettle, heat up to reflux, and react for 2 - 4 h; stop the reaction and concentrate to dryness; then add dichloromethane to dissolve, control the temperature at 0 - 10 °C, add 108.0 g of triethylamine, stir for 30 min, add 50.0 g of dimethylamine hydrochloride, react for 2 - 3 h, end the reaction, wash with water, concentrate the organic phase, and purify by column chromatography to obtain 56.8 g of the intermediate N,N-dimethylbenzamide with a yield of 93%.

[0091] Example 3

[0092] Add benzoic acid (100 g) and thionyl chloride (243.6 g) into a 2500 mL reaction flask. Close the reaction kettle and heat up to reflux for 2 - 4 h. Stop the reaction and concentrate to dryness. Then add dichloromethane to dissolve. Control the temperature at 0 - 10 °C, add 183 g of triethylamine, stir for 30 min, add 73.5 g of dimethylamine hydrochloride, react for 2 - 3 h. After the reaction is completed, wash with water. Concentrate the organic phase and purify by column chromatography to obtain 117.2 g of intermediate N,N-dimethylbenzamide with a yield of 96%.

[0093] Example 4

[0094] Add benzoic acid (100 g) and thionyl chloride (214.4 g) into a 2500 mL reaction flask. Close the reaction kettle and heat up to reflux for 2 - 4 h. Stop the reaction and concentrate to dryness. Then add dichloromethane to dissolve. Control the temperature at 0 - 10 °C, add 205 g of triethylamine, stir for 30 min, add 73.5 g of dimethylamine hydrochloride, react for 2 - 3 h. After the reaction is completed, wash with water. Concentrate the organic phase and purify by column chromatography to obtain 116 g of intermediate N,N-dimethylbenzamide with a yield of 95%.

[0095] Example 5

[0096] Add 3-bromobenzoic acid (20.1 g) and thionyl chloride (50.4 g) into a 250 mL reaction flask. Heat up to reflux for 2 - 4 h. Stop the reaction and concentrate to dryness. Then add dichloromethane to dissolve. Control the temperature at 0 - 10 °C, add 25.3 g of triethylamine, stir for 30 min, add 12.0 g of dimethylamine hydrochloride, react for 2 - 3 h. After the reaction is completed, wash with water. Concentrate the organic phase and purify by column chromatography to obtain 20.5 g of intermediate 3-bromo-N,N-dimethylbenzamide with a yield of 90%.

[0097] Example 6

[0098] Add p-methoxybenzoic acid (15.2 g) and thionyl chloride (59.6 g) into a 250 mL reaction flask. Heat up to reflux for 2 - 4 h. Stop the reaction and concentrate to dryness. Then add dichloromethane to dissolve. Control the temperature at 0 - 10 °C, add 25.5 g of triethylamine, stir for 30 min, add 12.3 g of dimethylamine hydrochloride, react for 2 - 3 h. After the reaction is completed, wash with water. Concentrate the organic phase and purify by column chromatography to obtain 16.1 g of intermediate p-methoxy-N,N-dimethylbenzamide with a yield of 89%.

[0099] Example 7

[0100] Add 4-chlorobenzoic acid (15.7 g) and thionyl chloride (59.6 g) to a 250 mL reaction flask, heat to reflux, and react for 2 - 4 h; stop the reaction and concentrate to dryness; then add dichloromethane to dissolve, control the temperature at 0 - 10 °C, add 26.0 g of triethylamine, stir for 30 min, add 12.3 g of dimethylamine hydrochloride, react for 2 - 3 h, after the reaction is completed, wash with water, concentrate the organic phase, and purify by column chromatography to obtain 17.1 g of the intermediate 4-chloro-N,N-dimethylbenzamide with a yield of 93%.

[0101] Example 8

[0102] Add 2-furoic acid (11.2 g) and thionyl chloride (55.5 g) to a 250 mL reaction flask, heat to reflux, and react for 2 - 4 h; stop the reaction and concentrate to dryness; then add dichloromethane to dissolve, control the temperature at 0 - 10 °C, add 25.0 g of triethylamine, stir for 30 min, add 12.2 g of dimethylamine hydrochloride, react for 2 - 3 h, after the reaction is completed, wash with water, concentrate the organic phase, and purify by column chromatography to obtain 12.7 g of the intermediate N,N-dimethylfuran-2-carboxamide with a yield of 91%.

[0103] Synthesis of Compound c

[0104] Example 9

[0105] Add 11 g of N,N-dimethylbenzamide, 110 mL of THF, 0.2 g of iodine, and 2.2 g of magnesium shavings to a 2500 mL reaction flask, add 4-bromo-1-butene (10.9 g) dropwise under nitrogen protection, control the temperature at 5 - 15 °C (control the dropping amount, pay attention not to add too much at the beginning; the reaction has an induction period, and then add the remaining raw materials after initiation); after dropping, stir for 1 - 2 h, heat to 20 - 30 °C, and stir for 1 h. Add dilute hydrochloric acid and stir for 0.5 h, separate the phases; wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 10 g of 1-phenyl-4-penten-1-one with a yield of 90%.

[0106] Example 10

[0107] Add 100 g of N,N-dimethylbenzamide (Compound b), 1000 mL of THF, 1.7 g of iodine, and 20.4 g of magnesium chips into a 2500 mL reaction flask. Under nitrogen protection, add 4-bromo-1-butene (110.6 g) dropwise, controlling the temperature at 5 - 15 °C (control the dropping rate and be careful not to add too much at the beginning; there is an induction period for the reaction, and add the remaining raw materials dropwise after initiation); after the dropping is complete, stir for 1 - 2 h, raise the temperature to 20 - 30 °C, and stir for 1 h. Add dilute hydrochloric acid and stir for 0.5 h, then separate the phases; wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 99.8 g of 1-phenyl-4-penten-1-one with a yield of 93%.

[0108] Example 11

[0109] Add 160 mL of THF, 2.1 g of magnesium chips, 0.2 g of iodine, and 2 g of 4-bromo-1-butene into a 250 mL reaction flask, and stir at room temperature; after the reaction is initiated, control the temperature at 15 - 25 °C, add 4-bromo-1-butene (9.2 g) dropwise, and after the dropping is complete, continue the reaction for 1 - 2 h. Then, at 15 - 25 °C, add N,N-dimethyl-3-bromobenzamide (20.5 g) dropwise to the reaction solution; after the dropping is complete, stir for 2 h, add dilute hydrochloric acid and stir for 0.5 h, then separate the phases; wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 17.8 g of 1-(3-bromophenyl)-4-penten-1-one with a yield of 83%.

[0110] Example 12

[0111] Add 160 mL of THF, 2.7 g of magnesium chips, 0.2 g of iodine, and 2 g of 4-bromo-1-butene into a 250 mL reaction flask, and stir at room temperature; after the reaction is initiated, control the temperature at 15 - 25 °C, add 4-bromo-1-butene (12.5 g) dropwise, and after the dropping is complete, continue the reaction for 1 - 2 h. Then, at 15 - 25 °C, add N,N-dimethyl-4-methoxybenzamide (16.0 g) dropwise to the reaction solution; after the dropping is complete, stir for 2 h, add dilute hydrochloric acid and stir for 0.5 h, then separate the phases; wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 13.0 g of 1-(p-methoxyphenyl)-4-penten-1-one with a yield of 76%.

[0112] Example 13

[0113] Add THF (170 mL), magnesium chips (2.7 g), iodine (0.3 g) and 4-bromo-1-butene (2 g) into a 250 mL reaction flask, and stir at room temperature. After the reaction is initiated, control the temperature at 15 - 25 °C, and dropwise add 4-bromo-1-butene (12.9 g). After the addition is complete, continue the reaction for 1 - 2 h. Then, at 15 - 25 °C, dropwise add N,N-dimethyl-4-chlorobenzamide (17.1 g) into the reaction solution. After the addition is complete, stir for 2 h, add dilute hydrochloric acid and stir for 0.5 h, then separate the phases. Wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 1-(4-chlorophenyl)-4-penten-1-one, 14.7 g, with a yield of 81%.

[0114] Example 14

[0115] Add THF (160 mL), magnesium chips (2.7 g), iodine (0.3 g) and 4-bromo-1-butene (2 g) into a 250 mL reaction flask, and stir at room temperature. After the reaction is initiated, control the temperature at 15 - 25 °C, and dropwise add 4-bromo-1-butene (12.3 g). After the addition is complete, continue the reaction for 1 - 2 h. Then, at 15 - 25 °C, dropwise add N,N-dimethylfuran-2-carboxamide (12.7 g) into the reaction solution. After the addition is complete, stir for 2 h, add dilute hydrochloric acid and stir for 0.5 h, then separate the phases. Wash with saturated brine, concentrate the organic phase, and purify by column chromatography to obtain 1-(furan-2-yl)pent-4-en-1-one, 10.8 g, with a yield of 79%.

[0116] Synthesis of 1,4-dicarbonyl compound

[0117] Example 15

[0118] Add 5 g of 1-phenyl-4-penten-1-one, methanol (50 mL) into a 100 mL reaction flask, displace the air with nitrogen three times for protection. Under nitrogen protection, add sodium bicarbonate and stir for 30 min. Pass ozone (prepared by oneself with an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas through, the amount of oxygen passed in is about 5 g), control the temperature at -10 - 0 °C, and it takes 2 - 3 h. Control the reaction for 3 - 5 h, add 3 g of dimethyl sulfide, control the reaction for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate, wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 1-phenyl-4-pentanal-1-one, 4.4 g, with a yield of 86%.

[0119] The NMR characterization parameters are as follows:

[0120] 11H NMR (400 MHz, CDCl3): δ 9.89 (s, 1H), 7.98 (d, J = 8.1 Hz, 2H), 7.57 (t, J = 6.8 Hz, 1H), 7.46 (t, J = 7.2 Hz, 2H), 3.32 (t, J = 6.2 Hz, 2H), 2.92 (t, J = 6.2 Hz, 2H).

[0121] Example 16

[0122] Add 50 g of 1-phenyl-4-penten-1-one and 500 mL of methanol to a 1000 mL reaction flask. Replace the air with nitrogen three times for protection. Add sodium bicarbonate under nitrogen protection and stir for 30 min. Pass ozone (prepared by oneself with an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas through, the amount of oxygen passed in is about 70 g). Control the temperature at -10 - 0 °C, take 2 - 3 h, control the reaction temperature for 3 - 5 h. Add 29.5 g of dimethyl sulfide and control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 45.6 g of 1-phenyl-4-pentanal-1-one, with a yield of 90%.

[0123] Example 17

[0124] Add 17.0 g of 1-(3-bromophenyl)-4-penten-1-one and 170 mL of methanol to a 250 mL reaction flask. Replace the air with nitrogen three times for protection. Pass ozone (prepared by oneself with an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas through, the amount of oxygen passed in is about 20 g). Control the temperature at -10 - 0 °C, take 2 - 3 h, control the reaction temperature for 3 - 5 h. Add 6.7 g of dimethyl sulfide and control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 15.1 g of 1-(3-bromophenyl)-4-pentanal-1-one, with a yield of 88%.

[0125] Example 18

[0126] Add 13.0 g of 1-(p-methoxyphenyl)-4-penten-1-one and 170 mL of methanol to a 250 mL reaction flask. Replace the air with nitrogen three times for protection. Pass ozone (prepared by oneself with an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas through, the amount of oxygen passed in is about 15 g). Control the temperature at -10 - 0 °C, take 2 - 3 h, control the reaction temperature for 3 - 5 h. Add 6.3 g of dimethyl sulfide and control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 11.3 g of 1-(p-methoxyphenyl)-4-pentanal-1-one, with a yield of 86%.

[0127] Example 19

[0128] Add 14.7 g of 1-(4-chlorophenyl)pent-4-en-1-one and 150 mL of methanol into a 250 mL reaction flask. Protect by displacing with nitrogen three times. Pass ozone (prepared by oneself through an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas in, the amount of oxygen introduced is about 15 g). Control the temperature at -10 - 0 °C, take 2 - 3 hours, control the reaction temperature for 3 - 5 h, add 7.0 g of dimethyl sulfide, control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 13.1 g of 1-(4-chlorophenyl)pent-4-al-1-one, with a yield of 88%.

[0129] Example 20

[0130] Add 10.8 g of 1-(furan-2-yl)pent-4-en-1-one and 110 mL of methanol into a 250 mL reaction flask. Protect by displacing with nitrogen three times and stir for 30 min. Pass ozone (prepared by oneself through an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas in, the amount of oxygen introduced is about 12 g). Control the temperature at -10 - 0 °C, take 2 - 3 hours, control the reaction temperature for 3 - 5 h, add 6.7 g of dimethyl sulfide, control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 8.2 g of 1-(furan-2-yl)pent-4-al-1-one, with a yield of 75%.

[0131] Example 21

[0132] Add 14.7 g of 1-(4-chlorophenyl)pent-4-en-1-one and 150 mL of methanol into a 250 mL reaction flask. Protect by displacing with nitrogen three times. Pass ozone (prepared by oneself through an ozone generator, connect an oxygen cylinder to the ozone machine and then let the gas in, the amount of oxygen introduced is about 25 g). Control the temperature at -10 - 0 °C, take 2 - 3 hours, control the reaction temperature for 3 - 5 h, add 8 g of dimethyl sulfide, control the reaction temperature for 2 - 3 h. After the reaction is completed, add water, extract with ethyl acetate. Wash the organic phase with semi-saturated brine, dry with anhydrous sodium sulfate, concentrate the organic phase, and purify by column chromatography to obtain 13.1 g of 1-(4-chlorophenyl)pent-4-al-1-one, with a yield of 88%.

[0133] Example 22

[0134] Preparation method of 2-phenylfuran compounds, comprising the following steps: Add 1 g of 1-phenyl-4-penten-1-one, toluene (10 mL) into a 50 mL reaction flask, heat up to 60 - 70 °C, add 0.1 g of p-toluenesulfonic acid, control the temperature for reaction for 2 - 3 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 0.6 g of the product 2-phenylfuran, with a yield of 70%.

[0135] Its nuclear magnetic characterization parameters are as follows:

[0136] 1 H NMR(CDCl3,400MHz): δ7.67(m,2H),7.47(m,1H),7.38(m,2H),7.25(m,1H),6.65(m,1H),6.47(m,1H).

[0137] Example 23

[0138] Preparation method of 2-phenylfuran compounds, comprising the following steps: Add 20 g of 1-phenyl-4-penten-1-one, toluene (200 mL) into a 1000 mL reaction flask, heat up to 60 - 70 °C, add p-toluenesulfonic acid (1.5 g), control the temperature for reaction for 2 - 3 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase to dryness, and obtain 14.2 g of the product 2-phenylfuran, with a yield of 80%.

[0139] Example 24

[0140] Add 1 g of 1-phenyl-4-penten-1-one, toluene (10 mL) into a 50 mL reaction flask, heat up to 30 - 40 °C, add p-toluenesulfonic acid (0.1 g), control the temperature and dropwise add a THF solution of methylamine, control the temperature for reaction for 2 - 3 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase to dryness, and obtain 0.7 g of 1-methyl-2-phenylpyrrole, with a yield of 75%.

[0141] Its nuclear magnetic characterization parameters are as follows:

[0142] 1 H NMR(400MHz,CDCl3): δ7.33 - 7.26(m,4H),7.22 - 7.16(m,1H),6.61(dd,J = 2.7Hz,J = 1.9Hz,1H),6.16 - 6.12(m,1H),6.13 - 6.09(m,1H),3.54(s,3H).

[0143] Example 25

[0144] Add 20 g of 1-phenyl-4-penten-1-one, 200 mL of toluene into a 1000 mL reaction flask, heat up to 30 - 40 °C, add 1.8 g of p-toluenesulfonic acid, dropwise add a THF solution of methylamine (2 M, 66.0 mL) while controlling the temperature, react for 2 - 3 h while controlling the temperature. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 17.2 g of 1-methyl-2-phenylpyrrole with a yield of 89%.

[0145] Example 26

[0146] Add 1 g of 1-phenyl-4-penten-1-one, 10 mL of toluene into a 50 mL reaction flask, heat up to 30 - 40 °C, add 0.1 g of p-toluenesulfonic acid, add 0.9 g of aniline, react for 2 - 3 h while controlling the temperature. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, concentrate the organic phase, and purify by column chromatography to obtain 1.2 g of 1,2-diphenylpyrrole with a yield of 88%.

[0147] The NMR characterization parameters are as follows:

[0148] 1 H NMR(CDCl3,400MHz):δ7.30(m,3H),7.17(td,J=14.5,7.2Hz,7H),6.94(s,1H),6.44(s,1H),6.36(s,1H).

[0149] Example 27

[0150] Add 20 g of 1-phenyl-4-penten-1-one, 200 mL of toluene into a 1000 mL reaction flask, heat up to 30 - 40 °C, add 1.5 g of p-toluenesulfonic acid, add 16 g of aniline, react for 2 - 3 h while controlling the temperature. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 24.5 g of 1,2-diphenylpyrrole with a yield of 89%.

[0151] Example 28

[0152] Add 1 g of 1-phenyl-4-penten-1-one, 10 mL of toluene (1 g) into a 50 mL reaction flask, heat up to 30 - 40 °C, add 0.1 g of p-toluenesulfonic acid, add 1 g of benzylamine, react for 2 - 3 h while controlling the temperature. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 1.2 g of 1-benzyl-2-phenylpyrrole with a yield of 85%.

[0153] The NMR characterization parameters are as follows:

[0154] 11H NMR (400 MHz, CDCl3): δ 7.34 (m, 4H), 7.33 - 7.24 (m, 4H), 7.05 - 7.01 (m, 2H), 6.77 - 6.76 (m, 1H), 6.30 - 6.29 (m, 2H), 5.17 (s, 2H).

[0155] Example 29

[0156] Add 20 g of 1-phenyl-4-penten-1-one and 200 mL of toluene to a 1000 mL reaction flask. Heat to 30 - 40 °C, add p-toluenesulfonic acid (1.5 g), add benzylamine (18 g), control the temperature for reaction for 2 - 3 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 25.6 g of 1-benzyl-2-phenylpyrrole, with a yield of 89%.

[0157] Example 30

[0158] Add 1-(3-bromophenyl)-4-penten-1-one (4.8 g) and toluene (45 mL) to a 100 mL reaction flask. Add p-toluenesulfonic acid (0.4 g), heat to reflux, and azeotropically remove water. React for 5 - 6 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 3.8 g of 2-(3-bromophenyl)furan, with a yield of 85%.

[0159] The NMR characterization parameters are as follows:

[0160] 1 1H NMR (400 MHz, CDCl3) δ 7.86 (t, J = 1.7 Hz, 1H), 7.62 (dd, J = 7.8, 1.2 Hz, 1H), 7.51 (d, J = 1.5 Hz, 1H), 7.42 - 7.40 (m, 1H), 7.30 - 7.28 (m, 1H), 6.71 (d, J = 3.4 Hz, 1H), 6.52 (dd, J = 3.4, 1.8 Hz, 1H).

[0161] Example 31

[0162] Add 1-(p-methoxyphenyl)-4-penten-1-one (11.3 g) and toluene (60 mL) to a 100 mL reaction flask. Add p-toluenesulfonic acid (1 g), heat to reflux, and azeotropically remove water. React for 5 - 6 h. After the reaction is completed, wash with water, wash with saturated sodium bicarbonate solution, separate the phases, concentrate the organic phase, and purify by column chromatography to obtain 8.5 g of 2-(p-methoxyphenyl)furan, with a yield of 83%.

[0163] The NMR characterization parameters are as follows:

[0164] 1 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.9 Hz, 2H), 7.43 (dd, J = 0.8, 1.7 Hz, 1H), 6.93 (d, J = 8.9 Hz, 2H), 6.52 (dd, J = 3.3, 0.7 Hz, 1H), 6.45 (dd, J = 3.3, 1.8 Hz, 1H), 3.84 (s, 3H).

[0165] Example 32

[0166] 1-(4-Methoxyphenyl)-4-penten-1-one (1.9 g), toluene (19 mL) were added to a 50 mL reaction flask. The temperature was raised to 60 - 70 °C, p-toluenesulfonic acid (0.2 g) was added, and p-chloroaniline (1.9 g) was added. The temperature was controlled for reaction for 7 - 8 h. After the reaction was completed, it was washed with water, washed with saturated sodium bicarbonate solution, phase-separated, the organic phase was concentrated, and purified by column chromatography to obtain 2.2 g of 1-(4-chlorophenyl)-2-(4-methoxyphenyl)furan, with a yield of 75%.

[0167] The NMR characterization parameters are as follows:

[0168] 1 1H NMR (400 MHz, CDCl3) δ 3.78 (3H, s), 6.35 (2H, d, J = 2.4 Hz), 6.78 (2H, d, J = 9.0 Hz), 6.88 (1H, t, J = 2.4 Hz), 7.03 - 7.11 (4H, m), 7.28 (2H, d, J = 9.4 Hz).

[0169] Example 33

[0170] 1-(4-Chlorophenyl)-4-penten-1-one (3.9 g), toluene (39 mL) were added to a 50 mL reaction flask. The temperature was raised to 50 - 60 °C, p-toluenesulfonic acid (0.3 g) was added, and a tetrahydrofuran solution of methylamine was added. The temperature was controlled for reaction for 5 - 6 h. After the reaction was completed, it was washed with water, washed with saturated sodium bicarbonate solution, phase-separated, the organic phase was concentrated, and purified by column chromatography to obtain 3.3 g of 1-methyl-2-(4-chlorophenyl)furan, with a yield of 86%.

[0171] The NMR characterization parameters are as follows:

[0172] 1 1H NMR (400 MHz, CDCl3) δ 7.41 - 7.35 (m, 4H), 6.76 (t, J = 2.2, 1H), 6.27 - 6.24 (m, 2H), 3.68 (s, 3H).

[0173] Example 34

[0174] 1-(furan-2-yl)-4-penten-1-one (8.2 g), toluene (82 mL) and p-toluenesulfonic acid (0.6 g) were added to a 100 mL reaction flask. The temperature was raised to reflux for azeotropic water removal, and the reaction was carried out for 5 - 6 h. After the reaction was completed, it was washed with water, washed with saturated sodium bicarbonate solution, phase-separated, the organic phase was concentrated, and purified by column chromatography to obtain 5.8 g of the product compound 1-(furan-2-yl)furan, with a yield of 80%.

[0175] The nuclear magnetic characterization parameters are as follows:

[0176] 1 H NMR (400 MHz, CDCl3) δ 7.42 (2H, d, J = 0.9), 6.57 (2H, d, J = 3.3), 6.47 (2H, dd, J = 1.7, 3.4).

[0177] The preferred specific embodiments of the present invention have been described in detail above. It should be understood that those of ordinary skill in the art can make many modifications and variations according to the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by those skilled in the art in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the protection scope determined by the claims.

Claims

1. A method for preparing a 1,4 - dicarbonyl compound, characterized in that, It includes the following steps: S1. Compound a reacts with thionyl chloride, triethylamine, and dimethylamine hydrochloride to form compound b; S2. Compound b reacts with iodine, magnesium chips, and 4-bromo-1-butene to form compound c; S3. Compound c reacts with ozone and dimethyl sulfide to obtain the compound shown in Formula I; wherein the structural formulas of compound a, b, c, and the compound shown in Formula I are as follows: R is selected from any one of hydrogen, chlorine, bromine, and methoxy.

2. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, The S1 step includes: S11. Compound a reacts with thionyl chloride to form an acyl chloride compound; S12. The acyl chloride compound reacts with triethylamine and dimethylamine hydrochloride to form compound b.

3. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, In the S1 step, the molar ratio of compound a, thionyl chloride, dimethylamine hydrochloride, and triethylamine is 1:(2 - 6):(1 - 2):(2 - 3).

4. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, The reaction solvent in the S2 step is any one of THF, ethylene glycol dimethyl ether, and 2-methyltetrahydrofuran.

5. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, In the S2 step, the molar ratio of compound b, 4-bromo-1-butene, magnesium chips, and iodine is 1:(1 - 1.5):(1.1 - 1.5):(0.001 - 0.1).

6. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, The reaction solvent in the S3 step is methanol, dichloromethane, or a mixed solvent of the two.

7. The method for preparing a 1,4 - dicarbonyl compound according to claim 1, characterized in that, In the S3 step, the molar ratio of compound c, oxygen, and dimethyl sulfide is 1:(2 - 10):(1 - 2), and the amount of oxygen used is the amount introduced into the ozone generator.

Images