CN110143875B - Preparation method of 4-acetoxyl-2-methyl-2-butenal - Google Patents
Preparation method of 4-acetoxyl-2-methyl-2-butenal Download PDFInfo
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- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
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- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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Abstract
A preparation method of 4-acetoxyl-2-methyl-2-butenal. The invention provides a preparation method of vitamin A important intermediate pentanal. The method comprises the following steps: (1) reacting 4-hydroxybutyraldehyde with (N, N-dimethyl) ammonium methyliodide to generate 2-methylene-4-hydroxybutyraldehyde; (2) isomerizing the 2-methylene-4-hydroxybutyraldehyde to obtain 4-hydroxy-2-methyl-2-butenal; (3) 4-hydroxy-2-methyl-2-butenal reacts with acetic anhydride to obtain 4-acetoxyl-2-methyl-2-butenal (pentanal). The method takes 4-hydroxybutyraldehyde as a starting raw material, is a common fine chemical intermediate, is cheap and easy to obtain, has a short reaction synthetic route, high reaction yield, low cost, simple operation and little environmental pollution, and is an effective synthetic route.
Description
Technical Field
The invention belongs to the field of chemical intermediate synthesis, and particularly relates to a preparation method of 4-acetoxyl-2-methyl-2-butenal.
Background
4-acetoxyl-2-methyl-2-butenal (hereinafter referred to as "five-carbon aldehyde") is an important intermediate for synthesizing vitamin A. Due to the importance of the pentanal in the vitamin A synthesis industry, the synthesis process of the pentanal has been a research hotspot for a long time.
Patent US5453547 discloses a synthetic route for the preparation of pentanal starting from dimethoxyacetone, the reaction formula is as follows: reacting dimethoxyacetone with acetylene and hydrogen to generate a compound 2, reacting the compound 2 with acetic anhydride to generate a compound 3, isomerizing the compound 3 under the action of a Cu catalyst to obtain a compound 4, and hydrolyzing the compound 4 to finally obtain the pentanal. The disadvantages of the route are that the process route is long, the yield is low, and the total yield of the route is 35-45%.
Patent US5424478 discloses a synthetic route for the preparation of pentanal starting from isoprene. Isoprene and sodium hypochlorite are added to obtain two configurational addition products, the cis-isomer is esterified under the action of acetic anhydride to obtain a compound 8, and then dimethyl sulfoxide (DMSO) is used as an oxidant to prepare the pentanal. The method can generate a large amount of waste water in the production process, and the pollution is serious. The synthetic route is as follows:
patent US4873362 describes a process for the preparation of penta-aldehydes from ethylene oxide. According to the method, ethylene oxide is used as a raw material, after the ring opening addition of the ethylene oxide and acetic acid, a compound 11 is prepared, the compound 11 is subjected to an oxidation reaction with oxygen under the catalysis of Ag to generate an intermediate 12, and the intermediate 12 is subjected to a condensation reaction with propionaldehyde to obtain the pentanal. The intermediate 12 of this process is extremely unstable and the selectivity of the condensation reaction with propionaldehyde is difficult to control. The process route is shown as the following formula:
patent CN103467287A discloses a synthetic route for preparing five-carbon aldehyde using ethylene oxide and acrolein as starting materials. According to the method, acrolein and ethylene oxide are used as initial raw materials, and are reacted under the action of an organic phosphine reagent to generate a compound 15, the compound is further acetylated to obtain an intermediate 16, and hydroisomerization is carried out under the action of a Pd catalyst to obtain the pentanal. In the route, a large amount of expensive organic phosphine reagent and palladium metal catalyst are consumed, and the efficiency of the intermediate 16 for generating the pentanal is low and is only 51%. The synthesis process is as follows:
US patent 4124619 discloses a process for preparing pentanal by butenediol, which comprises using 1, 4-butenediol 18 as raw material, first acylating with acetic anhydride to obtain 1, 4-butenediol 19, then reacting with CO/H under high pressure in the presence of noble metal Rh catalyst2The mixed gas acts to obtain a compound 20, the acid is decarboxylated under the action of protonic acid to obtain the enol ester 21, and finally the final product, namely the five-carbon aldehyde, is obtained through double bond isomerization. However, this method requires the use of expensive rhodium-based catalysts and palladium metal catalysts. The process route is shown as the following formula:
the above methods have corresponding disadvantages, and therefore, it is necessary to develop a new process for synthesizing pentanal.
Disclosure of Invention
The invention aims to provide a novel route for synthesizing 4-acetoxyl-2-methyl-2-butenal (pentanal), which has the advantages of cheap and easily obtained raw materials, short reaction synthesis route, high reaction yield, lower cost, simple operation and small environmental pollution.
In order to achieve the above purpose and achieve the above technical effects, the technical solution of the present invention is as follows:
a method of preparing 4-acetoxy-2-methyl-2-butenal (pentanal) comprising the steps of:
(1) reacting 4-hydroxybutyraldehyde with (N, N-dimethyl) ammonium methyliodide to obtain 2-methylene-4-hydroxybutyraldehyde, wherein the structure is shown as a formula I;
(2) catalyzing and isomerizing the 2-methylene-4-hydroxybutyraldehyde to obtain 4-hydroxy-2-methyl-2-butenal, wherein the structure is shown as a formula II;
(3) reacting 4-hydroxy-2-methyl-2-butenal with acetic anhydride to obtain 4-acetoxyl-2-methyl-2-butenal, wherein the structure is shown as a formula III;
the synthetic route is shown as the following formula:
in the present invention, the molar ratio of (N, N-dimethyl) ammonium methyliodide to 4-hydroxybutyraldehyde in step (1) is (1-1.5) to 1, preferably (1.2-1.3): 1.
in the invention, a base is added in the step (1), wherein the base is a mixture of n-butyllithium and organic amine, the organic amine is preferably one or more of diethylamine, triethylamine, diisopropylamine, pyridine and pyrrole, and diisopropylamine is more preferred; the mol ratio of the organic amine to the 4-hydroxybutyraldehyde is (2-4): 1, more preferably (2.5-3): 1; the molar ratio of the n-butyl lithium to the 4-hydroxybutyraldehyde is (1.5-3.0): 1, more preferably (2.0-2.2): 1.
in the invention, the base in the step (1) is dissolved in an organic solvent A, wherein the organic solvent is selected from one or more of toluene, tetrahydrofuran, n-hexane and dioxane, and tetrahydrofuran is preferred; the dosage ratio of the solvent to the 4-hydroxybutyraldehyde is (0.8-2) L: 1mol, preferably (1-1.5) L: 1 mol.
In the invention, after the alkali in the step (1) is dissolved in the solvent, the mixture is continuously stirred for 0.5 to 2.5 hours, preferably 1 to 1.5 hours at the temperature of between 40 ℃ below zero and 10 ℃ below zero, preferably between 30 ℃ below zero and 20 ℃ below zero; then adding 4-hydroxy butyraldehyde and stirring for 0.5-2.5h, preferably 1-1.5 h; then, (N, N-dimethyl) methylene ammonium iodide is added, and the reaction solution is reacted at room temperature for 6 to 12 hours, preferably 8 to 10 hours.
In the invention, after the reaction in the step (1) is finished, a reaction liquid is extracted by using dichloromethane, an organic phase is subjected to reduced pressure rectification after solvent removal to obtain the 2-methylene-4-hydroxybutyraldehyde, specifically, the theoretical plate number of a packing rectification tower is 20, the operation pressure condition is 1kPa, the reflux ratio is 2:1, and the fraction at 38-39 ℃ is collected to obtain the 2-methylene-4-hydroxybutyraldehyde.
In the invention, the catalyst in the step (2) is Pd (OAc)2、Pd(PPh3)4、Ru3(CO)12、RhCl3、RhCl3.3H2O、RuHCl(PPh3)3、RuCl2(PPh3)3And Ru (CO) H2(PPh3)3Preferably Ru3(CO)12(ii) a The molar ratio of the catalyst to the 2-methylene-4-hydroxybutyraldehyde is (0.01-0.05): 1, preferably (0.015 to 0.02): 1.
in the invention, a base is required to be added in the step (2), the base is selected from one or more of diethylamine, triethylamine, diisopropylamine, pyridine, pyrrole, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide, and triethylamine is preferred; the molar ratio of the base to 2-methylene-4-hydroxybutyraldehyde is (1-1.5):1, preferably (1.1-1.2): 1.
In the invention, a solvent B is required to be added into the reaction system in the step (2), the solvent is one or more of toluene, xylene, tetrahydrofuran, dioxane, acetonitrile and dimethyl sulfoxide, and toluene is preferred; the ratio of solvent to 2-methylene-4-hydroxybutyraldehyde is (0.8-2) L: 1mol, preferably (1-1.5) L: 1 mol.
In the invention, the reaction temperature in the step (2) is 60-120 ℃, preferably 80-100 ℃; the reaction time is 8-12h, preferably 10-11 h.
In the invention, after the isomerization reaction in the step (2) is finished, the reaction solution is subjected to reduced pressure rectification after desolventizing to obtain 4-hydroxy-2-methyl-2-butenal, specifically, the theoretical plate number of a packing rectification tower is 20, the operating pressure condition is 1kPa, the reflux ratio is 1:1, and the fraction at 58-60 ℃ is collected to obtain the 4-hydroxy-2-methyl-2-butenal.
In the invention, the molar ratio of acetic anhydride to 4-hydroxy-2-methyl-2-butenal in the step (3) is (3-5): 1, preferably (4-4.5): 1.
in the present invention, the reaction temperature in step (3) is 80 to 150 ℃, preferably 100 ℃ to 120 ℃.
In the present invention, the reaction time of step (3) is 4 to 6 hours, preferably 5 to 5.5 hours.
In the invention, after the esterification reaction in the step (3) is finished, the reaction liquid is subjected to vacuum rectification to obtain 4-acetoxyl-2-methyl-2-butenal, specifically, the theoretical plate number of a packing rectification tower is 20, the operating pressure condition is 1kPa, the reflux ratio is 3:1, and fractions at 80-82 ℃ are collected to obtain the 4-acetoxyl-2-methyl-2-butenal.
The invention has the positive effects that:
(1) 4-hydroxy butyraldehyde is adopted as a starting material, so that the method is simple, easy to obtain and low in cost;
(2) the use of expensive phosphine catalysts is avoided in the reaction process;
(3) the synthesis route is short, the total yield is high, and the total yield of the route can reach more than 72 percent and is higher than 55 to 65 percent in the prior art by taking 4-hydroxybutyraldehyde as a starting raw material;
(4) the waste water generated in the reaction is less and is environment-friendly.
Detailed Description
The technical solutions of the present invention are further described below, but not limited thereto, and modifications or equivalent substitutions may be made to the technical solutions of the present invention without departing from the scope of the technical solutions of the present invention.
Gas chromatographic analysis: the chromatographic type is as follows: agilent WAX 1701.42249; carrier gas: high-purity nitrogen; sample introduction mode: an autosampler; nitrogen flow rate: 64.5 ml/min; vaporization chamber temperature: 280 ℃; split-flow sample introduction, split-flow ratio: 1: 40; sample introduction amount: 0.2 μ l; the column flow rate was 1.5 ml/min; column temperature: first-order temperature programming, wherein the initial temperature is 100 ℃, the temperature is kept for 2 minutes, then the temperature is raised to 230 ℃ at the speed of 15 ℃/min, and the temperature is kept for 15 minutes; the total running time is 25.67 min; the temperature of the detector is 300 ℃; and (4) selecting an external standard method for quantification.
NMR analysis: nuclear magnetic resonance data (1H 400MHz,13C100 MHz) were measured by a Varian 400NMR spectrometer, the dissolution reagent was CDCl3。
Some of the reagent specifications and sources in the examples and comparative examples
Example 1
(1) Preparation of 2-methylene-4-hydroxybutanal:
1L of tetrahydrofuran is added into a 3L glass three-neck flask, mechanical stirring is started, the rotating speed is set to be 800rpm, the temperature is reduced to minus 30 ℃, then 2mol of N-butyl lithium and 2.5mol of diisopropylamine are added into the tetrahydrofuran, after 0.5h of reaction, 1mol of 4-hydroxybutyraldehyde is added, stirring is carried out for 0.5h, 1mol of (N, N-dimethyl) methylene ammonium iodide is added, and then the reaction is carried out for 8h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recycled under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plate numbers to remove reaction liquid after solvent under the condition of 1kPa with the reflux ratio of 2:1, fractions at 38-39 ℃ on the tower top are collected to obtain 2-methylene-4-hydroxybutyraldehyde, and gas chromatography is carried outThe 2-methylene-4-hydroxybutyraldehyde content was analyzed to be 98.9%, with a yield of 95%.1H NMR(400MHz,C6D6)δ:9.14(s,1H),5.66(d,J＝1.2Hz,1H),5.26(s,1H),3.39-3.35(m,2H),2.23-2.20(m,2H),0.76(br,1H,OH).13C NMR(100MHz,C6D6)δ:194.7,147.2,135.8,60.7,31.7。
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 0.8mol of 1L of toluene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, and then adding 0.96mol of triethylamine and 0.012mol of Ru3(CO)12And then reacted at 100 ℃ for 10 hours. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 97.8 percent and the yield to be 94 percent.1H NMR(CDCl3)δ：1.85(q,3H,J＝7.0Hz),5.27(dq,2H,J＝7.0,1.7Hz),6.46(tq,1H,J＝7.0,1.7Hz),9.48(s,1H),12.31(s,1H)；13C NMR(100MHz,C6D6)δ：19.3,68.4,140.3,147.2,193.5。
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 2mol of acetic anhydride into a 3L glass three-neck flask, heating to 100 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 100 +/-5 ℃, and continuing to react for 5h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plate numbers under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the tower top to obtain 4-acetoxyl group-2-methyl-2-butenal, and analyzing the content of the 4-acetoxyl group-2-methyl-2-butenal by gas chromatography to be 99.1%, and the yield is 95%.1H NMR(400MHz,CDCl3)δ9.46(s,1H),6.52-6.48(m,1H),4.90(d,J＝6.0Hz,2H),2.13(s,3H),1.80(d,J＝1.1Hz,3H)；13C NMR(100MHz,CDCl3)δ：18.3,21.2,45.0,70.4,142.3,147.2,196.5。
Example 2
(1) Preparation of 2-methylene-4-hydroxybutanal:
adding 1L of toluene into a 3L glass three-neck flask, starting mechanical stirring, setting the rotating speed to 800rpm, cooling to-40 ℃, then adding 1.5mol of N-butyl lithium and 2mol of diisopropylamine, reacting for 1h, adding 1mol of 4-hydroxybutyraldehyde, stirring for 1h, adding 1mol of (N, N-dimethyl) methylene ammonium iodide, and then reacting for 6h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove a reaction liquid after a solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 99% through gas chromatography analysis, and the yield is 91%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 0.8L of dimethylbenzene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, adding 1.2mol of triethylamine and 0.012mol of Pd (OAc)2And then reacted at 100 ℃ for 12 hours. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 98.2 percent and the yield to be 93 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 1.5mol of acetic anhydride into a 3L glass three-neck flask, heating to 120 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 120 +/-5 ℃, and continuing to react for 5.5h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the top of the tower to obtain 4-acetoxyl group-2-methyl-2-butenal, and performing gas chromatography to analyze that the content of the 4-acetoxyl group-2-methyl-2-butenal is 99.1%, and the yield is 90%.
Example 3
(1) Preparation of 2-methylene-4-hydroxybutanal:
1.5L of tetrahydrofuran was charged into a 3L flask, stirring was started, the rotation speed was set at 800rpm, the temperature was lowered to-10 ℃, then 3mol of N-butyllithium and 2.5mol of diisopropylamine were added thereto, after 2.5 hours of reaction, 1mol of 4-hydroxybutyraldehyde was added, stirring was carried out for 2.5 hours, 1.5mol of (N, N-dimethyl) methyleneammonium iodide was added, and then reaction was carried out at room temperature for 12 hours. After the reaction is finished, 0.5L of water is added into the system, dichloromethane is used for extraction for three times, 0.5L of water is used for extraction each time, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove reaction liquid after solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 97.2% through gas chromatography analysis, and the yield is 96%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 0.64L of toluene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, and adding 0.8mol of triethylamine and 0.008mol of Ru3(CO)12And then reacted at 120 ℃ for 11 h. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 98.1 percent and the yield to be 93 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 2.5mol of acetic anhydride into a 3L glass three-neck flask, heating to 100 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 80 +/-5 ℃, and continuing to react for 5h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the top of the tower to obtain 4-acetoxyl group-2-methyl-2-butenal, and analyzing the content of the 4-acetoxyl group-2-methyl-2-butenal by gas chromatography to be 98.9%, and the yield is 94%.
Example 4
(1) Preparation of 2-methylene-4-hydroxybutanal:
2L of tetrahydrofuran is added into a 4L glass three-neck flask, mechanical stirring is started, the rotating speed is set to be 800rpm, the temperature is reduced to minus 30 ℃, then 2.2mol of N-butyl lithium and 2.2mol of diisopropylamine are added into the tetrahydrofuran, after 1.5h of reaction, 1mol of 4-hydroxybutyraldehyde is added, stirring is carried out for 1.5h, 1.1mol of (N, N-dimethyl) methylene ammonium iodide is added, and then the reaction is carried out for 10h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove a reaction liquid after a solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 98.3% by gas chromatography analysis, and the yield is 92%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 1.6L of toluene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, and adding 0.88mol of triethylamine and 0.04mol of Ru3(CO)12And then reacted at 80 ℃ for 10 hours. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by a packed tower with 20 theoretical plate numbers under the condition of 1kPa to remove the reaction liquid of the solvent, wherein the reflux ratio is 1:1, collecting the reaction liquid in a towerThe distillate with the temperature of 58-60 ℃ is topped to obtain 4-hydroxy-2-methyl-2-butenal, the content of the 4-hydroxy-2-methyl-2-butenal is 97.9 percent by gas chromatographic analysis, and the yield is 92 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 2.25mol of acetic anhydride into a 3L glass three-neck flask, heating to 150 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 150 +/-5 ℃, and continuing to react for 4h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the top of the tower to obtain 4-acetoxyl group-2-methyl-2-butenal, and performing gas chromatography to analyze that the content of the 4-acetoxyl group-2-methyl-2-butenal is 99.3%, and the yield is 90%.
Example 5
(1) Preparation of 2-methylene-4-hydroxybutanal:
0.8L of tetrahydrofuran is added into a 3L glass three-neck flask, mechanical stirring is started, the rotating speed is set to 800rpm, the temperature is reduced to minus 30 ℃, then 2.5mol of N-butyl lithium and 3mol of diisopropylamine are added into the mixture, 1mol of 4-hydroxybutyraldehyde is added after 1h of reaction, stirring is carried out for 1h, 1.2mol of (N, N-dimethyl) methylene ammonium iodide is added, and then the reaction is carried out for 10h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove a reaction liquid after a solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 98.6% by gas chromatography analysis, and the yield is 95%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 1.2L of toluene and 2 under protection0.8mol of-methylene-4-hydroxybutyraldehyde, stirring for 5min, adding 0.96mol of sodium hydroxide and 0.012mol of Ru3(CO)12And then reacted at 120 ℃ for 12 hours. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 97.9 percent and the yield to be 90 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 2mol of acetic anhydride into a 3L glass three-neck flask, heating to 90 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 90 +/-5 ℃, and continuing to react for 6h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the top of the tower to obtain 4-acetoxyl group-2-methyl-2-butenal, and analyzing the content of the 4-acetoxyl group-2-methyl-2-butenal by gas chromatography to be 98.6%, and the yield is 91%.
Example 6
(1) Preparation of 2-methylene-4-hydroxybutanal:
adding 1L of tetrahydrofuran into a 3L glass three-neck flask, starting mechanical stirring, setting the rotating speed to 800rpm, cooling to-30 ℃, then adding 3mol of N-butyl lithium and 4mol of triethylamine, reacting for 0.5h, adding 1mol of 4-hydroxybutyraldehyde, stirring for 2.5h, adding 1.5mol of (N, N-dimethyl) methylene ammonium iodide, and then reacting for 10h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove a reaction liquid after a solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 99.1% through gas chromatography analysis, and the yield is 92%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 0.8L of dimethylbenzene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, and adding 1.04mol of triethylamine and 0.016mol of Ru3(CO)12And then reacted at 60 ℃ for 8 h. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 98 percent and the yield to be 90 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 1.5mol of acetic anhydride into a 3L glass three-neck flask, heating to 130 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 130 +/-5 ℃, and continuing to react for 6h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding 0.5L of dichloromethane into the system for extraction, continuously performing three times, combining organic phases, washing the organic phases to be neutral by using 10% sodium hydroxide solution, separating the organic phases, washing the organic phases twice by using saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent is removed, wherein the reflux ratio is 3:1, collecting fractions at 80-82 ℃ at the top of the tower to obtain 4-acetoxyl group-2-methyl-2-butenal, and analyzing the content of the 4-acetoxyl group-2-methyl-2-butenal by gas chromatography to be 99%, and the yield is 91%.
Comparative example 1
Similar procedure and procedure as in example 1 were used, except that 1, 2-dichloroethane was used as solvent in step (1) and Rh (CO) was used in step (2)2(acac) is a catalyst, and the reaction temperature in the step (3) is controlled to be 40 ℃.
(1) Preparation of 2-methylene-4-hydroxybutanal:
1L of 1, 2-dichloroethane is added into a 3L glass three-neck flask, mechanical stirring is started, the rotating speed is set to 800rpm, the temperature is reduced to minus 30 ℃, then 2mol of N-butyl lithium and 2.5mol of diisopropylamine are added into the mixture, after 0.5h of reaction, 1mol of 4-hydroxybutyraldehyde is added into the mixture, stirring is carried out for 0.5h, 1.1mol of (N, N-dimethyl) methylene ammonium iodide is added, and then the reaction is carried out for 8h at room temperature. After the reaction is finished, 0.5L of water is added into the system, extraction is carried out for three times by using dichloromethane, 0.5L of water is added into the system, organic phases are combined, dichloromethane is recovered under reduced pressure, mother liquor is rectified by a packed tower with 20 theoretical plates under the condition of 1kPa to remove a reaction liquid after a solvent, the reflux ratio is 2:1, fractions at 38-39 ℃ on the top of the tower are collected to obtain 2-methylene-4-hydroxybutyraldehyde, the content of the 2-methylene-4-hydroxybutyraldehyde is 91.0% by gas chromatography analysis, and the yield is 45%.
(2) Preparation of 4-hydroxy-2-methyl-2-butenal:
3L glass three-necked flask, N2By substitution three times, followed by N2Adding 1L of toluene and 0.8mol of 2-methylene-4-hydroxybutyraldehyde under protection, stirring for 5min, and then adding 0.96mol of triethylamine and 0.012mol of Rh (CO)2(acac) followed by a reaction at 100 ℃ for 10 h. After the reaction is finished, recovering toluene under reduced pressure, rectifying the mother liquor by using a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 1:1, collecting the fraction at 58-60 ℃ at the top of the tower to obtain 4-hydroxy-2-methyl-2-butenal, and analyzing the content of the 4-hydroxy-2-methyl-2-butenal by gas chromatography to be 95.1 percent and the yield to be 63 percent.
(3) Preparation of 4-acetoxy-2-methyl-2-butenal:
adding 2mol of acetic anhydride into a 3L glass three-neck flask, heating to 40 ℃, dropwise adding 0.5mol of 4-hydroxy-2-methyl-2-butenal under stirring for 30min, controlling the temperature to be 40 +/-5 ℃, and continuing to react for 5h after the dropwise adding is finished. After the reaction is finished, cooling to normal temperature, adding a proper amount of dichloromethane into the system for extraction, washing with 10% sodium hydroxide solution to be neutral, separating an organic phase, washing twice with saturated salt solution, recovering dichloromethane under reduced pressure, rectifying the mother liquor by a packed tower with 20 theoretical plates under the condition of 1kPa to remove the reaction liquid after the solvent, wherein the reflux ratio is 3:1, collecting the fraction at 80-82 ℃ at the top of the tower to obtain 4-acetoxy-2-methyl-2-butenal, and analyzing the content of the 4-acetoxy-2-methyl-2-butenal by gas chromatography to be 98.6%, and the yield is 39%.
Claims (20)
1. A preparation method of five-carbon aldehyde comprises the following steps:
(1) reacting 4-hydroxybutyraldehyde with (N, N-dimethyl) ammonium methyliodide to obtain 2-methylene-4-hydroxybutyraldehyde;
(2) catalyzing and isomerizing 2-methylene-4-hydroxybutyraldehyde to obtain 4-hydroxy-2-methyl-2-butenal;
(3) 4-hydroxy-2-methyl-2-butenal reacts with acetic anhydride to obtain 4-acetoxyl-2-methyl-2-butenal.
2. The method according to claim 1, wherein the molar ratio of (N, N-dimethyl) methyleneammonium iodide to 4-hydroxybutyraldehyde in step (1) is (1-1.5): 1.
3. The method according to claim 2, wherein the molar ratio of (N, N-dimethyl) ammonium methyliodide to 4-hydroxybutyraldehyde in step (1) is (1.2-1.3): 1.
4. the preparation method according to claim 1 or 2, characterized in that, a base is added in the step (1), and the base is a mixture of n-butyl lithium and organic amine; the mol ratio of the organic amine to the 4-hydroxybutyraldehyde is (2-4): 1; the molar ratio of the n-butyl lithium to the 4-hydroxybutyraldehyde is (1.5-3.0): 1.
5. the method according to claim 4, wherein the organic amine in step (1) is one or more selected from the group consisting of diethylamine, triethylamine, diisopropylamine, pyridine and pyrrole; the mol ratio of the organic amine to the 4-hydroxybutyraldehyde is (2.5-3): 1; the molar ratio of the n-butyl lithium to the 4-hydroxybutyraldehyde is (2.0-2.2): 1.
6. the method according to claim 5, wherein the organic amine in the step (1) is diisopropylamine.
7. The method according to claim 4, wherein the base in step (1) is first dissolved in an organic solvent A selected from one or more of toluene, tetrahydrofuran, n-hexane and dioxane; the dosage ratio of the solvent to the 4-hydroxybutyraldehyde is (0.8-2) L: 1 mo.
8. The method according to claim 7, wherein the organic solvent A in step (1) is tetrahydrofuran; the dosage ratio of the solvent to the 4-hydroxybutyraldehyde is (1-1.5) L: 1 mol.
9. The preparation method according to claim 7, wherein the alkali is dissolved in the solvent in the step (1), and then the mixture is continuously stirred for 0.5 to 2.5 hours at the temperature of between-40 and-10 ℃; then adding 4-hydroxy butyraldehyde and stirring for 0.5-2.5 h; then (N, N-dimethyl) methylene ammonium iodide is added, and the reaction solution reacts for 6-12h at room temperature.
10. The preparation method according to claim 9, wherein the alkali is dissolved in the solvent in the step (1), and then the stirring is continued for 1 to 1.5 hours at a temperature of between-30 and-20 ℃; then adding 4-hydroxy butyraldehyde and stirring for 1-1.5 h; then (N, N-dimethyl) methylene ammonium iodide is added, and the reaction solution reacts for 8-10h at room temperature.
11. The process according to claim 1, wherein the catalyst used in the step (2) is Pd (OAc)2、Pd(PPh3)4、Ru3(CO)12、RhCl3、RhCl3 .3H2O、RuHCl(PPh3)3、RuCl2(PPh3)3And Ru (CO) H2(PPh3)3One or more of; the molar ratio of the catalyst to the 2-methylene-4-hydroxybutyraldehyde is (0.01-0.05): 1.
12. the method according to claim 11, wherein the catalyst in the step (2) is Ru3(CO)12(ii) a The molar ratio of the catalyst to the 2-methylene-4-hydroxybutyraldehyde is (0.015-0.02): 1.
13. the preparation method according to claim 1, wherein a base is added in the step (2), and the base is selected from one or more of diethylamine, triethylamine, diisopropylamine, pyridine, pyrrole, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide; the molar ratio of the alkali to the 2-methylene-4-hydroxybutyraldehyde is (1-1.5): 1.
14. The method according to claim 13, wherein the base in step (2) is triethylamine; the molar ratio of the alkali to the 2-methylene-4-hydroxybutyraldehyde is (1.1-1.2): 1.
15. The preparation method according to claim 1, wherein a solvent B is added to the reaction system in the step (2), and the solvent is one or more of toluene, xylene, tetrahydrofuran, dioxane, acetonitrile and dimethyl sulfoxide; the ratio of solvent to 2-methylene-4-hydroxybutyraldehyde is (0.8-2) L: 1 mol.
16. The method according to claim 15, wherein the solvent B in step (2) is toluene; the ratio of solvent to 2-methylene-4-hydroxybutyraldehyde is (1-1.5) L: 1 mol.
17. The method according to claim 1, wherein the reaction temperature in the step (2) is 60 to 120 ℃; the reaction time is 8-12 h.
18. The method according to claim 17, wherein the reaction temperature in the step (2) is 80 to 100 ℃; the reaction time is 10-11 h.
19. The method according to claim 1, wherein the molar ratio of acetic anhydride to 4-hydroxy-2-methyl-2-butenal in the step (3) is (3-5): 1; the reaction temperature is 80-150 ℃; the reaction time is 4-6 h.
20. The method according to claim 19, wherein the molar ratio of acetic anhydride to 4-hydroxy-2-methyl-2-butenal in the step (3) is (4-4.5): 1; the reaction temperature is 100-120 ℃; the reaction time is 5-5.5 h.
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