CN112920042A - Method for preparing alkane carboxylic acid by increasing alkane carbon chain - Google Patents
Method for preparing alkane carboxylic acid by increasing alkane carbon chain Download PDFInfo
- Publication number
- CN112920042A CN112920042A CN202110113263.3A CN202110113263A CN112920042A CN 112920042 A CN112920042 A CN 112920042A CN 202110113263 A CN202110113263 A CN 202110113263A CN 112920042 A CN112920042 A CN 112920042A
- Authority
- CN
- China
- Prior art keywords
- carboxylic acid
- reaction
- compound
- crude product
- acyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
- C07C51/31—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation of cyclic compounds with ring-splitting
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/023—Preparation; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing alkane carboxylic acid by increasing alkane carbon chains. The method comprises the following steps: (1) cyclopentanone or cyclohexanone firstly reacts with secondary amine compound to generate corresponding 1-position secondary amine substituted cyclopentene or cyclohexene crude product, namely, the schotkenylamine; (2) carrying out electrophilic reagent reaction on the schotkenylamine and acyl halide to form a 2-acyl cyclic ketone compound; (3) under the action of alkali, the 2-acyl cyclic ketone compound is subjected to ring opening to generate a carbonyl carboxylic acid compound, and the carbonyl carboxylic acid compound is subjected to Volvox-Huang Minlon reduction reaction to obtain the corresponding alkane carboxylic acid. The method can flexibly select and use cyclopentanone or cyclohexanone to realize the requirement of increasing to different carbon numbers according to the different carbon numbers required to be increased and the different sources of the target recarburized alkane carboxylic acid or the corresponding acyl halide thereof. The method has simple reaction process and no complex operation difficulty, and is suitable for industrial mass production.
Description
Technical Field
The invention relates to a synthetic method of alkane carboxylic acid, in particular to a method for preparing alkane carboxylic acid by increasing alkane carbon chains, and belongs to the technical field of chemical industry.
Background
In organic synthesis, the construction of the carbon skeleton is an extremely important step, which involves the growth of the carbon chain. The reactions of carbon chain growth in organic chemistry are numerous and have different application occasions, and the following methods are adopted for common carbon chain growth:
the use of organometallic compounds to extend the carbon chain is common: the Grignard reagent reacts with aldehyde, ketone, ester and alkylene oxide to generate nucleophilic addition reaction to generate corresponding alcohol, and then a series of reactions are carried out to obtain corresponding carboxylic acid, the Grignard reagent reacts with carbon dioxide to prepare carboxylic acid with one more carbon, and the reaction can start from halohydrocarbon to obtain carboxylic acid with an increased carbon chain, which is suitable for primary, secondary and tertiary halohydrocarbon, allyl and phenyl halohydrocarbon.
The organic physical agent and halogenated hydrocarbon are coupled to prepare reaction for increasing carbon chain, wherein the alkyl of organic lithium can be methyl, primary alkyl, secondary alkyl, allyl, benzyl, vinyl, aryl and other alkyl. The alkyl in the halogenated hydrocarbon can be primary alkyl and secondary alkyl, and also can be ethylene hydrocarbon, aromatic hydrocarbon, allyl and benzyl, and the alkyl in the dihydrocarbyl copper lithium can be primary alkyl, and also can be other alkyls, such as vinyl, aryl, allyl and the like, so that the coupling reaction has wide selection range.
Alkyne has certain acidity and can react with active metal such as sodium or sodium amide to generate alkyne anions which have strong nucleophilicity and can generate nucleophilic substitution with halogenated hydrocarbon, wherein the halogenated hydrocarbon must be primary halogenated hydrocarbon, and secondary halogen and tertiary halogen react with the alkyne sodium to mainly generate corresponding elimination products.
The alkyl halide can react with metal sodium, and the generated organic sodium compound immediately reacts with the alkyl halide to generate alkane. This reaction is called the "Wurtz reaction". The wurtz reaction can be used to prepare structurally symmetric alkanes containing even numbers of carbon atoms from alkyl halides (primarily primary alkyl halides). Different halogenated hydrocarbons are put together to react and produce two different alkanes, which are difficult to separate.
Addition reaction of phosphorus ylide, vittuy-Horner reaction (Wittig-Horner). The addition reaction of aldehyde ketone and Vittuy reagent is one method of synthesizing olefin and conjugated olefin, and may be used in synthesizing olefin with specific structure.
Nucleophilic addition reaction of alkyne mainly reacts with carboxylic ester to prepare acid alkenyl ester which can not be directly esterified by enol. In addition, the reaction of alkyne and chloro-carboxylic ester under the action of methyllithium to synthesize alkyne ester is also used.
The above is the most common method for increasing the carbon chain length to make alkyl carboxylic acids. It is obvious that the reagents and raw materials used in the above methods have the disadvantages of high risk and difficulty in use to different extents, and it is needless to say that different carburisation methods are selected for different compounds. The novel technology uses cyclohexanone and cyclopentanone as raw materials, and can simply, quickly, conveniently and environmentally connect 5 to 7 carbon atoms on the basis of the existing common fatty acid to synthesize rare fatty acid. The invention has the advantages of reasonable circuit, simple operation, low danger and great advantages in industrial production.
Disclosure of Invention
The invention aims to overcome the defects of strict requirements on reagents, strict operation requirements, unsuitability for industrial production and the like in the existing method for increasing the length of a carbon chain, and provides a method for increasing 5 or 6 carbon atoms of the existing alkyl carboxylic acid, which is simple and easy to operate and is more suitable for industrial production.
In order to achieve the purpose, the invention adopts the following technical means:
the invention relates to a method for preparing alkane carboxylic acid by increasing alkane carbon chains, which comprises the following steps:
(1) cyclopentanone or cyclohexanone firstly reacts with secondary amine compound to generate corresponding 1-position secondary amine substituted cyclopentene or cyclohexene crude product, namely, the schotkenylamine;
(2) carrying out electrophilic reagent reaction on the schotkenylamine and acyl halide to form a 2-acyl cyclic ketone compound;
(3) under the action of strong alkali, the 2-acyl cyclic ketone compound is subjected to ring opening to generate a carbonyl carboxylic acid compound, and the carbonyl carboxylic acid compound is subjected to Volvox-Huang Minlon reduction reaction to obtain the corresponding alkane carboxylic acid.
Among them, it is preferable that the schotkenylamine reaction in step (1) is carried out with p-toluenesulfonic acid as a catalyst.
Among them, it is preferable that the secondary amine compound described in the step (1) includes: piperidine, diethylamine, dimethylamine, morpholine and tetrahydropyrrole.
Among them, preferably, the acyl halide in the step (2) is acyl chloride.
Among them, preferably, the strong base in the step (3) is sodium hydroxide or potassium hydroxide.
Preferably, the method comprises the following steps:
(1) adding cyclopentanone or cyclohexanone, a secondary amine compound, p-toluenesulfonic acid as a catalyst and toluene as an entrainer into a reaction bottle, stirring, heating and refluxing for reaction until the separated water reaches the calculated amount, and then carrying out reduced pressure distillation to recover toluene to generate a corresponding 1-position secondary amine substituted cyclopentene or cyclohexene crude product, namely, sertraline amine;
(2) adding chloroform into the crude product of the Stroke enamine obtained in the step (1) for dilution, adding triethylamine as an acid-binding agent, cooling to below 10 ℃, slowly dropping acyl chloride, and continuing stirring for reaction after dropping to obtain a 2-acyl cyclic ketone compound; then adding a hydrochloric acid solution, heating and refluxing for 1.5-2.5 hours, separating liquid, separating a lower chloroform layer and a lower water layer, washing the chloroform layer twice with water, then drying with anhydrous sodium sulfate, and filtering to obtain a crude product of the 2-acyl cyclic ketone compound, wherein the crude product is directly used in the next step;
(3) adding a potassium hydroxide aqueous solution into the 2-acyl cyclic ketone compound crude product obtained in the step (2), heating and refluxing for 1-2 hours, cooling, then adjusting to be neutral by using diluted hydrochloric acid, separating an organic layer to be a carbonyl carboxylic acid compound crude product, adding diethylene glycol and potassium hydroxide into a reaction bottle, stirring until the potassium hydroxide is dissolved, adding the obtained carbonyl carboxylic acid compound crude product and hydrazine hydrate, heating to 140 ℃ and 150 ℃, reacting for 1-2 hours, evaporating water under reduced pressure, keeping the temperature for reacting for 2-4 hours after the temperature in the reaction system reaches 200 ℃ and 210 ℃, distilling diethylene glycol under reduced pressure, adding water after evaporation to dissolve residues, extracting impurities by ethyl acetate for 3 times, adjusting the aqueous solution to be acidic, extracting a product by using ethyl acetate, drying by using anhydrous sodium sulfate, and distilling under reduced pressure to obtain an alkane carboxylic acid pure product.
Of these, it is preferable that cyclohexanone and morpholine in step (1) are added to the reaction flask in a molar ratio of 1-1.5:1-1.5, and then p-toluenesulfonic acid is added in an amount of 1.0-1.5% by mass of cyclohexanone.
Among them, it is preferable that the hydrochloric acid solution in the step (2) is a 30% w/w hydrochloric acid solution.
Among them, it is preferable that, in the step (3), to the 2-acyl cyclic ketone compound obtained in the step (2), a 2-fold volume of 37% w/v aqueous potassium hydroxide solution is added.
In the present invention, the objective carbon-enriched alkane carboxylic acid is first prepared into the corresponding acid halide, or the acid halide which has been industrially produced is directly purchased. Different methods for preparing acyl halides from alkane carboxylic acids are well known and will not be described in detail herein.
Compared with the prior art, the invention has the beneficial effects that:
the method can flexibly select and use cyclopentanone or cyclohexanone to realize the requirement of increasing to different carbon numbers according to the difference of the carbon numbers required to be increased and the difference of the target recarburized alkane carboxylic acid or the corresponding acyl halide source thereof.
The reaction process of the present invention can be summarized as follows:
from the above reaction process, it can be seen that the total length of the alkane carboxylic acid depends on the size of the carbon number n in the cyclic ketone and the acyl halide terminal R3While the structure is changed only depending on the acyl halide terminal R3Acyl halide terminal R3Has a wide selection range ofAccording to different target products, selecting proper acyl halide end R3Namely, the invention can provide rich choices for synthesizing long-chain alkane carboxylic acids with different sizes and types.
The long-chain alkane carboxylic acid prepared by the method has simple reaction process and no complex operation difficulty, and is suitable for industrial mass production.
Drawings
FIG. 1 is an infrared spectrum of 1-morpholine-1-cyclohexene;
FIG. 2 is an infrared spectrum of 2-isobutyrylcyclohexanone;
FIG. 3 is an infrared spectrum of 8-methylnonanoic acid;
FIG. 4 is an infrared spectrum of 1-morpholine-1-cyclopentene;
FIG. 5 is an infrared spectrum of 2-isobutyryl cyclopentanone;
FIG. 6 is an infrared spectrum of 7-methyloctanoic acid;
FIG. 7 is an infrared spectrum of 2- (3-methylbutyryl) cyclohexanone;
FIG. 8 is an infrared spectrum of 9-methyl decanoic acid;
FIG. 9 is an infrared spectrum of 2-oleoyl cyclohexanone;
FIG. 10 is an infrared spectrum of cis-15-eicosatetraenoic acid.
Detailed Description
The present invention is further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become more apparent as the description of the specific embodiments proceeds. The examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
Example 18 Synthesis of methylnonanoic acid
8-methylnonanoic acid
78.5g of cyclohexanone, 83.6g of morpholine, 1.0g of catalyst p-toluenesulfonic acid (TsOH) and 200mL of entrainer toluene are added into a 500mL reaction flask, stirred and heated under reflux until the water is separated to the calculated amount (14.4g), and then 200mL of toluene is recovered by reduced pressure distillation, so that 170g of crude 1-morpholine-1-cyclohexene is obtained, and an infrared spectrum of the crude 1-morpholine-1-cyclohexene is shown in FIG. 1.
Adding 300.0mL of chloroform into 100.0g of the obtained 1-morpholine-1-cyclohexene crude product for dilution, adding 121.7g of triethylamine, cooling to below 10 ℃, slowly dripping 127.3g of isobutyryl chloride, and after dripping, continuing to stir for reaction for 3 hours. Then adding 110.0mL of 30% w/w hydrochloric acid aqueous solution, heating and refluxing for 2 hours, separating liquid, separating a chloroform layer and a water layer, neutralizing the water layer with potassium hydroxide, separating liquid, collecting a mixture of triethylamine and morpholine, drying and fractionating to recover the triethylamine and morpholine for later use. The chloroform layer was washed twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 55.3g of crude 2-isobutyrylcyclohexanone compound whose infrared spectrum is shown in FIG. 2.
Adding the obtained crude product into an alkali solution in which 61.2g of potassium hydroxide is dissolved in 88.5g of water, carrying out reflux reaction for 1 hour, cooling, adjusting the reaction solution to be neutral by using diluted hydrochloric acid, and separating an organic layer to obtain the crude carbonyl carboxylic acid compound. 248.9g of diethylene glycol and 3.0 equivalent of potassium hydroxide are added into a reaction bottle, the mixture is stirred until the potassium hydroxide is dissolved, the obtained carbonyl carboxylic acid compound crude product and 45.1g of hydrazine hydrate are added, the temperature is raised to 145 ℃, water is evaporated under reduced pressure after 1 hour of reaction, the temperature is kept for reaction for 3 hours after the temperature in a reaction system reaches 210 ℃, the diethylene glycol is distilled under reduced pressure, water is added after the evaporation is finished to dissolve residues, ethyl acetate is used for extracting impurities for 3 times, the aqueous solution is adjusted to be acidic, the product is extracted by ethyl acetate, anhydrous sodium sulfate is dried and then distilled under reduced pressure, and 42.3g of pure 8-methylnonanoic acid is obtained, and the infrared spectrogram of the pure 8-methylnonanoic acid is shown in figure 3.
EXAMPLE 27 Synthesis of methyl octanoic acid
7-Methyloctanoic acid
84.1g cyclopentanone, 87.1g morpholine, catalyst p-toluenesulfonic acid 1.0g and 200mL entrainer toluene were added into a 500mL reaction flask, stirred, heated under reflux to react until the water was separated to the calculated amount (18.1g), and then the toluene was recovered by distillation under reduced pressure to 200mL, giving 163g crude 1-morpholine-1-cyclopentene, whose infrared spectrum is shown in FIG. 4.
Adding 500mL of chloroform into the obtained 1-morpholine-1-cyclopentene crude product for dilution, adding 210.2g of triethylamine, cooling to below 10 ℃, slowly dripping 220.8g of isobutyryl chloride, and continuing to stir for reaction for 3 hours after dripping. Then adding 110.0mL of 30% w/w hydrochloric acid aqueous solution, heating and refluxing for 2 hours, separating liquid, separating a chloroform layer and a water layer, neutralizing the water layer with potassium hydroxide, separating liquid, collecting a mixture of triethylamine and morpholine, drying and fractionating to recover the triethylamine and morpholine for later use. The chloroform layer was washed twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated to give 91.2g of a crude 2-isobutyrylcyclopentanone compound whose infrared spectrum is shown in FIG. 5.
Adding the obtained crude product into an alkaline solution in which 109.5g of potassium hydroxide is dissolved in 145.9g of water, carrying out reflux reaction for 1 hour, cooling, adjusting the reaction solution to be neutral by using diluted hydrochloric acid, and separating an organic layer to obtain the crude carbonyl carboxylic acid compound. Adding 410.4g of diethylene glycol and 3.0 equivalent of potassium hydroxide into a reaction bottle, stirring until the potassium hydroxide is dissolved, adding the obtained carbonyl carboxylic acid compound crude product and 80.9g of hydrazine hydrate, heating to 145 ℃, reacting for 1 hour, continuing to evaporate water, keeping the temperature for reacting for 3 hours after the temperature in the reaction system reaches 210 ℃, distilling the diethylene glycol under reduced pressure, adding water to dissolve residues after the evaporation is finished, extracting impurities by ethyl acetate for 3 times, adjusting the aqueous solution to be acidic, extracting a product by ethyl acetate, drying by anhydrous sodium sulfate, distilling under reduced pressure to obtain 68.3g of a pure product, namely 7-methyloctanoic acid, wherein an infrared spectrogram of the product is shown in figure 6.
Example 39 Synthesis of methyl decanoic acid
9-methyl decanoic acid
According to the method in example 1, 100.0g of the obtained 1-morpholine-1-cyclohexene crude product is diluted by adding 300.0mL of chloroform, 121.7g of triethylamine is added, the temperature is reduced to below 10 ℃, 144.1g of isovaleryl chloride is slowly dropped, and after dropping, the reaction is continued to be stirred for 3 hours. Then 110.0mL of 30% hydrochloric acid aqueous solution is added, liquid separation is carried out after heating reflux reaction for 2 hours, a chloroform layer and an aqueous layer are separated, the aqueous layer is separated after being neutralized by potassium hydroxide, a mixture of triethylamine and morpholine is collected, and then drying and fractional distillation are carried out to recover the triethylamine and the morpholine for standby. The chloroform layer was washed twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated to give 65.5g of a crude 2- (3-methylbutyryl) cyclohexanone compound, whose infrared spectrum is shown in FIG. 7.
Adding the obtained crude product into an alkali solution in which 66.5g of potassium hydroxide is dissolved in 104.8g of water, carrying out reflux reaction for 1 hour, cooling, adjusting the reaction solution to be neutral by using diluted hydrochloric acid, and separating an organic layer to obtain the crude carbonyl carboxylic acid compound. 294.8g of diethylene glycol and 3.0 equivalent of potassium hydroxide are added into a reaction bottle, the mixture is stirred until the potassium hydroxide is dissolved, the obtained carbonyl carboxylic acid compound crude product and 49.2g of hydrazine hydrate are added, the temperature is raised to 145 ℃, water is continuously distilled after the reaction is carried out for 1 hour, the temperature is kept for reaction for 3 hours after the temperature in a reaction system reaches 210 ℃, diethylene glycol is distilled under reduced pressure, water is added after the distillation is finished to dissolve residues, ethyl acetate is used for extracting impurities for 3 times, the aqueous solution is adjusted to be acidic, then ethyl acetate is used for extracting a product, anhydrous sodium sulfate is used for drying, and distillation under reduced pressure is carried out to obtain 40.1g of a pure product, namely 9-methyl decanoic acid, wherein an infrared spectrogram of the product is shown in.
EXAMPLE 4 Synthesis of cis-15-eicosatetraenoic acid
Cis-15-eicosatetraenoic acid
According to the method of example 1, 100.0g of the crude 1-morpholine-1-cyclohexene was diluted with 300.0mL of chloroform, 121.7g of triethylamine was added, the temperature was lowered to 10 ℃ or below, 224.8g of oleoyl chloride (80%) was slowly added dropwise, and after completion of the addition, the reaction was stirred for 3 hours. Then adding 110.0mL of 30% w/w hydrochloric acid aqueous solution, heating and refluxing for 2 hours, separating liquid, separating a chloroform layer and a water layer, neutralizing the water layer with potassium hydroxide, separating liquid, collecting a mixture of triethylamine and morpholine, drying and fractionating to recover the triethylamine and morpholine for later use. The chloroform layer was washed twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated to give 313.5g of a mixture of 2-oleoyl cyclohexanone compound and oleic acid, and the infrared spectrum of 2-oleoyl cyclohexanone was as shown in FIG. 9.
Adding the obtained crude product into an alkali solution in which 160.1g of potassium hydroxide is dissolved in 500.0g of water, carrying out reflux reaction for 1 hour, cooling, adjusting the reaction solution to be neutral by using diluted hydrochloric acid, and separating an organic layer to obtain the crude carbonyl carboxylic acid compound. Adding 1500g of diethylene glycol and 3.0 equivalent of potassium hydroxide into a reaction bottle, stirring until the potassium hydroxide is dissolved, adding the obtained carbonyl carboxylic acid compound crude product and 118.3g of hydrazine hydrate, heating to 145 ℃, reacting for 1 hour, continuing to evaporate water, keeping the temperature for reacting for 3 hours after the temperature in the reaction system reaches 210 ℃, distilling the diethylene glycol under reduced pressure, adding water to dissolve residues after the evaporation is finished, extracting impurities by ethyl acetate for 3 times, adjusting the aqueous solution to acidity, extracting a product by ethyl acetate, drying by anhydrous sodium sulfate, and distilling under reduced pressure to obtain 82.6g of pure cis-15-arachidonic acid, wherein an infrared spectrogram of the pure cis-15-eicosatetraenoic acid is shown in figure 10.
Claims (9)
1. A method for preparing alkane carboxylic acid by increasing alkane carbon chain, which is characterized by comprising the following steps:
(1) cyclopentanone or cyclohexanone firstly reacts with secondary amine compound to generate corresponding 1-position secondary amine substituted cyclopentene or cyclohexene crude product, namely, the schotkenylamine;
(2) carrying out electrophilic reagent reaction on the schotkenylamine and acyl halide to form a 2-acyl cyclic ketone compound;
(3) under the action of strong alkali, the 2-acyl cyclic ketone compound is subjected to ring opening to generate a carbonyl carboxylic acid compound, and the carbonyl carboxylic acid compound is subjected to Volvox-Huang Minlon reduction reaction to obtain the corresponding alkane carboxylic acid.
2. The process of claim 1, wherein the step (1) of reacting the schotkenylamine is carried out in the presence of p-toluenesulfonic acid as a catalyst.
3. The method of claim 1, wherein the secondary amine compound of step (1) comprises: piperidine, diethylamine, dimethylamine, morpholine and tetrahydropyrrole.
4. The method of claim 1, wherein the acid halide in step (2) is an acid chloride.
5. The method of claim 1, wherein the strong base in step (3) is sodium hydroxide or potassium hydroxide.
6. The method of claim 1, comprising the steps of:
(1) adding cyclopentanone or cyclohexanone, a secondary amine compound, p-toluenesulfonic acid as a catalyst and toluene as an entrainer into a reaction bottle, stirring, heating and refluxing for reaction until the separated water reaches the calculated amount, and then carrying out reduced pressure distillation to recover toluene to generate a corresponding 1-position secondary amine substituted cyclopentene or cyclohexene crude product, namely, sertraline amine;
(2) adding chloroform into the crude product of the Stroke enamine obtained in the step (1) for dilution, adding triethylamine as an acid-binding agent, cooling to below 10 ℃, slowly dropping acyl chloride, and continuing stirring for reaction after dropping to obtain a 2-acyl cyclic ketone compound; then adding a hydrochloric acid solution, heating and refluxing for 1.5-2.5 hours, separating liquid, separating a lower chloroform layer and a lower water layer, washing the chloroform layer twice with water, then drying with anhydrous sodium sulfate, and filtering to obtain a crude product of the 2-acyl cyclic ketone compound, wherein the crude product is directly used in the next step;
(3) adding a potassium hydroxide aqueous solution into the 2-acyl cyclic ketone compound crude product obtained in the step (2), heating and refluxing for 1-2 hours, cooling, then adjusting to be neutral by using diluted hydrochloric acid, separating an organic layer to be a carbonyl carboxylic acid compound crude product, adding diethylene glycol and potassium hydroxide into a reaction bottle, stirring until the potassium hydroxide is dissolved, adding the obtained carbonyl carboxylic acid compound crude product and hydrazine hydrate, heating to 140-150 ℃, reacting for 1-2 hours, evaporating water under reduced pressure, keeping the temperature for reacting for 2-4 hours after the temperature in the reaction system reaches 200-210 ℃, distilling diethylene glycol under reduced pressure, adding water to dissolve residues after evaporation, extracting impurities by ethyl acetate for 3 times, adjusting the aqueous solution to be acidic, extracting a product by using ethyl acetate, drying by using anhydrous sodium sulfate, and distilling under reduced pressure to obtain an alkane carboxylic acid pure product.
7. The process of claim 6, wherein cyclohexanone and morpholine are added to the reaction flask in step (1) in a molar ratio of 1-1.5:1-1.5, followed by addition of 1.0-1.5% by mass of cyclohexanone as p-toluenesulfonic acid.
8. The method of claim 6, wherein the hydrochloric acid solution in step (2) is a 30% w/w hydrochloric acid solution.
9. The method according to claims 1 to 6, wherein to the 2-acyl cyclic ketone compound obtained in the step (2) in the step (3), a 2-fold volume of 37% w/v aqueous potassium hydroxide solution is added.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110113263.3A CN112920042A (en) | 2021-01-27 | 2021-01-27 | Method for preparing alkane carboxylic acid by increasing alkane carbon chain |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110113263.3A CN112920042A (en) | 2021-01-27 | 2021-01-27 | Method for preparing alkane carboxylic acid by increasing alkane carbon chain |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112920042A true CN112920042A (en) | 2021-06-08 |
Family
ID=76167302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110113263.3A Pending CN112920042A (en) | 2021-01-27 | 2021-01-27 | Method for preparing alkane carboxylic acid by increasing alkane carbon chain |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112920042A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115340449A (en) * | 2022-09-02 | 2022-11-15 | 常州佳德医药科技有限公司 | Method for preparing 2-acetyl cyclopentanone by one-pot method |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1472627A (en) * | 1974-09-10 | 1977-05-04 | Science Union & Cie | Benzylaminoalkanoic acids process for their preparation and pharmaceutical compositions containing them |
| CN106083554A (en) * | 2016-06-12 | 2016-11-09 | 南京工业大学 | A kind of one kettle way prepares the method for 2 acetyl cyclohexanones |
-
2021
- 2021-01-27 CN CN202110113263.3A patent/CN112920042A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1472627A (en) * | 1974-09-10 | 1977-05-04 | Science Union & Cie | Benzylaminoalkanoic acids process for their preparation and pharmaceutical compositions containing them |
| CN106083554A (en) * | 2016-06-12 | 2016-11-09 | 南京工业大学 | A kind of one kettle way prepares the method for 2 acetyl cyclohexanones |
Non-Patent Citations (1)
| Title |
|---|
| HARUMI KAGA等: "A short route to dihydrocapsaicinoids", 《SYNTHESIS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115340449A (en) * | 2022-09-02 | 2022-11-15 | 常州佳德医药科技有限公司 | Method for preparing 2-acetyl cyclopentanone by one-pot method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH11349536A (en) | Synthesis of monoester or diester of 9,10-endoethano-9,10-dihydroanthracene-11,11-dicarboxylic acid and new monoester or diester obtained by the method | |
| CN112920042A (en) | Method for preparing alkane carboxylic acid by increasing alkane carbon chain | |
| EP1213279B1 (en) | Venlafaxine production process | |
| JPH08245661A (en) | Di(1,1,3,3-tetramethylbutyl)phosphine and its production | |
| KR900001006B1 (en) | Process for the optical resolution of racemic mixtures of alpha-naphthyl propionic acid | |
| EP0348813B1 (en) | Process for producing halogenated sulfone | |
| EP0461653A1 (en) | Process for producing beta-carotene, and intermediate compounds useful for the process | |
| JP4357748B2 (en) | Alcohol production method | |
| JP4183850B2 (en) | Method for producing glyceryl ether | |
| JP4086982B2 (en) | Process for producing N- (1,1-dimethyl-3-oxobutyl) acrylamide | |
| US4092366A (en) | Synthesis of Vitamin A, intermediates and conversion thereof to Vitamin A | |
| JP4014926B2 (en) | Recrystallization method of adamantanetriols | |
| JP2003500465A (en) | Method for producing alkoxy cinnamate | |
| JP3254746B2 (en) | Terminal acetylene compound and method for producing the same | |
| CN1034659C (en) | One-step synthesis of ortho-formate | |
| JPS6130544A (en) | Preparation of 1,3,5-trialkyl-2,4,6-tris(3,5-dialkyl-4-hydroxybenzyl)benzene | |
| JPH08245508A (en) | Unsaturated carboxylic acid ester and its production | |
| JP7190422B2 (en) | Method for producing 4-methyl-5-nonanone and 4-methyl-5-nonanol | |
| JP4644593B2 (en) | Method for producing E, Z-1,3,5-alkatriene | |
| KR0152056B1 (en) | Process for production of aromatic aldoximes | |
| WO2024023154A1 (en) | Process | |
| JP2013166701A (en) | Production method of long-chain saturated aliphatic primary alcohol | |
| CN114213230A (en) | Method for preparing 1, 3-dihydroxyacetone | |
| CN117105888A (en) | Synthesis method of MPLA acyl chain intermediate | |
| CN114262264A (en) | Vitamin K1Heck reaction synthesis method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210608 |
|
| RJ01 | Rejection of invention patent application after publication |