CN111018664B - Synthesis method of 2-alkyl-1, 3-propanediol compound - Google Patents
Synthesis method of 2-alkyl-1, 3-propanediol compound Download PDFInfo
- Publication number
- CN111018664B CN111018664B CN201911378918.9A CN201911378918A CN111018664B CN 111018664 B CN111018664 B CN 111018664B CN 201911378918 A CN201911378918 A CN 201911378918A CN 111018664 B CN111018664 B CN 111018664B
- Authority
- CN
- China
- Prior art keywords
- alkyl
- compound
- propanediol
- catalyst
- synthesizing
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/10—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of ethers, including cyclic ethers, e.g. oxiranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/14—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group
- C07C29/141—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of a —CHO group with hydrogen or hydrogen-containing gases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- 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
- C07C45/61—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
- C07C45/64—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 introduction of functional groups containing oxygen only in singly bound form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention discloses a method for synthesizing a 2-alkyl-1, 3-propanediol compound, which comprises the following steps: step 1, taking 2-alkylacrolein 1D as a raw material, and carrying out addition reaction with an alcohol compound 1E under the action of a catalyst to obtain a beta-aldehyde ether intermediate 1F, wherein the catalyst is selected from a 3, 4-di (formate) -phthalimide compound 1A, a 5-formate-2, 3-naphthalimide compound 1B or a 5, 8-di (formate) -2, 3-naphthalimide compound 1C; and 2, carrying out catalytic hydrogenation and ether bond protecting group removal on the intermediate 1F sequentially to obtain the 2-alkyl-1, 3-propanediol compound. The method provided by the invention has the advantages of cheap and easily available raw materials, recoverable catalyst, mild reaction conditions, high yield of more than 70 percent and greatly reduced cost.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and discloses a synthesis method of a 2-alkyl-1, 3-propanediol compound.
Background
The 2-alkyl-1, 3-propanediol compound is an organic synthesis intermediate and has more applications in liquid crystal materials, medicines and the like.
At present, the common industrialized synthetic methods are mainly as follows: firstly, synthesizing 2-alkyl diethyl malonate by using diethyl malonate; reducing the ester group with sodium borohydride, lithium aluminum hydride, red aluminum, etc. to obtain 2-alkyl-1, 3-propanediol, the reaction equation is as follows:
in the method, the product of the first step reaction has more by-product diethyl 2, 2-di (alkyl) malonate to be separated, the separation cost is high, and at least 10 percent of yield is lost; in the second step, 2 times of equivalent and high-price sodium borohydride (or lithium aluminum hydride, red aluminum) and the like are needed, so the method has higher cost for synthesizing the 2-alkyl-1, 3-propanediol.
Disclosure of Invention
The invention aims to reduce the production cost of 2-alkyl-1, 3-propanediol and provides a new method for synthesizing 2-alkyl-1, 3-propanediol, and the total yield can reach more than 70 percent; in addition, among various raw materials, alcohol compounds, hydrogen and the like are common cheap chemical raw materials, and the catalyst is not used in large amount and can be recycled and reused; the product cost is obviously lower than that of the prior art which takes diethyl malonate as raw material.
In order to achieve the above objects, the present invention provides a method for synthesizing a 2-alkyl-1, 3-propanediol-based compound, the 2-alkyl-1, 3-propanediol-based compound having the following general formula 1H:
the synthesis method comprises the following steps:
step 1, taking 2-alkylacrolein 1D as a raw material, and adding the 2-alkylacrolein 1D and an alcohol compound 1E under the action of a catalyst to obtain a beta-aldehyde ether intermediate 1F, wherein the reaction equation is as follows:
wherein, R is 3 、R 4 、R 5 All selected from the group of organic radicals (which may be the same or different, and may be selected from any one or combination of more) consisting of hydrogen atoms, aromatic radicals, aliphatic radicals of C1-9, and hetero atoms, wherein the hetero atoms include any one or more of N, O, si or halogen elements;
the catalyst is selected from any one or more of a compound 1A, a compound 1B or a compound 1C;
wherein R is 1 、R 2 All selected from the group of organic groups consisting of aromatic groups, aliphatic groups of C1-9, and heteroatoms (which may be the same or different, and may be selected from any one or combination of more), wherein the heteroatoms include any one or more of N, O, si or halogen;
and 2, carrying out catalytic hydrogenation and ether bond protecting group removal on the beta-aldehyde ether intermediate 1F to obtain the 2-alkyl-1, 3-propanediol compound 1H.
Alternatively, said R 3 、R 4 、R 5 Selected from C1-5 aliphatic group or C1-5 heteroatom substituent or hydrogen, the heteroatom comprises any one or more of O, F, si or N.
Optionally, step 1 includes:
step 1.1, adding the catalyst and the alcohol compound 1E into a container, and uniformly mixing;
step 1.2, stirring at 0-80 ℃, and adding or dropping 2-alkylacrolein 1D into the container in batches; after the addition, stirring is continued and the reaction is carried out for 1 to 48 hours under the condition of heat preservation, thus obtaining the beta-aldehyde ether intermediate 1F.
Optionally, the alcohol compound 1E is selected from any one or more of methanol, ethanol, propanol, isopropanol, allyl alcohol, butanol, isobutanol, tert-butanol, tert-amyl alcohol, benzyl alcohol, cyclopentanol, cyclohexanol, ethylene glycol, and 2-hydroxytetrahydrofuran.
Alternatively, the alcohol compound 1E is used in an amount of 1.0 to 100 times in terms of a molar ratio as compared with the 2-alkylacrolein 1D.
Alternatively, the catalyst is used in an amount of 0.5% to 10% by mole based on 2-alkylacrolein 1D.
Optionally, in step 2, the catalyst used for catalytic hydrogenation is selected from hydrogenation catalysts capable of reducing aldehyde groups to hydroxyl groups at a temperature below 120 ℃.
Optionally, in step 2, the reaction temperature of the catalytic hydrogenation is between 60 and 120 ℃; the hydrogen pressure is between 0.4 and 8.0MPa, and the reaction time takes the reactant not to absorb hydrogen (or central control analysis, and most aldehyde groups are hydrogenated and reduced) as an end point.
Optionally, the step 2 includes:
step 2.1, catalytic hydrogenation: the beta-aldehyde ether intermediate 1F is subjected to hydrogenation catalysis to generate a beta-hydroxymethyl ether intermediate 1G;
step 2.2, removing ether bond protecting groups, such as acid catalytic hydrolysis, benzyl ether hydrogenolysis and the like, and obtaining the 2-alkyl-1, 3-propanediol compound 1H, the reaction equation is as follows:
alternatively, when R 4 、R 5 Any one of the two is H, and when the other one is phenyl, the beta-aldehyde ether intermediate is shown as a general formula 1F', and is directly hydrogenated and removed with benzyl protecting group through catalytic hydrogenation, and the reaction equation is as follows:
in the method for synthesizing the 2-alkyl-1, 3-propylene glycol, alcohol compounds, hydrogen and the like are common cheap chemical raw materials in various raw materials; 2-alkylacroleins can be prepared in high yields from inexpensive fatty aldehydes and formaldehyde; only the catalyst has higher price, but the catalyst has small dosage and can be recycled and reused; and the process condition is mild, the operation is simple and convenient, and the total yield can reach more than 70 percent, so the product cost is obviously lower than that of the prior production method taking diethyl malonate as a raw material.
Detailed Description
The following examples illustrate the invention in detail: the embodiment is implemented on the premise of the technical scheme of the invention, and gives a detailed implementation mode and a specific operation process. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention.
As used herein, "liquid temperature" refers to the temperature of a solution.
In order to reduce the cost of raw materials and improve the reaction yield, the technical idea of the application is as follows: taking 2-alkylacrolein 1D as a raw material, and adding the 2-alkylacrolein 1D with a compound 1E such as alcohols under the action of the selected catalysts (1A, 1B and 1C) to obtain a beta-aldehyde ether intermediate 1F; then the 2-alkyl-1, 3-propanediol 1H is obtained through the classical chemical reaction of reducing aldehyde group by catalytic hydrogenation and removing ether protecting group, and the total yield can reach more than 70%.
However, this method has the following technical difficulties, and there has not been any report or attempt.
Most critically, a suitable catalyst is required to allow the reaction of 2-alkylacrolein with the alcohol compound to obtain the β -aldehyde ether intermediate, corresponding to the following reaction equation:
most of the documents before the present invention use strong acid or basic catalysts (such as acetic acid; 1, 8-diazabicycloundec-7-ene, etc.) to catalyze the reaction, however, the yield is generally only 40-50%, the residual raw materials or byproducts after the reaction are too much, for example, the acid catalyst can catalyze aldehyde group and alcohol compound to generate acetal byproduct; the basic catalyst can cause the self-polymerization side reaction of 2-alkylacrolein which is one of the raw materials, and the chemical property of the product (beta-aldehyde ether intermediate 1F) is unstable, and the product can be easily decomposed and changed back to two raw materials under the conditions of strong acidity and alkalinity, so that the catalyst has no industrial practical value.
Although a few documents report that the reaction yield reaches over 80 percent by using o-benzoyl sulfimide or o-diphenyldisulfonimide as a catalyst; however, since the product of this reaction (β -aldehyde ether intermediate 1F) has a large molecular polarity and poor chemical stability, there is no suitable method for completely removing the residual phthalimide (or phthalimide) after the reaction is completed. The o-benzoylsulfonyl imide and the o-diphenyldisulfonyl imide both contain sulfur, and even if only ppm-level residues exist in the product of the reaction, the hydrogenation reduction of aldehyde groups can not be completed due to serious catalyst poisoning during the subsequent hydrogenation reaction of the invention.
In order to solve the problems, the invention optimizes 3 new catalysts which are not reported before through creative work: 3, 4-bis (formate) -phthalimide compound (1A), 5-formate-2, 3-naphthalimide compound (1B), and 5, 8-bis (formate) -2, 3-naphthalimide compound (1C). The main structure of the 3 catalysts is phthalic acid (or o-naphthalene) dicarboxamide, and originally, the solubility of the compounds in various organic solvents is not very good, so that one or two ester groups are added to the main structure of the compounds, and two advantages are generated: first, the increased ester groups improve the solubility of such compounds in most organic solvents. Secondly, if the ester group is hydrolyzed to a carboxyl group by acid or base catalyzed hydrolysis, the catalyst is changed to an amide plus carboxyl group structure, and the solubility is greatly reduced and precipitated from the solvent. Then filtered (recovered) and the filter cake can be changed back to the catalyst by carrying out the esterification reaction again. The 3 catalysts can not only lead 2-alkyl acrolein to smoothly react with alcohol compounds, but also lead the yield of the beta-aldehyde ether intermediate 1F to reach more than 80 percent; and the subsequent hydrogenation reaction is not adversely affected, and the catalyst can be conveniently recycled, so that the corresponding process route of the invention has feasibility and practical value.
In the process of preparing the beta-aldehyde ether intermediate 1F by the catalytic addition reaction, a certain amount of solvent can be added if necessary. If the added alcohol compound is sticky and not good for stirring, or is in a solid state (at the reaction temperature), or the added alcohol compound has poor dissolving effect on the catalyst, the solvent needs to be added, otherwise, no additional solvent is needed.
If a solvent is added, the solvent can be one or more of petroleum ether, cyclohexane, methylcyclohexane, benzene, toluene, xylene, ethyl acetate, tetrahydrofuran, methyl cyclopentyl ether, dioxane, methyl tert-butyl ether and the like. In fact, more solvents are available for the reaction; basically, any organic solvent can be used as long as it has a neutral pH and can dissolve the alcohol compound and the catalyst.
The amount of the solvent may be 0 to 30 times (mass ratio) the amount of the 2-alkylacrolein to be added.
The beta-aldehyde ether intermediate 1F is subjected to catalytic hydrogenation to reduce aldehyde groups, and various classical mature aldehyde compounds can be hydrogenated to obtain alcohol compounds. The hydrogenation catalyst is only required to reduce aldehyde groups to hydroxyl groups at the temperature of below 120 ℃, and any one or combination of any more of palladium catalyst, ruthenium catalyst and platinum catalyst can be selected, such as raney nickel or palladium carbon. The amount of the hydrogenation catalyst to be used varies depending on the kind of the catalyst, and for example, the amount of Raney nickel is generally 10 to 25 mass% based on the raw material 2-alkylacrolein; the amount of palladium on carbon used is generally 0.5 to 5 mass% based on the starting 2-alkylacrolein.
The reaction condition for removing ether protecting group can adopt various classical mature ether bonds to remove protecting group to obtain alcohol compound reaction conditions, such as acid catalytic hydrolysis, benzyl ether hydrogenolysis and the like, and has mild condition and high yield. If the ether bond protecting group to be removed is a benzyl group, the benzyl protecting group from which the ether bond is removed can be removed simultaneously with the catalytic hydrogenation.
The obtained crude solution of 2-alkyl-1, 3-propanediol 1H can be further processed by various common organic compound purification methods, such as extraction, liquid separation, reduced pressure distillation (rectification), crystallization, steam distillation and the like, and finally the 2-alkyl-1, 3-propanediol with the purity of more than 98 percent is obtained.
The following is further illustrated with reference to the examples.
Example 1
The synthetic route is as follows:
460g (10 mol) of absolute ethanol and 0.145g (0.0005 mol) of 3, 4-bis (ethylformate) -phthalimide were added to a 1000ml three-necked glass flask under nitrogen. Cooling the reaction solution to about 0 ℃ with stirring, and then adding 8.4g (0.1 mol) of 2-ethylacrolein (2A); after the addition, the temperature is kept between 0 and 10 ℃ and the stirring is continued for 48 hours.
The reaction mixture was transferred to an autoclave, and 2.1g of Raney nickel was added thereto. After nitrogen replacement, continuously introducing hydrogen, and carrying out catalytic hydrogenation at the liquid temperature of 110-120 ℃ and the hydrogen pressure of 8 MPa. After about 10 hours, it was confirmed that no hydrogen absorption occurred. And cooling the hydrogenation reaction liquid to room temperature, then replacing with nitrogen, taking out the reaction liquid, and filtering to recover the Raney nickel.
The filtrate was transferred to another clean 1000ml three-necked flask, and 100g of 10% sulfuric acid was additionally added thereto, followed by heating with stirring until ethanol refluxed for 8 hours. After the temperature is reduced, the reaction liquid is neutralized to be neutral by sodium hydroxide solution, and then ethanol and water are removed by decompression and concentration. The concentrated residue was extracted 3 times with 50ml of ethyl acetate each time; the ethyl acetate layers are combined and concentrated again under reduced pressure to give about 10.2g (theoretical yield 10.4 g) of a concentrated residue, i.e. crude 2-ethyl-1, 3-propanediol (2D). The content thereof was about 86.1% by gas chromatography.
Comparative example 1
The 3, 4-bis (ethylformate) -phthalimide employed in example 1 was replaced with an equal mass of DBU (1, 8-diazabicycloundec-7-ene); the rest of the operation was the same as in example 1. The crude product obtained was analyzed by gas chromatography, wherein the content of the objective product (2-ethyl-1, 3-propanediol, 2D) was only 51%, and about 29% of 2-methylbutanol, and other various impurities were further contained. It can be seen that the DBU catalyst does not achieve the objects of the present invention, and the preferred catalysts of the present invention have unexpected technical effects.
Comparative example 2
0.0145g of 3, 4-bis (ethylformate) -phthalimide, as used in example 1, was replaced by 0.6g (0.01 mol) of acetic acid; the rest of the operation was the same as in example 1. The resulting crude product was analyzed by gas chromatography and contained only 46% of the desired product (2-ethyl-1, 3-propanediol, 2D), about 33% of 2-methylbutanol, and about 16% of 2-methylbutanal. It can be seen that acetic acid as a catalyst does not achieve the object of the present invention.
Example 2
The synthetic route is as follows:
200g of toluene, 7.4g (0.1 mol) of t-butanol and 2.68g (0.01 mol) of 5-carbothoxy-2, 3-naphthalimide are introduced into a 500ml three-necked glass flask under nitrogen. While stirring, 16.8g (0.1 mol) of 2- (3, 4-difluoro) phenylacrolein (3A) was further added to the reaction solution; after the addition, the temperature is kept between 70 and 80 ℃ and the stirring is continued for 1 hour.
The reaction mixture was transferred to an autoclave, and 0.084g of 5% palladium on carbon was added thereto. After nitrogen replacement, hydrogen is continuously introduced, and catalytic hydrogenation is carried out under the conditions that the liquid temperature is 90-100 ℃ and the hydrogen pressure is 0.4 MPa. After about 8 hours, it was confirmed that hydrogen absorption did not occur. And cooling the hydrogenation reaction liquid to room temperature, then replacing with nitrogen, taking out the reaction liquid, and filtering to recover the palladium-carbon.
The filtrate was transferred to another clean 500ml three-necked flask, and 50g of 5% sulfuric acid was further added thereto, followed by heating to reflux toluene for 5 hours with stirring. Cooling to room temperature again, and then separating liquid to remove a sulfuric acid layer; washing with 100ml (each time) of 2% potassium hydroxide solution for 2 times to remove 5-ethyl formate-2, 3-naphthalimide; finally, the organic layer is washed by water to be neutral and separated. The organic layer was concentrated under reduced pressure to remove toluene to give a pale yellow paste (solidified after cooling); after 2 crystallization of the residue with 4 times (by mass/volume) chloroform, 14.7g (theoretical yield 18.8 g) of 2- (3, 4-difluoro) phenyl-1, 3-propanediol (3D) was obtained, which was analyzed by gas chromatography to have a purity of 98.3%.
Example 3
The synthetic route is as follows:
a1000 ml three-necked glass bottle was charged with 540g of tetrahydrofuran, 21.6g (0.2 mol) of benzyl alcohol, and 1.64g (0.005 mol) of 5, 8-bis (ethylformate) -2, 3-naphthalimide under nitrogen atmosphere. Under stirring, 18.0g (0.1 mol) of 2- (4-propyl) cyclohexylacrolein (4A) was further added to the reaction solution; after the addition, the temperature is kept between 40 ℃ and 50 ℃ and the stirring is continued for 5 hours.
The reaction solution was transferred to an autoclave, and 0.9g of 3% palladium on carbon was added. After nitrogen replacement, hydrogen is continuously introduced, and catalytic hydrogenation is carried out at the liquid temperature of 60-70 ℃ and the hydrogen pressure of 2.0 MPa. About 10 hours, after confirming that no hydrogen absorption phenomenon exists; and cooling the hydrogenation reaction liquid to room temperature, then replacing with nitrogen, taking out the reaction liquid, and filtering to recover the palladium-carbon.
The filtrate obtained is washed 2 times with 50ml (each time) of a 2% potassium hydroxide solution to remove 5, 8-bis (ethylformate) -2, 3-naphthalimide; then concentrating under reduced pressure to remove tetrahydrofuran to obtain light yellow paste (cooling and solidifying); after 2 crystallization of the residue with 5 times (by mass/volume) petroleum ether, 15.4g (theoretical yield 20.0 g) of 2- (4-propyl) cyclohexyl-1, 3-propanediol (4C) was obtained, which was analyzed by gas chromatography to have a purity of 98.6%.
In conclusion, the invention takes 2-alkylacrolein as raw material, and the 2-alkylacrolein and compounds such as alcohols are added under the action of the catalyst designed by the invention to obtain a beta-aldehyde ether intermediate; the 2-alkyl-1, 3-propanediol is obtained through the classical chemical reaction of reducing aldehyde group by catalytic hydrogenation and removing ether protecting group, and the total yield can reach more than 70%.
While the present invention has been described in detail with reference to the preferred embodiments, it should be understood that the above description should not be taken as limiting the invention. Various modifications and alterations to this invention will become apparent to those skilled in the art upon reading the foregoing description. Accordingly, the scope of the invention should be determined from the following claims.
Claims (10)
1. A method for synthesizing a 2-alkyl-1, 3-propanediol compound, the 2-alkyl-1, 3-propanediol compound having the following general formula 1H:
the synthesis method is characterized by comprising the following steps:
step 1, taking 2-alkylacrolein 1D as a raw material, and adding the 2-alkylacrolein 1D and an alcohol compound 1E under the action of a catalyst to obtain a beta-aldehyde ether intermediate 1F, wherein the reaction equation is as follows:
wherein, R is 3 、R 4 、R 5 Are all selected from hydrogen atoms, aromatic groups and C1-9 aliphatic groups;
the catalyst is selected from any one or more of the following 3, 4-di (formate) -phthalimide compound 1A, 5-formate-2, 3-naphthalimide compound 1B or 8-di (formate) -2, 3-naphthalimide compound 1C;
wherein R is 1 、R 2 All C1-9 aliphatic groups;
and 2, carrying out catalytic hydrogenation and ether bond protecting group removal on the beta-aldehyde ether intermediate 1F to obtain the 2-alkyl-1, 3-propanediol compound 1H.
2. The method of synthesizing a 2-alkyl-1, 3-propanediol-based compound according to claim 1, wherein R is 1 、R 2 All selected from C1-5 aliphatic groups; said R 3 、R 4 、R 5 Selected from C1-5 aliphatic group or hydrogen.
3. The method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 1, wherein the step 1 comprises:
step 1.1, adding the catalyst and the alcohol compound 1E into a container, and uniformly mixing;
step 1.2, stirring at 0-80 ℃, and adding or dripping 2-alkylacrolein 1D into the container in batches; and after the addition is finished, continuing stirring and carrying out heat preservation reaction for 1-48 hours to obtain the beta-aldehyde ether intermediate 1F.
4. The method for synthesizing 2-alkyl-1, 3-propanediol according to claim 1, wherein the alcohol compound 1E is selected from the group consisting of methanol, ethanol, propanol, isopropanol, allyl alcohol, butanol, isobutanol, tert-butanol, tert-amyl alcohol, benzyl alcohol, cyclopentanol, cyclohexanol, ethylene glycol, and 2-hydroxytetrahydrofuran.
5. The method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 1, wherein the alcohol compound 1E is used in an amount of 1.0 to 100 times in terms of molar ratio as compared with the 2-alkylacrolein 1D.
6. The method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 1, wherein the amount of the catalyst used is 0.5 to 10% by mole relative to 2-alkylacrolein 1D.
7. The method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 1, wherein the step 2 comprises:
step 2.1, catalytic hydrogenation: the beta-aldehyde ether intermediate 1F is subjected to hydrogenation catalysis to generate a beta-hydroxymethyl ether intermediate 1G;
step 2.2, removing ether bond protecting groups to obtain a 2-alkyl-1, 3-propanediol compound 1H;
the reaction equation for this step 2 is as follows:
8. the method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 7, wherein in step 2, the catalyst used for the catalytic hydrogenation is a hydrogenation catalyst capable of reducing an aldehyde group to a hydroxyl group at 120 ℃ or lower.
9. The method for synthesizing a 2-alkyl-1, 3-propanediol compound according to claim 7, wherein in the step 2, the reaction temperature of the catalytic hydrogenation is 60 to 120 ℃; the pressure of hydrogen is between 0.4 and 8.0 MPa.
10. The method of claim 1, wherein R is the number of ring atoms in the ring structure of the 2-alkyl-1, 3-propanediol compound 4 、R 5 Any one of the beta-aldehyde ether intermediates is H, and when the other one is phenyl, the beta-aldehyde ether intermediate is shown as a general formula 1F', and is directly hydrogenated and subjected to benzyl protecting group removal through catalytic hydrogenation, wherein the reaction equation is as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911378918.9A CN111018664B (en) | 2019-12-27 | 2019-12-27 | Synthesis method of 2-alkyl-1, 3-propanediol compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911378918.9A CN111018664B (en) | 2019-12-27 | 2019-12-27 | Synthesis method of 2-alkyl-1, 3-propanediol compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111018664A CN111018664A (en) | 2020-04-17 |
| CN111018664B true CN111018664B (en) | 2023-04-14 |
Family
ID=70194717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911378918.9A Active CN111018664B (en) | 2019-12-27 | 2019-12-27 | Synthesis method of 2-alkyl-1, 3-propanediol compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111018664B (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400201A (en) * | 2001-07-31 | 2003-03-05 | 中国石油化工股份有限公司 | Preparation method of 1,3-propylene glycol |
| CN101412705A (en) * | 2008-11-06 | 2009-04-22 | 浙江工业大学 | Method for synthesizing 2-methyl-2-propyl-1,3-propanediol dimethyl carbonate compound |
| CN102399160A (en) * | 2011-12-21 | 2012-04-04 | 武汉武药科技有限公司 | Method for synthesizing chloramphenicol |
| RU2013138525A (en) * | 2013-08-20 | 2014-01-10 | Федеральное государственное унитарное предприятие "Государственный научный центр "Научно-исследовательский институт органических полупродуктов и красителей" (ФГУП "ГНЦ "НИОПИК") | METHOD FOR PRODUCING DIALKYL ETHERS OF 4,5-Dicyanophthalic Acid |
| CN105152857A (en) * | 2015-08-19 | 2015-12-16 | 上海应用技术学院 | Preparation method of 2-phenyl-1,3-propanediol |
| CN105523886A (en) * | 2014-10-24 | 2016-04-27 | 中国石油化工股份有限公司 | Method for synthesis of 1, 3-propanediol |
| CN105585419A (en) * | 2014-10-24 | 2016-05-18 | 中国石油化工股份有限公司 | 1,3-propanediol synthesis method |
| CN107721821A (en) * | 2017-10-13 | 2018-02-23 | 北京博迩科技有限公司 | A kind of method for preparing 1,3 propane diols |
| CN107892645A (en) * | 2017-10-26 | 2018-04-10 | 苏州盖德精细材料有限公司 | A kind of method of the high efficiency synthesis propane diols of 2 phenyl 1,3 |
| CN109970511A (en) * | 2019-04-19 | 2019-07-05 | 江苏扬农化工集团有限公司 | A kind of method of HPPO by-product resource utilization synthesis 1,3- propylene glycol |
| CN110105169A (en) * | 2019-06-13 | 2019-08-09 | 厦门大学 | The method that ethylene oxide coupling synthesis gas prepares 1,3- propylene glycol |
| CN110386856A (en) * | 2018-04-19 | 2019-10-29 | 万华化学集团股份有限公司 | A kind of method that acrolein hydration adds hydrogen to prepare 1,3- propylene glycol |
-
2019
- 2019-12-27 CN CN201911378918.9A patent/CN111018664B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1400201A (en) * | 2001-07-31 | 2003-03-05 | 中国石油化工股份有限公司 | Preparation method of 1,3-propylene glycol |
| CN101412705A (en) * | 2008-11-06 | 2009-04-22 | 浙江工业大学 | Method for synthesizing 2-methyl-2-propyl-1,3-propanediol dimethyl carbonate compound |
| CN102399160A (en) * | 2011-12-21 | 2012-04-04 | 武汉武药科技有限公司 | Method for synthesizing chloramphenicol |
| RU2013138525A (en) * | 2013-08-20 | 2014-01-10 | Федеральное государственное унитарное предприятие "Государственный научный центр "Научно-исследовательский институт органических полупродуктов и красителей" (ФГУП "ГНЦ "НИОПИК") | METHOD FOR PRODUCING DIALKYL ETHERS OF 4,5-Dicyanophthalic Acid |
| CN105523886A (en) * | 2014-10-24 | 2016-04-27 | 中国石油化工股份有限公司 | Method for synthesis of 1, 3-propanediol |
| CN105585419A (en) * | 2014-10-24 | 2016-05-18 | 中国石油化工股份有限公司 | 1,3-propanediol synthesis method |
| CN105152857A (en) * | 2015-08-19 | 2015-12-16 | 上海应用技术学院 | Preparation method of 2-phenyl-1,3-propanediol |
| CN107721821A (en) * | 2017-10-13 | 2018-02-23 | 北京博迩科技有限公司 | A kind of method for preparing 1,3 propane diols |
| CN107892645A (en) * | 2017-10-26 | 2018-04-10 | 苏州盖德精细材料有限公司 | A kind of method of the high efficiency synthesis propane diols of 2 phenyl 1,3 |
| CN110386856A (en) * | 2018-04-19 | 2019-10-29 | 万华化学集团股份有限公司 | A kind of method that acrolein hydration adds hydrogen to prepare 1,3- propylene glycol |
| CN109970511A (en) * | 2019-04-19 | 2019-07-05 | 江苏扬农化工集团有限公司 | A kind of method of HPPO by-product resource utilization synthesis 1,3- propylene glycol |
| CN110105169A (en) * | 2019-06-13 | 2019-08-09 | 厦门大学 | The method that ethylene oxide coupling synthesis gas prepares 1,3- propylene glycol |
Non-Patent Citations (2)
| Title |
|---|
| Copper-Catalyzed Stereospecific Hydroboration of Internal Allylic Alcohols;Enhui Ji等;《Eur.J.Org.Chem.2019》;20191130;全文 * |
| Diastereoselective Ni-catalyzed 1,4-hydroboration of chiral dienols;Robert J.Ely等;《Tetrahedron Letters (2015)》;20151231;第56卷;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111018664A (en) | 2020-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107805205B (en) | Preparation method of (R) -3-aminobutanol | |
| TWI403496B (en) | Process for obtaining ditrimethylolpropane and trimethylolpropane-enriched product streams from the secondary streams of trimethylolpropane preparation | |
| HU198437B (en) | Process for producing mono- or bis-carbonyl-compounds | |
| US9353032B2 (en) | Method for the production of neopentyl glycol | |
| JP5372258B2 (en) | Process for producing 1,4-disubstituted cyclohexane derivatives | |
| CN102180769B (en) | Method for synthesizing 1,2-pentanediol | |
| KR20060132860A (en) | Methods for preparing 1,3-butylene glycol | |
| KR870001141B1 (en) | Process for preparing 4-alkoxy-anilines | |
| CN111018664B (en) | Synthesis method of 2-alkyl-1, 3-propanediol compound | |
| CA1319707C (en) | Process for the preparation of serinol | |
| US4067905A (en) | Preparation of 2-amino-n-butanol | |
| CN115073300B (en) | 4- (perfluoropropane-2-yl) -2-trifluoromethyl aniline and preparation method and application thereof | |
| KR100529763B1 (en) | Production method for benzenedimethanol compound | |
| CN109836374B (en) | Environment-friendly preparation method of vitamin B6 | |
| US20050054879A1 (en) | Process for producing alicyclic aldehydes | |
| JP3319007B2 (en) | Method for producing N- (α-alkoxyethyl) formamide | |
| KR20020064670A (en) | Production of dimethylolcarboxylic acid | |
| JPH07116089B2 (en) | Method for producing 3-methoxybutanol | |
| WO2002034703A2 (en) | Method of making fluorinated alcohols | |
| CN114436873B (en) | Preparation method of tranexamic acid | |
| JPH0359887B2 (en) | ||
| CN112661694B (en) | Preparation method of 4- (dimethoxymethyl) -piperidine | |
| CN114957060A (en) | Synthetic method of 6-ethylthio-3-hepten-2-one | |
| KR100817816B1 (en) | Production process for halogenated aromatic methylamine | |
| JPH059427B2 (en) |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |