A preparation method of 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde

Abstract

The invention discloses a method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde, comprising the following steps: a) reacting acetaldehyde of formula III with a primary amine of formula IV to obtain N-alkylethyleneimine of formula V; b) reacting 1,4-dihalo-2-butene of formula II with N-alkylethyleneimine of formula V in the presence of a Grignard reagent of formula VI, and then hydrolyzing under acidic conditions to obtain a compound of formula VII; c) reacting the compound of formula VII with formaldehyde of formula VIII in the presence of a catalyst to obtain a compound of formula IX; d) in a hydrogen atmosphere, in the presence of a catalyst and a pyridine auxiliary agent, causing the compound of formula IX to undergo a hydroisomerization reaction to obtain 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde of formula I; the reaction equation is as follows: The method has the advantages of easy availability of raw materials, high reaction yield, simple operation, easy industrial production, and the like.

Description

Technical Field

[0001] The invention relates to a method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde, and belongs to the field of organic synthesis. Background Art

[0002] 2,7-Dimethyl-2,4,6-octatriene-1,8-dialdehyde, referred to as "decene aldehyde", has a molecular formula of C 10 H 12 O2, molecular weight is 164.2, CAS: 5056-17-7, decadecene aldehyde is usually a light yellow powdery solid, melting point 157.0-159.0℃, easily soluble in methanol, dichloromethane, petroleum ether, ethyl acetate, slightly soluble in water, is a key intermediate in the synthesis of carotenoids, and has important applications in the synthesis of β-carotene, canthaxanthin, astaxanthin, and lycopene.

[0003] The synthesis methods of 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde reported in the literature are mainly the following:

[0004]

[0005] The above route is a process route reported in patents US20020128520, US6673972, US5300658, US5382732, etc., using furan as the starting material, and reacting with methanol in two steps to obtain 1,1,4,4-tetramethoxy-2-butene, 1,1,4,4-tetramethoxy-2-butene condenses with propenyl methyl ether under Lewis acid catalysis to obtain an addition product, and then undergoes acidic and alkaline elimination to form a double bond to obtain the product. This route uses bromine, which is expensive, toxic, and chemically active and unstable. In addition, there are many side reactions in the addition reaction of acetal, and the addition product is still a diacetal structure, which can be further condensed with propenyl methyl ether to undergo a telomerization reaction to form a polymer.

[0006] The above route is the process route of patent US5276209, which uses 1-ethoxy-1-propylene as the starting material, and reacts with triethyl orthoformate under Lewis acid catalysis to obtain 1,1,3,3-tetraethoxy-2-methylpropane, and eliminates one molecule of ethanol under the action of acid to form a 2-methyl-3-ethoxy-2-butenal compound, which is added with acetylene diGrignard reagent, and then dehydrated to form olefinic bonds, and the triple bond is partially hydrogenated to form a double bond, and finally the acetal is deprotected to synthesize decadecene aldehyde through seven steps. The process has a long reaction step, and the first three steps are difficult to control, and the total yield of decadecene aldehyde is only 21%.

[0007] Patents US6297416B1 and US6403838 report the above-mentioned method of using 4-acetoxy-2-methyl-2-butene-1-aldehyde, a raw material for synthesizing vitamin A, as a starting material, first using neopentyl glycol to form an acetal protection, then alkaline hydrolysis, the obtained hydroxy compound is halogenated, reacted with sodium sulfide to form a sulfide compound, the sulfide is oxidized to become sulfoxide, and then reacted with sodium dithionite for desulfurization and dimerization condensation to obtain a decadecene aldehyde. This route has a total of seven steps of reaction, involving protection and deprotection, and the reaction process is cumbersome, which is not conducive to industrial production.

[0008] Patent EP523534A2 uses sodium benzenesulfinate as a linker to react with two molecules of 2-(3-chloro-1-methyl-1-propenyl)-5,5-dimethyl-1,3-dioxane to obtain a sulfone compound, and then a strong base is used to eliminate the benzenesulfonyl group to obtain decadecene aldehyde. The raw material 2-(3-chloro-1-methyl-1-propenyl)-5,5-dimethyl-1,3-dioxane used in this route is obtained by acetal protection, alkaline hydrolysis, and halogenation of 4-acetoxy-2-methyl-2-butene-1-aldehyde, a raw material for synthesizing vitamin A. The reaction route is complicated and difficult to process. The reaction yield of this route is low, with a total yield of only 15%.

[0009] Patent US5471005A reports that propionaldehyde and methyl formate undergo Claisen condensation reaction, followed by esterification to obtain 2-methyl-3-alkoxy-2-propenal, which is then added with acetylene di-Grignard reagent to reduce triple bonds to double bonds, and then dehydrated to form conjugated double bonds to obtain ten carbon olefin aldehyde. This process route is cumbersome, and side reactions are easily generated during the condensation process, making it difficult to carry out industrial production.

[0010] Patent US5107030A uses 1,4-dihalo-2-butene as raw material, reacts phosphite to obtain a bisphosphonate compound, and then reacts with acetone dimethyl acetal to obtain decadecene aldehyde through Wittig-Horner reaction and deprotection. The total yield is reported to be 39%. The main raw material of this route, acetone dimethyl acetal, has no industrial product supply and is difficult to be used for industrial synthesis of decadecene aldehyde.

[0011] Patent CN101234957A has made improvements to the synthesis method of decadecene aldehyde. Trans-1,4-dichloro-2-butene is used as the starting material, and 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde is synthesized through Grignard reaction, condensation reaction and acidic hydrolysis reaction. The difficulty of this route is also that there is no report on large-scale production of acetone aldehyde dimethyl acetal.

[0012]

[0013] Patent CN108752178A uses 1,4-dibromo-2-butene as raw material, first undergoes a Grignard reaction to generate a Grignard reagent, and then adds ethylene oxide to form a diol compound. Then, through oxidation, condensation, and isomerization, 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde is synthesized. This method avoids the use of the raw material acetal dimethyl acetal, but requires the use of ethylene oxide, which is more dangerous, and has a long process and a complicated process.

[0014] In summary, it can be seen that the current method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde has the problems of difficult purchase of raw materials, low reaction yield, long reaction route, complicated process, etc. Therefore, it is necessary to seek a new synthesis method of 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde to solve the above technical problems. Summary of the invention

[0015] In view of the above problems existing in the prior art, the present invention aims to provide a novel method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde. The method has the advantages of easy availability of raw materials, high reaction yield, simple operation, and easy industrial production.

[0016] To achieve the above purpose, the technical solution of the present invention is as follows:

[0017] The present invention provides a method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde, comprising the following steps:

[0018] a) reacting an acetaldehyde of formula III with a primary amine of formula IV to obtain an N-alkylethyleneimine of formula V;

[0019] b) reacting 1,4-dihalo-2-butene of formula II with N-alkylethyleneimine of formula V in the presence of a Grignard reagent of formula VI, followed by hydrolysis under acidic conditions to obtain a compound of formula VII;

[0020] c) reacting a compound of formula VII with formaldehyde of formula VIII in the presence of a catalyst to obtain a compound of formula IX;

[0021] d) in a hydrogen atmosphere, in the presence of a catalyst and a pyridine auxiliary agent, the compound of formula IX undergoes a hydroisomerization reaction to obtain 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde of formula I;

[0022] The reaction equation is as follows:

[0023]

[0024] Wherein, R1 in the primary amine of formula IV is the same as R1 in the N-alkyl ethyleneimine of formula V, and is selected from a C6-C8 chain or cyclic hydrocarbon group;

[0025] R2 in the Grignard reagent of formula VI is selected from a C1-C6 hydrocarbon group;

[0026] X in the 1,4-dihalo-2-butene of formula II is halogen, preferably chlorine or bromine, more preferably bromine;

[0027] X in the Grignard reagent of formula VI is halogen, preferably chlorine or bromine, more preferably chlorine.

[0028] In step a) of the present invention, the acetaldehyde is an aqueous solution with a concentration of 20-80wt%, preferably 30-50wt%, more preferably 35wt% acetaldehyde aqueous solution;

[0029] The primary amine is selected from one or more of n-hexylamine, cyclohexylamine, aniline, benzylamine, o-methylaniline, m-methylaniline, p-methylaniline, phenylethylamine, α-phenylethylamine, β-phenylethylamine, preferably one or more of aniline and benzylamine;

[0030] The molar ratio of the primary amine to acetaldehyde is 1:1-1.5, preferably 1:1-1.2.

[0031] In step a) of the present invention, the reaction temperature is 20-60°C, preferably 30-40°C, and the reaction time is 1-4h, preferably 1.5-3h;

[0032] Preferably, the reaction is carried out under solvent conditions; the solvent is selected from C1-C6 alcohol solvents, preferably one or more of ethanol, methanol, isopropanol, cyclohexanol, more preferably ethanol;

[0033] The amount of the solvent used is 8-18 times the mass of acetaldehyde, preferably 14-18 times.

[0034] In step a) of the present invention, the reaction is preferably carried out under a nitrogen atmosphere; after the reaction is completed, post-treatment operations such as decompression and desolvation are also included, which are conventional operations in the field and are not specifically limited. For example, in some specific examples of the present invention, the reaction solution can be decompressed at 10 KPaA and 50°C to recover the solvent to obtain the compound of formula V.

[0035] In step b) of the present invention, the 1,4-dihalo-2-butene is selected from 1,4-dichloro-2-butene and 1,4-dibromo-2-butene, preferably 1,4-dibromo-2-butene;

[0036] The Grignard reagent is selected from methylmagnesium chloride, ethylmagnesium chloride, cyclohexylmagnesium chloride, n-butylmagnesium chloride, methylmagnesium bromide, ethylmagnesium bromide, vinylmagnesium bromide, isopropylmagnesium bromide, preferably ethylmagnesium chloride;

[0037] The molar ratio of the 1,4-dihalo-2-butene to the N-alkylethyleneimine is 1:2.1-2.5, preferably 1:2.2-2.4;

[0038] The molar ratio of the 1,4-dihalo-2-butene to the Grignard reagent is 1:2.8-3.5, preferably 1:3-3.3.

[0039] In step b) of the present invention, the reaction temperature is -5°C to 5°C, preferably 0-5°C, and the reaction time is 1.5-4h, preferably 2-3h;

[0040] Preferably, the reaction is carried out under solvent conditions; the solvent is preferably tetrahydrofuran;

[0041] The amount of the solvent used is 4-8 times, preferably 5-6 times, the mass of 1,4-dihalo-2-butene.

[0042] In step b) of the present invention, the Grignard reagent is prepared as a solution with a concentration of 0.5-3 mol / L, preferably as a tetrahydrofuran solution (the solvent in the Grignard reagent is not included in the amount of the reaction solvent);

[0043] The Grignard reagent is added continuously, preferably dropwise, for a time of 0.5-2.5 h, preferably 1.5-2 h (the time of addition is not included in the above reaction time).

[0044] In step b) of the present invention, the reaction is preferably carried out under a nitrogen atmosphere; after the reaction is completed, the reaction is quenched by adding water, and the molar ratio of the water to the Grignard reagent is 1:1-1.2, preferably 1:1-1.1, and most preferably 1:1;

[0045] The water is preferably added dropwise for 0.5-1.5 h, preferably 1-1.5 h, and the quenching temperature is -5°C-5°C, preferably 0-5°C, which is the same as the reaction temperature.

[0046] In step b) of the present invention, the hydrolysis under acidic conditions is carried out by adding an acid to the reaction solution after quenching with water to carry out hydrolysis;

[0047] Preferably, the reaction solution is first filtered, and then the obtained filtrate is hydrolyzed by adding acid;

[0048] The acid is an acid aqueous solution with a concentration of 5-20wt%, preferably 5-10wt%, wherein the acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid, and the most preferred concentration is 5wt% hydrochloric acid;

[0049] The amount of the acid used is 0.1-0.4, preferably 0.2-0.3, of the molar amount of 1,4-dihalo-2-butene;

[0050] The hydrolysis temperature is 20-50°C, preferably 30-40°C, and the hydrolysis time is 10-20h, preferably 12-15h.

[0051] In step b) of the present invention, the hydrolysis is preferably carried out under a nitrogen atmosphere; after the reaction is completed, post-treatment operations such as reduced pressure distillation, washing, and drying are also included, which are conventional operations in the field and are not specifically limited. For example, in some specific examples of the present invention, the reaction solution can be first distilled at 10 KPaA and 40°C to recover the low-boiling point solvent and by-products, and after no product is distilled out, the temperature is increased and the pressure is reduced to 0.1 KPaA and 100°C to recover the high-boiling point by-products. After no fraction is distilled out, the obtained solid is washed with water and dried to obtain the compound of formula VII.

[0052] In step c) of the present invention, the formaldehyde is paraformaldehyde;

[0053] The catalyst is selected from one or more of diethylamine, triethylamine, di-n-propylamine, tri-n-propylamine, diisopropylamine, and triethanolamine, preferably triethylamine;

[0054] The molar ratio of the compound of formula VII to paraformaldehyde is 1:2.1-2.5, preferably 1:2.2-2.4;

[0055] The amount of the catalyst used is 1-5%, preferably 2-4%, of the molar amount of the compound of formula VII.

[0056] In step c) of the present invention, the reaction temperature is 40-60°C, preferably 50-60°C, and the reaction time is 3-8h, preferably 4-6h;

[0057] Preferably, the reaction is carried out under solvent conditions; the solvent is selected from C1-C4 alcohol solvents, preferably one or more of isopropanol, isobutanol, and tert-butanol, more preferably isopropanol;

[0058] The amount of the solvent used is 4-8 times, preferably 5-6 times, the mass of the compound of formula VII.

[0059] In step c) of the present invention, the reaction is preferably carried out under a nitrogen atmosphere; after the reaction is completed, post-treatment operations such as neutralization, concentration, and water washing are also included, which are conventional operations in the field and are not specifically limited. For example, in some specific examples of the present invention, the reaction solution can be added with concentrated hydrochloric acid (preferably 36wt% concentrated hydrochloric acid) in an amount equivalent to the catalyst, and then the solvent is recovered at 10kpa and 50°C, and the remaining solid is washed with water and dried. The obtained solid is the crude product of the compound of formula IX.

[0060] In step d) of the present invention, the hydrogen atmosphere is a mixed gas of hydrogen and nitrogen, wherein the volume concentration of hydrogen is 0.5-2%, preferably 1-1.5%, and the remaining gas is nitrogen;

[0061] The mixed gas is continuously introduced into the reaction system at a flow rate of 500-1500 ml / min / mol, preferably 750-1000 ml / min / mol, based on the molar amount of the compound of formula IX.

[0062] In step d) of the present invention, the catalyst is a supported platinum catalyst selected from one or more of platinum / alumina, platinum / silicon dioxide, platinum / carbon, platinum / calcium carbonate, platinum / alumina, preferably platinum / alumina;

[0063] Preferably, in the supported platinum catalyst, the loading amount of platinum is 1-10%, preferably 3-5%;

[0064] The amount of the catalyst used is 0.5-5%, preferably 2-3%, of the mass of the compound of formula IX.

[0065] In step d) of the present invention, the pyridine auxiliary agent is pyridine or substituted pyridine, and the substituted pyridine is selected from one or more of pyridine-2-carboxaldehyde, 2-aminopyridine, 2-methylpyridine, 4-methylpyridine, 4-cyanopyridine, 2-hydroxypyridine, 4-hydroxypyridine, 2-mercaptopyridine, 2-bromopyridine, 4-bromopyridine, etc., preferably 2-bromopyridine;

[0066] The dosage of the pyridine auxiliary agent is 5-10% of the catalyst mass, preferably 6-8%.

[0067] In step d) of the present invention, the hydroisomerization reaction is carried out at a temperature of 70-100° C., preferably 80-90° C., for a time of 6-10 h, preferably 7-8 h;

[0068] Preferably, the reaction is carried out under solvent conditions; the solvent is selected from C6-C9 aromatic hydrocarbon solvents, preferably one or more of toluene and xylene, more preferably toluene;

[0069] The amount of the solvent used is 3-5 times, preferably 4-4.5 times, the mass of the compound of formula IX.

[0070] In step d) of the present invention, the pyridine auxiliary agent is prepared as a solution with a concentration of 1-5 wt %, wherein the solvent is selected from C6-C9 hydrocarbons, preferably prepared as a toluene solution (the solvent in the auxiliary agent is not included in the amount of reaction solvent).

[0071] In step d) of the present invention, after the reaction is completed, post-treatment operations such as filtration, washing, and drying are also included, which are conventional operations in the field and are not specifically limited. For example, in some specific examples of the present invention, the catalyst can be recovered by filtering the reaction solution while hot while maintaining it at above 70°C, and the filtrate is filtered after cooling to room temperature. The filter cake is washed twice with an equal amount of toluene as the reaction solvent, and the product is obtained after drying.

[0072] The present invention adds a pyridine auxiliary agent in the hydroisomerization step (there are lone pairs of electrons on the nitrogen atom in the pyridine auxiliary agent, which can combine with the active center of the noble metal to inhibit the activity of the catalyst. Since hydroisomerization requires a lower catalyst activity and hydrogenation requires a higher catalyst activity, the selectivity of hydroisomerization can be improved), which can partially inhibit the catalyst activity, inhibit the generation of hydrogenation by-products, and improve the reaction selectivity and yield.

[0073] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0074] The invention provides a new method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde. The route is simple, the raw materials are easily available, and there is no special toxicity or danger. The total yield of the product can reach more than 85% at most, the process is simple, and it is convenient for industrial production. DETAILED DESCRIPTION

[0075] The following examples will further illustrate the method provided by the present invention, but the present invention is not limited to the listed examples, and should also include any other known changes within the scope of the rights claimed by the present invention.

[0076] The sources of the main raw materials in the examples and comparative examples of the present invention are as follows. Other sources are obtained from commercial channels unless otherwise specified:

[0077] 1,4-Dichloro-2-butene: Nantong Runfeng Petrochemical Co., Ltd.;

[0078] 1,4-Dibromo-2-butene: Hubei Zhenbo Chemical Co., Ltd.

[0079] The main analytical methods used in the examples and comparative examples of the present invention are:

[0080] Gas chromatography analysis conditions: Agilent gas chromatograph polysiloxane column HP-5 was used for online determination, the vaporization chamber temperature was 250°C, the detector temperature was 250°C, the column temperature was programmed to rise: 50°C, 1 min; 80°C, 1 min; 10°C / min to 250°C, 10 min, and the injection volume was 0.2 μL.

[0081] Example 1

[0082] Preparation of compound V, the steps are:

[0083] Weigh 62.93g of 35wt% acetaldehyde aqueous solution (0.5mol), 31.04g of aniline (0.33mol), and 188.79g of ethanol in a three-necked flask and react at 60℃ for 1h under nitrogen atmosphere. After the reaction, spin dry the reaction liquid at 10KPaA and 50℃. The solid obtained is the compound of formula V, with the structure

[0084] The result of gas analysis was M / z=119, and the structure corresponded to the library structure.

[0085] The product has a yield of 97.6% and a purity of 99.5%.

[0086] Example 2

[0087] Preparation of compound V, the steps are:

[0088] Weigh 110.13g of 20wt% acetaldehyde aqueous solution (0.5mol), 44.65g of benzylamine (0.42mol), and 314.64g of methanol in a three-necked flask and react at 40°C for 2h under nitrogen atmosphere. After the reaction, spin dry the reaction solution at 10KPaA and 50°C. The resulting solid is the compound of formula V, with the structure

[0089] The result of gas analysis was M / z=133, and the structure corresponded to the library spectrum.

[0090] The product has a yield of 97.2% and a purity of 99.5%.

[0091] Example 3

[0092] Preparation of compound V, the steps are:

[0093] Weigh 27.53g of 80wt% acetaldehyde aqueous solution (0.5mol), 49.59g of cyclohexylamine (0.5mol), and 377.57g of ethanol in a three-necked flask and react at 20℃ for 4h under nitrogen atmosphere. After the reaction, spin dry the reaction liquid at 10KPaA and 50℃. The obtained solid is the compound of formula V, with the structure

[0094] The result of gas analysis was M / z=125, and the structure corresponded to the library structure.

[0095] The product has a yield of 96.8% and a purity of 99.3%.

[0096] Example 4

[0097] Preparation of compound VII, the steps are:

[0098] 64.17 g 1,4-dibromo-2-butene (0.3 mol), 75.45 g compound V obtained in Example 1 (0.63 mol), and 256.69 g tetrahydrofuran were added to a three-necked flask, and cooled to -5°C under nitrogen atmosphere. 420 ml 2 mol / L ethyl magnesium chloride tetrahydrofuran solution was added dropwise over 0.5 h. After the addition was completed, the reaction was continued at -5°C for 4 h.

[0099] After the reaction was completed, 15.12 g of water (0.84 mol) was added dropwise at -5°C over 0.5 h to quench the reaction. After the addition was completed, the reaction solution was filtered, 87.6 g of 5 wt% hydrochloric acid (0.12 mol) was added to the filtrate, and the temperature was raised to 20°C under a nitrogen atmosphere for 15 h.

[0100] After the reaction is completed, the low boiling point product and solvent are recovered at 10 KPaA and 40°C, and then the temperature is increased and the pressure is reduced to 0.1 KPaA and 100°C to recover the high boiling point by-product. After no fraction is distilled out, the obtained product is washed twice with 80 g of water and dried to obtain product V.

[0101] 1 H-NMR (500MHz, CDCl3): δ = 9.75 (2H), 5.46 (2H), 2.45 (4H), 2.41 (4H) ppm.

[0102] The product yield is 95.2% and the product purity is 98.3%.

[0103] Example 5

[0104] Compound VII is prepared by the following steps:

[0105] 64.17 g 1,4-dibromo-2-butene (0.3 mol), 100.39 g compound V obtained in Example 2 (0.75 mol), and 513.38 g tetrahydrofuran were added to a three-necked flask, and cooled to 5°C under nitrogen atmosphere. 525 ml 2 mol / L n-butyl magnesium chloride tetrahydrofuran solution was added dropwise over 2.5 h. After the addition was completed, the reaction was continued at 5°C for 1.5 h.

[0106] After the reaction, 20.79 g of water (1.155 mol) was added dropwise at 5° C. for 1 h to quench the reaction. After the addition was completed, the reaction solution was filtered, and 58.8 g of 10 wt% sulfuric acid aqueous solution (0.06 mol) was added to the filtrate, and the temperature was raised to 50° C. under a nitrogen atmosphere for 10 h.

[0107] After the reaction is completed, the low boiling point product and solvent are recovered at 10 KPaA and 40°C, and then the temperature is increased and the pressure is reduced to 0.1 KPaA and 100°C to recover the high boiling point by-product. After no fraction is distilled out, the obtained product is washed twice with 80 g of water and dried to obtain product V.

[0108] 1 H-NMR (500MHz, CDCl3): δ = 9.75 (2H), 5.46 (2H), 2.45 (4H), 2.41 (4H) ppm.

[0109] The product yield is 94.9% and the product purity is 98.1%.

[0110] Example 6

[0111] Preparation of compound VII, the steps are:

[0112] 37.5 g 1,4-dichloro-2-butene (0.3 mol), 87.01 g compound V obtained in Example 3 (0.69 mol), and 225 g tetrahydrofuran were added to a three-necked flask, and cooled to 0°C under nitrogen atmosphere. 900 ml 1 mol / L methyl magnesium bromide tetrahydrofuran solution was added dropwise over 2 h. After the addition was completed, the reaction was continued at 0°C for 3 h.

[0113] After the reaction, 19.44 g of water (1.08 mol) was added dropwise at 0° C. for 1.5 h to quench the reaction. After the addition was completed, the reaction solution was filtered, and 44.1 g of 20 wt% phosphoric acid aqueous solution (0.09 mol) was added to the filtrate, and the temperature was raised to 40° C. under a nitrogen atmosphere for 20 h.

[0114] After the reaction is completed, the low boiling point product and solvent are recovered at 10 KPaA and 40°C, and then the temperature is increased and the pressure is reduced to 0.1 KPaA and 100°C to recover the high boiling point by-product. After no fraction is distilled out, the obtained product is washed twice with 80 g of water and dried to obtain product V.

[0115] 1 H-NMR (500MHz, CDCl3): δ = 9.75 (2H), 5.46 (2H), 2.45 (4H), 2.41 (4H) ppm.

[0116] The product yield is 94.6% and the product purity is 97.8%.

[0117] Example 7

[0118] Compound IX is prepared by the following steps:

[0119] 28.52 g of the compound of formula VII prepared in Example 4 (0.2 mol), 13.82 g of paraformaldehyde (0.46 mol), 0.61 g of triethylamine (0.006 mol), and 140.18 g of isopropanol were placed in a three-necked flask and reacted at 50° C. for 5 h under a nitrogen atmosphere.

[0120] After the reaction is completed, 0.61 g of 36 wt% concentrated hydrochloric acid is added to the reaction solution, and the solvent is recovered at 10 KPaA and 50°C. The solid is washed with water and dried to obtain a crude product of Formula IX.

[0121] 1 H-NMR (500MHz, CDCl3): δ=9.87(2H), 6.33(2H), 6.02(2H), 5.40(2H), 2.62(4H)ppm.

[0122] The pure yield is 97.0% and the crude product purity is 97.0%.

[0123] Example 8

[0124] Compound IX is prepared by the following steps:

[0125] 28.58 g of the compound of formula VII prepared in Example 5 (0.2 mol), 12.61 g of paraformaldehyde (0.42 mol), 1.49 g of triethanolamine (0.01 mol), and 224.29 g of isobutanol were placed in three wells and reacted at 60° C. under a nitrogen atmosphere for 3 h.

[0126] After the reaction is completed, 1.01 g of 36 wt% concentrated hydrochloric acid is added to the reaction solution, and the solvent is recovered at 10 KPaA and 50°C. The solid is washed with water and dried to obtain a crude product of Formula IX.

[0127] 1 H-NMR (500MHz, CDCl3): δ=9.87(2H), 6.33(2H), 6.02(2H), 5.40(2H), 2.62(4H)ppm.

[0128] The pure yield is 96.6% and the crude product purity is 96.8%.

[0129] Example 9

[0130] Compound IX is prepared by the following steps:

[0131] 28.67 g of the compound of formula VII prepared in Example 6 (0.2 mol), 15.02 g of paraformaldehyde (0.50 mol), 0.20 g of diisopropylamine (0.002 mol), and 112.14 g of tert-butanol were placed in three wells and reacted at 40° C. for 8 h under a nitrogen atmosphere.

[0132] After the reaction is completed, 0.20 g of 36 wt% concentrated hydrochloric acid is added to the reaction solution, and the solvent is recovered at 10 KPaA and 50°C. The solid is washed with water and dried to obtain a crude product of Formula IX.

[0133] 1 H-NMR (500MHz, CDCl3): δ=9.87(2H), 6.33(2H), 6.02(2H), 5.40(2H), 2.62(4H)ppm.

[0134] The pure yield is 96.1% and the crude product purity is 96.4%.

[0135] Example 10

[0136] The preparation steps of compound I are:

[0137] Preparation of auxiliary agent solution: dissolve 1 g of 2-bromopyridine in 99 g of toluene and fully disperse it to prepare an auxiliary agent solution with a concentration of 1 wt % for later use.

[0138] 33.86g of the crude product of Formula IX prepared in Example 7, 0.66g of a platinum-alumina catalyst with a loading of 3wt%, 5.25g of the prepared auxiliary solution, and 126.16g of toluene were added to a three-necked flask. A hydrogen-nitrogen mixed gas with a volume concentration of 1% was introduced at a flow rate of 200ml / min per mol of the crude product of Formula IX. The temperature was raised to 90°C and the reaction was carried out for 8h.

[0139] After the reaction was completed, ventilation was stopped and the catalyst was recovered by hot filtration. The filtrate was cooled to room temperature and filtered, and the filter cake was washed twice with 65.68 g of toluene each time and dried. The obtained solid was the product, and the gas chromatography-mass spectrometry result was M / z=164, and the gas phase retention time was consistent with that of the standard product.

[0140] The yield is 95.0% and the product purity is 99.5%.

[0141] Embodiment 11

[0142] The preparation steps of compound I are:

[0143] Preparation of auxiliary agent solution: dissolve 1 g of 2-aminopyridine in 99 g of xylene and disperse thoroughly to prepare an auxiliary agent solution with a concentration of 1 wt % for later use.

[0144] 33.93g of the crude product of Formula IX prepared in Example 8, 1.64g of a platinum-carbon catalyst with a loading of 1wt%, 16.42g of the prepared auxiliary solution, and 147.94g of xylene were added to a three-necked flask. A hydrogen-nitrogen mixed gas with a volume concentration of 2% was introduced at a flow rate of 100ml / min per mol of the crude product of Formula IX. The temperature was raised to 100°C and the reaction was carried out for 6h.

[0145] After the reaction was completed, ventilation was stopped and the catalyst was recovered by hot filtration. The filtrate was cooled to room temperature and filtered, and the filter cake was washed twice with 82.10 g of toluene each time and dried. The obtained solid was the product, and the gas chromatography-mass spectrometry result was M / z=164, and the gas phase retention time was consistent with that of the standard product.

[0146] The pure yield is 94.5% and the product purity is 99.3%.

[0147] Example 12

[0148] The preparation steps of compound I are:

[0149] Preparation of auxiliary agent solution: dissolve 1 g of pyridine in 99 g of cyclohexane, disperse thoroughly, and prepare an auxiliary agent solution with a concentration of 1 wt % for later use.

[0150] 34.07 g of the crude product of Formula IX prepared in Example 9, 0.16 g of a platinum-silicon dioxide catalyst with a loading of 10 wt%, 0.99 g of the prepared auxiliary solution, and 97.54 g of ethylbenzene were added to a three-necked flask. A hydrogen-nitrogen mixed gas with a volume concentration of 0.5% was introduced at a flow rate of 300 ml / min per mol of the crude product of Formula IX. The temperature was raised to 70°C and the reaction was carried out for 10 hours.

[0151] After the reaction was completed, ventilation was stopped and the catalyst was recovered by hot filtration. The filtrate was cooled to room temperature and filtered, and the filter cake was washed twice with 49.26 g of toluene each time and dried. The obtained solid was the product, and the gas chromatography-mass spectrometry result was M / z=164, and the gas phase retention time was consistent with that of the standard product.

[0152] The pure yield is 94.0% and the product purity is 99.2%.

[0153] Comparative Example 1

[0154] Preparation of compound I: Compound I was prepared by referring to the method of Example 1 of patent CN1918099A.

[0155] The yield is 72.5%, and the purity is 98.2%.

[0156] Comparative Example 2

[0157] Preparation of Compound I: Refer to the preparation method of Example 10, except that no pyridine auxiliary solution is added.

[0158] The yield is 78.0%, and the purity is 93.2%.

[0159] Comparative Example 3

[0160] Preparation of Compound I: Refer to the preparation method of Example 10, except that the pyridine auxiliary is replaced by an equal mass of 3-bromofuran.

[0161] The yield is 79.1%, and the purity is 93.7%.

[0162] The above specific implementations do not limit the technical solutions of the present invention in any form. Any simple modification, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention fall within the protection scope of the present invention.

Claims

1. A method for preparing 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde, characterized in that: The following steps are involved: a) reacting an acetaldehyde of formula III with a primary amine of formula IV to obtain an N-alkylethyleneimine of formula V; b) reacting 1,4-dihalo-2-butene of formula II with N-alkylethyleneimine of formula V in the presence of a Grignard reagent of formula VI, followed by hydrolysis under acidic conditions to obtain a compound of formula VII; c) reacting a compound of formula VII with formaldehyde of formula VIII and / or paraformaldehyde in the presence of a catalyst to obtain a compound of formula IX; d) in a hydrogen atmosphere, in the presence of a catalyst and a pyridine auxiliary agent, the compound of formula IX undergoes a hydroisomerization reaction to obtain 2,7-dimethyl-2,4,6-octatriene-1,8-dialdehyde of formula I; The reaction equation is as follows: Wherein, R1 in the primary amine of formula IV is the same as R1 in the N-alkyl ethyleneimine of formula V, and is selected from a C6-C8 chain or cyclic hydrocarbon group; R2 in the Grignard reagent of formula VI is selected from a C1-C6 hydrocarbon group; X in the 1,4-dihalo-2-butene of formula II is halogen; X in the Grignard reagent of formula VI is a halogen; In step c), the catalyst is selected from one or more of diethylamine, triethylamine, di-n-propylamine, tri-n-propylamine, diisopropylamine, and triethanolamine; In step d), the catalyst is a supported platinum catalyst; the pyridine auxiliary agent is pyridine or a substituted pyridine, and the substituted pyridine is selected from one or more of pyridine-2-carboxaldehyde, 2-aminopyridine, 2-methylpyridine, 4-methylpyridine, 4-cyanopyridine, 2-hydroxypyridine, 4-hydroxypyridine, 2-mercaptopyridine, 2-bromopyridine, and 4-bromopyridine.

2. The preparation method according to claim 1, characterized in that: X in the 1,4-dihalo-2-butene of formula II is chlorine or bromine.

3. The preparation method according to claim 1, characterized in that: X in the Grignard reagent of formula VI is chlorine or bromine.

4. The preparation method according to claim 1, characterized in that: In step a), the acetaldehyde is an aqueous solution with a concentration of 20-80wt%; The primary amine is selected from one or more of n-hexylamine, cyclohexylamine, aniline, benzylamine, o-methylaniline, m-methylaniline, p-methylaniline, phenylethylamine, α-phenylethylamine, and β-phenylethylamine; The molar ratio of the primary amine to acetaldehyde is 1:1-1.

5.

5. The preparation method according to claim 4, characterized in that: In step a), the acetaldehyde is an aqueous solution with a concentration of 30-50 wt%.

6. The preparation method according to claim 4, characterized in that: In step a), the primary amine is selected from one or more of aniline and benzylamine.

7. The preparation method according to claim 4, characterized in that: In step a), the molar ratio of the primary amine to acetaldehyde is 1:1-1.

2.

8. The preparation method according to claim 1, characterized in that: In step a), the reaction temperature is 20-60° C. and the reaction time is 1-4 h.

9. The preparation method according to claim 8, characterized in that: The reaction temperature is 30-40°C and the reaction time is 1.5-3h.

10. The preparation method according to claim 1, characterized in that: In step a), the reaction is carried out under solvent conditions; the solvent is selected from C1-C6 alcohol solvents; The amount of the solvent used is 3-6 times the mass of acetaldehyde.

11. The preparation method according to claim 10, characterized in that: The solvent is selected from one or more of ethanol, methanol, isopropanol, and cyclohexanol; The amount of the solvent used is 4-5 times the mass of acetaldehyde.

12. The preparation method according to claim 1, characterized in that: In step a), the reaction is carried out under a nitrogen atmosphere.

13. The preparation method according to claim 1, characterized in that: In step b), the 1,4-dihalo-2-butene is selected from 1,4-dichloro-2-butene and 1,4-dibromo-2-butene; The Grignard reagent is selected from methylmagnesium chloride, ethylmagnesium chloride, cyclohexylmagnesium chloride, ethylmagnesium bromide, vinylmagnesium bromide, isopropylmagnesium bromide; The molar ratio of the 1,4-dihalo-2-butene to the N-alkylethyleneimine is 1:2.1-2.5; The molar ratio of the 1,4-dihalo-2-butene to the Grignard reagent is 1:2.8-3.

5.

14. The preparation method according to claim 1, characterized in that: In step b), the molar ratio of 1,4-dihalo-2-butene to N-alkylethyleneimine is 1:2.2-2.4; The molar ratio of the 1,4-dihalo-2-butene to the Grignard reagent is 1:3-3.

3.

15. The preparation method according to claim 1, characterized in that: In step b), the reaction temperature is -5°C to 5°C, and the reaction time is 1.5 to 4 hours; In step b), the Grignard reagent is prepared as a solution with a concentration of 0.5-3 mol / L; The Grignard reagent is added continuously over a period of 0.5-2.5 hours. In step b), the reaction is carried out under a nitrogen atmosphere; After the reaction is completed, the step of quenching the reaction by adding water is further included, wherein the molar ratio of the amount of water to the amount of the Grignard reagent is 1:1-1.

2.

16. The preparation method according to claim 15, characterized in that: The reaction temperature is 0-5°C and the reaction time is 2-3h.

17. The preparation method according to claim 1, characterized in that: In step b), the reaction is carried out under solvent conditions; The amount of the solvent used is 4-8 times the mass of 1,4-dihalo-2-butene.

18. The preparation method according to claim 17, characterized in that: The solvent is tetrahydrofuran.

19. The preparation method according to claim 17, characterized in that: The amount of the solvent used is 5-6 times the mass of 1,4-dihalo-2-butene.

20. The preparation method according to claim 15, characterized in that: The Grignard reagent is prepared as a tetrahydrofuran solution.

21. The preparation method according to claim 1, characterized in that: The Grignard reagent is added dropwise over a period of 1.5-2 hours.

22. The preparation method according to claim 15, characterized in that: The molar ratio of the water to the Grignard reagent is 1:1-1.

1.

23. The preparation method according to claim 15, characterized in that: The water is added dropwise for 0.5-1.5 hours, and the quenching temperature is -5°C-5°C.

24. The preparation method according to claim 23, characterized in that: The dropping time is 1-1.5h, and the quenching temperature is 0-5°C.

25. The preparation method according to claim 1, characterized in that: In step b), the hydrolysis under acidic conditions is carried out by adding acid to the reaction solution after quenching with water to carry out hydrolysis; The acid is an acid aqueous solution with a concentration of 5-20wt%, wherein the acid is selected from hydrochloric acid, sulfuric acid, and phosphoric acid; The amount of the acid used is 0.1-0.4 times the molar amount of 1,4-dihalo-2-butene; The hydrolysis temperature is 20-50°C and the time is 10-20h; In step b), the hydrolysis is carried out under a nitrogen atmosphere.

26. The preparation method according to claim 25, characterized in that: The reaction solution is first filtered, and then acid is added to the obtained filtrate for hydrolysis.

27. The preparation method according to claim 25, characterized in that: The acid is an acid aqueous solution with a concentration of 5-10 wt%.

28. The preparation method according to claim 25, characterized in that: The amount of the acid used is 0.2-0.3 times the molar amount of 1,4-dihalo-2-butene.

29. The preparation method according to claim 25, characterized in that: The hydrolysis temperature is 30-40°C and the time is 12-15h.

30. The preparation method according to claim 1, characterized in that: In step c), the molar ratio of the compound of formula VII to paraformaldehyde is 1:2.1-2.5; The amount of the catalyst used is 1-5% of the molar amount of the compound of formula VII.

31. The preparation method according to claim 1, characterized in that: The molar ratio of the compound of formula VII to paraformaldehyde is 1:2.2-2.4; The amount of the catalyst used is 2-4% of the molar amount of the compound of formula VII.

32. The preparation method according to claim 1, characterized in that: In step c), the reaction temperature is 40-60° C. and the reaction time is 3-8 hours.

33. The preparation method according to claim 32, characterized in that: In step c), the reaction temperature is 50-60° C. and the reaction time is 4-6 hours.

34. The preparation method according to claim 1, characterized in that: In step c), the reaction is carried out under solvent conditions; the solvent is selected from C1-C4 alcohol solvents; The amount of the solvent used is 4-8 times the mass of the compound of formula VII.

35. The preparation method according to claim 34, characterized in that: The solvent is selected from one or more of isopropanol, isobutanol, and tert-butanol; The amount of the solvent used is 5-6 times the mass of the compound of formula VII.

36. The preparation method according to claim 1, characterized in that: In step c), the reaction is carried out under a nitrogen atmosphere.

37. The preparation method according to claim 1, characterized in that In step d), the hydrogen atmosphere is a mixed gas of hydrogen and nitrogen, wherein the volume concentration of hydrogen is 0.5-2%, and the rest of the gas is nitrogen; The mixed gas is continuously introduced into the reaction system at a flow rate of 500-1500 ml / min / mol based on the molar amount of the compound of formula IX; In step d), the catalyst is selected from one or more of platinum / alumina, platinum / silicon dioxide, platinum / carbon, platinum / calcium carbonate, and platinum / alumina; In the supported platinum catalyst, the loading amount of platinum is 1-10%; The amount of the catalyst is 0.5-5% by mass of the compound of formula IX; In step d), the pyridine auxiliary agent is 2-bromopyridine; The dosage of the auxiliary agent is 5-10% of the mass of the catalyst.

38. The preparation method according to claim 37, characterized in that: The volume concentration of hydrogen is 1-1.5%.

39. The preparation method according to claim 37, characterized in that: The mixed gas is continuously introduced into the reaction system at a flow rate of 750-1000 ml / min / mol based on the molar amount of the compound of formula IX.

40. The preparation method according to claim 37, characterized in that: In the supported platinum catalyst, the supported amount of platinum is 3-5%.

41. The preparation method according to claim 37, characterized in that: The amount of the catalyst used is 2-3% of the mass of the compound of formula IX.

42. The preparation method according to claim 37, characterized in that: The dosage of the auxiliary agent is 6-8% of the mass of the catalyst.

43. The preparation method according to claim 1, characterized in that In step d), the hydroisomerization reaction temperature is 70-100° C. and the time is 6-10 h; In step d), the pyridine auxiliary agent is prepared as a solution with a concentration of 1-5 wt %, wherein the solvent is selected from C6-C9 hydrocarbons.

44. The preparation method according to claim 43, characterized in that: The hydroisomerization reaction temperature is 80-90°C and the reaction time is 7-8h.

45. The preparation method according to claim 43, characterized in that: The pyridine auxiliary agent is prepared as a toluene solution.

46. ​​The preparation method according to claim 43, characterized in that The reaction is carried out under solvent conditions; the solvent is selected from C6-C9 aromatic hydrocarbon solvents; The amount of the solvent used is 3-5 times the mass of the compound of formula IX.

47. The preparation method according to claim 43, characterized in that The solvent is selected from one or more of toluene and xylene; The amount of the solvent used is 4-4.5 times the mass of the compound of formula IX.

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