Method for synthesizing nylon 11 monomer
By optimizing the reaction steps of hydroformylation, reducing amination, hydrogenation and hydrolysis, and using specific catalysts and reducing agents, the problems of severe reaction conditions and poor selectivity in the production of nylon 11 monomers are solved, achieving a more efficient and economical production process .
Patent Information
- Application Number
- CN202310722069.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-19
- Publication Date
- 2024-12-20
AI Technical Summary
In the prior art, the production of nylon 11 monomer ω-aminoundecanoic acid has problems such as severe reaction conditions, poor selectivity, small catalyst circulation coefficient, slow reaction rate and high temperature, resulting in high production costs and large energy consumption.
Using mild hydroformylation, reducing amination, hydrogenation and hydrolysis reaction steps, using acetylacetonate dicarbonyl rhodium and Xantphos as catalysts, palladium catalyst Pd/C and hydrogen as reducing agents, alkali catalyzed hydrolysis, optimize reaction conditions to improve selection and reduce energy consumption.
It significantly improves the energy efficiency of reaction selectivity and output, reduces production costs, and makes the production of nylon 11 monomer more economical and suitable for industrial large-scale production.
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Abstract
Description
Technical Field
[0001] The invention belongs to the field of organic chemistry, and in particular relates to a method for synthesizing nylon 11 monomer, namely ω-aminoundecanoic acid. Background Art
[0002] Nylon 11 monomer ω-aminoundecanoic acid is a very important industrial raw material. It can be used as a long carbon chain polyester monomer for the synthesis of biodegradable plastics. It can be obtained by cracking castor oil whose main component is 12-hydroxy-9-octadecenoic acid triglyceride to obtain octadecenoic acid, and then performing a series of simple reactions. However, the cracking reaction usually has a high temperature and low selectivity. In addition to the cracking reaction, the construction of long carbon chain alkyl can also be achieved through the polymerization reaction of 1,3-butadiene. ω-aminoundecanoic acid can also be obtained by the polymerization reaction of 1,3-butadiene and malonate to construct a long carbon chain, and then a series of conversion reactions are performed.
[0003] Hata's research group published a study on the palladium-catalyzed polymerization of 1,3-butadiene and malonate in 1971. The polymerization was carried out with dimethyl malonate as a nucleophile and 1,3-butadiene, triphenylphosphine palladium dichloride (PdCl2PPh3) as a catalyst, and sodium phenolate as a base at 85°C for 3 hours. The final mass ratio (TON value) of 1,3-butadiene to palladium catalyst involved in the reaction was 500, and when the nucleophile was diethyl malonate, under this reaction condition, the TON value could reach 5000. The specific reaction conditions of the reaction are as follows:
[0004]
[0005] In 1980, Baker's research group synthesized key drug intermediate compounds A / B and then synthesized pheromones by palladium-catalyzed polymerization of diethyl malonate and 1,3-butadiene. The specific reaction conditions are shown in the figure below:
[0006]
[0007] The above-mentioned prior art ω-aminoundecanoic acid production methods generally have problems such as severe reaction conditions and poor reaction selectivity. Compound A / B has great application and derivative value, but there is little research on the palladium-catalyzed polymerization of malonate and 1,3-butadiene. The existing reaction conditions have a low catalyst circulation coefficient, a slow catalyst reaction rate, and a high reaction temperature. Summary of the invention
[0008] In view of the problems existing in the above-mentioned synthetic process of nylon 11 monomer, the inventors have changed the reaction conditions of each step and developed a process with mild reaction and significantly improved reaction selectivity, which can significantly reduce the energy consumption per unit output of the product, thereby reducing the production cost and making the production of nylon 11 monomer more economical. Therefore, the present invention includes the following technical solutions:
[0009] A method for synthesizing nylon 11 monomer comprises the following steps:
[0010] The 4,9-diene decanoate shown in formula III is subjected to hydroformylation, reductive amination, hydrogenation, and hydrolysis to obtain the nylon 11 monomer shown in formula IV:
[0011]
[0012] Wherein R is selected from C1-C6 alkyl, C5-C8 substituted or unsubstituted cycloalkyl, substituted or unsubstituted aromatic group. The substitution refers to substitution by halogen, methoxy or cyano, and the halogen is selected from F, Cl, Br, I.
[0013] The C1-C6 alkyl group is a straight or branched alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, etc.;
[0014] The above cycloalkyl group may be cyclopentyl, cyclohexyl, or cycloheptyl;
[0015] The above aromatic group is selected from phenyl, benzyl, p-methoxyphenyl, p-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 3-chloro-4-fluorophenyl, 4-bromomethylphenyl, 3-cyanophenyl, 2-bromo-4-fluorophenyl, 2,4-dichlorophenyl, 5,6,7,8-tetrahydro-2-naphthyl, 4-tert-butylphenyl, and 2,4,6-trimethylphenyl.
[0016] Preferably, R is selected from methyl, ethyl, isopropyl.
[0017] In one embodiment, in the hydroformylation reaction, the hydroformylation catalyst is selected from acetylacetonato dicarbonyl rhodium, (1,5-cyclooctadiene) chlororhodium dimer, tetracarbonyl dichlororhodium, bis(1,5-cyclooctadiene) tetrafluoroborate rhodium, bis(1,5-cyclooctadiene) hexafluorophosphonic acid rhodium, preferably acetylacetonato dicarbonyl rhodium; the phosphine ligand is selected from Xantphos, triphenylphosphine, 2,2'-bis[(1,1'-biphenyl-2,2'-diyl)phosphite]-3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl, triphenyl phosphite, preferably Xantphos. When the catalyst is acetylacetonato dicarbonyl rhodium and the phosphine ligand is Xantphos, the mass ratio of the catalyst to the phosphine ligand is approximately 1:1-10.
[0018] In the reductive amination reaction, a palladium catalyst is used, and the palladium catalyst is selected from Pd(acac)2, Pd(OAc)2, Pd2(dba)3, Pd(dba)2, Pd(PPh3)2Cl2, Pd(PPh3)4, 10% Pd / C or 5% Pd / C, and the amine source is selected from ammonium formate, ammonia methanol solution, ammonium acetate, preferably ammonium formate. When the amine source is ammonium formate, the mass ratio of ammonium formate to compound III is about 1:1-3; in this step of the reaction, the palladium catalyst can smoothly carry out the catalytic reaction without the need for a phosphine ligand;
[0019] In the hydrogenation reaction, the reducing agent is hydrogen, and the hydrogenation catalyst used is selected from Raney nickel, palladium carbon (Pd / C), Raney nickel, Raney cobalt, Pt / C, Ru / C, Rh / C, preferably palladium / carbon.
[0020] The hydrolysis reaction is carried out under base catalysis, and the base used is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, and lithium hydroxide; the solvent used in the hydrolysis reaction is selected from water, methanol, ethanol, isopropanol, or a mixture of two or more thereof, preferably a mixed solvent of alcohol and water.
[0021] The second aspect of the present invention provides a method for synthesizing 4,9-diene decanoate represented by the above formula III, comprising the following steps:
[0022] A. 1,3-butadiene and the malonate of formula I are subjected to palladium-catalyzed polymerization reaction to obtain the compound 2-(2,7-octadienyl) malonate of formula II;
[0023] B. Compound II is hydrolyzed and decarboxylated to obtain 4,9-diene decanoate shown in formula III:
[0024]
[0025] wherein R is defined as above.
[0026] Preferably, the solvent used in the above step A is an alcohol corresponding to the R group. For example, when R is a methyl group, the solvent is methanol; when R is an ethyl group, the solvent is ethanol; when R is an isopropyl group, the solvent is isopropanol.
[0027] The palladium catalyst used in step A is selected from Pd(acac)2, Pd(OAc)2, Pd2(dba)3, Pd(dba)2, Pd(PPh3)2Cl2 or Pd(PPh3)4, the phosphine ligand is selected from triphenylphosphine, tri(2-methoxyphenyl)phosphine, tri(2,4,6-trimethoxyphenyl)phosphine, tri(2,6-dimethoxybenzene)phosphine, 10-phenyl-10H-phenylphosphine oxide, tri(4-methoxyphenyl)phosphine, preferably triphenylphosphine, and the mass ratio of the palladium catalyst to the phosphine ligand is 1:1-100.
[0028] The telomerization reaction in step A is carried out in the presence of a base, and the base is selected from an organic base and an inorganic base. The base can be selected from sodium methoxide, sodium ethoxide, sodium tert-butoxide, sodium phenolate (PhONa), sodium bicarbonate, or a mixture of two or more thereof, preferably sodium phenolate (PhONa) or sodium bicarbonate.
[0029] The solvent used in the hydrolysis reaction in the above step B is a mixed solvent of alcohol and water, and the alcohol is selected from methanol, ethanol, and isopropanol. The base used is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, and lithium hydroxide.
[0030] The solvent used in the decarboxylation reaction of step B is selected from N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide or N-methylpyrrolidone, and the reaction temperature is 120°C-200°C.
[0031] The nylon 11 monomer preparation method provided by the invention has mild reaction conditions, few side reactions, and lower energy consumption per unit output of the product than that of the prior art, thereby reducing production costs and being suitable for industrial large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of dimethyl 2-(2,7-octadienyl)malonate (Compound II).
[0033] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of methyl 4,9-dienedecanoate (compound III).
[0034] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of nylon 11 monomer (compound IV). DETAILED DESCRIPTION
[0035] The synthesis route of the nylon 11 monomer ω-aminoundecanoic acid of the present invention is as follows.
[0036]
[0037] We have optimized the process of nylon 11 monomer synthesis route. Through a large number of comparative experiments, the preparation process conditions of precursor compounds II and III have been comprehensively optimized. For example, in the optimization of the synthesis process of compounds II and III, theoretically and based on empirical practice, the R group in step A and step B, that is, the alcohol group, can be a C1-C4 alkyl group, including methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and tert-butyl. However, it was found through experiments that the reaction rate and product yield when R is methyl, ethyl, and isopropyl are significantly higher than those of n-propyl, n-butyl, isobutyl, and tert-butyl, which may be related to the adaptability of palladium catalysts and phosphine ligands to the reaction raw materials. On the other hand, the use of methanol or ethanol in the hydrolysis reaction of step B also has the economic advantage of being cheap and readily available. Therefore, it is a better choice to select R as methyl or ethyl.
[0038] In the reaction of synthesizing nylon 11 monomer (IV) from compound III, when the catalyst selected for the hydroformylation reaction is acetylacetonato dicarbonyl rhodium and the phosphine ligand is Xantphos, their combination has certain advantages over other catalyst / phosphine ligand combinations in terms of increasing the reaction rate and increasing the catalyst circulation coefficient. In the reductive amination reaction, the combination of palladium catalyst as palladium carbon Pd / C and amine source as ammonium formate has certain advantages over other palladium catalyst / amine source combinations in terms of increasing the reaction rate and increasing the catalyst circulation coefficient, and the palladium carbon Pd / C used can continue to be used for the next hydrogenation reaction, which has the effect of reducing the use of expensive catalysts and reducing costs.
[0039] In step A of the present invention, using substrate dimethyl malonate (R is methyl in formula I), palladium catalyst Pd(acac)2 and triphenylphosphine PPh3 are combined to catalyze the reaction, and TON (substrate dosage / catalyst dosage, indicating the maximum number of turns that the catalyst can make) can reach more than 150,000, which is much higher than the TON reported value of the prior art. Since palladium catalysts are relatively expensive, the process conditions of the present invention can reduce the cost of raw materials and have economic advantages.
[0040] Herein, the term "compound represented by formula X" is sometimes expressed as "formula X" or "compound X", which is understandable to those skilled in the art. For example, the compound represented by formula III and compound III both refer to the same compound 4,9-diene decanoate.
[0041] In a specific embodiment, after the reaction of each of the above steps is completed, post-treatment and purification operations such as filtration, washing, drying, and recrystallization can be performed according to common knowledge in the art.
[0042] The present invention is further described below by examples. It should be understood that these examples are only for illustrative purposes, rather than limiting the present invention. Various changes or adjustments made by those skilled in the art based on the present invention should all fall within the scope of protection of the present invention.
[0043] This article involves the addition amount, content and concentration of various substances, and the percentages mentioned here refer to the mass percentages unless otherwise specified.
[0044] In the examples herein, if no specific description is given for the reaction temperature or the operating temperature, the temperature generally refers to room temperature (10-40° C.).
[0045] Example
[0046] Reagents: The reactants and catalysts used in the examples of the present invention are all chemically pure and can be used directly or after simple purification as needed. The reagents were purchased from China Pharmaceutical (Group) Shanghai Chemical Reagent Company, Shanghai Zhongwei Chemical Co., Ltd. and Shanghai Bid Pharmaceutical Technology Co., Ltd.
[0047] Testing instruments:
[0048] NMR instrument models: Bruker AV-500 and Bruker AV-600;
[0049] Gas chromatograph (GC), model: Shimadzu 2030, detector: FID, gas chromatography column model: 30-mG0301-31.
[0050] Example 1: Preparation of Compound II (R is methyl)
[0051]
[0052] Pd(acac)2 (1.5 mg, 0.005 mmol), PPh3 (2.6 mg, 0.01 mmol), PhONa (1.161 g, 10 mmol) and a magnetic stirrer were added to a 300 mL autoclave. After replacing the gas in the autoclave with argon, dimethyl malonate (50 mL, 0.5 mol) and anhydrous methanol (110 mL) were added under an argon flow. The autoclave weight was recorded as 4993.2 g. The autoclave was placed in an ethyl acetate-liquid nitrogen bath, and 1,3-butadiene (ca. 0.8 mmol, ca. 44 g) that had passed through two scrubbers containing phosphorus pentoxide and calcium oxide-calcium chloride was frozen into it. After the gas was filled, the autoclave weight was recorded as 5039.2 g. The autoclave was placed in a heated aluminum block preheated to 60°C. After 20 hours of reaction, the unreacted 1,3-butadiene was released into a well-ventilated fume hood. After the gas was completely released, the kettle weight at this time was recorded as 5038.9g. 33.9g of isooctane was added as an internal standard, and the reaction effect was obtained by gas phase analysis. The ratio of the amount of 1,3-butadiene to the palladium catalyst substance involved in the polymerization reaction was 160000. And 45g of the product 2-(2,7-octadienyl) dimethyl malonate (II) was obtained by reduced pressure distillation. The NMR spectrum is shown in Figure 1 shown.
[0053] 1 H NMR(500MHz, CDCl3)δ:5.89-5.74(m,1H),5.59-5.46(m,1H),5.46-5.30(m,1H),5.06-4.87(m,2 H), 3.72 (s, 6H), 3.42 (t, J = 7.6Hz, 1H), 2.69-2.54 (m, 2H), 2.12-1.94 (m, 4H), 1.52-1.35 (m, 2H).
[0054] Example 2: Preparation of Compound III (R is methyl)
[0055]
[0056] Compound II (400mmol, 96g), potassium hydroxide (800mmol, 40g), methanol (400mL) and water (200mL) were added to a 1000mL three-necked round-bottom flask equipped with a magnetic stirrer and a spherical condenser. After reflux for 12 hours, the solvent was dried and water (300mL) and ethyl acetate (300mL) were added. Under sufficient stirring, hydrochloric acid (1M) was added until the pH of the aqueous phase was 1. The organic phase was separated and DMSO (200mL) was added and the temperature was raised to 140°C for 4 hours. After removing DMSO by vacuum distillation, the remaining liquid was poured into a 1000mL three-necked round-bottom flask and methanol (400mL) was added. Concentrated sulfuric acid was added dropwise to the solution until small droplets of reflux began to appear on the wall of the flask. After reflux for 24 hours, the methanol was dried and ethyl acetate and saturated sodium bicarbonate solution were added until the saturated sodium bicarbonate solution no longer bubbled. The organic phase was separated, ethyl acetate was dried by spin drying, and 64 g of colorless liquid was obtained by vacuum distillation with a yield of 88%, which was methyl 4,9-dienedecanoate (III). Figure 2 shown.
[0057] 1 H NMR (500MHz, CDCl3) δ5.86-5.74(m,1H),5.50-5.31(m,2H),5.04-4.96(m,1H),4.96-4.90(m, 1H),3.66(s,3H),2.41-2.34(m,2H),2.34-2.27(m,2H),2.10-1.95(m,4H),1.48-1.38(m,2H).
[0058] Example 3: Preparation of Nylon 11 Monomer (IV)
[0059]
[0060] Acetylacetonato dicarbonyl rhodium (0.1mmol, 27mg), Xantphos (174mg, 0.3mmol) were added to a 300mL autoclave, and anhydrous toluene (40mL) and compound III (30mmol, 5.46g) were added under an argon flow. After carbon monoxide was filled and vented three times, carbon monoxide (20bar) and hydrogen (10bar) were filled and the autoclave was transferred to a heated aluminum block and heated to 80°C for 4 hours. After cooling to room temperature, the gas was released, the solvent was dried by rotary evaporation, and a light yellow liquid was obtained by vacuum distillation. The above obtained liquid, methanol (200mL), ammonium formate (16.9g) and Pd / C (5%, 300mg) were added to a 500mL Schlenk bottle, stirred at room temperature for 12 hours, and filtered. The above filtrate was added with palladium / carbon (5%, 500mg) and placed in a 500mL three-necked round-bottom flask. The solution was degassed and replaced with a hydrogen atmosphere and stirred at room temperature for 12 hours. After filtration, the resulting solution was dried and potassium hydroxide (40mmol, 2.24g), methanol (300mL) and water (20mL) were added to reflux and stirred for 12 hours, then the solvent was dried and water (300mL) and ethyl acetate (300mL) were added. Hydrochloric acid (1mol / L) was added to the two phases until the pH value of the aqueous phase was 1. 3.68g of white solid was obtained by filtration, with a total yield of 61% in three steps, which is ω-aminoundecanoic acid (IV). The NMR spectrum is shown as Figure 3 shown.
[0061] 1 H NMR (500MHz, CD3OD) δ2.93–2.86 (m, 2H), 2.16 (t, J = 7.4Hz, 2H), 1.71–1.51 (m, 5H), 1.43–1.27 (m, 14H).
[0062] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention and should be included in the scope of the present invention.
Claims
1. A method for synthesizing nylon 11 monomer, comprising the following steps: The 4,9-diene decanoate shown in formula III is subjected to hydroformylation, reductive amination, hydrogenation, and hydrolysis to obtain the nylon 11 monomer shown in formula IV: Wherein R is selected from C1-C6 alkyl, C5-C8 substituted or unsubstituted cycloalkyl, substituted or unsubstituted aromatic group.
2. The method according to claim 1, characterized in that: The C1-C6 alkyl group is a straight or branched alkyl group selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, etc.; The cycloalkyl group is cyclopentyl, cyclohexyl, or cycloheptyl; The aromatic group is selected from phenyl, benzyl, p-methoxyphenyl, p-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-trifluoromethylphenyl, 2,5-dichlorophenyl, 3-chlorophenyl, 3-chloro-4-fluorophenyl, 4-bromomethylphenyl, 3-cyanophenyl, 2-bromo-4-fluorophenyl, 2,4-dichlorophenyl, 5,6,7,8-tetrahydro-2-naphthyl, 4-tert-butylphenyl, and 2,4,6-trimethylphenyl.
3. The method according to claim 1, characterized in that: R is selected from methyl, ethyl, isopropyl.
4. The method according to claim 1, characterized in that: In the hydroformylation reaction, the hydroformylation catalyst is selected from acetylacetonato dicarbonyl rhodium, (1,5-cyclooctadiene) rhodium chloride dimer, tetracarbonyl dirhodium dichloride, bis(1,5-cyclooctadiene) rhodium tetrafluoroborate, bis(1,5-cyclooctadiene) rhodium hexafluorophosphonate, and the phosphine ligand is selected from Xantphos, triphenylphosphine, 2,2'-bis[(1,1'-biphenyl-2,2'-diyl)phosphite]-3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl, triphenyl phosphite; In the reductive amination reaction, a palladium catalyst is used, the palladium catalyst is selected from Pd(acac)2, Pd(OAc)2, Pd2(dba)3, Pd(dba)2, Pd(PPh3)2Cl2, Pd(PPh3)4, 10% Pd / C or 5% Pd / C, and the amine source is selected from ammonium formate, ammonia methanol solution, and ammonium acetate; In the hydrogenation reaction, the hydrogenation catalyst used is selected from Raney nickel, palladium carbon (Pd / C), Raney nickel, Raney cobalt, Pt / C, Ru / C, Rh / C, and the reducing agent is hydrogen; and / or The hydrolysis reaction is carried out under base catalysis, and the base used is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, and lithium hydroxide; the solvent used in the hydrolysis reaction is selected from water, methanol, ethanol, isopropanol, or a mixture of two or more thereof.
5. A method for synthesizing 4,9-diene decanoate represented by formula III as claimed in claim 1, comprising the following steps: A. 1,3-butadiene and the malonate of formula I are subjected to palladium-catalyzed polymerization reaction to obtain the compound 2-(2,7-octadienyl) malonate of formula II; B. Compound II is hydrolyzed and decarboxylated to obtain 4,9-diene decanoate shown in formula III:
6. The method according to claim 5, characterized in that: The solvent used in step A is the alcohol corresponding to the R group.
7. The method according to claim 5, characterized in that: The palladium catalyst used in step A is selected from Pd(acac)2, Pd(OAc)2, Pd2(dba)3, Pd(dba)2, Pd(PPh3)2Cl2 or Pd(PPh3)4, and the phosphine ligand is selected from triphenylphosphine, tri(2-methoxyphenyl)phosphine, tri(2,4,6-trimethoxyphenyl)phosphine, tri(2,6-dimethoxybenzene)phosphine, 10-phenyl-10H-phenylphosphine oxide, tri(4-methoxyphenyl)phosphine, and the mass ratio of the palladium catalyst to the phosphine ligand is 1:1-100.
8. The method according to claim 5, characterized in that: The telomerization reaction in step A is carried out in the presence of a base selected from an organic base and an inorganic base.
9. The method according to claim 5, characterized in that: The solvent used in the hydrolysis reaction in step B is a mixed solvent of alcohol and water, and the base used is selected from potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, and lithium hydroxide.
10. The method according to claim 5, characterized in that: The solvent used in the decarboxylation reaction of step B is selected from N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide or N-methylpyrrolidone, and the reaction temperature is 120°C-200°C.