Preparation method of long-chain fatty amine, acylamino long-chain fatty acid, long-chain omega-amino fatty acid and long-chain nylon

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of long-chain fatty amine, acylamino long-chain fatty acid, long-chain omega-amino fatty acid and long-chain nylon. The preparation method of the long-chain fatty amine comprises the following steps: mixing sodium hypohalide and an organic solvent, and carrying out Hofmann rearrangement reaction to obtain a transition-state reaction solution; and then adjusting the transition state reaction liquid to be alkaline, and carrying out hydrolysis reaction to obtain the long-chain fatty amine. Wherein the structural formula of the long-chain fatty amine is shown in the specification, and n represents an even number of 8-14; the transition state reaction liquid comprises an isocyanate intermediate; and the organic solvent is mutually soluble with water. According to the invention, long-chain fatty amine is prepared from renewable long-chain fatty acid, and precursor substances of long-chain nylon such as nylon 11 and the like are prepared by adopting a chemical and microbial coupling method.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing long-chain fatty amines, amide-based long-chain fatty acids, long-chain ω-amino fatty acids, and long-chain nylon. Background Technology

[0002] n-Undecane is a key chemical intermediate used in the manufacture of products such as decane. A common synthetic method for n-undecane is the catalytic hydrogenation reduction of n-undecyl alcohol. There are also preparation processes using nitroundecane, undecyl azide, and undecane nitrile under catalysis, as shown in the synthetic routes below. Figure 1 As shown. The conventional synthesis of n-undecane requires noble metals as catalysts, and its raw materials, such as nitroundecane, undecyl azide, and undecanenitrile, also have certain toxicity.

[0003] Nylon 11 (hereinafter also abbreviated as "PA11") is a long-chain soft nylon synthesized from castor oil. The preparation process of Nylon 11 mainly uses castor oil as raw material, which is cracked to obtain 10-undecenoic acid, and then subjected to addition, ammonolysis, and polymerization to form nylon 11 resin, followed by modification and molding to obtain the product. The main steps are: preparation of 10-undecenoic acid from castor oil (castor → pressing → castor oil → esterification → methyl ricinoleate → cracking → methyl 10-undecenoate → hydrolysis → 10-undecenoic acid) → bromination (11-bromoundecanoic acid) → ammonolysis (11-aminoundecanoic acid) → polymerization → nylon 11 → molding → product. Although the production process of Nylon 11 using castor oil as raw material uses renewable castor oil, it has problems such as low yield, high energy consumption, high cost, and many by-products. Moreover, the process is complex and the production route is long.

[0004] In recent years, with the development of biotechnology research, more and more enzyme-catalyzed reactions have been applied to the production research of ω-amino fatty acids. Different starting materials lead to different biosynthetic pathways. For example, starting from free fatty acids, ω-hydroxy fatty acids (hereinafter referred to as "ω-HFAs") are formed by terminal hydroxylation using P450 hydroxylase; starting from fatty acid esters or lactones, ω-HFAs are generated by hydrolysis using esterases. Then, ω-aldehyde fatty acids are generated by oxidation using alcohol dehydrogenases, and finally, ω-amino fatty acids are generated by amination of the aldehyde acid using transaminases or amine dehydrogenases. Patent CN 110643555 B is based on this idea, constructing E. coli genetically engineered bacteria to prepare 12-aminododecanoic acid using lauric acid as a raw material. Patent CN 110643555 B provides a method for the biological preparation of 12-aminododecanoic acid, but this method has a technical drawback: the intermediate fatty aldehyde and 12-aminododecanoic acid are biotoxic to the bacterial strain and have a toxic effect on the production strain, which is not conducive to large-scale production.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] In this invention, the difficulty in preparing n-undecylamine lies in the reaction process of preparing n-undecylamine from lauramide; specifically, the reaction system of the Hoffmann rearrangement reaction is usually a homogeneous reaction in the aqueous phase. Lauramide is almost insoluble in alkaline solution, so the usual aqueous phase reaction leads to low yield of the target product and increased byproducts, such as acylurea. The literature "ChemInformAbstract: Synthesis of Alkyl‐and Cycloalkylamines by Rearrangement" (PurchaseR , Sainsbury M. Cheminform, 2010, 41(51):365-418.DOI:10.1002 / chin.201051242.) discloses the Hoffmann rearrangement of three simple carboxylamides. In order to solve the above problems, it is disclosed that an alcohol is used as a solvent, sodium alkoxide is used instead of sodium hydroxide, the amide is dissolved in the sodium alkoxide-alcohol reaction system, and then bromine is added dropwise, which can accelerate the reaction rate, lower the temperature, and reduce the formation of acylurea. However, liquid bromine is highly corrosive and toxic, and its rapid reaction makes it difficult to control, increasing operational difficulty and control costs. The literature "New strategies for the Hofmann reaction" (Rane DS, Sharma MM. Journal of Chemical Technology & Biotechnology, 2010, 59(3):271-277.DOI:10.1002 / jctb.280590310.) reported that the Hofmann rearrangement of lauramide needs to be carried out in methanol. This reaction needs to be carried out at 52-55℃ and then refluxed for 2 hours. It can yield methyl carbamate, but cannot yield long-chain aliphatic amines.

[0007] To overcome the problem of lauramide's insolubility in water and simultaneously improve the yield of n-alkylamines, this invention utilizes sodium hypohalite as a rearrangement reagent under alkaline conditions and a water-miscible organic solvent as a dispersant to achieve a homogeneous reaction. This yields a transitional intermediate primarily composed of isocyanate intermediates, which is beneficial for the formation of long-chain fatty amines. Furthermore, this invention proposes a chemo-bioconjugation method for preparing long-chain ω-amino fatty acids, precursor compounds of long-chain nylon, using long-chain fatty amines.

[0008] Based on this, the present invention has the following technical solution: In a first aspect, the present invention provides a method for preparing a long-chain fatty amine, comprising: taking... Sodium hypohalite and an organic solvent are mixed to carry out a Hoffmann rearrangement reaction to obtain a transition state reaction solution; then the transition state reaction solution is adjusted to alkaline and a hydrolysis reaction is carried out to obtain the long-chain aliphatic amine. The structural formula of the long-chain fatty amine is as follows: n represents an even number from 8 to 14; the transition state reaction solution includes isocyanate intermediates; the organic solvent is miscible with water.

[0009] In this invention, the transition state reaction solution includes isocyanate intermediates and carbamate intermediates, wherein the isocyanate intermediates are predominant in the transition state reaction solution; preferably, the mass ratio of the isocyanate intermediates to carbamate intermediates is (2~15):1.

[0010] This invention optimizes the reaction conditions by ensuring that the dominant intermediate (isocyanate intermediate) is in the majority in the reaction system, which helps to form long-chain fatty amines and ultimately enables the one-pot Hoffmann rearrangement to produce long-chain fatty amines.

[0011] Preferably, the The molar ratio of sodium hypohalite to sodium hypohalite is (0.4~0.8):1.

[0012] This invention discovers that, relative to When the amount of sodium hypohalate is insufficient, the product is a carbamate intermediate and the reaction is incomplete; while when the amount of sodium hypohalate is excessive, both isocyanate and carbamate intermediates can be obtained, with isocyanate intermediates being the main ones; and the hydrolysis efficiency of isocyanate is better than that of carbamate intermediates, which is conducive to the formation of aliphatic amines.

[0013] Preferably, the organic solvent includes one or more of methanol, ethanol, and DMF.

[0014] More preferably, the organic solvent includes methanol and / or ethanol.

[0015] Preferably, the Hoffmann rearrangement reaction is carried out at 20-30°C.

[0016] This invention has found that, in order to obtain the long-chain fatty amines in a one-pot process, the temperature of the Hoffmann rearrangement reaction needs to be kept within the above-mentioned range; when the reaction temperature is higher than the above-mentioned range, the product is mainly acylurethane, which is not conducive to obtaining the product by hydrolysis under alkaline conditions.

[0017] Preferably, n is 10; that is, long-chain fatty amines. It is undecylamine, and It is lauramide.

[0018] Preferably, the pass It is prepared by amidation reaction.

[0019] In this invention, those skilled in the art can use conventional amidation reactions to... Prepared .

[0020] As a preferred option, Mix with a nitrogen source, then heat to 120℃~200℃ to dehydrate and generate .

[0021] In this invention, the nitrogen source can be one or a mixture of several of ammonia water, ammonia gas, urea, ammonium carbonate and ammonium bicarbonate.

[0022] In a preferred embodiment of the present invention, n-undecylamine is prepared by the following reaction route: .

[0023] Methods for preparing n-undecylamine include: Step 1: Amide reaction. Lauric acid is thoroughly mixed with a nitrogen source, and then heated to 120℃~200℃ to dehydrate and generate lauramide.

[0024] Step 2: Hoffmann rearrangement. Lauramide and sodium hypohalite are subjected to the Hoffmann rearrangement reaction at room temperature; then, the transition state reaction solution is adjusted to alkaline with an alkaline solution to carry out the hydrolysis reaction.

[0025] Preferably, step 2 includes: reacting lauramide with sodium hypohalite at room temperature with a Hofmann rearrangement reaction for 3-3.5 h; then adjusting the transition reaction solution to alkaline with an alkaline solution and carrying out a hydrolysis reaction for 0.5-10 h. After the reaction is complete, the crude product (oil phase) is separated, and the oil phase is purified by molecular distillation to obtain n-undecylamine.

[0026] Secondly, the present invention provides a method for preparing amide-based long-chain fatty acids, comprising: S1: Prepared using the method described above for preparing long-chain fatty amines n represents an integer from 8 to 14; S2: Will Acylation protection was performed to obtain ; S3: Will The amide-based long-chain fatty acid was prepared by microbial oxidation as both a culture medium and a raw material. The structural formula of the amide-based long-chain fatty acid is as follows: R represents methyl or phenyl.

[0027] In this invention, the amide-based long-chain fatty acid can be acetyl long-chain fatty amine, propionyl long-chain fatty amine, butyryl long-chain fatty amine, benzoyl long-chain fatty amine, oxaloyl long-chain fatty amine, succinyl long-chain fatty amine, and phthaloyl long-chain fatty amine, etc. Preferably, it is acetyl long-chain fatty amine or benzoyl long-chain fatty amine; more preferably, it is acetyl long-chain fatty amine.

[0028] In S1 of this invention, when n is an odd number between 8 and 14, those skilled in the art can also obtain the product through a reduction reaction using conventional, publicly available techniques. No restrictions are imposed here.

[0029] Preferably, the microorganisms include cytochrome P450 enzyme (CYP), fatty alcohol oxidase (FAO), and fatty aldehyde dehydrogenase (FALDH).

[0030] In this invention, The alkyl moiety has a normal long-chain alkyl structure, which allows microorganisms to oxidize its terminal methyl group via metabolic pathways, ultimately generating compounds with carboxylic acid groups. The general process of microbial terminal group oxidation is as follows: first, fatty alcohols are generated under the catalysis of cytochrome P450 enzymes (CYP); then, fatty alcohols are further oxidized to fatty aldehydes under the catalysis of fatty alcohol oxidase (FAO); finally, they are oxidized to carboxyl compounds under the catalysis of fatty aldehyde dehydrogenase (FALDH). This biocatalytic process has high selectivity and efficiency and can be carried out under mild conditions, reducing the side reactions and environmental pollution that may occur in chemical synthesis.

[0031] Preferably, the microorganisms include Bacillus spp. ( Bacillus ), Pseudomonas spp. Pseudomonas ), Microbes ( Microbacterium ) and yeast ( Yeast One or more of them.

[0032] More preferably, the microorganisms include the yeast genus ( Yeast The yeast genus includes Candida (…). Candida Cryptococcus genus ( Cryptococcus ), Hansenula genus ( Hansenuta ), Pichia pastoris ( Pichia ), Rhodotorula genus ( Rhodotorula ), Globosa ( Torulapsis ), genus *Mycosaccharomyces* ( Trichosporon ), Yeast ( Saccharornyces ), Yeast genus ( Brettanomyces ), genus *Pteris* ( Sporobolomyces ) and Loude yeast ( Lodderomyces One or more of them.

[0033] More preferably, the microorganism includes the Candida genus ( Candida The Candida genus includes Candida tropicalis (…). Candida tropicalis ) and / or Candida albicans ( Candida cloacae ).

[0034] In microbial fermentation, conventional alkanes are in the liquid phase at fermentation temperatures, while... At the fermentation temperature, it is a solid. In this invention, it is prepared into an aqueous dispersion using an emulsifier. This operation has the following advantages: (1) it facilitates precise operation of the feeding process during fermentation; (2) compared with solid powder, aqueous dispersion is more conducive to the raw materials being consumed and transformed by microorganisms, thereby improving production efficiency.

[0035] As a preferred option, in S3, It is mixed with an emulsifier to form an aqueous dispersion, which is then added to a fermentation medium for fermentation.

[0036] More preferably, the emulsifier includes Tween; The mass ratio of the emulsifier to the emulsifier is 1~2:0.2~1.

[0037] Preferably, S3 includes: S31: Seed culture: Cultivate microorganisms at pH 5~6.5 and 27~31℃ until the seed liquid OD600≥20; S32: Fermentation culture: Add the seed culture obtained in S31 to... Fermentation was carried out at pH 7.5~8.0 and 27~31℃ to obtain fermentation broth; S33: Extraction: Centrifuge or filter the fermentation broth to remove bacterial cells and proteins, obtaining a clear fermentation broth; then decolorize the clear fermentation broth with activated carbon, stirring at 40-80℃ for 1-3 hours. After decolorization, filter to remove the activated carbon, obtaining a clear broth. Precipitate with 10-40% sulfuric acid solution until the pH is between 3 and 5. Filter to collect the solid, and finally wash and dry the solid sequentially to obtain... .

[0038] Preferably, in S33 above, the amount of activated carbon used is 0.5~1.5% (w / V), based on the amount of the fermentation liquid.

[0039] In this invention, those skilled in the art can select conventional culture media as the culture media for S31 and S32 based on known technologies disclosed in the prior art, without further limitation.

[0040] In this invention, for S2, those skilled in the art can use acylation schemes already disclosed in the prior art to... Acylation protection was performed to obtain .

[0041] Preferably, S2 includes: Acid anhydrides and / or acids undergo acylation reactions in the presence of a catalyst to yield... .

[0042] In this invention, the acid anhydride includes acetic anhydride, benzoic anhydride, phthalic anhydride, and succinic anhydride, etc.; the acid includes organic acids such as formic acid, acetic acid, propionic acid, and butyric acid; furthermore, it can also be an acyl chloride reagent of organic acid, specifically, acetyl chloride, propionyl chloride, and butyryl chloride, etc.

[0043] In this invention, the catalyst can be an acidic compound such as concentrated sulfuric acid, p-toluenesulfonic acid, or concentrated hydrochloric acid; or an alkaline compound such as anhydrous sodium acetate, sodium carbonate, potassium carbonate, pyridine, or triethylamine; or a Lewis acid-base catalyst or anion-cation exchange resin, etc.

[0044] Preferably, n is 10 or 11.

[0045] As a preferred embodiment of the present invention The reaction pathways include: .

[0046] Furthermore, The reaction pathways include: .

[0047] In this context, R represents methyl or phenyl.

[0048] As a preferred embodiment of the present invention The preparation method includes the following steps. In the following preparation method, R is taken as a methyl group: Step 1: Amide reaction. Mix n-undecylamine and triethylamine, then slowly add acetyl chloride to obtain a reaction mixture. Maintain the temperature at 45-50°C and react for 8-12 hours. After the reaction is complete, add 10-30 times the volume of water to the reaction solution to precipitate the product. Filter to obtain a white solid. Elute the white solid in situ until the washing solution is neutral. Dry the solid to obtain acetylated undecylamine.

[0049] Step 2: Fermentation and transformation.

[0050] (1) Seed culture: Microorganisms were cultured at pH 5~6.5, 27~31℃, rotation speed 300~800r / min, ventilation control dissolved oxygen DO value not less than 20%, and tank pressure 0~0.05 MPa until the seed liquid OD600≥20; (2) Fermentation culture: Add the seed liquid obtained in (1) and ferment at pH 7.5~8.0 and 27~31℃ to obtain fermentation broth; the substrate concentration in the fermentation broth is controlled at 0.1~10%; the fermentation time is 100~150h.

[0051] (3) Extraction: The fermentation broth was pretreated to a pH between 8 and 13 by heating to 50-90°C and maintaining the temperature for 50-70 minutes. The fermentation broth was then centrifuged or filtered to remove bacterial cells and proteins, yielding a clear fermentation broth. This broth was then decolorized with activated carbon and stirred at 40-80°C for 1-3 hours. After decolorization, the activated carbon was removed by filtration, yielding a clear broth. Acid precipitation was performed using a 10-40% sulfuric acid solution until the pH was between 3 and 5. The solid was collected by filtration, and then washed and dried to obtain a crude product. The crude product was recrystallized using an organic solvent method to obtain a refined fermentation product.

[0052] In this invention, the organic solvent used for recrystallization is one or a mixture of several of the following: methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, acetic acid, ethyl acetate, butyl acetate, and isobutyl acetate.

[0053] As a preferred embodiment of the present invention The reaction pathways include: .

[0054] Furthermore, The reaction pathways include: .

[0055] or,

[0056] .

[0057] In this invention, through chemical-biological coupling, microorganisms (especially Candida albicans, etc.) can be used to produce long-chain ω-amino fatty acids that do not exist in nature.

[0058] As a preferred method, the acid hydrolysis is as follows (taking 11-aminoundecanoic acid as an example): Hydrolysis is carried out using a 3-6M sulfuric acid solution as the solvent at a concentration of 10-100 g / L, at a hydrolysis temperature of 100-121℃, for 12-24 hours. After hydrolysis, the solution is cooled to room temperature, and product crystals precipitate. The product is filtered and washed in situ until the washing solution is neutral in pH. The product is then collected to obtain 12-aminododecanoic acid.

[0059] The alkaline hydrolysis method is as follows (taking 11-aminoundecanoic acid as an example): Hydrolysis is carried out using a 5-10M sodium hydroxide or potassium hydroxide solution at a concentration of 20-150 g / L, at a hydrolysis temperature of 50-100℃, for 12-24 hours. After hydrolysis, the solution is cooled to room temperature, and the pH is adjusted to between 2 and 4, causing product crystals to precipitate. The product is filtered and washed in situ until the washing solution reaches a neutral pH. The product is then collected to obtain 11-aminoundecanoic acid.

[0060] In this invention, those skilled in the art can use conventional, existing technologies to... Hydrolysis protection is obtained .

[0061] Preferably, n is 10 or 11.

[0062] As a preferred embodiment of the present invention, the reaction route of 11-aminoundecanoic acid includes: .

[0063] Furthermore, the reaction route for 11-aminoundecanoic acid includes: .

[0064] Fourthly, the present invention provides a method for preparing long-chain nylon, wherein long-chain ω-amino fatty acids are prepared using the method for preparing long-chain ω-amino fatty acids, and then polymerized under nitrogen protection to obtain the long-chain nylon.

[0065] In this invention, those skilled in the art can use conventional and publicly available technologies to polymerize long-chain ω-amino fatty acids to obtain long-chain nylon, and no further limitations are made here.

[0066] In specific implementation, those skilled in the art can apply the scheme of this invention to the preparation of long-chain nylons using long-chain fatty acids as starting materials, such as nylon 11, nylon 12, nylon 13, nylon 14, nylon 15, nylon 16, etc.

[0067] Based on the above technical solution, the beneficial effects of the present invention are as follows: The present invention provides a method for preparing long-chain fatty amines, amide-based long-chain fatty acids, long-chain ω-amino fatty acids, and long-chain nylon. This method prepares long-chain fatty amines from renewable long-chain fatty acids and simultaneously uses a chemical-microbial coupling method to prepare precursors for long-chain nylons such as nylon 11. Overall, this invention provides new ideas for the application of plant-based renewable long-chain fatty acids, broadens the channels for microbial utilization, and achieves effective cross-integration of chemical and microbial application technologies. Attached Figure Description

[0068] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0069] Figure 1 This is a common synthetic route for n-undecylamine in the background technology.

[0070] Figure 2 This is the carbon spectrum of lauramide in Example 1 provided by the present invention.

[0071] Figure 3 This is the carbon spectrum of n-undecylamine in Example 1 provided by the present invention.

[0072] Figure 4 This is the carbon spectrum of acetylated undecylamine in Example 1 provided by the present invention.

[0073] Figure 5 This is the carbon spectrum of acetyl undecanoic acid in Example 1 provided by the present invention.

[0074] Figure 6 This is the gas chromatogram of dodecylamine in Example 2 provided by the present invention.

[0075] Figure 7 These are liquid chromatographic images of the reaction solution in Example 2 of the present invention, wherein the top, middle and bottom are respectively: liquid chromatographic image of benzoic acid (top); liquid chromatographic image of benzoyldodecylamine (middle); and liquid chromatographic image of benzamide dodecanoic acid (bottom).

[0076] Figure 8 This is the infrared spectrum of 12-aminododecanoic acid in Example 2 provided by the present invention.

[0077] Figure 9 This is a liquid chromatogram of the reaction product in Example 3 provided by the present invention.

[0078] Figure 10 The reaction product in Example 4 provided by this invention 1 H-NMR spectrum.

[0079] Figure 11 This is the liquid phase spectrum of the reaction product in Example 5 provided by the present invention. Detailed Implementation

[0080] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0081] Unless otherwise specified, all raw materials used in the embodiments are commercially available conventional raw materials, and the technical means used are conventional means well known to those skilled in the art.

[0082] Example 1

[0083] This embodiment provides a 11-amino-undecanoic acid, the reaction route of which is shown below: .

[0084] Its preparation method includes the following steps: Step 1: Ammoniation. 10g of lauric acid and 30g of urea were placed in a 500ml round-bottom reaction flask, stirred thoroughly, and reacted in a metal bath. Under stirring, the temperature was first rapidly increased to 145℃ and stabilized for 30min, then increased to 160℃ and stirred for another 5h. After the reaction was complete, the mixture was cooled and washed with water to obtain lauramide. Its carbon spectrum (C-NMR) is shown below. 13 C-NMR DMSO) such as Figure 2 As shown.

[0085] Step 2: Hoffmann rearrangement. 1.99 g (approx. 0.01 mol) of lauramide was dissolved in 50 ml of anhydrous ethanol and allowed to cool to room temperature. Approx. 0.011 mol of available chlorine solution (NaClO) was cooled to 0°C in an ice-water bath and then slowly added to the clear lauramide ethanol solution at room temperature. The reaction was allowed to proceed for 3–3.5 h at room temperature. After the reaction was complete, 100 ml of sodium hydroxide solution (approx. 0.05 mol) was added, and hydrolysis was carried out at 100°C for 2 h. After the reaction was complete, the oil phase was collected while hot and purified by molecular distillation to obtain n-undecylamine. Its carbon spectrum (…) 13 C-NMR DMSO) such as Figure 3 As shown.

[0086] Step 3: Amide reaction. Take 171g of undecylamine, add an appropriate amount of triethylamine, and stir at 30℃. Then slowly add 300ml of acetyl chloride, completing the addition within 4 hours. After the addition is complete, control the temperature at 45-50℃ and react for 8-12 hours. After the reaction is complete, pour the reaction solution into 20 times the volume of water, stir, and allow the product to precipitate. Then filter to obtain a white solid. Elute the white solid in situ until the washing solution is neutral. Dry the solid to obtain acetylated undecylamine. Its carbon spectrum (C10) 13C-NMR DMSO) such as Figure 4 As shown.

[0087] Step 4: Fermentation and transformation.

[0088] Using acetylacetonine as a raw material, the corresponding product was produced by microbial oxidation using Candida sp. DC12. 100g of acetylacetonine and approximately 30g of Tween 60 were dissolved in water to a final volume of 500g. An aqueous emulsion was prepared using an ultrasonic emulsification pump, followed by fermentation culture.

[0089] The strain used in this embodiment is Candida albicans. Reference: Production of long-chain mixed dicarboxylic acids by fermentation of n-alkane [J]. Acta Microbiologica Sinica, 1980, 20(1): 88-93. This strain can be purchased from the Institute of Microbiology, Chinese Academy of Sciences.

[0090] (1) Seed preparation: YPD medium was used: 20 g / L glucose, 10 g / L yeast extract, 20 g / L peptone, natural pH, and cultured on a shaker at 220 rpm at 29.5℃ for about 12 hours. When the OD600 of the seed culture was ≥20, the cells were robust and free of contaminants under a microscope, and then transferred to a 5L fermenter for further culture.

[0091] (2) 5L fermenter culture: Culture medium composition: KH₂PO₄ 8 g / L, NaCl 1 g / L, KNO₃ 7 g / L, MgSO₄·7H₂O 0.5 g / L, urea 1.2 g / L, yeast extract 2 g / L, corn steep liquor 46 g / L, sucrose 20 g / L. Fermentation conditions: inoculum 10%; tank temperature 29.5℃; dissolved oxygen (DO) ≥ 5%; no tank pressure; pH: approximately 7.5~8.0 during conversion; rotation speed 300~800 r / min; incubation time approximately 120 h. The input of conversion material was calculated at 30 g / L, and the yield after fermentation was 15 g / L.

[0092] (3) Extraction: For the fermentation broth obtained in step (2), adjust the pH to between 8 and 10 and heat for 30 minutes. Centrifuge or filter to remove bacterial cells and proteins to obtain a clear fermentation broth. Decolorize the clear fermentation broth with activated carbon by adding 1% (w / V) of activated carbon and stirring at 40-80℃ for 1-3 hours. Filter to remove the activated carbon and obtain a clear broth. Precipitate with 10-40% sulfuric acid solution until the pH is between 3 and 5. Filter to collect the solid and wash it three times with hot water in situ. Dry to obtain the crude product acetyl undecanoic acid. Its carbon spectrum ( 13 C-NMR DMSO) such as Figure 5 As shown.

[0093] Step 5: Remove the protecting group.

[0094] Using the crude product as raw material, deprotection was carried out by alkaline hydrolysis. Specifically, 20 g of the crude product was hydrolyzed at a concentration of 100 g / L using 5M KOH solution as the solvent at 100℃ for 12-24 h. After hydrolysis, the solution was cooled to room temperature, and product crystals precipitated. The crystals were filtered and washed in situ until the pH of the washing solution was neutral to obtain 11-aminoundecanoic acid (ESI+ 2O2).

[0095] Example 2

[0096] This embodiment provides a 12-amino-dodecanoic acid, the reaction route of which is shown below: .

[0097] In this embodiment, n-dodecylamine is obtained by the following method.

[0098] Step 1: Ammoniation. 10g of lauric acid and 30g of urea were placed in a 500ml round-bottom reaction flask, stirred thoroughly, and reacted in a metal bath. Under stirring, the temperature was first rapidly increased to 145℃ and stabilized for 30min, then increased to 160℃ and stirred for another 5h. After the reaction was complete, the mixture was cooled and washed with water to obtain lauramide. Its carbon spectrum (C-NMR) is shown below. 13 C-NMR DMSO) such as Figure 2 As shown.

[0099] Step 2: Reduction. 1.99 g (approximately 0.01 mol) of lauramide was dissolved in 50 ml of anhydrous ethanol and allowed to cool to room temperature. 0.38 g of sodium borohydride was placed in 10 ml of anhydrous ethanol, and then 0.65 g of glacial acetic acid was slowly added. The mixture was stirred at room temperature for 3 hours. The lauramide ethanol solution was slowly added to the sodium borohydride reaction solution, and then refluxed for 8 hours. After the reaction was complete, heating was stopped, and 6M hydrochloric acid solution was slowly added to the system. After no more gas was released, the organic phase was vacuum filtered to remove the solid, yielding the ethanol phase. The ethanol was removed by rotary evaporation to obtain dodecylamine. The gas chromatogram of dodecylamine is shown below. Figure 6 As shown, RT is 9.972 min.

[0100] The preparation method of 12-amino-dodecanoic acid includes the following steps: Step 1: Amide reaction.

[0101] Take 18.5 g of n-dodecylamine, add an appropriate amount of triethylamine, dissolve in 60 ml of DMF solution, and keep warm and stir at 30 °C. Then slowly add 25 g of benzoic anhydride. After the addition is complete, control the temperature at 80 °C and react for 8 hours. After the reaction is complete, pour the reaction solution into 6 times the volume of water, adjust the pH to about 8 with NaOH solution, stir, and allow the product to precipitate. Then filter to obtain the product benzoyldodecylamine.

[0102] Step 2: Fermentation and transformation.

[0103] The specific method is as described in step four of Example 1. The reaction process was monitored by HPLC, and the residence times (RT) of benzoic acid (RT 3.095 min), benzoyldodecanoic acid (RT 13.744 min), and benzamide dodecanoic acid (RT 3.826 min) were as follows: Figure 7 As shown.

[0104] Step 3: Remove the protecting group.

[0105] Using the crude product from step two as raw material, deprotection was performed via acid hydrolysis. Specifically, 10 g of the crude product was hydrolyzed at a concentration of 50 g / L using 4M sulfuric acid solution at 121°C for 2 hours. After hydrolysis, the product was cooled to room temperature, and crystals precipitated. The crystals were filtered and washed in situ until the washing solution reached neutral pH, and the product was collected. 12-Aminododecanoic acid was obtained. The product was analyzed by FTIR, and the chromatogram was compared with that of a standard (see [link to standard chromatogram]). Figure 8 The results showed that 12-aminododecanoic acid was obtained.

[0106] Example 3

[0107] This embodiment provides an 11-aminoundecanoic acid, the preparation method of which differs from that of Example 1 only in that the reaction temperature is 55°C when preparing n-undecanoic acid in step two.

[0108] The results showed that the reaction product was mainly acylurea, and n-undecylamine could not be obtained. The liquid chromatogram of the product is shown below. Figure 9 As shown, RT10.32min is the raw material lauramide, and RT13.545min is acylurea.

[0109] Example 4

[0110] This embodiment provides a 11-aminoundecanoic acid, the preparation method of which differs from that of Example 1 only in that: when preparing n-undecanoic acid in step two, the molar ratio of lauramide to NaClO is 1:1.

[0111] 1 See the H-NMR spectrum. Figure 10 The results showed that the reaction product was a mixture of lauramide and (N-undecyl)carbamate, and the reaction was incomplete, which increased the difficulty of hydrolysis.

[0112] Example 5

[0113] This embodiment provides an 11-aminoundecanoic acid, the preparation method of which differs from that of Example 1 only in that: in step two, when preparing n-undecanoic acid, ethanol is replaced with an equal amount of DMF.

[0114] HPLC chromatograms are shown below. Figure 11The results showed that, apart from the raw material lauramide (RT 10.626 min), the reaction byproducts accounted for the majority, which burdened the hydrolysis and separation.

[0115] Example 6

[0116] This embodiment provides a 11-aminoundecanoic acid, the only difference between its preparation method and that of Example 1 is that no emulsifier is added in step four when preparing acetylundecanoic acid.

[0117] The results showed that the yield was 0.8 g / L after fermentation, which was less than 1 g / L.

[0118] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A process for the preparation of long chain fatty amines, characterized in that, Comprising: The long-chain fatty amine is obtained by mixing sodium hypohalite and an organic solvent to perform a Hofmann rearrangement reaction to obtain a transition state reaction solution, and then adjusting the transition state reaction solution to be alkaline to perform a hydrolysis reaction. , sodium hypohalite and an organic solvent to perform a Hofmann rearrangement reaction to obtain a transition state reaction solution, and then adjusting the transition state reaction solution to be alkaline to perform a hydrolysis reaction. The long-chain fatty amine has a structural formula as shown in the following formula (I) n represents an even number of 8-14; the transition state reaction solution comprises an isocyanate intermediate; the organic solvent is miscible with water; Preferably, the molar ratio of the sodium hypohalite to the compound of formula (I) is (0.4-0.8):

1. and the molar ratio of the sodium hypohalite to the compound of formula (I) is (0.4-0.8):

1.

2. The method for preparing long-chain fatty amines according to claim 1, characterized in that, The organic solvent comprises one or several of methanol, ethanol and DMF.

3. The process for the preparation of long chain fatty amines according to claim 1 or 2, characterized in that, The Hofmann rearrangement reaction is carried out at 20-30℃.

4. The process for the preparation of long chain fatty amines according to any one of claims 1 to 3, characterized in that, n is 10.

5. The process for the preparation of long chain fatty amines according to any one of claims 1 to 4, characterized in that, The By after the amidation reaction.

6. A method for producing an amido long chain fatty acid, characterized by, Comprising: S1 : using the method for preparing long-chain fatty amines according to any one of claims 1 to 5 to prepare ; n represents an integer from 8 to 14; S2: adding carrying out acylation protection to obtain ; S3: adding The amido long chain fatty acids are prepared by microbial oxidation; The structural formula of the amido long chain fatty acid is ; R represents a methyl group or a phenyl group.

7. The method for producing amido-long chain fatty acids according to claim 6, wherein In S3, the The emulsifier is mixed to form a water phase dispersion, which is then added to the fermentation medium for fermentation culture; preferably, the emulsifier includes Tween; the The mass ratio of the emulsifier to the fermentation medium is 1-2:0.2-1.

8. The method for producing amido long chain fatty acid according to claim 6 or 7, characterized by, n is 10 or 11.

9. A method for the preparation of long-chain ω-amino fatty acids, characterized by, Comprising: The amide-based long-chain fatty acid was prepared using the method described in any one of claims 6 to 8. Then, under acidic or alkaline conditions, hydrolysis protection is performed by heating to obtain the long-chain ω-amino fatty acid; the structural formula of the long-chain ω-amino fatty acid is as follows: Preferably, n is 10 or 11.

10. A process for the preparation of long chain nylon characterized by, The long-chain omega-amino fatty acid is prepared by the method of claim 9, and then polymerization is carried out under nitrogen protection to obtain the long-chain nylon.

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