Method for synthesizing 2-(3-hydroxypropyl) cyclododecanone by microchannel reactor
By performing OCP synthesis in the microchannel reactor, the problems of low selectivity and yield, long reaction time and large peroxide use in traditional methods are solved, and efficient and safe OCP synthesis is achieved, reducing production costs.
Patent Information
- Application Number
- CN202510002496.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-02
- Publication Date
- 2025-04-11
AI Technical Summary
The method for synthesizing 2-(3-hydroxypropyl)cyclododecone (OCP) in the prior art has problems of selectivity and low yield, and the traditional kettle reaction device has a long reaction time and a large amount of peroxide, resulting in high cost.
The OCP synthesis was carried out using a microchannel reactor, and the reaction was obtained by pumping cyclododecone, allyl alcohol and peroxides into multiple reaction modules in the microchannel reactor in turn, and OCP products were obtained by decompression distillation.
The high selectivity and high conversion rate of OCP are achieved, the reaction time is short and the amount of peroxide is reduced, the production cost is reduced, and the purity and safety of the product are improved.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone (OCP) by using a microchannel reactor, and belongs to the field of chemical synthesis and process. Background Art
[0002] Compared with other synthetic musks, the aroma of macrocyclic musk is more elegant and luxurious, and is closest to natural musk. According to the current reports on the safety of spices in various countries around the world, macrocyclic musk is also the safest musk fragrance. In the future, ketone and monolactone musks in macrocyclic musk will be the key development direction.
[0003] Cyclopentadecanolide is an important macrocyclic musk, which not only has the scent of musk, but also has the fragrance of ambergris. Its fragrance is rich and delicate, but it is expensive (>200,000 / ton). It is currently widely used in perfumes, flavors, cosmetics, food, medicine and other fields. The annual market demand exceeds 15,000 tons and is in short supply. 2-(3-Hydroxypropyl)cyclododecanone (OCP) is a key intermediate for the synthesis of cyclopentadecanolide. At present, the method for synthesizing OCP in industry and literature patents is mainly through the free radical addition of cyclododecanone (CDON) and allyl alcohol (AA), which generally has the problems of low selectivity and yield. Considering the high synthesis cost of cyclopentadecanolide, it is particularly important to improve the selectivity and yield of OCP synthesis. Traditional industries (Symrise and Firmenich) use kettle reactors to produce OCP. This method has a long reaction time (>6 hours), a large amount of peroxide (minimum 40wt% AA), and allyl alcohol is completely converted, but the highest selectivity is only 57%.
[0004] Microchannel reactor is one of the technologies that the fine chemical industry is optimistic about to improve intrinsic safety. In the future, this technology will become an important trend in the process selection of the fine chemical industry. Compared with traditional kettle reactors, microchannel reactors have the advantages of fast reaction, controllable process, unmanned continuous operation, and reduced safety hazards. However, not all chemical reactions can be achieved with this reactor. The applicable reaction must be a fast reaction system, because the channel of the reactor generally stays for a few minutes, and the reaction is too slow. However, the addition reaction of CDON and AA is a slow reaction (it needs to be kept warm for 3 hours after adding the material to improve the conversion rate), which is usually not suitable for microchannel reactors.
[0005] Therefore, in order to overcome the above-mentioned process defects and apply the technical advantages of microreactors, it is of great significance to develop a highly selective continuous method for synthesizing OCP in a microchannel reactor. Summary of the invention
[0006] The present invention aims to provide a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone (OCP) by using a microchannel reactor, so as to overcome the defects of a traditional reactor and the disadvantages of a large amount of peroxide used, a long production cycle, low product selectivity and high cost in the prior art.
[0007] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:
[0008] The present invention provides a method for synthesizing 2-(3-hydroxypropyl)cyclododecanone (OCP) using a microchannel reactor, comprising the following steps:
[0009] (1) Cyclododecanone (CDON), allyl alcohol (AA) and peroxide are pumped into a microchannel reactor and reacted in turn through a plurality of reaction modules connected in series in the microchannel reactor;
[0010] (2) The material at the outlet of the microchannel reactor is subjected to reduced pressure distillation to obtain 2-(3-hydroxypropyl)cyclododecanone.
[0011] In one embodiment, the peroxide in step (1) is selected from one or more of tert-butyl hydroperoxide (TBHP), di-tert-butyl peroxide (DTBP), hydrogen peroxide, peracetic acid, benzoyl peroxide, etc., preferably one or more of tert-butyl hydroperoxide and di-tert-butyl peroxide.
[0012] In one embodiment, the mass ratio of allyl alcohol to peroxide in step (1) is 1:0.1-0.6, such as 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, etc., preferably 1:0.2-0.3;
[0013] In a specific application, the allyl alcohol and the peroxide are fed by a metering pump, and can be preheated or not preheated before feeding, preferably not preheated;
[0014] Preferably, the allyl alcohol and the peroxide are mixed and fed simultaneously, and the mixing method can be selected to be mixed before preheating or during the preheating period, preferably before preheating;
[0015] Specifically, the allyl alcohol and the peroxide are efficiently and fully mixed by a static tubular mixer, and the static mixer is selected from SD, SH, SK, SX, SMV, SMXL and Kenics types, preferably SH type.
[0016] The above-mentioned raw material mixing method and preheating method are conventional operations in the field and can be selected based on experience. There are no special requirements for this.
[0017] In one embodiment, the volume ratio of the feed flow rate of cyclododecanone (CDON) pumped into the microchannel reactor in step (1) to the total flow rate of allyl alcohol and peroxide is 2-20, for example, a volume ratio of 14:1, 12:1, 10:1, 8:1, 6:1, etc.
[0018] In one embodiment, the cyclododecanone in step (1) is fed by a high temperature melt pump, and the feed temperature is 80-120° C., preferably 100-110° C.;
[0019] In specific applications, in order to stabilize the required feed temperature, the feed pipeline of cyclododecanone usually needs to be insulated, and the insulation temperature is 80-120°C, preferably 100-110°C.
[0020] In one embodiment, the inner diameter of the microchannel reactor in step (1) is 0.5-5 mm, for example, 0.5 mm, 1 mm, 1.5 mm, 2 mm, 2.5 mm, 3 mm, 3.5 mm, 4 mm, 4.5 mm, 5 mm, etc., preferably 0.6-1.2 mm;
[0021] Specifically, the total liquid holding capacity in the microchannel reactor is 300-1200 ml, for example, 300 ml, 400 ml, 500 ml, 600 ml, 700 ml, 800 ml, 900 ml, 1000 ml, 1100 ml, 1200 ml, etc.;
[0022] Specifically, the microchannel reactor has multiple groups of reaction modules connected in series, the number of which is 3-6 groups, for example, 3, 4, 5, 6 groups, etc.;
[0023] The microchannel reactor can be an existing device purchased directly from the market, or can be assembled by itself through existing reaction modules, and there is no special requirement for this.
[0024] In one embodiment, during the reaction process of step (1), the inlet and outlet temperatures of the microchannel reactor are 170-120°C, for example, 170°C, 160°C, 150°C, 140°C, 130°C, 120°C, etc., preferably 160-140°C, and the inlet and outlet temperatures may be the same or different;
[0025] The pressure of the microchannel reactor is 0-4MPa, such as 0MPa, 0.5MPa, 1MPa, 1.5MPa, 2MPa, 2.5MPa, 3MPa, 3.5MPa, 4MPa, etc., preferably 2-3MPa;
[0026] Specifically, the total residence time of materials in the microchannel reactor is 10-80 min, for example, 10 min, 20 min, 30 min, 40 min, 50 min, 60 min, 70 min, 80 min, etc., preferably 15-70 min.
[0027] In one embodiment, in step (1), in order to ensure the residence time of the material in the microchannel reactor and improve the reaction conversion rate, the reaction is carried out by reflux for cyclic reaction. The specific operation method is: the outlet of the microchannel reactor is connected to the feed of cyclododecanone by a loop, so that part of the material is cyclically reacted in the microchannel reactor;
[0028] Preferably, the proportion of materials for circulating reaction in the microchannel reactor is 10-20wt%, for example, 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt%, 16wt%, 17wt%, 18wt%, 19wt%, 20wt%, etc.;
[0029] Preferably, the loop is usually subjected to heat preservation treatment, and the heat preservation temperature is 80-120°C.
[0030] In one embodiment, the reduced pressure distillation in step (2) has a temperature of 240-200°C, preferably 220-210°C, and a vacuum degree of 2-0.2 mbar, preferably 0.5-0.3 mbar.
[0031] In the method of the present invention, the purity of the OCP product obtained by the reduced pressure distillation in step (2) is 80-95%, and is basically stable at a purity of 90-95%, and can be directly used in the field of fragrance synthesis.
[0032] Compared with the prior art, the present invention has the following advantages:
[0033] (1) The present invention adopts a microchannel reactor to synthesize 2-(3-hydroxypropyl)cyclododecanone (OCP), which has a short reaction time, high product conversion rate and selectivity, easy operation, high safety, and can effectively overcome the shortcomings of using traditional reaction equipment, and is both efficient and safe.
[0034] (2) The method of the present invention can effectively reduce the amount of peroxide used, thus overcoming the shortcomings of the prior art such as large amount of peroxide used, long production cycle, high cost, and environmental pollution.
[0035] (3) The product conversion rate of the present invention can be as high as 99% (AA basis) or more, and the product selectivity can be as high as 79% (AA basis) or more. DETAILED DESCRIPTION
[0036] In order to facilitate the understanding of the present invention, the present invention will be further described below in conjunction with examples. It should be understood that the following examples are only for a better understanding of the present invention and do not mean that the present invention is limited to the following examples.
[0037] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
[0038] Unless otherwise specified, the reagents, materials and instruments used in the following examples are conventional reagents, conventional materials and conventional instruments in the art and can be obtained commercially.
[0039] The microchannel reactor used in the embodiment of the present invention is an MR microreactor produced by Zhongshan Zhian Company.
[0040] Examples 1-9
[0041] OCP was prepared using a microchannel reactor (inner diameter 0.8 mm, 3 reaction modules connected in series, total liquid holding volume 300 ml):
[0042] AA and peroxide with a mass ratio of 1:0.15 are efficiently and fully mixed by an SD type static tubular mixer, and the mixed solution is pumped into the preheating premixer at a volume flow rate V1 by a metering pump, and then enters the microchannel reactor; at the same time, CDON is pumped into the microchannel reactor at a volume flow rate V2 by a high-temperature melt pump to mix and react with the mixture of AA and peroxide, the pump head temperature is 110°C, and the CDON pipeline is kept at 100°C;
[0043] The outlet of the microchannel reactor is connected to the feed of cyclododecanone by a loop, so that 10 wt% of the material is circulated in the microchannel reactor for reaction, and the loop insulation temperature is 100° C.;
[0044] The inlet and outlet temperatures of the microchannel reactor are T1 and T2, respectively, the pressure is P, the residence time is t, and the sample is sampled for GC characterization to obtain the reaction conversion rate;
[0045] The sampled material was collected in a round bottom flask and distilled at 160°C in an oil bath under reduced pressure (1 mbar) to remove excess CDON and other light components, other light components mainly being tert-butyl alcohol. The product OCP was distilled under reduced pressure (0.3 mbar) at an oil temperature of 220°C. The product was characterized by gas phase to obtain its purity and the reaction selectivity was calculated. The specific reaction conditions and analysis results of Examples 1-9 are shown in Table 1.
[0046] Table 1 Reaction conditions and analysis results of Examples 1-9
[0047]
[0048] Examples 10-12
[0049] OCP was prepared using a microchannel reactor (1.0 mm inner diameter, 5 reaction modules in series, total liquid holding capacity 800 ml):
[0050] AA and peroxide with a mass ratio of 1:0.20 were efficiently and fully mixed by an SH-type static tubular mixer, and the mixed solution was directly pumped into the microchannel reactor at a volume flow rate V1 by a metering pump; at the same time, CDON was pumped into the microchannel reactor at a volume flow rate V2 by a high-temperature melt pump to mix and react with the mixture of AA and peroxide, the pump head temperature was 100°C, and the CDON pipeline was kept at 90°C;
[0051] The outlet of the microchannel reactor is connected to the feed of cyclododecanone by a loop, so that 15 wt% of the material is circulated in the microchannel reactor for reaction, and the loop insulation temperature is 90° C.
[0052] The inlet and outlet temperatures of the microchannel reactor are T1 and T2, respectively, the pressure is P, the residence time is t, and the sample is sampled for GC characterization to obtain the reaction conversion rate;
[0053] The sampled material was collected in a round-bottom flask and distilled at 160°C in an oil bath under reduced pressure (1 mbar) to remove excess CDON and other light components, other light components mainly being tert-butyl alcohol. The product OCP was distilled under reduced pressure (0.3 mbar) at an oil temperature of 220°C. The product was characterized by gas phase to obtain its purity and the reaction selectivity was calculated. The specific reaction conditions and analysis results of Examples 10-12 are shown in Table 2.
[0054] Table 2 Reaction conditions and analysis results of Examples 10-12
[0055]
[0056] Examples 13-18
[0057] OCP was prepared using a microchannel reactor (1.2 mm inner diameter, 6 reaction modules in series, total liquid holding capacity 1000 ml):
[0058] AA and peroxide with a mass ratio of 1:0.25 are efficiently and fully mixed by an SH-type static tubular mixer, and the mixed solution is pumped into the preheating premixer at a volume flow rate V1 by a metering pump, and then enters the microchannel reactor; at the same time, CDON is pumped into the microchannel reactor at a volume flow rate V2 by a high-temperature melt pump to mix and react with the mixture of AA and peroxide, the pump head temperature is 120°C, and the CDON pipeline is kept at 110°C;
[0059] The outlet of the microchannel reactor is connected to the feed of cyclododecanone by a loop, so that 20 wt% of the material is circulated in the microchannel reactor for reaction, and the loop insulation temperature is 110° C.;
[0060] The inlet and outlet temperatures of the microchannel reactor are T1 and T2, respectively, the pressure is P, the residence time is t, and the sample is sampled for GC characterization to obtain the reaction conversion rate;
[0061] The sampled material was collected in a round bottom flask and distilled at 160°C in an oil bath under reduced pressure (1 mbar) to remove excess CDON and other light components, other light components mainly being tert-butyl alcohol. The product OCP was distilled under reduced pressure (0.3 mbar) at an oil temperature of 220°C. The product was characterized by gas phase to obtain its purity and the reaction selectivity was calculated. The specific reaction conditions and analysis results of Examples 13-18 are shown in Table 3.
[0062] Table 3 Reaction conditions and analysis results of Examples 13-18
[0063]
[0064]
[0065] Comparative Examples 1-3
[0066] The reaction materials and conditions in Example 7 were followed, except that the microchannel reactor was replaced with a 250 ml reactor made of 316L material. After the feeding was completed, the pressure and temperature were maintained for the corresponding time, and the stirring speed was 400 r / min. The analysis results are shown in Table 4.
[0067] Table 4 Comparative Examples 1-3 Reaction conditions and analysis results
[0068]
[0069] It is easy to understand that the above embodiments are only examples for clear explanation and do not mean that the present invention is limited thereto. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from this are still within the protection scope of the present invention.
Claims
1. A method for synthesizing 2-(3-hydroxypropyl)cyclododecanone using a microchannel reactor, characterized in that: The following steps are involved: (1) pumping cyclododecanone, allyl alcohol and peroxide into a microchannel reactor, and reacting through a plurality of reaction modules connected in series in the microchannel reactor in sequence; (2) The material at the outlet of the microchannel reactor is subjected to reduced pressure distillation to obtain 2-(3-hydroxypropyl)cyclododecanone.
2. The method according to claim 1, characterized in that The peroxide in step (1) is selected from one or more of tert-butyl hydroperoxide, di-tert-butyl peroxide, hydrogen peroxide, peracetic acid, and benzoyl peroxide, preferably one or more of tert-butyl hydroperoxide and di-tert-butyl peroxide.
3. The method according to claim 1, characterized in that In step (1), the mass ratio of allyl alcohol to peroxide is 1:0.1-0.6, preferably 1:0.2-0.
3.
4. The method according to claim 1, characterized in that: The volume ratio of the feed flow rate of the cyclododecanone pumped into the microchannel reactor in step (1) to the total flow rate of allyl alcohol and peroxide is 2-20.
5. The method according to claim 1, characterized in that The cyclododecanone in step (1) is fed by a high-temperature melt pump, and the feeding temperature is 80-120°C, preferably 100-110°C.
6. The method according to claim 1, characterized in that The inner diameter of the microchannel reactor in step (1) is 0.5-5 mm, preferably 0.6-1.2 mm; and / or The total liquid holding volume in the microchannel reactor in step (1) is 300-1200 ml; and / or In step (1), a plurality of reaction modules are connected in series in the microchannel reactor, the number of which is 3-6.
7. The method according to claim 1, characterized in that The inlet and outlet temperatures of the microchannel reactor in step (1) are 170-120° C., preferably 160-140° C.; and / or The pressure of the microchannel reactor in step (1) is 0-4 MPa, preferably 2-3 MPa; and / or The total residence time of the material in the microchannel reactor in step (1) is 10-80 min, preferably 50-60 min.
8. The method according to claim 1, characterized in that: In step (1), the outlet of the microchannel reactor is connected to the feed of cyclododecanone by a loop, so that part of the material undergoes a cyclic reaction in the microchannel reactor; Preferably, the proportion of materials undergoing circulation reaction in the microchannel reactor is 10-20wt%.
9. The method according to claim 1, characterized in that: The reduced pressure distillation in step (2) has a temperature of 240-200° C., preferably 220-210° C., and a vacuum degree of 2-0.2 mbar, preferably 0.5-0.3 mbar.