A preparation method of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol

Abstract

The present invention relates to a preparation method of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and belongs to the technical field of organic chemistry. The preparation method of the present invention comprises the following steps: under a protective atmosphere, 1,2-dibromotetrafluoroethane is mixed with ethyl allyl ether in an organic solvent, and a free radical initiator is added to react to obtain an intermediate compound; the obtained intermediate compound is reacted with a reducing agent, and after the reaction is completed, the product is collected to obtain the 5-bromo-4,4,5,5-tetrafluoro-1-pentanol; the free radical initiator is a mixture of Cp2TiCl2 and iron powder. The preparation method improves the reaction yield, the initiator dosage is less and easier to handle, it is easier to carry out amplification transfer, the operation is simpler, and it has more industrial value. And after the initiator and the reducing agent are replaced and optimized by the technology of the present invention, the operation is simple, and the waste output is greatly reduced.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, and in particular to a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. Background Art

[0002] Photoresists are light-sensitive films that transfer images to a substrate. They form both negative and positive images. The photoresist is applied to a substrate to form a photoresist layer, which is then exposed to an excitation energy source, such as ultraviolet light, through a patterned photomask to form a latent image in the photoresist layer. The photomask has areas that are opaque to the excitation radiation and areas that are transparent, defining the image that is desired to be transferred to the underlying substrate. The latent image pattern in the resist layer is developed to produce a relief image.

[0003] 5-Bromo-4,4,5,5-tetrafluoro-1-pentanol is a fluorinated fatty alcohol and an important intermediate for the synthesis of photoresists and photoacid generators. Its structural formula is shown below:

[0004]

[0005] JP2022051549 reported that a target product was obtained by reacting allyl alcohol and tetrafluorodibromide through free radical addition, oxidative dehalogenation, and reduction. In the oxidative dehalogenation step, there is a byproduct in which the hydroxyl group is oxidized by the halogen and is not removed, resulting in low product yield and purity. The reaction process is as follows:

[0006]

[0007] It can be seen that the amount of free radical initiator used in the prior art is large, the free radical initiation reaction is not easy to control, the conversion rate and yield are unstable during multi-batch production, which makes it difficult to estimate the output in the later stage. In addition, the prior art has too many unit operations in the R&D and production process, and produces a lot of wastewater and solid waste in the production process. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, which uses 1,2-dibromotetrafluoroethane, which is readily available in the market, as a starting material, uses Cp2TiCl2 / Fe as a free radical initiator to initiate a reaction to generate an intermediate, and then uses safe and cheap vitamin C or sodium borohydride as a reducing agent for reduction to obtain 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. This preparation method improves the reaction yield, the amount of initiator used is less and easier to handle, it is easier to carry out amplification and transfer, the operation is simpler, and it has more industrial value. After replacing and optimizing the initiator and the reducing agent through the technology of the present invention, the operation is simple and the waste output is greatly reduced.

[0009] The present invention is achieved through the following technical solutions:

[0010] The first object of the present invention is to provide a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, comprising the following steps:

[0011] (1) Under a protective atmosphere, 1,2-dibromotetrafluoroethane and ethyl allyl ether are mixed in an organic solvent, and a free radical initiator is added to react to obtain an intermediate compound;

[0012] (2) reacting the obtained intermediate compound with a reducing agent, and after the reaction is completed, collecting the product to obtain the 5-bromo-4,4,5,5-tetrafluoro-1-pentanol;

[0013] In step (1), the free radical initiator is a mixture of Cp2TiCl2 and iron powder.

[0014] In one embodiment of the present invention, in step (1), the organic solvent is selected from one or more of anhydrous ethanol, N,N-dimethylformamide and ethylene glycol.

[0015] In one embodiment of the present invention, in one embodiment of the present invention, the molar ratio of Cp2TiCl2 to iron powder is 1:10~1:30.

[0016] In one embodiment of the present invention, in step (1), the molar ratio of the 1,2-dibromotetrafluoroethane to the Cp2TiCl2 in the free radical initiator is 1:0.02-0.03.

[0017] In one embodiment of the present invention, in step (1), the molar ratio of the 1,2-dibromotetrafluoroethane to the ethyl allyl ether is 1:1-10.

[0018] In one embodiment of the present invention, in step (1), the reaction conditions are 55°C to 65°C for 30 min to 4 h; preferably 58°C to 60°C.

[0019] In one embodiment of the present invention, in step (2), the reducing agent is selected from sodium borohydride and / or vitamin C.

[0020] In one embodiment of the present invention, in step (2), the molar ratio of the intermediate compound to the reducing agent is 1:1-10; preferably, the molar ratio of the intermediate compound to the reducing agent is 1:(0.8-8).

[0021] In one embodiment of the present invention, step (2) further comprises adding methanol or an acid-binding agent triethylamine to react; the sodium borohydride is added to the reaction together with methanol, and methanol is used to activate the sodium borohydride to generate a more reducible boric acid methanol ester intermediate; the acid-binding agent triethylamine is added to the reaction together with vitamin C to bind the bromide ions generated by the reaction.

[0022] In one embodiment of the present invention, the molar ratio of the intermediate compound to methanol is 1:1-10.

[0023] In one embodiment of the present invention, in step (2), the reaction temperature is -30°C to 30°C; and the reaction time is 18 h to 24 h.

[0024] In one embodiment of the present invention, after collecting the product, the process further comprises the step of purifying 5-bromo-4,4,5,5-tetrafluoro-1-pentanol by distillation under reduced pressure.

[0025] In one embodiment of the present invention, the scheme specifically includes the following steps:

[0026] (1) Add organic solvent, 1,2-dibromotetrafluoroethane, ethyl allyl ether, and iron powder under nitrogen protection, heat with external temperature, have strong reflux in the reactor, monitor the temperature of the reaction solution and slowly heat it up, keep the temperature to react, cool the reaction solution, filter to obtain 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution, and use it directly in the next reaction;

[0027] (2) Under nitrogen protection, a reducing agent is added to a reaction vessel to react with methanol or triethylamine, and then post-processed to obtain 5-bromo-4,4,5,5-tetrafluoro-1-pentanol.

[0028] The above technical solution of the present invention has the following advantages compared with the prior art:

[0029] The invention provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. The method adopts industrial raw materials 1,2-dibromotetrafluoroethane and ethyl allyl ether as starting raw materials and uses a relatively safe solvent for reaction to prepare 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. A higher reaction yield and a higher product purity are achieved. The process flow is simple to operate and there are no harsh reaction conditions, so the method is more likely to be used in industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein:

[0031] Figure 1 It is the H NMR spectrum of the product prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0032] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0033] The present invention provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. In the first step reaction, it is found that when Cp2TiCl2 / Fe is used to initiate the reaction, all intermediates can be generated, and when other initiators are used, a certain proportion of isomers will be generated.

[0034]

[0035] The reducing agents used in the second step reaction include sodium borohydride, vitamin C, lithium aluminum hydride and borane-tetrahydrofuran. It was found that the yields of sodium borohydride and vitamin C were relatively high; among them, vitamin C had a milder reaction, a higher yield, and was easier to handle. After the reaction was completed, it was only necessary to filter out the solids in the reaction and then directly carry out distillation purification.

[0036] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods, and the materials, reagents, etc. used are all available from commercial sources unless otherwise specified.

[0037] The CAS numbers of the reagents used in the present invention are shown in the table below:

[0038] Table 1

[0039] Example 1

[0040] This embodiment provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and the specific method is as follows:

[0041] Step 1: Under nitrogen protection, add 24 L of anhydrous ethanol, 6 kg of 1,2-dibromotetrafluoroethane, 2.33 kg of ethyl allyl ether, 115 g of dichlorobis(pentafluoropentane), and 388 g of iron powder to a 50 L reactor, raise the external temperature to 60°C, and strongly reflux the reaction until the internal temperature of the reaction solution reaches 58-60°C. Keep the reaction warm for 30 min, and monitor that there is no residual raw material by GC (the chromatographic column used is DB-1; this test is a central control test, and its main purpose is to detect the progress of the reaction). The reaction solution is cooled, and the reaction solution is filtered through diatomaceous earth to obtain a 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution, which is directly used in the next step of the reaction;

[0042] Step 2: Under nitrogen protection, add 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution to a 50 L reactor, cool to below -5°C, add 485 g of sodium borohydride, control the temperature to below -5°C, add 1 kg of methanol dropwise, keep warm for 18 h, monitor GC and see if there is any residual raw material, add 10 kg of water to the reaction solution, add 8 kg of dichloromethane to extract twice, combine the organic phases, wash twice with 8 kg of water, and concentrate to obtain 5242 g of crude 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and then simply distill under reduced pressure to obtain 4230 g of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, with a total yield of 76% for the two steps and a GC purity of 98%.

[0043] The obtained product was characterized by NMR. Figure 1 shown.

[0044] NMR data: 1 H NMR (400 MHz, Chloroform-d) δ 3.74 (t, J = 6.2 Hz, 2H), 2.22 (tt, J = 18.0, 8.6 Hz, 2H), 1.87 (dq, J = 12.3, 6.3 Hz, 2H). Example 2

[0045] This embodiment provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and the specific method is as follows:

[0046] Step 1: Under nitrogen protection, add 24 L of anhydrous ethanol, 6 kg of 1,2-dibromotetrafluoroethane, 2.33 kg of ethyl allyl ether, 115 g of dichlorobis(pentafluoropentane), and 388 g of iron powder to a 50 L reactor, raise the external temperature to 60°C, and strongly reflux the reaction until the internal temperature of the reaction solution reaches 58-60°C. Keep the reaction warm for 30 min. After GC monitoring, no raw materials remain. The reaction solution is cooled, and the reaction solution is filtered through diatomaceous earth to obtain a 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution, which is directly used in the next step reaction;

[0047] Step 2: Under nitrogen protection, add 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution to a 50 L reactor, cool to 15°C-25°C, add 2.4 kg triethylamine and 8134 g vitamin C, keep warm for 24 h, monitor by GC to see if there is no residual raw material, filter the reaction solution to remove the solid in the reaction, wash the filtrate twice with water to obtain a crude product of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and then perform simple reduced pressure distillation to obtain 4692 g of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol. The total yield of the two steps is 85%, and the GC purity is 99.5%. Comparative Example 1

[0048] This comparative example provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and the specific method is as follows:

[0049] The steps are the same as in Example 1;

[0050] Step 2: Under nitrogen protection, add 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution to a 50 L reactor, cool to below -5°C, slowly add 485 g of lithium aluminum hydride solid in batches, keep warm for 18 h, monitor GC and no raw material remains, add 10 kg of water to the reaction solution, add 8 kg of dichloromethane to extract twice, combine the organic phases, wash twice with 8 kg of water, and concentrate to obtain 3356 g of crude 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and then simply distill under reduced pressure to obtain 1224 g of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, with a total yield of 22% for the two steps and a GC purity of 97%. Comparative Example 2

[0051] This comparative example provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and the specific method is as follows:

[0052] The steps are the same as in Example 1;

[0053] Step 2: Under nitrogen protection, add 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution to a 50 L reactor, cool to below -5°C, slowly add 13 L borane tetrahydrofuran, keep warm for 18 h, monitor GC and see if there is no residual raw material, add 10 kg water to the reaction solution, add 8 kg dichloromethane to extract twice, combine the organic phases, wash twice with 8 kg water, and concentrate to obtain 1225 g of crude 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and then simply distill under reduced pressure to obtain 536 g of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, with a total yield of 10% for the two steps and a GC purity of 97%. Comparative Example 3

[0054] This comparative example provides a method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and the specific method is as follows:

[0055] Step 1: Under nitrogen protection, add 24 L of anhydrous ethanol, 6 kg of 1,2-dibromotetrafluoroethane, 2.33 kg of ethyl allyl ether, 115 g of dichlorobis(pentafluoropentane), and 450 g of zinc powder to a 50 L reactor, raise the external temperature to 60°C, and strongly reflux the reaction until the internal temperature of the reaction solution reaches 58-60°C. Keep the reaction warm for 30 min. No raw material remains under GC monitoring. The reaction solution is cooled, filtered through diatomaceous earth, and 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution is obtained, which is directly used in the next step reaction;

[0056] Step 2: Under nitrogen protection, add 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane ethanol solution to a 50 L reactor, cool to below -5°C, add 485 g of sodium borohydride, control the temperature to below -5°C, add 1 kg of methanol dropwise, keep warm for 18 h, monitor GC and see if there is no residual raw material, add 10 kg of water to the reaction solution, add 8 kg of dichloromethane to extract twice, combine the organic phases, wash twice with 8 kg of water, and concentrate to obtain 3566 g of crude 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, and then simply distill under reduced pressure to obtain 1233 g of 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, with a total yield of 22% for the two steps and a GC purity of 96%.

[0057] Obviously, the above embodiments are merely examples for clear explanation and are not intended to limit the implementation methods. For those skilled in the art, 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 these are still within the protection scope of the invention.

Claims

1. A method for preparing 5-bromo-4,4,5,5-tetrafluoro-1-pentanol, characterized in that: The following steps are involved: (1) Under a protective atmosphere, 1,2-dibromotetrafluoroethane and ethyl allyl ether are mixed in an organic solvent, and a free radical initiator is added to react to obtain an intermediate compound; the intermediate compound is 1,4-dibromo-5-ethoxy-1,1,2,2-tetrafluoropentane; (2) reacting the obtained intermediate compound with a reducing agent, and after the reaction is completed, collecting the product to obtain the 5-bromo-4,4,5,5-tetrafluoro-1-pentanol; In step (1), the free radical initiator is a mixture of Cp2TiCl2 and iron powder; In step (2), the reducing agent is selected from sodium borohydride and / or vitamin C.

2. The preparation method according to claim 1, characterized in that: In step (1), the organic solvent is selected from one or more of anhydrous ethanol, N,N-dimethylformamide and ethylene glycol.

3. The preparation method according to claim 1, characterized in that: The molar ratio of Cp2TiCl2 to iron powder is 1:10-1:

30.

4. The preparation method according to claim 1, characterized in that: In step (1), the molar ratio of the 1,2-dibromotetrafluoroethane to the Cp2TiCl2 in the free radical initiator is 1:0.02-0.

03.

5. The preparation method according to claim 1, characterized in that: In step (1), the molar ratio of the 1,2-dibromotetrafluoroethane to the ethyl allyl ether is 1:1-10.

6. The preparation method according to claim 1, characterized in that: In step (1), the reaction conditions are 55°C to 65°C for 30 min to 4 h.

7. The preparation method according to claim 1, characterized in that: In step (2), the molar ratio of the intermediate compound to the reducing agent is 1:1-10.

8. The preparation method according to claim 1, characterized in that: In step (2), the reaction temperature is -30°C to 30°C; And / or, the reaction time is 18 h to 24 h.

9. The preparation method according to claim 1, characterized in that: After the product is collected, the method further comprises the step of purifying 5-bromo-4,4,5,5-tetrafluoro-1-pentanol by distillation under reduced pressure.

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