A semi-fluorocarbon for clearing emulsified silicone oil fillings, and a preparation method and application thereof

Abstract

The application discloses a kind of semi-fluorocarbon for removing emulsified silicone oil filling and its preparation method and application, comprising, olefin and perfluoroalkyl iodine are dissolved in acetonitrile, initiator is added and reacted under light source, to obtain fluorine-containing iodoalkane;Fluorine-containing iodoalkane is dissolved in isopropyl alcohol, and after adding reducing agent and heating reaction, it is washed to obtain semi-fluorocarbon with the structure of CF3 (CF2) 3 (CH2) 4CH3, named semi-fluorinated nonafluorononane;Wherein, the molar ratio of the olefin and perfluoroalkyl iodine is 1:1-1.4, and the initiator is cuprous chloride.The application controls the proportion of raw materials, carries out reaction under the condition of suitable initiator, simultaneously preferably zinc powder is used as reducing agent, effectively improves product purity and product yield, and operation process is simple, safe, and CF3 (CF2) 3 (CH2) 4CH3 prepared has not only good stability, but also good biocompatibility, no cytotoxicity, no skin sensitization, no acute eye irritation, can dissolve or wrap emulsified silicone oil droplets, and play a great role in the removal of emulsified silicone oil.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic chemistry, and particularly relates to a semifluorinated alkane for removing emulsified silicone oil filling, a preparation method and application thereof. BACKGROUND

[0002] Due to the outermost electron arrangement, the maximum nuclear charge number in the same period, the characteristics of large electronegativity and small atomic radius, the hydrogen atoms in organic compounds can be mostly replaced by fluorine atoms to form a large number of organic fluorine compounds. After introducing fluorine into organic compounds, due to the characteristics of fluorine element, significant changes in physical and chemical properties often occur, thereby being applied to multiple fields. Currently, large-scale production of organic fluorine products includes small-molecule fluorine-containing compounds such as fluorine-containing refrigerants, blowing agents, extinguishing agents, high-molecular fluorine-containing compounds such as fluoroplastics and fluororubber, and fluorine-containing pesticides and pharmaceutical intermediates.

[0003] The semifluorinated alkane has a molecular formula of CF3(CF2) n (CH2) m CH3, is a compound in which part of hydrogen atoms in an alkane molecule are replaced by fluorine atoms, is a very economically valuable intermediate, has certain chemical activity, can derive many fluorine-containing organic compounds, can be used as a reaction intermediate, is a basic material for producing fluorine-containing fine chemicals and high-molecular materials, can meet special purposes and special purposes of top industries that cannot be replaced by general organic compounds, and has a very broad development prospect.

[0004] However, the existing fluorine-containing alkane is usually prepared by using fluorine-containing olefins as raw materials, reacting with hydrogen, and through reduction or hydrogenation, such as a method of reducing fluorine-containing olefins at room temperature by using a palladium catalyst, or a method of adding hydrogen fluoride to halogenated olefins by using a hydrogen fluoride-quaternary ammonium fluoride-solvent hydrogen fluoride system to prepare corresponding fluorine-containing alkanes, such as a method of reducing CF3CF=CF2 by using a palladium catalyst supported on BaSO4, activated carbon and the like in a liquid phase reaction. However, in these methods, the reaction conditions are relatively harsh, the environment for preparation is required to be relatively high, and in order to improve the selectivity of the fluorine-containing alkane as the target product, the reaction speed needs to be slowed down, and it is difficult to realize high-efficiency production on an industrial scale.

[0005] At present, the method for synthesizing semifluorinated alkane in the prior art is an addition reaction of olefins and perfluoroalkyl iodine catalyzed by transition metals to generate iodides, and then the iodides are reduced and deiodinated to generate semifluorinated alkane. The temperature is relatively high, and the product may contain impurities such as metal ion residues. At present, the most commonly used method is a sulfination dehalogenation reaction to generate iodides, and then the iodides are also reduced and deiodinated to generate semifluorinated alkane. The literature mainly reports a process for synthesizing perfluoroalkane, and the synthesis of semifluorinated nonafluorononane is less researched and reported due to reasons such as great difficulty in synthesis, difficulty in process control, high content of by-products, and poor composition distribution of the product.

[0006] Therefore, how to obtain a semi-fluorinated alkane preparation method with mild reaction conditions and suitable for mass industrial production has become a major problem to be solved for many manufacturers in the industry. SUMMARY

[0007] This section is intended to summarize some aspects of the embodiments of the present application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of the specification to avoid obscuring the purpose of this section, the abstract and the title, and such simplifications or omissions cannot be used to limit the scope of the present application.

[0008] In view of the above and / or problems existing in the prior art, the present application is proposed.

[0009] Therefore, the purpose of the present application is to overcome the deficiencies in the prior art and provide a semi-fluorinated alkane preparation method.

[0010] To solve the above technical problems, the present application provides the following technical solutions: olefins and perfluoroalkyl iodine are dissolved in acetonitrile, an initiator is added and reacted under a light source to obtain fluorine-containing iodoalkane;

[0011] The fluorine-containing iodoalkane is dissolved in isopropyl alcohol, a reducing agent is added and heated to react, and then washed to obtain semi-fluorinated alkane with the structure CF3(CF2)3(CH2)4CH3, which is named semi-fluorinated nonafluorononane;

[0012] The molar ratio of the olefins to the perfluoroalkyl iodine is 1:1-1.4, and the initiator is cuprous chloride.

[0013] As a preferred scheme of the semi-fluorinated alkane preparation method of the present application, the equivalent ratio of the olefins to the initiator is 1:0.2-0.5.

[0014] As a preferred scheme of the semi-fluorinated alkane preparation method of the present application, the perfluoroalkyl iodine is perfluorobutyl iodine.

[0015] As a preferred scheme of the semi-fluorinated alkane preparation method of the present application, the molar ratio of the fluorine-containing iodoalkane to the reducing agent is 1:1-1.5.

[0016] As a preferred scheme of the semi-fluorinated alkane preparation method of the present application, the reducing agent includes one or two of zinc powder, magnesium powder or iron powder.

[0017] As a preferred scheme of the semi-fluorinated alkane preparation method of the present application, the temperature of the heating reaction is 20-80℃.

[0018] As a preferred scheme of the preparation method of the semifluorinated hydrocarbon, the heating reaction comprises: after heating, standing until the material is completely separated into two phases, taking out the upper layer material, adding pure water and hydrochloric acid, and stirring until the material is clear and transparent.

[0019] After the material is separated, the lower layer liquid is taken out, which is the semifluorinated hydrocarbon.

[0020] Another object of the present application is to overcome the deficiencies in the prior art and provide a semifluorinated hydrocarbon for removing emulsified silicone oil filling.

[0021] Still another object of the present application is to overcome the deficiencies in the prior art and provide an application of the semifluorinated hydrocarbon in removing emulsified silicone oil filling.

[0022] To solve the above technical problems, the present application provides the following technical scheme: the semifluorinated hydrocarbon is mixed with the emulsified silicone oil filling to achieve the removal effect, wherein the volume ratio of the semifluorinated hydrocarbon to the emulsified silicone oil filling is 1:1.4-1.6.

[0023] As a preferred scheme of the application of the semifluorinated hydrocarbon in removing emulsified silicone oil filling, the removal rate of the semifluorinated hydrocarbon to the emulsified silicone oil filling is 100%.

[0024] The present application has the following beneficial effects:

[0025] The present application effectively improves the product purity and product yield by controlling the proportion of raw materials, performing the reaction under appropriate initiator conditions, and preferably using zinc powder as a reducing agent. The operation process is simple and safe, which provides a direction for batch industrial production of semifluorinated hydrocarbons. The prepared CF3(CF2)3(CH2)4CH3 not only has good stability, but also has good biocompatibility, no cytotoxicity, no skin sensitization, and no acute eye irritation. The emulsified silicone oil droplets can be dissolved or wrapped, which plays a great role in the removal of emulsified silicone oil in intraocular filling. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed in the embodiment description. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor. Among them:

[0027] Figure 1 The fluorine nuclear magnetic resonance spectrum of the fluorine-containing alkane compound prepared in Example 1 of the present application.

[0028] Figure 2 The hydrogen nuclear magnetic resonance spectrum of the fluorine-containing alkane compound prepared in Example 1 of the present application.

[0029] Figure 3 The physical diagram of the silicone oil injected into physiological saline used in the present application.

[0030] Figure 4 The schematic diagram of the emulsified silicone oil in the present application.

[0031] Figure 5 The standing diagram of the emulsified silicone oil prepared in Example 1 of the present application after extraction with semifluorinated alkanes. DETAILED DESCRIPTION

[0032] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the description and examples.

[0033] In the following description, a large number of specific details are set forth in order to facilitate a thorough understanding of the present application, but the present application can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0034] Secondly, the "one embodiment" or "embodiment" referred to herein means that the specific features, structures or characteristics can be included in at least one implementation of the present application. "In one embodiment" appearing in different places in the specification does not mean the same embodiment, nor is it an embodiment that is independent of or selected from other embodiments.

[0035] The olefin used in the present application is n-pentene;

[0036] The silicone oil used in the present application is Bausch & Lomb silicone oil;

[0037] The preparation method of the emulsified silicone oil used in the present application is as follows:

[0038] Take 1 mL of silicone oil and 4 mL of physiological saline, mix and ultrasonic at 60℃ for 4h to obtain the emulsified silicone oil.

[0039] The present application determines the residue of silicone oil by GC-MS technology;

[0040] The raw materials used in the present application are commercially available in the art without special instructions.

[0041] Example 1

[0042] The present embodiment provides a preparation method of semifluorinated alkanes, specifically:

[0043] 1) n-pentene 1.0 mol and perfluorobutyl iodine 1.2 mol are dissolved in acetonitrile, 0.2 mol of cuprous chloride is added, and the reaction is carried out under 365nm LED light source for 24h to obtain fluorine-containing iodinated alkane;

[0044] 2) Fluoroiodoalkane 1.0 mol was dissolved in isopropyl alcohol, zinc powder 1.2 mol was added, and after reaction at 50°C, the material was left to stand until it was completely separated into two phases, the upper layer material was taken out, 20 ml of pure water was added to produce a precipitate, 5 ml of hydrochloric acid was added and stirred until the material was clear and transparent;

[0045] 3) After the material was separated, the lower layer liquid was taken out to obtain the product semifluorinated nonafluorononane.

[0046] Example 2

[0047] The difference between this example and Example 1 is that the zinc powder in step 2) is replaced with magnesium powder.

[0048] The rest of the preparation method is the same as that of Example 1, and the semifluorinated nonafluorononane of this example is obtained.

[0049] Example 3

[0050] The difference between this example and Example 1 is that the amount of zinc powder in step 2) is adjusted to 1.3 mol.

[0051] The rest of the preparation method is the same as that of Example 1, and the semifluorinated nonafluorononane of this example is obtained.

[0052] The purity and yield of the semifluorinated nonafluorononane prepared in Examples 1-5 were tested, and the results are shown in Table 1.

[0053] Table 1

[0054]

[0055]

[0056] As can be seen from Table 1, the purity of the semifluorinated alkane product prepared by the present application is greater than 96%, and the yield is greater than 83%, especially when zinc powder is used as the reducing agent and the molar ratio of fluoroiodoalkane to zinc powder is 1:1.2, the purity and yield of the product prepared are the highest. This is because magnesium powder is more likely to cause molecular self-coupling rather than two-molecular coupling, and it can also reduce iodinated fluorinated alkane, but it results in poor product purity and low yield. Zinc powder is relatively safe and mild, and it can also fully reduce fluoroiodoalkane, while effectively absorbing by-products such as zinc iodide, preventing them from competing with the product, thereby improving the purity and yield of the product.

[0057] Comparative Example 1

[0058] Comparative Example 1 is based on Example 1, and the difference between Comparative Example 1 and Example 1 is that the amount of perfluorobutyl iodide in step 1) is adjusted to 1 mol.

[0059] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 1.

[0060] Comparative Example 2

[0061] Comparative Example 2 is based on Example 1, and the difference between Comparative Example 2 and Example 1 is that the amount of perfluorobutyl iodide in step 1) is adjusted to 1.1 mol.

[0062] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 2.

[0063] Comparative Example 3

[0064] Comparative Example 3 is based on Example 1, and the difference between Comparative Example 3 and Example 1 is that the amount of perfluorobutyl iodide in step 1) is adjusted to 1.3 mol.

[0065] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 3.

[0066] Comparative Example 4

[0067] Comparative Example 4 is based on Example 1, and the difference between Comparative Example 4 and Example 1 is that the amount of cuprous chloride in step 1) is adjusted to 0.1 mol.

[0068] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 4.

[0069] Comparative Example 5

[0070] Comparative Example 5 is based on Example 1, and the difference between Comparative Example 5 and Example 1 is that the amount of cuprous chloride in step 1) is adjusted to 0.3 mol.

[0071] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 5.

[0072] Comparative Example 6

[0073] Comparative Example 6 is based on Example 1, and the difference between Comparative Example 6 and Example 1 is that the zinc powder in step 2) is replaced with magnesium powder.

[0074] The remaining preparation method is the same as that of Example 1 to obtain the semifluorinated nonafluorononane of Comparative Example 6.

[0075] Comparative Example 7

[0076] Comparative Example 7 is based on Example 1, and the difference between Comparative Example 7 and Example 1 is that the amount of zinc powder in step 2) is adjusted to 1.1 mol.

[0077] The remaining preparation method is the same as that of Example 1, and the semi-fluorinated nonafluorononane of Comparative Example 7 is obtained.

[0078] Comparative Example 8

[0079] Comparative Example 8 is based on Example 1, and the difference between Comparative Example 8 and Example 1 is that the reaction temperature in step 2) is adjusted to 40°C.

[0080] The remaining preparation method is the same as that of Example 1, and the semi-fluorinated nonafluorononane of Comparative Example 8 is obtained.

[0081] Comparative Example 9

[0082] Comparative Example 9 is based on Example 1, and the difference between Comparative Example 9 and Example 1 is that the reaction temperature in step 2) is adjusted to 60°C.

[0083] The remaining preparation method is the same as that of Example 1, and the semi-fluorinated nonafluorononane of Comparative Example 9 is obtained.

[0084] The purity and yield of the semi-fluorinated nonafluorononane obtained in Comparative Examples 1 to 9 are tested, and compared with Example 1, and the results are shown in Table 2.

[0085] Table 2

[0086]

[0087] According to Table 2, it can be seen that as the amount of perfluorobutyl iodide increases, the purity and yield of the product increase, but when the amount of perfluorobutyl iodide exceeds 1.2 mol, the purity and yield of the product begin to decrease, because the addition of more perfluorobutyl iodide is not conducive to the forward reaction, and thus the purity and yield decrease. When the amount of cuprous chloride is adjusted, less cuprous chloride is not enough to initiate the reaction, and when 0.3 mol of cuprous chloride is added, the purity and yield of the reaction are not as good as those of 0.2 mol of cuprous chloride, because the addition of too much initiator promotes the reverse reaction, which is contrary to the high yield and purity of the reaction.

[0088] When iron powder is used as the reducing agent, the purity and yield of the product decrease, because the activity of iron powder is not as good as that of zinc powder, and the amount of reduction is relatively less than that of zinc powder, and the effect is poor. When the amount of zinc powder is too small, the yield of the product also decreases, because the fluorine-containing iodinated alkane is not fully reduced. When the reaction temperature decreases, the yield decreases, because the reaction activity is poor at too low a temperature, and the purity and yield of the product are relatively poor at too high a temperature because the side reaction increases.

[0089] In the conditions of embodiment 1, when perfluorobutyl iodide is used as raw material, zinc powder is used as reducing agent, and the molar ratio of fluorine-containing iodoalkane to zinc powder is 1:1.2, the product has the highest purity and yield, because perfluorobutyl iodide is not easy to lose during feeding and reaction, and it is easier to participate in the reaction. Zinc powder is more stable than magnesium powder and iron powder, and has the highest yield. The molar ratio of fluorine-containing iodoalkane to zinc powder is 1:1.2, which is the best. If the amount is too small, the reaction will not be sufficient. If the amount is too large, the yield will not be improved, and the reaction effect is the best at this time.

[0090] Comparative example 10

[0091] Comparative example 10 is based on embodiment 1. The difference between comparative example 10 and embodiment 1 is that sodium dithionite is used instead of cuprous chloride in step 1).

[0092] The rest of the preparation method is the same as that of embodiment 1, and semi-fluorinated nonafluorononane of comparative example 10 is obtained.

[0093] Comparative example 11

[0094] Comparative example 11 is based on embodiment 1. The difference between comparative example 11 and embodiment 1 is that thiourea dioxide is used instead of cuprous chloride in step 1).

[0095] The rest of the preparation method is the same as that of embodiment 1, and semi-fluorinated nonafluorononane of comparative example 11 is obtained.

[0096] The purity and yield of semi-fluorinated nonafluorononane obtained in comparative examples 10-11 are tested and compared with embodiment 1, and the results are shown in Table 3.

[0097] Table 3

[0098]

[0099]

[0100] As can be seen from Table 3, only when cuprous chloride is used as initiator, the product has the highest purity and yield, because sodium dithionite and thiourea dioxide as thermal initiator require higher reaction temperature, and need to be used in excess to achieve better results. Therefore, the present technical solution is more mild and suitable for large-scale industrial production.

[0101] Embodiment 4

[0102] The present embodiment provides an application of semi-fluorinated nonafluorononane in removing emulsified silicone oil, specifically:

[0103] The semi-fluorinated nonafluorononane and the emulsified silicone oil are mixed and shaken for 2 minutes at a volume ratio of 1:1.4, and then left to stand for 4 hours.

[0104] According to the attached Figure 5 It can be seen that over time, the solution forms a stable clear two-phase solution, the content of silicon in the water phase slowly decreases until none, and part of the solution of the semifluorinated nonafluorononane is detected to find that the content of silicon further increases. This is because the semifluorinated nonafluorononane extracts the emulsified silicone oil, so that the emulsified silicone oil is completely dissolved and wrapped by the semifluorinated nonafluorononane, and the semifluorinated nonafluorononane has good solubility, thereby facilitating the extraction of the emulsified silicone oil from the water phase into the semifluorinated nonafluorononane and being completely removed.

[0105] Comparative Example 12

[0106] Comparative Example 12 is used to explore the influence of changing the volume ratio of semifluorinated nonafluorononane and emulsified silicone oil on the removal effect of emulsified silicone oil, specifically:

[0107] The volume ratio of semifluorinated nonafluorononane and emulsified silicone oil is adjusted to 1:1.3, 1.5, and 1.6 respectively, and the performance parameters of the mixed solution are determined. The results are shown in Table 4.

[0108] Table 4

[0109]

[0110] According to Table 4, it can be seen that when the volume ratio of emulsified silicone oil decreases, the removal effect of emulsified silicone oil shows a slow increasing trend. When the volume of emulsified silicone oil increases, the time for removing silicone oil also increases relatively. When the volume ratio of semifluorinated nonafluorononane and emulsified silicone oil is 1:1.3, although the emulsified silicone oil is also completely removed, the required standing time is still 4h. Then we increase the volume of emulsified silicone oil to explore the maximum volume of emulsified silicone oil that can be removed by the same volume of semifluorinated nonafluorononane in 4h. It is found that when the volume ratio of semifluorinated nonafluorononane and emulsified silicone oil is 1:1.4, the removal rate of silicone oil is also 100%. That is, under this ratio, the removal effect of emulsified silicone oil and the required time are both optimal.

[0111] Comparative Example 13

[0112] Comparative Example 13 provides a method of flushing residual emulsified silicone oil in the eye with balanced salt solution.

[0113] Comparative Example 14

[0114] Comparative Example 14 provides a method of flushing residual emulsified silicone oil in the eye with air-balanced salt solution exchange.

[0115] Comparative Examples 13-14 test the residual situation after removing emulsified silicone oil in the eye and are compared with Example 1. The results are shown in Table 5.

[0116] Table 5

[0117]

[0118] As can be seen from Table 5, flushing with balanced salt solution and air-balanced salt solution leaves some emulsified silicone oil, because these two methods are essentially rinsing the emulsified silicone oil, taking it away by the flowing liquid, but cannot completely remove the emulsified silicone oil adhering to the skin in the eye. The well-prepared semifluorinated nonafluorononane of Example 1 can well remove the emulsified silicone oil in the eye, which is of great significance to the ophthalmic medical field.

[0119] It should be noted that the above examples are only used to illustrate the technical solutions of the present application but not limit the present application. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalently replaced without departing from the spirit and scope of the present application, and all modifications and equivalent replacements should be covered in the scope of the claims of the present application.

Claims

1. A process for the preparation of semifluorinated hydrocarbons for the removal of emulsified silicone oil fillings, characterized in that: The method comprises the steps of: The olefin and the perfluoroalkyl iodine are dissolved in acetonitrile, an initiator is added, and the reaction is carried out under a light source to obtain fluorine-containing iodoalkane; The fluorine-containing iodoalkane is dissolved in isopropyl alcohol, a reducing agent is added, and the reaction is carried out after heating and cleaning treatment to obtain semifluoroalkane with the structure of CF3(CF2)3(CH2)4CH3, which is named semifluorinated nonafluorononane; The molar ratio of the olefin to the perfluoroalkyl iodine is 1:1.2, and the initiator is cuprous chloride; The equivalent ratio of the olefin to the initiator is 1:0.2; The molar ratio of the fluorine-containing iodoalkane to the reducing agent is 1:1.2; The reducing agent is zinc powder; The temperature of the heating reaction is 50℃.

2. The method of claim 1, wherein: The perfluoroalkyl iodine is perfluorobutyl iodine.

3. The method of claim 1, wherein: The heating reaction comprises the following steps: after heating, the material is left to stand until it is completely separated into two phases, the upper layer of the material is taken out, pure water and hydrochloric acid are added, and the material is stirred until it is clear and transparent; After the material is separated, the lower layer of the liquid is taken out, which is semifluoroalkane.

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