A method for synthesizing a tetrafluoro-substituted bromine-containing alkyl alcohol

Abstract

The application provides a synthesis method of a tetrafluoro-substituted bromine-containing alkyl alcohol, which comprises the following steps: taking a compound shown in formula II as raw material, and reacting with 1,2-dibromotetrafluoroethane under a free radical initiation system to obtain a tetrafluoro-substituted bromine-containing alkyl alcohol shown in formula I, wherein n in the formula I and the formula II represents a positive integer of 1-4, R in the formula II represents one of hydrogen, deuterium, C1-C6 alkyl or C1-C6 acyl; and the free radical initiation system contains a free radical initiator which is composed of persulfate and formate. The synthesis method has the characteristics of low material cost, high overall yield, low wastewater pollution, high production safety and low metal residue.

Description

Technical Field

[0001] This patent relates to the field of organic synthesis technology of fluorine-containing compounds, and in particular to a method for synthesizing tetrafluoro-substituted bromoalkyl alcohols. Background Technology

[0002] Fluorine-containing compounds are widely used in the pharmaceutical and photoresist fields due to their unique physiological, pharmaceutical, and photophysical properties. Small-molecule tetrafluorosubstituted bromoalkyl alcohols, as an important intermediate, have significant application value in the industry.

[0003] Small molecule tetrafluorosubstituted bromoalkyl alcohols with no more than eight carbon atoms contain chemically reactive bromine substituents and alcohol hydroxyl substituents, but lack a benzene ring structure for reaction localization, making their synthesis quite complicated.

[0004] In existing technologies, some reports describe the use of iodine-substituted tetrafluorobutane as one of the starting materials to prepare these compounds through a four-step reaction involving carboxyl substitution, decarboxylation, acylation, and reduction. However, the overall yield is low, the cost of using iodine-substituted raw materials is high, the use of thionyl chloride as a reagent generates large amounts of wastewater with severe pollution, and the use of sodium borohydride as an explosive reagent carries low safety. Other reports describe the use of iodine-substituted tetrafluoroethane as one of the starting materials to prepare these compounds through a three-step reaction involving addition, hydrogenation, and reduction. However, the cost of using iodine-substituted raw materials is high, and the use of palladium on carbon for catalytic hydrogenation is not only costly but also carries high risks, low safety, and numerous byproducts. Still others report the use of inexpensive bromine-substituted tetrafluoroethane as one of the starting materials to prepare these compounds through a two-step reaction involving addition and reductive dehalogenation. However, the use of titanium-containing reagents as addition agents leads to titanium metal residues in these compounds, which are difficult to remove. Reports indicate that this type of compound is prepared by using inexpensive bromine-substituted tetrafluoroethane as one of the starting materials, followed by a two-step reaction of addition and reduction dehalogenation. However, the reduction dehalogenation using sodium borohydride, a readily explosive reagent, poses a safety risk.

[0005] Therefore, existing technologies can only solve some of the technical problems, and there is a lack of a synthesis method that can comprehensively solve the technical problems of high material costs, low overall yield, high wastewater pollution, low production safety, and high metal residue. Summary of the Invention

[0006] To address the aforementioned technical problems in the prior art, this invention provides a method for synthesizing tetrafluoro-substituted bromoalkyl alcohols, which features low material costs, high overall yield, low wastewater pollution, high production safety, and low metal residue.

[0007] On one hand, the present invention provides a method for synthesizing a tetrafluoro-substituted bromoalkyl alcohol, using the compound shown in Formula II as a starting material, reacting it with 1,2-dibromotetrafluoroethane in a free radical initiation system to obtain a tetrafluoro-substituted bromoalkyl alcohol as shown in Formula I, wherein n in Formula I and Formula II represents a positive integer from 1 to 4, and R in Formula II represents one of hydrogen, deuterium, C1-C6 alkyl or C1-C6 acyl; the free radical initiation system contains a free radical initiator, which is composed of persulfate and formate; .

[0008] The term C1 means that there is one carbon atom, the term C6 means that there are six carbon atoms, and the term C1-C6 means that there are one to six carbon atoms, including two, three, four or five. The alkyl group in C1-C6 refers to an alkyl substituent with one to six carbon atoms, and the acyl group in C1-C6 refers to an acyl substituent with one to six carbon atoms.

[0009] In a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the C1-C6 alkyl groups are selected from methyl, ethyl, propyl, butyl, pentyl, or hexyl, and the C1-C6 acyl groups are selected from formyl, acetyl, propionyl, butyryl, valerate, or hexanoyl. The alkyl substituents of the present invention include isomers, for example, but not limited to, propyl including n-propyl and isopropyl, butyl including n-butyl, isobutyl, and tert-butyl, and propionyl including n-propylacyl and isopropylacyl.

[0010] As a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, Formula II represents one of the compounds with the following structure:

[0011]

[0012]

[0013]

[0014] ;

[0015] Formula I represents one of the compounds with the following structure:

[0016] .

[0017] As a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the persulfate is selected from one or more of the group consisting of ammonium persulfate, sodium persulfate and potassium persulfate, and the formate is selected from one or more of the group consisting of ammonium formate, sodium formate and potassium formate.

[0018] It is understood that choosing ammonium, sodium, or potassium ions as the cation for persulfates and formates is a preferred option, but other cations are also within the scope of this invention, provided that the metal residue caused by other cations is low. For example, and without limitation, other cations include quaternary ammonium ions. It is generally believed that organic or inorganic reagents containing only sodium or potassium have low metal residues, while those containing other metal elements, such as precious or heavy metals, have high metal residues. The metal elements mentioned in this invention can exist in ionic form, such as sodium or potassium ions, or in other forms, such as some elements in a catalyst existing in a coordinated form, existing as elements or compounds, or having their specific form changed after the reaction of some reagents. It is understood that high and low residues are relative, but not absolute. Generally, the metal content of sodium and potassium is required to be controlled below 10 ppm (10000 ppb), while the content of other metal elements is required to be controlled below 20 ppb, a difference of 500 times. Here, ppm refers to parts per million, and ppb refers to parts per billion. Therefore, when the residual amount of sodium in the product is 1 ppm, the residual amount of sodium is considered low, while when the residual amount of other metals such as titanium in the product is 1 ppm, the residual amount of titanium is considered high.

[0019] Existing technologies use distillation to remove most metal elements. When the controlled content upper limit is high, such as for potassium and sodium, the residual potassium and sodium in the distillation product already meet the content control requirements. Therefore, distillation is considered effective for removing potassium and sodium metal residues. When the controlled content upper limit is low, such as for metal elements other than potassium and sodium, although distillation can still remove most of the metal elements, the residual metal in the distillation product does not meet the corresponding content control requirements due to the lower control upper limit. Therefore, distillation is ineffective or has low efficiency in removing these metals. Those skilled in the art will understand that once reagents containing metal elements other than potassium or sodium are added to the reaction system, the efficiency of distillation in removing metal residues is low or ineffective. Currently, there is a lack of effective, simple, and easy-to-implement alternative methods for removing metal residues.

[0020] The persulfate and formate described in this invention are not limited in state; they can be powders or lumps, contain water of crystallization or not, contain solvents to form solvent complexes or not, and can be adsorbed onto a support to improve the initiation effect or not. The support described in this invention refers to a support that can improve the dispersion effect of the free radical initiator, exemplified but not limited to, such as carbon powder or silica.

[0021] As a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the molar ratio of Formula II to the persulfate is 1:2.2-5, and the molar ratio of Formula II to the formate is 1:1.7-5.

[0022] As a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the molar ratio of Formula II to 1,2-dibromotetrafluoroethane is 1:1-5.

[0023] The molar ratio of Formula II to other substances refers to the molar ratio of the compound represented by Formula II to other substances.

[0024] In a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the free radical initiation system contains an organic solvent, which contains one or more of the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,4-dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran. The organic solvent can be a single solvent or a mixture of two or more solvents, and the proportions of the components in the mixture are not limited. The organic solvent may contain water, but the water content shall not exceed the volume of the organic solvent. It is understood that, in addition to the organic solvents in the preferred embodiment described above, other solvents can be selected in the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention. For example, but not limited to, aromatic solvents such as toluene or xylene, alkane solvents such as n-hexane or cyclohexane, and alcohol solvents such as propanol can also be used.

[0025] In a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the reaction temperature of the synthesis method is 25-80 degrees Celsius. More preferably, the reaction temperature is 30-70 degrees Celsius. Even more preferably, the reaction temperature is 30-60 degrees Celsius. Even more preferably, the reaction temperature is 40-50 degrees Celsius. The reaction temperature in this invention refers to a reaction temperature range, which can remain constant within a certain range, for example, a fixed reaction temperature of 40-50 degrees Celsius. Different reaction temperatures can also be selected, such as initially selecting 30-35 degrees Celsius and then selecting 40-50 degrees Celsius. The difference in the reaction temperature range of the present invention is not limited; it can differ by 5 degrees Celsius, 10 degrees Celsius, or 9 degrees Celsius. All reaction temperatures described in this invention are in degrees Celsius. As a free radical initiation system, the initial energy source is not limited; thermal initiation or photoinitiation can be used. The thermal initiation described in this invention refers to initiation where the ambient temperature is sufficient to provide the reaction energy, and additional heating is not necessarily required. For example, if the ambient temperature reaches 30 degrees Celsius and a specific reaction requires a temperature of 30 degrees Celsius, then no additional heating is needed. However, if the ambient temperature reaches 30 degrees Celsius and a specific reaction requires a temperature of 25 degrees Celsius, or even cooling may be necessary. The photoinitiation described in this invention refers to initiation where the reaction energy is provided through light illumination.

[0026] As a preferred embodiment of the method for synthesizing tetrafluoro-substituted bromoalkyl alcohols according to the present invention, the compound represented by Formula II is selected from one of 3-en-1-butanol, 4-penten-1-ol, 5-hexen-1-ol, allyl methyl ether, 3-butenyl methyl ether, or butenyl acetate; the persulfate is selected from one of potassium persulfate, sodium persulfate, or ammonium persulfate; the formate is selected from one of sodium formate dihydrate, ammonium formate, or potassium formate; the molar ratio of Formula II to the persulfate is 1:2.2-5; the molar ratio of Formula II to the formate is 1:1.7-5; and the molar ratio of Formula II to 1,2-dibromotetrafluoroethane is 1:1-5.

[0027] As a preferred embodiment of the method for synthesizing tetrafluorosubstituted bromoalkyl alcohols according to the present invention, the synthesis method is selected from one of the following synthesis methods: Method a: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, or 2-methyltetrahydrofuran; and the reaction temperature is selected from 30-35 degrees Celsius, 35-40 degrees Celsius, 40-50 degrees Celsius, or 70-80 degrees Celsius. Method b: The reactants are 1,2-dibromotetrafluoroethane, 4-penten-1 alcohol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method c: The reactants are 1,2-dibromotetrafluoroethane, 5-hexen-1 alcohol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method d: The reactants are 1,2-dibromotetrafluoroethane, allyl methyl ether, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method e: The reactants are 1,2-dibromotetrafluoroethane, 3-butenylmethyl ether, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method f: The reactants are 1,2-dibromotetrafluoroethane, butenyl acetate, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method g: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, sodium persulfate and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method h: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, potassium persulfate and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method i: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and ammonium formate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method j: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and potassium formate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method k: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, sodium persulfate, potassium persulfate, sodium formate dihydrate, and potassium formate; the reaction solvent is a mixture of N,N-dimethylformamide and 2-methyltetrahydrofuran or a mixture of N-methylpyrrolidone and 2-methyltetrahydrofuran; the reaction temperature is 40-50 degrees Celsius.

[0028] It should be noted that, unless otherwise specified, all figures used in this specification and claims to represent feature dimensions, quantities, and physical properties should be understood to be modified by the term "about" in all cases. The standard meaning of the term "about" is that the value is allowed to fluctuate within ±10%. Therefore, unless the context otherwise requires or contradicts this, the numerical parameters listed in the foregoing specification and appended claims are approximations, and those skilled in the art can appropriately modify these approximations to obtain the desired characteristics using the teachings disclosed herein. The use of numerical ranges indicated by endpoints includes all numbers within that range and any range within that range; for example, 1 to 5 includes 1, 1.2, 1.4, 1.55, 2, 2.75, 3, 3.80, 4, and 5, etc. The range of values ​​expressed by endpoints should also take into account the fluctuation of the range, that is, the effect of the term "about" on the range. For example, 1 to 5 should also include the range of values ​​between 0.9 and 1 and between 5.0 and 5.5, including values ​​such as 0.9, 0.95, 0.99, 5.1, 5.2, and 5.5.

[0029] Compared with existing technologies, the technical solution of this invention innovatively introduces persulfate and formate as a free radical initiation system, enabling the reaction to be completed in one step to prepare the tetrafluorosubstituted bromoalkyl alcohol described in this invention. For free radical initiation systems, when the raw materials contain double bonds, cyclization or polymerization reactions may occur. The technical solution of this invention can avoid cyclization or polymerization reactions. Through creative effort, the technical solution of this invention has the following beneficial effects compared with existing technologies:

[0030] 1. Low material cost. The technical solution of this invention does not use high-cost tetrafluoroethane iodotetrafluoroethane but low-cost tetrafluoroethane bromotetrafluoroethane, and does not use expensive materials such as palladium catalysts or titanium-containing addition reagents, resulting in low material cost.

[0031] 2. High synthesis efficiency. The technical solution adopts a one-step method, eliminating the need for intermediate purification. Post-processing is simple, avoiding cumbersome operations that could lead to the loss of the target compound during purification. Furthermore, the wide reaction conditions of the reactants make the synthesis process window easy to control, resulting in high synthesis efficiency.

[0032] 3. Low wastewater pollution. The technical solution of this invention does not use materials such as thionyl chloride and methanesulfonyl chloride, which will generate a large amount of wastewater in the post-treatment process. The post-treatment is simple and the wastewater pollution is low.

[0033] 4. High production safety. The technical solution of this invention does not use highly hazardous materials such as sodium borohydride, highly toxic materials such as methanesulfonyl chloride, or high-pressure process steps such as hydrogenation, thus improving the safety of personnel in production.

[0034] 5. Low metal residue. The technical solution of this invention does not use palladium catalysts or reagents containing titanium addition agents or other reagents containing metals that are difficult to remove, resulting in low metal residue. Attached Figure Description

[0035] To more clearly illustrate the technical solution of the present invention, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0036] Figure 1 A schematic diagram of the chemical reaction for preparing 6-bromo-5,5,6,6-tetrafluorohexane-1-ol (I-2) by the synthetic method of this invention. Detailed Implementation

[0037] To further illustrate the technical means and effects of the present invention in order to achieve the intended purpose, the following detailed description of the specific implementation methods, steps, structures, features and effects of the synthesis method proposed according to the present invention is provided in conjunction with the accompanying drawings and embodiments.

[0038] The foregoing and other technical contents, features, and effects of the present invention will be clearly presented in the following detailed description of preferred embodiments with reference to the accompanying drawings. Through the description of the specific embodiments, a more in-depth and specific understanding can be gained of the technical means and effects adopted by the present invention to achieve the intended purpose. However, the accompanying drawings are only provided for reference and illustration and are not intended to limit the present invention.

[0039] Regarding the abbreviations and symbols used in this invention, abbreviations that are easily understood by those skilled in the art are used. Some abbreviations are illustrated below: ml refers to milliliters, g refers to grams, h refers to hours, DMF refers to N,N-dimethylformamide, DMAC refers to N,N-dimethylacetamide, NMP refers to N-methylpyrrolidone, and 3-en-1-butanol refers to 3-buten-1-ol. Example

[0040] The general steps of the synthesis example are as follows: An organic solvent is added to the reaction flask and stirring is started. Then, 1,2-dibromotetrafluoroethane and the compound shown in Formula II are added, followed by the addition of a free radical initiator. The reaction is stirred at a certain temperature for a certain time. Then, pure water and an organic solvent are added for extraction. After extraction, the organic phase is concentrated and distilled to obtain the corresponding compound shown in Formula I. The feed-to-yield ratio is calculated, and the yield is calculated. The order of material addition is not limited. The organic solvent, 1,2-dibromotetrafluoroethane, the compound shown in Formula II, and the free radical initiator can be added sequentially or simultaneously. The solvent can be added first, followed by 1,2-dibromotetrafluoroethane, or vice versa. In this example, the solvent is added first, followed by the materials. The organic solvent used for extraction is not limited. Examples include toluene, ethyl acetate, methyl tert-butyl ether, or isopropyl ether. In this example, methyl tert-butyl ether is used as the organic solvent for extraction.

[0041] Example 1: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 30-35 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.1 g of pure product, with a yield of 88%.

[0042] Example 2: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 35-40 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.3 g of pure product, with a yield of 89.2%.

[0043] Example 3: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.7 g of pure product, with a yield of 92.2%.

[0044] Example 4: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 70-80 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.77 g of pure product, with a yield of 85.2%.

[0045] Example 5: 130 ml of DMF was added to the reaction flask and stirred. 13 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.1 g of pure product, with a yield of 79.8%.

[0046] Example 6: Add 130 ml of DMF to the reaction flask and start stirring. Add 65 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate. Stir at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, extract, concentrate the organic phase, and distill. 12.30 g of pure product was obtained, with a yield of 97.3%.

[0047] Example 7: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 26.0 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.60 g of pure product, with a yield of 91.7%.

[0048] Example 8: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 57 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 12.95 g of pure product, with a yield of 86.5%.

[0049] Example 9: 130 ml of DMAC was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.69 g of pure product, with a yield of 92.4%.

[0050] Example 10: 130 ml of NMP was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 9.68 g of pure product, with a yield of 76.5%.

[0051] Example 11: 130 ml of 2-methyltetrahydrofuran was added to a reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.1 g of pure product, with a yield of 80.1%.

[0052] Example 12: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 4.2 g of 4-penten-1 alcohol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 9.85 g of pure product, with a yield of 74.6%.

[0053] Example 13: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 5.02 g of 5-hexen-1-ol, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 8.52 g of pure product, with a yield of 63%.

[0054] Example 14: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of allyl methyl ether, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.6 g of pure product, with a yield of 83.6%.

[0055] Example 15: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 4.3 g of 3-butenylmethyl ether, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.2 g of pure product, with a yield of 84.1%.

[0056] Example 16: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 4.3 g of 3-butenylmethyl ether, 57 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 11.2 g of pure product, with a yield of 91.6%.

[0057] Example 17: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 5 g of butenyl acetate, 25.1 g of ammonium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 9.77 g of pure product, with a yield of 88.1%.

[0058] In Example 18, 130 ml of DMF was added to a reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 5 g of butenyl acetate, 50 g of ammonium persulfate, and 26 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.06 g of pure product, with a yield of 90.8%.

[0059] Allyl methyl ether is a compound with the structure shown in Formula II-9, 3-butenyl methyl ether is a compound with the structure shown in Formula II-10, and butenyl acetate is a compound with the structure shown in Formula II-26.

[0060] Example 19: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 26.2 g of sodium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.6 g of pure product, with a yield of 83.7%.

[0061] Example 20: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 29.7 g of potassium persulfate, and 10.4 g of sodium formate dihydrate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 9.9 g of pure product, with a yield of 78.3%.

[0062] Example 21: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 6.3 g of ammonium formate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 8.22 g of pure product, with a yield of 65.2%.

[0063] Example 22: 130 ml of DMF was added to the reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 25.1 g of ammonium persulfate, and 12.3 g of potassium formate were added. The mixture was stirred at 40-50 degrees Celsius for 4 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 9.89 g of pure product, with a yield of 78.5%.

[0064] Example 23: 100 ml each of DMF and 2-methyltetrahydrofuran were added to a reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 14.85 g of sodium persulfate, 13.1 g of potassium persulfate, 5.2 g of sodium formate dihydrate, and 6.15 g of potassium formate were added. The mixture was stirred at 40-50 degrees Celsius for 6 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.1 g of pure product, with a yield of 80.2%.

[0065] Example 24: 100 ml each of NMP and 2-methyltetrahydrofuran were added to a reaction flask and stirred. 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, 29.7 g of sodium persulfate, 13.1 g of potassium persulfate, 10.4 g of sodium formate hydrate, and 6.15 g of potassium formate were added. The mixture was stirred at 40-50 degrees Celsius for 6 hours. After adding purified water and organic solvent, the mixture was extracted, the organic phase was concentrated, and distilled to obtain 10.6 g of pure product, with a yield of 84.1%.

[0066] Comparative Implementation 1: Add 130 ml of DMF to the reaction flask and start stirring. Add 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, and 10.4 g of sodium formate dihydrate. Stir at 40-50 degrees Celsius for 4 hours. No product was detected.

[0067] Comparative Implementation 1: Add 130 ml of DMF to the reaction flask and start stirring. Add 26 g of 1,2-dibromotetrafluoroethane, 3.6 g of 3-en-1-butanol, and 25.1 g of ammonium persulfate. Stir at 40-50 degrees Celsius for 4 hours. No product was detected.

[0068] The key point of this invention lies in the innovative introduction of persulfate and formate as a free radical initiation system. Using this free radical initiation system, the reaction can be completed in one step to obtain the target product. For free radical initiation systems, when the starting material contains double bonds, cyclization or polymerization reactions may occur. Through in-depth research and clear examples, this invention demonstrates that using the technical solution of this invention can avoid cyclization or polymerization reactions, primarily yielding the tetrafluorosubstituted bromoalkyl alcohol described in this invention.

[0069] Traditional initiation systems employ single, expensive, or high-metal-residue reagents. The initiation system of this invention differs significantly from existing technologies. For example, regarding metal residue, the embodiments of this invention do not use metal salts other than sodium or potassium salts, eliminating the risk of high metal residue from the source. In contrast, existing technologies using palladium catalysts or titanium reagents result in high metal residue, increasing both raw material and post-processing costs, and generating substantial amounts of wastewater and waste solvents.

[0070] Although no specific embodiments are provided, those skilled in the art will understand that when the hydrogen atom on the hydroxyl group of the raw material is replaced by a deuterium atom, the hydroxyl group of the deuterated alcohol will undergo hydrogen-deuterium exchange in conventional organic solvents and water, causing the deuterated alcohol hydroxyl group to become a non-deuterated alcohol hydroxyl group. Therefore, the tetrafluorosubstituted bromoalkyl alcohol described in this invention can still be obtained.

[0071] Although there is no direct, specific theoretical support, when the hydrogen atom on the hydroxyl group of the alcohol in the raw material is replaced by an acyl or alkyl group, the result of using the technical solution of this invention is similar to the effect of the hydrogen atom not being replaced. This invention infers that by using persulfate and formate as a free radical initiation system, the ether bond or ester bond breaks during the reaction, thereby achieving the same effect as using an alcohol with an unsubstituted hydrogen atom as the raw material.

[0072] The synthesis methods described in the examples demonstrate that the preparation of the tetrafluorosubstituted bromoalkyl alcohols of this invention requires no intermediate purification, simplifying post-processing and eliminating the need for cumbersome operations that could lead to the loss of the target compound during purification. Furthermore, the wide range of reaction conditions for the reactants, including a wide temperature range, a wide feed ratio of persulfate and formate, and a wide range of solvent choices, makes the synthesis process window easily controllable, resulting in high synthesis efficiency. Another manifestation of this efficiency is the high synthesis yield, as shown in the examples.

[0073] The above description of the disclosed embodiments enables those skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art. The present invention is not to be limited to the embodiments shown herein, but only requires conformity with the principles and features disclosed herein.

Claims

1. A method for synthesizing tetrafluoro-substituted bromoalkyl alcohols, characterized in that, Using the compound shown in Formula II as a starting material, it reacts with 1,2-dibromotetrafluoroethane in a free radical initiation system to obtain a tetrafluorosubstituted bromoalkyl alcohol as shown in Formula I. In Formula I and Formula II, n represents a positive integer from 1 to 4, and R in Formula II represents one of hydrogen, deuterium, C1-C6 alkyl, or C1-C6 acyl. The free radical initiation system contains a free radical initiator, which is composed of persulfate and formate. 。 2. The synthesis method according to claim 1, characterized in that, The alkyl group of C1-C6 is selected from one of methyl, ethyl, propyl, butyl, pentyl or hexyl, and the acyl group of C1-C6 is selected from one of formyl, acetyl, propionyl, butyryl, valeryl or hexanoyl.

3. The synthesis method according to claim 1, characterized in that, Formula II represents one of the compounds with the following structure: ； Formula I represents one of the compounds with the following structure: 。 4. The synthesis method according to claim 1, characterized in that, The persulfate is selected from one or more of the group consisting of ammonium persulfate, sodium persulfate and potassium persulfate, and the formate is selected from one or more of the group consisting of ammonium formate, sodium formate and potassium formate.

5. The synthesis method according to claim 1, characterized in that, The molar ratio of Formula II to the persulfate is 1:2.2-5, and the molar ratio of Formula II to the formate is 1:1.7-5.

6. The synthesis method according to claim 1, characterized in that, The molar ratio of Formula II to 1,2-dibromotetrafluoroethane is 1:1-5.

7. The synthesis method according to claim 1, characterized in that, The free radical initiation system contains an organic solvent, which contains one or more of the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, 1,4-dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran.

8. The synthesis method according to claim 1, characterized in that, The reaction temperature of the synthesis method is 25-80 degrees Celsius.

9. The synthesis method according to claim 1, characterized in that, The compound represented by Formula II is selected from one of 3-en-1-butanol, 4-penten-1-ol, 5-hexen-1-ol, allyl methyl ether, 3-butenyl methyl ether, or butenyl acetate; the persulfate is selected from one of potassium persulfate, sodium persulfate, or ammonium persulfate; the formate is selected from one of sodium formate dihydrate, ammonium formate, or potassium formate; the molar ratio of Formula II to the persulfate is 1:2.2-5; the molar ratio of Formula II to the formate is 1:1.7-5; and the molar ratio of Formula II to 1,2-dibromotetrafluoroethane is 1:1-5.

10. The synthesis method according to claim 1, characterized in that, The synthesis method is selected from one of the following synthesis methods: Method a: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is selected from N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, or 2-methyltetrahydrofuran; and the reaction temperature is selected from 30-35 degrees Celsius, 35-40 degrees Celsius, 40-50 degrees Celsius, or 70-80 degrees Celsius. Method b: The reactants are 1,2-dibromotetrafluoroethane, 4-penten-1 alcohol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method c: The reactants are 1,2-dibromotetrafluoroethane, 5-hexen-1 alcohol, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method d: The reactants are 1,2-dibromotetrafluoroethane, allyl methyl ether, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method e: The reactants are 1,2-dibromotetrafluoroethane, 3-butenylmethyl ether, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method f: The reactants are 1,2-dibromotetrafluoroethane, butenyl acetate, ammonium persulfate, and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method g: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, sodium persulfate and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method h: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, potassium persulfate and sodium formate dihydrate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method i: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and ammonium formate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method j: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, ammonium persulfate, and potassium formate; the reaction solvent is N,N-dimethylformamide; and the reaction temperature is 40-50 degrees Celsius. Method k: The reactants are 1,2-dibromotetrafluoroethane, 3-en-1-butanol, sodium persulfate, potassium persulfate, sodium formate dihydrate, and potassium formate; the reaction solvent is a mixture of N,N-dimethylformamide and 2-methyltetrahydrofuran or a mixture of N-methylpyrrolidone and 2-methyltetrahydrofuran; the reaction temperature is 40-50 degrees Celsius.

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