Method for synthesizing fluoroolefins by deoxidizing alcohol compounds

Abstract

Alcohols as a class of abundant, diverse and easily accessible basic chemicals, widely exist in various drug molecules, agrochemicals, natural products. Fluoroolefins exhibit wide application value in medicinal chemistry and synthetic chemistry, can precisely regulate the molecular spatial conformation, reactivity and stability, thereby improving the biological activity and reaction selectivity of compounds, and providing an important way for drug structure optimization and synthetic method innovation. The present application takes fluoropropenoic acid and alcohol derivatives as reaction substrates, realizes the efficient method of deoxidation of alcohol compounds to synthesize fluoroolefins under mild conditions. The method has the advantages of mild reaction condition, high product selectivity, simple operation and easy to obtain raw materials. It provides an efficient and convenient synthesis method for deoxidation of alcohol compounds to synthesize fluoroolefin compounds.

Description

Technical Field

[0001] This invention relates to compound preparation, specifically to the field of organic compound synthesis. More specifically, it relates to a method for synthesizing fluoroolefins from readily available alcohols through deoxygenation. Background Technology

[0002] Alcohols, as a class of abundant, structurally diverse, and readily available basic chemicals, are widely found in various drug molecules, agrochemicals, natural products, biomass degradation products, and everyday chemical raw materials, exhibiting extremely rich structural diversity and functional group compatibility. The hydroxyl functional groups in their molecular structures are easily transformed and modified, and can be converted into highly reactive reaction intermediates through simple activation, providing an ideal research platform for the efficient construction of complex molecular skeletons. Using alcohols as electrophiles to construct new carbon-carbon bonds through deoxygenation functionalization reactions not only efficiently expands the diversity of molecular skeletons and achieves precise control and rapid upgrading of molecular structures, but also provides a simple, efficient, and environmentally friendly new strategy for the modular synthesis of complex molecules, diversity-oriented synthesis, and the efficient preparation of drug lead compounds. This type of transformation method has advantages such as mild reaction conditions, good functional group tolerance, and wide applicability, showing great application potential and broad development prospects in organic synthesis, medicinal chemistry, fine chemicals, and green catalysis.

[0003] Furthermore, the introduction of fluorine atoms can effectively regulate the metabolic stability, lipophilicity, and bioavailability of parent molecules, making it a crucial structural modification strategy in drug molecule design. Monofluoroolefins, as a key class of fluorine-containing functional skeletons, are not only important intermediates for constructing various complex fluorine-containing molecules but also serve as ideal bioisosteres for peptide bonds, significantly enhancing molecular conformational stability and resistance to peptidase degradation. Due to their unique electronic effects and spatial structures, fluoroolefins exhibit wide-ranging applications in medicinal chemistry and synthetic chemistry, allowing for precise control of molecular spatial conformation, reactivity, and stability, thereby improving the bioactivity and reactivity selectivity of compounds and providing important pathways for drug structure optimization and synthetic method innovation. Simultaneously, they demonstrate significant advantages in improving oral bioavailability, prolonging in vivo half-life, and reducing toxic side effects, making them indispensable key structural units in modern drug development and organic synthesis. Therefore, developing efficient and highly selective synthetic methods for monofluoroolefins using widely available and structurally diverse alcohols as inexpensive precursors has significant theoretical and practical value in organic synthetic chemistry and drug molecule creation. However, there is currently no effective strategy for synthesizing fluoroolefins through the deoxygenation of readily available alcohols. Summary of the Invention

[0004] Given that alcohols are a class of basic chemicals that are abundant, structurally diverse, and readily available, and are widely present in various drug molecules, as well as the important value of fluoroolefins in pharmaceutical synthesis and organic chemistry, this invention patent realizes an efficient method for the deoxygenation synthesis of fluoroolefins from alcohols under mild conditions.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: a method for the deoxygenation synthesis of fluoroolefins from alcohol compounds, characterized in that: fluoroacrylic acid and alcohol derivatives are used as reaction substrates, and the reaction is carried out under light irradiation at room temperature for 12 hours in a solvent of N,N-dimethylacetamide (DMAc) and acetonitrile (CH3CN) with the promotion of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4-CzIPN) photocatalyst and triethylenediamine (DABCO), to obtain a class of fluoroolefin compounds with the general formula:

[0006]

[0007] Preferably, the mass of the alcohol derivative is three times the mass of the fluoroacrylic acid.

[0008] Preferably, the amount of 4-CzIPN is 5% of the amount of fluoroacrylic acid.

[0009] Preferably, the mass of DABCO is 50% of the mass of fluoroacrylic acid.

[0010] Preferably, the reaction temperature is room temperature, the light wavelength is 420 nm, and the reaction time is 12 hours.

[0011] This method offers mild reaction conditions, high product selectivity, simple operation, and readily available raw materials. The synthesized fluoroolefin compounds have high application value in organic chemistry, medicinal chemistry, and materials science. It provides an efficient and convenient synthetic method for synthesizing fluoroolefin compounds from widely existing alcohols through deoxygenation. Detailed Implementation

[0012] The technical solution of the present invention will be further described below through specific embodiments:

[0013] Example 1

[0014] The reaction formula for this embodiment is as follows:

[0015]

[0016] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0017] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 65% and the product purity was greater than 99%.

[0018] Example 2

[0019] The reaction formula for this embodiment is as follows:

[0020]

[0021] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0022] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 63% and the product purity was greater than 99%.

[0023] Example 3

[0024] The reaction formula for this embodiment is as follows:

[0025]

[0026] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0027] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 68%, and the product purity was greater than 99%.

[0028] Example 4

[0029] The reaction formula for this embodiment is as follows:

[0030]

[0031] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0032] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 56%, and the product purity was greater than 99%.

[0033] Example 5

[0034] The reaction formula for this embodiment is as follows:

[0035]

[0036] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0037] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 68%, and the product purity was greater than 99%.

[0038] Example 6

[0039] The reaction formula for this embodiment is as follows:

[0040]

[0041] (1) Fluoroacrylic acid (0.2 mmol, 1.0 equiv), alcohol derivatives (0.6 mmol, 3.0 equiv), 4-CzIPN (5 mol%), and DABCO (5 mol%) were added to a sealed reaction tube with a side arm and a magnetic inlet under air. The reaction tube was evacuated and then filled with nitrogen. 1 mL of DMAc and 1 mL of CH3CN were added to the reaction tube and the mixture was irradiated with light at room temperature for 12 hours.

[0042] (2) The solvent in the organic phase obtained in step (1) was evaporated to obtain the crude product. The crude product was then purified by silica gel column chromatography. The separation yield was 66%, and the product purity was greater than 99%.

[0043] The amounts of each substance used and the reaction conditions were experimentally extended to the examples to demonstrate that the technical solution of the present invention has good functional group compatibility.

[0044] The present invention has been described in detail above. The above description is only an embodiment of the present invention and should not be construed as limiting the scope of this application. All equivalent changes and modifications made within the scope of this application should still fall within the scope of the present invention.

[0045] Attached Figure Description

[0046] Figure 1 The proton NMR spectrum of product 1 prepared in this invention;

[0047] Figure 2 The nuclear magnetic resonance fluorine spectrum of product 1 prepared in this invention;

[0048] Figure 3 The carbon NMR spectrum of product 1 prepared in this invention;

[0049] Figure 4 The proton NMR spectrum of product 2 prepared in this invention;

[0050] Figure 5 The nuclear magnetic resonance fluorine spectrum of product 2 prepared in this invention;

[0051] Figure 6 The carbon NMR spectrum of product 2 prepared in this invention;

[0052] Figure 7 The proton NMR spectrum of product 3 prepared in this invention;

[0053] Figure 8 The nuclear magnetic resonance fluorine spectrum of product 3 prepared in this invention;

[0054] Figure 9 The carbon NMR spectrum of product 3 prepared in this invention;

[0055] Figure 10 The proton NMR spectrum of product 6 prepared in this invention;

[0056] Figure 11 The nuclear magnetic resonance fluorine spectrum of product 6 prepared in this invention;

[0057] Figure 12 The nuclear magnetic resonance carbon spectrum of product 6 prepared in this invention.

Claims

1. A method for synthesizing fluoroolefins by deoxygenation of alcohols, characterized in that: Using fluoroacrylic acid and alcohol derivatives as reaction substrates, a class of fluoroolefin compounds with the general formula were obtained by reacting in N,N-dimethylacetamide and acetonitrile solvents at room temperature under 420 nm light irradiation for 12 hours, with 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile as a photocatalyst and triethylenediamine as a promoter. Where R is hydrogen or methoxy, and R1, R2, and R3 are methyl, alkyl, or cyclohexyl.

2. The method for synthesizing fluoroolefins by deoxygenation of alcohol compounds according to claim 1, wherein the amount of alcohol derivative is 3 times the amount of fluoroacrylic acid; the amount of 4-CzIPN is 5% of the amount of fluoroacrylic acid; and the amount of DABCO is 50% of the amount of fluoroacrylic acid.

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