A kind of synthetic method of fluoroallyl alcohol

Abstract

The invention belongs to the field of organic synthetic chemistry and relates to a synthetic method for fluoroallyl alcohol. With fluoroacrylic acid and alcohol compound as reaction raw materials, with tris (2-phenylpyridine) iridium as catalyst, triethylenediamine as base, tert-butyl peroxybenzoate as initiator, acetonitrile as solvent, react under illumination conditions to obtain a class of important fluoroallyl alcohol compounds. The reaction raw materials are easy to obtain, product yield and selectivity are high, functional group compatibility is good, substrate application range is wide, and synthesis economic value is high. For fluoroallyl alcohol, efficient, convenient and economical preparation method is provided.

Description

Technical Field

[0001] The present invention relates to compound preparation, belonging to the field of organic synthesis, and specifically to a method for synthesizing fluoroallyl alcohol. Background Art

[0002] Alcohols are among the most readily available and important organic compounds, occurring extensively in natural products and pharmaceuticals. Fluoroallyl alcohols, among them, are versatile building blocks and important synthetic building blocks. Efficient synthesis of these compounds is a significant need in synthetic and medicinal chemistry.

[0003] Conventional synthesis involves the nucleophilic addition reaction of a Grignard reagent with a fluoroacrylic acid derivative (Formula 1). However, this method requires a long route, high Grignard reagent activity, poor functional group compatibility, harsh reaction conditions, and a relatively low temperature, making the operation cumbersome.

[0004]

[0005] The ring-opening reaction of gem-difluorocyclopropylstannane can also be used to synthesize fluoroallyl alcohol (Formula 2). However, the reaction has a long synthesis process and requires a low temperature of -78 degrees Celsius. The synthesis of gem-difluorocyclopropylstannane is difficult and the substrate application range is narrow.

[0006]

[0007] In addition, the Nozaki-Hiyama-Kishi reaction also provides a method for preparing fluoroallyl alcohols (Formula 3). However, this reaction requires the use of an excess of toxic metallic chromium, has a narrow substrate application range, and can only be used to synthesize secondary alcohols.

[0008] Summary of the Invention

[0009] Alcohol compounds are readily available and inexpensive, and the direct synthesis of fluoroallyl alcohols from these low-molecule alcohols holds significant synthetic value. This invention addresses the shortcomings of current fluoroallyl alcohol synthesis methods, including long reaction routes, a narrow substrate range, poor functional groups, the need for excessive amounts of toxic reagents, and harsh reaction conditions. Using inexpensive and readily available alcohol compounds as raw materials, the present invention efficiently and conveniently synthesizes fluoroallyl alcohols.

[0010] To solve the above technical problems, the present invention adopts the following technical solution: a method for synthesizing fluoroallyl alcohol, characterized in that: fluoroacrylic acid and an alcohol compound are used as raw materials, tris(2-phenylpyridine)iridium is used as a catalyst, triethylenediamine is used as a base, tert-butyl perbenzoate is used as an initiator, and acetonitrile is used as a solvent, and a reaction is carried out according to the following reaction formula to obtain a class of fluoroallyl alcohol compounds having the general formula (I):

[0011]

[0012] Wherein R1 is hydrogen, halogen, ester group, cyano group, trifluoromethyl group, etc.; R2 is hydrogen, methyl group, and R3 is methyl, ethyl, ester group, cyano group, carbonyl group, halogen group, etc.

[0013] Preferably, the amount of tris(2-phenylpyridine)iridium is 1% of the amount of fluoroacrylic acid.

[0014] Preferably, the amount of triethylenediamine as the base is 1 times the amount of fluoroacrylic acid.

[0015] Preferably, the amount of t-butyl perbenzoate is 3 times the amount of fluoroacrylic acid.

[0016] Preferably, the wavelength of the illumination is 465 nanometers, the reaction time is 24 to 48 hours, and the reaction temperature is room temperature.

[0017] This method, for the first time, achieves the efficient and highly selective preparation of fluoroallyl alcohol using alcohol and fluoroacrylic acid as raw materials. The reaction utilizes readily available, inexpensive raw materials, and produces high product yields and selectivity. The reaction system features a simple feed system, good functional group compatibility, a wide range of substrates, and high synthetic economic value. This provides an efficient, convenient, and economical method for the preparation of fluoroallyl alcohol. DETAILED DESCRIPTION

[0018] The technical solution of the present invention is further described below through specific implementation methods:

[0019] Example 1, the reaction formula of this embodiment is as follows:

[0020]

[0021] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-phenylacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of isopropanol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 48 hours.

[0022] (2) The solvent in the organic phase obtained in step (1) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 71%, Z / E>30:1, and the product purity was 100%.

[0023] Example 2

[0024] The reaction formula of this embodiment is shown below:

[0025]

[0026] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-(p-fluorophenyl)acrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of isopropanol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 48 hours.

[0027] (2) The solvent in the organic phase obtained in step (1) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 71%, Z / E>30:1, and the product purity was 100%.

[0028] Example 3

[0029] The reaction formula of this embodiment is shown below:

[0030]

[0031] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-iodophenylacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of isopropanol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 48 hours.

[0032] (2) The solvent in the organic phase obtained in step (1) was dried to obtain a crude product, which was then purified using a silica gel column. The separation yield was 68%, Z / E>30:1, and the product purity was 100%.

[0033] Example 4

[0034] The reaction formula of this embodiment is shown below:

[0035]

[0036] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-phenylacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of ethylene glycol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 36 hours.

[0037] (2) The solvent in the organic phase obtained in step (1) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 63%, Z / E>30:1, and the product purity was 100%.

[0038] Example 5

[0039] The reaction formula of this embodiment is shown below:

[0040]

[0041] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and 2-fluoro-3-phenylacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic element. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of 1,4-butanediol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 36 hours.

[0042] (2) The solvent in the organic phase obtained in step (1) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 55%, Z / E>30:1, and the product purity was 100%.

[0043] Example 6

[0044] The reaction formula of this embodiment is shown below:

[0045]

[0046] (1) Under air, tris(2-phenylpyridine)iridium (1 mol%), triethylenediamine (1 equiv), and vitamin E-derived fluoroacrylic acid (0.2 mmol) were added to a sealed reaction tube with a branch tube and a magnetic rod. The reaction tube was evacuated with argon three times. Under argon protection, 0.5 mL of acetonitrile and 0.5 mL of ethanol were added to the reaction tube. The reaction was allowed to proceed at room temperature under 465 nm light for 36 hours.

[0047] (2) The solvent in the organic phase obtained in step (1) was dried by spin drying to obtain a crude product, which was then purified using a silica gel column. The separation yield was 58%, Z / E>30:1, and the product purity was 100%.

[0048] The amounts of the substances used and the reaction conditions were the same as those in the examples to carry out an experimental expansion to illustrate that the technical solution of the present invention has good functional group compatibility.

[0049] The present invention has been described in detail above. The above descriptions are merely embodiments of the present invention and should not limit the scope of implementation of the present application. In other words, all equivalent changes and modifications made within the scope of the present application should still fall within the scope of the present invention.

[0050]

[0051] BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of the product 3 prepared in the present invention;

[0053] Figure 2 This is the nuclear magnetic resonance fluorine spectrum of the product 3 prepared in the present invention;

[0054] Figure 3 This is the carbon NMR spectrum of the product 3 prepared in the present invention.

[0055] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the product 5 prepared in the present invention;

[0056] Figure 5 This is the nuclear magnetic resonance fluorine spectrum of the product 5 prepared in the present invention;

[0057] Figure 6 This is the carbon NMR spectrum of product 5 prepared in the present invention.

[0058] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of the product 8 prepared in the present invention;

[0059] Figure 8 This is the nuclear magnetic resonance fluorine spectrum of the product 8 prepared in the present invention;

[0060] Figure 9 This is the carbon NMR spectrum of the product 8 prepared in the present invention.

[0061] Figure 10 This is the hydrogen nuclear magnetic resonance spectrum of the product 45 prepared in the present invention;

[0062] Figure 11 The NMR fluorine spectrum of the product 45 prepared in the present invention;

[0063] Figure 12 This is the carbon NMR spectrum of product 45 prepared in the present invention.

[0064] Figure 13 This is the hydrogen nuclear magnetic resonance spectrum of the product 50 prepared in the present invention;

[0065] Figure 14 The NMR fluorine spectrum of the product 50 prepared in the present invention;

[0066] Figure 15 This is the carbon NMR spectrum of the product 50 prepared in the present invention.

Claims

1. A method for synthesizing fluoroallyl alcohol, characterized in that: Fluoroacrylic acid and alcohol compounds are used as raw materials, tris(2-phenylpyridine)iridium is used as a catalyst, triethylenediamine is used as a base, tert-butyl perbenzoate is used as an initiator, and acetonitrile is used as a solvent. According to the following reaction formula, irradiation with 465 nm light and reaction at room temperature for 24 to 48 hours are performed to obtain a class of fluoroallyl alcohol compounds having the general formula (I): Wherein R1 is hydrogen, halogen, cyano, or trifluoromethyl; R2 is hydrogen or methyl; and R3 is methyl, ethyl, cyano, carbonyl, or halogen.

2. A method for synthesizing fluoroallyl alcohol, characterized in that: The amount of tris(2-phenylpyridine)iridium was 1% of the amount of fluoroacrylic acid.

3. A method for synthesizing fluoroallyl alcohol, characterized in that: The amount of triethylenediamine was 1 times the amount of fluoroacrylic acid.

4. A method for synthesizing fluoroallyl alcohol, characterized in that: The amount of t-butyl peroxybenzoate was 3 times the amount of fluoroacrylic acid.

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