阅读说明：本技术 一种氟代乙醛-氧-芳基肟类化合物及其合成方法 (Fluoroacetaldehyde-oxygen-aryl oxime compound and synthesis method thereof ) 是由 翁志强 林波 黄扬杰 吴伟 陈守雄 郑国才 林棋 于 2021-02-01 设计创作，主要内容包括：本发明属于有机氟的化学合成技术领域,涉及一种氟代乙醛-氧-芳基肟类化合物及其合成方法,以芳基羟胺,氟烷基乙醛水(醇)合物为原料,在酸性条件下反应得到氟代乙醛-氧-芳基肟类化合物。本发明制备的氟代乙醛-氧-芳基肟类化合物为白色固体或液体,热稳定性好,不易吸潮,无腐蚀性,便于保存,便于运输,便于空气中使用,反应原料易得,可作为氟代乙腈的前驱体使用。该方法实现了数十克数量级的合成,具有进一步工业化应用的潜力。(The invention belongs to the technical field of organic fluorine chemical synthesis, and relates to a fluoroacetal-oxygen-aryl oxime compound and a synthesis method thereof. The prepared fluoroacetal-oxygen-aryl oxime compound is white solid or liquid, has good thermal stability, is not easy to absorb moisture, has no corrosiveness, is convenient to store and transport, is convenient to use in the air, has easily available reaction raw materials, and can be used as a precursor of fluoroacetonitrile. The method realizes synthesis of tens of grams and has potential for further industrial application.)

1. A fluoroacetal-oxo-aryl oxime compound characterized by: the fluoro acetaldehyde-oxygen-aryl oxime compound is any one of the following formulas 1 to 8:

。

2. the method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 1, characterized in that: aryl hydroxylamine and fluoroalkyl acetaldehyde water (alcohol) compound are used as raw materials to synthesize the fluoroacetal-oxygen-aryl oxime compound under acidic condition.

3. The method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 2, characterized in that: the molar ratio of aryl hydroxylamine to fluoroalkyl acetaldehyde hydrate is (0.5-2) to (1-4).

4. The method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 2, characterized in that: the aryl hydroxylamine is any one of the following formulas 1 to 4:

。

5. the method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 2, characterized in that: the fluoroalkyl acetaldehyde water (alcohol) hydrate is any one of the following formulas 1-2:

。

6. the method for synthesizing fluoroacetal-oxo-aryl oximes according to any one of claims 2 to 5, characterized in that: the specific synthesis steps are as follows: in the air atmosphere, putting aryl hydroxylamine compound and fluoroalkyl acetaldehyde hydrate (alcohol) into a reactor with a magnetic stirring bar, and reacting under an acidic condition to obtain the fluoroacetal-oxygen-aryl oxime compound.

7. The method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 6, characterized in that: the reaction temperature is 40-80 ℃.

8. The method for synthesizing fluoroacetal-oxo-aryl oximes according to claim 6, characterized in that: the reaction time was 24 h.

Technical Field

The invention belongs to the technical field of chemical synthesis of organic fluorine, and particularly relates to a fluoroacetal-oxygen-aryl oxime compound and a synthesis method thereof.

Background

The fluoroacetonitrile is a synthon for synthesizing fluorine-containing heterocyclic compounds, such as trifluoroacetonitrile, is used as an electrophilic reagent for synthesizing trifluoromethyl-containing heterocyclic compounds, and has important application in the fields of pesticides, medicines and the like. However, the trifluoroacetonitrile is a gas with low boiling point (-64 ℃ to-65 ℃) and high toxicity, is not easy to prepare and store, and is difficult to perform experimental operation in a common laboratory. Therefore, it is necessary to develop a safe, easy to handle reagent that generates trifluoroacetonitrile in situ.

The invention reports a method for synthesizing a fluoroacetaldehyde-oxygen-aryl oxime compound by using an easily obtained and easily prepared aryl hydroxylamine and a fluoroalkyl acetaldehyde water (alcohol) compound as raw materials and reacting under an acidic condition, wherein the aryl hydroxylamine and the fluoroalkyl acetaldehyde water (alcohol) compound can be used as a precursor of fluoroacetonitrile.

Disclosure of Invention

The prepared fluoroacetal-oxygen-aryl oxime compound is white solid or liquid, has good thermal stability, is not easy to absorb moisture, has no corrosivity, is convenient to store, transport and use in the air, has easily available reaction raw materials, and can be used as a precursor of fluoroacetonitrile.

In order to achieve the purpose, the invention adopts the following technical scheme:

a fluoroacetal-O-aryloxime compound having any one of the following formulae 1 to 8:

。

a synthetic method of a fluoroacetal-oxygen-aryl oxime compound takes aryl hydroxylamine and fluoroalkyl acetaldehyde water (alcohol) compound as raw materials, and the fluoroacetal-oxygen-aryl oxime compound is obtained by reaction under acidic conditions.

Further, the molar ratio of aryl hydroxylamine to fluoroalkyl acetaldehyde hydrate is (0.5-2) to (1-4).

Furthermore, aryl hydroxylamine and fluoroalkyl acetaldehyde water (alcohol) compound are used as raw materials, and the fluoroacetal-oxygen-aryl oxime compound is obtained under an acidic condition, and the reaction formula is as follows:

。

further, the aryl hydroxylamine is any one of the following formulas 1 to 4:

。

further, the fluoroalkyl acetaldehyde water (alcohol) hydrate is any one of the following formulas 1 to 2:

further, the synthetic method of the fluoroacetaldehyde-oxygen-aryl oxime compound comprises the following specific steps: in the air atmosphere, putting aryl hydroxylamine compound and fluoroalkyl acetaldehyde water (alcohol) compound into a reactor with a magnetic stirrer, heating to 40-80 ℃ under an acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, removing the solvent by rotary evaporation, and purifying through a silica gel column to obtain the fluoroacetal-oxygen-aryl oxime compound.

The invention has the beneficial effects that:

the invention takes simple and easily obtained aryl hydroxylamine and fluoroalkyl acetaldehyde water (alcohol) compound as raw materials to synthesize the fluoroacetal-oxygen-aryl oxime compound by one step under the acidic condition. The prepared fluoroacetal-oxygen-aryl oxime compound is a white solid or liquid, has good thermal stability, is not easy to absorb moisture, has no corrosiveness, is convenient to store, transport and use in the air, has cheap and easily available reaction raw materials, and can be used as a precursor of fluoroacetonitrile.

Detailed Description

In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.

Example 1

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.8 mmol of trifluoroacetic aldehyde hydrate, heating to 40 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (isolated yield 67%).¹H NMR (400 MHz, CDCl₃) δ 8.87 (d, J = 2.7 Hz, 1H), 8.50 (dd, J = 9.3, 2.7 Hz, 1H), 8.11 (q, J = 3.9 Hz, 1H), 7.92 (d, J = 9.3 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 155.18 (s), 145.46 (q, J = 38.9 Hz), 142.69 (s), 136.68 (s), 129.39 (s), 122.01 (s), 118.75 (q, J = 272.8 Hz), 117.49 (s). ¹⁹F NMR (376 MHz, CDCl₃) δ -66.64 (d, J= 3.9 Hz). melting point 65.1-66.5 ℃.

Example 2

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.8 mmol of trifluoroacetic aldehyde hydrate, heating to 50 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (yield 50%). NMR data are given in example 1.

Example 3

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.8 mmol of trifluoroacetic aldehyde hydrate, heating to 60 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (yield 54%). NMR data are given in example 1.

Example 4

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.8 mmol of trifluoroacetic aldehyde hydrate, heating to 70 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (yield 50%). NMR data are given in example 1.

Example 5

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.8 mmol of trifluoroacetic aldehyde hydrate, heating to 80 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (yield 35%). NMR data are given in example 1.

Example 6

Placing a polytetrafluoroethylene magnet particle in a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2-nitrophenylhydroxylamine (formula 3) and 0.8 mmol of trifluoro acetaldehyde hydrate, heating at 60 deg.C under acidic condition, stirring for reaction for 24 hr, cooling to room temperature, and reacting with water under stirringAfter three times of ethyl acetate/water extraction, organic phases are combined, and organic solvents are removed by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (2-nitrophenyl) oxime (isolated yield 67%).¹H NMR (400 MHz, CDCl₃) δ 7.98 (m, 2H), 7.67 (d, J = 8.3 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 151.37 (s), 143.36 (q, J = 38.4 Hz), 134.80 (s), 125.77 (s), 124.06 (s), 119.23 (q, J = 272.1 Hz), 117.50 (s). ¹⁹F NMR (376 MHz, CDCl₃) δ -66.59 (d, J = 3.8 Hz).

Example 7

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 4-nitrophenylhydroxylamine (formula 2) and 0.8 mmol of trifluoro acetaldehyde hydrate, heating to 60 ℃ under an acidic condition, stirring for reaction for 24 hours, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing an organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2,2, 2-trifluoroacetaldehyde-oxy- (4-nitrophenyl) oxime (isolated yield 67%).¹H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 9.2 Hz, 2H), 7.90 (q, J = 3.9 Hz, 1H), 7.34 (d, J = 9.2 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 162.45 (s), 143.99 (s), 142.59 (q, J = 38.4 Hz), 125.93 (d, J = 5.7 Hz), 119.27 (q, J = 272.0 Hz), 114.76 (s). ¹⁹F NMR (376 MHz, CDCl₃) δ -66.58 (d, J = 3.9 Hz).

Example 8

Putting a polytetrafluoroethylene magnet into a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 4-cyanophenylhydroxylamine (formula 4) and 0.6 mmol of trifluoroacetic aldehyde hydrate, heating to 60 ℃ under acidic condition, stirring for reaction for 24h, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product is processed by silica gel column chromatography, ethyl acetate/petroleum ether is taken as eluent to obtain 2,2, 2-Trifluoroacetaldehyde-oxy- (4-cyanophenyl) oxime (74% yield).¹H NMR (400 MHz, CDCl₃) δ 7.87 (q, 3.7 Hz, 1H), 7.67 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 161.04 (s), 142.19 (q, J = 38.3 Hz), 134.17 (s), 119.31 (q, 266.7 Hz), 118.58 (s), 115.28 (s), 107.61 (s). ¹⁹F NMR (376 MHz, CDCl₃) δ -66.60 (d, J= 3.7 Hz) melting point 62.1-63.3 ℃.

Example 9

Placing a polytetrafluoroethylene magnet into a 5 mL reaction tube in an air atmosphere, adding 0.2 mmol of 2, 4-dinitrophenylhydroxylamine (formula 1) and 0.6 mmol of difluoroacetaldehyde hemiethanol, heating to 50 ℃ under an acidic condition, stirring for reaction for 24 hours, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2, 2-difluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime (yield 54%).¹H NMR (400 MHz, CDCl₃) δ 8.87 (d, J = 2.6 Hz, 1H), 8.48 (dd, J = 9.3, 2.7 Hz, 1H), 8.05 (dt, J = 6.5, 3.5 Hz, 1H), 7.88 (d, J = 9.3 Hz, 1H), 6.36 (td, J = 53.4, 6.0 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 155.65 (s), 150.17 (t, J = 32.7 Hz), 142.43 (s), 136.75 (s), 129.41 (s), 122.16 (s), 117.43 (s), 110.25 (t, J = 238.7 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ -117.89 (dd, J= 53.4, 3.5 Hz). melting point 53.0-54.8 ℃.

Example 10

Placing a polytetrafluoroethylene magnet particle in a 5 mL reaction tube in the air atmosphere, adding 0.2 mmol of 4-nitrophenylhydroxylamine (formula 2) and 0.6 mmol of difluoroacetaldehyde hemiethanol, heating to 50 ℃ under an acidic condition, stirring for reaction for 24 hours, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the obtained crude product is subjected to silica gel column chromatography, ethyl acetate/petroleum ether is taken as eluent, and 2, 2-difluoroacetaldehyde-oxygen-(4-Nitrophenyl) oxime (yield 93%).¹H NMR (400 MHz, CDCl₃) δ 8.24 (m, 2H), 7.85 (dt, J = 6.5, 3.4 Hz, 1H), 7.29 (m, 2H), 6.33 (td, J = 53.7, 6.2 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 162.74 (s), 147.34 (t, J = 32.7 Hz), 143.67 (s), 125.92 (s), 114.62 (s, J = 12.8 Hz), 110.96 (t, J = 236.9 Hz).¹⁹F NMR (376 MHz, CDCl₃) δ -117.38 (dd, J = 53.7, 3.3 Hz).

Example 11

Placing a polytetrafluoroethylene magnet particle in a 5 mL reaction tube in air atmosphere, adding 0.2 mmol of 2-nitrophenylhydroxylamine (formula 3) and 0.6 mmol of difluoroacetaldehyde hemiethanol, heating to 50 ℃ under an acidic condition, stirring for reaction for 24 hours, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2, 2-difluoroacetaldehyde-oxy- (2-nitrophenyl) oxime (yield 90%).¹H NMR (400 MHz, CDCl₃) δ 7.94 (m, 2H), 7.61 (m, 2H), 7.21 (ddd, J = 8.5, 6.7, 2.0 Hz, 1H), 6.31 (td, J = 53.7, 6.2 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 151.47 (s), 147.92 (t, J = 32.6 Hz), 134.51 (s), 125.58 (s), 123.47 (s), 117.30 (s), 110.74 (t, J = 237.3 Hz). ¹⁹F NMR (376 MHz, CDCl₃) δ -117.51 (dd, J = 53.6, 3.4 Hz).

Example 12

Placing a polytetrafluoroethylene magnet particle in a 5 mL reaction tube in an air atmosphere, adding 0.2 mmol of 4-cyanophenylhydroxylamine (formula 4) and 0.6 mmol of difluoroacetaldehyde hemiethanol, heating to 50 ℃ under an acidic condition, stirring for reaction for 24 hours, cooling to room temperature, extracting with ethyl acetate/water for three times, combining organic phases, and removing the organic solvent by rotary evaporation; the crude product obtained was subjected to silica gel column chromatography using ethyl acetate/petroleum ether as eluent to give 2, 2-difluoroacetaldehyde-oxy- (4-cyanophenyl) oxime (yield 89%).¹H NMR (400 MHz, CDCl₃) δ 7.83 (dt, J = 6.5, 3.3 Hz, 1H), 7.65 (m, 2H), 7.28 (m, 2H), 6.31 (td, J = 53.7, 6.3 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 161.30 (s), 146.96 (t, J = 32.7 Hz), 134.14 (s), 118.73 (s), 115.21 (s), 111.03 (t, J = 236.8 Hz), 107.15 (s).¹⁹F NMR (376 MHz, CDCl₃) δ -117.29 (dd, J= 53.8, 3.4 Hz).

Reaction steps for preparing trifluoroacetonitrile:

a5 mL reaction tube is filled with a Teflon magnet, 0.2 mmol of 2,2, 2-trifluoroacetaldehyde-oxy- (2, 4-dinitrophenyl) oxime is added, a certain amount of base (such as triethylamine, cesium carbonate and potassium tert-butoxide) is added, and after stirring, trifluoroacetonitrile is generated (nuclear magnetic yield > 99%).

The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.