A method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride

Abstract

The invention discloses a method for synthesizing naphthyl propargyl fluorine compounds from sulfur hexafluoride, and belongs to the technical field of organic intermediate synthesis. The synthesis method comprises the following steps: placing a naphthyl propargyl alcohol compound, a photocatalyst, a base, and a solvent in a reaction vessel, filling it with sulfur hexafluoride gas, and reacting under blue light illumination to obtain a naphthyl propargyl fluorine compound. Beneficial effect: Compared with other methods for synthesizing propargyl fluorine compounds, the reaction conditions of the present invention are mild, the reaction raw materials used (including propargyl alcohol and N,N-diisopropylethylamine) are cheap and easy to obtain, and SF6 gas can be well utilized with lower energy under blue light irradiation. The reaction has the characteristics of low cost, low energy consumption and environmental friendliness.

Description

Technical Field

[0001] The invention relates to the technical field of organic intermediate synthesis, in particular to a method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride. Background Art

[0002] Sulfur hexafluoride (SF6) gas is in a gaseous state at room temperature and pressure, with a critical temperature of 45.6°C and a sublimation point of -63.8°C at normal pressure. SF6 also possesses a highly symmetrical octahedral structure centered on sulfur and strong SF bonds, resulting in excellent thermal and chemical stability, making it a key component in cutting-edge scientific research and production. Under the same conditions, SF6's insulation capacity is over 2.5 times that of air and nitrogen, and its arc-extinguishing capability is 100 times that of air, making it widely used in power systems. High-purity electronic-grade SF6 is often used as an electronic etchant in the production of integrated circuits such as chips.

[0003] However, SF6 is a strong greenhouse gas, with a greenhouse gas effect 23,500 times that of carbon dioxide, and is extremely difficult to degrade naturally. Its lifespan is as long as 3,200 years, causing immeasurable impact on global warming. In 1997, the Kyoto Protocol listed SF6 as a restricted emission gas. Therefore, the resource utilization of SF6 gas, which is used in large quantities, is particularly important. On the other hand, the SF6 molecule has six fluorine atoms and is a rich source of fluorine. In the field of chemistry, SF6 can convert ordinary compounds into high-value fluorine-containing compounds, thereby further realizing the synthesis or modification of fluorine-containing drugs and biologically active molecules. Therefore, SF6 shows extremely high application potential and research value. At present, ultraviolet light or carbene is usually used to activate SF6. The specific methods are:

[0004] Method 1: Using allyl alcohol as the substrate, a blue LED light as the light source, and a metal iridium complex of (4,4'-di-tert-butyl-2,2'-bipyridyl)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate as the photocatalyst, SF6 is photocatalytically activated at room temperature to achieve the conversion of allyl alcohol to allyl fluoride compounds (Angew. Chem. Int. Ed. 2016, 55, 15072-15075):

[0005]

[0006] This method demonstrates the feasibility of photocatalytically activating sulfur hexafluoride gas and converting allyl alcohol to allyl fluoride. The authors also compared the use of propargyl alcohol under these conditions and found that the conversion of the hydroxyl group in propargyl alcohol could not be achieved.

[0007] Method 2: Using ultraviolet light as the light source, electron-rich nitrogen heterocyclic carbene activated gas SF6 is used at 80 degrees Celsius to obtain 2,2-difluoroimidazoline or 2,2-difluoroimidazolidine and thio derivatives of the carbene precursor, wherein 2,2-difluoroimidazoline or 2,2-difluoroimidazolidine can be used in situ for the fluorination conversion of allyl alcohol (Chem. Commun. 2018, 54, 9753-9756).

[0008]

[0009] This method requires expensive nitrogen heterocyclic carbenes during the reaction process. It also requires ultraviolet light as an excitation light source, which requires high energy and consumes a lot of energy. In addition, the reaction only reports the conversion of allyl alcohol and saturated chain alcohols to the corresponding fluorides, and its application in the fluorination of propargyl alcohol has not been reported.

[0010] Method 3: Using ultraviolet light as the light source, SF6 as the fluorinating agent and 4,4-dimethoxybenzophenone as the organic photocatalyst at room temperature, fluorinated sugars are generated through photocatalytic reaction.

[0011]

[0012] This method uses glucose as a substrate, which is relatively simple and has certain differences from the present method in terms of substrate. In addition, the reaction has a low yield under blue light and requires a higher-energy ultraviolet lamp to excite the photocatalyst. Summary of the Invention

[0013] The technical problem to be solved by the present invention is how to provide a method for synthesizing naphthyl propargyl fluoride compounds through sulfur hexafluoride, which has simple operation, good functional group tolerance, a wide range of substrate types, high SF6 utilization, easy promotion in industrial production, and high reaction yield.

[0014] The present invention solves the above technical problems through the following technical means:

[0015] A method for synthesizing a naphthyl propargyl fluoride compound from sulfur hexafluoride comprises the following steps: placing a naphthyl propargyl alcohol compound, a photocatalyst, a base, and a solvent in a reaction vessel, filling the reaction vessel with sulfur hexafluoride gas, and reacting under blue light to obtain a naphthyl propargyl fluoride compound; the naphthyl propargyl alcohol compound has the structural formula Wherein R1 is hydrogen or alkyl.

[0016] Description: Under the irradiation of light, naphthyl propargyl alcohol compounds undergo fluorination reaction under the combined action of SF6, alkali and photocatalyst to generate naphthyl propargyl fluoride compounds; the reaction formula is as follows:

[0017]

[0018] Wherein, the gaseous fluorination agent is sulfur hexafluoride, wherein R1 is hydrogen or an alkyl group.

[0019] Beneficial Effects: The present invention provides a broadly applicable method for synthesizing propargyl fluorides, particularly aromatic and aliphatic propargyl fluorides. Therefore, there are practically no strict restrictions on the number and types of substituents in alcohol compounds and their derivatives.

[0020] Preferably, the naphthyl propargyl alcohol compound is

[0021] Preferably, the molar ratio of the base to the naphthyl-containing propargyl alcohol compound is 4 to 6:1; further preferably, the molar ratio of the base to the naphthyl-containing propargyl alcohol compound is 5:1. When the molar ratio of the base to the naphthyl-containing propargyl alcohol compound is 5:1, the yield of the final product is high.

[0022] Preferably, the base is one of N,N-diisopropylethylamine (DIPEA), triethylamine (Et3N), and pyridine; more preferably, N,N-diisopropylethylamine (DIPEA). When the base is N,N-diisopropylethylamine (DIPEA), the yield of the final product is high.

[0023] Preferably, the molar ratio of the photocatalyst to the naphthyl propargyl alcohol compound is 0.0005-0.02:1, and the preferred molar ratio of the photocatalyst to the naphthyl propargyl alcohol compound is 0.01:1 or 0.015:1. When the molar ratio of the photocatalyst to the naphthyl propargyl alcohol compound is 0.01:1 or 0.015:1, the yield of the final product is high.

[0024] Preferably, the photocatalyst is one or more of [Ir(ppy)2(dtbbpy)]PF6 and 4-CzIPN, and more preferably [Ir(ppy)2(dtbbpy)]PF6. When the photocatalyst is [Ir(ppy)2(dtbbpy)]PF6, the yield of the final product is high.

[0025] Note: The Chinese name of [Ir(ppy)2(dtbbpy)]PF6 is (4,4-di-tert-butyl-2,2-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate; the Chinese name of 4-CzIPN is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile.

[0026] Preferably, the solvent is one or more of dichloromethane, tetrahydrofuran, and acetonitrile, more preferably dichloromethane. When the solvent is dichloromethane, the yield of the final product is high.

[0027] Preferably, the molar concentration of the naphthyl-containing propargyl alcohol compound in the solvent is 0.1 mmol / mL.

[0028] The present invention is carried out in a single organic solvent system; if necessary, other organic solvents may also be present in the system, but from the perspective of reaction yield and simplicity of operation, it is preferably not added with other organic solvents, that is, a single organic solvent is used as the reaction solvent.

[0029] Preferably, the wavelength of the blue light is 465 nm.

[0030] Preferably, the reaction temperature is room temperature.

[0031] Preferably, the reaction time is 18 to 24 hours, preferably 24 hours.

[0032] The reaction temperature and reaction time of the present invention can be determined by technicians according to different alcohol compounds and actual needs.

[0033] The present invention provides a refining process for naphthyl-containing propargyl fluoride compounds produced by the method. After the reaction is completed, the solvent is removed in vacuo, and the refined phenyl-containing propargyl fluoride compounds are obtained by column chromatography separation.

[0034] The advantages of the present invention are:

[0035] 1. The present invention uses readily available alcohols as reaction substrates, SF6 as a fluorination agent, and inexpensive and readily available DIPEA as a base. The reaction temperature is room temperature, and under the conditions of blue light as a light source and (4,4-di-tert-butyl-2,2-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate as a photocatalyst, a simple and efficient synthesis of propargyl fluoride compounds is achieved. Compared with other methods for synthesizing propargyl fluoride compounds, the present invention offers mild reaction conditions, uses readily available and inexpensive raw materials (including propargyl alcohol and N,N-diisopropylethylamine), and can effectively utilize SF6 gas at low energy levels under blue light irradiation. The reaction is characterized by low cost, low energy consumption, and environmental friendliness.

[0036] 2. The present invention is applicable to a variety of propargyl alcohol compounds, including aromatic propargyl alcohol, aliphatic propargyl alcohol, and heterocyclic propargyl alcohol, and can thus produce a variety of propargyl fluoride compounds.

[0037] 3. The present invention can be widely used in drug synthesis and total synthesis of natural products in industry and academia, and has high application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 This is the H NMR spectrum of 2-(1-fluoropropyl-2-alkynyl-1-yl)naphthalene described in Example 1. DETAILED DESCRIPTION

[0039] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0040] The raw materials used in the following specific examples can all be purchased commercially, and each reagent was purified by means known in the art before use when necessary.

[0041] In the present invention, "propargyl alcohol fluorine compounds" have the meaning commonly understood by those skilled in the art, that is, compounds in which the α position of the alkynyl group is substituted by fluorine (-F), such as 2-propyne-1-fluorine and its various derivatives.

[0042] In the present invention, "propargyl alcohol compounds" have the meaning commonly understood by those skilled in the art, that is, compounds in which the α position of the alkynyl group is substituted by oxygen (-OH), such as 2-propyn-1-ol, 1-phenyl-1-heptyn-3-ol, 1,4-diphenylbut-3-yn-2-ol and various derivatives thereof.

[0043] The raw materials used in the following specific examples can all be purchased commercially, and each reagent was purified by means known in the art before use when necessary.

[0044] 1 H NMR and 13 C NMR measurements were performed using a Bruker Avance 400 spectrometer. The test temperature was room temperature, the solvent was deuterated chloroform, and the references were: 1 H NMR: CHCl3 7.260 ppm; 13 C NMR: CHCl3: 77.000 ppm.

[0045] Example 1: Synthesis of 2-(1-fluoropropyl-2-alkynyl-1-yl)naphthalene

[0046] In an 8 mL sample vial equipped with a magnetic stirrer, the photocatalyst [Ir(ppy)2(dtbbpy)]PF6 (2.0 mg, 2 mmol%) and 1-(2-naphthyl)prop-2-yn-1-ol (54.6 mg, 1.0 eq, 0.3 mmol) were added and dissolved in DCM (3.0 mL) to form a 1-(2-naphthyl)prop-2-yn-1-ol solution. The sample vial was capped and the solution was bubbled with a balloon filled with SF6 gas for 5 minutes. After that, the base DIPEA (261.3 μL, 5.0 eq, 1.5 mmol) was added. The mixture was then irradiated with 465 nm LED blue light for 24 hours with stirring at room temperature. After completion of the reaction, the solvent was removed in vacuo, and the mixture was concentrated by rotary evaporation and then subjected to column chromatography to obtain 112.3 mg of 2-(1-fluoropropyl-2-ynyl-1-yl)naphthalene in a 61% yield.

[0047] Product 2-(1-fluoropropyl-2-alkynyl-1-yl)naphthalene: 1 H NMR (400MHz, CDCl3) δ8.04(s,1H),7.94-7.88(m,3H),7.68(d,1H),7.59-7.53(m,2H),6.26(dd,J=48.0,2.0Hz,1H),2.97(dd,J=5.6,2.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ133.7 (d, J = 2.1Hz), 133.4 (d, J = 21.0Hz), 132.9 (d, J = 1.6Hz), 128.7 (d, J = 1.3Hz), 128.4 (d, J = 1.4Hz), 127.7 (d, J = 1.5Hz), 126.9 (d, J = 1.4Hz), 126.8 (d, J = 5.9Hz), 126.6, 124.2 (d, J = 3.2Hz), 83.0 (d, J = 168.6Hz), 79.3 (d, J = 28.7Hz), 78.7 (d, J = 9.8Hz). 19 F NMR (376MHz,CDCl3)δ-157.5.

[0048]

[0049]

[0050] As can be seen from Example 1, the method of the present invention is to start from various types of cheap and readily available propargyl alcohol compounds, use commercial SF6 as a fluorinating agent, adopt cheap and readily available DIPEA as a base, the reaction temperature is room temperature, and under blue light as a light source and [Ir(ppy)2(dtbbpy)]PF6 as a photocatalyst, naphthyl propargyl fluorine compounds are synthesized simply and efficiently. The method has good applicability for aromatic propargyl alcohol, aliphatic propargyl alcohol and propargyl alcohol compounds containing other functional groups. It is a kind of reaction condition mild, the reaction raw materials used (including propargyl alcohol, DIPEA) are all cheap and readily available, can be well utilized SF6 gas with lower energy under blue light irradiation, and has low raw material price, low energy consumption, environmental friendliness, and a general synthesis method that can be promoted in industry.

[0051] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride, characterized in that: The method comprises the following steps: placing a naphthyl propargyl alcohol compound, a photocatalyst, a base, and a solvent in a reaction vessel, filling the reaction vessel with sulfur hexafluoride gas, and reacting the reaction vessel under blue light to obtain a naphthyl propargyl fluoride compound; the naphthyl propargyl alcohol compound has the structural formula: , wherein R1 is hydrogen or alkyl; the photocatalyst is [Ir(ppy)2(dtbbpy)]PF6, the base is N,N-diisopropylethylamine, and the solvent is dichloromethane.

2. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The naphthyl-containing propargyl alcohol compound is .

3. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The molar ratio of the base to the naphthyl-containing propargyl alcohol compound is 4-6:

1.

4. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 3, characterized in that: The molar ratio of the base to the naphthyl-containing propargyl alcohol compound is 4:

1.

5. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The molar ratio of the photocatalyst to the naphthyl-containing propargyl alcohol compound is 0.0005-0.02:

1.

6. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 5, characterized in that: The molar ratio of the photocatalyst to the naphthyl-containing propargyl alcohol compound is 0.02:

1.

7. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The molar concentration of the naphthyl-containing propargyl alcohol compound in the solvent is 0.1 mmol / mL.

8. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The wavelength of the blue light is 465 nm.

9. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: The reaction temperature is room temperature, and the reaction time is 18 to 24 hours.

10. The method for synthesizing naphthyl propargyl fluoride compounds from sulfur hexafluoride according to claim 1, characterized in that: After the reaction is completed, the solvent is removed in vacuo and the product is separated by column chromatography to obtain a naphthyl-containing propargyl fluoride compound.

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