A method for deoxygenation-reductive olefination of methyl ketone compounds

Abstract

The present invention discloses a method for deoxidation-reduction-alkenylation of methyl ketone compounds, characterized by comprising the following steps: mixing a methyl ketone compound, a reducing agent, and a solvent under the action of a protective gas and a catalyst, and then heating the mixture to react to obtain an alkenylation product; the structural formula of the methyl ketone compound is: #imgabs0#; the structural formula of the alkenylation product is: #imgabs1#. The beneficial effects of the present invention are as follows: (1) the raw materials of the present invention are widely available and easy to obtain, with low cost, and the synthesis of some raw materials is simple and efficient; the preparation method is simple to operate and the reaction conditions are mild; (2) no toxic or harmful gases are generated after the reaction, which has little impact on the atmosphere and also protects the health of operators; (3) the present invention has wide applicability and high yield; (4) in the present invention, the methyl ketone is directly deoxidized and reduced to the corresponding olefin without the participation of metal reagents, which not only has low cost and good functional group compatibility, but also has high chemical selectivity and conversion rate, and good applicability.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for deoxygenation-reductive olefination of methyl ketone compounds. Background Art

[0002] Carbonyl compounds are important natural resources, and their catalytic reduction reactions are a hot topic in the field of organic synthesis. In particular, the reductive deoxygenation of aromatic ketones to obtain the corresponding alkanes or alkenes is a powerful tool for synthesizing biofuels from biomass feedstocks. In 1969, Shapiro proposed an effective strategy for converting ketones to alkenes, namely, the ketone reacts with (p-phenylsulfonyl)hydrazine to obtain the corresponding hydrazone, and the hydrazone reacts with a strong base (such as n-butyllithium) to obtain the alkenes. Subsequently, Carney and Hiegel improved the Clemmensen reduction process and also obtained a method for reducing aromatic ketones to aromatic alkenes. Although traditional methods have been widely used, their substrate range is limited and metal waste is generated. The development of a broadly applicable and simple alkenylation reaction is a very meaningful topic. In recent years, methods for the direct deoxygenation of ketones to olefins catalyzed by rhenium (ChemCatChem, 2015, 7(7): 1177-83), molybdenum, rhodium (Green Chemistry, 2016, 18(9): 2675-81), and nickel (JACS Au, 2022, 2(8): 1929-34) complexes have been developed, opening up new avenues for the green and efficient synthesis of olefins. However, they still face problems such as the instability of metal reagents and limited substrate range. Metal-free catalysis often requires high temperature and high pressure (Angew.Chem. Int. Ed., 2015, 54(29): 8511-4), or the addition of strong acid or excess base, as well as complex catalysts and the need for step-by-step reactions. Therefore, it is particularly important to develop a metal-free, mild, and simple catalytic system for the deoxygenation reduction of ketones to olefins. Summary of the Invention

[0003] In view of the shortcomings of the prior art, the present invention aims to provide a method for the deoxygenation-reductive olefination of methyl ketone compounds.

[0004] To achieve the above object, the present invention provides the following technical solutions:

[0005] A method for deoxygenation-reductive olefination of methyl ketone compounds,

[0006] The steps include:

[0007] Under the action of protective gas and catalyst, a methyl ketone compound, a reducing agent and a solvent are mixed, and then the temperature is raised to react to obtain an olefination product;

[0008] The structural formula of the methyl ketone compound is: ;

[0009] The structural formula of the alkenylation product is: .

[0010] As a further improvement of the present invention,

[0011] The methyl ketone compound is 4-biphenylacetophenone or 4-chlorobiphenylacetophenone or 2-phenylacetophenone or 2-naphthylacetophenone or 4-tert-butylacetophenone or 4-bromoacetophenone or 4-iodoacetophenone or 3-chloroacetophenone or 2-benzofuranylacetophenone.

[0012] As a further improvement of the present invention,

[0013] The catalyst is tris(pentafluorophenyl)borane.

[0014] As a further improvement of the present invention,

[0015] The reducing agent is pinacol borane.

[0016] As a further improvement of the present invention,

[0017] The reaction temperature is 60-100°C.

[0018] As a further improvement of the present invention,

[0019] The reaction time is 10 to 15 hours.

[0020] As a further improvement of the present invention,

[0021] The solvent is n-hexane.

[0022] As a further improvement of the present invention,

[0023] The molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 0.5-1.5:0.03-0.08:1.5-2.

[0024] As a further improvement of the present invention,

[0025] The molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 1.0:0.05:1.8.

[0026] As a further improvement of the present invention,

[0027] The protective gas is nitrogen.

[0028] Reaction equation of the present invention is:

[0029]

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] (1) The raw materials of the present invention are widely available and easy to obtain, with low cost, and the synthesis of some raw materials is simple and efficient; the preparation method is simple to operate, the reaction conditions are mild, energy consumption is reduced, and the reaction selectivity is strong, and the target product can be directly synthesized with a yield of up to 95%;

[0032] (2) The present invention does not generate any toxic or harmful gases after the reaction, which has little impact on the atmosphere and also protects the health of the operators;

[0033] (3) The present invention has wide applicability and high yield. It is an important supplement to the deoxygenation reduction method of methyl ketone to olefin synthesis, and provides an important idea for the synthesis of dyes and drug molecules from biomass raw materials.

[0034] (4) In the present invention, methyl ketone is directly deoxidized and reduced to the corresponding olefin without the involvement of metal reagents. This not only has low cost and good functional group compatibility, but also has high chemical selectivity and conversion rate and good universality. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a schematic diagram of the reaction principle of Example 1 of the present invention;

[0036] Figure 2 Schematic diagram of the reaction principle of the prior art. DETAILED DESCRIPTION Example 1

[0037] The preparation of 4-biphenylethylene has the following structural formula:

[0038]

[0039] Under nitrogen atmosphere, 0.5 mmol of raw material 4-biphenylacetone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 92%. 1H NMR (400 MHz, CDCl3) δ 7.65 (dd, J = 11.7, 8.3 Hz, 4H), 7.59 – 7.44 (m, 4H), 7.41 (d, J = 7.3 Hz, 1H), 6.82 (dd, J = 17.6, 10.9 Hz, 1H), 5.86 (d, J = 17.6 Hz, 1H), 5.34 (d, J = 10.9 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 140.8, 140.6, 136.7, 136.7, 128.8, 127.3, 127.2, 127.0, 126.7,113.9. Example 2

[0040] The preparation of 4-chlorophenylstyrene has the following structural formula:

[0041]

[0042] Under nitrogen atmosphere, 0.5 mmol of raw material 4-chlorobiphenyl acetone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 87%. 1H NMR (400 MHz, CDCl3) δ 7.48 (dd, J = 16.5, 7.9 Hz, 7H), 7.38 (d, J = 8.3 Hz, 2H), 6.74 (dd, J = 17.6, 10.9 Hz, 1H), 5.78 (d, J = 17.6Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H).13C NMR (126 MHz, CDCl3) 139.4, 139.3,137.1, 136.4, 133.5, 129.1, 128.3, 127.2, 126.9, 114.3. Example 3

[0043] Preparation of 2-biphenylethylene, the structural formula is as follows:

[0044]

[0045] Under nitrogen atmosphere, 0.5 mmol of the raw material 2-biphenylacetophenone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 75%. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 5.0 Hz, 1H), 7.52 –7.28 (m, 8H), 6.78 (dd, J = 17.5, 11.0 Hz, 1H), 5.76 (d, J = 17.5 Hz, 1H), 5.24 (d, J = 10.6 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 141.0, 136.1, 135.9,130.2, 129.9, 128.1, 127.8, 127.6, 127.1, 125.8, 114.8. Example 4

[0046] The preparation of 2-naphthylethylene has the following structural formula:

[0047]

[0048] Under nitrogen atmosphere, 0.5 mmol of raw material 2-naphthyl ethyl ketone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 74%. 1H NMR (400 MHz, CDCl3) δ 7.82 – 7.76 (m, 3H), 7.74 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.48 – 7.40 (m, 2H), 6.87 (dd, J = 17.6, 10.9 Hz,1H), 5.86 (d, J = 17.6 Hz, 1H), 5.33 (d, J = 10.9 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 137.0, 135.1, 133.6, 133.2, 128.2, 128.1, 127.7, 126.4, 126.3,126.0, 123.2, 114.2. Example 5

[0049] Preparation of 4-tert-butylstyrene, the structural formula is as follows:

[0050]

[0051] Under nitrogen atmosphere, 0.5 mmol of raw material 4-tert-butylacetophenone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 82%. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 0.8 Hz, 4H), 6.80 (ddd, J = 17.6, 10.9, 0.7 Hz, 1H), 5.81 (d, J = 17.6 Hz, 1H), 5.29 (d, J =10.9 Hz, 1H), 1.42 (s, 9H).13C NMR (126 MHz,) δ 151.0, 136.7, 135.0, 126.1,125.6, 113.1,34.7, 31.4. Example 6

[0052] Preparation of 4-bromostyrene, the structural formula is as follows:

[0053]

[0054] Under nitrogen atmosphere, 0.5 mmol of raw material 4-bromoacetophenone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 91%. 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 8.4 Hz, 2H), 7.32 (d,J = 8.4 Hz, 2H), 6.70 (dd, J = 17.6, 10.9 Hz, 1H), 5.79 (dd, J = 17.6, 0.5Hz, 1H), 5.33 (d, J = 10.9 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 136.6, 135.9,131.8, 127.9, 121.7, 114.7. Example 7

[0055] Preparation of 4-iodostyrene, the structural formula is as follows:

[0056]

[0057] Under nitrogen atmosphere, 0.5 mmol of raw material 4-iodoacetophenone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 83%. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 2H), 7.26 (s,1H), 7.14 (d, J = 8.2 Hz, 2H), 6.63 (dd, J = 17.6, 10.9 Hz, 1H), 5.75 (d, J =17.6 Hz, 1H), 5.27 (d, J = 10.9 Hz, 1H).13C NMR (126 MHz, CDCl3) δ 137.6,137.1, 135.9, 128.0, 114.8, 93.1. Example 8

[0058] Preparation of 3-chlorostyrene, the structural formula is as follows:

[0059]

[0060] Under a nitrogen atmosphere, 0.5 mmol of 3-chloroacetophenone, 0.025 mmol of tris(pentafluorophenyl)borane as a catalyst, and 0.9 mmol of pinacol borane were added. The reaction was continued at 80°C for 12 hours. The product was isolated by column chromatography in a 95% yield. H NMR (400 MHz, CDCl₃) δ 7.44 (s, 1H), 7.35 – 7.29 (m, 2H), 7.29 – 7.18 (m, 2H), 7.12 (d, J = 7.2 Hz, 1H), 5.81 (d, J = 17.6 Hz, 1H), 5.35 (d, J = 10.9 Hz, 1H).

[0061] 13C NMR (126 MHz, CDCl3) δ 139.6, 135.8, 129.9, 127.9, 126.3, 124.6,115.5, 29.9. Example 9

[0062] Preparation of 2-vinylbenzofuran, the structural formula is as follows:

[0063]

[0064] Under nitrogen atmosphere, 0.5 mmol of raw material 2-benzofurylethanone, catalyst tris(pentafluorophenyl)borane (0.025 mmol), pinacol borane (0.9 mmol), and n-hexane (1.0 mL) were added as solvent. The reaction was carried out at 80°C for 12 hours. The product was separated by column chromatography with a yield of 47%. 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.6 Hz, 1H), 7.50 (d,J = 8.3 Hz, 1H), 7.31 (d, J = 5.1 Hz, 1H), 7.25 (d, J = 7.3 Hz, 1H), 6.64 (s,2H), 6.01 (d, J = 17.5 Hz, 1H), 5.43 (d, J = 11.2 Hz, 1H).13C NMR (126 MHz, )δ 154.9, 154.8, 128.8, 125.3, 124.7, 122.8, 121.0, 115.8, 111.0, 104.8.

[0065] Ingredients:

[0066] name factory 4-Biphenylacetophenone Anaiji Chemical 4-Chlorobiacetophenone Anaiji Chemical 2-Biphenylacetophenone Anaiji Chemical 2-Naphthyl ethyl ketone Anaiji Chemical 4-tert-Butylacetophenone Anaiji Chemical 4-Bromoacetophenone Anaiji Chemical 4-iodoacetophenone Anaiji Chemical 3-Chloroacetophenone Anaiji Chemical 2-Benzofuranylacetone Anaiji Chemical tris(pentafluorophenyl)borane Inokai Pinacol borane Braingwei n-hexane Sinopharm

[0067] Prior art patent No. 202411165213.X, entitled "A Method for Ketone Deoxygenation Reduction," discloses a method for ketone deoxygenation reduction. The method comprises: mixing a ketone compound, a composite catalyst, a reducing agent, and an organic solvent to obtain a mixed raw material; subjecting the mixed raw material to a reduction reaction under an inert gas atmosphere to obtain a reaction product; and separating the reaction product by column chromatography to obtain an alkane compound. The composite catalyst comprises lutetium chloride and tris(pentafluorophenyl)borane, wherein the amount n1 of lutetium chloride and the amount n2 of tris(pentafluorophenyl)borane satisfy the relationship: n1:n2 = 2:1. This method, through the synergistic catalytic action of lutetium chloride and tris(pentafluorophenyl)borane, can achieve deoxygenation reduction of various ketone compounds under mild conditions to obtain structurally diverse alkane compounds, thereby reducing the difficulty of deoxygenation reduction of ketone compounds.

[0068] However, the existing technology mainly reduces ketone compounds into olefin compounds, and cannot reduce them into olefin compounds, that is, cannot form double bonds.

[0069] Compared with the existing technology, Figure 1 Taking Example 1 as an example, the reaction principle of the present invention is specifically as follows:

[0070] First, tris(pentafluorophenyl)borane B(C6F5)3 activates pinacol borane HBpin to form intermediate B. Biphenyl acetone then undergoes hydroboration with intermediate A to form intermediate B, while simultaneously regenerating tris(pentafluorophenyl)borane B(C6F5)3. Intermediate B further coordinates with intermediate A to form intermediate C, which then undergoes borylation to form intermediates D and E. Intermediate E then undergoes C-O bond cleavage to remove a member of (OBpin)2, forming a carbon cation intermediate F. Finally, intermediate F loses H+ to form the product biphenylethylene.

[0071] The patented reaction principle of the prior art refers to Figure 2 , specifically:

[0072] First, tris(pentafluorophenyl)borane B(C6F5)3 activates pinacol borane HBpin to form intermediate B. Acetophenone coordinates with LuCl3 to form intermediate A. Intermediate A and intermediate B undergo hydroboration to form intermediate C, while simultaneously regenerating tris(pentafluorophenyl)borane B(C6F5)3 and LuCl3. Intermediate C further reacts with intermediate B to form intermediate D, which undergoes further borylation to form intermediates F and intermediate E. Intermediate F then undergoes C-O bond cleavage to remove a member of (OBpin)2 to form a carbon cation intermediate G. Finally, intermediate G is attacked by H- ions to form ethylbenzene, and tris(pentafluorophenyl)borane B(C6F5)3 is regenerated to complete the cycle.

[0073] The reaction mechanisms of the two are different, and the reaction temperature, the equivalent amount of pinacol borane used, the choice of catalyst, and the choice of solvent are completely different. The most obvious difference lies in the working principle of the catalyst and the final carbon cation intermediate step. In this application, the carbon cation undergoes dehydrogenation of protons to produce olefins. In the patent of the prior art, the carbon cation combines with H anions to produce alkanes, and lutetium chloride activates the substrate ketone. In addition, the reaction temperature, solvent, and HBpin dosage will affect the entire mechanism process.

[0074] Carbocations are intermediates in organic reactions. Both reaction systems contain carbocation intermediates and HBpin. The hydride ion of HBpin acts as a nucleophile, attacking the carbocation, resulting in the patented alkane. By avoiding this affinity attack by the hydride ion and selectively deprotonating the carbocation, the patented alkene product is obtained. This selectivity is closely related not only to the catalyst but also to temperature, solvent, and the amount of pinacol borane used. The solvent's effect on the carbocation: In the 1,4-dioxane solvent, the coordination effect of oxygen enhances the stability of the carbocation, allowing it to react with excess pinacol borane to produce the alkane. This reaction is relatively easy, requiring no heating, and should not be used, as elevated temperatures would cause the carbocation to deprotonate, yielding the alkene. The effect of temperature on the reactivity of the carbocation: Increasing temperature favors the deprotonation of the carbocation intermediate to produce the alkene. However, this is also affected by the solvent and the amount of pinacol borane. Hexane, a non-polar solvent, does not coordinate and stabilize the carbocation, making it highly reactive. Furthermore, if an excess of pinacol borane is added to the reaction system, significant alcohol and alkane byproducts will be produced. Regarding the effect of pinacol borane on the reaction: If olefins are desired, the amount of pinacol borane should be neither too high nor too low. The 1.8 equivalents was arrived at through trial and error. Any greater amount will produce alcohols and alkanes as byproducts. Any less will also produce alcohols as byproducts. Furthermore, if the solvent used is changed to, for example, 1,4-dioxane, the 1.8 equivalents of pinacol borane will also produce byproducts, preventing the olefin from being obtained in high yield. Therefore, the selective production of olefins depends on the synergistic effects of solvent, temperature, and pinacol borane dosage.

[0075] Compared with the prior art, the present invention has the following beneficial effects:

[0076] (1) The raw materials of the present invention are widely available and easy to obtain, with low cost, and the synthesis of some raw materials is simple and efficient; the preparation method is simple to operate, the reaction conditions are mild, energy consumption is reduced, and the reaction selectivity is strong, and the target product can be directly synthesized with a yield of up to 95%;

[0077] (2) The present invention does not generate any toxic or harmful gases after the reaction, which has little impact on the atmosphere and also protects the health of the operators;

[0078] (3) The present invention has wide applicability and high yield. It is an important supplement to the deoxygenation reduction method of methyl ketone to olefin synthesis, and provides an important idea for the synthesis of dyes and drug molecules from biomass raw materials.

[0079] (4) In the present invention, methyl ketone is directly deoxidized and reduced to the corresponding olefin without the involvement of metal reagents. This not only has low cost and good functional group compatibility, but also has high chemical selectivity and conversion rate and good universality.

[0080] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiment. All technical solutions based on the concept of the present invention are within the scope of protection of the present invention. It should be noted that for those skilled in the art, various improvements and modifications that do not depart from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A method for deoxygenation-reductive olefination of methyl ketone compounds, characterized in that: The steps include: Under the action of protective gas and catalyst, a methyl ketone compound, a reducing agent and a solvent are mixed, and then the temperature is raised to react to obtain an olefination product; The structural formula of the methyl ketone compound is: ; The methyl ketone compound is specifically 4-biphenylacetophenone or 4-chlorobiphenylacetophenone or 2-biphenylacetophenone or 2-naphthylacetophenone or 4-tert-butylacetophenone or 4-bromoacetophenone or 4-iodoacetophenone or 3-chloroacetophenone or 2-benzofuranylacetophenone; The structural formula of the alkenylation product is: ; The catalyst is tris(pentafluorophenyl)borane; The reducing agent is pinacol borane; The solvent is n-hexane.

2. The method for deoxygenation-reductive olefination of a methyl ketone compound according to claim 1, characterized in that: The reaction temperature is 60-100°C.

3. The method for deoxygenation-reductive olefination of a methyl ketone compound according to claim 1, characterized in that: The reaction time is 10 to 15 hours.

4. The method for deoxygenation-reductive olefination of a methyl ketone compound according to claim 1, wherein: The molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 0.5-1.5:0.03-0.08:1.5-2.

5. The method for deoxygenation-reductive olefination of a methyl ketone compound according to claim 1, wherein: The molar ratio of the methyl ketone compound, the catalyst and the reducing agent is 1.0:0.05:1.

8.

6. The method for deoxygenation-reductive olefination of a methyl ketone compound according to claim 1, wherein: The protective gas is nitrogen.

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