A method of photocatalytic synthesis of aniline compounds containing heptafluoroisopropyl substitution

Abstract

The application discloses a method for photocatalytic synthesis of aniline compounds containing heptafluoroisopropyl substitution, which comprises the following steps: mixing o-methylaniline, 2-bromoheptafluoropropane and an iridium photocatalyst, adding an ultradry solvent, stirring and reacting the reaction mixture under a light source, and maintaining the reaction temperature at room temperature to obtain the target product, i.e. the aniline compound containing heptafluoroisopropyl substitution. The application adopts photocatalysis, does not need heating, has no solid waste problem, is more environmentally friendly compared with a traditional sodium hydrosulfite reduction reaction, and has a much higher photocatalytic reaction yield than the traditional reduction reaction, low catalyst consumption, high yield and good selectivity.

Description

Technical Field

[0001] This invention belongs to the field of organic compound synthesis technology, specifically relating to a method for photocatalytic synthesis of aniline compounds containing heptafluoroisopropyl substituted compounds. Background Technology

[0002] Heptafluoroisopropyl-substituted aniline compounds are important organic synthesis intermediates with wide applications in the pharmaceutical and pesticide industries. In the pharmaceutical field, they serve as intermediates for the synthesis of antibiotics, antitumor drugs, and antiviral drugs. In the pesticide field, they are a crucial intermediate for the synthesis of the pesticide flubendiamide.

[0003] The classic method involves reducing heptafluoroisopropyl bromide with sodium hydrosulfite to generate a heptafluoroisopropyl radical, which then reacts with other substrates. This method can also be used to react with o-methylaniline to produce a pesticide intermediate containing a heptafluoroisopropyl-substituted aniline compound. However, this method generates a large amount of solid waste, and because the reaction occurs in a two-phase (water-oil) medium, an additional phase transfer catalyst is required, which also introduces new solid waste pollution. The reaction equation is as follows:

[0004]

[0005] The latest reported method (10.1039 / d4qo01660b) can also be used to synthesize aniline compounds containing heptafluoroisopropyl substituted compounds, but it requires the more expensive heptafluoroisopropyl iodine as a raw material and trimethoxyphosphine as a catalyst, which is toxic and highly irritating. The reaction equation is as follows:

[0006] Summary of the Invention

[0007] The purpose of this section is to outline some aspects of embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0008] In view of the problems existing in the above and / or prior art, the present invention is proposed.

[0009] One objective of this invention is to provide a method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups. This method uses photocatalysis, requires no heating, and avoids solid waste issues, making it more environmentally friendly than the traditional sodium hydrosulfite reduction reaction.

[0010] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a method for photocatalytic synthesis of aniline compounds containing heptafluoroisopropyl substituted compounds, comprising,

[0011] The compound shown in Formula I was mixed with the compound shown in Formula II and the photocatalyst iridium, and an ultra-dry solvent was added. The reaction mixture was stirred under a light source and the reaction temperature was maintained at room temperature to obtain the target product, an aniline compound containing heptafluoroisopropyl substituted heptafluoro.

[0012]

[0013] R1 is selected from hydrogen, methyl, and halogen; R2 is selected from bromine and iodine.

[0014] The photocatalyst iridium is [Ir(dFCF3ppy)2(bpy)]PF6, and its structural formula is:

[0015]

[0016] In a preferred embodiment of the photocatalytic synthesis method of heptafluoroisopropyl-substituted aniline compounds of the present invention, the molar ratio of o-methylaniline to 2-bromoheptafluoropropane is 1:1.05.

[0017] In a preferred embodiment of the photocatalytic synthesis method of heptafluoroisopropyl-substituted aniline compounds of the present invention, the molar ratio of the photocatalyst iridium to o-methylaniline is 0.001 to 0.01:1; the preferred molar ratio is 0.001:1.

[0018] As a preferred embodiment of the photocatalytic synthesis method of heptafluoroisopropyl-substituted aniline compounds of the present invention, the solvent includes one of acetonitrile, methanol, acetone, dichloromethane, ethyl acetate, tetrahydrofuran, and dichloroethane; the preferred solvent is dichloroethane.

[0019] As a preferred embodiment of the photocatalytic synthesis method of heptafluoroisopropyl-substituted aniline compounds of the present invention, wherein: the light source has a power of 10W and an illumination wavelength of 365-400nm; preferably, the illumination wavelength is 365nm.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] This invention uses photocatalysis, which requires no heating and eliminates solid waste issues. It is more environmentally friendly than the traditional sodium hydrosulfite reduction reaction. Furthermore, the photocatalytic reaction yield of this invention is much higher than that of the traditional reduction reaction, with low catalyst dosage, high yield, and good selectivity. Attached Figure Description

[0022] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0023] Figure 1 The nuclear magnetic resonance hydrogen spectrum of the target product obtained in Example 1 of this invention. Detailed Implementation

[0024] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0025] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0026] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0027] Unless otherwise specified, all raw materials used in the examples are commercially available.

[0028] Example 1

[0029] In a dry reaction flask, o-methylaniline (1 mmol), 2-bromoheptafluoropropane (1.05 mmol), and the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added sequentially. Then, 10 mL of ultra-dry dichloroethane (DCE) solvent was added, and the flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, wavelength 365 nm) (approximately 3.0 cm from the reaction system) and maintained at near room temperature by water cooling, with the room temperature controlled at 25°C in an air-conditioned room. After the reaction was complete, 10 mL of water was added to dilute the reaction mixture, and extraction was performed with ethyl acetate (3 × 10 mL). The combined organic phases were concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).

[0030] The structural formula of the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 is:

[0031]

[0032] The reaction formula is:

[0033]

[0034] The target product was characterized, and its proton nuclear magnetic resonance spectrum is shown below. Figure 1 As shown.

[0035] 1 H NMR (400MHz, Chloroform-d) δ7.27(s,1H),7.25(d,J=7.6Hz,1H),6.73(d,J=7.9Hz,1H),3.87(s,2H),2.21(s,3H).

[0036] 13 C NMR(101MHz,Chloroform-d)δ146.9,127.6(d,J=11.1Hz),124.6(d,J=10.1Hz),122.1(d,J=2.0Hz) ,120.8(qd,J=286.84Hz,27.3Hz),115.6(d,J=20.2Hz),114.4(d,J=2.0Hz),93.2–89.9(m),17.40.

[0037] 19 F NMR(376MHz,Chloroform-d)δ-76.00(d,J=7.5Hz,6F),-181.57–-181.68(m,1F).

[0038] Characterization data showed that the obtained reaction product was an aniline compound substituted with heptafluoroisopropyl (purity > 98%); the product yield was calculated to be 98%.

[0039] Example 2

[0040] This Example 2 is based on Example 1, except that the photocatalyst is replaced with Ru(bpy)3(PF6)2, and other conditions remain the same as in Example 1.

[0041] The structural formula of the photocatalyst Ru(bpy)3(PF6)2 is:

[0042]

[0043] The reaction product obtained was an aniline compound substituted with heptafluoroisopropyl, and the product yield was calculated to be 40%.

[0044] Example 3

[0045] This Example 3 is based on Example 1, except that the photocatalyst is replaced with Ru(bpy)3Cl2·6H2O, while other conditions remain the same as in Example 1.

[0046] The structural formula of the photocatalyst Ru(bpy)3Cl2·6H2O is:

[0047]

[0048] The reaction product obtained was an aniline compound substituted with heptafluoroisopropyl, and the yield of the product was calculated to be 33%.

[0049] Comparative Example 1

[0050] Comparative Example 1 is based on Example 1, except that the photocatalyst is replaced with CoTPP, and all other conditions are the same as in Example 1.

[0051] The structural formula of the photocatalyst CoTPP is:

[0052]

[0053] The results showed that the target product could not be obtained.

[0054] Comparative Example 2

[0055] Comparative Example 2 is based on Example 1, except that the photocatalyst is replaced with Salcomine, and all other conditions are the same as in Example 1.

[0056] The structural formula of the photocatalyst Salcomine is:

[0057]

[0058] The results showed that the target product could not be obtained.

[0059] Example 4

[0060] This Example 4 is based on Example 1, but the amount of photocatalyst added is adjusted, while other conditions remain the same as in Example 1. The results are shown in Table 1.

[0061] Table 1

[0062] <![CDATA[Photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6]]> Yield (%) 0.0005 mmol 88 0.001mmol 98 0.005mmol 98 0.01mmol 98

[0063] Example 5

[0064] This fifth example is based on the first example, but the solvent type is adjusted while other conditions remain the same as in the first example. The results are shown in Table 2.

[0065] Table 2

[0066]

[0067]

[0068] Example 6

[0069] This embodiment 6 is based on embodiment 1, but the light wavelength is adjusted while other conditions remain the same as in embodiment 1. The results are shown in Table 3.

[0070] Table 3

[0071] Light wavelength Yield (%) 365nm 98 395~400nm 90 450~455nm 45 530~535nm 39 595~600nm 19

[0072] Example 7

[0073] In a dry reaction flask, o-bromoaniline (1 mmol), 2-bromoheptafluoropropane (1.05 mmol), and the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added sequentially. Then, 10 mL of ultra-dry DCE solvent was added, and the flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, wavelength 365 nm) (approximately 3.0 cm from the reaction system) and maintained at near room temperature by water cooling, with the room temperature controlled by an air-conditioned room at 25°C. After the reaction was complete, 10 mL of water was added to dilute the reaction mixture, and extraction was performed with ethyl acetate (3 × 10 mL). The combined organic phases were concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).

[0074] The reaction formula is:

[0075]

[0076] The target product was characterized.

[0077] 1 H NMR (400MHz, Chloroform-d) δ7.64 (d, J=2.2Hz, 1H), 7.39–7.27 (m, 1H), 6.80 (dd, J=8.7, 0.9Hz, 1H), 4.19 (s, 2H).

[0078] 13C NMR(101MHz,Chloroform-d)δ146.42,130.17(d,J=12.1Hz),125.88(d,J=10.1Hz),120.76(qd, J=270.7Hz),116.60(d,J=21.2Hz),115.07(d,J=2.0Hz),108.72(d,J=3.0Hz),92.63–89.31(m).

[0079] 19 F NMR(376MHz,Chloroform-d)δ-76.09(d,J=7.5Hz,6F),-181.44–-181.56(m,1F).

[0080] Characterization data showed that the obtained reaction product was 2-bromo-4-heptafluoroisopropylaniline (purity > 98%); the product yield was calculated to be 95%.

[0081] Example 8

[0082] In a dry reaction flask, m-toluidine (1 mmol), 2-bromoheptafluoropropane (1.05 mmol), and photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added sequentially. Then, 10 mL of ultra-dry DCE solvent was added, and the flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, wavelength 365 nm) (approximately 3.0 cm from the reaction system) and maintained at near room temperature by water cooling, with the room temperature controlled by an air-conditioned room at 25°C. After the reaction was complete, 10 mL of water was added to dilute the reaction mixture, and extraction was performed with ethyl acetate (3 × 10 mL). The organic phases were combined and concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).

[0083] The reaction formula is:

[0084]

[0085] The target product was characterized.

[0086] 1 H NMR (400MHz, Chloroform-d) δ7.30–7.19(m,1H),6.53(dt,J=4.3,2.2Hz,2H),3.80(s,2H),2.42(d,J=8.5Hz,3H).

[0087] 13C NMR(101MHz,Chloroform-d)δ148.17,140.09,127.96,121.25(qd,J=286.8Hz,29.3Hz),119.15( d,J=1.1Hz), 113.60(d,J=20.2Hz), 112.04(d,J=1.1Hz), 95.98–93.24(m), 21.84(d,J=15.2Hz).

[0088] 19 F NMR(376MHz,Chloroform-d)δ-75.06(s,6F),-177.73(s,1F).

[0089] Characterization data showed that the obtained reaction product was 3-methyl-4-heptafluoroisopropylaniline (purity > 98%); the product yield was calculated to be 95%.

[0090] Example 9

[0091] In a dry reaction flask, aniline (1 mmol), 2-bromoheptafluoropropane (1.05 mmol), and the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added sequentially. Then, 10 mL of ultra-dry DCE solvent was added, and the flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, wavelength 365 nm) (approximately 3.0 cm from the reaction system) and maintained at near room temperature by water cooling, with the room temperature controlled at 25°C in an air-conditioned room. After the reaction was complete, 10 mL of water was added to dilute the reaction mixture, and extraction was performed with ethyl acetate (3 × 10 mL). The organic phases were combined and concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).

[0092] The reaction formula is:

[0093]

[0094] The target product was characterized.

[0095] 1 H NMR (400MHz, Chloroform-d) δ7.39 (d, J = 8.4Hz, 2H), 6.73 (d, J = 8.7Hz, 2H), 3.88 (s, 2H).

[0096] 13C NMR(101MHz,Chloroform-d)δ148.73,126.98(dp,J=10.1Hz,2.0Hz),120.85(qd,J =287.8Hz, 28.3Hz), 115.71 (d, J = 10.1Hz), 114.63 (d, J = 3.0Hz), 93.34–90.04 (m).

[0097] 19 F NMR(376MHz,Chloroform-d)δ-76.12(d,J=7.5Hz,6F),-181.60–-181.72(m,1F).

[0098] Characterization data showed that the obtained reaction product was 4-heptafluoroisopropylaniline (purity > 98%); the product yield was calculated to be 98%.

[0099] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method of photocatalytic synthesis of a compound containing a heptafluoroisopropyl substituted aniline characterized by: The compound shown as formula I is mixed with the compound shown as formula II and an iridium photocatalyst, a super-dry solvent is added, the reaction mixture is stirred under a light source, the reaction temperature is maintained at room temperature, and a target product containing a heptafluoroisopropyl-substituted aniline compound shown as formula III or formula IV is obtained; the light source has a power of 10 W and a wavelength of 365-400 nm; R1 is selected from one of hydrogen, methyl and halogen; R2 is selected from one of bromine and iodine; or (Formula I); (Formula II); (Formula III) or (Formula IV); The iridium photocatalyst is [Ir(dFCF3ppy)2(bpy)]PF6, and a structural formula thereof is as follows: The molar ratio of the compound shown as formula I to the compound shown as formula II is 1:1.

05. 。 2. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 1, wherein: The molar ratio of the iridium photocatalyst to the compound shown as formula I is 0.001-0.01:

1.

3. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 1, wherein: The molar ratio of the iridium photocatalyst to the compound shown as formula I is 0.001:

1.

4. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 3, wherein: The solvent includes one of acetonitrile, methanol, acetone, dichloromethane, ethyl acetate, tetrahydrofuran and dichloroethane.

5. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 1, wherein: The solvent is dichloroethane.

6. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 5, wherein: The light source has a power of 10 W and a wavelength of 365 nm.

7. The method of photocatalytic synthesis of heptafluoroisopropyl substituted aniline compounds as claimed in claim 1, wherein: ​

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