Method for photocatalytic synthesis of heptafluoroisopropyl substituted aniline compound

Abstract

The method comprises the following steps: mixing o-methylaniline, 2-bromoheptafluoropropane and a photocatalyst iridium, adding an ultra-dry solvent, carrying out a stirring reaction on the reaction mixture under a light source, and maintaining the reaction temperature at room temperature to obtain the target product heptafluoroisopropyl substituted aniline compound. Photocatalysis is adopted, heating is not needed, no solid waste problem exists, compared with a traditional sodium hydrosulfite reduction reaction, the method is more environmentally friendly, the photocatalytic reaction yield is far higher than that of the traditional reduction reaction, the catalyst dosage is low, the yield is high, and selectivity is good.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic compound synthesis, and specifically relates to a method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups. Background Art

[0002] Aniline compounds substituted with heptafluoroisopropyl groups are important organic synthesis intermediates and are widely used in the fields of medicine and pesticides. In the medical field, they can be used as intermediates for the synthesis of antibiotics, anti-tumor drugs, antiviral drugs, etc. In the pesticide field, they are important intermediates for the synthesis of the pesticide flubendiamide.

[0003] Classically, sodium dithionite is used to reduce heptafluoroisopropyl bromide to generate heptafluoroisopropyl radicals, which then react with other substrates. This method can also be used to react with o-toluidine to produce aniline compounds substituted with heptafluoroisopropyl groups, which are pesticide intermediates. However, this method produces a large amount of solid waste, and since the reaction is in a two-phase medium of water and oil, a phase transfer catalyst needs to be added additionally, which will also introduce 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 substituted with heptafluoroisopropyl groups, but it requires the use of more expensive heptafluoroisopropyl iodide as a raw material and trimethoxyphosphine as a catalyst. However, this catalyst is toxic and has strong irritation. The reaction equation is as follows:

[0006] Summary of the Invention

[0007] The purpose of this part is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Simplifications or omissions may be made in this part, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this part, the abstract, and the title. However, such simplifications or omissions shall not be used to limit the scope of the present invention.

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

[0009] One of the purposes of the present invention is to provide a method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups. By using photocatalysis, heating is not required, and there is no solid waste problem, which is more environmentally friendly than the traditional sodium dithionite reduction reaction.

[0010] To solve the above technical problems, the present invention provides the following technical solution: A method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups, comprising,

[0011] Mix the compound shown in Formula I with the compound shown in Formula II and the photocatalyst iridium, add an ultra-dry solvent, stir the reaction mixture under a light source, maintain the reaction temperature at room temperature, and obtain the target product, an aniline compound substituted with heptafluoroisopropyl;

[0012]

[0013] Among them, R1 is selected from one of hydrogen, methyl, and halogen; R2 is selected from one of bromine and iodine;

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

[0015]

[0016] As a preferred embodiment of the method for photocatalytic synthesis of an aniline compound substituted with heptafluoroisopropyl of the present invention, wherein: the molar ratio of o-toluidine to 2-bromoheptafluoropropane is 1:1.05.

[0017] As a preferred embodiment of the method for photocatalytic synthesis of an aniline compound substituted with heptafluoroisopropyl of the present invention, wherein: the molar ratio of the photocatalyst iridium to o-toluidine is 0.001-0.01:1; the preferred molar ratio is 0.001:1.

[0018] As a preferred embodiment of the method for photocatalytic synthesis of an aniline compound substituted with heptafluoroisopropyl of the present invention, wherein: 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 method for photocatalytic synthesis of an aniline compound substituted with heptafluoroisopropyl of the present invention, wherein: the light source has a power of 10W and a light irradiation wavelength of 365-400nm; the preferred light irradiation wavelength is 365nm.

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

[0021] The present invention adopts photocatalysis, does not require heating, has no solid waste problem, is more environmentally friendly than the traditional sodium dithionite reduction reaction, and the photocatalytic reaction yield of the present invention is much higher than that of the traditional reduction reaction, with low catalyst dosage, high yield, and good selectivity. Description of the Drawings

[0022] To more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings. Among them:

[0023] Figure 1 1H NMR spectrum of the target product obtained in Example 1 of the present invention. Detailed implementation manners

[0024] To make the above objects, features, and advantages of the present invention more apparent and understandable, the following will describe the detailed implementation manners of the present invention in conjunction with the embodiments of the specification.

[0025] In the following description, many specific details are set forth to fully understand the present invention. However, the present invention can also be implemented in other ways different from those described herein. Those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed below.

[0026] Secondly, the so-called "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that can be included in at least one implementation manner 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 separate or alternative embodiment that mutually excludes other embodiments.

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

[0028] Example 1

[0029] In a dry reaction flask, o-toluidine (1 mmol), 2-bromoheptafluoropropane (1.05 mmol), and the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added in sequence. Subsequently, 10 mL of ultradry dichloroethane (DCE) solvent was added, and then the reaction flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, light wavelength 365 nm) (the distance between the light source and the reaction system was about 3.0 cm), and maintained at a temperature close to room temperature through water cooling. The room temperature was controlled by an air-conditioned room environment at 25 °C. After the reaction was completed, 10 mL of water was added to the reaction mixture for dilution, and extraction was carried out with ethyl acetate (3 × 10 mL). After combining the organic phases, it was 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 above target product was characterized, and the 1H NMR spectrum is as Figure 1 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] According to the characterization data, the prepared reaction product is an aniline compound substituted with heptafluoroisopropyl group (purity > 98%); the product yield was calculated, and the result was 98%.

[0039] Example 2

[0040] In this Example 2, based on Example 1, the photocatalyst was replaced with Ru(bpy)3(PF6)2, and other conditions were the same as those in Example 1.

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

[0042]

[0043] The prepared reaction product is an aniline compound substituted with heptafluoroisopropyl group, and the product yield was calculated, and the result was 40%.

[0044] Example 3

[0045] Based on Example 1, in this Example 3, the photocatalyst was replaced with Ru(bpy)3Cl2·6H2O, and other conditions were kept the same as those in Example 1.

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

[0047]

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

[0049] Comparative Example 1

[0050] Based on Example 1, in this Comparative Example 1, the photocatalyst was replaced with CoTPP, and other conditions were kept the same as those in Example 1.

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

[0052]

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

[0054] Comparative Example 2

[0055] Based on Example 1, in this Comparative Example 2, the photocatalyst was replaced with Salcomine, and other conditions were kept the same as those in Example 1.

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

[0057]

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

[0059] Example 4

[0060] Based on Example 1, in this Example 4, the addition amount of the photocatalyst was adjusted, and other conditions were kept the same as those 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 0.001 mmol 98 0.005 mmol 98 0.01 mmol 98

[0063] Example 5

[0064] Based on Example 1, in this Example 5, the solvent type was adjusted, and other conditions were kept the same as those in Example 1. The results are shown in Table 2.

[0065] Table 2

[0066]

[0067]

[0068] Example 6

[0069] On the basis of Example 1, the light wavelength was adjusted in this Example 6, and other conditions were the same as those in Example 1. The results are shown in Table 3.

[0070] Table 3

[0071] Light wavelength Yield (%) 365 nm 98 395 - 400 nm 90 450 - 455 nm 45 530 - 535 nm 39 595 - 600 nm 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 in sequence. Subsequently, 10 mL of ultra-dry DCE solvent was added, and then the reaction flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, light wavelength 365 nm) (the distance between the light source and the reaction system was about 3.0 cm), and maintained at a state close to room temperature by water cooling. The room temperature was controlled by the air-conditioned room environment at 25 °C. After the reaction was completed, 10 mL of water was added to the reaction mixture for dilution, and extraction was carried out with ethyl acetate (3 × 10 mL). After combining the organic phases, it was 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 as follows:

[0075]

[0076] The above 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] 1313C NMR (101 MHz, Chloroform-d) δ 146.42, 130.17 (d, J = 12.1 Hz), 125.88 (d, J = 10.1 Hz), 120.76 (qd, J = 270.7 Hz), 116.60 (d, J = 21.2 Hz), 115.07 (d, J = 2.0 Hz), 108.72 (d, J = 3.0 Hz), 92.63–89.31 (m).

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

[0080] According to the characterization data, the prepared reaction product is 2-bromo-4-heptafluoroisopropyl aniline (purity > 98%); the product yield was calculated, and the result was 95%.

[0081] Example 8

[0082] In a dry reaction flask, m-toluidine (1 mmol), 2-bromoheptafluoropropane (1.05 mmol) and the photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added in sequence. Subsequently, 10 ml of ultra-dry DCE solvent was added, and the reaction flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, light wavelength 365 nm) (the distance between the light source and the reaction system was about 3.0 cm), and maintained at a state close to room temperature by water cooling. The room temperature was controlled by the air-conditioned room environment at 25 °C. After the reaction was completed, 10 mL of water was added to the reaction mixture for dilution, and extraction was carried out with ethyl acetate (3 × 10 mL). After combining the organic phases, it was concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).

[0083] The reaction equation is:

[0084]

[0085] Characterize the above target product.

[0086] 1 1H NMR (400 MHz, Chloroform-d) δ 7.30–7.19 (m, 1H), 6.53 (dt, J = 4.3, 2.2 Hz, 2H), 3.80 (s, 2H), 2.42 (d, J = 8.5 Hz, 3H).

[0087] 1313C NMR (101 MHz, Chloroform-d) δ 148.17, 140.09, 127.96, 121.25 (qd, J = 286.8 Hz, 29.3 Hz), 119.15 (d, J = 1.1 Hz), 113.60 (d, J = 20.2 Hz), 112.04 (d, J = 1.1 Hz), 95.98–93.24 (m), 21.84 (d, J = 15.2 Hz).

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

[0089] According to the characterization data, the prepared reaction product is 3-methyl-4-heptafluoroisopropyl aniline (purity > 98%); the product yield is calculated, and the result is 95%.

[0090] Example 9

[0091] In a dry reaction flask, aniline (1 mmol), 2-bromoheptafluoropropane (1.05 mmol) and photocatalyst [Ir(dFCF3ppy)2(bpy)]PF6 (0.001 mmol) were added successively. Subsequently, 10 ml of ultra-dry DCE solvent was added, and then the reaction flask was sealed with a rubber stopper. The reaction mixture was stirred under a specified light source (10 W, light wavelength 365 nm) (the distance between the light source and the reaction system was about 3.0 cm), and maintained at a temperature close to room temperature by water cooling, and the room temperature was controlled by the environment of an air-conditioned room at 25 °C. After the reaction was completed, 10 mL of water was added to the reaction mixture for dilution, and extraction was carried out with ethyl acetate (3 × 10 mL). After combining the organic phases, it was 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] Characterize the above target product.

[0095] 1 1H NMR (400 MHz, Chloroform-d) δ 7.39 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 3.88 (s, 2H).

[0096] 1313C NMR (101 MHz, Chloroform-d) δ 148.73, 126.98 (dp, J = 10.1 Hz, 2.0 Hz), 120.85 (qd, J = 287.8 Hz, 28.3 Hz), 115.71 (d, J = 10.1 Hz), 114.63 (d, J = 3.0 Hz), 93.34–90.04 (m).

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

[0098] According to the characterization data, the prepared reaction product is 4-heptafluoroisopropyl aniline (purity > 98%); the product yield was calculated, and the result was 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 them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention.

Claims

1. A method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups, characterized in that: including Mix the compound shown in Formula I with the compound shown in Formula II and the photocatalyst iridium, add an ultradry solvent, stir and react the reaction mixture under a light source while maintaining the reaction temperature at room temperature to obtain a target product, an aniline compound substituted with heptafluoroisopropyl; wherein, R1 is selected from one of hydrogen, methyl, and halogen; R2 is selected from one of bromine and iodine; wherein, the photocatalyst iridium is [Ir(dFCF3ppy)2(bpy)]PF6, and its structural formula is:

2. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl group as claimed in claim 1, wherein: The molar ratio of the compound shown in Formula I to the compound shown in Formula II is 1:1.

05.

3. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl group as claimed in claim 1, wherein: The molar ratio of the photocatalyst iridium to the compound shown in Formula I is 0.001 - 0.01:

1.

4. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups as claimed in claim 3, characterized in that: The molar ratio of the photocatalyst iridium to the compound shown in Formula I is 0.001:

1.

5. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl group as claimed in claim 1, wherein: The solvent includes one of acetonitrile, methanol, acetone, dichloromethane, ethyl acetate, tetrahydrofuran, and dichloroethane.

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

7. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups as claimed in claim 1, wherein: The light source has a power of 10 W and a light wavelength of 365 - 400 nm.

8. The method for photocatalytic synthesis of aniline compounds substituted with heptafluoroisopropyl groups as claimed in claim 7, wherein: The light source has a power of 10 W and a light wavelength of 365 nm.

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