A method for photocatalytic synthesis of quaternary carbon vicinal diamines

Abstract

This invention belongs to the field of organic synthesis technology, and discloses a method for photocatalytic synthesis of quaternary carbon 1-diamine, comprising the following steps: (1) adding magnetic electrodes, raw materials, and solvent sequentially into a photoreaction tube with an outer condenser, blowing argon gas through a fine needle, and then sealing the tube. (2) Circulating condenser water through the outer side of the photoreaction tube, placing the tube on a magnetic stirrer, turning on the magnetic stirrer, and simultaneously irradiating it with a blue LED light. (3) Vacuum concentrating the mixture obtained in step 2, and separating it by column chromatography to obtain the target compound, quaternary carbon 1-diamine. This invention utilizes inexpensive and readily available indigo-derived ketimine and N,N-xylene and its derivatives as raw materials, and successfully synthesizes quaternary carbon 1-diamine compounds under visible light catalysis conditions through the combined catalytic action of a photocatalyst and Brønsted acid. The conditions of this invention are mild, and the raw materials are inexpensive, readily available, and all are commercially available reagents.

Description

Technical Field

[0001] This invention relates to a method for photocatalytic synthesis of quaternary carbon 1,2-diamines, belonging to the field of organic synthesis technology. Background Technology

[0002] As a class of amino derivatives, ovoid diamines play an indispensable role in the structure of drug molecules and natural products. Furthermore, these structures are also important components of ligands and catalysts. Therefore, the preparation of ovoid diamines is currently a research hotspot in the synthetic and pharmaceutical fields, and the continuous development of new synthetic routes is essential. However, traditional preparation methods, such as the Corey and Raimondi methods, involve harsh conditions and the use of large amounts of metal reagents, which can cause environmental pollution to some extent. With the development of green chemistry, visible light photocatalysis, with its green and mild reaction characteristics, has attracted the attention of researchers and has been successfully applied to the preparation of ovoid diamines. However, current photocatalysis reactions are limited to the preparation of tertiary ovoid diamines (Angew. Chem. Int. Ed. 2016, 55, 6776–6779; Org. Chem. Front. 2019, 6, 2245–2249; Org. Biomol. Chem., 2022, 20, 4522-4525), while more challenging methods for synthesizing quaternary ovoid diamines are rarely reported. Summary of the Invention

[0003] To address the problems and shortcomings of existing technologies, the present invention aims to provide a photocatalytic method for the synthesis of quaternary carbon 1,4-diamines. This invention utilizes the co-catalytic action of a photocatalyst and Brønsted acid to achieve the preparation of quaternary carbon 1,4-diamines via the α-aminoalkylation reaction of indigo-derived ketimines. The methods employed in this invention are green and mild, and the operation is simple, overcoming the drawbacks of traditional synthesis methods that require stringent reaction conditions and large quantities of metal reagents.

[0004] To achieve the above-mentioned objectives, the technical solution adopted by this invention is as follows:

[0005] A method for photocatalytic synthesis of quaternary carbon o-diamines includes the following steps:

[0006] Step 1: Place the magnetic particle into a photoreaction tube with an outer condenser. Then, sequentially add 0.1-0.3 mmol of indigo-derived ketimine, 0.3-0.9 mmol of N,N-dimethylamine and its derivatives, 0.03-0.09 mol of Brønsted acid, and 0.001-0.005 mmol of photocatalyst to the photoreaction tube. Next, add 0.5-1.0 mL of degassing solvent. Purge the tube with a fine needle and introduce argon gas for 10-20 minutes, then seal it. The indigo-derived ketimine is selected from 1-methyl-3-(phenylimino)indol-2-one, 1-methyl-3-(p-tolylamino)indol-2-one, 3-((2-methoxyphenyl)imino)-1-methylindol-2-one, and 3-((4-chlorophenyl)imino)-1-methylindol-2-one. The N,N-xylene and its derivatives are selected from 4,N,N-trimethylaniline, 4-chloro-N,N-dimethylaniline or 4-methoxy-N,N-dimethylaniline; the Brønsted acid is selected from benzoic acid or glacial acetic acid; the photocatalyst is selected from tris(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate) or tripyridine ruthenium chloride hexahydrate; and the degassing solvent is selected from acetonitrile or DMSO.

[0007] Step 2: Pass condensate water through the outside of the photoreaction tube from Step 1, place the photoreaction tube on a magnetic stirrer, turn on the magnetic stirrer, stir for 8-48 hours, and irradiate with a blue LED light at room temperature for 8-48 hours.

[0008] Step 3: After the reaction is complete, the crude product is concentrated under vacuum and separated by column chromatography. The eluent is ethyl acetate and petroleum ether in a volume ratio of 1:10-20. The eluent containing the target product is detected by TLC and collected. The target compound, quaternary carboxy-1,2-diamine, is obtained by concentration under reduced pressure.

[0009] The beneficial effects of this invention are as follows: A method for photocatalytic synthesis of quaternary carbon 1-diamine includes the following steps: (1) placing a magnetic stirrer, raw materials, and solvent into a photoreaction tube with an external cooling water flow, blowing argon gas through a fine needle, and then sealing it. (2) Circulating cooling water through the outside of the photoreaction tube, placing the photoreaction tube on a magnetic stirrer, stirring with the magnetic stirrer, and simultaneously irradiating with a blue LED light. (3) Vacuum concentrating the mixture obtained in step 2, separating it by column chromatography, and concentrating under reduced pressure to obtain the target compound, quaternary carbon 1-diamine. Compared with existing technologies, this invention has the following advantages: First, the visible light photocatalytic reaction conditions are mild and the operation is simple; second, the raw materials are inexpensive and readily available, and all are commercial reagents; third, the reaction yield is high, and gram-scale reactions are achieved with a high yield. Attached Figure Description

[0010] Figure 1 This is the 1H NMR spectrum of the target compound quaternary carbon o-diamine 3aa from Example 1.

[0011] Figure 2 This is the carbon NMR spectrum of the target compound quaternary carbon o-diamine 3aa from Example 1.

[0012] Figure 3 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3ba, from Example 7.

[0013] Figure 4 This is the carbon NMR spectrum of the target compound quaternary carbon o-diamine 3ba from Example 7.

[0014] Figure 5 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3ca, from Example 8.

[0015] Figure 6 This is the carbon NMR spectrum of the target compound, quaternary carbon 3ca, from Example 8.

[0016] Figure 7 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3da, from Example 9.

[0017] Figure 8 This is the carbon NMR spectrum of the target compound, quaternary carbon o-diamine 3da, from Example 9.

[0018] Figure 9 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3ea, from Example 10.

[0019] Figure 10 This is the carbon NMR spectrum of the target compound quaternary carbon o-diamine 3ea from Example 10.

[0020] Figure 11 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3fa, from Example 11.

[0021] Figure 12 This is the carbon NMR spectrum of the target compound quaternary carbon o-diamine 3fa from Example 11.

[0022] Figure 13 This is the 1H NMR spectrum of the target compound quaternary carbon o-diamine 3ab from Example 12.

[0023] Figure 14 This is the carbon NMR spectrum of the target compound quaternary carbon o-diamine 3ab from Example 12.

[0024] Figure 15 This is the 1H NMR spectrum of the target compound, quaternary carbon o-diamine 3ac, from Example 13.

[0025] Figure 16 This is the carbon NMR spectrum of the target compound, quaternary carbon o-diamine 3ac, from Example 13. Detailed Implementation

[0026] Example 1

[0027]

[0028] Step 1: Place the magnetic particle into a photoreaction tube with a condenser wall. Then, add 0.2 mmol of 1-methyl-3-(phenylimino)indol-2-one as 1a, 0.6 mmol of 4,N,N-trimethylaniline as 2a, 0.06 mol of benzoic acid, and 0.004 mmol of tris(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate) salt to the photoreaction tube in sequence. Then, add 0.5 mL of acetonitrile. Purge the tube with a fine needle and introduce argon gas for 20 min before sealing.

[0029] Step 2: Pass condensate water through the outside of the photoreaction tube from Step 1, place the reaction tube on a magnetic stirrer, turn on the magnetic stirrer, stir for 24 hours, and irradiate with a blue LED lamp at room temperature for 24 hours.

[0030] Step 3: After the reaction is complete, the crude product is concentrated under vacuum and separated by column chromatography using ethyl acetate and petroleum ether at a volume ratio of 1:10. The eluent containing the target product is detected by TLC and collected. The product is then concentrated under reduced pressure to obtain the target compound, quaternary carbodiamine 3aa (61.8 mg, yield 83.2%). The 1H NMR spectrum is shown below. Figure 1 As shown, the carbon NMR spectrum is as follows. Figure 2 As shown.

[0031] Characterization data of the target compound, quaternary carbon o-diamine 3aa:

[0032] 1 HNMR(600MHz,Chloroform-d)δ7.38–7.31(m,2H),7.06–7.03(m,3H),6.95(t,J=7.9Hz,2H),6.90(d,J=7.7Hz,1H),6.84(d,J=8.5Hz,2H ),6.64(t,J=7.3Hz,1H),6.18(d,J=8.1Hz,2H),3.82(d,J=14.7Hz,1H),3.67(d,J=14.7Hz,1H),3.21(s,3H),2.81(s,3H),2.26(s,3H). 13CNMR(151MHz,Chloroform-d)δ177.86,148.42,145.20,143.13,129.62,129.33(d,J=8.7Hz),129.01,12 4.35,122.96,119.02,115.15,113.61,108.54,65.60,63.37,40.86,26.51,20.25.HRMS(ESI)calcdfor:C 24 H 25 N3O[M+Na] + :394.1890,found394.1888.

[0033] Example 2

[0034] The reaction operation and steps were the same as in Example 1, except that the photocatalyst was replaced by tris(2,2'-bipyridine)ruthenium(II) di(hexafluorophosphate) salt with tris(bipyridine)ruthenium chloride hexahydrate. After treatment, the target compound quaternary carbide o-diamine 3aa (46.5 mg, yield 62.7%) was obtained.

[0035] Example 3

[0036] The reaction operation and steps were the same as in Example 1, except that Brønsted acid was replaced with glacial acetic acid instead of benzoic acid. After treatment, the target compound, quaternary carboxy-1,4-diamine 3aa (43.6 mg, yield 58.7%), was obtained.

[0037] Example 4

[0038] The reaction operation and steps were the same as in Example 1, except that the degassing solvent was changed from acetonitrile to DMSO. After treatment, the target compound, quaternary carbodiamine 3aa (48.8 mg, yield 65.8%), was obtained.

[0039] Example 5

[0040] The reaction operation and steps were the same as in Example 1, except that the amount of photocatalyst was changed from 0.004 mmol to 0.002 mmol. After treatment, the target compound quaternary carbide 3aa (55.2 mg, yield 74.3%) was obtained.

[0041] Example 6

[0042] The reaction operation and steps were the same as in Example 1, except that the stirring time and light exposure time were changed from 24h to 18h. After treatment, the target compound quaternary carbodiamine 3aa (57.0mg, yield 76.8%) was obtained.

[0043] Example 7

[0044]

[0045] The reaction steps and operations were the same as in Example 1, except that 1-methyl-3-(phenylimino)indol-2-one was replaced with 1-methyl-3-(p-tolylamino)indol-2-one as 1b. After treatment, the target compound, quaternary carbodiamine 3ba (55.4 mg, yield 71.9%), was obtained. The 1H NMR spectrum is shown below. Figure 3 As shown, the carbon NMR spectrum is as follows. Figure 4 As shown.

[0046] Characterization data of the target compound, quaternary carbon o-diamine 3ba:

[0047] 1 HNMR(600MHz,Chloroform-d)δ7.38(d,J=7.2Hz,1H),7.33(t,J=7.7Hz,1H),7.07–7.01(m,3H),6.88(d,J=7.8Hz,1H),6.83(d,J=8.6Hz,2H),6.76(d, J=8.2Hz,2H),6.13(d,J=8.4Hz,2H),4.72(s,1H),3.83(d,J=14.8Hz,1H),3 .66(d,J=14.8Hz,1H),3.19(s,3H),2.80(s,3H),2.26(s,3H),2.12(s,3H). 13 CNMR(151MHz,Chloroform-d)δ178.03,148.46,143.23,142.82,129.55(d,J=6.9Hz),129.23,128.41,127.27,1 24.43,122.89,115.58,113.61,108.47,65.93,63.33,40.83,26.45,20.32(d,J=21.6Hz).HRMS(ESI)calcdfor:C 25 H 27 N3O[M+H] + 386.2227, found 386.2224.

[0048] Example 8

[0049]

[0050] The reaction steps and operations were the same as in Example 1, except that 1-methyl-3-(phenylimino)indol-2-one was replaced with 3-((2-methoxyphenyl)imino)-1-methylindol-2-one as 1c. After treatment, the target compound, quaternary carbodiamine 3ca (48.1 mg, yield 59.9%), was obtained. The 1H NMR spectrum is shown below. Figure 5 As shown, the carbon NMR spectrum is as follows. Figure 6 As shown.

[0051] Characterization data of the target compound, quaternary carbon o-diamine 3ca:

[0052] 1 HNMR(600MHz,Chloroform-d)δ7.32(t,J=8.1Hz,2H),7.01(d,J=8.3Hz,3H),6 .88(d,J=7.7Hz,1H),6.75(d,J=8.5Hz,2H),6.70(d,J=7.9Hz,1H),6.59(t,J=7 .7Hz,1H),6.46(t,J=7.7Hz,1H),5.63(d,J=7.9Hz,1H),5.34(s,1H),3.94(d, J=14.6Hz,1H),3.81(d,J=14.6Hz,1H),3.19(s,3H),2.76(s,3H),2.25(s,3H). 13 CNMR(151MHz,Chloroform-d)δ177.74,147.89,147.59,143.23,135.07,129.39(d,J=6.2Hz),129.18,126.89,124.51,12 2.79,120.89,118.05,113.53,111.74,109.75,108.38,65.62,62.86,55.54,41.03,26.49,20.26.HRMS(ESI)calcdfor:C 25 H 27 N3O2[M+H] + 402.2176, found 402.2174.

[0053] Example 9

[0054]

[0055] The reaction steps and operations were the same as in Example 1, except that 1-methyl-3-(phenylimino)indol-2-one was replaced with 3-((4-chlorophenyl)imino)-1-methylindol-2-one as 1d. After treatment, the target compound, quaternary carbodiamine 3da (62.7 mg, yield 77.4%), was obtained. The 1H NMR spectrum is shown below. Figure 7 As shown, the carbon NMR spectrum is as follows. Figure 8 As shown.

[0056] Characterization data of the target compound, quaternary carbon o-diamine 3da:

[0057] 1 HNMR(600MHz,Chloroform-d)δ7.35(t,J=7.4Hz,2H),7.06(t,J=7.9Hz,3H),6.90(t,J=7.9Hz,3H),6.84(d,J=8.5Hz,2H), 6.10(d,J=8.8Hz,2H),4.88(s,1H),3.80(d,J=14.8Hz,1H),3.65(d,J=14.8Hz,1H),3.21(s,3H),2.81(s,3H),2.26(s,3H). 13 CNMR(151MHz,Chloroform-d)δ177.57,148.40,143.90,143.12,129.68,129.53,128.92(d,J=7.5Hz),127.56 ,124.30,123.85,123.07,116.44,113.67,108.68,65.66,63.29,40.89,26.51,20.25.HRMS(ESI)calcdfor:C 24 H 24 ClN3O[M+H] + 406.1681,fo und406.1671.

[0058] Example 10

[0059]

[0060] The reaction steps and operations were the same as in Example 1, except that 1-methyl-3-(phenylimino)indol-2-one was replaced with 3-((2,5-dichlorophenyl)imino)-1-methylindol-2-one as 1e. After treatment, the target compound, quaternary carbodiamine 3ea (35.8 mg, yield 40.8%), was obtained. The 1H NMR spectrum is shown below. Figure 9 As shown, the carbon NMR spectrum is as follows. Figure 10 As shown.

[0061] Characterization data of the target compound, quaternary carbon o-diamine 3ea:

[0062] 1HNMR(600MHz,Chloroform-d)δ7.37(t,J=7.7Hz,1H),7.30(d,J=7.2Hz,1H),7.11–7.00(m,4H),6.95(d,J=7.8Hz,1H),6.84(d,J=8.5Hz, 2H), 6.52 (d, J = 8.4Hz, 1H), 5.63 (d, J = 2.1Hz, 1H), 3.83 (d, J = 14.8Hz, 1H), 3.77 (d, J = 14.8Hz, 1H), 3.27 (s, 3H), 2.89 (s, 3H), 2.26 (s, 3H). 13 CNMR(151MHz,Chloroform-d)δ176.69,148.11,142.96,142.19,132.90,129.81(d,J=5.6Hz),129.63,128.21,127.78 ,124.33,123.28,118.94,118.49,113.99,113.13,108.77,65.07,63.00,41.17,26.62,20.27.HRMS(ESI)calcdfor:C 24 H 24 Cl2N3O[M+H] + 440.1291, found 440.1294.

[0063] Example 11

[0064]

[0065] The reaction steps and operations were the same as in Example 1, except that 1-methyl-3-(phenylimino)indol-2-one was replaced with 1-ethyl-3-(phenylimino)indol-2-one as 1f. After treatment, the target compound, quaternary carbodiamine 3fa (62.6 mg, yield 81.3%), was obtained. The 1H NMR spectrum is shown below. Figure 11 As shown, the carbon NMR spectrum is as follows. Figure 12 As shown.

[0066] Characterization data of the target compound, quaternary carbon o-diamine 3fa:

[0067] 1HNMR(600MHz,Chloroform-d)δ7.37(d,J=7.2Hz,1H),7.32(t,J=8.2Hz,1H),7. 04(d,J=8.6Hz,3H),6.97–6.89(m,3H),6.83(d,J=8.6Hz,2H),6.63(t,J=7.3Hz, 1H),6.19(d,J=7.8Hz,2H),4.73(s,1H),3.84(d,J=14.7Hz,1H),3.77(q,J=7.2H z,2H),3.65(d,J=14.7Hz,1H),2.79(s,3H),2.26(s,3H),1.18(t,J=7.2Hz,3H). 13 CNMR(151MHz,Chloroform-d)δ176.31,147.41,144.21,141.21,128.56,128.20,127.88,126.26,123.52, 121.67,118.00,114.28,112.49,107.65,64.49,62.25,39.78,33.84,19.20,11.40.HRMS(ESI)calcdfor:C 25 H 27 N3O[M+H] + 386.2227, found386.2227.

[0068] Example 12

[0069]

[0070] The reaction steps and operations were the same as in Example 1, except that 4,N,N-trimethylaniline was replaced with 4-chloro-N,N-dimethylaniline as 2b. After treatment, the target compound, quaternary carbodiamine 3ab (47.3 mg, yield 60.5%), was obtained. The 1H NMR spectrum is shown below. Figure 13 As shown, the carbon NMR spectrum is as follows. Figure 14 As shown.

[0071] Characterization data of the target compound, quaternary carbon o-diamine 3ab:

[0072] 1HNMR(600MHz,Chloroform-d)δ7.48(s,1H),7.33(t,J=7.7Hz,1H),7.12(d,J=8.9Hz,2H),7.05(t,J=7.5Hz,1H),6.96(t,J=7.8Hz,2H),6.83 (d,J=7.7Hz,1H),6.74(d,J=8.9Hz,2H),6.71(s,1H),6.33(s,2H),4.01(d,J=13.5Hz,1H),3.82(d,J=13.5Hz,1H),3.12(s,3H),2.72(s,3H). 13 CNMR(151MHz,Chloroform-d)δ177.49,166.94,148.54,143.20,129.54,129.05,128.75,124.48,1 23.01,122.78,119.57,115.55,114.36,108.61,65.74,62.41,40.86,26.48HRMS(ESI)calcdfor:C 23 H 22 ClN3O[M+Na] + 414.1344, found 414.1351

[0073] Example 13

[0074]

[0075] The reaction steps and operations were the same as in Example 1, except that 4,N,N-trimethylaniline was replaced with 4-methoxy-N,N-dimethylaniline as 2c. After treatment, the target compound, quaternary carboxy-o-diamine 3ac (53.6 mg, yield 69.2%), was obtained. The 1H NMR spectrum is shown below. Figure 15 As shown, the carbon NMR spectrum is as follows. Figure 16 As shown.

[0076] Characterization data of the target compound, quaternary carbon o-diamine 3ac:

[0077] 1HNMR(600MHz,Chloroform-d)δ7.34(t,J=8.4Hz,2H),7.04(t,J=7.4Hz,1H),6.95(t,J=7.8Hz,2H),6.89(dd,J=13.3,8.5Hz,3H),6.82(d,J=9.0Hz,2H),6.64(t,J=7.3Hz,1H),6.19(d,J=7.9Hz,2H),4.82(s,1H),3.79(s,1H),3.77(s,3H),3.63(d,J=14.6Hz,1H),3.21(s,3H),2.78(s,3H). 13 CNMR(151MHz,Chloroform-d)δ177.87,152.60,145.21,143.16,129.40,129.27,129.00,124.30,122.93,119.02,115.41,115.15,114.51,108.51,65.47,64.17,55.72,41.32,26.49.HRMS(ESI)calcdfor:C 25 H 27 N3O2[M+H] + 388.2020,found388.2030。

Claims

1. A method for photocatalytic synthesis of quaternary carbon o-diamine compound 3, characterized in that, The reaction formula is: ； The method includes the following steps: Step 1: Place the magnetic particle into a photoreaction tube with an outer condenser. Then, add 0.1-0.3 mmol of indigo-derived ketimine compound 1, 0.3-0.9 mmol of N,N-dimethylamine and its derivative 2, 0.03-0.09 mol of Brønsted acid, and 0.001-0.005 mmol of photocatalyst to the photoreaction tube in sequence. Then, add 0.5-1.0 mL of degassing solvent. Purge the tube with a fine needle and introduce argon gas for 10-20 min, then seal it. Compound 1 is selected from one of the following structures: 、 、 、 、 、 ； Derivative 2 is selected from one of the following structures: ； The Brønsted acid is selected from benzoic acid or glacial acetic acid; the photocatalyst is selected from tris(2,2'-bipyridine)ruthenium(II)bis(hexafluorophosphate) or tris(bipyridine)ruthenium chloride hexahydrate; and the degassing solvent is selected from acetonitrile or DMSO. Step 2: Pass condensate water through the outside of the photoreaction tube from Step 1, place the photoreaction tube on a magnetic stirrer, turn on the magnetic stirrer, stir for 8-48 hours, and irradiate with a blue LED light at room temperature for 8-48 hours. Step 3: After the reaction is complete, the crude product is concentrated under vacuum and separated by column chromatography using ethyl acetate and petroleum ether at a volume ratio of 1:10-20. The eluent is detected by TLC, and the eluent containing the target product is collected. The eluent is then concentrated under reduced pressure to obtain compound 3. Compound 3 is... , , , , , , , .

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