A synthetic method for constructing pyrazole derivatives containing n-bond

Abstract

The application discloses a synthetic method for constructing N-B bond-containing pyrazole derivatives, and the method is characterized in that, under light conditions, an iridium metal complex is used as a photosensitizer, and an alkenyl diazo compound 1 is reacted with an azaheterocyclic carbene borane compound 2 in a solvent. In the reaction process, the azaheterocyclic carbene borane compound 2 generates an azaheterocyclic carbene boron radical cation through a single electron transfer process under the action of visible light and the photosensitizer, and the azaheterocyclic carbene boron radical cation then completes an addition-cyclization reaction on the alkenyl diazo compound 1. The method is driven by visible light as a green energy source, and the reaction is carried out in an air atmosphere, has a short reaction time and high efficiency, and is easy to operate.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for constructing pyrazole derivatives containing NB bonds. Background Technology

[0002] Nitrogen-containing heterocyclic small molecule compounds accounted for 70% of the top 200 best-selling drugs globally in 2021, proving that nitrogen heterocyclic molecules are inseparable from our lives. Pyrazole heterocycles, as one type of five-membered aromatic ring containing two nitrogen atoms, have wide applications in pharmaceuticals, bioactive molecules, and natural products. In the pharmaceutical field, commercially available drugs include mavacoxib, celecoxib, and razaxaban. Furthermore, they have wide applications in insecticides due to their high efficiency, low toxicity, and low residue characteristics.

[0003] Therefore, chemists have developed many strategies for synthesizing pyrazoles. In earlier years, they were mainly obtained through cyclization reactions of 1,3-amphiphilic reagents with hydrazine compounds; or through [3+2] cycloaddition reactions of diazo compounds with different types of alkynes. However, these traditional methods usually require harsh conditions: high temperature, toxic solvents, and excessively long reaction times. Furthermore, the type of pyrazole is determined by the starting reagent, limiting the scope for later modification. These drawbacks severely restrict the development of pyrazole chemistry.

[0004] Furthermore, the functionalization of the nitrogen atom at the first position of pyrazole is the most important method for synthesizing various potential drug molecules, but most current methods achieve the transformation of the pyrazole ring. Various aromatic rings are introduced into the starting material to pave the way for later modifications or transformations. However, green, mild, and efficient synthesis and transformation of the nitrogen atom at the first position are rarely reported. Summary of the Invention

[0005] Our research group discovered that under blue LED illumination, nitrogen-heterocyclic carbene boron compound 2 generates nitrogen-heterocyclic carbene boron radical cations through a single-electron transfer process under the action of visible light and photosensitizer. These nitrogen-heterocyclic carbene boron radical cations then complete the addition cyclization reaction of alkenyl diazo compound 1.

[0006]

[0007] Based on the above research background, this invention provides a synthetic method for constructing pyrazole derivatives containing NB bonds. Various borated pyrazole derivatives are easily prepared by using alkenyl diazo derivatives and nitrogen-containing heterocyclic carbene borane compounds in acetonitrile as a solvent. This method is carried out in an air atmosphere, using a catalytic amount of iridium complex as a photosensitizer, and visible light as a green energy source.

[0008] This invention provides a method for synthesizing pyrazole derivatives containing NB bonds. The method involves dissolving an alkenyl diazo compound 1, a nitrogen heterocyclic carbene borane compound 2, a metallic iridium photosensitizer, and an equivalent amount of DABCO in acetonitrile under an air atmosphere, reacting the mixture under light irradiation, and then separating and purifying the product to obtain the target product 3.

[0009] The synthesis route is shown below:

[0010]

[0011] The reaction requires the addition of a catalytic amount of a metallic iridium complex as a photosensitizer.

[0012] Substituent R in compound 1 1 For ester, ketone or amide, R 2 It is aryl, amino, or alkyl, R 3 It is a methyl group.

[0013] Substituent R in compound 2 4 It is methyl, benzyl, or butyl, R 5 It is hydrogen.

[0014] The separation and purification were performed by silica gel column chromatography, with pure ethyl acetate as the eluent.

[0015] The target compound 3 of this invention can achieve selective fluorination of the pyrazole ring through a simple, mild, and green method. Monofluorination can improve the metabolic stability and lipophilicity of the molecule, providing a strategy for the later modification of potential drugs.

[0016]

[0017] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0018] 1. The raw materials used are easy to prepare. The nitrogen-containing heterocyclic carbene borane 2 has a very stable structure and can be stored at room temperature.

[0019] 2. The reaction process requires only a catalytic amount of metallic iridium photosensitizer.

[0020] 3. The reaction conditions are mild, the reaction time is short, and it is easy to operate.

[0021] 4. Using oxygen from the air as an oxidant and hydrogen and water as byproducts aligns with the principles of green chemistry. Detailed Implementation

[0022] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0023] Example 1:

[0024]

[0025] In a 10 mL reaction flask, alkenyldiazo 1a (0.9 mmol, 127.0 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), DABCO (0.3 mmol, 34.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.006 mmol, 5.4 mg), and acetonitrile (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(dichloromethane) = 1:0-2:1, preferably V(ethyl acetate):V(dichloromethane) = 1:0 in this example], yielding a pure, white solid with a yield of 71%.

[0026] Compound 3aa was tested and found to be:

[0027] 1 H NMR (400MHz, CDCl3, 300K): δ7.50 (d, J = 2.1Hz, 1H), 6.84 (s, 2H), 6.71 (d, J = 2.1Hz, 1H), 4.31 (q, J = 7.1Hz, 2H), 3.63 (s, 6H), 1.33 (t, J = 7.1Hz, 3H).

[0028] 13 C NMR (100MHz, CDCl3, 300K): δ163.6,144.4,136.6,121.1,107.8,60.1,35.9,14.4.

[0029] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.05 (t, J=96.4Hz).

[0030] High resolution: Calculated value: [M+H] + 249.1517, Measured value: 249.1517.

[0031] Example 2:

[0032]

[0033] In a 10 mL reaction flask, alkenyldiazo 1a (0.3 mmol, 42.0 mg), azahexacyclic carbene borane 2a (0.1 mmol, 13.0 mg), DABCO (0.1 mmol, 14.0 mg), photosensitizer (0.006 mmol), and acetonitrile (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(dichloromethane) = 1:0-2:1, preferably V(ethyl acetate):V(dichloromethane) = 1:0] to obtain a pure product, a white solid.

[0034] photosensitizer Yield (%) Rhodamine 6G Trace 4CzIPN Trace <![CDATA[Ru(bpy)3Cl26H2O]]> 33 <![CDATA[fac-Ir(ppy)3]]> 35 <![CDATA[Ir(ppy)2(dtbbpy)PF6]]> 50

[0035] Example 3:

[0036]

[0037] In a 10 mL reaction flask, alkenyl diazo 1a, azacyclic carbene borane 2a, DABCO, Ir(ppy)2(dtbbpy)PF6 (2 mol%), and acetonitrile were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(dichloromethane) = 1:0-2:1, preferably V(ethyl acetate):V(dichloromethane) = 1:0] to obtain a pure product, a white solid.

[0038] 1a 2a DABCO MeCN(mL) Yield 0.6mmol 0.3mmol 0.3mmol 1 61％ 0.6mmol 0.3mmol 0.3mmol 2 56％ 0.9mmol 0.3mmol 0.3mmol 1 71％

[0039] Example 4:

[0040] In a 10 mL reaction tube, alkenyldiazo 1a (0.9 mmol, 126.0 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), DABCO (0.3 mmol, 34.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.006 mmol, 5.4 mg), and solvent (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(petroleum ether) = 1:0-1:1, preferably V(ethyl acetate):V(petroleum ether) = 1:1] to obtain a pure product, a white solid.

[0041] solvent Yield (%) water 22 ethanol 54 Potassium carbonate 60

[0042] Example 5:

[0043]

[0044] In a 10 mL reaction tube, alkenyldiazo 1b (0.9 mmol, 139.0 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), DABCO (0.3 mmol, 34.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.006 mmol, 5.4 mg), and acetonitrile (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(petroleum ether) = 1:0-1:1, preferably V(ethyl acetate):V(dichloromethane) = 1:1], yielding a pure, white solid with a yield of 70%.

[0045] Compound 3ba was tested and found to be:

[0046] 1 H NMR (400MHz, CDCl3, 300K): δ7.50 (d, J=2.1Hz, 1H), 6.84 (s, 2H), 6.69 (d, J=2.1Hz, 1H), 4.20 (t, J=6.9Hz, 2H), 3.64 (s, 6H), 1.78–1.68 (m, 2H), 0.96 (t, J=7.4Hz, 3H).

[0047] 13 C NMR (100MHz, CDCl3, 300K): δ163.7,144.4,136.5,121.1,107.7,65.6,35.9,22.1,10.4.

[0048] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.07 (t, J=93.0Hz).

[0049] High resolution: Calculated value: [M+H] + 263.1674, measured value: 249.1675.

[0050] Example 6:

[0051]

[0052] In a 10 mL reaction tube, alkenyldiazo 1c (0.9 mmol, 139.0 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), DABCO (0.3 mmol, 34.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.006 mmol, 5.4 mg), and acetonitrile (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(petroleum ether) = 1:0-1:1, preferably V(ethyl acetate):V(dichloromethane) = 1:1], yielding a pure, white solid with a yield of 75%.

[0053] Compound 3ca was tested and found to be:

[0054] 1 H NMR (400MHz, CDCl3, 300K): δ7.50(d,J=2.1Hz,1H),6.84(s,2H),6.67(d,J=2.1Hz,1H),5.24–5.14(m,1H),3.65(s,6H),1.31(d,J=6.3Hz,6H).

[0055] 13 C NMR (100MHz, CDCl3, 300K): δ163.2,144.8,136.4,121.1,107.6,67.2,35.9,22.0.

[0056] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.10 (t, J=88.7Hz).

[0057] High resolution: Calculated value: [M+H] + 263.1674, measured value: 249.1674.

[0058] Example 7:

[0059]

[0060] In a 10 mL reaction tube, alkenyldiazo 1d (0.9 mmol, 151.2 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), DABCO (0.3 mmol, 34.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.006 mmol, 5.4 mg), and acetonitrile (1 mL) were added under air atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(ethyl acetate):V(petroleum ether) = 1:0-1:1, preferably V(ethyl acetate):V(petroleum ether) = 1:1 in this example], yielding a pure product, a white solid, with a yield of 60%.

[0061] Compound 3da was tested and found to be:

[0062] 1 H NMR (400MHz, CDCl3, 300K): δ7.48 (d, J = 2.1Hz, 1H), 6.84 (s, 2H), 6.60 (d, J = 2.1Hz, 1H), 3.69 (s, 6H), 1.53 (s, 9H).

[0063] 13 C NMR (100MHz, CDCl3, 300K): δ162.9,145.6,136.2,121.1,107.3,79.9,36.0,28.3.

[0064] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.35 (t, J=74.4Hz).

[0065] High resolution: Calculated value: [M+H] + 277.1830, measured value: 277.1831.

[0066] Example 8:

[0067]

[0068] In a 10 mL reaction tube, alkenyldiazo 1e (0.9 mmol, 162 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 69%.

[0069] Compound 3ea was tested and found to be:

[0070] 1 H NMR (400MHz, CDCl3, 300K): δ7.48 (d, J=2.1Hz, 1H), 6.85 (s, 2H), 6.63 (d, J=2.1Hz, 1H), 5.34–5.27(m,1H),3.64(s,6H),1.95–1.85(m,2H),1.81–1.71(m,4H),1.61–1.53(m,2H)

[0071] 13 C NMR (100MHz, CDCl3, 300K): δ163.4,144.6,136.3,121.1,107.5,76.5,35.9,32.6,23.7.

[0072] 11 B NMR (128.4MHz, CDCl3, 300K): δ-17.12–-21.63(m).

[0073] High resolution: Calculated value: [M+H] + 289.1830, Measured value: 289.1830.

[0074] Example 9:

[0075]

[0076] In a 10 mL reaction tube, alkenyldiazo 1f (0.9 mmol, 221 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 68%.

[0077] Compound 3fa was tested and found to be:

[0078] 1 H NMR (400MHz, CDCl3, 300K): δ7.48 (d, J = 2.1Hz, 1H), 6.84 (s, 2H), 6.59 (d, J = 2. 1Hz,1H),3.69(s,6H),2.22(d,J=2.5Hz,6H),2.16(s,3H),1.71–1.62(m,6H).

[0079] 13 C NMR (100MHz, CDCl3, 300K): δ162.6,145.7,136.1,121.1,107.3,80.0,41.4,36.3,36.1,30.8.

[0080] 11 B NMR (128.4MHz, CDCl3, 300K): δ-16.93–-21.58(m).

[0081] High resolution: Calculated value: [M+H] + 355.2300, measured value: 355.2301.

[0082] Example 10:

[0083]

[0084] In a 10 mL reaction tube, 1 g (0.9 mmol, 204 mg) of alkenyldiazo, 0.3 mmol (33.0 mg) of azahexacyclic carbene borane 2a, 0.004 mmol (3.6 mg) of Ir(ppy)2(dtbbpy)PF6, and 1 mL of acetonitrile were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 75%.

[0085] Compound 3ga was tested and found to be:

[0086] 1 H NMR (400MHz, CDCl3, 300K): δ7.54(s,1H),7.43(d,J=7.1Hz,2H),7.28–7.23(m,3H),6.84(s,2H),6.79(s,1H),5.09(s,2H),3.65(s,6H).

[0087] 13 C NMR (100MHz, CDCl3, 300K): δ162.7,143.5,136.8,131.8,128.5,128.2,122.4,121.2,108.3,86.0,83.7,52.4,36.0.

[0088] 11 B NMR (128.4MHz, CDCl3, 300K): δ-17.09–-21.16(m).

[0089] HRMS(ESI)m / z:[M+H] + Calcd for C 18 H 20 BN4O2 + :335.1674;Found:335.1674

[0090] High resolution: Calculated value: [M+H] + 335.1674, measured value: 335.1674.

[0091] Example 11:

[0092]

[0093] In a 10 mL reaction tube, alkenyldiazo 1h (0.9 mmol, 182 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 77%.

[0094] Compound 3ha was tested and found to be:

[0095] 1 H NMR (400MHz, CDCl3, 300K): δ7.52 (d, J=2.1Hz, 1H), 7.45–7.39 (m, 2H), 7.36 –7.28(m,3H),6.83(s,2H),6.74(d,J=2.1Hz,1H),5.32(s,2H),3.64(s,6H).

[0096] 13 C NMR (100MHz, CDCl3, 300K): δ163.3,143.9,136.5,128.3,128.1,127.8,121.1,108.0,65.6,35.8.

[0097] 11 B NMR (128.4MHz, CDCl3, 300K): δ-17.08–-21.04(m).

[0098] High resolution: Calculated value: [M+H] + 311.1674, Measured value: 311.1674.

[0099] Example 12:

[0100]

[0101] In a 10 mL reaction tube, alkenyldiazo 1i (0.9 mmol, 150 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 77%.

[0102] Compound 3ia was tested and found to be:

[0103] 1 H NMR (400MHz, CDCl3, 300K): δ7.51(d,J=2.1Hz,1H),6.84(s,2H),6.72(d,J=2 .1Hz,1H),5.02(s,1H),4.90(s,1H),4.68(s,2H),3.65(s,6H),1.78(s,3H).

[0104] 13 C NMR (100MHz, CDCl3, 300K): δ163.1,143.9,140.4,136.5,121.1,112.2,107.8,67.0,35.9,19.5.

[0105] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.13 (t, J=90.8Hz).

[0106] HRMS(ESI)m / z:[M+H] + Calcd for C 13 H 20 BN4O2 + Found: 275.1674;

[0107] High resolution: Calculated value: [M+H] + 275.1674, Measured value: 275.1674.

[0108] Example 13:

[0109]

[0110] In a 10 mL reaction tube, alkenyldiazo 1j (0.9 mmol, 164 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 54%.

[0111] Compound 3ja was tested and found to be:

[0112] 1 H NMR (400MHz, CDCl3, 300K): δ7.30 (s, 1H), 6.82 (s, 2H), 4.31 (q, J = 7.0Hz, 2H), 3.63 (s, 6H), 2.25 (s, 3H), 1.33 (t, J = 7.1Hz, 3H).

[0113] 13 C NMR (100MHz, CDCl3, 300K): δ164.2,141.6,136.7,121.1,119.6,77.3,77.0,76.7,59.7,35.9,14.4,10.0.

[0114] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.14 (t, J=93.4Hz).

[0115] HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 20 BN4O2 + Found: 263.1674;

[0116] High resolution: Calculated value: [M+H] + 263.1674, Measured value: 263.1674.

[0117] Example 14:

[0118]

[0119] In a 10 mL reaction tube, alkenyldiazo 1k (0.9 mmol, 167 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 53%.

[0120] Compound 3ka was tested:

[0121] 1 H NMR (400MHz, CDCl3, 300K): δ7.30 (s, 1H), 6.82 (s, 2H), 4.31 (q, J = 7.0Hz, 2H), 3.63 (s, 6H), 2.25 (s, 3H), 1.33 (t, J = 7.1Hz, 3H)

[0122] 13 C NMR (100MHz, CDCl3, 300K): δ190.0,148.8,139.4,136.1,131.2,130.7,127.4,121.0,120.6,36.1,10.3.

[0123] 11 B NMR (128.4MHz, CDCl3, 300K): δ-11.79–-27.73(m).

[0124] HRMS(ESI)m / z:[M+H] + Calcd for C 16 H 20 BN4O + Found: 295.1725; Found: 295.1727.

[0125] High resolution: Calculated value: [M+H] + 295.1725, measured value: 295.1727.

[0126] Example 15:

[0127]

[0128] In a 10 mL reaction tube, alkenyldiazo 1L (0.9 mmol, 140 mg), azahexacyclic carbene borane 2A (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 40%.

[0129] Compound 3la was tested and found to be:

[0130] 1 H NMR (400MHz, CDCl3, 300K): δ7.49(d,J=1.6Hz,1H),6.85(s,2H),6.66(d,J=1.1Hz,1H),3.69(s,3H),3.68(s,6H),3.41(s,3H).

[0131] 13 C NMR (100MHz, CDCl3, 300K): δ164.2,145.5,135.8,121.0,107.5,77.3,77.0,76.7,60.9,35.9.

[0132] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.31 (t, J=94.2Hz).

[0133] HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 19 BN5O2 + :264.1626; Found:335.1674

[0134] High resolution: Calculated value: [M+H] + 264.1626, Measured value: 264.1626.

[0135] Example 16:

[0136]

[0137] In a 10 mL reaction tube, alkenyldiazo 1m (0.9 mmol, 171 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 43%.

[0138] Compound 3ma was tested and found to contain:

[0139] 1 H NMR (400MHz, CDCl3, 300K): δ7.56(d,J=1.9Hz,1H),7.17(d,J=1.8Hz,1H),6.84(s,2H),5.97(s,1H),3.75(s,6H),2.58(s,3H),2.25(s,3H).

[0140] 13 C NMR (100MHz, CDCl3, 300K): δ151.3,145.0,144.9,135.9,121.1,111.7,110.2,77.3,77.0,76.7,36.1,14.4,13.9.

[0141] 11 B NMR (128.4MHz, CDCl3, 300K) δ-16.26–-22.02(m).

[0142] HRMS(ESI)m / z:[M+H] + Calcd for C 14 H 20 BN6O + Found: 299.1786; Found: 299.1785

[0143] High resolution: Calculated value: [M+H] + 299.1786, measured value: 299.1785.

[0144] Example 17:

[0145]

[0146] In a 10 mL reaction tube, alkenyldiazo 1n (0.9 mmol, 222 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 72%.

[0147] Compound 3na was tested and found to be:

[0148] 1 H NMR (400MHz, CDCl3, 300K): δ7.51 (d, J=2.1Hz, 1H), 6.94 (s, 1H), 6.92–6.88 (m, 1H), 6.84 (s,2H),6.78–6.75(m,1H),6.72(d,J=2.1Hz,1H),5.94(s,2H),5.22(s,2H),3.66(s,6H).

[0149] 13 C NMR (100MHz, CDCl3, 300K): δ163.3,147.6,147.3,143.9,136.6,130.4,122.1,121.1,109.0,108.0,101.0,65.6,35.9.

[0150] 11 B NMR (128.4MHz, CDCl3, 300K): δ-16.39–-21.93(m).

[0151] High resolution: Calculated value: [M+H] + 355.1572, measured value: 355.1574.

[0152] Example 18:

[0153]

[0154] In a 10 mL reaction tube, alkenyldiazo 1o (0.9 mmol, 155 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1], yielding a pure, white solid with a yield of 42%.

[0155] Compound 3oa was tested and found to be:

[0156] 1 H NMR (400MHz, CDCl3, 300K): δ8.18(d,J=7.5Hz,2H),7.55(s,1H),7.48(t,J=7.3Hz,1H),7.39(t,J=7.6Hz,2H),6.86(s,2H),3.75(s,6H).

[0157] 13 C NMR (100MHz, CDCl3, 300K): δ188.8,151.9,138.7,136.1,131.6,130.5,127.6,121.1,108.6,36.1.

[0158] 11 B NMR (128.4MHz, CDCl3, 300K): δ-15.68–-24.06(m).

[0159] High resolution: Calculated value: [M+H] + 281.1568, Measured value: 281.1568.

[0160] Example 19:

[0161]

[0162] In a 10 mL reaction tube, alkenyldiazo 1p (0.9 mmol, 162 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 87%.

[0163] Compound 3pa was tested and found to be:

[0164] 1 H NMR (400MHz, CDCl3, 300K): δ7.07 (s, 1H), 6.82 (s, 2H), 4.31 (q, J = 7.0Hz, 2H), 3.59 (s, 6H) ),2.26–2.16(m,1H),1.32(t,J=7.0Hz,3H),0.85(d,J=8.2Hz,2H),0.45(d,J=5.0Hz,2H).

[0165] 13 C NMR (100MHz, CDCl3, 300K): δ164.1,142.0,133.1,127.8,121.1,77.3,77.0,76.7,59.7,35.8,14.4,8.4,6.0.

[0166] 11 B NMR (128.4MHz, CDCl3, 300K): δ-13.55–-25.38(m).

[0167] High resolution: Calculated value: [M+H] + 289.1830, Measured value: 289.1830.

[0168] Example 20:

[0169]

[0170] In a 10 mL reaction tube, alkenyldiazo 1q (0.9 mmol, 151 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 60%.

[0171] Compound 3qa was tested and found to be:

[0172] 1 H NMR (400MHz, CDCl3, 300K): δ6.84 (s, 2H), 6.52 (s, 1H), 4.28 (q, J = 7.1Hz, 2H), 3 .55(s,6H),2.68(q,J=7.5Hz,2H),1.31(t,J=7.1Hz,3H),1.21(t,J=7.5Hz,3H).

[0173] 13 C NMR (100MHz, CDCl3, 300K): δ163.82,150.54,142.76,121.07,105.69,77.32,77.00,76.68,59.83,35.73,20.29,14.39,13.14.

[0174] 11 B NMR (128.4MHz, CDCl3, 300K): δ-20.78 (t, J = 40.3Hz). HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 22 BN4O2 + Found: 277.1830; Found: 277.1823.

[0175] High resolution: Calculated value: [M+H] + 277.1830, measured value: 277.1823.

[0176] Example 21:

[0177]

[0178] In a 10 mL reaction tube, alkenyldiazo 1r (0.9 mmol, 243 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 60%.

[0179] Compound 3ra was tested and found to be:

[0180] 1 H NMR (400MHz, CDCl3, 300K): δ7.14(s,1H),6.82(s,2H),3.79(s,3H),3.58(s,6H),0.98(s,9H),0.13(s,6H).

[0181] 13 C NMR (100MHz, CDCl3, 300K): δ163.2,141.8,133.3,126.5,121.1,77.3,77.0,76.7,50.8,35.8,25.7,18.2,-5.1.

[0182] 11 B NMR (128.4MHz, CDCl3, 300K): δ2.39–-53.07(m).

[0183] High resolution: Calculated value: [M+H] + 365.2175, measured value: 365.2170.

[0184] Example 22:

[0185]

[0186] In a 10 mL reaction tube, alkenyldiazo 1s (0.9 mmol, 243 mg), azahexacyclic carbene borane 2a (0.3 mmol, 33.0 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 55%.

[0187] Compound 3ab was tested and found to be:

[0188] 1 H NMR (400MHz, CDCl3, 300K): δ6.83 (s, 2H), 6.66 (s, 1H), 4.28 (q, J = 7.1Hz, 2H), 3.59 (s, 6H), 3.57 (s, 2H), 2.23 (s, 6H), 1.31 (t, J = 7.1Hz, 3H).

[0189] 13 C NMR (100MHz, CDCl3, 300K): δ163.7,145.1,121.0,108.8,77.3,77.0,76.7,59.9,55.1,45.2,35.8,14.4.

[0190] 11 B NMR (128.4MHz, CDCl3, 300K): δ-11.22–-27.11(m).

[0191] High resolution: Calculated value: [M+H] + 306.2096, measured value: 306.2095.

[0192] Example 23:

[0193]

[0194] In a 10 mL reaction tube, alkenyldiazo 1a (0.9 mmol, 126 mg), azahexacyclic carbene borane 2b (0.3 mmol, 55.8 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 70%.

[0195] Compound 3ab was tested and found to be:

[0196] 1 H NMR (400MHz, CDCl3, 300K): 7.49 (d, J = 2.2Hz, 1H), 7.35–7.29 (m, 3H), 7.23–7.19 (m, 2H), 6.84 (d, J = 1.7Hz, 1H), 6. 73(d,J=1.7Hz,1H),6.70(d,J=2.0Hz,1H),5.28(s,2H),4.32(q,J=7.1Hz,2H),3.68(s,3H),1.34(t,J=7.1Hz,3H).

[0197] 13 C NMR (100MHz, CDCl3, 300K): δ163.6,144.4,136.5,135.2,128.9,128.4,128.3,121.7,119.6,107.8,60.0,52.2,36.0,14.4.

[0198] 11 B NMR (128.4MHz, CDCl3, 300K): δ-13.33–-26.85(m).

[0199] HRMS(APCI)m / z:[M+H] + Calcd for C 17 H 22 BN4O2 + :325.1830; Found:325.1830.

[0200] High resolution: Calculated value: [M+H] + 325.1830, measured value: 325.1830.

[0201] Example 24:

[0202]

[0203] In a 10 mL reaction tube, alkenyldiazo 1a (0.9 mmol, 126 mg), azahexacyclic carbene borane 2b (0.3 mmol, 45.6 mg), Ir(ppy)2(dtbbpy)PF6 (0.004 mmol, 3.6 mg), and acetonitrile (1 mL) were added under atmospheric atmosphere and reacted under blue light. The reaction was monitored by TLC (thin-layer chromatography) until the reaction was complete. The organic solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 1:1-0:1, preferably V(petroleum ether):V(ethyl acetate) = 0:1] to obtain a pure product, a white solid, with a yield of 80%.

[0204] Compound 3ac was tested and found to be:

[0205] 1 H NMR (400MHz, CDCl3, 300K): δ7.49(d,J=2.1Hz,1H), 6.89–6.82(m,2H), 6.71(d,J=2.2Hz,1H), 4.32(q,J=7.1Hz,2H), 4.05–4.00(m,2H),3.65(s,3H),1.68–1.59(m,2H),1.33(t,J=7.1Hz,3H),1.30–1.23(m,2H),0.89(t,J=7.4Hz,3H).

[0206] 13 C NMR (100MHz, CDCl3, 300K): δ163.7,144.4,136.5,121.3,119.7,107.8,60.0,48.7,36.0,32.5,19.6,14.4,13.5.

[0207] 11 B NMR (128.4MHz, CDCl3, 300K): δ-19.10 (t, J=84.1Hz).

[0208] High resolution: Calculated value: [M+H] + 291.1987, measured value: 291.1988.

Claims

1. A method for constructing pyrazole derivatives containing NB bonds, characterized in that: Under light conditions, alkenyl diazo compound 1 and nitrogen heterocyclic carbene borane compound 2 are reacted in a solvent. Under visible light and photosensitizer, nitrogen heterocyclic carbene borane compound 2 generates nitrogen heterocyclic carbene boron radical cation through a single electron transfer process. The nitrogen heterocyclic carbene boron radical cation then completes the addition cyclization reaction of alkenyl diazo compound 1. The synthesis route is shown below: ； Alkenyldiazo compound 1 is selected from compounds with the following structures: ； The substituent R in nitrogen-containing heterocyclic carbene borane compound 2 4 It is methyl, benzyl, or butyl, R 5 It is hydrogen; Target product 3 is selected from compounds with the following structures: ； The photosensitizer is an iridium metal complex Ir(ppy)2(dtbbpy)PF6; The reaction system also contains a base, which is 1,4-diazabicyclo[2.2.2]octane.

2. The synthesis method according to claim 1, characterized in that: The reaction takes place under the illumination of blue LED lights.

3. The synthesis method according to claim 1, characterized in that: The reaction uses trace amounts of oxygen from the air as an oxidant.

4. The synthesis method according to claim 1, characterized in that: After the reaction, the target product was obtained by separation and purification. The separation and purification were carried out by silica gel column chromatography, and the eluent was pure ethyl acetate.

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