Electrosynthesis method of 1-pyrroline

Abstract

The invention discloses an electrosynthesis method of 1-pyrroline, which comprises the following steps: by taking a platinum sheet as a cathode, a carbon rod as an anode and tetrabutylammonium perchlorate or tetrabutylammonium tetrafluoroborate as an electrolyte under the catalysis of constant current, carrying out one-pot dimerization cyclization on styrene and azidotrimethylsilane to prepare a 1-pyrroline derivative, and carrying out post-treatment on the obtained reaction mixed solution, and carrying out column chromatography separation to obtain a pure product of 1-pyrroline. According to the method, the 1-pyrroline derivative can be obtained only through one-step reaction, the operation steps are few, an oxidizing agent, an additive and metal are not used, the post-treatment process is simple, and the product is easy to separate.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical synthesis, and particularly relates to a method for preparing 1-pyrroline. Background Art

[0002] 1-Pyrroline derivatives are a class of organic synthetic intermediates with diverse biological activities and widespread applications in chemistry, materials science, and drug design. To date, the classic 5-exo-trig cyclization reaction remains a powerful tool for the synthesis of 1-pyrroline derivatives. This reaction requires a metal, an oxidant, and other catalysts to generate a nitrogen radical or nitrogen-metal complex, which then adds to the olefin. This requires not only complex presynthesis of the substrate but also a second molecule to complete the cyclization. Therefore, the preparation of 1-pyrroline derivatives from simpler substrates and conditions is highly desirable.

[0003] Furthermore, electrochemical organic synthesis techniques are currently demonstrating remarkable synthetic capabilities, attracting increasing interest among organic researchers. This technology not only overcomes the issues of additives and external oxidants, as well as low yields, but also offers ease of operation under mild conditions, allowing experiments to be started and stopped simply by controlling the current. Therefore, the search for green and efficient methods for the electrosynthesis of 1-pyrroline derivatives is a crucial research topic. Summary of the Invention

[0004] The object of the present invention is to provide a green and efficient method for preparing 1-pyrroline derivatives from styrene and azidotrimethylsilane.

[0005] The technical solution for achieving the purpose of the present invention is:

[0006] In a first aspect, the present invention provides a method for preparing 1-pyrroline, comprising the steps of: subjecting styrene and trimethylsilyl azide to an electrochemical reaction in an electrolyte solution to synthesize a target product:

[0007]

[0008] In the formula, R includes but is not limited to any one of methyl, ethyl, tert-butyl, alkoxy, chloromethyl, halogen, and trifluoromethyl, and the substitution position can be ortho, para, or meta.

[0009] Furthermore, the electrolyte in the electrolyte solution is tetrabutylammonium perchlorate or tetrabutylammonium tetrafluoroborate, and the solvent is a mixed solvent of dichloroethane and hexafluoroisopropanol in a volume ratio of 5 to 10:1, preferably 8:1.

[0010] Furthermore, the electrochemical reaction uses a carbon rod as an anode and a platinum sheet as a cathode, and the current is a constant current of 3 mA to 20 mA, preferably a constant current of 3 mA to 10 mA, and more preferably a constant current of 5 mA.

[0011] Furthermore, the electrochemical reaction is carried out at 0-40°C, preferably room temperature.

[0012] Furthermore, the electrochemical reaction time is not less than 6 hours.

[0013] Furthermore, the molar ratio of the electrolyte to the styrene is 0.2-1 times, preferably 0.5 times.

[0014] Furthermore, the molar ratio of the amount of azidotrimethylsilane used is 1-3 times, preferably 1.5 times, of the amount of styrene used.

[0015] Furthermore, the raw materials and electrolyte are added under the protection of an inert gas, preferably argon.

[0016] Compared with the prior art, the present invention has the following significant advantages:

[0017] (1) The synthetic method of the present invention is simple and efficient, and 1-pyrroline derivatives can be obtained through a one-step reaction, with fewer steps, avoiding the use of oxidants and additives, simplifying the post-processing process, and being easy to separate the product, thereby greatly simplifying the operational requirements;

[0018] (2) The reaction conditions of the present invention are easy to implement and do not require harsh conditions such as low temperature, high temperature, light, pressure, strong acid and strong base, thus avoiding special requirements such as biocatalysis and precious metal catalysis;

[0019] (3) Styrene used in the present invention exhibits excellent reactivity under electrochemical conditions. Dimerization followed by cyclization with azidotrimethylsilane is a known simple method for synthesizing 1-pyrroline derivatives from the most readily available starting materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of 2,5-diphenyl-3,4-dihydro-2H-pyrrole prepared in Example 1 of the present invention.

[0021] Figure 2 This is the carbon nuclear magnetic resonance spectrum of 2,5-diphenyl-3,4-dihydro-2H-pyrrole prepared in Example 1 of the present invention.

[0022] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of 2,5-bis(4-isopropoxyphenyl)-3,4-dihydro-2H-pyrrole prepared in Example 2 of the present invention.

[0023] Figure 4 This is the carbon nuclear magnetic resonance spectrum of 2,5-bis(4-isopropoxyphenyl)-3,4-dihydro-2H-pyrrole prepared in Example 2 of the present invention.

[0024] Figure 5This is the hydrogen nuclear magnetic resonance spectrum of 2,5-di-o-tolyl-3,4-dihydro-2H-pyrrole prepared in Example 3 of the present invention.

[0025] Figure 6 This is the carbon nuclear magnetic resonance spectrum of 2,5-di-o-tolyl-3,4-dihydro-2H-pyrrole prepared in Example 3 of the present invention. DETAILED DESCRIPTION

[0026] The present application is further described below with reference to specific embodiments.

[0027] It should be noted that the terms such as "upper", "lower", "left", "right", and "middle" cited in this specification are only for the convenience of description and are not used to limit the scope of implementation. Changes or adjustments to their relative relationships should be regarded as the scope of implementation of this application without substantially changing the technical content.

[0028] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs; the term "and / or" used herein includes any and all combinations of one or more of the associated listed items.

[0029] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or those recommended by the manufacturer. All reagents or instruments used, if the manufacturer is not specified, are commercially available conventional products.

[0030] As used herein, the term "about" is used to provide flexibility and imprecision associated with a given term, measurement, or value. One skilled in the art can readily determine the degree of flexibility for a particular variable.

[0031] As used herein, the term "at least one of" is intended to be synonymous with "one or more of." For example, "at least one of A, B, and C" explicitly includes only A, only B, only C, and combinations of each thereof.

[0032] Concentration, amount and other numerical data can be presented in range format in this article.Should be understood that such range format is only used for convenience and brevity, and should be flexibly interpreted as not only including the numerical value clearly described as range limit, but also including all independent numerical values ​​or subranges encompassed within the scope, just as each numerical value and subrange are clearly described.For example, the numerical range of about 1 to about 4.5 should be interpreted as not only including the limit value of 1 to about 4.5 clearly described, but also including independent numerals (such as 2,3,4) and subranges (such as 1 to 3,2 to 4 etc.).The same principle is applicable to the scope of only narrating a numerical value, such as "less than about 4.5", which should be interpreted as including all above-mentioned values ​​and scopes.In addition, no matter how the breadth of described scope or feature is, this explanation should be applicable.

[0033] The method for preparing 1-pyrroline derivatives of the present invention comprises the following steps:

[0034] (1) In a dry three-necked flask, under constant current, use dichloroethane and hexafluoroisopropanol as a mixed solvent, tetrabutylammonium perchlorate as the electrolyte, a carbon rod as the anode, and a platinum sheet as the cathode. (2) Styrene and trimethylsilyl azide are added to the three-necked flask under argon protection, stirred, and energized. (3) The reaction mixture is stirred until the reaction is complete, and the resulting reaction mixture is post-treated and separated by a chromatographic column to obtain a pure 1-pyrroline derivative.

[0035] Example 1:

[0036] A magnet and tetrabutylammonium perchlorate (0.25 mmol, 0.5 equivalents) were added to a dry three-necked flask (20 mL) equipped with a graphite rod anode (φ = 6 mm, 90 mm) and a platinum sheet cathode (10 mm × 10 mm × 0.2 mm). Dichloroethane (8 mL), hexafluoroisopropanol (1 mL), trimethylsilyl azide (1.5 equivalents), and styrene (0.5 mmol, 1.0 equivalents) were then injected into the flask via syringe. The reaction mixture was stirred and electrolyzed at a constant current of 5 mA for 12 hours at room temperature. After the reaction was completed, the solvent was removed under reduced pressure. Flash column chromatography was performed on silica gel using a mixture of petroleum ether / ethyl acetate = 30:1 as the eluent to obtain the 1-pyrroline product with an isolated yield of 75%. Characterization by hydrogen and carbon nuclear magnetic resonance spectra is shown in the figure. Figure 1 and Figure 2 .

[0037] 2,5-Diphenyl-3,4-dihydro-2H-pyrrole. 1H NMR(500MHz, CDCl3)δ7.95(d,J=6.4Hz,2H),7.44(t,J=7.2Hz,3H),7.32(dd,J=11.6,7.0Hz,4H),7.26–7.22 (m,1H),5.32(t,J=7.7Hz,1H),3.21–3.14(m,1H),3.06–2.97(m,1H),2.63–2.56(m,1H),1.95–1.87(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.7,144.6,134.4,130.6,128.4,127.9,126.8,126.5,76.0,35.6,32.4.

[0038] Example 2:

[0039] According to the method of Example 1, 4-isopropoxystyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 82%. The H NMR and C NMR characterizations are shown in Figure 3 and Figure 4 .

[0040] 2,5-bis(4-isopropoxyphenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.86(d,J=8.8Hz,2H),7.19(d,J=8.5Hz,2H),6.91(d,J=8 .8Hz,2H),6.85(d,J=8.6Hz,2H),5.21(t,J=7.5Hz,1H),4.62(dt,J=12.1,6.1H z,1H),4.51(dd,J=12.2,6.2Hz,1H),3.16–3.10(m,1H),2.99–2.93(m,1H),2.5 6–2.49(m,1H),1.90–1.82(m,1H),1.36(d,J=6.1Hz,6H),1.32(d,J=6.1Hz,6H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ172.7,159.9,156.8,136.8,129.5,127.6,115.9,115.4,75.3,69.9,69.8,35.4,32.5,22.1,22.0.

[0041] Example 3:

[0042] According to the method of Example 1, 2-methylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 72%.

[0043] 2,5-Di-o-tolyl-3,4-dihydro-2H-pyrrole. 1 HNMR (500MHz, CDCl3) δ7.53 (d, J=7.5Hz, 1H), 7.31–7.22 (m, 4H), 7.21–7.12 (m, 3H), 5.50 (t, J= 7.7Hz,1H),3.08–3.02(m,2H),2.64(s,3H),2.61–2.57(m,1H),2.43(s,3H),1.75–1.68(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ175.6,142.9,137.5,134.6,131.4,130.1,129.2,129.0,126.5,126.1,125.6,125.4,73.6,38.7,31.2,22.1,19.6.

[0044] Example 4:

[0045] According to the method of Example 1, 4-methylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 76%.

[0046] 2,5-Di-p-tolyl-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.83(d,J=8.1Hz,2H),7.23(d,J=8.0Hz,2H),7.19(d,J=8.0Hz,2H),7.14(d,J=7.9Hz,2H),5.27( t,J=7.6Hz,1H),3.17–3.11(m,1H),3.02–2.94(m,1H),2.60–2.52(m,1H),2.40(s,3H),2.33(s,3H),1.91–1.85(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.3,141.7,140.8,136.3,131.7,129.1,129.0,127.9,126.5,75.7,35.5,32.4,21.5,21.1.

[0047] Example 5:

[0048] According to the method of Example 1, 4-ethylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 72%.

[0049] 2,5-bis(4-ethylphenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.86(d,J=8.1Hz,2H),7.26(d,J=5.7Hz,2H),7.21(d,J=8.0Hz,2H),7.16(d,J=7.9Hz,2H),5.28(t,J=7.5Hz,1H),3.19–3.12(m,1 H),3.03–2.95(m,1H),2.70(q,J=7.6Hz,2H),2.64(q,J=7.6Hz,2H),2.59–2 .53(m,1H),1.94–1.86(m,1H),1.26(t,J=7.6Hz,3H),1.22(t,J=7.6Hz,3H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.4,142.7,141.9,128.0,127.9,127.8,126.5,119.8,75.7,35.5,32.4,28.8,28.5,15.6,15.4.

[0050] Example 6:

[0051] According to the method of Example 1, 4-tert-butylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 77%.

[0052] 2,5-bis(4-(tert-butyl)phenyl)-3,4-dihydro-2H-pyrrole. 1 HNMR (500MHz, CDCl3) δ7.88(d,J=8.3Hz,2H),7.45(d,J=8.3Hz,2H),7.35(d,J=8.2Hz,2H),7.22(d,J=8.2Hz,2H),5.27( t,J=7.6Hz,1H),3.20–3.14(m,1H),3.02–2.95(m,1H),2.60–2.52(m,1H),1.95–1.88(m,1H),1.35(s,9H),1.31(s,9H). 13 C{ 1H}NMR (126MHz, CDCl3) δ173.2,153.9,149.6,141.6,131.7,127.7,126.3,125.4,125.3,75.7,35.5,34.9,34.4,32.3,31.4,31.2.

[0053] Example 7:

[0054] According to the method of Example 1, 4-methoxystyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 83%.

[0055] 2,5-bis(4-methoxyphenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.90(d,J=8.7Hz,2H),7.23(d,J=8.6Hz,2H),6.94(d,J=8.7Hz,2H),6.88(d,J=8.6Hz,2H),5.24(t ,J=7.6Hz,1H),3.86(s,3H),3.80(s,3H),3.17–3.11(m,1H),3.00–2.93(m,1H),2.58–2.52(m,1H),,1.91–1.83(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ172.6,161.5,158.4,137.0,129.5,127.6,127.3,113.8,113.7,75.3,55.3,55.2,35.4,32.6.

[0056] Example 8:

[0057] According to the method of Example 1, 4-ethoxystyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 79%.

[0058] 2,5-bis(4-ethoxyphenyl)-3,4-dihydro-2H-pyrrole. 1H NMR (500MHz, CDCl3) δ7.87(d,J=8.7Hz,2H),7.20(d,J=8.5Hz,2H),6.92(d,J=8.7Hz,2H),6.85(d,J=8.5Hz,2H),5.22(t,J=7.5Hz,1H),4.08(q,J=7.0H z,2H),4.01(q,J=7.0Hz,2H),3.16–3.09(m,1H),2.98–2.92(m,1H),2.57–2 .50(m,1H),1.89–1.81(m,1H),1.43(t,J=5.0Hz,3H),1.40(t,J=5.0Hz,3H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ172.7,160.9,157.8,136.9,129.5,127.6,114.4,114.2,75.3,63.5,63.4,35.4,32.6,14.8,14.7.

[0059] Example 9:

[0060] According to the method of Example 1, 4-fluorostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 70%.

[0061] 2,5-bis(4-fluorophenyl)-3,4-dihydro-2H-pyrrole. 1 HNMR (500MHz, CDCl3) δ7.94(dd,J=8.8,5.5Hz,2H),7.26(t,J=4.2Hz,2H),7.12(t,J=8.7Hz,2H),7.02(t,J=8 .7Hz,2H),5.28(t,J=7.8Hz,1H),3.20–3.13(m,1H),3.04–2.96(m,1H),2.64–2.57(m,1H),1.91–1.83(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ172.8,140.1,139.2,130.1,130.0,128.1,128.0,115.6,115.5,115.3,115.2,75.2,35.6,32.5. 19 F NMR (470MHz, CDCl3) δ-109.24,-116.15.

[0062] Example 10:

[0063] According to the method of Example 1, 4-chlorostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 71%.

[0064] 2,5-bis(4-chlorophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.87(d,J=8.4Hz,2H),7.41(d,J=8.4Hz,2H),7.31(d,J=8.3Hz,2H),7.23(d,J=8.3H z,2H),5.28(t,J=7.7Hz,1H),3.18–3.12(m,1H),3.03–2.96(m,1H),2.65–2.58(m,1H),1.90–1.83(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.3,132.7,129.3,128.8,128.6,127.9,75.1,35.6,32.3.

[0065] Example 11:

[0066] According to the method of Example 1, 4-chloromethylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 69%.

[0067] 2,5-bis(4-(chloromethyl)phenyl)-3,4-dihydro-2H-pyrrole. 1 HNMR (500MHz, CDCl3) δ7.93(d,J=8.0Hz,2H),7.45(d,J=8.0Hz,2H),7.35(d,J=8.2Hz,2H),7.28(d,J=7.9Hz,2H),5.30( t,J=7.4Hz,1H),4.62(s,2H),4.58(s,2H),3.19–3.14(m,1H),3.04–2.97(m,1H),2.63–2.57(m,1H),1.93–1.87(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.5,144.7,140.0,136.1,128.8,128.7,128.3,126.9,126.3,75.6,46.1,45.7,35.6,32.3.

[0068] Example 12:

[0069] According to the method of Example 1, 4-bromostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 75%.

[0070] 2,5-bis(4-bromophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.79(d,J=8.5Hz,2H),7.57(d,J=8.5Hz,2H),7.46(d,J=8.4Hz,2H),7.18(d,J=8.3H z,2H),5.24(t,J=7.8Hz,1H),3.16–3.10(m,1H),3.01–2.94(m,1H),2.64–2.57(m,1H),1.89–1.81(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.0,143.4,133.1,131.7,131.5,129.4,128.2,125.3,120.6,75.4,35.5,32.4.

[0071] Example 13:

[0072] According to the method of Example 1, 4-trifluoromethylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 39%.

[0073] 2,5-bis(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ8.05(d,J=7.7Hz,2H),7.71(d,J=7.7Hz,2H),7.61(d,J=7.5Hz,2H),7.43(d,J=7.6H z,2H),5.39(t,J=7.5Hz,1H),3.24–3.18(m,1H),3.10–3.03(m,1H),2.72–2.66(m,1H),1.96–1.88(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.4,148.0,128.3,126.8,125.6,125.5,75.6,35.8,32.2. 19 F NMR(470MHz, CDCl3)δ-62.38,-62.83.

[0074] Example 14:

[0075] According to the method of Example 1, 2-methoxystyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 76%.

[0076] 2,5-bis(2-methoxyphenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.92(d,J=7.6Hz,1H),7.39(t,J=7.8Hz,1H),7.21(d,J=7.7Hz,1H),7.00(t,J=7.5Hz,1H),6.9 7–6.87(m,4H),5.53(t,J=7.6Hz,1H),3.87(d,J=5.8Hz,6H),3.18–3.04(m,2H),2.61–2.53(m,1H).1.77–1.69(m,1H) 13 C{ 1 H}NMR (126MHz, CDCl3) δ174.5,158.3,156.5,133.4,131.2,130.3,127.5,126.8,120.6,120.5,111.3,110.2,69.2,55.4,55.3,38.8,31.8.

[0077] Example 15:

[0078] According to the method of Example 1, 2-chlorostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 71%.

[0079] 2,5-bis(2-chlorophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.70(d,J=7.2Hz,1H),7.45(d,J=7.5Hz,1H),7.39(d,J=7.8Hz,1H),7.37–7.31(m,3H),7.27 –7.19(m,2H),5.63(t,J=7.6Hz,1H),3.25–3.19(m,1H),3.16–3.09(m,1H),2.82–2.75(m,1H),1.82–1.76(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ175.7,141.9,135.1,132.5,130.6,130.3,130.2,129.3,128.0,127.4,127.0,126.8,72.9,39.1,31.9.

[0080] Example 16:

[0081] According to the method of Example 1, 2-fluorostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 68%.

[0082] 2,5-bis(2-fluorophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR(500MHz, CDCl3)δ8.08(t,J=7.6Hz,1H),7.45–7.41(m,1H),7.29(t,J=7.5Hz,1H),7.24–7.19(m,2H),7.12– 7.03(m,3H),5.50(t,J=7.8Hz,1H),3.25–3.20(m,1H),3.15–3.08(m,1H),2.69–2.62(m,1H),1.90–1.82(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ171.9,132.2,132.1,130.3,128.3,128.2,127.8,124.2,124.1,116.4,116.2,115.3,115.1,68.9,38.6,31.6. 19 F NMR (470MHz, CDCl3) δ-112.38,-118.65.

[0083] Example 17:

[0084] According to the method of Example 1, 3-methylstyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 71%.

[0085] 2,5-Dimethylbenzene-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.83(s,1H),7.69(d,J=7.6Hz,1H),7.32(t,J=7.6Hz,1H),7.25(s,1H),7.22(t,J=7.5Hz,1H),7.08(dd,J=19.4,8 .0Hz,3H),5.27(t,J=7.7Hz,1H),3.21–3.13(m,1H),3.03–2.96(m,1H),2.61–2.54(m,1H),2.40(s,3H),2.34(s,3H),1.93–1.87(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.7,144.5,138.1,138.0,134.4,131.4,128.4,128.3,127.6,127.2,125.2,123.6,76.0,35.6,32.4,21.5,21.3.

[0086] Example 18:

[0087] According to the method of Example 1, 2-bromostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 69%.

[0088] 2,5-bis(2-bromophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.64(d,J=8.0Hz,1H),7.57(t,J=8.4Hz,2H),7.37(d,J=7.3Hz,2H),7.30(dd,J=14.7,7.3Hz,2H),7 .13(t,J=7.6Hz,1H),5.60(t,J=7.9Hz,1H),3.25–3.19(m,1H),3.11–3.04(m,1H),2.86–2.79(m,1H),1.80–1.72(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ158.8,143.5,133.4,132.5,130.6,130.0,128.3,127.7,127.4,122.7,121.0,75.4,39.2,32.0.

[0089] Example 19:

[0090] According to the method of Example 1, 3-bromostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 63%.

[0091] 2,5-bis(3-bromophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ8.10(s,1H),7.83(d,J=7.8Hz,1H),7.59(d,J=8.6Hz,1H),7.44(s,1H),7.39(d,J=7.4Hz,1H),7.31(t,J=7 .9Hz,1H),7.24–7.20(m,2H),5.27(t,J=7.9Hz,1H),3.20–3.11(m,1H),3.01–2.96(m,1H),2.66–2.58(m,1H),1.92–1.84(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ172.9,146.6,136.1,133.7,130.9,130.1,130.0,129.6,126.5,125.2,122.8,122.7,75.5,35.6,32.3.

[0092] Example 20:

[0093] According to the method of Example 1, 3-chlorostyrene was used instead of styrene, and other conditions remained unchanged to obtain 1-pyrroline product with an isolated yield of 64%.

[0094] 2,5-bis(3-chlorophenyl)-3,4-dihydro-2H-pyrrole. 1 H NMR (500MHz, CDCl3) δ7.94(s,1H),7.79(d,J=7.7Hz,1H),7.44(d,J=8.0Hz,1H),7.38(d,J=7.8Hz,1H),7.28(d,J=5.6Hz,2H),7.24 (s,1H),7.19(d,J=7.4Hz,1H),5.27(t,J=7.8Hz,1H),3.19–3.12(m,1H),3.03–2.95(m,1H),2.66–2.58(m,1H),1.92–1.84(m,1H). 13 C{ 1 H}NMR (126MHz, CDCl3) δ173.1,146.2,134.7,130.8,129.8,128.0,127.1,126.6,126.1,124.7,75.4,35.6,32.2.

[0095] The above examples are for screening a range of substrates for substituents and substitution positions according to the present invention. Below, styrene will be used as a representative substrate, strictly applying a single variable approach to screen reaction conditions. (Other substrates do not affect the optimization of reaction conditions.)

[0096] Example 21:

[0097] According to the method of Example 1, other electrolytes were used instead of tetrabutylammonium perchlorate, and other conditions remained unchanged to obtain the 1-pyrroline product 2,5-diphenyl-3,4-dihydro-2H-pyrrole. The isolated yield is shown in Table 1.

[0098] Table 1: Effect of electrolyte type on target product yield

[0099]

[0100] Example 22:

[0101] According to the method of Example 1, other solvents were used instead of dichloroethane and hexafluoroisopropanol (HFIP), and other conditions remained unchanged to obtain the 1-pyrroline product 2,5-diphenyl-3,4-dihydro-2H-pyrrole. The isolated yield is shown in Table 2.

[0102] Table 2: Effect of organic solvents on target product yield

[0103]

[0104]

[0105] Example 23:

[0106] According to the method of Example 1, the constant current and reaction time were changed, and other conditions remained unchanged to obtain the 1-pyrroline product 2,5-diphenyl-3,4-dihydro-2H-pyrrole. The isolated yield is shown in Table 3.

[0107] Table 3: Target product yields at different currents and reaction times

[0108]

[0109] The above-mentioned implementation cases are only preferred implementation cases in the present invention, but the implementation methods of the present invention are not limited to the above-mentioned implementation cases. For example, various combinations of the schemes in the embodiments and any other changes, modifications, substitutions, and combinations made without departing from the spirit and principles of the present invention should be equivalent replacement methods and are within the scope of protection of the present invention.

Claims

1. A method for preparing 1-pyrroline, characterized in that, include: Steps for synthesizing the target product by electrochemical reaction of styrene and trimethylsilyl azide in an electrolyte solution: In the formula, R is any one of methyl, ethyl, tert-butyl, alkoxy, chloromethyl, halogen, and trifluoromethyl, and the substitution position is ortho, para, or meta.

2. The method according to claim 1, wherein The electrolyte in the electrolyte solution is tetrabutylammonium perchlorate or tetrabutylammonium tetrafluoroborate, and the solvent is a mixed solvent of dichloroethane and hexafluoroisopropanol in a volume ratio of 5 to 10:1, preferably a mixed solvent of dichloroethane and hexafluoroisopropanol in a volume ratio of 8:

1.

3. The method according to claim 1, wherein The electrochemical reaction uses a carbon rod as the anode and a platinum sheet as the cathode.

4. The method according to claim 1, wherein The electrochemical reaction adopts a constant current, and the current is 3 mA to 20 mA, preferably 3 mA to 10 mA, and more preferably 5 mA.

5. The method according to claim 1, wherein The electrochemical reaction is carried out at 0-40°C, preferably room temperature.

6. The method according to claim 1, wherein The electrochemical reaction time is not less than 6 hours.

7. The method according to claim 1, wherein The amount of electrolyte used is 0.2-1 times the molar amount of styrene used, preferably 0.5 times the molar amount.

8. The method according to claim 1, wherein The amount of azidotrimethylsilane used is 1-3 times the molar amount of styrene used, preferably 1.5 times the molar amount.

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