An electro-synthesis of 1-pyrrolines

Abstract

The application discloses an electro-synthesis method of 1-pyrroline, which comprises the following steps: using a platinum sheet as a cathode, a carbon rod as an anode, using tetrabutylammonium perchlorate or tetrabutylammonium tetrafluoroborate as an electrolyte under constant current catalysis, and one-pot dimerization cyclization of styrene and azidotrimethylsilane to prepare 1 ‑ pyrroline derivative, and after post-treatment of the obtained reaction mixture, 1 ‑ pyrroline is obtained through column chromatography separation. ‑ The application can obtain 1 ‑ pyrroline derivative through only one reaction step, has few operation steps, avoids use of oxidants, additives and metals, and has a simple post-treatment process and easy product separation.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis, and specifically relates to a method for preparing 1-pyrrololine. Background Technology

[0002] 1-Pyrrololine derivatives are a class of organic synthetic intermediates with diverse biological activities, finding wide applications in chemistry, materials science, and drug design. To date, the classic 5-exo-trig cyclization reaction has provided strong support for the synthesis of 1-pyrrololine derivatives. This reaction requires metals, oxidants, and other catalysts to generate nitrogen radicals or nitrogen-metal complexes, thereby achieving the addition to an olefin. This not only necessitates complex pre-synthesis of the substrate but also requires the completion of cyclization by another molecule. Therefore, the preparation of 1-pyrrololine derivatives from simple substrates and conditions is essential.

[0003] Furthermore, electrochemical organic synthesis technology currently exhibits superior synthetic capabilities, increasingly attracting the interest of organic chemists. This technology not only solves problems such as the use of additives and external oxidants, and low yields, but also allows for simple operation under mild conditions, with experiments easily started and stopped by controlling the current. Therefore, finding green and efficient methods for the electrosynthesis of 1-pyrrolline derivatives is an important research topic. Summary of the Invention

[0004] The purpose of this invention is to provide a simple, green, and efficient method for preparing 1-pyrrololine derivatives from styrene and azidotrimethylsilane.

[0005] The technical solution to achieve the objective of this invention is:

[0006] In a first aspect, the present invention provides a method for preparing 1-pyrroline, comprising the step of synthesizing the target product by electrochemically reacting styrene and azidetrimethylsilane in an electrolyte solution:

[0007]

[0008] In the formula, R includes, but is not limited to, any one of methyl, ethyl, tert-butyl, alkoxy, chloromethyl, halogen, and trifluoromethyl groups, 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 mixture 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 the anode and a platinum sheet as the cathode, with a constant current of 3 mA to 20 mA, preferably 3 mA to 10 mA, and more preferably 5 mA.

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

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

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

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

[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 synthesis method of the present invention is simple and efficient. 1-pyrrololine derivatives can be obtained in just one reaction. There are few operation steps, the use of oxidants and additives is avoided, the post-processing is simple, the product is easy to separate, and the operation requirements are greatly simplified.

[0018] (2) The reaction conditions of the present invention are easy to achieve 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 noble metal catalysis.

[0019] (3) The styrene used in this invention exhibits excellent reactivity under electrochemical conditions. Cyclomerization with azidotrimethylsilane after dimerization is a known simple method for synthesizing 1-pyrroline derivatives from the most readily available starting materials. Attached Figure Description

[0020] Figure 1 This is the 1H NMR spectrum of 2,5-diphenyl-3,4-dihydro-2H-pyrrole prepared in Example 1 of this invention.

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

[0022] Figure 3 This is the 1H NMR spectrum of 2,5-bis(4-isopropoxyphenyl)-3,4-dihydro-2H-pyrrole prepared in Example 2 of this invention.

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

[0024] Figure 5This is the 1H NMR spectrum of 2,5-di-o-tolyl-3,4-dihydro-2H-pyrrole prepared in Example 3 of this invention.

[0025] Figure 6 This is the carbon NMR spectrum of 2,5-di-o-tolyl-3,4-dihydro-2H-pyrrole prepared in Example 3 of this invention. Detailed Implementation

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

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

[0028] Unless otherwise defined, 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 pertains; the term “and / or” as used herein includes any and all combinations of one or more of the associated listed items.

[0029] Unless otherwise specified in the examples, the procedures should be performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0030] As used herein, the term “about” is used to provide for the flexibility and imprecision associated with a given term, measure, or value. Those 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 thereof.

[0032] Concentration, amount, and other numerical data may be presented in range format herein. It should be understood that such range format is used solely for convenience and brevity and should be flexibly interpreted to include not only the values ​​explicitly stated as the limits of the range, but also all individual values ​​or subranges encompassed within the range, as if each value and subrange were explicitly stated. For example, a range of values ​​from about 1 to about 4.5 should be interpreted to include not only the explicitly stated limits of 1 to 4.5, but also individual numbers (such as 2, 3, 4) and subranges (such as 1 to 3, 2 to 4, etc.). The same principle applies to ranges that describe only a single value, such as “less than about 4.5,” which should be interpreted to include all the aforementioned values ​​and ranges. Furthermore, this interpretation should apply regardless of the breadth of the range or characteristic described.

[0033] The method for preparing 1-pyrrololine derivatives according to the present invention includes the following steps:

[0034] (1) In a dry three-necked flask, under constant current, dichloroethane and hexafluoroisopropanol were used 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 azidotrimethylsilane were added to the three-necked flask under argon protection, stirred, and electrified. (3) After the reaction was completed, the resulting reaction mixture was post-treated, and the pure 1-pyrrolline derivative was obtained by column chromatography.

[0035] Example 1:

[0036] A magnetic flux and tetrabutylammonium perchlorate (0.25 mmol, 0.5 equivalence) were added to a dry three-necked flask (20 mL) containing a graphite rod anode (φ = 6 mm, 90 mm) and a platinum cathode (10 mm × 10 mm × 0.2 mm). Then, dichloroethane (8 mL), hexafluoroisopropanol (1 mL), azidotrimethylsilane (1.5 equivalence), and styrene (0.5 mmol, 1.0 equivalence) were injected separately into the flask using a 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 complete, the solvent was removed under reduced pressure. The product was purified by flash column chromatography on silica gel using a petroleum ether / ethyl acetate mixture of 30:1 as the eluent, yielding 75% 1-pyrrolline. The 1H and 1C NMR spectra are shown below. 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] Following the method of Example 1, 4-isopropoxystyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product, with a separation yield of 82%. Nuclear magnetic resonance (NMR) 1H and 1C spectroscopy characterization are shown below. 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] Following the method of Example 1, 2-methylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 4-methylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 4-ethylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 4-tert-butylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 4-methoxystyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 4-ethoxystyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 4-fluorostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 4-chlorostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 4-chloromethylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 4-bromostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 4-trifluoromethylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 2-methoxystyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 2-chlorostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation 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] Following the method of Example 1, 2-fluorostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 3-methylstyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrololine product with a separation yield of 71%.

[0085] 2,5-di-m-toluene-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] Following the method of Example 1, 2-bromostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 3-bromostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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] Following the method of Example 1, 3-chlorostyrene was used instead of styrene, with other conditions remaining unchanged, to obtain the 1-pyrrolidone product with a separation 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 embodiments are for screening the range of substituents and substrates for the substitution positions of the present invention. Below, styrene will be used as a representative substrate, and the reaction conditions will be strictly screened using a single-variable method. (Other substrates do not affect the optimization of reaction conditions).

[0096] Example 21:

[0097] Following the method of Example 1, other electrolytes were used instead of tetrabutylammonium perchlorate, and other conditions remained unchanged, to obtain the 1-pyrrolino product 2,5-diphenyl-3,4-dihydro-2H-pyrrole. The separation yields are shown in Table 1.

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

[0099]

[0100] Example 22:

[0101] Following the method of Example 1, other solvents were used instead of dichloroethane and hexafluoroisopropanol (HFIP), while other conditions remained unchanged, to obtain the 1-pyrrolinoline product 2,5-diphenyl-3,4-dihydro-2H-pyrrole. The separation yields are shown in Table 2.

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

[0103]

[0104]

[0105] Example 23:

[0106] Following the method of Example 1, by changing the constant current and reaction time while keeping other conditions unchanged, the 1-pyrrololine product 2,5-diphenyl-3,4-dihydro-2H-pyrrole was obtained, and the separation yields are shown in Table 3.

[0107] Table 3: Yields of target products under different currents and reaction times

[0108]

[0109] The above embodiments are merely preferred embodiments of the present invention, but the implementation of the present invention is not limited to the above embodiments. Any changes, modifications, substitutions, or combinations made without departing from the spirit and principle of the present invention, such as various combinations of solutions in the embodiments, should be considered equivalent replacements and are all within the protection scope of the present invention.

Claims

1. A method for preparing 1-pyrrololine, characterized in that, include: The steps for synthesizing the target product by electrochemical reaction of R-substituted styrene and azidotrimethylsilane in an electrolyte solution: ; In the formula, R is any group selected from methyl, ethyl, tert-butyl, alkoxy, chloromethyl, halogen, and trifluoromethyl, and the substitution position is ortho, para, or meta. The solvent in the electrolyte solution is a mixture of dichloroethane and hexafluoroisopropanol in a volume ratio of 5 to 10:

1. The electrochemical reaction uses a constant current, ranging from 3 mA to 20 mA.

2. The method as described in claim 1, characterized in that, The electrolyte in the electrolyte solution is tetrabutylammonium perchlorate or tetrabutylammonium tetrafluoroborate.

3. The method as described in claim 1, characterized in that, The solvent in the electrolyte solution is a mixture of dichloroethane and hexafluoroisopropanol in an 8:1 ratio.

4. The method as described in claim 1, characterized in that, The electrochemical reaction uses a carbon rod as the anode and a platinum sheet as the cathode.

5. The method as described in claim 1, characterized in that, The current is 3 mA to 10 mA.

6. The method as described in claim 1 or 5, characterized in that, The current is 5 milliamps.

7. The method as described in claim 1, characterized in that, The electrochemical reaction is carried out at 0~40℃.

8. The method as described in claim 1 or 7, characterized in that, The electrochemical reaction takes place at room temperature.

9. The method as described in claim 1, characterized in that, The electrochemical reaction time shall not be less than 6 hours.

10. The method as described in claim 1, characterized in that, The amount of electrolyte used is 0.2-1 times the molar amount of R-substituted styrene.

11. The method as described in claim 1 or 10, characterized in that, The amount of electrolyte used is 0.5 times the molar amount of R-substituted styrene.

12. The method as described in claim 1, characterized in that, The amount of azidotrimethylsilane used is 1-3 times the molar amount of R-substituted styrene.

13. The method as described in claim 1 or 12, characterized in that, The amount of azidotrimethylsilane used is 1.5 times the molar amount of R-substituted styrene.

Images