注册 English

Synthesis of Pyrazolines by Cascade Oxidation/Halogenoamino-cyclization Reaction of Homoallylhydrazides

Pengfei Li ,  Danfeng Huang ,  Tianyu Yang ,  Zhoubin Deng ,  Kehu Wang ,  Junjiao Wang ,  Yingpeng Su ,  Yulai Hu

downloadPDF
Citation:  Li Pengfei, Huang Danfeng, Yang Tianyu, Deng Zhoubin, Wang Kehu, Wang Junjiao, Su Yingpeng, Hu Yulai. Synthesis of Pyrazolines by Cascade Oxidation/Halogenoamino-cyclization Reaction of Homoallylhydrazides[J]. Chinese Journal of Organic Chemistry, 2019, 39(10): 2920-2929. doi: 10.6023/cjoc201903073 shu

高烯丙基酰肼氧化/卤胺环化串联反应合成吡唑啉类化合物

  • .

    西北师范大学化学化工学院 兰州 730070

    • 通讯作者: 胡雨来, huyl@nwnu.edu.cn
  • 基金项目:

    国家自然科学基金（Nos.21662030，21861033）资助项目

    国家自然科学基金 21861033

    国家自然科学基金 21662030

摘要: 探索了以N-碘代丁二酰亚胺（NIS）作为卤化试剂，通过高烯丙基酰肼化合物的串联氧化/卤胺环化反应合成吡唑啉类化合物.该方法反应条件温和，不需要添加剂，以良好的收率得到吡唑啉类化合物.

English

  • 1.   Introduction

    Nitrogen-containing heterocycles are vastly distributed in natural products, drugs and agricultural chemicals.[1] As a class of important heterocycle, pyrazoline derivatives show broad bioactivities such as anticancer, [2] antidepressant, [3] anticonvulsant, [4] antibacterial[5] and antimalarial activities.[6] Furthermore, they also attracted attentions in material science because of their luminescent and nonlinear optical properties.[7] In view of their broad applications, many efforts have been devoted to the synthesis of the pyrazoline derivatives over the past decades. Typically, pyrazolines were synthesized by aza-Michael addition/cyclo- condensation reactions of hydrazines with α, β-unsaturated aldehydes or ketones, [8] 1, 3-dipolar cycloaddition of diazoalkanes or nitrilimines with alkenes[9] and cyclocondensation of hydrazines with dihalides or ditosylates.[10] As an easy available 1, 2-dinitro building blocks, hydrazones were also used to construct the pyrazolines.[11~14] For instance, [4+1]-annulations of α-chloro acylhydrazone with maleimides, diazo esters or sulfur ylides have been developed to synthesize pyrazolines.[12] A visible-light photocatalytic transformation of β, γ-unsaturated hydrazones into pyrazolines was also reported recently.[13] In our previous works on synthesis of trifluoromethyl compounds, we found that trifluoromethylated homoallylic N-acylhydra- zines could be conveniently transformed into trifluoromethyl pyrazolines by halogenation reagents such as N-iodosuccinimide (NIS), N-bromosuccinimide (NBS) and N-chlorosuccinimide (NCS).[15] Herein, we report that this process could also be applied to non-trifluoromethylated homoallylhydrazides to construct pyrazolines in good to excellent yields (Scheme 1).

    Scheme 1

    Scheme 1.  Methods for synthesis of pyrazolines from homoallylhydrazides
    下载: 全尺寸图片 幻灯片

    2.   Results and discussion

    Based on our previous reaction conditions, [15] N'-(1- phenylbut-3-en-1-yl)benzohydrazide (1a) was taken as substrate to react with NIS (2a) in tetrahedron (THF) at room temperature. After 4 h, N-benzoyl-5-iodomethyl-3- phenylpyrazoline (3a) was obtained in 91% yield (Table 1). In order to investigate the generalities of the substrates, the effects of different N-acyl groups in homoallylic acylhydrazines 1 were examined. The results in Table 1 showed that both of the aromatic and aliphatic acyl groups were suitable for the reaction, but the substrate with aromatic acyl groups gave the corresponding products in higher yield than that with aliphatic acyl groups.

    Table 1

    Table 1.  Substrate scope of the reactiona
    下载: 导出CSV

    Next, the influence of R2 group of homoallylhydrazides 1 on the reaction was studied (Table 2). The homoallylhydrazides 1 with different R2 groups were taken as substrates to react with NIS under the standard reaction conditions. When R2 groups were aromatic groups, all the corresponding products obtained in high yields whenever the substitutes on phenyl rings were electron-withdrawing groups or electron-donating groups (3aa~3ai). However, the yields of the products decreased when R2 groups were aliphatic groups (3aj~3am).

    Table 2

    Table 2.  Substrate scope of the reactiona
    下载: 导出CSV

    After the investigation of the effects of R1 and R2 groups on the reaction separately, their combined influences on the reaction were checked further. As shown in Table 3, when both R1 and R2 groups were aromatic groups, the corresponding products were obtained in good to excellent yields (3ba~3fa). Especially, when R1 groups were electron-poor aromatic groups, the reactions gave the corresponding products in higher yields than those with elec-tron-rich aromatic groups. If R1 groups were electron-rich aromatic groups and R2 groups were electron-poor aromatic groups, the yields of products were lower (3ea and 3fa). When one or both of R1 or R2 were aliphatic groups, the yields of the corresponding products decreased. As an extreme example, there was no product formed when R1 and R2 groups were sterically hindered isopropyl groups (3la).

    Table 3

    Table 3.  Substrate scope of the reactiona
    下载: 导出CSV

    Next, the influences of halogen sources such as NIS (2a), NBS (2b) and NCS (2c) on the reaction were investigated. The results were collected in Table 4. Among the three halogen sources, NIS gave the products in the highest yields and NCS gave the products in the lowest yields when the same substrates were tested.

    Table 4

    Table 4.  Substrate scope of the reactiona
    下载: 导出CSV

    To demonstrate the synthetic utility of this methodology, a gram-scale reaction was performed by using homoal- lylhydrazide 1a as substrate under the standard reaction conditions (Eq. 1). The reaction proceeded very well to give the product 3a in 85% yield. More importantly, these dihydropyrazole products could be easily converted into pyrazoles through a simple operation. For example, N-free pyrazole 4 was obtained from 3a in 88% yield in the presence of KOH under refluxing in ethanol for 30 min (Eq. 2).

    The mechanism for the oxidative halocyclization of homoallylhydrazides with N-halogensuccinimide can refer to our previous work.[15]

    3.   Conclusions

    In conclusion, a novel and efficient cascade oxide-tion/ iodoaminocyclization reaction of homoallylic N-acylhy- drazines has been developed, which provides a concise method for the synthesis of potentially bioactive pyrazoline derivatives. This process tolerates a wide range of substrates to produce the products in good to excellent yields. Especially, the products possess a halogen group, which can be used for further transformation into more complex pyrazoline derivatives. Further investigations on this reaction for the synthesis of other heterocycles are underway in our laboratory.

    4.   Experimental section

    4.1   Materials and methods

    All of the commercially available reagents and solvents were used without further purification. Homoallylhydrazides were prepared through condensation of hydrazides with aldehydes and allyl bromide according to the literature procedure.[16] Flash chromatography was performed using silica gel 60 (230-400 mesh). Analytical thin layer chromatography (TLC) was conducted using silica gel GF254. TLC plates were analysed by an exposure to ultraviolet (UV) light and/or submersion in a phosphomolybdic acid solution or in Iodine vapour. 1H NMR spectra were measured on 600 and 400 MHz spectrometers. 13C NMR spectra were measured on 150 and 100 MHz spectrometers.

    4.2   General procedure for the synthesis of 3

    Homoallylhydrazides 1 (0.15 mmol, 1 equiv.), NIS, NBS or NCS 2 (0.6 mmol, 4 equiv.) were placed in a dried round-bottom flask (50 mL) fitted with a magnetic bar. Tetrahydrofuran (5 mL) was then added. The mixture was stirred at room temperature. When the starting materials were consumed completely as monitored by TLC, the saturated Na2S2O3 solution (10 mL) was poured into the mixture and stirred for 10 min. Tetrahydrofuran was removed under vacuum and the mixture was extracted with ethyl acetate (10 mL×3). The combined organic phases were dried (MgSO4) and concentrated. Purification of the residue by silica gel column chromatography (230~400 mesh) using ethyl acetate and petroleum ether as eluent furnished the pure products 3.

    (5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone (3a): 53 mg, yield 91%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:3]; yellowish solid, m.p. 106~107 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.98 (d, J=7.2 Hz, 2H), 7.69 (dd, J=7.2, 1.2 Hz, 2H), 7.51~7.48 (m, 1H), 7.46~7.43 (m, 2H), 7.42~7.38 (m, 3H), 4.93~4.88 (m, 1H), 3.76 (dd, J=10.2, 6.6 Hz, 1H), 3.69 (dd, J=9.6, 2.4 Hz, 1H), 3.48 (dd, J=17.4, 10.8 Hz, 1H), 3.10 (dd, J=17.4, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 167.1, 154.3, 134.1, 131.0, 131.0, 130.4, 130.0, 128.7, 127.6, 126.7, 57.9, 39.2, 9.6; HRMS (ESI) calcd for C17H16IN2O [M+H]+ 391.0302; found 391.0298.

    (2-Fluorophenyl)(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3b): 54 mg, yield 88%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:10]; yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.62~7.59 (m, 3H), 7.48~7.34 (m, 4H), 7.21 (t, J=7.6 Hz, 1H), 7.13 (t, J=8.8 Hz, 1H), 4.93~4.86 (m, 1H), 3.75~3.69 (m, 2H), 3.53 (dd, J=18.0, 11.2 Hz, 1H), 3.14 (dd, J=18.0, 4.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 164.2, 159.3 (d, JC-F=250.1 Hz), 154.8, 131.9 (d, JC-F=8.3 Hz), 130.8, 130.6, 130.0 (d, JC-F=3.2 Hz), 128.6, 126.7, 124.0 (d, JC-F=15.8 Hz), 123.7 (d, JC-F=3.5 Hz), 115.6 (d, JC-F=21.8 Hz), 57.8, 39.9, 8.7; HRMS (ESI) calcd for C17H14FI- N2NaO [M+Na]+ 431.0027; found 431.0012.

    (3-Fluorophenyl)(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3c): 54 mg, yield 89%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:3]; white solid, , m.p. 115~116 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.78 (d, J=7.2 Hz, 1H), 7.72 (d, J=9.6 Hz, 1H), 7.69 (d, J=7.8 Hz, 2H), 7.45~7.40 (m, 4H), 7.20 (t, J=8.4 Hz, 1H), 4.92~4.85 (m, 1H), 3.78~3.76 (m, 1H), 3.67 (d, J=9.0 Hz, 1H), 3.50 (dd, J=17.4, 10.8 Hz, 1H), 3.11 (dd, J=17.4, 4.8Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.5, 162.0 (d, JC-F=247.2 Hz), 154.9, 136.1 (d, JC-F=7.4 Hz), 130.8, 130.7, 129.3 (d, JC-F=7.8 Hz), 128.8, 126.8, 125.8 (d, JC-F=3.0 Hz), 118.1 (d, JC-F=21.2 Hz), 117.2 (d, JC-F=23.6 Hz), 57.9, 39.2, 9.3; HRMS (ESI) calcd for C17H14FIN2NaO [M+Na]+ 431.0027; found 431.0021.

    (4-Fluorophenyl)(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3d): 58 mg, yield 94%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:5]; white solid, m.p. 114~115 ℃; 1H NMR (600 MHz, CDCl3) δ: 8.04 (dd, J=8.4, 5.4 Hz, 2H), 7.68 (d, J=7.8 Hz, 2H), 7.45~7.40 (m, 3H), 7.12 (t, J=8.4 Hz, 2H), 4.91~4.87 (m, 1H), 3.76 (dd, J=10.2, 7.2 Hz, 1H), 3.68 (dd, J=10.2, 2.4 Hz, 1H), 3.49 (dd, J=18.0, 11.4 Hz, 1H), 3.10 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.8, 164.4 (d, JC-F=250.4 Hz), 154.6, 132.6 (d, JC-F=8.7 Hz), 130.9, 130.6, 130.1 (d, JC-F=3.2 Hz), 128.7, 126.7, 114.7 (d, JC-F=21.6 Hz), 57.9, 39.2, 9.5; HRMS (ESI) calcd for C17H15FIN2O [M+H]+ 409.0208; found 409.0195.

    (5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(o-tolyl)methanone (3e): 47 mg, yield 78%; Rf=0.4 [V(ethylacetate):V(petroleum ether)=1:10]; yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J=6.4 Hz, 2H), 7.43 (d, J=6.8 Hz, 1H), 7.38~7.31 (m, 4H), 7.23 (t, J=5.6 Hz, 2H), 4.92~4.85 (m, 1H), 3.84 (dd, J=10.0, 6.4 Hz, 1H), 3.70 (dd, J=10.0, 2.4 Hz, 1H), 3.50 (dd, J=18.0, 11.2 Hz, 1H), 3.11 (dd, J=18.0, 5.2 Hz, 1H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 168.9, 154.5, 135.6, 135.5, 130.8, 130.4, 130.1, 129.3, 128.6, 128.0, 126.6, 125.1, 57.3, 39.7, 20.0, 9.4; HRMS (ESI) calcd for C18H17IN2NaO [M+Na]+ 427.0278; found 427.0286.

    (5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(m-tolyl)methanone (3f): 48 mg, yield 80%; Rf=0.4 [V(ethylacetate):V(petroleum ether)=1:10]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.78 (d, J=8.4 Hz, 2H), 7.69~7.67 (m, 2H), 7.43~7.38 (m, 3H), 7.35~7.30 (m, 2H), 4.93~4.88 (m, 1H), 3.75 (dd, J=10.2, 7.2 Hz, 1H), 3.70 (dd, J=10.2, 3.0 Hz, 1H), 3.49 (dd, J=17.4, 10.8 Hz, 1H), 3.11 (dd, J=17.4, 4.8 Hz, 1H), 2.42 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 167.3, 154.2, 137.4, 134.0, 131.8, 131.0, 130.5, 130.4, 128.7, 127.5, 127.2, 126.7, 57.9, 39.2, 21.4, 9.6; HRMS (ESI) calcd for C18H17IN2NaO [M+Na]+ 427.0278; found 427.0279.

    (5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(p-tolyl)methanone (3g): 51 mg, yield 84%; Rf=0.45 [V(ethylacetate):V(petroleum ether)=1:10]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.91 (d, J=8.4 Hz, 2H), 7.69 (dd, J=7.2, 3.0 Hz, 2H), 7.42~7.39 (m, 3H), 7.25 (d, J=7.2 Hz, 2H), 4.92~4.88 (m, 1H), 3.73 (dd, J=10.2, 6.6 Hz, 1H), 3.70 (dd, J=9.6, 3.0 Hz, 1H), 3.47 (dd, J=17.4, 10.8 Hz, 1H), 3.09 (dd, J=18.0, 5.4 Hz, 1H), 2.42 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 167.0, 154.1, 141.5, 131.1, 131.0, 130.4, 130.2, 128.7, 128.4, 126.7, 58.0, 39.1, 21.5, 9.7; HRMS (ESI) calcd for C18H17IN2NaO [M+Na]+ 427.0278; found 427.0266.

    (4-Chlorophenyl)(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3h): 55 mg, yield 86%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:6]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.94 (d, J=8.4 Hz, 2H), 7.68 (d, J=7.2Hz, 2H), 7.45~7.38 (m, 5H), 4.91~4.85 (m, 1H), 3.76 (dd, J=10.2, 6.6 Hz, 1H), 3.68~3.66 (m, 1H), 3.51~3.45 (m, 1H), 3.13~3.08 (m, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.9, 154.8, 137.2, 132.4, 131.5, 130.8, 130.6, 128.7, 127.9, 126.7, 57.9, 39.2, 9.4; HRMS (ESI) calcd for C17H14ClIN2NaO [M+Na]+ 446.9732; found 446.9751.

    Furan-2-yl(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3i): 49 mg, yield 86%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:5]; yellow solid, m.p. 168~169 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.78 (t, J=9.6 Hz, 2H), 7.65~7.63 (m, 2H), 7.47~7.46 (m, 3H), 6.57 (t, J=1.8 Hz, 1H), 4.92~4.89 (m, 1H), 3.71 (dd, J=9.6, 2.4 Hz, 1H), 3.63 (dd, J=9.6, 7.8 Hz, 1H), 3.48 (dd, J=18.0, 10.8 Hz, 1H), 3.11 (dd, J=18.0, 3.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 156.3, 155.1, 145.8, 145.6, 130.9, 130.7, 128.8, 126.7, 119.5, 111.7, 58.2, 39.0, 9.0; HRMS (ESI) calcd for C15H13IN2NaO2 [M+Na]+ 402.9914; found 402.9932.

    (5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(naphthalen-2-yl)methanone (3j): 57 mg, yield 86%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:5]; yellow solid, m.p. 165~166 ℃; 1H NMR (600 MHz, CDCl3) δ: 8.55 (s, 1H), 8.05 (dd, J=8.4, 1.2 Hz, 1H), 7.96 (d, J=8.4 Hz, 1H), 7.90~7.87 (m, 2H), 7.69 (dd, J=7.2, 1.2 Hz, 2H), 7.59~7.53 (m, 2H), 7.43~7.39 (m, 3H), 4.99~4.94 (m, 1H), 3.75 (dd, J=10.2, 6.6 Hz, 1H), 3.70 (dd, J=10.2, 3.0 Hz, 1H), 3.49 (dd, J=17.4, 10.8 Hz, 1H), 3.11 (dd, J=17.4, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.8, 165.2, 163.5, 154.6, 132.6, 132.5, 130.8, 130.6, 130.1, 130.0, 128.7, 126.7, 114.8, 114.6, 57.9, 39.2, 9.5; HRMS (ESI) calcd for C21H17IN2NaO [M+Na]+ 463.0278; found 463.0255.

    1-(5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)ethan-1-one (3k): 37 mg, yield 75%; Rf=0.6 [V(ethyl-acetate):V(petroleum ether)=1:5]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 7.73~7.71 (m, 2H), 7.42~7.40 (m, 3H), 4.70~4.66 (m, 1H), 3.60 (dd, J=10.2, 3.0 Hz, 1H), 3.52 (dd, J=10.2, 7.2 Hz, 1H), 3.43 (dd, J=18.0, 10.8 Hz, 1H), 3.04 (dd, J=18.0, 4.8 Hz, 1H), 2.39 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 169.5, 153.6, 131.0, 130.4, 128.7, 126.6, 57.0, 39.9, 21.9, 9.4; HRMS (ESI) calcd for C12H14IN2O [M+H]+ 329.0145; found 329.0142.

    1-(5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)-2-methylpropan-1-one (3l): 36 mg, yield 68%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:5]; yellowish oil. 1H NMR (600 MHz, CDCl3) δ: 7.73~7.71 (m, 2H), 7.42~7.40 (m, 3H), 4.67~4.63 (m, 1H), 3.61 (dd, J=10.2, 6.6 Hz, 1H), 3.56 (dd, J=10.2, 3.0 Hz, 1H), 3.49~3.45 (m, 1H), 3.41 (dd, J=17.4, 10.8 Hz, 1H), 3.02 (dd, J=17.4, 4.8 Hz, 1H), 1.25 (d, J=6.6 Hz, 3H), 1.18 (d, J=6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 176.0, 153.3, 131.2, 130.3, 128.7, 126.5, 56.9, 39.5, 32.0, 19.4, 18.5, 9.7; HRMS (ESI) calcd for C14H18IN2O [M+H]+ 357.0458; found 357.0458.

    Cyclohexyl(5-(iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3m): 46 mg, yield 78%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:4]; white solid, m.p. 116~117 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.74~7.72 (m, 2H), 7.45~7.41 (m, 3H), 4.66~4.62 (m, 1H), 3.62 (dd, J=10.2, 7.2 Hz, 1H), 3.55 (dd, J=10.2, 2.4 Hz, 1H), 3.41 (dd, J=17.4, 10.8 Hz, 1H), 3.22~3.17 (m, 1H), 3.01 (dd, J=17.4, 4.8 Hz, 1H), 2.00 (d, J=14.4 Hz, 1H), 1.84~1.80 (m, 3H), 1.71 (d, J=13.8 Hz, 1H), 1.57~1.48 (m, 2H), 1.43~1.23 (m, 3H); 13C NMR (150 MHz, CDCl3) δ: 175.2, 153.2, 131.3, 130.3, 128.7, 126.5, 56.8, 41.8, 39.5, 29.3, 28.4, 26.0, 25.9, 25.7, 9.9; HRMS (ESI) calcd for C17H21IN2NaO [M+Na]+ 419.0591; found 419.0586.

    1-(5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)dodecan-1-one (3n): 51 mg, yield 73%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:4]; white solid, m.p. 120~121 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.74~7.71 (m, 2H), 7.44~7.40 (m, 3H), 4.70~4.66 (m, 1H), 3.61~3.55 (m, 2H), 3.43 (dd, J=18.0, 11.4 Hz, 1H), 3.04 (dd, J=18.0, 5.4 Hz, 1H), 2.83~2.78 (m, 1H), 2.70~2.65 (m, 1H), 1.74~1.69 (m, 2H), 1.41~1.37 (m, 2H), 1.34~1.25 (m, 15H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.5, 153.3, 131.2, 130.3, 128.7, 126.5, 57.0, 39.7, 34.2, 31.9, 30.9, 29.7, 29.6, 29.5, 29.4, 29.3, 25.0, 22.7, 14.1, 9.6; HRMS (ESI) calcd for C22H34IN2O [M+H]+ 469.1710; found 469.1690.

    1-(5-(Iodomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)octadecan-1-one (3o): 60 mg, yield 72%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; white solid, m.p. 118~119 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.73~7.72 (m, 2H), 7.43~7.40 (m, 3H), 4.70~4.66 (m, 1H), 3.61~3.55 (m, 2H), 3.42 (dd, J=18.0, 11.4 Hz, 1H), 3.04 (dd, J=18.0, 5.4 Hz, 1H), 2.83~2.78 (m, 1H), 2.70~2.65 (m, 1H), 1.74~1.69 (m, 2H), 1.36~1.25 (m, 28H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.4, 153.2, 131.2, 130.3, 128.7, 126.5, 57.0, 39.7, 34.2, 31.9, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 25.0, 22.7, 14.1, 9.6; HRMS (ESI) calcd for C28H46IN2O [M+H]+ 553.2649; found 553.2634.

    (4-Fluorophenyl)(3-(2-fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3aa): 55 mg, yield 87%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:4]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 8.04 (dd, J=8.4, 5.4 Hz, 2H), 7.80 (t, J=7.2 Hz, 1H), 7.40 (dd, J=13.8, 7.2 Hz, 1H), 7.18 (t, J=7.8 Hz, 1H), 7.14~7.11 (m, 3H), 4.88~4.84 (m, 1H), 3.81 (dd, J=10.2, 6.6 Hz, 1H), 3.63~3.61 (m, 1H), 3.60~3.57 (m, 1H), 3.22~3.17 (m, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.9, 164.4 (d, JC-F=250.5 Hz), 161.2 (d, JC-F=252.5 Hz), 151.5 (d, JC-F=2.9 Hz), 132.6 (d, JC-F=8.9 Hz), 132.1 (d, JC-F=8.6 Hz), 130.0 (d, JC-F=3.2 Hz), 128.9 (d, JC-F=3.0 Hz), 124.5 (d, JC-F=3.5 Hz), 119.0 (d, JC-F=10.9 Hz), 116.6 (d, JC-F=22.0 Hz), 114.7 (d, JC-F=21.6 Hz), 57.8 (d, JC-F=2.7 Hz), 41.5 (d, JC-F=7.8 Hz), 9.7; HRMS (ESI) calcd for C17H14F2IN2O [M+H]+ 427.0113; found 427.0113.

    (4-Fluorophenyl)(3-(3-fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ab): 59 mg, yield 92%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:4]; yellow oil. 1H NMR (600 MHz, CDCl3) δ 8.02 (dd, J=11.4, 6.0 Hz, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.39 (dd, J=12.6, 7.8 Hz, 2H), 7.14~7.11 (m, 3H), 4.91~4.87 (m, 1H), 3.79 (dd, J=10.2, 6.6 Hz, 1H), 3.66 (dd, J=10.2, 2.4 Hz, 1H), 3.47 (dd, J=18.0, 11.4 Hz, 1H), 3.07 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 166.0, 164.4 (d, JC-F=250.5 Hz), 162.8 (d, JC-F=245.4 Hz), 153.5 (d, JC-F=3.0 Hz), 133.1 (d, JC-F=7.9 Hz), 132.5 (d, JC-F=8.7 Hz), 130.4 (d, JC-F=8.5 Hz), 129.9 (d, JC-F=3.3 Hz), 122.5 (d, JC-F=2.9 Hz), 117.5 (d, JC-F=21.3 Hz), 114.8 (d, JC-F=21.6 Hz), 113.4 (d, JC-F=22.8 Hz), 58.0, 39.2, 9.5; HRMS (ESI) calcd for C17H13F2IN2NaO [M+Na]+ 448.9933; found 448.9932.

    (4-Fluorophenyl)(3-(4-fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ac): 61 mg, yield 95%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:4]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 8.02 (dd, J=10.2, 5.4 Hz, 2H), 7.68 (dd, J=9.0, 4.8 Hz, 2H), 7.14~7.09 (m, 4H), 4.92~4.87 (m, 1H), 3.77 (dd, J=10.2, 6.6 Hz, 1H), 3.67 (dd, J=10.2, 2.4 Hz, 1H), 3.47 (dd, J=18.0, 11.4 Hz, 1H), 3.08 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 165.9, 164.4 (d, JC-F=250.5 Hz), 164.1 (d, JC-F=250.2 Hz), 153.6, 132.5 (d, JC-F=8.7 Hz), 130.1 (d, JC-F=3.2 Hz), 128.6 (d, JC-F=8.6 Hz), 127.2 (d, JC-F=3.3 Hz), 116.0 (d, JC-F=21.8 Hz), 114.8 (d, JC-F=20.1 Hz), 58.0, 39.3, 9.6; HRMS (ESI) calcd for C17H13F2IN2NaO [M+Na]+ 448.9933; found 448.9925

    (4-Fluorophenyl)(5-(iodomethyl)-3-(o-tolyl)-4, 5-dihy-dro-1H-pyrazol-1-yl)methanone (3ad): 52 mg, yield 83%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 8.00 (dd, J=9.0, 6.6 Hz, 2H), 7.41 (d, J=7.8 Hz, 1H), 7.30 (t, J=6.6 Hz, 1H), 7.26 (t, J=7.2 Hz, 2H), 7.08 (t, J=8.4 Hz, 2H), 4.84~4.79 (m, 1H), 3.83 (dd, J=10.2, 6.6 Hz, 1H), 3.64~3.62 (m, 1H), 3.59~3.53 (m, 1H), 3.15~3.10 (m, 1H), 2.49 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 166.2, 164.3 (d, JC-F=250.2 Hz), 155.4, 138.0, 132.3 (d, JC-F=8.7 Hz), 131.9, 130.2 (d, JC-F=3.3 Hz), 129.8, 129.7, 129.0, 126.0, 114.6 (d, JC-F=21.6 Hz), 56.6, 41.4, 23.3, 9.9; HRMS (ESI) calcd for C18H16FIN2NaO [M+Na]+ 445.0184; found 445.0182.

    (4-Fluorophenyl)(5-(iodomethyl)-3-(m-tolyl)-4, 5-dihy-dro-1H-pyrazol-1-yl)methanone (3ae): 54 mg, yield 86%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 8.04 (dd, J=9.0, 5.4 Hz, 2H), 7.49 (d, J=10.2 Hz, 2H), 7.30 (t, J=7.8 Hz, 1H), 7.25 (s, 1H), 7.13 (d, J=8.4 Hz, 2H), 4.90~4.86 (m, 1H), 3.75 (dd, J=10.2, 6.6 Hz, 1H), 3.67 (dd, J=10.2, 2.4 Hz, 1H), 3.47 (dd, J=18.0, 11.4 Hz, 1H), 3.09 (dd, J=18.0, 5.4 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 165.8, 164.4 (d, JC-F=251.4 Hz), 154.9, 138.5, 132.6 (d, JC-F=8.7 Hz), 131.4, 130.8, 130.1 (d, JC-F=3.4 Hz), 128.7, 127.3, 123.9, 114.7 (d, JC-F=21.6 Hz), 57.8, 39.3, 21.4, 9.6; HRMS (ESI) calcd for C18H16FIN2NaO [M+Na]+ 445.0184; found 445.0164.

    (4-Fluorophenyl)(5-(iodomethyl)-3-(p-tolyl)-4, 5-dihy-dro-1H-pyrazol-1-yl)methanone (3af): 57 mg, yield 90%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:4]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 8.04 (dd, J=7.8, 6.0 Hz, 2H), 7.57 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.8 Hz, 2H), 7.12 (d, J=8.0 Hz, 2H), 4.90~4.85 (m, 1H), 3.73 (dd, J=9.6, 7.2 Hz, 1H), 3.67 (dd, J=9.6, 2.4 Hz, 1H), 3.46 (dd, J=18.0, 11.4 Hz, 1H), 3.08 (dd, J=18.0, 5.4 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 165.7, 164.4 (d, JC-F=250.4 Hz), 154.7, 141.0, 132.6 (d, JC-F=8.7 Hz), 130.2 (d, JC-F=3.4 Hz), 129.5, 128.1, 126.7, 114.7 (d, JC-F=21.6 Hz), 57.9, 39.2, 21.5, 9.6; HRMS (ESI) calcd for C18H16FIN2NaO [M+Na]+ 445.0184; found 445.0177.

    (3-(4-Chlorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-py-razol-1-yl)(4-fluorophenyl)methanone (3ag): 61 mg, yield 93%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:3]; yellow solid, m.p. 113~114 ℃; 1H NMR (600 MHz, CDCl3) δ: 8.01 (dd, J=9.0, 6.6 Hz, 2H), 7.61 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.4 Hz, 2H), 7.13 (t, J=8.4 Hz, 2H), 4.91~4.88 (m, 1H), 3.78 (dd, J=10.2, 7.2 Hz, 1H), 3.66 (dd, J=10.2, 4.2 Hz, 1H), 3.46 (dd, J=17.4, 11.4 Hz, 1H), 3.08 (dd, J=18.0, 4.2 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.9, 164.4 (d, JC-F=250.5 Hz), 153.5, 136.6, 132.5 (d, JC-F=8.9 Hz), 130.0 (d, JC-F=3.3 Hz), 129.4, 129.0, 127.9, 114.8 (d, JC-F=21.6 Hz), 58.0, 39.2, 9.5; HRMS (ESI) calcd for C17H13ClFIN2NaO [M+Na]+ 464.9637; found 464.9617.

    (4-Fluorophenyl)(5-(iodomethyl)-3-(4-(trifluoromethyl)-phenyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ah): 68 mg, yield 96%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:3]; white solid, m.p. 111~112 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.02 (dd, J=9.2, 5.6 Hz, 2H), 7.79 (d, J=8.0 Hz, 2H), 7.67 (d, J=8.4 Hz, 2H), 7.13 (t, J=8.8 Hz, 2H), 4.95~4.89 (m, 1H), 3.83 (dd, J=10.4, 6.6 Hz, 1H), 3.65 (dd, J=10.4, 2.4 Hz, 1H), 3.51 (dd, J=18.0, 11.2 Hz, 1H), 3.12 (dd, J=18.0, 5.2 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 166.1, 164.5 (d, JC-F=250.7 Hz), 153.1, 134.3, 132.5 (d, JC-F=8.9 Hz), 132.1 (q, JC-F=32.7 Hz), 129.8 (d, JC-F=3.2 Hz), 126.9, 125.7 (q, JC-F=3.8 Hz), 123.7 (q, JC-F=270.8 Hz), 114.8 (d, JC-F=21.6 Hz), 58.1, 39.1, 9.6; HRMS (ESI) calcd for C18H13F4I-N2NaO [M+Na]+ 498.9901; found 498.9902.

    (4-Fluorophenyl)(5-(iodomethyl)-3-(4-methoxyphenyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ai): 56 mg, yield 86%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 8.04 (dd, J=9.0, 5.4 Hz, 2H), 7.63 (d, J=9.0 Hz, 2H), 7.12 (t, J=8.4 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 4.90~4.85 (m, 1H), 3.84 (s, 3H), 3.73 (dd, J=10.2, 7.8 Hz, 1H), 3.68 (dd, J=10.2, 2.4 Hz, 1H), 3.45 (dd, J=17.4, 10.8 Hz, 1H), 3.07 (dd, J=17.4, 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 165.6, 164.2 (d, JC-F=250 Hz), 161.5, 154.3, 132.5 (d, JC-F=8.7 Hz), 130.2 (d, JC-F=3.1 Hz), 128.3, 123.4, 114.6 (d, JC-F=21.5 Hz), 114.1, 57.8, 55.3, 39.2, 9.5; HRMS (ESI) calcd for C18H16FIN2NaO2 [M+Na]+ 461.0133; found 461.0148.

    (4-Fluorophenyl)(5-(iodomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3aj): 25 mg, yield 49%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:3]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.92 (dd, J=9.0, 5.4 Hz, 2H), 7.08 (t, J=6.4 Hz, 2H), 4.73~4.69 (m, 1H), 3.74 (dd, J=10.2, 6.6 Hz, 1H), 3.55 (dd, J=10.2, 2.4 Hz, 1H), 3.08 (dd, J=18.6, 10.8 Hz, 1H), 2.65 (dd, J=18.6, 5.4 Hz, 1H), 2.04 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 165.7, 164.3 (d, JC-F=250.1 Hz), 156.3, 132.2 (d, JC-F=8.7 Hz), 130.3 (q, JC-F=3.3 Hz), 114.7 (d, JC-F=21.6 Hz), 57.2, 43.2, 16.0, 9.9; HRMS (ESI) calcd for C12H12FIN2NaO [M+Na]+ 368.9871; found 368.9866.

    (4-Fluorophenyl)(3-heptyl-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ak): 50 mg, yield 77%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:2]; colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.94 (dd, J=8.4, 5.6 Hz, 2H), 7.08 (t, J=8.4 Hz, 2H), 4.71~4.65 (m, 1H), 3.76 (dd, J=10.0, 6.4 Hz, 1H), 3.53 (dd, J=10.0, 2.0 Hz, 1H), 3.05 (dd, J=18.4, 11.2 Hz, 1H), 2.66 (dd, J=18.4, 5.2 Hz, 1H), 2.37~2.32 (m, 2H), 1.63~1.55 (m, 2H), 1.31~1.26 (m, 8H), 0.89 (t, J=7.8 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 165.6, 164.2 (d, JC-F=249.9 Hz), 163.3, 132.5 (d, JC-F=8.7 Hz), 130.2 (d, JC-F=3.2 Hz), 114.6 (d, JC-F=21.5 Hz), 56.9, 41.6, 31.7, 30.1, 29.2, 28.9, 26.2, 22.6, 14.0, 10.1; HRMS (ESI) calcd for C18H24FIN2NaO [M+Na]+ 453.0810; found 453.0822.

    (3-Cyclohexyl-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)(4-fluorophenyl)methanone (3al): 34 mg, yield 53%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.97 (t, J=6.8 Hz, 2H), 7.07 (t, J=8.8 Hz, 2H), 4.71~4.65 (m, 1H), 3.76 (dd, J=10.0, 5.4 Hz, 1H), 3.53 (dd, J=10.0, 2.4 Hz, 1H), 3.05 (dd, J=18.4, 11.2 Hz, 1H), 2.67 (dd, J=18.4, 4.8 Hz, 1H), 2.39~2.35 (m, 1H), 1.88 (d, J=10.4 Hz, 2H), 1.80 (d, J=5.6 Hz, 2H), 1.70 (d, J=12.8 Hz, 1H), 1.41~1.17 (m, 5H); 13C NMR (150 MHz, CDCl3) δ: 165.5, 164.2 (d, JC-F=249.9 Hz), 163.3, 132.5 (d, JC-F=8.7 Hz), 130.2 (d, JC-F=3.2 Hz), 114.6 (d, JC-F=21.5 Hz), 56.6, 39.6, 39.2, 30.2, 25.8, 25.6, 10.2; HRMS (ESI) calcd for C17H20FIN2NaO [M+Na]+ 437.0497; found 437.0507.

    (E)-(4-Fluorophenyl)(5-(iodomethyl)-3-styryl-4, 5-dihy-dro-1H-pyrazol-1-yl)methanone (3am): 33 mg, yield 50%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 7.97 (dd, J=6.4, 4.2 Hz, 2H), 7.48 (d, J=7.2 Hz, 2H), 7.37 (t, J=7.2 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.11 (t, J=9.0 Hz, 2H), 7.02 (d, J=16.2 Hz, 1H), 6.86 (d, J=16.2 Hz, 1H), 4.84~4.80 (m, 1H), 3.75 (dd, J=10.2, 6.6 Hz, 1H), 3.65 (dd, J=10.2, 2.4 Hz, 1H), 3.33 (dd, J=17.4, 11.4 Hz, 1H), 2.96 (dd, J=17.4, 7.2 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.8, 164.4 (d, JC-F=250.4 Hz), 155.6, 137.9, 135.5, 132.4 (d, JC-F=8.9 Hz), 130.0 (d, JC-F=3.2 Hz), 129.2, 128.9, 127.1, 120.3, 114.8 (d, JC-F=21.6 Hz), 57.7, 38.0, 9.6; HRMS (ESI) calcd for C19H16FIN2NaO [M+ Na]+ 457.0184; found 457.0184.

    (5-(Iodomethyl)-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol-1-yl)(p-tolyl)methanone (3ba): 52 mg, yield 84%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.91 (d, J=8.0 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H), 4.92~4.85 (m, 1H), 3.73~3.68 (m, 2H), 3.44 (dd, J=17.6, 11.2 Hz, 1H), 3.06 (dd, J=17.6, 4.8 Hz, 1H), 2.41 (s, 3H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 166.9, 154.2, 141.4, 140.7, 131.2, 130.2, 129.3, 128.3, 128.2, 126.6, 57.9, 39.1, 21.5, 21.5, 9.7; HRMS (ESI) calcd for C19H20IN2O [M+H]+ 419.0615; found 419.0624.

    (4-Chlorophenyl)(3-(4-chlorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ca): 58 mg, yield 85%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:3]; yellow solid, m.p. 146~147 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.92 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.4 Hz, 2H), 4.91~4.86 (m, 1H), 3.78 (dd, J=10.2, 6.6 Hz, 1H), 3.66 (dd, J=10.2, 2.4 Hz, 1H), 3.46 (dd, J=18.0, 11.4 Hz, 1H), 3.07 (dd, J=17.4, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 166.0, 153.6, 137.3, 136.6, 132.3, 131.5, 129.3, 129.0, 128.0, 127.9, 58.0, 39.2, 9.4; HRMS (ESI) calcd for C17H13Cl2IN2NaO [M+Na]+ 480.9342; found 480.9345.

    (4-Chlorophenyl)(3-(4-fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3da): 59 mg, yield 88%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow oil. 1H NMR (400 MHz, CDCl3) δ: 7.92 (d, J=8.4 Hz, 2H), 7.60 (dd, J=8.8, 5.6 Hz, 2H), 7.42 (d, J=8.8 Hz, 2H), 7.10 (t, J=8.8 Hz, 2H), 4.91~4.85 (m, 1H), 3.77 (dd, J=10.4, 6.8 Hz, 1H), 3.66 (dd, J=10.4, 2.8 Hz, 1H), 3.47 (dd, J=18.0, 11.2 Hz, 1H), 3.08 (dd, J=18.0, 5.6 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 165.9, 164.1 (d, JC-F=250.5 Hz), 153.7, 137.2, 132.4, 131.4, 128.7 (d, JC-F=8.7 Hz), 127.9, 127.1 (d, JC-F=3.2 Hz), 116.0 (d, JC-F=21.9 Hz), 57.9, 39.3, 9.4; HRMS (ESI) calcd for C17H13ClFIN2NaO [M+Na]+ 464.9637; found 464.9635.

    (3-(4-Fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-py-razol-1-yl)(p-tolyl)methanone (3ea): 42 mg, yield 66%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellowish solid, m.p. 125~126 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.88 (d, J=12.0 Hz, 2H), 7.67 (dd, J=12.6, 7.8 Hz, 2H), 7.25 (d, J=12.0 Hz, 2H), 7.08 (t, J=13.2 Hz, 2H), 4.92~4.87 (m, 1H), 3.74 (dd, J=10.2, 7.2 Hz, 1H), 3.67 (dd, J=10.2, 2.4 Hz, 1H), 3.42 (dd, J=18.0, 11.4 Hz, 1H), 3.04 (dd, J=17.4, 5.4 Hz, 1H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 167.0, 163.9 (d, JC-F=250.1 Hz), 153.0, 141.5, 131.1, 130.1, 128.5 (d, JC-F=8.6 Hz), 128.3, 127.3 (d, JC-F=3.3 Hz), 115.8 (d, JC-F=21.9 Hz), 58.0, 39.2, 21.5, 9.7; HRMS (ESI) calcd for C18H16FIN2NaO [M+Na]+ 445.0184; found 445.0183.

    (3-(4-Chlorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-py-razol-1-yl)(p-tolyl)methanone (3fa): 43 mg, yield 66%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow solid, m.p. 145~146 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=5.6 Hz, 2H), 7.60 (d, J=5.6 Hz, 2H), 7.35 (d, J=5.6 Hz, 2H), 7.25 (d, J=5.6 Hz, 2H), 4.90~4.86 (m, 1H), 3.74 (dd, J=10.4, 7.2 Hz, 1H), 3.66 (dd, J=9.8, 1.6 Hz, 1H), 3.42 (dd, J=13.0, 7.6 Hz, 1H), 3.03 (dd, J=12.6, 3.6 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:167.0, 152.9, 141.5, 136.3, 131.0, 130.1, 129.6, 128.9, 128.3, 127.9, 58.0, 39.0, 21.5, 9.6; HRMS (ESI) calcd for C18H16ClIN2NaO [M+Na]+ 460.9894; found 460.9884.

    1-(3-(4-Fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)ethan-1-one (3ga): 22 mg, yield 43%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.73 (dd, J=9.0, 5.4 Hz, 2H), 7.12 (t, J=9.0 Hz, 2H), 4.72~4.68 (m, 1H), 3.61 (dd, J=10.2, 3.0 Hz, 1H), 3.55 (dd, J=10.2, 7.8 Hz, 1H), 3.44 (dd, J=18.0, 11.4 Hz, 1H), 3.04 (dd, J=18.0, 5.4 Hz, 1H), 2.39 (s, 3H); 13C NMR (150 MHz, CDCl3) δ: 169.4, 163.9 (d, JC-F=250.1 Hz), 152.6, 128.5 (d, JC-F=8.6 Hz), 127.3 (d, JC-F=3.3 Hz), 115.8 (d, JC-F=21.9 Hz), 57.1, 40.0, 21.8, 9.3; HRMS (ESI) calcd for C12H13FIN2O [M+H]+ 347.0057; found 347.0045.

    1-(3-(4-Fluorophenyl)-5-(iodomethyl)-4, 5-dihydro-1H-pyrazol-1-yl)octadecan-1-one (3ha): 64 mg, yield 76%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellowish solid, m.p. 132~134 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.72 (dd, J=9.0, 5.4 Hz, 2H), 7.12 (t, J=9.0 Hz, 2H), 4.71~4.6 (m, 1H), 3.58 (d, J=4.8 Hz, 2H), 3.41 (dd, J=18.0, 11.4 Hz, 1H), 3.01 (dd, J=17.4, 4.8 Hz, 1H), 2.82~2.77 (m, 1H), 2.69~2.64 (m, 1H), 2.34 (t, J=7.8 Hz, 1H), 1.74~1.68 (m, 2H), 1.63 (t, J=7.2 Hz, 1H), 1.30~1.25 (m, 26H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ: 172.5, 164.0 (d, JC-F=249.9 Hz), 152.3, 128.5 (d, JC-F=8.6 Hz), 127.5 (d, JC-F=3.3 Hz), 115.9 (d, JC-F=21.9 Hz), 57.1, 39.8, 34.2, 31.9, 29.7, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4, 29.4, 29.3, 29.2, 29.1, 25.0, 24.7, 22.7, 14.1, 9.5; HRMS (ESI) calcd for C28H44FIN2NaO [M+Na]+ 593.2380; found 593.2367.

    1-(5-(Iodomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)-2-methylpropan-1-one (3ia): 27 mg, yield 62%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:1); yellow oil. 1H NMR (600 MHz, CDCl3) δ 4.42~4.38 (m, 1H), 3.52 (dd, J=10.2, 6.6 Hz, 1H), 3.38 (dd, J=10.2, 2.4 Hz, 1H), 3.24~3.20 (m, 1H), 2.96 (dd, J=18.0, 10.8 Hz, 1H), 2.50 (dd, J=18.0, 4.8 Hz, 1H), 1.96 (s, 3H), 1.12 (d, J=7.2 Hz, 3H), 1.05 (d, J=6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.5, 154.9, 56.2, 43.5, 31.7, 19.4, 18.4, 15.9, 10.1; HRMS (ESI) calcd for C9H15IN2NaO [M+ Na]+ 317.0127; found 317.0128.

    Cyclohexyl(5-(iodomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)methanone (3ja): 37 mg, yield 73%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 4.48~4.44 (m, 1H), 3.59 (dd, J=10.2, 6.6 Hz, 1H), 3.43 (dd, J=10.2, 2.4 Hz, 1H), 3.05~2.98 (m, 2H), 2.56 (dd, J=18.6, 4.8 Hz, 1H), 2.03 (s, 3H), 1.91 (d, J=15.6 Hz, 1H), 1.80~1.77 (m, 3H), 1.68 (d, J=10.8 Hz, 1H), 1.52~1.44 (m, 2H), 1.35~1.26 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.6, 154.7, 56.1, 43.4, 41.5, 29.3, 28.3, 25.9, 25.8, 25.6, 15.9, 10.3; HRMS (ESI) calcd for C12H19IN2NaO [M+Na]+ 357.0440; found 357.0432.

    1-(5-(Iodomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)octadecan-1-one (3ka): 44 mg, yield 60%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:2]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 4.52~4.48 (m, 1H), 3.54 (dd, J=10.2, 7.2 Hz, 1H), 3.48 (dd, J=10.2, 3.0 Hz, 1H), 3.02 (dd, J=18.6, 10.2 Hz, 1H), 2.69~2.64 (m, 1H), 2.60~2.51 (m, 2H), 2.03 (s, 3H), 1.68~1.63 (m, 3H), 1.31~1.25 (m, 27H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.8, 154.8, 56.4, 43.7, 34.2, 31.9, 29.8, 29.7, 29.6, 29.5, 29.4, 29.4, 29.3, 25.0, 22.7, 15.9, 14.1, 9.9; HRMS (ESI) calcd for C23H44IN2O [M+H]+ 491.2498, found 491.2488.

    (E)-1-(5-(Iodomethyl)-3-styryl-4, 5-dihydro-1H-pyrazol-1-yl)ethan-1-one (3ma): 25 mg, yield 48%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:2]; yellowish oil. 1H NMR (600 MHz, CDCl3) δ: 7.49 (d, J=7.8 Hz, 2H), 7.38 (t, J=7.2 Hz, 2H), 7.33 (t, J=7.2 Hz, 1H), 7.02 (d, J=16.8 Hz, 1H), 6.83 (d, J=17.4 Hz, 1H), 4.66~4.62 (m, 1H), 3.59 (dd, J=10.2, 3.0 Hz, 1H), 3.52 (dd, J=10.2, 7.8 Hz, 1H), 3.30 (dd, J=18.0, 11.4 Hz, 1H), 2.92 (dd, J=18.0, 5.4 Hz, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 169.3, 154.6, 137.5, 135.6, 129.1, 128.9, 127.1, 120.4, 56.9, 38.7, 21.8, 9.3; HRMS (ESI) calcd for C14H16IN2O [M+H]+ 355.0307; found 355.0306.

    (5-(Bromomethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone (3bb): 45 mg, yield 87%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:2]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 7.99 (d, J=7.8 Hz, 2H), 7.69 (d, J=7.2 Hz, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.44 (t, J=7.8 Hz, 2H), 7.41~7.38 (m, 3H), 5.13~5.10 (m, 1H), 3.92 (dd, J=10.2, 6.6 Hz, 1H), 3.84 (d, J=10.8 Hz, 1H), 3.46 (dd, J=17.4, 11.4 Hz, 1H), 3.26 (dd, J=17.4, 4.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 167.1, 155.0, 134.0, 131.0, 130.9, 130.4, 130.0, 128.6, 127.6, 126.7, 58.3, 44.7, 35.9; HRMS (ESI) calcd for C17H16BrN2O [M+H]+ 343.0446; found 343.0436.

    (5-(Chloromethyl)-3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone (3bc): 27 mg, yield 60%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:2]; colorless oil. 1H NMR (600 MHz, CDCl3) δ 7.98 (d, J=6.6 Hz, 2H), 7.68 (d, J=7.8, 1.8 Hz, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.44 (t, J=7.8 Hz, 2H), 7.42~7.38 (m, 3H), 5.15~5.11 (m, 1H), 4.07 (dd, J=10.8, 6.0 Hz, 1H), 3.95 (dd, J=10.8, 2.4 Hz, 1H), 3.46 (dd, J=18.0, 11.4 Hz, 1H), 3.31 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 167.1, 155.0, 134.0, 131.0, 130.9, 130.5, 130.0, 128.7, 127.6, 126.7, 58.3, 44.7, 35.9; HRMS (ESI) calcd for C17H16ClN2NaO [M+Na]+ 321.0771; found 321.0781.

    (5-(Bromomethyl)-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol-1-yl)(p-tolyl)methanone (3cb): 43 mg, yield 78%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 7.91 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 7.25 (d, J=7.8 Hz, 2H), 7.20 (d, J=7.8 Hz, 2H), 5.12~5.08 (m, 1H), 3.87 (dd, J=10.2, 6.0 Hz, 1H), 3.85 (dd, J=10.8, 3.6 Hz, 1H), 3.44 (dd, J=18.0, 11.4 Hz, 1H), 3.23 (dd, J=17.4, 5.4 Hz, 1H), 2.41 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 166.9, 154.6, 141.4, 140.8, 131.2, 130.2, 129.4, 128.3, 128.2, 126.7, 57.9, 37.1, 34.1, 21.5, 21.4; HRMS (ESI) calcd for C19H20BrN2O [M+H]+ 371.0759; found 371.0761.

    (5-(Chloromethyl)-3-(p-tolyl)-4, 5-dihydro-1H-pyrazol--yl)(p-tolyl)methanone (3cc): 30 mg, yield 62%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.91 (d, J=8.0 Hz, 2H), 7.58 (d, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 5.13~5.07 (m, 1H), 4.01 (dd, J=11.2, 6.0 Hz, 1H), 3.95 (dd, J=11.2, 2.8 Hz, 1H), 3.43 (dd, J=17.6, 11.2 Hz, 1H), 3.28 (dd, J=17.6, 4.2 Hz, 1H), 2.41 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 167.0, 154.9, 141.4, 140.7, 131.2, 130.2, 129.3, 128.4, 128.3, 126.7, 58.3, 44.7, 35.9, 21.5, 21.4; HRMS (ESI) calcd for C19H20ClN2O [M+H]+ 327.1259; found 327.1262

    (5-(Bromomethyl)-3-(4-fluorophenyl)-4, 5-dihydro-1H-pyrazol-1-yl)(4-fluorophenyl)methanone (3db): 44 mg, yield 78%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 8.02 (dd, J=9.0, 5.4 Hz, 2H), 7.68 (dd, J=9.0, 5.4 Hz, 2H), 7.14~7.08 (m, 4H), 5.15~5.11 (m, 1H), 3.95 (dd, J=10.2, 6.0 Hz, 1H), 3.82 (dd, J=10.2, 2.4 Hz, 1H), 3.47 (dd, J=18.0, 11.4 Hz, 1H), 3.24 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 165.9, 164.4 (d, JC-F=250.5 Hz), 164.1 (d, JC-F=250.5 Hz), 154.0, 132.5 (d, JC-F=8.9 Hz), 130.0 (d, JC-F=3.3 Hz), 128.7 (d, JC-F=8.4 Hz), 127.2 (d, JC-F=3.2 Hz), 115.9 (d, JC-F=21.9 Hz), 114.5 (d, JC-F=21.6 Hz), 58.0, 37.2, 34.0; HRMS (ESI) calcd for C17H14BrF2N2O [M+H]+ 379.0252; found: 379.0252

    (5-(Chloromethyl)-3-(4-fluorophenyl)-4, 5-dihydro-1H-pyrazol-1-yl)(4-fluorophenyl)methanone (3dc): 25 mg, yield 50%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:3]; yellow solid, m.p. 101~102 ℃; 1H NMR (600 MHz, CDCl3) δ: 8.02 (dd, J=8.4, 5.4 Hz, 2H), 7.68 (dd, J=8.4, 5.4 Hz, 2H), 7.14~7.09 (m, 4H), 5.16~5.12 (m, 1H), 4.09 (dd, J=11.4, 6.0 Hz, 1H), 3.94 (dd, J=11.4, 2.4 Hz, 1H), 3.47 (dd, J=18.0, 11.4 Hz, 1H), 3.30 (dd, J=18.0, 5.4 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ: 166.0, 164.4 (d, JC-F=250.7 Hz), 164.1 (d, JC-F=250.4 Hz), 154.2, 132.5 (d, JC-F=8.7 Hz), 130.0 (d, JC-F=3.3 Hz), 128.7 (d, JC-F=8.6 Hz), 127.2 (d, JC-F=3.2 Hz), 116.0 (d, JC-F=21.9 Hz), 114.7 (d, JC-F=21.6 Hz), 58.4, 44.7, 35.9; HRMS (ESI) calcd for C17H13ClF2N2NaO [M+Na]+ 357.0582; found 357.0568.

    (5-(Bromomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)(cyclohexyl)methanone (3eb): 30 mg, yield 69%; Rf=0.5 [V(ethylacetate):V(petroleum ether)=1:2]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 4.71~4.67 (m, 1H), 3.73 (dd, J=10.2, 6.0 Hz, 1H), 3.58 (dd, J=10.2, 3.0 Hz, 1H), 3.05~2.97 (m, 2H), 2.71 (dd, J=18.0, 5.4 Hz, 1H), 2.02 (s, 3H), 1.87 (d, J=13.2 Hz, 1H), 1.77~1.74 (m, 3H), 1.67 (d, J=11.4 Hz, 1H), 1.50~1.44 (m, 2H), 1.35~1.19 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.7, 155.1, 56.2, 41.5, 41.4, 34.4, 29.2, 28.3, 25.9, 25.8, 25.6, 15.9; HRMS (ESI) calcd for C12H19BrN2NaO [M+Na]+309.0573; found 309.0576.

    (5-(Chloromethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)(cyclohexyl)methanone (3ec): 18 mg, yield 50%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:2]; yellow oil. 1H NMR (600 MHz, CDCl3) δ: 4.73~4.69 (m, 1H), 3.87 (dd, J=10.8, 6.0 Hz, 1H), 3.70 (dd, J=10.8, 3.0 Hz, 1H), 3.06~2.98 (m, 2H), 2.79 (dd, J=18.0, 4.8 Hz, 1H), 2.04 (s, 3H), 1.87 (d, J=13.2 Hz, 1H), 1.77 (t, J=13.2, 3H), 1.68 (d, J=13.8 Hz, 1H), 1.51~1.44 (m, 2H), 1.38~1.21 (m, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.7, 155.3, 56.6, 44.8, 41, 5, 40.1, 29.1, 28.4, 25.9, 25.7, 25.6, 15.9; HRMS (ESI) calcd for C12H20ClN2O [M+H]+ 243.1259; found 243.1266.

    1-(5-(Bromomethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)octadecan-1-one (3fb): 37 mg, yield 56%; Rf=0.6 [V(ethylacetate):V(petroleum ether)=1:2]; colorless oil. 1H NMR (600 MHz, CDCl3) δ: 4.73~4.70 (m, 1H), 3.71 (dd, J=10.2, 6.6 Hz, 1H), 3.63 (dd, J=10.2, 3.0 Hz, 1H), 3.02 (dd, J=18.0, 11.4 Hz, 1H), 2.74 (dd, J=18.6, 4.8 Hz, 1H), 2.69~2.634 (m, 1H), 2.58~2.53 (m, 1H), 2.03 (s, 3H), 1.67~1.62 (m, 2H), 1.35~1.25 (m, 28H), 0.88 (t, J=6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.9, 155.2, 56.4, 41.6, 34.2, 34.1, 31.9, 29.7, 29.6, 29.6, 29.6, 29.5, 29.4, 29.3, 29.3, 24.9, 22.7, 15.9, 14.1; HRMS (ESI) calcd for C23H44BrN2O [M+H]+ 443.2637; found 443.2624.

    1-(5-(Chloromethyl)-3-methyl-4, 5-dihydro-1H-pyrazol-1-yl)octadecan-1-one (3fc): 32 mg, yield 53%; Rf=0.55 [V(ethylacetate):V(petroleum ether)=1:2]; yellow solid, m.p. 101~102 ℃; 1H NMR (600 MHz, CDCl3) δ: 4.75~4.71 (m, 1H), 3.85 (dd, J=11.4, 6.6 Hz, 1H), 3.74 (dd, J=11.4, 3.0 Hz, 1H), 3.01 (dd, J=18.6, 10.8 Hz, 1H), 2.80 (dd, J=18.0, 4.8 Hz, 1H), 2.69~2.64 (m, 1H), 2.59~2.54 (m, 1H), 2.34 (t, J=7.8 Hz, 1H), 2.03 (s, 3H), 1.66~1.62 (m, 3H), 1.30~1.25 (m, 26H), 0.88 (t, J=6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 172.0, 155.5, 56.7, 44.8, 40.3, 34.1, 31.9, 29.7, 29.7, 29.6, 29.6, 29.6, 29.5, 29.4, 29.4, 29.3, 29.3, 29.2, 29.1, 24.9, 24.7, 22.7, 15.9, 14.1; HRMS (ESI) calcd for C23H44ClN2O [M+H]+ 399.3142; found 399.3141.

    4.3   General procedure for the synthesis of 4

    3a (0.2 mmol) was dissolved in CH3CH2OH (2 mL), KOH (2.0 equiv.) was added into the reaction mixture, and then the reaction mixture was refluxed for 30 min until the reaction was completed monitored by TLC analysis. The solvent was removed under vacuum. The crude product was purified by flash chromatography on silica gel using a mixture of petroleum ether and ethyl acetate as an eluting solvent to give the desired product methyl-3-phenyl-1H-pyrazole (4)[17] 28 mg, yield 88%. Rf=0.5 [V(ethylace-tate):V(petroleum ether)=1:2]; yellow solid, m.p. 101~102 ℃; 1H NMR (600 MHz, CDCl3) δ: 7.70 (d, J=7.8 Hz, 2H), 7.35 (d, J=7.8 Hz, 2H), 7.80 (t, J=7.8 Hz, 1H), 6.33 (s, 1H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 149.9, 143.2, 132.5, 128.6, 127.7, 125.7, 102.0, 11.6

    Supporting Information Copies of 1H NMR, 13C NMR spectra and the HRMS data of compounds 3 and 4. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn/.


    1. [1]

      (a) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
      (b) Blair, L. M.; Sperry, J. J. Nat. Prod. 2013, 76, 794.

    2. [2]

      (a) Shaharyar, M.; Abdullah, M. M.; Bakht, M. A.; Majeed, J. Eur. J. Med. Chem. 2010, 45, 114.
      (b) Johnson, M.; Younglove, B.; Lee, L.; LeBlanc, R.; Holt, H., Jr.; Hills, P.; Mackay, H.; Brown, T.; Mooberry, S. L.; Lee, M. Bioorg. Med. Chem. Lett. 2007, 17, 5897.
      (c) Manna, F.; Chimenti, F.; Fioravanti, R.; Bolasco, A.; Secci, D.; Chimenti, P.; Ferlinib, C.; Scambia, G. Bioorg. Med. Chem. Lett. 2005, 15, 4632.

    3. [3]

      Prasad, Y. R.; Rao, A. L.; Prasoona, L.; Murali, K.; Kumar, P. R. Bioorg. Med. Chem. Lett. 2005, 15, 5030. doi: 10.1016/j.bmcl.2005.08.040

    4. [4]

      Oezdemir, Z.; Kandilci, H. B.; Guemuesel, B.; Calis, U.; Bilgin, A. A. Eur. J. Med. Chem. 2007, 42, 373. doi: 10.1016/j.ejmech.2006.09.006

    5. [5]

      (a) Manojkumar, P.; Ravi, T. K.; Gopalakrishnan, S. Eur. J. Med. Chem. 2009, 44, 4690.
      (b) Chimenti, F.; Bizzarri, B.; Manna, F.; Bolasco, A.; Secci, D.; Chimenti, P.; Granese, A.; Rivanera, D.; Lilli, D.; Scaltritoc, M. M.; Brenciaglia, M. I. Bioorg. Med. Chem. Lett. 2005, 15, 603.

    6. [6]

      Acharya, B. N.; Saraswat, D.; Tiwari, M.; Shrivastava, A. K.; Ghorpade, R.; Bapna, S.; Kaushik, M. P. Eur. J. Med. Chem. 2010, 45, 430. doi: 10.1016/j.ejmech.2009.10.023

    7. [7]

      (a) Bliznyuk, V. N.; Seliman, A. F.; Ishchenko, A. A.; Derevyanko, N. A.; DeVo, T. A. ACS Appl. Mater. Interfaces 2016, 8, 12843.
      (b) Szukalski, A.; Sznitko, L.; Cyprych, K.; Miniewicz, A.; Mysliwiec, J. J. Phys. Chem. C 2014, 118, 8102.
      (c) Dwivedi, Y.; de Boni, L.; Goncalves, P. J.; Mairink, L. M.; Menegatti, R.; Fonseca, T. L.; Zilio, S. C. Spectrochim. Acta, Part A 2013, 105, 483.

    8. [8]

      (a) Mahé, O.; Dez, I.; Levacher, V.; Brière, J.-F. Angew. Chem. Int. Ed. 2010, 49, 7072.
      (b) Lévai, A.; Jekő, J. J. Heterocycl. Chem. 2006, 43, 111.

    9. [9]

      (a) Du, T.; Du, F.; Ning, Y.; Peng, Y. Org. Lett. 2015, 17, 1308.
      (b) Simovic, D.; Di, M.; Marks, V.; Chatfield, D. C.; Rein, K. S. J. Org. Chem. 2007, 72, 650.
      (c) Kano, T.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2006, 128, 2174.
      (d) Ruano, J. L. G.; De Diego, S. A. A.; Blanco, D.; Castro, A. M. M.; Martín, M. R.; Ramos, J. H. R. Org. Lett. 2001, 3, 3173.

    10. [10]

      Ju, Y.; Varma, R. S. J. Org. Chem. 2006, 71, 135. doi: 10.1021/jo051878h

    11. [11]

      (a) Cheng, J.; Xu, P.; Li, W.; Cheng Y.; Zhu, C. Chem. Commun. 2016, 52, 11901.
      (b) Wang, G.; Huang, T.; Lin, L.; Feng, X. Org. Lett. 2013, 15, 76.
      (c) Sibi, M. P.; Stanley, L. M.; Soeta, T. Adv. Synth. Catal. 2006, 348, 2371.
      (d) Sibi, M. P.; Stanley, L. M.; Jasperse, C. P. J. Am. Chem. Soc. 2005, 127, 8276.

    12. [12]

      (a) Huang, R.; Tao, H.-Y.; Wang, C.-J. Org. Lett. 2017, 19, 1176.
      (b) Attanasi, O. A.; Crescentini, L. D.; Favi, G. J. Org. Chem. 2014, 79, 8331.
      (c) Chen, J.-R.; Jörres, M.; Bolm, C. J. Am. Chem. Soc. 2012, 134, 6924.

    13. [13]

      (a) Hu, X.-Q.; Chen, J.-R.; Beauchemin, M.; Xiao, W.-J. Chem. Eur. J. 2016, 22, 14141.
      (b) Hu, X.-Q.; Chen, J.-R.; Beauchemin, M.; Xiao, W.-J. Angew. Chem. Int. Ed. 2014, 53, 12163.

    14. [14]

      (a) Yang, M.-N.; Yan, D.-M.; Zhao, Q.-Q.; Chen, J.-R.; Xiao, W.-J. Org. Lett. 2017, 19, 5208.
      (b) Zhao, Q.-Q.; Chen, J.; Yan, D.-M.; Chen, J.-R.; Xiao, W.-J. Org. Lett. 2017, 19, 3620.
      (c) Wu, X.; Wang, M.; Zhang, G.; Zhao, Y.; Wang, J.; Ge, H. Chem. Sci. 2015, 6, 5882.
      (d) Hu, X.-Q.; Deng, Q.-H.; Zou, Y.-Q.; Xiao, W.-J. Eur. J. Org. Chem. 2014, 3082.

    15. [15]

      Wang, Y.; Wang, K.-H.; Su, Y.; Yang, Z.; Wen, L.; Liu, L.; Wang, J.; Huang, D.; Hu, Y. J. Org. Chem. 2018, 83, 939. doi: 10.1021/acs.joc.7b02934

    16. [16]

      陆爱玲, 王凤娇, 黄丹凤, 王克虎, 苏瀛鹏, 徐艳丽, 胡雨来, 有机化学, 2014, 34, 948. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract343765.shtmlLu, A.; Wang, F.; Huang, D.; Wang, K.-H.; Su, Y.; Xu, Y.; Hu, Y. Chin. J. Org. Chem. 2014, 34, 948(in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract343765.shtml

    17. [17]

      Wen, J.; Fu, Y.; Zhang, R.-Y.; Zhang, J.; Chen, S.-Y.; Yu, X.-Q. Tetrahedron 2011, 67, 9618. doi: 10.1016/j.tet.2011.09.074

  • Scheme 1  Methods for synthesis of pyrazolines from homoallylhydrazides

    下载: 全尺寸图片 幻灯片

    Table 1.  Substrate scope of the reactiona
    下载: 导出CSV

    Table 2.  Substrate scope of the reactiona
    下载: 导出CSV

    Table 3.  Substrate scope of the reactiona
    下载: 导出CSV

    Table 4.  Substrate scope of the reactiona
    下载: 导出CSV
  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  14
  • 文章访问数:  1856
  • HTML全文浏览量:  109
文章相关
  • 发布日期:  2019-10-25
  • 收稿日期:  2019-03-29
  • 修回日期:  2019-04-26
  • 网络出版日期:  2019-10-21
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net