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Article

Metal-Free Cascade Formation of C–C and C–N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties

by
Yao Tang
,
Nvjiang Wu
,
Junyu Xu
,
Xiaopo Zhang
*,
Youbin Li
* and
Xuesong Wang
*
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Key Laboratory for Research and Development of Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Academy of Medical Sciences, Hainan Medical University, Haikou 571199, China
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(12), 2792; https://doi.org/10.3390/molecules29122792
Submission received: 2 May 2024 / Revised: 7 June 2024 / Accepted: 9 June 2024 / Published: 12 June 2024
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

:
A straightforward and efficient methodology has been developed for the synthesis of 3-cyano-2-pyridones via the C–C and C–N bond formation processes. A total of 51 diverse 3-cyano-2-pyridone derivatives were obtained in moderate to excellent yields. This reaction featured advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions. A plausible mechanism for the reaction was proposed. 3-cyano-2-pyridones as ricinine analogues for insecticidal properties were evaluated, and the compound 3ci (LC50 = 2.206 mg/mL) showed the best insecticidal property.

1. Introduction

2-pyridone is considered a privileged heteroaromatic skeleton endowed with pharmaceutical properties and biological activities [1,2,3,4,5,6,7,8,9,10]. They are also widely applicable in organic synthesis, materials science, and polymer chemistry, which are used as valuable building blocks for the synthesis of nitrogen-containing heterocycles like pyridines, quinolizidines, β-lactams, piperidines, and indolizidine alkaloids [11,12,13,14,15,16,17,18,19,20,21,22,23,24]. Owing to their multifarious and prominent properties, 2-pyridones often display promising therapeutical areas such as antifungal, anti-HIV, antibacterial, antiepileptic, anti-inflammatory, and antitumoral activities [25,26,27,28,29,30,31,32,33,34,35,36,37]. As shown in Figure 1A, very typical commercial drugs based on the 2-pyridone scaffold include ciclopirox [38], pifenidone [39], gimeracil [40], and ricinine [41,42,43]. Due to their importance and utility in chemical and pharmaceutical applications, extensive effort has been devoted to the development of efficient methods for the synthesis of diversely functionalized 2-pyridones.
Typically, transition metals such as ruthenium, nickel, and rhodium have been exploited in the cycloaddition of 1,6-diynes with isocyanates towards 2-pyridones [44,45,46,47]. Complementarily, several other methods involving FeCl3-catalyzed intramolecular cascade reactions of acetoacetanilide with 3-formyl chromone [48], Ni-catalyzed reactions of alkynes via azazirconacycles [49], gold-catalyzed cycloisomerization of N-alkenyl alkynylamides [50], and indium-catalyzed domino reactions of 3-formylchromones with N-methyl-1-(methylthio)-2-nitroethenamine [51] have also been developed. However, the cytotoxicity of trace transition metals has limited their utilization in the fields of pharmaceutical application. Moreover, a literature survey implied that other existing approaches to 2-pyridones focus on ring-closing metathesis of α-amino acrylamides [52], t-BuOK-mediated condensation of enones with cyanoacetamides [53], CsF-catalyzed reaction of α,β-unsaturated diester chromones with aromatic amines [54], tandem Blaise reaction of nitriles with propiolates [55], heteropolyacid-catalyzed reaction of amines and acetylenic esters [56], intramolecular ketene trapping of enamine-dioxinones [57], nucleophilic addition of malonic esters with alkynyl imines [58], addition reaction of 2-(phenylsulfinyl)acetamide and α,β-unsaturated ketones [59]. Nevertheless, those reported methods for the synthesis of 2-pyridones suffer from considerable disadvantages, like expensive catalysts [44,45,46,47] and contamination of heavy metals [56], which have limited their potential application in the life science and pharmaceutical industries. Consequently, the development of efficient and environmentally benign procedures for the synthesis of 2-pyridones continues to be of great significance.
Ricinine [60] has been reported to exhibit pharmacological activities such as antifertility, antiimplantation, antinociceptive, anticancer, antidiabetic, and insecticidal activities (Figure 1A). On the other hand, ynones have emerged as valuable building blocks for the construction of complex heterocyclic rings, such as indole, pyrrole, pyridine, triazole, quinoline, thiazole, pyrimidine, and so on [61,62,63,64,65,66,67,68,69,70,71,72,73]. Recently, Trofimov and co-workers [74] reported the condensation of acylethynylpyrroles and 2-cyano-N-methylacetamide to form N-methyl-3-cyano-2-pyridones (Figure 1B). However, considerable disadvantages like the relatively poor functional scopes (only 2 examples of N-methyl-3-cyano-2-pyridone as ricinine analogues) and the deficiency of biological activity assays still exist in this process. Inspired by the aforementioned works and previous reports [60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76], our primary aim is to develop an easy and efficacious synthetic strategy for the expeditious assembly of 3-cyano-2-pyridones from the cycloaddition of ynones and 2-cyanoacetamide (Figure 1C). Simultaneously, we strive to identify 3-cyano-2-pyridones that serve as ricinine analogues and display potent insecticidal properties.

2. Results and Discussion

2.1. Optimization of the Reaction Conditions

In an initial effort, we began our investigation with the cascade cycloaddition of 1,3-diphenylprop-2-yn-1-one 1aa and 2-cyano-N-methylacetamide 2aa in 1,4-dioxane in the presence of K2CO3 as a base at 100 °C for 8 h (Table 1). To our delight, the preliminary result showed the desired product 3aa was obtained with an 81% yield (entry 1). The yield was decreased when the transition-metal-free reaction was conducted with Na2CO3 or Cs2CO3 instead of K2CO3 (entries 2–3). Moreover, various kinds of bases were screened, whereas no reaction or trace transformation was observed, neither strong inorganic bases such as NaOH, NaH, EtONa, LiOtBu, NaOtBu, and KOtBu (entries 4–9) nor organic bases including Et3N, DBU, and DABCO (entries 10–12) involving the transformation. Further investigation showed that this reaction was highly solvent-dependent (entries 13–19). When the reaction was carried out in DMSO, DMF, and NMP, an acceptable yield of 3aa was detected (entries 13–15). However, other solvents, such as CH3CN, toluene, THF, and EtOH, afforded only a trace amount of the desired product 3aa (entries 16–19). Finally, decreasing the amount of K2CO3 lowered the yield (entry 20), while no obvious deviation was observed when the loading of K2CO3 was increased (entries 21–22). On the basis of the above results, the optimal conditions for this transformation were obtained as follows: K2CO3 (1.2 equiv.) in 1,4-dioxane at 100 °C for 8 h.

2.2. Scope of the Reaction

With the optimum conditions in hand, the generality and scope of this metral-free cascade reaction of ynones and 2-cyanoacetamides were explored, and the results are shown in Table 2. Firstly, we studied the scope of alkynones with substituents in Ar–R1 (entries 2–20). The reaction shows preference for electron-rich alkynones (Me, OMe) (entries 2–6), which provided the corresponding products in relatively higher yields than their counterparts bearing electron-withdrawing groups (F, Cl, Br, I, CF3) (entries 7–20). Compared to the yield of 3ab and the yield of 3ad (87% vs. 73%), we found that the steric hindrance influenced this reaction. Particularly, a 2-naphthyl-substituted substrate could also be subjected to the reaction, and the corresponding product, 3au, was obtained with a 90% yield. Moreover, both alkyl- and heterocyclyl involving-alkynones were also suitable candidates for this transformation, and the corresponding products, 3av, 3aw, and 3ax were obtained in 83%, 76%, and 84% yields, respectively.
As for regioisomeric substrates, alkynones with substituents in Ar–R2 were also investigated (entries 25–34). Similar to alkynones with functional groups in Ar–R1, the cycloaddition reactions proceeded smoothly to give the corresponding 3-cyano-2-pyridones in satisfactory yields. Notably, both electronic effect (entries 25–29 vs. entries 30–34) and steric hindrance influence (3bg vs. 3bh) existed in this reaction. As outlined in Table 2, electron-donating and para-substituted alkynones were good substrates, leading to the target products in moderate to excellent yields (entries 25–29). Interestingly, alkynones with cyclopropyl, n-hexyl, and 2-thienyl groups were also tolerated in this procedure and provided 3-cyano-2-pyridones in satisfactory yield (entries 35–37).
Additionally, alkynones with substituents in Ar–R1 and Ar–R2 were also evaluated under the standard reaction conditions. The corresponding 3-cyano-2-pyridones were obtained in moderate to excellent yields regardless of the electron-donating or electron-withdrawing groups at benzene rings (entries 38–45). Encouragingly, alkynones bearing two electron-rich functional groups provided excellent yields because of the strong electron-donating effect (entries 38–40). However, with ortho-functional group substrates, the yields of corresponding products decreased, maybe due to the steric hindrance (entries 41–42 and 44–45). Furthermore, alkynones possessing a naphthyl and cyclopropyl ring were carried out in this cascade reaction system and furnished the desired products 3ci, 3cj, and 3ck in 88%, 80%, and 60% yields, respectively (entries 46–48). Finally, 2-cyanoacetamides with functional groups phenyl and benzyl were tested and provided the products in moderate yield (entries 49–50), while 2-cyanoacetamide involved in the transformation obtained the 3-cyano-2-pyridone in excellent yield (entry 51).

2.3. Gram-Scale of the Reaction

To demonstrate the reliability and practicality of this present synthetic protocol, a gram-scale preparation was performed using starting materials 1aa, where the desired product, 3aa, was isolated in an 83% yield (Scheme 1).

2.4. Plausible Mechanism of the Reaction

On the basis of the aforementioned observations and previous reports [74], the mechanistic pathways of this cascade methodology were proposed and presented in Scheme 2. Initially, 2-cyano-N-methylacetamide 2aa undergoes a K2CO3-initiated deprotonation of the CH2 group to give carbanion A, and then the nucleophilic addition of carbanion A to the triple bond of ynone 1aa produces carbanion B. Subsequently, the carbanion B is quenched by a proton of the medium to generate intermediate C. Finally, an intramolecular cycloaddition of the intermediate C results in the formation of the cyclization product 3aa.

2.5. Study of the Insecticidal Properties of 3-Cyano-2-Pyridones

A literature survey implied that ricinine is well known as a compound with a high level of biological activity and has been proven valuable due to its insecticidal properties [77]. Based on the structure of ricinine, we have prepared several 3-cyano-2-pyridones with novel scaffolds as ricinine analogues to evaluate their insecticidal activity (see the experimental details in Supplementary Materials). Fortunately, in the trials of killing mealworm, we observed that the compounds 3au (LC50 = 3.245 mg/mL) and 3bc (LC50 = 3.579 mg/mL) exhibited powerful pesticidal activity using ricinine as a positive control. These results implied that 2-naphthyl and para-n-butyl benzene are good functional groups in the 3-cyano-2-pyridone framework as insecticides. Subsequently, the suitable functional candidate 3ci (LC50 = 2.206 mg/mL) bearing 2-naphthyl and para-n-butyl benzene groups was obtained, and the insecticidal activity was evaluated. Upon comparing the LC50 values in Figure 2, we found that the compound 3ci was the best candidate drug with insecticidal properties.

3. Experimental Section

3.1. General Methods and Materials for the Synthesis of 3-Cyano-2-Pyridones 3

Unless otherwise stated, all reagents were used directly without further purification. Silica gel was purchased from Qing Dao Hai Yang Chemical Industry Co. (Qinqdao, China). All melting points were determined on a Beijing Science Instrument Dianguang Instrument Factory XT4B (Beijing, China) melting point apparatus and uncorrected. 1H and 13C NMR spectra were measured on a 400 MHz JEOL JNM-ECZ400S/L1 spectrometer (Jeol Ltd., Tokyo, Japan), (1H 400 MHz, 13C 100 MHz), using CDCl3 as the solvent with tetramethylsilane (TMS) as the internal standard at room temperature. HRMS-ESI spectra were equipped with an ESI source and a TOF detector. PE is petroleum ether (60–90 °C).
A Typical Procedure for the Synthesis of 1-methyl-2-oxo-4,6-diphenyl-1,2-dihydropyridine-3-carbonitrile (3aa).
A suspension of 1,3-diphenylprop-2-yn-1-one 1aa (0.6 mmol, 123.6 mg), 2-cyano-N-methylacetamide 2aa (0.5 mmol, 49.0 mg), and K2CO3 (0.6 mmol, 82.8 mg) in 1,4-dioxane (2 mL) was stirred at 100 °C for 8 h. After 2aa was exhausted completely (monitored by TLC), it was cooled down to room temperature and saturated aqueous brine (20 mL) was added. The mixture was stirred for 10 min and then extracted by EtOAc (3 × 10 mL). The combined organic layers were dried over Na2SO4. Removal of the solvent gave a residue, which was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v) to afford 3aa as a yellow solid, 116 mg, 81% yield; mp 148–151 °C. 1H NMR (400 MHz, chloroform-d) δ 7.63 (d, J = 3.96 Hz, 2H), 7.53–7.47 (m, 6H), 7.40 (d, J = 3.88 Hz, 2H), 6.32 (s, 1H), 3.47 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ 161.7, 158.2, 154.0, 135.5, 134.1, 130.5, 130.3, 129.1 (2C), 128.9 (2C), 128.01 (2C), 127.97 (2C), 116.0, 109.1, 100.1, 35.0.
For 3aa (gram-scale), a mixture of 1,3-diphenylprop-2-yn-1-one 1aa (12.0 mmol, 2.47 g), 2-cyano-N-methylacetamide 2aa (10 mmol, 0.98 g), and K2CO3 (12.0 mmol, 1.66 g) in 1,4-dioxane (15 mL) was stirred at 100 °C for 8 h. After completion of the reaction (monitored by TLC), it was cooled down to room temperature, and the resulting solution was poured into water (100 mL), then extracted with EtOAc (3 × 50 mL). The combined EtOAc extracts were dried over Na2SO4 and concentrated. Then, the solvent was evaporated, and the residue was purified by chromatography (silica gel, PE/EtOAc = 3/1 v/v) to give 3aa in 83% yield (2.37 g).
A similar procedure was used for the preparation of products 3ab–3ck.
1-methyl-2-oxo-4-phenyl-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (3ab).
The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 130 mg, 87% yield; yellow soild; mp 131–134 °C. 1H NMR (400 MHz, CDCl3) δ 7.55 (s, 2H), 7.38 (s, 3H), 7.26 (d, J = 12.9 Hz, 4H), 6.23 (s, 1H), 3.41 (s, 3H), 2.35 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.9, 158.2, 154.6, 140.8, 135.8, 131.4, 130.6, 129.8 (2C), 129.0 (2C), 128.2 (2C), 128.1 (2C), 116.3, 109.3, 99.7, 35.2, 21.5. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O+ 301.1335; found, 301.1342.
1-methyl-2-oxo-4-phenyl-6-(m-tolyl)-1,2-dihydropyridine-3-carbonitrile (3ac). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 122 mg, 81% yield; yellow soild; mp 157–160 °C. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 2H), 7.47 (s, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.17 (s, 2H), 6.29 (s, 1H), 3.45 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 158.2, 154.3, 139.1, 135.6, 134.1, 131.0, 130.6, 128.9, 128.9 (2C), 128.5, 128.0 (2C), 125.0, 116.0, 109.1, 100.1, 35.1, 21.4. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O+ 301.1335; found, 301.1342.
1-methyl-2-oxo-4-phenyl-6-(o-tolyl)-1,2-dihydropyridine-3-carbonitrile (3ad). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 109 mg, 73% yield; yellow soild; mp 170–173 °C. 1H NMR (400 MHz, CDCl3) δ 7.63 (s, 2H), 7.47 (s, 3H), 7.41 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 7.5 Hz, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.26 (s, 1H), 3.30 (s, 3H), 2.19 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.6, 158.3, 153.7, 135.5, 135.4, 133.8, 130.8, 130.6, 130.3, 128.9 (2C), 128.1 (2C), 128.0, 126.6, 115.9, 108.6, 100.2, 33.7, 19.3. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O+ 301.1335; found, 301.1345.
6-(4-methoxyphenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ae). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 136 mg, 86% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 2H), 7.47 (s, 3H), 7.31 (s, 2H), 7.01 (s, 2H), 6.27 (s, 1H), 3.86 (s, 3H), 3.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.9, 161.1, 158.1, 154.1, 135.7, 130.5, 129.6 (2C), 128.9 (2C), 128.0 (2C), 126.4, 116.1, 114.4 (2C), 109.2, 99.8, 55.5, 35.1. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O2+ 317.1285; found, 317.1297.
6-(2-methoxyphenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3af). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 119 mg, 75% yield; yellow soild; mp 173–176 °C. 1H NMR (400 MHz, CDCl3) δ 7.64 (s, 2H), 7.46 (s, 4H), 7.25 (s, 1H), 7.05 (d, J = 2.7 Hz, 2H), 6.27 (s, 1H), 3.83 (s, 3H), 3.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 158.3, 156.4, 152.3, 135.9, 132.3, 130.6, 129.8, 129.0 (2C), 128.3 (2C), 123.3, 121.3, 116.4, 111.2, 109.4, 100.2, 55.7, 34.0. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O2+ 317.1285; found, 317.1289.
6-(4-fluorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ag). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 114 mg, 75% yield; brown soild; mp 147–150 °C. 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 2H), 7.46 (s, 3H), 7.40 (s, 2H), 7.20 (d, J = 7.7 Hz, 2H), 6.28 (s, 1H), 3.43 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 164.9 (d, J = 250.9 Hz), 161.6, 158.2, 152.9, 135.4, 130.6, 130.3 (d, J = 46.0 Hz, 2C), 128.9 (2C), 128.0 (2C), 116.5 (d, J = 22.0 Hz, 2C), 115.9, 109.3, 100.4, 35.0. 19F NMR (376 MHz, CDCl3) δ −109.13 (s, 1F). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13FN2NaO+ 327.0904; found, 327.0906.
6-(3-fluorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ah). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 111 mg, 73% yield; brown soild; mp 128–131 °C. 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 2H), 7.47 (s, 4H), 7.21 (d, J = 9.3 Hz, 2H), 7.14 (d, J = 8.8 Hz, 1H), 6.30 (s, 1H), 3.45 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 164.1 (d, J = 248.7 Hz), 161.8, 158.5, 152.7, 136.2 (d, J = 7.4 Hz), 135.6, 131.4 (d, J = 8.2 Hz), 131.0, 129.2 (2C), 128.3 (2C), 124.3, 117.8 (d, J = 20.8 Hz), 116.1, 115.8 (d, J = 22.9 Hz), 109.4, 101.0, 35.3. 19F NMR (376 MHz, CDCl3) δ −110.32 (s, 1F). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13FN2NaO+ 327.0904; found, 327.0912.
6-(2-fluorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ai). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 97 mg, 64% yield; brown soild; mp 161–164 °C. 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.53 (s, 1H), 7.47 (s, 3H), 7.34 (d, J = 5.7 Hz, 2H), 7.24 (s, 1H), 6.33 (s, 1H), 3.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 160.2 (d, J = 248.9 Hz), 158.2, 148.6, 135.4, 132.8 (d, J = 8.1 Hz), 130.7, 130.1, 128.9 (2C), 128.1 (2C), 125.2, 122.1 (d, J = 15.5 Hz), 116.4 (d, J = 20.9 Hz), 115.8, 109.7, 101.1, 34.2. 19F NMR (376 MHz, CDCl3) δ −112.26 (s, 1F). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13FN2NaO+ 327.0904; found, 327.0907.
6-(4-chlorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3aj). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 122 mg, 76% yield; brown soild; mp 171–174 °C. 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 7.9 Hz, 2H), 7.49 (s, 1H), 7.47 (s, 1H), 7.44 (s, 2H), 7.42 (d, J = 1.7 Hz, 1H), 7.37 (s, 1H), 7.36 (s, 1H), 6.27 (s, 1H), 3.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.7, 158.3, 153.0, 136.8, 135.5, 132.6, 130.8, 129.7 (2C), 129.6(2C), 129.1 (2C), 128.2 (2C), 116.1, 109.4, 100.5, 35.1. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13ClN2NaO+ 343.0609; found, 343.0616.
6-(3-chlorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ak). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 119 mg, 74% yield; brown soild; mp 162–165 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 2H), 7.48 (s, 4H), 7.39 (s, 1H), 7.30 (s, 1H), 7.24 (s, 1H), 6.29 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 158.3, 152.2, 135.7, 135.3, 135.2, 130.7, 130.5, 130.5, 129.0 (2C), 128.1, 128.0 (2C), 126.2, 115.8, 109.2, 100.8, 35.0. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13ClN2NaO+ 343.0609; found, 327.0610.
6-(2-chlorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3al). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 108 mg, 67% yield; brown soild; mp 151–154 °C. 1H NMR (400 MHz, CDCl3) δ 7.64 (s, 2H), 7.54 (d, J = 7.9 Hz, 1H), 7.48 (s, 4H), 7.43 (d, J = 7.4 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 6.28 (s, 1H), 3.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.5, 158.5, 151.1, 135.5, 133.3, 132.9, 131.9, 130.8, 130.30, 130.0, 129.1 (2C), 128.3 (2C), 127.8, 116.0, 109.1, 101.2, 33.8. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H14ClN2O+ 321.0789; found, 321.0786.
6-(4-bromophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3am). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 137 mg, 76% yield; brown soild; mp 176–179 °C. 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.6 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 7.7 Hz, 3H), 7.30 (d, J = 8.6 Hz, 2H), 6.27 (s, 1H), 3.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.7, 158.3, 153.0, 135.5, 133.1, 132.5 (2C), 130.8, 129.9 (2C), 129.1 (2C), 128.2 (2C), 125.0, 116.1, 109.3, 100.5, 35.1. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H14BrN2O+ 365.0284; found, 365.0287.
6-(2-bromophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3an). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 113 mg, 62% yield; yellow soild; mp 187–190 °C. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 6.5 Hz, 1H), 7.61 (s, 2H), 7.45 (s, 4H), 7.37 (d, J = 7.9 Hz, 2H), 6.25 (s, 1H), 3.33 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 158.5, 152.4, 135.5, 135.3, 133.4, 132.0, 130.8, 130.0, 129.0 (2C), 128.4, 128.3 (2C), 122.3, 116.0, 109.1, 101.0, 33.9. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H14BrN2O+ 365.0284; found, 365.0267.
1-methyl-2-oxo-4-phenyl-6-(4-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carbonitrile (3ao). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 115 mg, 65% yield; yellow soild; mp 166–169 °C. 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 2H), 7.58 (s, 4H), 7.47 (s, 3H), 6.30 (s, 1H), 3.43 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 158.3, 152.2, 137.5, 135.2, 132.6 (d, J = 32.7 Hz), 130.8, 129.0 (2C), 128.7 (2C), 128.0 (2C), 126.2, 126.2, 124.8, 115.7, 109.2, 101.0, 35.0. 19F NMR (376 MHz, CDCl3) δ −62.80 (s, 3F). HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H14F3N2O+ 355.1053; found, 355.1069.
6-(4-fluoro-2-methylphenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ap). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 112 mg, 70% yield; yellow soild; mp 187–190 °C. 1H NMR (400 MHz, CDCl3) δ 7.60 (s, 2H), 7.44 (s, 3H), 7.22 (s, 1H), 7.02 (s, 2H), 6.22 (s, 1H), 3.28 (s, 3H), 2.20 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 164.9 (d, J = 249.5 Hz), 161.8, 158.5, 153.0, 138.8 (d, J = 8.4 Hz), 135.6, 130.9, 130.4 (d, J = 22.7 Hz), 129.1 (2C), 128.3 (2C), 118.0 (d, J = 22.0 Hz), 116.1, 114.1 (d, J = 22.0 Hz), 109.2, 109.2, 100.7, 34.0, 19.8. 19F NMR (376 MHz, CDCl3) δ −110.18 (s, 1F). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C20H15FN2NaO+ 341.1061; found, 341.1061.
6-(2,4-dichlorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrilee (3aq). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 98 mg, 55% yield; yellow liquid; 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.9 Hz, 2H), 7.54 (s, 1H), 7.45 (s, 2H), 7.43 (s, 1H), 7.41 (s, 1H), 7.36 (d, J = 8.3 Hz, 1H), 6.25 (s, 1H), 3.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.3, 158.4, 150.0, 137.5, 135.3, 133.8, 131.7, 131.1, 130.9, 130.2, 129.1 (2C), 128.3, 128.2 (2C), 115.9, 109.3, 101.4, 33.8. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H13Cl2N2O+ 355.0399; found, 355.0397.
6-(2,3-dichlorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3ar). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 103 mg, 58% yield; brown soild; mp 204–207 °C. 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 3H), 7.44 (s, 3H), 7.35 (s, 1H), 7.27 (s, 1H), 6.23 (s, 1H), 3.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.2, 158.5, 150.3, 135.3, 135.2, 134.4, 132.5, 131.46, 130.9, 129.1 (2C), 128.5, 128.2 (3C), 115.8, 108.9, 101.5, 33.8. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H12Cl2N2NaO+ 377.0219; found, 377.0222.
6-(2-chloro-4-fluorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3as). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 95 mg, 56% yield; brown soild; mp 151–154 °C. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 2H), 7.46 (s, 3H), 7.38 (s, 1H), 7.29 (d, J = 5.4 Hz, 1H), 7.15 (s, 1H), 6.26 (s, 1H), 3.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 164.7 (d, J = 274.1 Hz), 161.2, 158.3, 149.9, 135.2, 134.2 (d, J = 10.2 Hz), 131.4 (d, J = 9.1 Hz), 130.8, 129.5, 129.4, 128.9 (2C), 128.1 (2C), 118.0 (d, J = 25.0 Hz), 115.7, 115.3 (d, J = 21.5 Hz), 109.3, 101.3, 33.7. 19F NMR (376 MHz, CDCl3) δ −106.66 (s, 1F). HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H13ClFN2O+ 339.0695; found, 339.0694.
6-(2,4-difluorophenyl)-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3at). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 92 mg, 57% yield; yellow soild; mp 136–139 °C. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.59 (s, 1H), 7.45 (d, J = 7.3 Hz, 3H), 7.41 (s, 1H), 7.08–7.03 (m, 1H), 7.01–6.96 (m, 1H), 6.30 (s, 1H), 3.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.0 (d, J = 11.5 Hz), 163.4 (d, J = 11.6 Hz), 161.5, 161.0 (d, J = 12.2 Hz), 158.4, 147.8, 135.5, 131.7 (d, J = 9.6 Hz), 131.0, 129.2 (2C), 128.3 (2C), 118.7 (d, J = 15.8 Hz), 116.0, 113.1 (d, J = 21.6 Hz), 110.2, 105.5 (d, J = 50.4 Hz), 105.2, 101.5, 34.4. 19F NMR (376 MHz, CDCl3) δ −104.13 (s, 1F), −107.54 (s, 1F). HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H13F2N2O+ 323.0990; found, 323.0997.
1-methyl-6-(naphthalen-2-yl)-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3au). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 152 mg, 90% yield; yellow soild; mp 191–194 °C. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.5 Hz, 1H), 7.90 (s, 3H), 7.66–7.63 (m, 2H), 7.62–7.58 (m, 2H), 7.48 (s, 3H), 7.46–7.43 (m, 1H), 6.41 (s, 1H), 3.50 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.7, 158.2, 154.1, 135.6, 133.5, 132.7, 131.4, 130.6, 128.9, 128.9 (2C), 128.3, 128.0 (3C), 127.9, 127.9, 127.4, 124.6, 116.0, 109.4, 100.2, 35.2. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C23H17N2O+ 337.1335; found, 337.1347.
6-cyclopropyl-1-methyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3av). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 104 mg, 83% yield; yellow soild; mp 154–157 °C. 1H NMR (400 MHz, CDCl3) δ 7.52 (s, 2H), 7.45 (s, 3H), 6.09 (s, 1H), 3.74 (s, 3H), 1.89 (s, 1H), 1.16 (s, 2H), 0.87 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 161.7, 158.4, 155.7, 135.9, 130.3, 128.8 (2C), 127.9 (2C), 116.1, 105.7, 99.0, 31.6, 15.0, 7.6 (2C). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C16H14N2NaO+ 273.0998; found, 273.1005.
1,6-dimethyl-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile (3aw). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 170 mg, 76% yield; yellow soild; mp 164–167 °C. 1H NMR (400 MHz, CDCl3) δ 7.56 (s, 2H), 7.47 (s, 3H), 6.23 (s, 1H), 3.58 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.7, 158.1, 151.6, 135.6, 130.4, 128.8 (2C), 127.9 (2C), 116.1, 108.1, 98.7, 31.8, 21.6.
1-methyl-2-oxo-4-phenyl-6-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (3ax). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 123 mg, 84% yield; yellow soild; mp 144–147 °C. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 2H), 7.55 (d, J = 3.9 Hz, 1H), 7.48 (d, J = 2.7 Hz, 3H), 7.29 (d, J = 3.7 Hz, 1H), 7.16 (d, J = 1.4 Hz, 1H), 6.46 (s, 1H), 3.62 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.6, 157.8, 147.0, 135.4, 134.1, 130.6, 130.0, 129.2, 128.9, 128.0 (2C), 127.9 (2C), 115.9, 110.4, 100.6, 35.0. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C17H12N2NaOS+ 315.0563; found, 315.0567.
1-methyl-2-oxo-6-phenyl-4-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (3ba). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 132 mg, 88% yield; white soild; mp 129–132 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 5H), 7.37 (s, 2H), 7.26 (s, 2H), 6.28 (s, 1H), 3.42 (s, 3H), 2.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 158.1, 153.8, 141.0, 134.2, 132.6, 130.3, 129.6 (2C), 129.1 (2C), 128.0 (4C), 116.2, 109.1, 99.8, 35.9, 21.4.
1-methyl-2-oxo-6-phenyl-4-(m-tolyl)-1,2-dihydropyridine-3-carbonitrile (3bb). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 126 mg, 84% yield; yellow soild; mp 159–162 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 3H), 7.39 (s, 4H), 7.32 (s, 1H), 7.27 (s, 1H), 6.28 (s, 1H), 3.44 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.9, 158.5, 154.1, 138.8, 135.7, 134.3, 131.4, 130.4, 129.2 (2C), 128.9, 128.7, 128.2 (2C), 125.3, 116.2, 109.3, 100.2, 35.1, 21.5. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O+ 301.1335; found, 301.134.
4-(4-butylphenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bc). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 146 mg, 85% yield; white liquid. 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 8.2 Hz, 2H), 7.51 (s, 3H), 7.38 (s, 2H), 7.27 (d, J = 8.3 Hz, 2H), 6.29 (s, 1H), 3.44 (s, 3H), 2.63 (s, 2H), 1.59 (s, 2H), 1.35 (s, 2H), 0.90 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 158.2, 153.8, 146.0, 134.3, 132.8, 130.3, 129.1 (2C), 129.0 (2C), 128.0 (2C), 128.0 (2C), 116.2, 109.1, 99.8, 35.5, 35.0, 33.3, 22.3, 13.9. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C23H23N2O+ 343.1805; found, 343.1818.
4-(4-methoxyphenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bd). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 151 mg, 95% yield; yellow soild; mp 139–142 °C. 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.9 Hz, 2H), 7.47 (s, 3H), 7.38 (s, 2H), 6.90 (d, J = 8.9 Hz, 2H), 6.26 (s, 1H), 3.77 (s, 3H), 3.38 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.0, 161.6, 157.6, 154.0, 134.4, 130.4, 130.0 (2C), 129.2 (2C), 128.2 (2C), 127.7, 116.7, 114.4 (2C), 109.2, 99.1, 55.5, 35.0. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O2+ 317.1285; found, 317.1293.
4-(3-methoxyphenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3be). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 146 mg, 92% yield; yellow soild; mp 149–152 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 3H), 7.39 (s, 2H), 7.33 (d, J = 5.8 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.11 (s, 1H), 6.99 (s, 1H), 6.30 (s, 1H), 3.79 (s, 3H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 159.8, 158.2, 154.3, 136.9, 135.0, 130.5, 130.1, 129.2 (2C), 128.2 (2C), 120.5, 116.6, 116.1, 113.4, 109.3, 100.2, 55.6, 35.2. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C20H17N2O2+ 317.1285; found, 317.1292.
4-(4-fluorophenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bf). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 113 mg, 74% yield; brown soild; mp 172–175 °C. 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.52 (s, 3H), 7.38 (s, 2H), 7.14 (d, J = 7.6 Hz, 2H), 6.26 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 165.3, 162.8, 161.6, 157.1, 154.3, 134.1, 131.6, 130.4 (2C), 130.3 (d, J = 8.7 Hz, 2C), 129.1 (2C), 128.0 (2C), 116.2 (d, J = 21.8 Hz), 108.9, 100.1, 35.1. 19F NMR (376 MHz, CDCl3) δ −109.15 (s, 1F).
4-(4-chlorophenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bg). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 121 mg, 75% yield; brown soild; mp 165–168 °C. 1H NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.53 (s, 1H), 7.51 (d, J = 2.3 Hz, 3H), 7.42 (s, 1H), 7.40 (s, 3H), 6.26 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.6, 157.0, 154.6, 137.0, 134.2, 134.1, 130.6, 129.6 (2C), 129.3 (2C), 129.3 (2C), 128.1 (2C), 116.0, 108.9, 100.1, 35.2. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H13ClN2NaO+ 343.0609; found, 343.0615.
4-(2-chlorophenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bh). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 97 mg, 60% yield; brown soild; mp 172–175 °C. 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 2.4 Hz, 2H), 7.48 (s, 3H), 7.38 (s, 2H), 7.37 (s, 2H), 6.22 (s, 1H), 3.47 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 156.7, 154.1, 134.9, 134.1, 131.8, 131.2, 130.6, 130.4, 130.0, 129.2 (2C), 128.2 (2C), 127.3, 115.2, 110.1, 102.8, 35.3.
4-(4-bromophenyl)-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bi). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 143 mg, 78% yield; white liquid. 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 2H), 7.51 (s, 5H), 7.38 (s, 2H), 6.25 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.5, 156.9, 154.5, 134.4, 134.0, 132.2 (2C), 130.4, 129.6 (2C), 129.1 (2C), 127.9 (2C), 125.2, 115.8, 108.7, 100.0, 35.1. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H14BrN2O+ 365.0284; found, 365.0292.
Methyl 4-(3-cyano-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridin-4-yl)benzoate (3bj). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 121 mg, 70% yield; orange soild; mp 121–124 °C. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.6 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H), 7.52 (s, 3H), 7.39 (s, 2H), 6.29 (s, 1H), 3.92 (s, 3H), 3.46 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 166.2, 161.4, 157.1, 154.5, 139.8, 134.0, 131.8, 130.5, 130.1 (2C), 129.2 (2C), 128.2 (2C), 128.0 (2C), 115.6, 108.7, 100.5, 52.4, 35.2. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C21H17N2O3+ 345.1234; found, 345.1240.
4-cyclopropyl-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bk). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 109 mg, 87% yield; white soild; mp 167–170 °C. 1H NMR (400 MHz, CDCl3) δ 7.45 (s, 3H), 7.28 (s, 2H), 5.49 (s, 1H), 3.28 (s, 3H), 2.21 (s, 1H), 1.20 (s, 2H), 0.88 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 164.2, 161.0, 154.2, 134.5, 130.3, 129.1 (2C), 128.1 (2C), 115.9, 102.8, 101.4, 34.7, 15.0, 11.4 (2C). HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C16H14N2NaO+ 273.0998; found, 273.1001.
4-hexyl-1-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (3bl). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 121 mg, 82% yield; yellow soild; mp 115–118 °C. 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 2.3 Hz, 3H), 7.32 (d, J = 3.1 Hz, 2H), 6.08 (s, 1H), 3.35 (s, 3H), 2.70–2.65 (m, 2H), 1.65–1.57 (m, 2H), 1.36 (s, 2H), 1.27 (d, J = 3.3 Hz, 2H), 1.26 (s, 2H), 0.86–0.81 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 162.5, 161.5, 153.9, 134.3, 130.3, 129.2 (2C), 128.1 (2C), 115.4, 109.2, 102.1, 35.0, 34.9, 31.5, 29.4, 29.0, 22.5, 14.1. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C19H22N2NaO+ 317.1624; found, 317.1627.
1-methyl-2-oxo-6-phenyl-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (3bm). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 117 mg, 80% yield; orange soild; mp 151–154 °C. 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 3.0 Hz, 1H), 7.52 (d, J = 2.1 Hz, 2H), 7.51 (d, J = 1.3 Hz, 1H), 7.49 (s, 1H), 7.42 (d, J = 5.1 Hz, 1H), 7.39 (d, J = 2.2 Hz, 1H), 7.38 (s, 1H), 6.36 (s, 1H), 3.42 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.9, 154.0, 151.3, 135.9, 134.2, 130.3, 129.1 (2C), 128.24, 128.0 (2C), 127.0, 126.9, 116.6, 108.3, 98.6, 38.3. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C17H12N2NaOS+ 315.0563; found, 315.0571.
4-(4-methoxyphenyl)-1-methyl-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (3ca). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 159 mg, 96% yield; orange soild; mp 155–158 °C. 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 2H), 7.28 (s, 4H), 6.93 (s, 2H), 6.26 (s, 1H), 3.80 (s, 3H), 3.41 (s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.1, 161.6, 157.7, 154.1, 140.7, 131.6, 129.9 (2C), 129.8 (2C), 128.1 (2C), 127.9, 116.7, 114.4 (2C), 109.1, 99.1, 55.5, 35.1, 21.5. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C21H19N2O2+ 331.1441; found, 331.1447.
4-(4-butylphenyl)-1-methyl-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (3cb). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 161 mg, 90% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H), 7.53 (s, 1H), 7.29 (s, 2H), 7.27 (s, 2H), 7.25 (s, 2H), 6.28 (s, 1H), 3.45 (s, 3H), 2.63 (t, J = 7.8 Hz, 2H), 2.42 (s, 3H), 1.64–1.55 (m, 2H), 1.38–1.31 (m, 2H), 0.91 (d, J = 14.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 162.1, 158.2, 154.2, 146.1, 140.8, 133.0, 131.6, 129.8 (2C), 129.1 (2C), 128.2 (2C), 128.1 (2C), 116.4, 109.3, 99.7, 35.6, 35.1, 33.4, 22.4, 21.5, 14.0. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C24H25N2O+ 357.1961; found, 357.1973.
4,6-bis(4-methoxyphenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3cc). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 170 mg, 98% yield; white soild; mp 162–165 °C. 1H NMR (400 MHz, CDCl3) δ 7.50 (s, 2H), 7.24 (s, 2H), 6.91 (s, 2H), 6.85 (s, 2H), 6.19 (s, 1H), 3.77 (s, 3H), 3.74 (s, 3H), 3.36 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.2, 161.5, 161.1, 157.5, 153.9, 129.8 (2C), 129.7 (2C), 127.8, 126.6, 116.7, 114.5 (2C), 114.3 (2C), 109.2, 98.7, 55.6, 55.5, 35.1.
4-(2-chlorophenyl)-6-(2-fluorophenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3cd). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 107 mg, 64% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 7.47 (d, J = 7.4 Hz, 1H), 7.37 (d, J = 5.8 Hz, 4H), 7.30 (d, J = 7.4 Hz, 1H), 7.22 (d, J = 8.5 Hz, 1H), 6.25 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.1, 160.4 (d, J = 249.1 Hz), 156.8, 148.8, 134.8, 133.2 (d, J = 8.2 Hz), 131.9, 131.4, 130.5, 130.4, 130.2, 127.5, 125.4, 122.1 (d, J = 15.4 Hz), 116.7 (d, J = 20.6 Hz), 115.1, 110.8, 103.9, 34.6. 19F NMR (376 MHz, CDCl3) δ −112.17 (s, 1F). HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H13ClFN2O+ 339.0695; found, 339.0708.
6-(2-bromophenyl)-4-(4-methoxyphenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3ce). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 135 mg, 68% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 6.6 Hz, 2H), 7.47 (s, 1H), 7.38 (s, 1H), 7.33 (s, 1H), 6.97 (d, J = 8.6 Hz, 2H), 6.25 (s, 1H), 3.83 (s, 3H), 3.33 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.7, 161.5, 157.8, 151.8, 135.4, 133.3, 131.7, 129.9 (2C), 129.8, 128.1, 127.5, 122.4, 116.3, 114.3 (2C), 108.7, 100.1, 55.4, 33.62. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C20H15BrN2NaO2+ 417.0209; found, 417.0212.
6-(4-cyanophenyl)-4-(4-methoxyphenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3cf). The compound was purified by column chromatography (silica gel, PE/EtOAc = 1/1 v/v): 92 mg, 70% yield; brown soild; mp 226–229 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.99 (s, 1H), 7.80 (s, 1H), 7.78 (s, 1H), 7.68 (s, 1H), 7.66 (s, 1H), 7.07 (s, 1H), 7.05 (s, 1H), 6.46 (s, 1H), 3.79 (s, 3H), 3.25 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 161.8, 161.5, 157.7, 152.9, 138.9, 133.2 (2C), 130.6 (2C), 130.2 (2C), 127.7, 118.8, 117.3, 114.9 (2C), 113.3, 109.2, 98.7, 56.0, 35.2.
4-(2-chlorophenyl)-6-(2,4-difluorophenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3cg). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 95 mg, 53% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.46 (s, 1H), 7.37 (s, 4H), 7.01 (s, 1H), 6.98 (s, 1H), 6.23 (s, 1H), 3.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 165.6 (t, J = 253.0 Hz, J = 488.0 Hz), 160.7, 156.5, 147.3, 134.4, 131.6, 131.2 (2C), 130.3, 129.9, 127.2, 118.2 (d, J = 15.5 Hz), 114.7, 112.8 (d, J = 21.5 Hz), 110.7, 105.2 (d, J = 49.9 Hz), 105.0, 104.0, 34.2. 19F NMR (376 MHz, CDCl3) δ −104.04 (s, 1F), −107.46 (s, 1F). HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H12ClF2N2O+ 357.0601; found, 357.0614.
4-(2-chlorophenyl)-6-(2,3-dichlorophenyl)-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3ch). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 115 mg, 59% yield; yellow soild; mp 178–181 °C. 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.44 (s, 1H), 7.37 (s, 2H), 7.35 (s, 2H), 7.29 (s, 1H), 6.19 (s, 1H), 3.34 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 160.8, 157.0, 150.2, 134.9, 134.5, 134.4, 132.6, 131.8, 131.4 (2C), 130.4, 130.0, 128.6, 128.2, 127.4, 114.9, 110.0, 104.1, 33.9. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C19H12Cl3N2O+ 389.0010; found, 389.0018.
4-(4-butylphenyl)-1-methyl-6-(naphthalen-2-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (3ci). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 145 mg, 88% yield; yellow soild; mp 144–147 °C. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.6 Hz, 1H), 7.91 (s, 3H), 7.59 (d, J = 1.5 Hz, 1H), 7.59 (s, 2H), 7.57–7.56 (m, 1H), 7.45 (d, J = 10.1 Hz, 1H), 7.26 (d, J = 8.3 Hz, 2H), 6.41 (s, 1H), 3.48 (s, 3H), 2.63 (t, J = 7.7 Hz, 2H), 1.59 (t, J = 8.4 Hz, 2H), 1.38–1.31 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 162.0, 158.3, 154.1, 146.1, 133.7, 133.0, 132.9, 131.7, 129.1, 129.1 (2C), 128.5, 128.2 (3C), 128.1, 128.0, 127.5, 124.8, 116.5, 109.6, 99.9, 35.6, 35.2, 33.4, 22.4, 14.0. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C27H25N2O+ 393.1961; found, 393.1964.
4-(2-chlorophenyl)-1-methyl-6-(naphthalen-2-yl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (3cj). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 149 mg, 80% yield; orange liquid. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.6 Hz, 1H), 7.90 (s, 3H), 7.59 (d, J = 3.1 Hz, 2H), 7.48 (s, 1H), 7.45 (s, 1H), 7.41 (s, 1H), 7.38 (d, J = 3.0 Hz, 2H), 6.35 (s, 1H), 3.53 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.4, 156.8, 154.2, 134.9, 133.7, 132.9, 131.8, 131.4, 131.3, 130.4, 130.1, 129.1, 128.5, 128.3, 128.1 (2C), 127.6, 127.4, 124.8, 115.2, 110.4, 103.0, 35.5. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C23H16ClN2O+ 371.0946; found, 371.0950.
6-(2-bromophenyl)-4-cyclopropyl-1-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (3ck). The compound was purified by column chromatography (silica gel, PE/EtOAc = 2/1 v/v): 99 mg, 60% yield; yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.44 (s, 1H), 7.36 (s, 1H), 7.24 (s, 1H), 5.46 (s, 1H), 3.23 (s, 3H), 2.28 (s, 1H), 1.26 (s, 2H), 0.89 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 164.4, 160.5, 152.1, 135.4, 133.3, 131.6, 129.7, 128.1, 122.3, 115.6, 102.4, 33.3, 15.0, 11.4, 11.3. HRMS (ESI-TOF) m/z: (M+H)+ Calcd for C16H14BrN2O+ 329.0284; found, 329.0283.
2-oxo-1,4-diphenyl-6-(m-tolyl)-1,2-dihydropyridine-3-carbonitrile (3da). The compound was purified by column chromatography (silica gel, PE/EtOAc = 6/1 v/v): 100 mg, 53% yield; white soild; mp204–207 °C. 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 2H), 7.50 (s, 3H), 7.26 (s, 3H), 7.10 (s, 2H), 7.03 (s, 2H), 6.94 (s, 1H), 6.88 (s, 1H), 6.43 (s, 1H), 2.19 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.3, 159.2, 153.7, 138.1, 137.3, 135.7, 134.1, 130.7, 130.2, 129.3, 129.0(2C), 128.9(2C), 128.6(3C), 128.1(2C), 128.0, 125.8, 115.7, 109.3, 101.1, 21.1. HRMS (ESI-TOF) m/z: (M+Na)+ Calcd for C25H18N2NaO+ 385.1311; found, 385.1320.
1-benzyl-2-oxo-4-phenyl-6-(m-tolyl)-1,2-dihydropyridine-3-carbonitrile (3db). The compound was purified by column chromatography (silica gel, PE/EtOAc = 10/1 v/v): 125 mg, 69% yield; white liquid. 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 2H), 7.46 (s, 3H), 7.26 (s, 2H), 7.21 (s, 3H), 6.98 (s, 1H), 6.93 (s, 2H), 6.89 (s, 1H), 6.27 (s, 1H), 5.20 (s, 2H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 161.8, 158.6, 154.6, 138.7, 136.3, 135.6, 134.0, 131.0, 130.8, 129.1, 129.1 (2C), 128.7, 128.6 (2C), 128.2 (2C), 127.7, 127.5 (2C), 125.3, 116.2, 109.6, 100.9, 49.7, 21.4.
2-oxo-4-phenyl-6-(m-tolyl)-1,2-dihydropyridine-3-carbonitrile (3dc). The compound was purified by column chromatography (silica gel, PE/EtOAc = 3/1 v/v): 129mg, 90% yield; white solid; mp 169–172 °C. 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.70 (s, 3H), 7.54 (s, 3H), 7.45 (s, 1H), 7.39 (s, 1H), 6.76 (s, 1H), 2.54 (s, 3H), 1.26 (s, 1H). 13C NMR (100 MHz, CDCl3) δ 164.1, 161.0, 151.0, 139.9, 136.1, 132.7, 131.5, 130.6, 129.3, 129.0 (2C), 128.1 (2C), 127.9, 124.3, 115.7, 106.5, 99.7, 21.4.

3.2. Insecticidal Properties Study Methods

The experimental details are presented in the Supplementary Materials.

4. Conclusions

In summary, we have developed an efficient and straightforward methodology to construct functional 3-cyano-2-pyridones. The C–C and C–N bond formation were the key procedures of this transformation. Our study presents the utilization of these pyridones for insecticidal properties, and compound 3ci was selected as the best insecticide. With advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions, further chemical modification and biological exploration of these types of compounds are underway in our laboratory.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules29122792/s1, Copies of NMR spectra for compounds 3aa–3dc (page 2). Insecticidal properties study methods (page 58).

Author Contributions

Conceptualization, Y.L. and X.W.; synthetic work and data curation, Y.T. and N.W.; biological experiments and interpretation of results, Y.T., J.X. and X.Z.; chemical characterization, Y.T. and X.W.; project administration and supervision, X.W.; validation, X.W.; writing—original draft, Y.T. and X.W.; writing—review and editing, N.W. and X.W.; funding acquisition, X.Z. All authors have read and agreed to the published version of the manuscript.

Funding

This work was funded by the Key Research and Development Program of Hainan Province (No. ZDYF2022SHFZ037), Hainan Provincial Association for Science and Technology Youth Science and Technology Talent Innovation Program (no. QCQTXM202214), the National Natural Science Foundation of China (no. 82360838), Fundamental Research Funds of Hainan Medical University (No. XRC180009).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available upon request from the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 29 02792 g001
Figure 1. (A) Selected 2-pyridone-containing drugs. (B) Previous report of the synthesis of 2-pyridones. (C) Our synthesis route to 3-cyano-2-pyridones.
Figure 1. (A) Selected 2-pyridone-containing drugs. (B) Previous report of the synthesis of 2-pyridones. (C) Our synthesis route to 3-cyano-2-pyridones.
Molecules 29 02792 g001
Molecules 29 02792 sch001
Scheme 1. Gram-scale of 3aa.
Scheme 1. Gram-scale of 3aa.
Molecules 29 02792 sch001
Molecules 29 02792 sch002
Scheme 2. Plausible mechanism.
Scheme 2. Plausible mechanism.
Molecules 29 02792 sch002
Molecules 29 02792 g002
Figure 2. The insecticidal properties of 3-cyano-2-pyridones.
Figure 2. The insecticidal properties of 3-cyano-2-pyridones.
Molecules 29 02792 g002
Table 1. Optimization of the reaction conditions a.
Table 1. Optimization of the reaction conditions a.
Molecules 29 02792 i001
EntryBaseSolventYield(%) b
1K2CO31,4-dioxane81
2Na2CO31,4-dioxane70
3Cs2CO31,4-dioxane74
4NaOH1,4-dioxaneTrace
5NaH1,4-dioxaneTrace
6EtONa1,4-dioxaneTrace
7LiOtBu1,4-dioxaneNR
8NaOtBu1,4-dioxaneTrace
9KOtBu1,4-dioxaneTrace
10Et3N1,4-dioxaneNR
11DBU1,4-dioxaneNR
12DABCO1,4-dioxaneNR
13K2CO3DMSO54
14K2CO3DMF66
15K2CO3NMP50
16K2CO3CH3CNTrace
17K2CO3TolueneTrace
18K2CO3THFTrace
19K2CO3CH3OHTrace
20 cK2CO31,4-dioxane45
21 dK2CO31,4-dioxane83
22 eK2CO31,4-dioxane85
a Reaction conditions: 1aa (0.6 mmol), 2aa (0.5 mmol), and base (1.2 mmol) in 2.0 mL of solvent at 100 °C for 8 h under N2. b Isolated yield based on 2aa. c 1.0 equiv. K2CO3. d 1.5 equiv. K2CO3. e 2.5 equiv. K2CO3. NR = no reaction. DMSO = dimethyl-sulfoxide, DMF = N,N-dimethylformamide, THF = tetrahydrofuran, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, DABCO = triethylenediamine.
Table 2. Chemical structures and synthesis yields of 3-cyano-2-pyridones a.
Table 2. Chemical structures and synthesis yields of 3-cyano-2-pyridones a.
Molecules 29 02792 i002
EntryR1R2R33Yield(%) b
1PhPhMe3aa81
24-MeC6H4PhMe3ab87
33-MeC6H4PhMe3ac83
42-MeC6H4PhMe3ad73
54-OMeC6H4PhMe3ae86
62-OMeC6H4PhMe3af75
74-FC6H4PhMe3ag75
83-FC6H4PhMe3ah73
92-FC6H4PhMe3ai64
104-ClC6H4PhMe3aj76
113-ClC6H4PhMe3ak74
122-ClC6H4PhMe3al67
134-BrC6H4PhMe3am75
142-BrC6H4PhMe3an62
154-CF3C6H4PhMe3ao65
162-Me-4-FC6H3PhMe3ap70
172,4-ClC6H3PhMe3aq55
182,3-ClC6H3PhMe3ar58
192-Cl-4-FC6H3PhMe3as56
202,4-FC6H3PhMe3at57
212-naphthylPhMe3au90
22cyclopropylPhMe3av83
23MePhMe3aw76
242-thienylPhMe3ax84
25Ph4-MeC6H4Me3ba88
26Ph3-MeC6H4Me3bb84
27Ph4-nButylC6H4Me3bc85
28Ph4-OMeC6H4Me3bd95
29Ph3-OMeC6H4Me3be92
30Ph4-FC6H4Me3bf74
31Ph4-ClC6H4Me3bg75
32Ph2-ClC6H4Me3bh60
33Ph4-BrC6H4Me3bi78
34Ph4-COOMeC6H4Me3bj70
35PhcyclopropylMe3bk87
36Phn-hexylMe3bl82
37Ph2-thienylMe3bm80
384-MeC6H44-OMeC6H4Me3ca96
394-MeC6H44-nButylC6H4Me3cb90
404-OMeC6H44-OMeC6H4Me3cc98
412-FC6H42-ClC6H4Me3cd64
422-BrC6H44-OMeC6H4Me3ce68
434-cynaoC6H44-OMeC6H4Me3cf70
442,4-FC6H32-ClC6H4Me3cg53
452,3-ClC6H32-ClC6H4Me3ch59
462-naphthyl4-nButylC6H4Me3ci88
472-naphthyl2-ClC6H4Me3cj80
482-BrC6H4cyclopropylMe3ck60
493-MeC6H4PhPh3da53
503-MeC6H4PhBn3db69
513-MeC6H4PhH3dc90
a Reaction conditions: the reactions were performed in a round-bottomed flask on a 0.6 mmol scale of 1, 0.5 mmol scale of 2 and 0.6 mmol scale of K2CO3 in 1,4-dioxane (2 mL) at 100 °C for 8 h. b Isolated yields.
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MDPI and ACS Style

Tang, Y.; Wu, N.; Xu, J.; Zhang, X.; Li, Y.; Wang, X. Metal-Free Cascade Formation of C–C and C–N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties. Molecules 2024, 29, 2792. https://doi.org/10.3390/molecules29122792

AMA Style

Tang Y, Wu N, Xu J, Zhang X, Li Y, Wang X. Metal-Free Cascade Formation of C–C and C–N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties. Molecules. 2024; 29(12):2792. https://doi.org/10.3390/molecules29122792

Chicago/Turabian Style

Tang, Yao, Nvjiang Wu, Junyu Xu, Xiaopo Zhang, Youbin Li, and Xuesong Wang. 2024. "Metal-Free Cascade Formation of C–C and C–N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties" Molecules 29, no. 12: 2792. https://doi.org/10.3390/molecules29122792

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