Synthesis and Insecticidal Activities of 1,3,5‐Trisubstituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines

A new series of 1,3,5‐trisubstituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines ( 3a – 3j ) were designed and synthesized as novel neonicotinoid analogues, and their structures were characterized by ¹H NMR, IR, elemental analysis and MS. The preliminary bioassay tests showed that most of the target compounds had good insecticidal activities against Nilaparvata lugens as well as Aphis medicaginis at 500 mg/L, while compound 3i had 100% mortality against Nilaparvata lugens at 20 mg/L.     

Synthesis and Insecticidal Activities of 1,5‐Disubstituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines

By extracting active moieties from typical insecticides and recombining to a same molecule, a series of novel title compounds were designed and synthesized as shown in Scheme 1. The structures of all compounds were confirmed by IR, ¹H NMR, MS, and elemental analysis. The preliminary bioassay showed that the partial target compounds gave 90% mortality against Tetranychus cinnabarnus at 500 mg/L.     

Synthesis of alicyclic N‐substituted 1,3‐amino alcohols via 1,3‐oxazines

Alicyclic N‐substituted 1,3‐amino alcohols 13‐18 were prepared in a facile way in a one‐pot procedure from 1,3‐oxazines 5‐8 in the presence of a ketone 9‐12 . The complex reaction involves palladium‐catalyzed reduction, debenzylation and/or transimination and further reduction.     

Optical Activity 1,5‐Substituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines: Synthesis and Insecticidal Activity

Twelve novel neonicotinoid analogues 1‐(2‐furfuryl)‐5‐substituted‐1,3,5‐hexahydrotriazine‐2‐N‐nitroimines 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l were synthesized. Their structures were characterized by ¹H NMR, IR, and elemental analysis. The preliminary bioassay tests showed that all the title compounds gave ≥90% mortality against Nilaparvata lugen 500 mg/L.     

One‐Pot Synthesis of 1,3,5‐Triarylpyrazoles

A series of novel 1,3,5‐triarylpyrazoles 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l , 3m , 3n , 3o , 3p , 3q , 3r , 3s , 3t , 3u , 3v , 3w , 3x were synthesized from flavanones, arylhydrazines, and trimethyl phosphate in an one‐pot procedure. Facile reaction process, easy after‐reaction workshop, and good yields are the distinct characteristics of the developed protocol. The target compounds were characterized by element analysis, infrared ray (IR), ¹H NMR spectra, and electrospray ionization‐mass spectrometry. The structure of representative compound 3h (C₂₃H₂₀N₂O₃, M_r = 372.42) was further confirmed by X‐ray diffraction. It crystallizes in monoclinic, space group P 2₁/c, a = 8.9720(5), b = 24.5523(13), c = 8.9687(6) Å, α = 90.0000, β = 102.6417(17), γ = 90.0000°, V = 1927.76(20) ų, Z = 4, μ(MoKα) = 0.086, F(000) = 784, D_c = 1.283 g/cm³, the final R = 0.0349 and wR = 0.0844 for 1668 observed reflections (I > 2σ(I))     

Mild Oxidation of 1,3,5‐Trisubstituted Pyrazolines with N‐Bromo‐sulphonamides

1,3,5‐Trisubstituted pyrazolines to pyrazoles are carried out efficiently in the presence of new reagents N,N,N′, N′‐tetrabromo‐benzene‐1,3‐disulfonylamine [TBBDA] and N,N′‐dibromo‐N,N′‐1,2‐ethanediylbis‐(p‐toluenesulphonamide) [BNBTS] in solvent‐free conditions with catalytic amounts of SiO₂ under microwave irradiation in high yields.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.     

Synthesis of Indolones via Radical Cyclization of N‐(2‐Halogenoalkanoyl)‐Substituted Anilines

The radical reactions of N‐(2‐halogenoalkanoyl)‐substituted anilines (anilides) of type 1 have been investigated under various conditions. Treatment of compounds 1a – 1o with Bu₃SnH in the presence of (2,2′‐azobis(isobutyronitrile) (AIBN) afforded a mixture of the indolones (oxindoles) 2a – 2o and the reduction products 5a – 5o (Table 1). In contrast, the N‐unsubstituted anilides 1p – 1s, 1u , and 1v gave the corresponding reduction products exclusively (Table 1). Similar results were obtained by treatment of 1 with Ni powder (Table 2) or wth Et₃B (Table 3). Anilides with longer N‐(phenylalkyl) chains such as 6 and 7 were inert towards radical cyclization, with the exception of N‐benzyl‐2‐bromo‐N,2‐dimethylpropanamide ( 6b ), which, upon treatment with Ni powder in i‐PrOH, afforded the cyclized product 9b in low yield (Table 4). Upon irradiation, the extended anilides 6, 7, 10 , and 11 yielded the corresponding dehydrobromination products exclusively (Table 5).     

Synthesis of novel N‐alkyl/aryl‐N′‐(4‐arylthiazol‐2‐yl)‐N″‐xylosyl guanidines

The reaction of 2,3,4‐tri‐O‐acetyl‐β‐D‐xylopyranosyl isothiocyanate ( 1 ) and 2‐amino‐4‐arylthiazoles ( 2 ) gave xylosylthioureas 3 . These thiourea derivatives reacted with alkyl/aryl amine in the presence of HgCl₂ to give a new series of N‐alkyl/aryl‐N″‐(4‐arylthiazol‐2‐yl)‐N″‐xylosyl guanidines 4 . Some of the synthesized guanidines were screened for their biological activity. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:688–694, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20379     

Synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines via a pictet‐spengler cyclisation

The synthesis of N‐methyl‐4‐pyridyl‐1,2,3,4‐tetrahydroisoquinolines (6a,b,c) was achieved via a Pictet‐Spengler cyclization of an activated amino group derivatized in a carbamate form. The obtained compounds have been designed as potential serotonin analogs.     

Synthesis,insecticidal activities,and molecular docking studies of 1,5‐disubstituted‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro)imines

A series of novel neonicotinoids analogs were designed by modifying the pharmacophore of imidacloprid to 1,3,5‐hexahydrotriazine conjugated to nitroimine (?NNO₂) and introducing the phenyl or arylmethyl at the 5‐position, and their insecticidal activities were evaluated. Introducing a heterocyclic methyl at 5‐position increased the insecticidal activities, whereas other phenyl, phenylmethyl or phenylethyl substituents were unfavorable to activities. Molecular docking study was also performed to clarify the interactions of the most potent analog 1‐((6‐chloropyridin‐3‐yl)methyl)‐5‐(3‐pyridylmethyl)‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro) imine ( 7s ) with the target nicotinic acetylcholine receptor, which explained the structure‐activity relationships observed in vitro, and revealed further possibilities for insecticide development. J. Heterocyclic Chem., (2011).     

Effective Synthesis of N‐Arylformamide from α‐Halo‐N‐arylacetamides

A convenient synthetic method for N‐arylformamide derivatives was successfully developed by reacting α‐iodo‐N‐arylacetamides with formamide. This method was applicable to α‐iodo‐N‐arylacetamide substrates bearing electron‐donating or electron‐withdrawing groups, N‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐iodoacetamide, 2‐iodo‐N‐(pyridin‐2‐yl)acetamide, and 2‐iodo‐N‐(naphthalen‐4‐yl)acetamide to give the corresponding N‐arylformamides in moderate to excellent yields (65–94%). A plausible mechanism was proposed to account for the new transformation.     

Synthesis of acrimarins from 1,3,5‐trioxygenated‐9‐acridone derivatives

1,3,5‐Trihydroxy‐9(10H)‐acridinone (1) was prepared from 3‐hydroxyanthranillic acid with phloroglucinol. 1,3‐Dihydroxy‐5‐methoxy‐9(10H)‐acridinone (2) was prepared from 3‐methoxyanthranillic acid and phloroglucinol. Methylation of 1 under different conditions gave 1‐hydroxy‐3,5‐dimethoxy (3), 1‐hydroxy‐3,5‐dimethoxy‐10‐methyl (4), 1‐hydroxy‐3,5‐dimethoxy‐4‐methyl (5), 1,3,5‐trimethoxy‐10‐methyl (6) and 1,3,5‐trimethoxy‐4,10‐dimethyl (7) analogues. Demethylation of 4 afforded the 1,3,5‐trihydroxy‐10‐methyl analogue 8. Condensation of acridones 1, 2, 3 and 4 individually with E‐suberenol (9) gave four novel acrimarins (acridone‐coumarin dimers) 10, 11, 12 and 13 respectively, while the acridone 8 gave previously reported acrimarin‐G (14).     

Enantioselective N‐Heterocyclic Carbene Catalyzed Cyclopentene Synthesis via the β‐Azolium Ylide

Herein we report the cycloisomerization of electron‐poor 1,5‐dienes via the β‐azolium ylide to give enantioenriched cyclopentenes. The reaction is mediated by a chiral N‐heterocyclic carbene (NHC) catalyst, exploits readily available substrates, has good generality (17 examples), and displays excellent enantioselectivity (mostly >94:6). Studies demonstrating the viability of a related dynamic kinetic resolution are reported, as are those with alternate tethers and derivatizations.