HETEROCYCLES

■ Contents

■ Gold-Catalyzed Skeletal Rearrangement Reactions of O-Propargylic and O-Homopropargylic Oximes

Itaru Nakamura* and Masahiro Terada

*Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

Au-catalyzed skeletal rearrangement reactions of O-propargylic oximes, which were derived from the condensation of N-propargyloxyamine with either formaldehyde or glyoxylate, afforded the corresponding 4-methylenated isoxazolines via C=N bond cleavage. The obtained isoxazolines underwent carbonyl–ene reactions, generating functionalized isoxazoles in good yields. Moreover, a sequence of Au-catalyzed reactions followed by a carbonyl–ene reaction of enantioenriched substrate produced isoxazoles having a chiral side chain, with excellent levels of chirality transfer. In contrast, the Au-catalyzed reactions of O-propargylic oximes bearing an electron-deficient aryl group on the oxime carbon proceeded via N–O bond cleavage, affording oxazines in good yields.

■ Facile and Efficient N-Boc Deprotection of Amide and Sulfonamide under Microwave Irradiation in Water

Zhi-you Huang,* Wen-sheng Li, Jia Xu, Bing-rong Xiang, Min-xin Li, Li-jun Chen, and Ye-she Wang

*College of Urban and Rural Construction, Shaoyang University, Shaoyang, 422000, P.R.China

Abstract

A facile and efficient microwave-assisted N-Boc deprotection of amide and sulfonamide in water was developed. With environmentally friendly, operational-simplicity, good substrate scope and excellent product yields, this methodology is superior to the existing approach. Significantly, the target compound was obtained after filtration and dry.

■ Direct β-Alkenylation of Thiophenes with Alkenyl Halides Catalyzed by a Dinuclear Palladium Complex

Nozomi Asahara and Naofumi Tsukada*

*Department of Chemistry, Faculty of Science, Shizuoka University, 836 Ohya, Shizuoka 422-8529, Japan

Abstract

Direct alkenylation of thiophenes with iodoalkenes proceeded in the presence of a dinuclear palladium complex formed by a chelate-bridging ligand. In most reactions, β-alkenylthiophenes were obtained with good to high regioselectivity.

■ Regioselective Synthesis of Some Novel Phosphonopyrazole, Phosphonopyrimidine and Phosphonodiazepine Compounds Containing Coumarin Ring

Tarik E. Ali* and Mohammed A. Assiri

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt

Abstract

A convenient regioselective synthesis of some novel phosphonopyrazole, phosphonopyrimidine and phosphonodiazepine derivatives containing a coumarin ring, was designed. The methodology involves one-pot reaction of 3-(2-bromoacetyl)-2H-chromen-2-one (1) with dimethylformamide dimethyl acetal and diethyl phosphite to give diethyl [2-bromo-3-oxo-3-(2-oxo-2H-chromen-3-yl)prop-1-en-1-yl]phosphonate (2). The successful heterocyclization of substrate 2 with 1,2-, 1,3- and 1,4-diamine reagents afforded the target products in moderate to good yields.

■ The Continuous-Flow Synthesis of 1H-Indazoles via Reaction of o-Fluorobenzaldehydes with tert-Butyl Carbazate under High Temperature

Wenjie Ye, Kai Zhu, Yiping Huang, Chuansong Duanmu, Yanxing Li, Jin Li, Weichuan Xu, and Feng Zhou*

*National & Local Joint Engineering Research Center for Deep Utilization Technology of Rock-salt Resource, Faculty of Chemical Engineering, Huaiyin Institute of Technology, Huai’an 223003, P. R. China

Abstract

Large amounts of 1H-indazoles have been developed and widely used in the production of diverse drugs. The reaction of 4-bromo-2,6-difluorobenzaldehyde with tert-butyl carbazate was selected as model transformation for the application of continuous-flow strategy to realize the efficient syntheses of 1H-indazoles in a highly controlled and safe manner. Various conditions (reaction temperature, residence time, solvent amount, the amount of tert-butyl carbazate, water content) were investigated under continuous-flow conditions to elucidate the benefits of using the continuous-flow strategy. The Box-Behnken design in response surface methodology was employed for the optimization of reaction conditions, and over 85% yield of 6-bromo-4-fluoro-1H-indazole could be achieved. Furthermore, the generality of the reaction conditions found optimal for the synthesis of 6-bromo-4-fluoro-1H-indazole was evaluated for the synthesis of several different 1H-indazoles.

■ Reactivity of 4-Bromoacetyl-1,2,3-triazoles towards Amines and Phenols: Synthesis and Antimicrobial Activity of Novel Heterocycles

Bakr F. Abdel-Wahab, Hanan A. Mohamed, Abdelbasset A. Farahat, Benson M. Kariuki, and Gamal A. El-Hiti*

*Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia

Abstract

The reactivity of 4-bromoacetyl-1H-1,2,3-triazoles towards amines and phenols was studied. Reaction of 4-bromoacetyl-1H-1,2,3-triazole (1a; R = H) with benzylamine (2) in the absence of any catalyst unexpectedly afforded heterocycle 2,5-bis(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)pyrazine (4) in 50% yield. Additionally, the reaction of 1b (R = Br) with 4-bromoaniline and of 1c (R = Me) or 1d (R = NO2) with 1H-benzotriazole in basic media gave the expected aminoketone products 8 and 9a or 9b in high yields. Furthermore, the reaction of 1c (R = Me) or 1e (R = Cl) with phenol or β-naphthol in basic media led to the production of keto-ethers 10 or 11, respectively in an excellent yield. Compound 10 showed the highest inhibitory effect against the growth of the tested pathogens.

■ Synthesis of 2,3-Anthracenedicarboxylic-Acid-Derived Fluorophore and Chemiluminophore Incorporating Dipicolylaminomethyl Receptors, and Their Luminescence Responses to Metal Ions

Naomi Yamazaki, Ayako Matsui, Kyosuke Satake, and Hideki Okamoto*

*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

2,3-Anthracenedicarboxylic-acid-derived carboximide 1 and cyclic-hydrazide 2, incorporating dipicolylaminomethyl receptors, have been respectively prepared as novel fluorescence and chemiluminescence probes for metal cations. Carboximide 1 was essentially non-fluorescent in acetonitrile whereas it produced intense fluorescence (λFLmax 470 nm) upon addition of Zn2+ (off–on response). Cyclic-hydrazide 2 gave off blue chemiluminescence emission (λCLmax 465 nm) after addition of alkaline H2O2 and iodide ion in dimethyl sulfoxide. Addition of metal cations, e.g. Zn2+, into the chemiluminescence system resulted in significant quenching of the chemiluminescence (on–off response). Therefore, the effects of the metal cation on the chemiluminescence behavior of cyclic-hydrazide 2 showed clear contrast to those on the fluorescence behavior of carboximide 1.

■ Efficient and Aqueous Synthesis of 3,4-Disubstituted Isoxazol-5(4H)-one Derivatives Using Piperazine under Green Conditions

Ziba Daroughezadeh and Hamzeh Kiyani*

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

Abstract

The one-pot, three-component, as well as expeditious synthesis of 3,4-disubstitted isoxazol-5(4H)-ones has been attained from the heterocyclization of various aryl/heteroaryl aldehydes, active methylene compounds, and hydroxylamine hydrochloride in the presence of piperazine as the efficient, low-cost, commercially available, and eco-friendliness basic organocatalyst. This double secondary amine catalyst was found that catalyzed the synthesis of isoxazol-5(4H)-ones under green conditions. The additional features of the present catalyst include readily available starting materials, relatively low catalyst loading, using water as a green solvent, broad substrate scope, simplicity, good to excellent reaction yields, faster synthesis, and avoiding the hazardous organic solvents.

■ An Efficient Method for the Synthesis of N-Aryl Substituted C1-Functionalized 1,2,3,4-Tetrahydroisoquinolines

Hairong Luo,* Fen Tian, Yi He, Xurong Liu, Jing Li, and Meihang Chen*

*College of Material and Chemical Engineering, Tongren University, Tongren,Guizhou 554300, China

Abstract

An efficient and facile cyclic iminium-ion-based strategy has been developed for the synthesis of structurally diverse N-aryl substituted C1-functionalized THIQs. Cyclic iminium ions generated in situ from 2-(2-bromomethyl)benzaldehyde reacted with acetone to furnish ketone moiety at C-1 position in THIQs in moderate to good yields.

■ Molecular Iodine Mediated Synthesis of 2,4,5-Trisubstituted Imidazoles Commencing from α-Methylene Ketones and Benzylic Primary Alcohols Using a One-Pot, Two-Step Approach

Lindokuhle P. Mabizela and Vineet Jeena*

*School of Chemistry and Physics, University of KwaZulu-Natal, Scottsville, Pietermaritzburg, 3209, South Africa

Abstract

A simple one-pot, two-step approach to 2,4,5-trisubstituted imidazoles has been developed commencing from α-methylene ketones and primary alcohols. Using an environmentally friendly, inexpensive, and readily available iodine-based system, a series of trisubstituted imidazoles were prepared in moderate to good yields under mild reaction conditions.

■ New Anti-TMV Isochromenes from Nicotiana tabacum-Derived Endophytic Fungus Aspergillus versicolor

Qiu-Fen Hu, Ling-Fang Zhang, Guang-Hai Zhang, Mei-Fen Bao, Yin-Ke Li, Dong Miao, Yu-Ping Wu, Gang Du,* and Guang-Hui Kong*

*Key Laboratory of Chemistry in Ethnic Medicinal Resources, Yunnan Minzu University, Kunming 60500, P. R. China

Abstract

Three new isochromenes, versicolols G-I (1-3), together with four known analogues (4-7) were isolated from the fermentation products of a Nicotiana tabacum-derived endophytic fungus Aspergillus versicolor. Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-3 were also tested for their anti-tobacco mosaic virus (anti-TMV) activities, and the results revealed that compound 1 exhibited high anti-TMV activity with inhibition rate of 41.6%, and this rate are higher than that of positive control. Compounds 2 and 3 also showed potential anti-TMV activities with inhibition rates of 22.8 and 26.5%, respectively.