HETEROCYCLES

■ Contents

■ Recent Advances in the Application of the Heck Reaction in the Synthesis of Heterocyclic Compounds

Majid M. Heravi* and Azadeh Fazeli

*Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran

Abstract

This brief review represents the synthesis of heterocyclic compounds via application of Heck reaction in recent years.

■ Selenium-Containing Heterocycles Using Selenoamides, Selenoureas, Selenazadienes, and Isoselenocyanates

Masayuki Ninomiya, Dinesh R. Garud, and Mamoru Koketsu*

*Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu, Gifu 501-1193, Japan

Abstract

In recent years, considerable attention has been devoted to the synthesis of selenium-containing heterocycles because of their interesting reactivities and potential pharmaceutical applications. The significant starting materials for the selenium-containing heterocycles synthesis are selenoamides, selenoureas, selenazadienes, and isoselenocyanates. This review article introduces the developed synthetic methods mainly on our findings.

■ Microwave Assisted Rapid Preparation of N-Alkyl-2-pyridones under Neutral Conditions by Hilbert-Johnson Reaction

Hirokazu Iida,* Machiko Suda, Etsuko Nakajima, Hiroko Hakamatsuka, Yuka Nagashima, Kouta Joho, Kenta Amemiya, Tatsuya Moromizato, Kiyoshi Matsumoto, Yasuoki Murakami, and Hiroshi Hamana*

*Faculty of Pharmaceutical Sciences, Chiba Institute of Science, 3 Shiomi-cho, Choshi, Chiba 288-0025, Japan

Abstract

The reactions of 2-methoxypyridine with haloalkanes without solvent and catalyst under microwave irradiation (100-200 °C, 5 min) yielded the corresponding N-alkyl-2(1H)-pyridones in good to moderate yields. However, the reactions were sensitive to length of haloalkanes. In contrast, the reactions of 2-alkoxypyridines with corresponding iodoalkanes under microwave irradiation (150 °C) proceeded rapidly without catalyst and solvent, and were complete within 5 min to afford N-alkyl-2(1H)-pyridones in good to excellent yields.

■ Ultrasonic-Assisted One-Pot Synthesis of Pyrazolo[1,2-a][1,2,4]triazole-1,3-diones

Davood Azarifar* and Razieh Nejat Yami

*Faculty of Chemistry, Bu-Ali Sina University, P.O. Box 4135, Hamedan 6517838683, Iran

Abstract

A facile and efficient one-pot three-component synthesis of pyrazolo[1,2-a][1,2,4]triazole-1,3-diones via condensation reaction between malononitrile, 4-phenylurazole and aromatic aldehydes in ethanol under the catalytic effect of triethylamine and ultrasonic-irradiation conditions has been explored. The advantages of this protocol include a simple workup, high rates, use of inexpensive non-toxic catalyst, improved yields, and use of ethanol as a relatively environmentally benign solvent.

■ Synthesis of Spiro[2-cyclopentene-1,3’-imidazo[1,2-a]pyridine] Derivatives and Their Interesting Behavior in 1H-NMR Spectra in Deuteriochloroform

Takashi Abe, Akikazu Kakehi,* Hiroyuki Suga, Yukihisa Okumura, and Kennosuke Itoh

*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

Ethyl 2’,3’-dihydro-2-methylthio-2’,4-dioxospiro[2-cyclopentene- 1,3’-imidazo[1,2-a]pyridine]-3-carboxylates were synthesized from the reactions of 3-[bis(methylthio)methylene]-2(3H)-imidazo[1,2-a]pyridinones with ethyl 4-chloroacetoacetate in the presence of a base. The 2-methylthio group in these spiro compounds was easily replaced with some primary and secondary amines to afford the corresponding 2-amino derivatives. Very interestingly, the proton signals of these spiro compounds in the 1H-NMR spectra in deuteriochloroform (CDCl3) changed with an increase in the sample concentration, and the analysis for the magnitude and the direction of each proton shift disclosed the conformational change of the cyclopentenone moiety in this molecule.

■ An Efficient Synthesis of 2-Aminobenzoxazoles and 2-Aminobenzothiazoles from 2-Aminophenols or 2-Aminothiophenols and Isoselenocyanates

Yuanyuan Xie,* Fan Zhang, Xiaodong Chen, and Jianjun Li

*Key Laboratory of Pharmaceutical Engineering of Ministry of Educations, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310014, China

Abstract

An expeditious method to access 2-aminobenzoxazoles and 2-aminobenzothiazoles from various substituted 2-aminophenols and 2-aminothiophenols, respectively, with isoselenocyanates in a one pot procedure is reported. Elemental Se precipitates nearly quantitatively in the reaction without any deselenizing agent and it can be reused. A possible mechanism for the formation of the target products is proposed.

■ Cyclization Reactions of 2-Isothiocyanatophenyl Ketones Giving 4-Hydroxyquinoline-2(1H)-thiones and 4-Alkylidene-1,4-dihydro-3,1-benzoxazine-2-thiones

Kazuhiro Kobayashi,* Toshihide Komatsu, Shuhei Fukamachi, and Hisatoshi Konishi

*Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

2-Isothiocyanatophenyl methyl ketones, generated in situ by treatment of 2-isocyanophenyl methyl ketones with sulfur in the presence of a catalytic amount of selenium and excess triethylamine, underwent electrocyclic reaction (ECR) via their enolate forms to give 4-hydroxyquinoline-2(1H)-thiones. The reaction products from ethyl 2-isothiocyanatophenyl ketones generated in situ from the corresponding isocyanides under similar conditions proved to be the ECR products, 4-hydroxy-3-methylquinoline-2(1H)-thiones and/or the ionic cyclization products, 4-ethylidene-1,4-dihydro-3,1-benzoxazine-2-thiones.

■ A Novel Pentose Synthesis via Palladium(II)-Catalyzed Cyclization of an Unstable Hemiacetal

Ken-ichiro Awasaguchi, Masahiro Miyazawa,* Ikuyo Uoya, Koichi Inoue, Koji Nakamura, Hajime Yokoyama, and Yoshiro Hirai*

*Department of Chemistry, Graduate School of Science and Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

PdCl2(PhCN)2 (5 mol%)-catalyzed cyclization of a hemiacetal derived from (E,2S,3R)-2,3-isopropylidenedioxy-6-(tetrahydro-2H-pyran-2-yl)-4-hexenal and methanol gave substituted furanoside in moderate yield, exclusively via 5-exo-mode cyclization, without the need for a reoxidant. New stereogenic centers at C1 and C4 on the tetrahydrofuran ring showed preferential 1R and 4R stereochemistry due to anomeric effect (no-σ*c-o) and A1,2 strain, respectively. This methodology was applied to stereocontrolled synthesis of pentoses: D-ribose and L-lyxose.

■ New Nonadride Analogues from a Freshwater Isolate of an Undescribed Fungus Belonging to the Order Pleosporales

Tomoo Hosoe, James B. Gloer,* Donald T. Wicklow, Huzefa A. Raja, and Carol A. Shearer

*Department of Chemistry, University of Iowa, Iowa City, IA 52242, U.S.A.

Abstract

Three new nonadride derivatives, tetrahydroepiheveadride (1), dideoxoepiheveadride (2) and deoxodihydroepiheveadride (3), and two new C-9 compounds, waquafranone A (7) and B (8), which were suggestive of precursors of nonadrides, along with other known compounds epiheveadride (4), deoxoepiheveadride (5), dihydroepiheveadride (6), sydonic acid (9), hydroxysydonic acid (10), folipastatin (11), and agonodepside B (12), from the newly described freshwater aquatic fungus Wicklowia aquatica. The chemical structures of 1 - 12 were elucidated by the spectroscopic and chemical investigation and, comparison to literature data.

■ New and Convenient Route for the Synthesis of Some New Pyrazol-5-yl-1H-imidazole Derivatives

Afsaneh Zonouzi,* Roghieh Mirzazadeh, Marzieh Talebi, Razieh Jafarypoor, Azadeh Peivandi, and Seik Weng Ng

*School of Chemistry, College of Science, University of Tehran, Tehran 14155-6455, Iran

Abstract

A simple and efficient method for the synthesis of some new pyrazol-5-yl-1H-imidazoles 4a-h is described. In this method oxazolones 5a-h were produced as minor products. The X-ray analysis confirmed the structures of 4 and 5.

■ One-Step Construction of 6-Aza-2-thiabicyclo[3.3.1]nona-3,7-diene Framework

Nagatoshi Nishiwaki* and Kazuya Kobiro

*School of Science and Technology, Kochi University of Technology, Tosayamada-cho, Kochi, 782-8502, Japan

Abstract

The 6-aza-2-thiabicyclo[3.3.1]nona-3,7-diene framework was constructed upon treatment of dielectrophilic 3,5-dinitro-1-methyl-2-pyridone with S,C-dinucleophilic ethyl 3-thioxobutanoate, in which two moieties are connected by forming two bonds in the single manipulation.

■ A Novofumigatamide, New Cyclic Tripeptide from Aspergillus novofumigatus

Kazuki Ishikawa, Tomoo Hosoe,* Takeshi Itabashi, Kayoko Takizawa, Takashi Yaguchi, and Ken-ichi Kawai

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

A new cyclic tripeptide, novofumigatamide (1) has been isolated from Aspergillus novofumigatus CBS117520. The relative structure of 1 was established on the basis of spectroscopic and physico-chemical data and chemical investigations. The absolute structure of 1 was determined by using a Marfey’s method. Compound 1 showed non-specific antifungal activities against some human pathogenic fungi and did not inhibit cell proliferation for any tumor cells.