HETEROCYCLES

■ Contents

■ Synthetic Routes towards Thiazolo[1,3,5]triazines (Review)

Anton V. Dolzhenko*

*School of Pharmacy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia 6845, Australia

Abstract

The present review summarizes information on the synthetic approaches to thiazolo[3,2-a][1,3,5]triazines and polyfused systems bearing this heterocyclic core since the first report on this structure in 1887. The methods allowing access to the heterocyclic systems comprising isomeric thiazolo[3,4-a][1,3,5]triazine scaffold are also included in the review. Data concerning potential applications of the thiazolo[1,3,5]triazines, particularly as biologically active agents are discussed.

■ Efficient Stereoselective Synthesis of Catechin Trimer Derivative Using Silver Lewis Acid-Mediated Equimolar Condensation

Yukiko Oizumi, Yoshihiro Mohri, Yasunao Hattori, and Hidefumi Makabe*

*Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan

Abstract

A stereoselective synthesis of benzylated catechin trimer under intermolecular condensasion is achieved using equimolar amount of dimeric catechin nucleophile and monomeric catechin electrophile catalyzed by AgOTf or AgBF4. The coupled product can be transformed into procyanidin C2 by a known procedure.

■ Synthesis and Reactivity of 6H-Dibenzo[c,e][1,2]oxaphosphinine 6-Sulfide, a Novel Thiophosphacyclic Molecule

Muriel Rakotomalala, Sebastian Wagner, Thomas Zevaco, Michael Ciesielski, Olaf Walter, and Manfred Döring*

*Institute of Catalysis Research and Technology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

Abstract

The new 6H-dibenzo[c,e][1,2]oxaphosphinine 6-sulfide (1) was synthesized and characterized by 1H-, 13C-, 31P-NMR, IR spectroscopy as well as X-ray diffraction and HR-MS. The reactivity of (1) was investigated with a series of test reactions, including Michael-type additions and the Atherton-Todd-reaction and finally compared to that of the parent 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide.

■ Synthesis of Novel Substituted 4-Hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles

Sergey I. Filimonov,* Zhanna V. Chirkova, Igor G. Abramov, Sergey I. Firgang, Galina A. Stashina, and Kyrill Yu. Suponitsky

*Yaroslavl State Technical University, Moscowsky Prospekt 88, 150023 Yaroslavl, Russia

Abstract

New method has been elaborated for synthesis of novel substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles by means of activated nucleophilic substitution of the bromine atom in 4-bromo-5-nitrophthalonitrile by treatment of the latter with sodium salts of substituted 3-cyano-2-hydroxy-3-phenyl acrylates followed by reductive cyclisation. The structure of the resulting substituted 4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6,7-dicarbonitriles has been determined by single crystal X-ray diffraction analysis.

■ Synthesis of New Imidazole 3-Oxides; Unexpected Deoxygenation of Some Derivatives in the Reaction with 2,2,4,4-Tetramethylcyclobutane-1,3-dithione

Grzegorz Mlostoń,* Marcin Jasinski, Dorota Rygielska, and Heinz Heimgartner*

*Department of Organic and Applied Chemistry, University of Łódź, Maritpwocza 68, PL-90-136 Łódź, Poland

Abstract

Whereas the reaction of a series of 1,4,5-trisubstituted imidazole 3-oxides with 2,2,4,4-tetramethylcyclobutane-1,3-dithione gave the corresponding imidazole-2-thiones by a sulfur-transfer reaction via [2+3] cycloaddition, an unexpected deoxygenation occurred in the case of 4-acetyl-1-(adamantan-1-yl)-5-methylimidazole 3-oxide. It was shown that the presence of an electron- withdrawing substituent at C(4) and the bulky 1-adamantyl group at N(1) are necessary to enable this reaction course. A reaction mechanism via a zwitterion, followed by a 1,3-cyclization and elimination of an oxathiirane, is proposed.

■ Synthesis of 3-Alkanesulfonyl-4(1H)-quinolinones from 3-Alkanesulfonyl-4-alkylsulfanylquinolines

Leszek Skrzypek,* Andrzej Maślankiewicz, and Kinga Suwińska

*Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland

Abstract

3-Alkanesulfonyl-4-alkylsulfanylquinolines (4) were transformed to 3-alkanesulfonyl-4(1H)-quinolinones (5) and (6). 1H-Derivatives 5 were obtained by acidic hydrolysis of compounds 4. 1-Alkyl derivatives 6 were prepared in three ways: a) via 1-alkylquinolinium salts 7 followed by their acidic hydrolysis to 6; b) in one-pot reactions of compounds 4 with alkyl bromides under Phase Transfer Catalysis (PTC) conditions; or c) by alkylation of 1H-derivatives 5 with alkyl bromides under PTC conditions.

■ Synthesis and Emission Properties of 1,6-Methano[10]annulene-3,4-dicarboximides

Shigeyasu Kuroda,* Naoko Tamura, Ryuta Miyatake, Naoko Matsumoto, Yoshikazu Horino, Daisuke Miyawaki, and Mitsunori Oda*

*Department of Environmental Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

A mixture of 1,6-methano[10]annulene-3,4-dicarboximide (1e) and 1,6-methano[10]annulene-3,4-dicarboxylic anhydride (3) was obtained through a two-step sequence involving cyanation and subsequent hydrolysis from ethyl 4-bromo-1,6-methano[10]annulene-3-carboxylate (5). Alkylations of 1e provided 1f and 1g, and the nucleophilic substitution of p-fluoronitrobenzene with 1e yielded 1i. Copper-catalyzed arylations of 1e with arylhalides gave 1a and 1h. Reactions of 3 with anilines afforded 1a and 1h. Emission properties of the imides obtained are also reported.

■ Synthesis of O2- and N3-(2-Phosphonomethoxy)ethyl Derivatives of 6-Phenyl- and 6-Pyridinyl-5-azacytosine

Miroslav Otmar,* Martin Dracinsky, Marcela Krecmerova, Jan Balzarini, Graciela Andrei, and Robert Snoeck

*Gilead Sciences and IOCB Research Centre, Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Flemingovo nam. 2, 16610 Prague 6, Czech Republic

Abstract

A series of hydrolytically stable O2- and N3-(2-phosphonomethoxy)- ethyl (PME) derivatives of 6-phenyl, pyridin-2, -3 and -4-yl-5-azacytosines was prepared by their alkylation with diisopropyl (2-chloroethoxy)methylphosphonate followed by the deprotection. No antitumor or antiviral activity was found except for 6-(pyridin-4-yl)-1,3,5-triazine-2,4-diamine (13d) which exhibited slight activity against feline herpesvirus in CrFK cell cultures with IC50 = 6.7 µg/mL.

■ Facile Synthesis of Pyrano[3,2-e]indoles via the Base-Promoted Pictet-Spengler Reaction of Nb-Benzylserotonin

Koji Yamada, Sayaka Yamaguchi, Noriyuki Hatae, Takumi Abe, Tatsunori Iwamura, and Minoru Ishikura*

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

A novel and simple protocol for the synthesis of 1-(2-aminoethyl)pyrano[3,2-e]indole derivatives has been developed using the Pictet-Spengler reaction of Nb-benzylserotonin with α,β–unsaturated aldehydes in the presence of Et3N in 2-propanol or MeOH.

■ Heck-Mizoroki Reaction of 4-Iodo-1H-pyrazoles

Yoshihide Usami,* Hayato Ichikawa, and Shinya Harusawa

*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The Heck-Mizoroki reaction of 1-protected-4-iodo-1H-pyrazoles with various kinds of alkenes was examined and found to yield 1-protected-4-alkenyl-1H-pyrazoles. P(OEt)3 was a suitable ligand for the cross-coupling reaction, together with the trityl group that acted as an appropriate protecting group of 1H-pyrazole.

■ Preparation and Reaction of Quinolinyl (or Pyridinyl)phosphonium Salts with Base and Pivalaldehyde

Minami Shimada, Osamu Sugimoto,* Akihiro Sato, and Ken-ichi Tanji

*Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

α- and γ-Heteroaryltriphenylphosphonium iodides were prepared by reaction of the corresponding heteroaryl iodides with triphenylphosphine. Reaction of β-heteroaryl iodides with triphenylphosphine in the presence of a palladium catalyst gave β-heteroaryltriphenylphosphonium iodides. Elimination of the heteroaryl group was achieved by treating the heteroaryltriphenylphosphonium iodides with a base. Further, the heteroaryl group was trapped with pivalaldehyde to introduce a pivaloyl substituent onto the heteroaromatic ring.

■ The First Hydroperoxydihydrochalcone in the Etlingera Genus: Etlinglittoralin from the Rhizomes of Etlingera littoralis

Chotika Jeerapong, Sarot Cheenpracha, Wisanu Maneerat, Uma Prawat, Thongchai Kruahong, and Surat Laphookhieo*

*Natural Products Research Laboratory, School of Science, Mae Fah Luang University, Tasud, Muang, Chiang Rai 57100, Thailand

Abstract

Etlinglittarolin (6), a monoterpene-substituted hydroperoxy dihydrochalcone, together with five known dihydrochacones including 2′, 6′-dihydroxy-4′-methoxydihydrochalcone (1), 2′,4′,6′-trihydroxydihydrochalcone (2), 2′,6′,4-trihydroxy-4′-methoxydihydrochalcone (3), methyllinderatin (4), and adunctin E (5), was isolated from the rhizomes of Etlingera littoralis. Their structures were elucidated by spectroscopic analysis.

■ Microwave-Assisted, Yb(OTf)3 /TfOH Cocatalyzed Synthesis of Xanthones and Thioxanthones by Intramolecular Friedel-Crafts Reaction under Solvent-Free Conditions

Jie Li, Can Jin, and Weike Su*

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

Abstract

An efficient method for the synthesis of biologically interesting xanthones and thioxanthones was achieved using Yb(OTf)3/TfOH as co-catalysts by a microwave radiation-mediated reaction. Both electron-rich and electron-poor substrates could be cyclized in good yields.

■ Synthesis of Caboxamycin and Its Derivatives Using Eco-Friendly Oxidation

Yoshinobu Tagawa,* Hiroki Koba, Kazuhiro Tomoike, and Kunihiro Sumoto

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

The reaction of 3-hydroxyanthranilic acid or methyl 3-hydroxyanthranilate with O-benzylsalicylaldehyde in xylenes gave benzoxazole derivatives, which lead to a novel benzoxazole antibiotic, caboxamycin via debenzylation or demethylation in good yield, in the presence of dry activated carbon and bubbling molecular oxygen. The present reaction involves the simple procedure, easy workup and environmentally benign materials such as reusable activated carbon and molecular oxygen.

■ A Facile and Efficient Synthesis of 3-Amino-5-bromopyridine Derivatives Using Microwave Irradiation

Reddeppa reddy Dandu,* Adam C. Rose, and Robert L. Hudkins

*Discovery Research, Cephalon Inc., 145 Brandywine Parkway, West Chester, PA 19380, U.S.A.

Abstract

A facile and general synthetic strategy was developed to synthesize 3-amino-5-bromopyridine derivatives under microwave heating conditions. The strategy involved reacting 3,5-dibromopyridine with an excess of an aliphatic amine using microwave heating, without the need to use either metal-mediated, base-promoted or harsh long thermal reaction times. The microwave approach enabled the rapid synthesis of 3-amino-5-bromopyridine derivatives in multi-gram quantities from commercially available starting materials.

■ One-Pot Synthesis of 4,5-Dihydro-3,1-benzoxazepine-2(1H)-thiones from 2-(2-Isocyanophenyl)ethanols via the Corresponding Isothiocyanates

Shuhei Fukamachi, Hisatoshi Konishi, and Kazuhiro Kobayashi*

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

Abstract

An efficient method for the preparation of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones under mild conditions has been developed. 2-(2-Isocyanophenyl)ethanols, easily accessible by treating 1-isocyano-2-(lithiomethyl)benzenes with aldehydes or ketones, were converted into the corresponding isothiocyanates on treatment with sulfur in the presence of a catalytic amount of selenium and excess triethylamine. These isothiocyanato alcohols were then treated with sodium hydride to give 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives in one pot.

■ Alkylation and Reduction of N-Alkyl-4-nitroindazoles with Anhydrous SnCl2 in Ethanol: Synthesis of Novel 7-Ethoxy-N-alkylindazole Derivatives

Najat Abbassi, El Mostapha Rakib,* Abdellah Hannioui, Mdaghri Alaoui, Mohamed Benchidmi, El Mokhtar Essassi, and Detlef Geffken

*Laboratory of Organic and Analytical Chemistry, Faculty of Sciences and Techniques, University Sultan Moulay Slimane, B.P. 523, Beni-Mellal, Morocco

Abstract

New series of indazoles substituted at the N-1 and N-2 positions and their 7-ethoxy derivatives have been synthesis starting from alkylation of 4-nitroindazole and reduction of alkyl-nitro-derivatives with anhydrous SnCl2 in ethanol. The structures of the products obtained were characterized using 1H NMR, 13C NMR, MS spectrometry and elemental analysis; the NMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers.