HETEROCYCLES

■ Contents

■ Reaction of 3,3,5,5-Tetramethylthiolane-2,4-dithione with Benzyne: Novel Formation of Benzodithiole

Kentaro Okuma,* Taeko Tsubone, Toshiyuki Shigetomi, Kosei Shioji, and Yoshinobu Yokomori

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

Abstract

Reaction of 3,3,5,5-tetramethylthiolane-2,4-thione with benzyne gave a new type of benzodithiole in 78% yield. Dithioester’s thiocarbonyl group initially attacked benzyne to afford the corresponding betaine, which finally rearranged to give benzodithiole. On the other hand, reaction of cyclic dithiolactone with benzyne recovered the starting dithiolactone in almost quantitatively.

■ Syntheses of Some 1-(α-Hydroxybenzyl)thieno[3,4-b]indolizine Derivatives and Their Unexpected Condensation Reactions

Akikazu Kakehi,* Hiroyuki Suga, Shin Hatayama, and Daisuke Kubo

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

Abstract

Some ethyl 3-(benzyl or methylthio)-1-(α-hydroxybenzyl)thieno[3,4-b]indolizine-9-carboxylates were prepared by the reduction of the corresponding 1-benzoyl derivatives with sodium borohydride. These compounds were considerably unstable and their treatment with acetic acid afforded the unexpected condensation products.

■ Total Synthesis of Murrastifoline-A by Way of the Pd-catalyzed Double N-Arylation of a Carbazolamine with a 2,2’-Dibromobiphenyl Derivative

Takafumi Kitawaki, Yoko Hayashi, and Noritaka Chida*

*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku Yokohama 223-8522, Japan

Abstract

The first total synthesis of murrastifoline-A (1), a biscarbazole alkaloid is described. The biscarbazole skeleton of 1 was effectively constructed by the Pd-catalyzed double N-arylation of carbazolamine (bottom-half segment, 3) with dibromobiphenyl derivative (top-half segment, 2) in one-step reaction. Both segments were synthesized starting from 2-amino-5-methylphenol (4).

■ Novel Method for the Synthesis of 2,5-Bisheteroaryl-3,6-dichloro-1,4-benzoquinones

Nelli G. Batenko, Gatis A. Karlivans, and Raimonds E. Valters*

*Faculty of Material Science and Applied Chemistry, Riga Technical University, Azenes St. 14/24, LV-1048, Riga, Latvia

Abstract

A new method for the synthesis of symmetrical and asymmetrical 2,5-bisheteroaryl-3,6-dichloro-1,4-benzoquinones with sulfur and/or nitrogen containing heterocycles has been elaborated on the basis of easily obtainable benzofuran (2).

■ 4-Substituted 3-Methylsulfanyl-5-, 6-, and 8-nitroquinolines from Nitro Derivatives of 4-Substituted 3’-Methylsulfinyl-3,4’-diquinolinyl Sulfides

Magdalena Kosiecka, Andrzej Maslankiewicz,* and Maria J. Maslankiewicz

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

Abstract

Potassium phenoxide reacted with 4-substituted 3’-methylsulfanyl-3,4’-diquinolinyl sulfides (1 or 3) at the substituent at the C4 position. 3’-Methylsulfinyl group promotes nucleophilic substitution of 4’-quinolinyl sulfur bond in sulfoxides (2) and (4) in which case, after treatment with potassium phenoxide, it led to 4-phenoxy-3-methylsulfinylquinoline (9) and 4-substituted 3-quinolinethiolates (5A, 6A or 7A), trapped by methylation to form 4-substituted 3-methylsulfanylquinolines (5a), (6a) and (7a) or their 5-, 6- and 8-nitro derivatives (5b,c), (6b,d) and (7b,d), respectively. Synthesis of 5-, 6- and 8-nitro-3-methylsulfanyl-4(1H)-quinolinones (10b,c,d) was described.

■ Synthesis of Quinoxaline 1,4-Dioxides from 5,6-Diethylbenzofuroxan on Silica Gel

Nobuo Sekimura, Hiroaki Saito, Shinichi Miyairi, and Tohru Takabatake*

*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan

Abstract

5,6-Diethylbenzofuroxan (1) and 5-ethylbenzofuroxan (2) were synthesized in good yield via oxidation of o-nitroanilines by sodium hypochlorite. 4-Ethylbenzofuroxan (3) was prepared by the photochemical decomposition of 2-ethyl-6-nitrophenyl azide (3N). ¹H-NMR spectrum showed that the compound (3) rapidly rearranges between the two unsymmetrical bicyclic structures at 296.8 K. The 4-ethyl group may possibly function as a barrier against molecular rearrangement. Quinoxalines yields depended on the enol content in β-keto esters or 1,3-diketones. A comparison of the reactivity of 1 with benzoylacetone was made with that of other benzofuroxans. The reaction of 1 condensed with the carbonyl compound better than other benzofuroxans.

■ Synthesis and Reactivity of N-Vinyl-1,2,3-dithiazolimines

Vladimir N. Yarovenko,* Andrey A. Es’kov, Pavel A. Kondrashev, Anatolii V. Ignatenko, Igor V. Zavarzin, Lidia G. Vorontsova, Igor P. Sedishev, Mikhail M. Krayushkin, and Zoya A. Starikova

*N. D. Zelinsky Institute of Organic Chemistry, Russia Academy of Science, Leninsky Prospekt 47, Moscow 119991, Russia

Abstract

A reaction of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) (1) with aziridines (2a-d) affords the N-vinyl-1,2,3-dithiazolimines (3a-d), which can be transformed into thiazole derivatives.

■ Concise Formal Synthesis of (S)-Gregatin B

Keizo Matsuo,* Masaru Kanayama, Jinyi Xu, Rie Takeuchi, Keiji Nishiwaki, and Yukihiro Asaka

*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

(S)-3-Acetyl-5-[(1E,3E)-1,3-hexadienyl]-4-hydroxy-5-methyl-2(5H)-furanone, known precursor for the synthesis of (S)-gregatin B, was synthesized in a fewer steps and higher overall yield starting from (R)-lactic acid.

■ Facile Synthesis of 2-Substituted 4H-1,3-thiazines and 3-Substituted 1,2-Isothiazoles via Benzyne Intermediates

Ramadas Sathunuru, Hongming Zhang, Chrles W. Rees, and Edward Biehl*

*Chemistry Department, Southern Methodist University, Dallas, TX 75275-0314, U.S.A.

Abstract

Substituted 2-dialkylamino-4H-1,3-benzothiazines were Synthesizedby the reaction of (phenyl)[o-(trimethylsilyl)aryl]iodonium triflates and dialkyl-aminothiazadienes in the presence of 1.5 equivalent of Bu₄NF. However, when these reactions were carried out in the presence of 4 equivalents of Bu₄NF, 3-substituted 1,2-benzisothiazoles were obtained. Additionally, the reaction of phenyl[(3-trimethylsilyl)-2-naphthyl]iodonium triflate with dialkylaminothia-zadienes in the presence of Bu₄NF gave 3-substituted 1,2-naphthisothiazoles. A possible mechaism for the latter reaction involving the trapping of a benzyne intermediate with a nitrile sulfide generated in situ by the reaction of dialkylaminothiazadiene, fluoride ion and trimethylsilyl fluoride is proposed.

■ Synthesis and Properties of 3-Arylcyclohepta[4,5]pyrrolo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and Related Compounds: Photo-induced Autorecycling Oxidation of Amines

Makoto Nitta,* Tomoyuki Morito, Yuhki Mitsumoto, and Shin-ichi Naya

*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

3-Phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]pyrrolo[1,2-a]-1,3,5- triazine-2,4(3H)-diones and the corresponding arylimino derivatives (5a,b) and (6a,b) were synthesized by the reaction of (1-azaazulen-2-yl)imino- triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. Related cation (11a), which was derived from methylation of 5a, is also prepared. The electrochemical reduction of these compounds exhibited more negative reduction potentials as compared with the related compounds. Some of these compounds underwent a photo-induced autorecycling oxidation toward some amines to give the corresponding imines in more than 100% yield.

■ A Short-step Convenient Synthesis of 2-Phenylbenzofuran from 3-Phenylcoumarin

Takeshi Kinoshita* and Koji Ichinose

*Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko-machi, Tsukui-gun, Kanagawa 199-0195, Japan

Abstract

The reaction mechanism of chemical conversion of (E)-β-[2-hydroxylphenylethylene]benzeneethanol into 2-phenylbenzofuran by DDQ, which involves loss of one carbon unit, was characterized and described. Five naturally occurring 2-phenylbenzofurans of not only the isoflavonoid but also stilbenoid origin were synthesized by use of this chemical scheme, which proved that this new scheme is a useful tool for quick synthesis of 2-phenylbenzofurans.

■ Flavone C-Glycosides from Isatis tinctoria Leaves

Yongxian Cheng, Bernd Schneider, Christine Oberthür, Heidemarie Graf, Sven Adler, and Matthias Hamburger*

*Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland

Abstract

Two new flavone C-glycosides, chrysoeriol 6-C-β-D-glucopyranosyl- (1→3)-β-glucopyranoside (1) and apigenin 6-C-β-D-glucopyranosyl-(1→3)-β-glucopyranoside (2) were isolated from a methanolic extract of Isatis tinctoria leaves and identified on the basis of spectral analysis and hydrolysis. Two known flavone C-glycosides, isoscoparin (3) and isovitexin (4), were also identified.

■ Synthesis of Ditopic Oligopyridines Using the Suzuki Coupling Reaction

Dirk Sielemann, Andreas Winter, and Nikolaus Risch*

*Chemistry Department, Faculty of Science, Paderborn University, Warburger Str. 100, 33098 Paderborn, Germany

Abstract

The synthesis of various bridged oligopyridines using the Suzuki cross-coupling reaction is reported. It is shown that these ditopic derivatives are versatile ligands for complexation reactions with diverse metal ions, such as Ru(II) and Pt(II).

■ A Convenient New Synthesis of 1,2-Diarylpyrroles from 3-Ethoxycarbonyl-4-oxo-4-phenylbutyraldehyde

Aurélie Delayen, Laurence Goossens, Raymond Houssin, and Jean-Pierre Hénichart*

*Institut de Chimie Pharmaceutique, Albert Lespagnol, Université de Lille 2, 3, rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France

Abstract

An efficient four-step synthesis of ethyl 1,2-diaryl-3-pyrrole carboxylates (4), an isomeric scaffold of pharmacologically active natural products, is reported. The key synthon 3-ethoxycarbonyl-4-oxo-4-phenylbutyraldehyde (3), whose new synthesis is detailed here, reacts conveniently with anilines to create the pyrrole ring.

■ Synthesis and Characterization of Bisindole-7,7’-dichloro-2,2’-diethoxycarbonyl-5,5’-bis-1H-indole

Zeghough Djidel,* Laib Nouari, Ouali Dehimi, Latelli H’mida, and Saadi Hocine

*Laboratory of Oragnic Synthesis ad Phytochemistry, M’sila University, P.O.Box 859, M’sila 28000, Algeria

Abstract

3,3’-Dichlorobenzidine is used for the preparation of 7,7’- dichloro-2,2’-diethoxycarbonyl-5,5’-bis-1H-indole. This was accomplished by converting the diamine to the diazonium salts. Reduction of this diazonium salts afforded dihydrazine which was condensed with ethyl pyruvate to give dihydrazone that is separated on column chromatography to provide the following isomers: syn-syn, syn-anti and anti-anti. Cyclization of the dihydrazone using polyphosphate ester gave 7,7’-dichloro-2,2’- diethoxycarbonyl- 5,5’- bis-1H-indole.

■ Three New Xanthones from the Roots of Securidaca inappendiculata

Li-jie Zhang,* Xue-dong Yang, Li-zhen Xu* and Shi-lin Yang

*Institute of Medical Plant Development, Chinese Academy of Medical Sceinces and Peking Union Medical College, Xibei Wang, Hai-Dian District, Beijing 100094, China

Abstract

Chemical investigation on the roots of Securidaca inappendiculata resulted in the isolation of three new xanthones, Securixanthones E, F and G. Their structures were characterized as 7-hydroxy-1,2-dimethoxyxanthone (1), 1,7-dihydroxy-2-methoxyxanthone (2), 3,7-dihydroxy-1,2,8-trimethoxyxanthone (3), respectively, on the basis of spectral evidence.

■ Synthesis of a New Family of Ligands with Bispyrazole Structure. Reactivity of Bispyrazolylmethyl Ethers

Pérez-Mayoral Elena, García-Amo María, López-Larrubia Pilar, Cerdán Sebastián, and Paloma Ballesteros*

*Instituto Universitario de Investigación, UNED, Senda del Rey 9, s/n, E-28040 Madrid, Spain

Abstract

We report the synthesis of a new family of chelating ligands containing bispyrazole structure. Some of them undergo an unusual reactivity when they react with methyl iminodiacetate. We propose a tentative mechanism that probably involves 4-chloromethylpyrazoles and the corresponding alcohols as reaction intermediates. The corresponding Gd-complexes exhibit interesting relaxivity properties being potential paramagnetic contrast agents.

■ Formal Synthesis of Epibatidine

Meng-Yang Chang* and Hua-Ping Chen

*Department of Applied Chemistry, National University of Kaohsiung, No. 700 Kaohsiung University Rd., Nan-Tzu District, Kaohsiung 811, Taiwan, R.O.C.

Abstract

A straightforward formal synthesis of epibatidine has been established starting from trans-(2S,4R)-4-hydroxyproline.

■ Interlocked Molecules Containing Quaternary Azaaromatic Moieties

Wanda Sliwa* and Teresa Zujewska

*Institute of Chemistry and Environmental Protection, Jan Dlugosz University of Czestochowa, Armii Krajowej 13/15, 42-201 Czestochowa, Poland

Abstract

In the first part of the review examples of rotaxanes bearing quaternary azaaromatic moieties are presented, followed by examples of catenanes, shown in the second part. Among rotaxanes those containing tetracationic cyclophane, crown ether unit or other rings, such as cyclodextrins, cucurbiturils and calixarenes are described.

■ Recent Advances in Macrosphelide Synthesis

Yuji Matsuya and Hideo Nemoto*

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

Natural macrosphelides are known as potent cell-cell adhesion inhibitors, which have novel three ester linkages in their 16-membered macrocyclic skeleton. In this review, recent synthetic studies of macrosphelides and relating compounds are surveyed, mainly including our approaches.