HETEROCYCLES

■ Condensation of 2-Hydroxytryptamine with Dimethyl 4-Ethyl-4-formylpimelane

Esahak Ali, Pulak K. Chakraborty, and Satyesh C. Pakrashi

*Indian Institute of Chemical Biology, Calcutta-700 032, India

Abstract

Condensation of 2-hydroxytryptamine (1) with dimethyl 4-ethyl-4-fomylpimelate (2) yielded the stereoisomeric oxindoles, 8A, 8B, 8C, and 8D which were separated and their stereochemistry assigned. The compounds 8A-D or their N-methyl derivatives, 5A-D could be selectively reduced to the oxindole-amines 9 or 3 by treatment with phosphorus oxychloride followed by sodium borohydride but the amines were isomerised under the reaction condition.

■ A Novel Procedure for the Reduction of Epoxides with Sodium Borohydride

Kenso Soai, Atsuhiro Ookawa, Hidekazu Oyamada, and Masako Takase

*Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

Epoxides were reduced to alcohols in good to high yield with a reducing system of sodium borohydride-t-butyl alcohol-methanol. The system had an excellent functional group selectivity.

■ Reactions with Thiohydantoins: New Routes for Synthesis of Imidazoquinolines and Imidazo-1,2,4-triazoles

Hamed A. Daboun, Mahfouz A. Abdel Aziz, and Fatma E. A. Yousif

*Department of Chemistry, Faculty of Science, , University of Cairo, Giza, Egypt

Abstract

A new route for synthesis of new imidazoquinazoline derivatives via reaction of anthranilic acid with 4-thiohydantoin, 5-arylidene-4-methylmercaptohydantoins and 5-arylidene-2-ethylmercaptohydantoins is reported. Synthesis and cbaracterization of new imidazo-1,2,4-triazoles via reaction of aldehydes with new 2- and 4-phenylhydrazonohydantoin derivatives is also reported and discussed.

■ Structures of Mahuannin A and B, Hypotensive Principles of Ephedra Roots

Hiroshi Hikino, Nobuyoshi Shimoyama, Yoshimasa Kasahara, Michiko Takahashi, and Chohachi Konno

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Two novel bisflavanols, mahuannin A and B, exhibiting the hypotensive activity have been isolated from the crude drug “mao-kon”, the roots of Ephedra plants. The stereostructures of mahuannin A and B, advanced on the basis of chemical and physical evidence, have been elucidated as those represented by formulas I and II.

■ The Synthesis and Characterisations or Retinoidal 4-Ylidenebutenolidas

Masayoshi Ito, Tsutomu Iwata, and Kiyoshi Tsukida

*Kobe Women’s College of Pharmacy, Motoyamakita, Higashinad, kobe, Hyogo 658, Japan

Abstract

Retinoidal 4-ylidenebutenolides [(5) and (18)] have been synthesised and their spectral characterisations have been described.

■ Synthesis of the Chiral Synthon for the Enantioselective Syntheses of the Eburnamine Type Alkaloids

Seiichi Takano, Masahiro Yonaga, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

A chiral synthon(5) for the syntheses of the medicinally important indole alkaloid (—)-eburnamonine(10) and the related eburnamine type alkaloids has been prepared in a goad yield from the known compound(12) originated from L-glutamic acid or D-mannitol.

■ Highly Regioselective 1,4-Addition of 2-Lithio-2-(2,6-dimethylpiperidino)acetonitrile to α,β-Unsaturated Ketones

Takeshi Wakamatsu, Satoshi Hobara, and Yoshio Ban

*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan

Abstract

2-Lithio-2-(2,6-dimethylpiperidino)acetonitrile, a formyl anion equivalent, readily reacts with α,β-unsaturated cyclic ketones to result in a successful conjugate 1,4-addition.

■ Reactions of 3-(1-Hydroxyethyl)azetidinones with Dialkylaminosulfur Trifluorides

Ching-Pong Mak, Karl Wagner, Christa Mayerl, and Hans Fliri

*Sandoz Research Institute, A-1235 Vieena, Austria

Abstract

Reactions of benzyl 3-(1-hydroxyethyl)-2-oxoazetidine-4-acetate with dialkylaminosulfur trifluorides under various conditions have been investigated. Formation of products was found to be highly dependent on temperature, presence or absence of base, and stereochemistry of the hydroxyethyl group.

■ Kinetically Controlled Alkylation and Protonation of the 2-Oxabicyclo[3.2.1]octan-3-one System

Seiichi Takano, Ken’ichi Masuda, Susumi Hatakeyama, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

Alkylation and protonation of the 2-oxabicyclo[3.2.1]octan-3-one system under the kinetic conditions have been examined.

■ Benzylidene(cyano)benzylamine as a 1,3-Dipole

Otohiko Tsuge and Kazunori Ueno

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

Benzylidene(cyano)benzylamine reacted as an azomethine ylide with DMAD and olefinic dipolarophiles, In most cases, however, the products derived from the initially formed [3 + 2] cycloadducts with the elimination of hydrogen cyanide were obtained.

■ Chemiluminescence of Monocyclic 3,6-Disubstituted Pyridazines: A Model for Luminol Chemiluminescence

Nobutaka Suzuki, Mamoru Kato, Kaniti Sano, and Yasuji Izawa

*Faculty of Engineering, Mie University, 1515 Uehama-cho, Tsu, Mie 514-5807, Japan

Abstract

Several monocyclic 3,6-disubstituted pyridazines (1-5) were oxidized by molecular oxygen under the basic conditions in dimethyl sulfoxide to yield corresponding maleic acids and/or its derivatives with chemiluminescent light emission.

■ Heterocage Compound [1]. Synthesis of Oxacage Tricyclic Systems: Oxabrendane, Oxahomobrendane, Oxaisotwistane, Oxahomoisotwistane and Oxatwistbrendane Skeleton with an Amino Function

Shun Inokuma, Akihiko Sugie, Koichi Moriguchi, Hiromi Shimomura, and Junki Katsube

*Sumitomo Pharmaceuticals Research Center, 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-0022, Japan

Abstract

A series of various oxacage tricyclic systems with versatile functional groups including an amino function were synthesized in order to examine their chemical, physicochemical and biological properties. The synthesis was based on the principle in which construction of the tricyclic systems was conducted by subjecting bicyclo[2.2.1]heptene or bicyclo[2.2.2]octene derivatives with an endo-hydroxyalkyl substituent to intramolecular cyclization.

■ Diazaarynes: 3,4- and 4,5-Didehydropyridazine by Electron Impact and Thermolytic Fragmentation of the Corresponding Dicarboxylic Anhydrides

Francesco De Sio, Stefano Chimichi, Rodolfo Nesi, and Lucia Cecchi

*CNR, Centro di Studio Sulla Chimica e la Struttura dei Composti Eterociclici e lolo Applicazioni, c/o Dipartimento di Chimica Organica “Ugo Schiff”, Università di Firenze, Via Gino Capponi 9, I-50121 Firenze, Italy

Abstract

The new hetarynes (1) and (2) have been advanced as intermediates in the vapour phase both for the electron impact and the pyrolytic fragmentation pattern of pyridazine-3,4- and 4,5-dicarboxylic acid anhydrides (10) and (11), respectively. The presence of a peak at m/e 78 in the mass spectra of these compounds, as well as the formation of the diazanaphthalenes (12) and (13), respectively, from their thermolysis in benzene, appeared to support this proposal.

■ Total Synthesis of (±)-Corynoline and (±)-6-Oxocorynoline

Mark Cushman and Yash Pal Gupta

*Department of Medicinal Chemistry and Molecular Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, 1333 Robert E. Heine Pharmacy Building, West Lafayette IN 47907, U.S.A.

Abstract

The condensation of α-methyl-3,4-methylenedioxyhomophthalic anhydride (7) with piperonylidenemethylamine (8) is utilized as the key step in a total synthesis of (±)-corynoline (1) and (±)-6-oxocorynoline (2).

■ Novel Stereoselective Synthesis of β-Lactams via Episulfonium Ion Intermediate

Masataka Ihara, Keiichiro Fukumoto, and Tetsuji Kametani

*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

A number of monocyclic β-lactams were synthesised by addition of benzenesulfenyl chloride to α,β-unsaturated olefins followed by base treatment in the presence of a phase transfer catalyst. The cyclization proceeds in a stereoselective manner mostprobably via an episulfonium ion intermediate.

■ Total Synthesis of (±)-Abresoline via [3+2]Cycloaddition

Seiichi Takano and Kozo Shishido

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

A total synthesis of (±)-abresoline (1) has been achieved via stereoselective [3+2]cycloaddition of the homoallylic alcohol (2) with 3,4,5,6-tetrahydropyridine 1-oxide.

■ Enantiomeric Synthesis of 2-Allyl-4-hydroxypyrrolidine Framework via Iodine-mediated Reaction

Seiichi Takano, Chiyoshi Kasahara, and Kunio Ogasawara

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The amide (14), prepared from the symmetric amine (12) and a chiral acid, (S)-(—)-proline, furnished a mixture of the epimeric (2S,4R/S)-(—)-2-allyl-4-hydroxypyrrolidine derivatives in good yieid upon reaction with iodine in an aqueous solvent. Chiralities of the both products are established by correlating them to (2S,4R)-(—)-4-hydroxyproline (27).

■ Biomimetic First Synthesis of the Aloenin Aglycon

Gerhard Bringmann and Stephan Schneider

*Organisch-Chemisches Institut, Universität Orléansring, D-4400 Münster, Germany

Abstract

Two approaches to the aglycon (3) of the biologically active bitter glucoside aloenin (2) are described. Especially the second synthesis, closely paralleling its biogenesis, provides a short and efficient first preparative access to this 2-pyrone.

■ Tetracyclic Phenothiazines. VIII. Metal Hydride Reductions of Some 1,2-Dihydro-3-keto-3H-pyrido[3,2,1-kl]phenothiazines

Lal C. Vishwakarma, Vidyadhar M. Paradkar, Arnold R. Martin, and Cor J. Grol

*Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, U.S.A.

Abstract

Aluminum hydride (alane) in ether reduces 1,2-dihydro-3-keto-3H-pyrido[3,2,1-kl]phenothiazines bearing hydrogen, thioether or dimethylaminomethyl substituents at the 2-position to the respective hydrocarbons. In the corresponding 2-carbethoxy derivative (a β-ketoester), the ester group is reduced to a hydroxymethyl or methyl function depending on the amount of reagent and its mode of generation. Reductions with borane in tetrahydrofuran afford mixtures of the corresponding hydrocarbons, alcohols and occasionally alkenes in varying amounts depending on the nature of the 2-substituent.

■ Facile Synthesis of Alkoxyoxazoline-carboxylate from 2-(N-Bromoacetyl)amino-2-alkenoate and Alcohol

Yoshiaki Sato, Yasuchika Yonezawa, and Chung-gi Shin

*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

The one-pot reaction of 2-(N-bromoacetyl)amino-2-alkenoate with sodium alkoxide in alcohol proceeded to give 4-alkoxyoxazoline-4-carboxylate. The structure and the formation mechanism were elucidated by the independent preparation from 2H-azirine-2-carboxylate in three steps.

■ A Spontaneous Ring Closure Reaction as a New Route to Isoquinoline Derivatives

Ole Riis Anderesen and Erik B. Pedersen

*Department of Chemistry, Odense University, Campusvej 55 DK-5230 Odense M., Denmark

Abstract

A spontaneous reaction takes place between benzaldehydes, malononitrile and N-methyl-4-piperidone to yield the compounds 1a-i which can be aromatized to the new dicyano-1,2,3,4-tetrahydroisoquinolinamines 2a-e. Tetrahydro-2,7-naphthyridines 3a,b were also isolated as by-products.

■ Rearrangement of Naphthyl Ethers Promoted by Titanium Tetrachloride. Synthesis of Naphtho[b]furans and 1,2-Dihydronaphtho[b]furans

Mohammad Reza Saidi

*Department of Chemistry, Isfahan University of Technology, Isfahan, Iran

Abstract

Rearrangement of {(β-bromoallyl)naphthalenes and allyl naphthyl ethers promoted by titanium tetrachloride produced naphtho{b}furans and 1,2-dihydronaphtho{b}furans, respectively.

■ Reaction of Phenyltrichloromethane with Semicarbazide and Thiosemicarbazide Derivatives

Hamid M. Hassaneen, Abdelfattah H. Shetta, Nehal M. Elwan, and Ahmad S. Shawali

*Department of Chemistry, Faculty of Science, , University of Cairo, Giza, Egypt

Abstract

Phenyltrichloromethane 1 reacts with 4-phenylsemicarbazide and yields ethyl N-phenylcarbamoylmethane hydrazonate 10. Thermolysis of 10 yields 3,4-diphenyl-1H-l,2,4-triazolin-5-one 9a, identified by its alternate synthesis from the amidrazone 14 and diphenyl carbonate. Hydrazinolysis of 10 and N-ethoxycarbonylbenzhydrazidoyl chloride 13 gives in both cases the tetrahydrotetrazene derivative 12. Reaction of 1 with thiosemicarbazide and its 4-phenyl derivative afforded the corresponding 2-phenyl-1,3,4-thiadiazole derivatives 16a and 16b, respectively.

■ High Pressure Addition Reactions of Some 3a,6a-Diazapentalenes

Kiyoshi Matsumoto, Shiro Hashimoto, Takane Uchida, and R. Morrin Acheson

*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Azacyclazine derivatives were obtained from 1-benzoyl-2-phenyl-3a,6a-diazapentalene with methyl propiolate and alcohols, and from 1,3-dibenzoyl-2-phenyl-3a,6a-diazapentalene with dimethyl acetylenedicarboxylate. The former diazapentalene with diphenylcyclopropenone yielded a pyrazole. These reactions only proceeded at 10 kbar pressure and the products were identified mainly from their ¹H and ¹³C nmr spectra.

■ Cyclodienones. 9. Reaction of 4-Halo-2,4,6-tri-tert-butyl-2,5-cyclohexadien-1-ones with Pyrazoles and Preparation of 1-(2-Hydroxyphenyl)- and 1-(4-Hydroxyphenyl)pyrazoles

Gouki Fukata, Takashi Itoh, and Masashi Tashiro

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

Reaction of 4-halo-2,4,6-tri-tert-butyl-2,5-cyclohexadien-1-one (1) with pyrazoles (8) afforded 4-(pyrazol-1-yl)-2,4,6-tri-tert-butyl-2,5-cyclohexadien-1-one (9), 1-(4-hydroxy-3,5-di-tert-butylphenyl)- and 1-(2-hydroxy-3,5-di-tert-butylphenyl)pyrazoles (10 and 11) together with by-products. De-tert-butylation of 9,10 and 11 was carried out in boiling 85% H₃PO₄ to give the corresponding 1-(4-hydroxyphenyl)- and 1-(2-hydroxyphenyl)pyrazoles (17 and 18) in good yields, respectively.

■ 4-Substituted Azetidinones as Intermediates for Carbapenem Synthesis

Teruo Tanaka and Tetsuo Miyadera

*Chemical Research Laboratories and Analytical & Metabolic Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

Abstract

4-Iodomethylazetidin-2-one (1) was prepared by [2+2]cycloaddition reaction of allyl iodide with chlorosulfonyl isocyanate and utilized for the synthesis of 4-(thiazolin-2-yl)methylazetidin-2-one (3).

■ vic-Iodothiocyanates and Iodoisothiocyanates. Part 6. The Synthesis of Thiirans

Richard C. Cambie, Peter S. Rutledge, Gary A. Strange, and Paul D. Woodgate

*Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand

Abstract

Treatment of the vic-iodothiocyanates of either cyclic or acyclic alkenes with lithium triethylborohydride (‘Super Hydride’) gives thiirans in high yields. The structure of the product from r-1-iodo-1-thiocyanatothyl-c-4-t-butylcyclohexane has been confirmed by an independent synthesis.

■ Azabenzoxazoles: Synthesis of 3-Methylisoxazolo[5,4-c]- and 2-Methyloxazolo[5,4-c]pyridines

Alfredo Camparini, Stefano Chimichi, Fabio Ponticelli, and Piero Tedeschi

*Istituto di Chimica Organica, Università di Siena, Pian dei Mantellini 44, 53100 Siena, Italy

Abstract

A convenient synthesis of 4-acetyl-3-hydroxypyridine is reported; this compound allows the preparation of the new isoxazolo[5,4-c]- and oxazolo[5,4-c]pyridine ring systems.

■ Formation of Exocyclic Terminal Methylene Groups in Piperidine Derivatives

Mervi Hämeilä and Mauri Lounasmaa

*Laboratory of Organic Chemistry, Helsinki University of Technology, P.O. Box 6100,FIN-02015 HUT, Espoo, Finland

Abstract

The preparation of exocyclic terminal methylene groups in piperidine derivatives by LiAlH₄ reduction of appropriate vinylogous urethanes, is described.

■ The Identity of Wang’s and Zhu’s "Nagarine" with Aconifine (10β-Hydroxyaconitine)

S. William Pelletier, Naresh V. Mody, and Chen Szu-ying

*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.