HETEROCYCLES

■ Contents

■ Chemistry of Hydrazonoalkanenitriles

Sayed M. Riyadh,* Ismail A. Abdelhamid, Hamada M. Ibrahim, Hamad M. Al-Matar, and Mohamed H. Elnagdi

*Department of Chemistry, Faculty of Science, Kuwait University, Safat 13060 Kuwait

Abstract

Reactions of arene and heteroaromatics diazonium salts with active methylene compounds having cyano group have been illustrated to afford hydrazonoalkanenitriles with a range of substituents. Structural investigation for hydrazonoalkanenitriles has been made. Furthermore the reactivity of hyrazonoalkanenitriles towards nucleophilic and electrophilic reagents has been displayed.

■ Oxidative Desymmetrization of meso-Cyclic Ethers (2): Recognition of the Core Structure of Substrates of the Mn(salen) Catalyst

Hidehiro Suematsu, Yuusuke Tamura, Hiroaki Shitama, and Tsutomu Katsuki*

*Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan

Abstract

Mn(salen) complexes bearing a binaphthyl chiral unit serve as catalysts for oxidative desymmetrization of meso-cyclic ethers. This study revealed that chiral recognition by the complex is strongly influenced by the core structure of substrates and this recognition is adjusted by an appropriate modification of the binaphthyl unit.

■ Synthesis of Oxathiolone Fused Chalcones Bearing O-Aminoalkyl Side Chain. Comparison of Stability of Isomeric Benzoxathiolones under Alkylation Reaction Conditions

Marek T. Konieczny,* Wojciech Konieczny, Danuta Pirska, Anita Bulakowska, Michal Sabisz, Andrzej Skladanowski, Roland Wakiec, Ewa Augustynowicz-Kopec, and Zofia Zwolska

*Department of Organic Chemistry, Medical University of Gdansk, 80-416 Gdansk, Poland

Abstract

Isomeric, oxathiolone fused chalcones bearing O-aminoalkyl side chain were synthesized by condensation of suitable benzoxathiolones with substituted benzaldehydes. The starting benzoxathiolones were prepared by O-alkylation of corresponding phenols with aminoalkyl chlorides, however, the reaction was often complicated by amino group catalyzed opening of the oxathiolone ring. The obtained chalcones were screened for antimicrobial and cytotoxic activity.

■ Reaction of Hydrazide of (Tetrazol-5-yl)acetic Acid with Isothiocyanates and Antimicrobial Investigations of Newly-Obtained Compounds

Monika Wujec,* Urszula Kosikowska, Piotr Paneth, and Anna Malm

*Department of Organic Chemistry, Medical University, 6 Staszica Str., 20-081 Lublin, Poland

Abstract

In the reaction of hydrazide of (tetrazol-5-yl)acetic acid (1) with isothiocyanate the respective thiosemicarbazide derivatives 2 were obtained. Further cyclization with 2% NaOH led to the formation of 3-[(tetrazol-5-yl)-methyl]-4-substituted-1,2,4-triazoline-5-thione 3. The structures of all new products were confirmed by analytical and spectroscopic methods. Five compounds were screened for their in vitro activity against some species of aerobic bacteria and fungi. Derivatives of 1,2,4-triazoline-5-thione can exist in two major tautomeric forms; thiole and thione. We have established experimentally that all obtained compounds 3, were in the thione form. Geometry optimization of tautomeric forms of 3c and 3f was carried out.

■ Studies Using (E)-6-Oxo-1-aryl-4-(2-N-piperidinyl)vinyl-1,6-dihydropyridazine-5-carbonitrile

Ismail Abdelshafy Abdelhamid,* Said Ahmed Soliman Ghozlan, Heinz Kolshorn, Herbert Meier, and Mohamed Hilmy Elnagdi

*Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt

Abstract

Condensing 1-aryl-4-methyl-1,6-dihydropyridazine-5-carbonitrile with triethyl orthoformate and piperidine afforded the trans-enamine 2. This could be converted into pyrido[3,4-d]pyridazine 3 upon treatment with primary aromatic amines. Reacting 2 with hydrazonoyl chlorides 5 afforded 7 rather than 6. Compound 2 gives also pyrido[3,4-d]pyridazine 10 upon treatment with acetic acid and ammonium acetate. Compound 2 afforded N-aminopyrido[3,4-d]pyridazine 11 upon treatment with hydrazine hydrate. Compound 11 reacted with triethyl orthoformate to give [1,2,4]triazolo[2’,3’:1,2]pyrido[4,3-d]pyridazin-10-one 12 and can be acetylated to 13. Compound 2 could be coupled with p-chlorobenzenediazonium chloride to give the pyridazino[4,5-d]pyridazine 17.

■ Quantum-Chemical Study of 1,2-Bis(dimethylethyleneguanidino)benzenes

Davor Margetic,* Waka Nakanishi, Takuya Kumamoto, and Tsutomu Ishikawa*

*Laboratory for Physical-Organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruder Boskovic Institute, Bijenicka c. 54, 10001 Zagreb, Croatia

Abstract

A series of 1,2-bis(dimethylethyleneguanidino)benzenes, (o-bisguanidinobenzenes) was investigated computationally using quantum-chemical calculations. The basicity of o-bisguanidinobenzenes was evaluated and compared with known molecules, to be comparable to these of neutral superbases such as 1,8-bis(dimethylethyleneguanidino)naphthalene and 1,8-bis(dimethylamino)naphthalene. Investigation of the influence of substituents on the rotational energies of o-bisguanidinobenzenes revealed that employed quantum-chemical calculations showed limited success in estimation of relative order of rotational barriers. Geometries of calculated metal complexes are in good accordance with experimental results. The most basic bidentate compounds form the most stable complexes, correlating basicity and complex stability.

■ Synthesis of 1’-Phenyl Substituted Nucleoside Analogs

Tamer Nasr, Yosuke Taniguchi, and Shigeki Sasaki*

*Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Abstract

1’-Phenyl substituted ribonucleoside analogs with all four nucleobases have been synthesized by the conventional N-glycosidation method.

■ A Stereocontrolled Construction of rel-(7S,8S,7’R,8’S)-7,7’-Epoxylignan Skeleton

Maria Kitamura, Hiromi Hayashi, Masahiro Yano, Tetsuaki Tanaka, and Naoyoshi Maezaki*

*Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-Kita, Tondabayashi, Osaka 584-8540, Japan

Abstract

We have developed a highly diastereoselective route to construct rel-(7S,8S,7’R,8’S)-7,7’-epoxylignan skeleton, wherein stereocontrolled Michael addition to γ-oxyenone intermediate and subsequent α-alkylation to the resulting ketone are keys to the synthesis.

■ Synthesis of 8-Substituted 12-Methyl-12H-imidazo[4’,5’: 2,3][1,4]diazepino[6,7,1-jk]carbazoles

Kayed A. Abu Safieh, Fouad H. Darras, Mikdad T. Ayoub, Mustafa M. El-Abadelah, Salim S. Sabri, and Wolfgang Voelter*

*Interfakultaeres Institut fuer Biochemie, Universitaet Tuebingen, Hoppe-Seyler Strasse 4, D-72076 Tuebingen, Germany

Abstract

A synthesis of model 8-substituted-12-methyl-12H-imidazo[4’, 5’: 2,3][1,4]-diazepino[6,7,1-jk]carbazoles (10a-c), based on the classical Bischler-Napieralski method, is described. Thus interaction of carbazole with 5-chloro-1-methyl-4-nitro-1H-imidazole (in the presence of sodium hydride) produced the corresponding 9-(1-methyl-4-nitro-1H-imidazole-5-yl)-9H-carbazole (7). Chemical reduction of the nitro group of 7 into the respective amino derivative 8, and subsequent acylation of the resulting amino group furnished the respective amides 9a-c. Cyclocondensation of the latter amides, using polyphosphoric acid under Bischler-Napieralski reaction conditions, delivered the target compounds 10a-c. The structures of these new pentacyclic heterocycles were supported by IR, MS, and NMR spectral data.

■ Microwave-Assisted Synthesis of N-2-Benzyl-3-(4-ethoxycarbonylphenyl)indazole Derivatives

Hua-Sin Chen, Li-Jiau Huang, Fung Fuh Wong,* Fang-Yu Lee, Che-Ming Teng, and Sheng-Chu Kuo*

*Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91 Hsueh-Shih Rd. Taichung, Taiwan 40402, R.O.C.

Abstract

The microwave-assisted synthesis for promoting N-2 substituted indazoles as the major products were successfully developed by treating 3-(4-ethoxycarbonylphenyl)indazoles with various substituted benzyl chloride (benzyl, o-chlorobenzyl, m-chlorobenzyl, and p-chlorobenzyl chloride) in the presence of two equivalents of triethylamine. The result was better than two trandional methods including the directly substitution with benzyl chloride and Mitsunobu reaction with benzyl alcohol.

■ Preparation of (R)-(+)-3-Phenyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ylium Bromide: Synthesis of (S)-(+)-Coniine, (R)-(-)-Coniceine and (R)-(+)-Anabasine

Alejandro Castro, Johana Ramírez, Jorge Juárez,* Joel L. Terán,* Laura Orea, Alberto Galindo, and Dino Gnecco

*Organic Synthesis Laboratory, Chemistry Centre, Science Institute, BUAP, Building 194, Science Complex, City University, 72570, Puebla, Pue., México

Abstract

We describe the transformation of (R)-(-)-1-(2’-hydroxy-1’-phenylethyl)piperidin-2-one 1 into (R)-(-)-3-phenyl-2,3,5,6,7,8-hexahydrooxazolo[3,2-a]pyridin-4-ylium bromide 2 using POBr₃. Reduction of 2 with Red-Al at -78 °C gave (3R,8aR)-(-)-3-phenylhexahydro-2H-oxazolo[3,8-a]pyridine 3 as a single diastereoisomer. The synthetic potential of these transformation is illustrated by the enantiopure synthesis of (S)-(+)-coniine, (R)-(-)-coniceine and (R)-(+)-anabasine.

■ 7,11-Diaryl-2,4-diazaspiro[5.5]undecane-1,5,9-triones: A New Series of Spiroheterocycles

Jitender M. Khurana,* Reema Arora, and Sarishti Satija

*Department of Chemistry, University of Delhi, Delhi-110007, India

Abstract

A novel two step synthesis of 7,11-diaryl-2,4-diazaspiro[5.5]undecane-1,5,9-triones has been reported based on double Michael addition of 2-thiobarbiturates or N,N’-diaryl-2-thiobarbiturates with dibenzalacetones followed by reductive desulfurization with nickel boride.

■ A New Method for the Synthesis of Pyrrolo[1,2-a]quinolines Based on Boron Trifluoride-Mediated Cyclization of 1-(2-Oxiranylphenyl)pyrroles

Kazuhiro Kobayashi,* Atsushi Takanohashi, Yasutoshi Himei, Takehiko Sano, Shuhei Fukamachi, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A simple synthesis of pyrrolo[1,2-a]quinolines carrying no substituent at all of the 1- to 5-positions based on boron trifluoride-mediated cyclization of 1-(2-oxiranylphenyl)pyrroles, which can be easily prepared from 2-(pyrrol-1-yl)benzaldehydes, is described.

■ Al₂O₃/MeSO₃H (AMA) as a Novel Heterogeneous System for Synthesis of Coumarins under Mild Conditions

Hashem Sharghi* and Mahboubeh Jokar

*Department of Chemistry, Shiraz University, Shiraz, 71454, I.R.Iran

Abstract

Al₂O₃/MeSO₃H (AMA) is found to be an efficient reagent for the Pechman condensation reaction of phenols and β- ketoesters under solvent free conditions. The reaction protocol is simple, cost- effective, solvent free and gives good isolated yield with high purity and good regioselectivity.

■ The Synthesis of Trans-A₂B-Corroles Bearing Acridine Moiety

Mariusz Tasior and Daniel T. Gryko*

*Institute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52,01-224 Warsaw, Poland.

Abstract

Three new acridine-corroles were synthesized. For the synthesis of dyad with acridine directly attached at position 10 of corrole core the new procedure has been developed which can be used for other sterically hindered aldehydes bearing basic nitrogen atoms.