HETEROCYCLES

■ Contents

■ The Hydrogenation of Heterocyclic Calix[4]arenes, a Transformation Leading to Novel Macrocyclic Ligands

Guillaume Journot, Christopher R. Jones, Valeria Blangy, and Reinhard Neier*

*Department of Chemistry, University of Neuchâtel, Avenue de Bellevaux 51, Case Postale 2, CH-2000 Neuchâtel, Switzerland

Abstract

The simple and efficient synthesis of calix[4]furan and calix[4]pyrrole has been known for more than 125 years. The connectivity of the heterocyclic calix[4]arenes is identical with the skeleton of the «pigments of life». The chemical properties, especially the ability to form complexes with transition metals, are totally different when comparing the artificial systems with the natural products. A direct way to confer metal binding capabilities to compounds derived from heterocyclic calix[4]arenes is the hydrogenation. We review the known hydrogenation reactions of calix[4]furan and calix[4]pyrrole and present our own work in this field. A short description of the metal binding process of our new calix[4]pyrrolidines (= the fully saturated calix[4]pyrrole) with copper will be discussed as a typical example of the metal binding capacities. The new calix[4]pyrrolidines can be structurally classified as new stiffened macrocyclic crown ethers or as saturated analogues of the porphyrin derived «pigments of life».

■ Cyclic Triolborate Salts: Novel Reagent for Organic Synthesis

Yasunori Yamamoto*

*Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Kita 13 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan

Abstract

This review summarizes metal-catalyzed C-C and C-N bond-forming reactions using novel heteroaryltriolborate salts for palladium- or copper-catalyzed cross-coupling reactions with arylhalides or amines and for rhodium-catalyzed addition reactions to α,β-unsaturated carbonyl compounds or imines.

■ Synthesis, Structure, and Theoretical Calculations of a Furan-Based Molecular Wire, N-[4-(2-Furanylmethyleneamino)benzylidene]furan-2-amine

Nathan C. Tice,* Jennifer R. Armstrong, Jeremy B. Maddox, Sarah A. Ward, Chad A. Snyder, and Jason O. E. Young

*Department of Chemistry, Butler University, 4600 Sunset Avenue, Indianapolis, IN, 46208, U.S.A.

Abstract

The formation of the furanyl aryl imine N-[4-(2-furanylmethyleneamino)benzylidene]furan-2-amine (1) was accomplished by the condensation of furfural with 1,4-benzenediamine. The structure of the dimine 1 was confirmed by X-ray crystallographic analysis and displayed the expected, “zigzag” or trans conformation about the imine bond. Quantum chemistry calculations were carried out to model the electronic and molecular structure of 1 and to corroborate experimental characterizations.

■ 1,3-Dipolar Cycloaddition of Ethyl Diazoacetate with (E)-3-Arylidenechroman-4-ones. A New Access to Spirocyclopropane Derivatives

Nadia Wannassi, Hanene Jelizi, Mohamed El Baker Rammah, Kabula Ciamala,* Michael Knorr, Karin Monnier-Jobé, Yoann Rousselin, Marek M. Kubicki, and Carsten Strohmann

*Institute of UTINAM UMR CNRS 6213, Faculty of Science and Technology, University of Franche-Comté, 16 Route de Gray, F-25030 Besançon, France

Abstract

(E)-3-Arylidenechroman-4-ones 1a–e (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-MeSC6H4, p-ClC6H4) react regioselectively (100%) with ethyl diazoacetate 2 in refluxing toluene to afford in good yields spiro-Δ2-pyrazolines ethyl 4’-oxo-4-aryl-spiro[chromanone-3’,5-pyrazole]-3-carboxylate 3a–e. The occurrence of Δ1-pyrazolines as reaction intermediates has been evidenced. The regio- and stereochemistry of spiranic compounds 3a-e has been established on the basis of spectroscopic data and elemental analyses, corroborated by a single crystal X-ray crystallographic analysis of one product 3a. The spiro-adducts 3a–e were brominated by NBS to give spirocyclic-substituted 3-bromo-4,5-dihydro-3H-pyrazoles 4a–e. The latter compounds evolve straightforwardly N2 in refluxing toluene to afford substituted spirocyclic 1-bromocyclopropane-1-carboxylates. The molecular structure of cyclopropane derivative 5e has been determined by means of a single-crystal X-ray diffraction study.

■ Recoverable and Reusable Catalyst for the Reaction of N-Tosyl Imines with Pyrrole: Synthesis of meso-Tetraarylporphyrins

Baris Temelli* and Saadet Seyma Ozdemir

*Department of Chemistry, Hacettepe University, 06800 Beytepe, Ankara, Turkey

Abstract

The direct and efficient synthesis of meso-substituted porphyrins from the reaction of N-tosyl imines with pyrrole in the presence of environmentally friendly catalysts, Cu(OTf)2 and Montmorillonite K-10 clay, is described. The advantages of the new method include mild reaction conditions and using environmentally friendly catalysts which can be recovered and reused after the reactions without any significant loss of catalytic activity.

■ Microwave-Assisted Synthesis of Substituted Naphtho[2,3-c]furan-1,3-dione Derivatives

Tomikazu Kawano,* Yu Ishikawa, and Minoru Hatanaka

*Department of Medicinal and Organic Chemistry, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Iwate 028-3694, Japan

Abstract

The self-condensation reaction of substituted phenylpropiolic acid derivatives (5a-d) by microwave irradiation at 100 °C for only three minutes proceeded smoothly to give substituted naphtho[2,3-c]furan-1,3-dione derivatives (1a-d) as single products in moderate to good yields, respectively.

■ Synthesis and Tuberculostatic Activity of Novel Diverse Heterocyclic Compounds Derived from Heterocyclic Carbohydrazides and Methyl 2-Heteroaroylhydrazinecarbodithioates

Katarzyna Gobis,* Henryk Foks, Ewa Augustynowicz-Kopeć, and Agnieszka Napiórkowska

*Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. Hallera 107, 80-416 Gdańsk, Poland

Abstract

A series of 1,3,4-oxadiazole-2-thiones (4, 5), 2-methylthio-1,3,4-thiadiazoles (15, 16) and 1,2,4-triazole-3-thiones (17-32) have been synthesized using high reactivity of various methyl 2-heteroaroylhydrazinecarbodithioates, that underwent cyclization in alkaline or acidic solution. Reaction of 4-(2-(methylthiocarbonothioyl)hydrazine) carbonyl)pyridine 1-oxide with morpholine led to 4-(5-morpholino-1,3,4-oxadiazol-2-yl)pyridine 1-oxide (11). 2-Methylthio-1,3,4-oxadiazoles (12-14) were obtained by the methylation of 1,3,4-oxadiazole-2-thiones (1, 4, 5) in alkaline solution. 1,2,4-Triazole-3-thiones (21-23, 31) obtained in reaction with aminoalcohols gave 1,2,4-triazolo[3,4-b][1,3]thiazines when refluxed in conc. HCl. The obtained compounds were tested in vitro towards Mycobacterium tuberculosis standard strain (H37Rv) and two “wild” strains, susceptible (Spec. 192) and resistant (Spec. 210).

■ Synthesis of 3-Substituted 4-Sulfanyl-8-methoxyisoquinolin-1(2H)-ones by the Reaction of Ethyl 2-[Lithio(sulfanyl)methyl]-6-methoxybenzoates with Aliphatic and Aromatic Nitriles

Kazuhiro Kobayashi,* Hiroo Hashimoto, and Kazuhiro Nakagawa

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

Abstract

A convenient method for the synthesis of 3-substituted 4-alkyl(or aryl)sulfanyl-8-methoxyisoquinolin-1(2H)-ones has been developed. Ethyl 2-(alkyl(or aryl)sulfanyl)methyl-6-methoxybenzoates, prepared by the reaction of readily available ethyl 2-halomethyl-6-methoxybenzoates with sodium thiolates, are deprotonated on treatment with lithium diisopropylamide (LDA) to generates the corresponding benzyl anions, which react cleanly with a variety of nitriles to provide generally good yields of the corresponding desired isoquinolin-1(2H)-ones.

■ Halenaquinone Derivatives from Tropical Marine Sponge Xestospongia sp.

Yeon-Ju Lee, Chang-Kwon Kim, Song-Kyu Park, Jong Soon Kang, Jong-Seok Lee, Hee Jae Shin, and Hyi-Seung Lee*

*Marine Natural Products Laboratory, Korea Ocean Research & Development Institute, Ansan PO Box 29, Ansan 426-744, Korea

Abstract

Chemical investigations of the tropical marine sponge of the genus Xestospongia have resulted in the isolation of a new halenaquinone derivative named xestosaprol N (8) together with known metabolites. Their structures were elucidated on the basis of mass spectrometry and detailed 2D NMR spectroscopic data.

■ Synthesis and Crystal Structure of Novel Chiral N-Dichloroacetyl-2-substituted-5-methyl-1,3-oxazolidines

Shuang Gao, Ying Fu, Li-Xia Zhao, Zhi-Yong Xing, and Fei Ye*

*Department of Applied Chemistry, College of Sciences, Northwest Agricultural University, Harbin 150030, Heilongjiang, China

Abstract

Chiral 1-amino-2-propanols 4-5 were prepared by racemic 1-amino-2-propanol and chiral tartaric acid. Then, chiral N-dichloroacetyl-2-substituted-5-methyl-1,3-oxazolidines 6-11 were synthesized by the reaction of chiral 1-amino-2-propanol with ketone and dichloroacetyl chloride. The structures of the compounds were characterized by IR, 1H NMR, 13C NMR, MS and elemental analysis. The configuration of 7 was determined by X-ray crystallography.

■ Novel Synthesis of 1,4-Phenylene Bridged Bis-Heterocyclic Tropone Compounds

Yang Li, Feng Li, and Wentao Gao*

*Institute of Superfine Chemicals, School of Chemistry and Chemical Engineering, Bohai University, 19 Keji Road, Jinzhou 121000, China

Abstract

A facile synthesis of novel 1,4-phenylene bridged bis-isoxazolo-, pyrazolo-, and pyrano-fused tropone compounds (2-6) is described, involving the cyclization reaction of 3,3’-{1,4-phenylenebis[(1E)-3-oxoprop-1-ene-1,3-diyl]} bis(tropolone) (1) with hydroxylamine hydrochloride, aromatic hydrazine hydrochlorides, and I2/DMSO/H2SO4 system, respectively. The substrate 1 was obtained via the Claisen-Schmidt condensation reaction between 3-acetyl-tropolone and terephthalaldehyde.

■ A Facile Synthesis of 2-Arylthiochroman-4-ones by the Reaction of 3-Aryl-1-(2-halophenyl)prop-2-en-1-ones with Sodium Hydrogensulfide

Kazuhiro Kobayashi,* Akihiro Kobayashi, and Miyuki Tanmatsu

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

Abstract

An efficient two-step procedure for the preparation of 2-arylthiochroman-4-ones has been developed. Thus, 3-aryl-1-(2-halophenyl)prop-2-en-1-ones, prepared by the condensation between 1-(2-halophenyl)ethanones and aromatic aldehydes in ethanol at room temperature, were treated with sodium hydrogensulfide in DMF at 80 ˚C to give 2-arylthiochroman-4-ones in good overall yields.

■ New Type of Matrix for Analysis of Low Molecular Weight Compounds by MALDI-TOF MS

Masamichi Nakakoshi,* Natsumi Funakoshi, Hiroki Nakajima, and Masayoshi Tsubuki*

*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Matrix for analysis of low molecular weight compound by MALDI-TOF MS was investigated. We found the new type of matrix, 5-aryl-1H-tetrazoles, which are suitable for the detection of low molecular weight compound ions. When propranolol hydrochloride was measured with 5-aryl-1H-tetrazoles, the strong matrix-derived peaks are not detected in low mass range.

■ Synthesis of Neoamphimedine

Shinsuke Nakahara,* Yoshio Mukai, and Akinori Kubo

*Meiji Pharmaceutical University, 2-552-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

The synthesis of neoamphimedine (from Xestospongia sp.), which is a potent antitumor agent both in vitro and in vivo, also can induce topoisomerase II-mediated catenation of plasmid DNA in vitro. The synthesis was achieved in twelve steps from 2,5-dimethoxyphenethylamine in 6% overall yield.