HETEROCYCLES

■ Contents

■ Synthesis of Furazane Conjugated New Heterocycles

Renaud Beaudegnies* and Sebastian Wendeborn

*Syngenta Crop Protection AG, Optimization Chemistry, CH-4002 Basel, Switzerland

Abstract

An improved route for the synthesis of 3-(4-aminofurazane-3-yl)-1,2,4-oxadiazole heterocycles using micro-wave irradiation is reported. The preparation of novel 4-(thiazol-4-yl)furazan-3-ylamine, 4-(pyrimidin-4-yl)furazan-3-ylamine and, 4-(pyrazolidin-3-yl)furazan-3-ylamine heterocycles are described.

■ Hydrothermolysis of the Fully Benzylated α-Cyclodextrin

Takashi Yamanoi,* Naoshi Inoue, Masaki Fujimoto, Hideaki Sasaura, and Akihiko Murota*

*The Noguchi Institute, 1-8-1, Kaga, Itabashi-ku, Tokyo 173-0003, Japan

Abstract

The treatment of the fully benzylated α-cyclodextrin with the hot compressed mixed solvent of dioxane/water (v/v=1/1) at 270 °C and 150 kg/cm² for 40 min afforded 2,3,6-tri-O-benzyl-D-glucopyranose in good yield. The hydrothermolysis of the fully benzylated α-cyclodextrin at 240 °C produced partially benzylated maltooligosaccharide derivatives.

■ Concise Synthesis of Pyrrolophenanthridine Alkaloids Using a Pd-Catalyzed Biaryl Coupling Reaction with Regioselective C-H Activation

Takashi Harayama,* Akihiro Hori, Hitoshi Abe, and Yasuo Takeuchi

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

The concise synthesis of the pyrrolophenanthridine alkaloids such as anhydrolycorine, assoanine, anhydrolycorin-7-one, and oxoassoanine, was achieved using the Pd-catalyzed biaryl coupling reaction of 1-(2-halobenzyl)-2,3-dihydroindole by applying the regioselective C-H activation method with intramolecular coordination of the benzylamino group to Pd.

■ Efficient Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones over Silica Sulfuric Acid as a Reusable Catalyst under Solvent-free Conditions

Peyman Salehi,* Minoo Dabiri, Mohammad Ali Zolfigol, and Mohammad Ali Bodaghi Fard

*Department of Phytochemistry, Aromatic and Medicinal Plants and Drug Research Institute, Shahid Beheshti University, Evin, Tehran 19835-389, Iran

Abstract

3,4-Dihydropyrimidin-2(1H)-ones and their sulfur analogues are efficiently synthesized by the three-component condensation of β-dicarbonyl compounds, aromatic and aliphatic aldehydes, and urea or thiourea in the presence of catalytic amounts of silica sulfuric acid under solvent-free conditions in high yields. The catalyst is recyclable and can be used several times without any decrease in the products yields.

■ Synthesis of 5-Substituted Indole Derivatives. Part 4: Naratriptan from α-Anilinoacetaldehyde Dimethylacetal by TiCl₄-Mediated Cyclisation

Béla Pete,* Gyula Simig, László Poszávácz, and László Toke

*Research Group of the Hungarian Academy of Sciences, Department of Organic Chemical Technology, Technical University of Budapest, H-1521 Budapest, Hungary

Abstract

N-Methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulfonamide (Naratriptan, 2) was prepared from N-methyl-N-phenylmethyl-2-(4-aminophenyl)-ethanesulfonamide (3b) through reductive alkylation with dimethoxyacetaldehyde followed by N-acylation and TiCl₄-mediated indolisation, according to Sundberg procedure. The isopropyl group proved to be a useful protecting group for sulfonate esters in a number of transformations but was cleaved in the presence of TiCl₄.

■ Highly Fluorescent Heterocycles Based on Pyrazino Fused 1,4,5,8-Tetraazafulvalenes

Christian Käpplinger, Rainer Beckert,* Jan Koci, Gabriela Braunerova, Karel Waisser, and Helmar Görls

*Institute for Organic and Macromolecular Chemistry, Friedrich Schiller University, Lessingstr. 8, D-07743 Jena, Germany

Abstract

Some new pyrazino-fused 1,4,5,8-tetraazafulvalenes of type (3-5) were synthesized and their structures were confirmed by IR, UV-VIS, ¹H NMR spectra and elemental analysis. The X-Ray crystal structure analysis of a single crystal of derivative (3c) revealed a nearly ideal planarized heterofulvalene subunit. The new prepared tricyclic tetraazafulvalenes of type (3) show strong red fluorescence at 605 nm.

■ 5-Alkynyl-4-chloro- and 4-Alkynyl-5-chloro-2-methylpyridazin-3(2H)-ones: Convenient Precursors for the Preparation of 2-Substituted Pyrrolo[2,3-d]pyridazinones

Omar R’kyek, Bert U. W. Maes, Guy L. F. Lemière,* and Roger A. Dommisse

*Department of Chemistry, University of Antwerp (RUCA), Groenenborgerlaan 171, B-2020 Antwerp, Belgium

Abstract

A new synthetic route towards the synthesis of 1,6-dihydro-7H-pyrrolo[2,3-d]pyridazin-7-ones (10a-f) and their regioisomers 1,5-dihydro-4H-pyrrolo[2,3-d]pyridazin-4-ones (9a,b) is described, based on the reaction of 5-alkynyl-4-chloro- (7a,b) and 4-alkynyl-5-chloropyridazinones (8) with different amines (ammonia, methylamine and propylamine) followed by a treatment with a NaOEt solution.

■ A Stereoselective Approach to Both 3,4-trans-Disubstituted Pyrrolidin-2-ones and Pyrrolidines. A Convenient Synthesis of (3R,4R)-4-Benzyl-3-pyrrolidinecarboxylic Acid

Roberta Galeazzi, Gianluca Martelli, Giovanna Mobbili, Mario Orena,* and Maria Panagiotaki

*Dipartimento di Scienze dei Materiali e della Terra - Università Politecnica delle Marche, Via Brecce Bianche, I-60131 Ancona, Italy

Abstract

Chiral 4-alkyloxymethyl- and silyloxymethylpyrrolidin-2-ones, (10a-c), underwent alkylation to give the corresponding 3,4-trans-disubstituted pyrrolidin-2-ones, (11a-g), in good yield and total stereoselection, as shown by ¹H NMR spectral data and n.O.e. experiments. Moreover compounds (11a-c) were converted into the corresponding 3,4-trans-disubstituted pyrrolidines, (12a-c). Removal of the chiral auxiliary from 12a, followed by protection of the nitrogen with t-Boc group, led to the corresponding derivative (13). Cleavage of the benzyl ether and subsequent oxidation of the hydroxy function afforded (3R,4R)-4-benzyl-3-pyrrolidinecarboxylic acid (4).

■ Synthesis of Multi-substituted Pyrazoles Utilizing the N-Alkylated 3-Hydroxy-3-propargyl- or Allenylisoindolines

Yong Hyun Choi, Kyung Soon Kim, Sangku Lee, Tae-Sook Jeong, Hee-Yoon Lee, Yong Hae Kim, and Woo Song Lee*

*Korea Research Institute of Bioscience and Biotechnology, 52 Oun, Yusong, Daejeon 305-333, Korea

Abstract

N-Alkyl-substituted phthalimides (1) were easily converted to di-, tri-, and tetra-substituted pyrazoles (10) via a one-pot addition-decyclization-cyclocondensation process. Then, the structure and the position of N1-substitution of the 1,3-pyrazole ring were determined by X-Ray crystallographic analysis and ¹H-nOe experiments.

■ Synthesis of the Tetrahydropteridine-2,4-dione Having a Substituted Methyl Group at 6-Position

Masaru Tada,* Tomoyuki Shimamura, and Takeaki Suzuki

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

Abstract

Lewis acid treatment of 5-amino-6-(N-2,3-epoxypropyl-N-tosyl)amino-1,3-dimethyluracil (3) gave the diazepine (4) fused to uracil ring, and the tosylate (5) from 4 underwent ring transformation to provide tetrahydropteridinediones (7 and 8) depending on the reaction conditions. Thus, heating in dry acetonitrile led to 6-tosyloxymethyltetrahydropteridine-2,4-dione (7) whereas that in wet acetonitrile to 6-hydroxymethyl derivative (8).

■ Synthesis of 8,9,10,11-Tetrahydroindolo[2,1-c]benzo[1,2,4]triazine. A New Ring Syntem

Paola Barraja, Patrizia Diana, Antonino Lauria, Alessandra Montalbano, Anna Maria Almerico, Gaetano Dattolo, and Girolamo Cirrincione*

*Dipartimento Farmacochimico Tossicologico e Biologico Università degli Studi di Palermo Via Archirafi 32, 90123 Palermo, Italy

Abstract

Indolo[2,1-c]benzo[1,2,4]triazine, a new ring system, was synthesized by diazotization of 2-amino-1 aryltetrahydroindoles followed by an intramolecular coupling of the diazonium group with the aryl moiety. All the new compounds were screened at the NCI for antiproliferative property but none of them showed significant activity.

■ Synthesis and Crystal Structure of 2’,4”-O-Bis(trimethylsilyl)erythromycin A 9-O-(1-Isopropoxycyclohexyl) Oxime

Jian-Hua Liang and Guo-Wei Yao*

*School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081, China

Abstract

The ratio of E/Z of 2’-,4”-O-bis(trimethylsilyl)erythromycin A 9-O-(1-isopropoxycyclohexyl) oxime were much higher prepared in CH₃CN than those in CH₂Cl₂. And the ratio would increase with elevation of temperature. Compared with 2’-OH, 4”-OH was liable to be silylated in the presence of 1,1,1,3,3,3-hexamethyldisilizane and an NH₄⁺. The crystal structure of E-title compound was determined by single-crystal X-Ray structure analysis to elucidate the origin of regioselectivity occurring at 6-hydroxyl group in the O-methylation of erythromycin A.

■ Synthesis and Characterization of a New Metal-free Azaphthalocyanine Containing Four Peripheral Ion Jacks

Xiguang Du,* Chunyu Ma, Xiaoke Hou, Gui Wang, Wancheng Li, and Guotong Du*

*Laboratory of Organic Synthesis, Department of Chemistry, Northeast Normal University, Changchun, 130024, China

Abstract

A synthesis of a new 1,10-phenanthroline-appended metal-free azaphthalocyanine(azaPc), which is generated from precursor, 10,12-diimino-11 H-pyrrolo[3,4-b]dipyrido[3,2-f:2’,3’-h]quinoxaline, is described. This azaPc is purified by absolute methanol in a Soxlet apparatus, then under high vacuum (10^-4Pa) and is unequivocally characterized by its elemental analysis and spectrometry.

■ Reactions of 9-Phosphorylacridines with Aqueous Hydrogen Peroxide Accompanied by Weak Chemiluminescence: Remarkable Substituent Effect on Emission Efficiency

Jiro Motoyoshiya,* Rie Shima, Yutaka Takaguchi, Yoshinori Nishii, and Hiromu Aoyama

*Department of Chemistry, Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan

Abstract

The reaction of 9-phosphorylacridines with aqueous hydrogen peroxide provides weak chemiluminescence, whose emission efficiency depends on the structures of the phosphorus groups. The bulky substituents in the phosphorus groups increased the chemiluminescence quantum yields, which can be explained by assuming that the present chemiluminescence reaction involves a CIEEL process via phospha-1,2-dioxetanes as the high-energy intermediates.

■ Synthesis of Novel Chiral Spiro Bis(pyrazole) Ligands

Shinobu Takizawa, Yuji Honda, Midori A. Arai, Takahiro Kato, and Hiroaki Sasai*

*The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047, Japan

Abstract

The first synthesis of spiro bis(pyrazole) ligands, 2,2’,4,4’-tetrahydro-6,6’-spirobi[5H-cycopentapyrazole] (1a) and 2,2’-dibenzyl-2,2’,4,4’-tetrahydro-6,6’-spirobi[5H-cycopentapyrazole] (1b) was achieved. The application of spiro bis(pyrazole) ligand to asymmetric catalysis was also examined.

■ Flavonol Glycosides in Two Diospyros Plants and Their Radical Scavenging Activity

Miyuki Furusawa, Tetsuro Ito, Ken-ichi Nakaya, Toshiyuki Tanaka,* Iliya Ibrahim, Munekazu Iinuma, Hiroko Murata, Yuka Inatomi, and Tsutomu Nakanishi

*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan

Abstract

Methanol extracts of leaves of Diospyros glaucifolia and D. kaki were showed the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Chromatographical separation and purification of methanol extracts resulted in isolation of three new flavonol glycosides [2”-(E)-p-coumaroylmyricitrin (3), 3”-(E)-p-coumaroylmyricitrin (4) and mearsetin 3-O-β-glucronopyranoside (11)] along with known phenolic compounds. These structures were determined by means of spectroscopic analysis. The scavenging activities of DPPH radical of the isolated compounds were examined.