HETEROCYCLES

■ Contents

■ Development of Epoxysilane Rearrangement and Its Application to Chirality Transfer

Michiko Sasaki, Hidaka Ikemoto, and Kei Takeda*

*Divison of Medicinal Chemisry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

Abstract

Development and synthetic application of epoxysilane rearrangement, a novel synthetic use of α,β-epoxysilanes, in which an anion-induced ring-opening of epoxide and Brook rearrangement in the resulting α-silyl alkoxide occur in a tandem fashion to provide a β-siloxy allyl anion, are described. Chirality transfer from epoxides to the position next to a nitrile group by taking advantage of the concerted process of the rearrangement is also reported.

■ Regioselective Ester Hydrolysis of Sialic Acid Derivatives Catalyzed by Molecularly Imprinted Polymers

Kiyoshi Ikeda,* Takashi Katsumata, Yuji Sugiyama, Keisuke Miyamoto, Kiyoshi Tanaka, and Masayuki Sato

*Department of Pharmaceutical Sciences, Hiroshima International University, 5-1-1, Hirokoshingai, Kure, Hiroshima, 737-0112, Japan

Abstract

Regioselective ester hydrolysis of sialic acid derivatives catalyzed by molecularly imprinted polymers was studied. A sialic acid derivative having 8-O-methylphosphonate was used as the template for molecular imprinting polymer (MIP). By mimicking the tetrahedral intermediate for ester hydrolysis, this MIP catalyzed the regioselective hydrolysis of the 8-O-acetyl group of per-O-acetylated sialic acid derivative at an increased rate.

■ Synthesis of 6-Substituted Purine Derivatives

Amal Al-Azmi* and K. Anita Kumari

*Department of Chemistry, Faculty of Science, Kuwait University, Safat 13060, P.O. Box 5969, Kuwait

Abstract

Hydroxylamine hydrochloride reacts readily with (5-amino-1-aryl-1H-imidazol-4-yl)iminoacetonitriles to furnish 5-amino-1-aryl-N-hydroxy-1H-imidazole-4-carboxamidines. When a mixture of 5-amino-1-aryl-N-hydroxy-1H-imidazole-4-carboxamidine and excess of triethyl orthoesters is reacted at room temperature novel purin-6-one oximes are obtained in moderate yields. Further, reaction of formamidines and ethyl acetoacetate with DBU afforded 6-carbamoylpurines. X-Ray analysis carried out on 9-(4-methoxyphenyl)-2-methyl-9H-purine-6-carboxamide monohydrate confirmed its structure. Diazotization of [5-amino-1-(4-methoxyphenyl)-1H-imidazol-4-yl]iminoacetonitrile in the presence of an excess of sodium nitrite and concentrated HCl gave 4-carboxy-5-chloro-1-(4-methoxyphenyl)imidazolidinium chloride via nucleophilic aromatic substitution reaction. However, (1-aryl-5-hydroxy-1H-imidazol-4-yl)imino-acetonitrile is obtained as product when (5-amino-1-aryl-1H-imidazol-4-yl)iminoacetonitriles (Ar = 4-MeC6H4 and Ar = 4-ClC6H4) were the reactants. The structure of 4-carboxy-5-chloro-1-(4-methoxyphenyl)imidazolidinium chloride was also established by X-ray analysis.

■ Stereoselective Synthesis of Isoquinuclidinones by Direct Imino-Diels-Alder Type Reaction Catalyzed by L-Proline

Noelia Quiñones, Fernándo Aznar,* and María-Paz Cabal

*instituto Universitario de Química Organometálica "Enrique Moles", Facultad de Química, Universidad de Oviedo, Julián Clavería 8, 33071- Oviedo, Spain

Abstract

A general synthesis of isoquinuclidinones (2-azabicyclo[2.2.2]octan-5-ones), has been developed by one-pot three component imino-Diels-Alder type reaction catalyzed by L-proline. Simple and commercially available α,β-unsaturated cyclic ketones, aromatic aldehydes and either aliphatic or aromatic primary amines were used. The reaction proceeds with excellent exo-diastereoselectivity (>99%) and moderated enantioselectivity (30-64%).

■ A Non-Acyl Azide Route to Isoquinolin-1(2H)-one Derivatives via β-Styril Carbamates

Chien-Chang Chen, Li-Yueh Chen, Rung-Yuan Lin, Che-Yi Chu, and Shenghong A. Dai*

*Department of Chemical Engineering, National Chung-Hsing University, Taichung, 40227, Taiwan, R.O.C.

Abstract

The efficient reactions of the phenyl acetaldehydes 1a-e and the enol ethers of benzyl ketones 1o-s with ethyl urethane lead to the formation of the β-styril carbamates 2, which are excellent precursors for generating isoquinolin-1(2H)-ones 4. Upon thermolysis at 230 °C in an inert organic solution, the carbamates decomposed into the transient β-styril isocyanate intermediates 3. The resulting isoquinolin-1(2H)-ones obtained were in good yields (65-93 %). This synthetic methodology allows the convenient preparation of isoquinolin-1(2H)-ones via a non-phosgene and non-acyl azide route from readily accessible starting materials.

■ One-Pot Synthesis of Three Types of 2,3-Disubstituted Thienopyridines from Halopyridinyl Ketones

Kazuhiro Kobayashi,* Taketoshi Kozuki, and Hisatoshi Konishi

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

Abstract

This report describes a one-pot synthesis of three types of thienopyridine derivatives from the respective halopyridinyl ketones. Thus, the reaction of 2-bromopyridin-3-yl ketones, derived from 2-bromopyridine, with sodium sulfide followed by successive treatment BrCH2EWG’s and sodium hydride afforded 2,3-disubstituted thieno[2,3-b]pyridines. Similar one-pot sequences starting from aryl 3-bromopyridin-4-yl ketones and aryl 4-chloropyridin-3-yl ketones could also be readily performed to afford 2,3-disubstituted thieno[2,3-c]pyridines and 2,3-disubstituted thieno[3,2-c]pyridines, respectively.

■ Synthesis of Optically Active P-Chirogenic Ferrocene-Fused Benzophosphole by Diastereoselective Intramolecular Cyclization of Phosphanylferrocene Derivatives

Shuji Yasuike, Jun-ichi Hagiwara, Hiroshi Danjo, Masatoshi Kawahata, Naoki Kakusawa, Kentaro Yamaguchi, and Jyoji Kurita*

*Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho, Kanagawa machi, Kanazawa 920-1181, Japan

Abstract

A novel optically active P-chirogenic ferrocene-fused benzo- phosphole, (SFc,RP)-4-phenylbenzo[b]ferroceno[d]phosphole, was synthesized by diastereoselective intramolecular cyclization of (SFc)-1-(diphenylphosphanyl)-2-(2-lithiophenyl)ferrocene intermediates in two routes. The geometry of the new P-chirogenic ferrocenophosphole including absolute configuration of the phosphorous was disclosed by single crystal X-ray analysis of the palladium complex derived from the reaction of the phosphole with di-μ-dichloro-bis{2-[(dimethylamino)methyl]phenyl-C1,N}dipalladium (II).

■ Benzylic Oxidation of N-Acyl-1,2,3,4-tetrahydroquinolines

Roxanne C. Higgins, Norman O. Townsend, and Yvette A. Jackson*

*Department of Chemistry, Mona Campus, University of the West Indies, Mona, Kingston 7, Jamaica

Abstract

Chromium hexacarbonyl/tert-butyl hydroperoxide has been identified as a general reagent for the benzylic oxidation of N-acyl-1,2,3,4-tetrahydroquinolines.

■ Bifunctional Organocatalyst to Promote the Biginelli Reaction under Mild Conditions

Nobuyuki Mase,* Daisuke Nakamura, Yasuhiro Kawano, Yuka Suzuki, and Kunihiko Takabe*

*Department of Molecular Science, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561, Shizuoka, Japan

Abstract

Binaphthyl compounds, which include a pyridinium ion moiety as an acid and pyridine moiety as a base, have been synthesized and evaluated as bifunctional organocatalysts for the three-component Biginelli reaction. 3,3'-(2,2'-Dimethoxy-1,1'-binaphthyl-3,3'-diyl)dipyridine in the presence of equimolar amount of methanesulfonic acid catalyzed the Biginelli reaction to give the desired product in up to 79% yield even at 25 °C.

■ Preparation of 1,4-Bis(3-ethynylthieno[3,2-b]thiophen-2-yl)benzene Derivatives as Peptide-Inspired Molecules

Kozo Toyota,* Hiroshi Katsuta, Yasutomo Tsuji, Takeaki Iwamoto, and Noboru Morita

*Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan

Abstract

1,4-Bis(3-ethynylthieno[3,2-b]thiophen-2-yl)benzene derivatives, as well as 1-(3-ethynylthieno[3,2-b]thiophen-2-yl)-4-(2-ethynyl-3-thienyl)benzene derivative and 2,5-bis(2-ethynyl-3-thienyl)thieno[3,2-b]thiophene derivative, containing thieno[3,2-b]thiophene moieties with pseudoaxis, was prepared and their UV-vis spectra were studied. Extension of π-system through the central aromatic ring was suggested by the UV-vis spectra.

■ Efficient Synthesis of 4-Substituted 4,5-Dihydroisoxazol-3-ols from Morita-Baylis-Hillman Bromides

Weihui Zhong,* Yongliang Liu, and Baoming Guo

*Key Laboratory of Pharmaceutical Engineering of Ministry of Educations, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310014, China

Abstract

An efficient synthesis of 4-substituted 4,5-dihydroisoxazol-3-ols was achieved with high regioselectivities and satisfactory yields via addition of N-hydroxyphthalimide to Morita-Baylis-Hillman (MBH) bromides with ester moiety, followed by hydrazinolysis and intramolecular cyclization. Surprised, the unexpected isoxazolidine-4-carbonitrile was obtained when using MBH bromide with nitrile moiety as substrate under the similar conditions.

■ Heteroarylamination and Heteroarylsulfidation of 2-Chloro-1-azaazulenes

Eiko Yoshioka, Kazuya Koizumi, Shinya Yamazaki, Hiroyuki Fujii, and Noritaka Abe*

*Graduate School of Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8512, Japan

Abstract

Heteroarylamination and heteroarylsulfidation of 2-chloro-1-azaazulenes (1) were investigated. Palladium catalyzed coupling of 2-amino-1-azaazulenes (2) with 1 underwent to give bis(1-azaazulen-2-yl)amine derivatives in good yields, but the reaction of 2-mercapto-1-azaazulenes (4) with 1 did not give good results in the same conditions. The reaction of 4 with 1 under basic conditions gave bis(1-azaazulen-2-yl) sulfide derivatives in good yields. Heteroarylamino-substitution was proceeded on the reaction of 4-amino-3-mercapto-4H-1,2,4-triazoles (6) with 1 in BuOH under reflux, whereas heteroarylsulfido-substitution was proceeded on the reaction of 6 with 1 in the presence of NaH in dioxane.

■ Thermolysis of N-Arylenamino-N-arylimine Hydrochloride Derivatives: A Short and Improved Synthesis of 2-Methylthieno[2,3-c]acridine Derivatives

Tuhin B. Maiti and Gandhi K. Kar*

*Department of Chemistry and Biochemistry, Presidency College, 86/1 College Street, Kolkata-700073, India

Abstract

A short and high yielding synthesis of 2-methylthieno[2,3-c]acridine derivatives 5(a-h) is described using thermal cyclization of anil hydrochloride derivatives. The anil hydrochlorides 4(a-i) were obtained by reaction of various aryl amines and 4-chloro-2-methyl-6,7-dihydrobenzo[b]thiophene-5-carbaldehyde (2) which in turn was synthesized via Villsmeir-Haack reaction of 2-methyl-6,7-dihydrobenzo[b]thiophen-4(5H)-one (1).

■ Studies with 3-Oxoalkanonitriles: Synthesis and Reactivity of 3-Oxo-3-(1-methylindoloyl)propanenitrile

Haider Behbehani,* Hamada Mohamed Ibrahim, and Saad Makhseed

*Department of Chemistry, Faculty of Science, Kuwait University, Safat 13060, P.O. Box 5969, Kuwait

Abstract

N-Methylindole was acylated at C-3 with cyanoacetic acid and acetic anhydride to yield 3-cyanoacetyl-1-methylindole which could be utilized for synthesis of a diversity of indole derivatives with heterocyclic substituent.

■ Synthesis and Stereochemistry of Novel Rigid Nitroxide Biradicals Based on Paramagnetic Pyrrolidine Core

Katsuaki Suzuki, Dmitrii G. Mazhukin,* Hiroki Takahashi, Yoshiaki Uchida, Rui Tamura,* and Igor A. Grigor’ev

*Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan

Abstract

We have synthesized new chiral racemic nitroxide biradical compounds cis-2 and trans-2 and determined their stereochemistry by X-ray crystallographic analyses.