HETEROCYCLES

■ Contents

■ SYNTHESIS AND CHARACTERIZATION OF TRIPHYRINS: A NEW FAMILY OF PORPHYRINOIDS

Daiki Kuzuhara and Hiroko Yamada*

*Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan

Abstract

This article reviews the recent reports about the syntheses, structures, photophysical and redox properties of newly synthesized [14]triphyrins(2.1.1), their metal complexes and their core-modified triphyrins, following the overview of the other triphyrin relatives containing three pyrrole rings and more than three methine carbons. Free-base [14]triphyrins(2.1.1) work as tridentate monovalent anionic cyclic ligands and a variety of metal complexes with Re(I), Mn(I), Ru(II), Pd(II), Pd(IV), Fe(II), Fe(III) and B(III) ions were obtained due to the flexible structure of the triphyrin macrocycles. The core-modified [14]triphyrin(2.1.1) was also expected, but the alkoxy-substituted compounds were obtained instead of the desired thiatriphyrin, probably because of the larger size of sulfur atom compared to nitrogen atom and the electronic repulsion between the lone pairs of inner nitrogen atoms.

■ Synthesis of Indoles: Sulfur-Assisted Reaction of 2-Nitrostilbenes with Carbon Monoxide

Rui Umeda, Yuuta Nishimoto, Tsukasa Mashino, and Yutaka Nishiyama*

*Faculty of Chemistry and Materials Engineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka 564-8680, Japan

Abstract

When 2-nitrostilbenes were treated with carbon monoxide in the presence of elemental sulfur, the reductive N-heterocyclization of the 2-nitrostilbenes smoothly proceeded to give the corresponding indoles in moderate to good yields.

■ Dimethyldioxirane Oxidation of N-Substituted-2-methylindoles to Indoxyls and Bisindoxyls

Alberto Aristeo-Dominguez, Myriam Meléndez-Rodríguez,* Oscar R. Suárez Castillo,* Yaneth M. A. Contreras-Martínez, Lizbeth Suárez-Ramírez, Nayely Trejo-Carbajal, Martha S. Morales-Ríos, and Pedro Joseph-Nathan

*Área Académica de Química, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma, Hidalgo, 42184, Mexico

Abstract

Oxidation of 2-methylindoles 12a-f with dimethyldioxirane (DMD) revealed that N-unprotected 12b,f and protected N-carbamate 2-methylindole 12c afforded indoxyls 16b,c and o-(N-propionyl)aminobenzoic acid 17f as the main products, while N-alkyl- or N-aryl-2-methylindoles 12a,d,e gave 1,5’-diphenyl-4’,5’-dihydro-3’H-spiro[indole-2,2’-pyrano[3,2-b]indol]-3(1H)-one (10), 2,3'-bisindolin-3-ones 13, dispiro[indole-2,2’-furan-5’,2”-indole]diones 14 or 2-[(3-oxoindolin-2-yl)methyl]-2-hydroxyindolin-3-ones 15. The structure of dimers 10, 13a,d,e, 14a,d and 15a,d followed from NMR measurements, X-ray diffraction analysis confirmed those structures of 13a,d,e, 14a,d and 15d, and some mechanistic implications are discussed.

■ Development of a Novel Method for Warfarin Synthesis via Lipase-Catalyzed Steroselective Michael Reaction

Kaoru Sano, Shun-ichi Saito, Yoshihiko Hirose, Yoshihito Kohari, Hiroto Nakano, Chigusa Seki, Michio Tokiwa, Mitsuhiro Takeshita, and Koji Uwai*

*Department of Applied Sciences, Graduate School of Engineering, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

Steroselective synthesis of warfarin by promiscuous lipase-catalyzed Michael addition of 4-hydroxycoumarin and benzylideneacetone has been developed. The best result was obtained using lipase AS as a catalyst in anhydrous dimethylsulfoxide (DMSO) with 1:3 molar ratio of 4-hydroxycoumarin to benzylideneacetone at 20ºC for 7 d. The yield and enantiomeric excess were 85% and 45%ee (R-form), respectively.

■ Synthesis of 5-Amino or 4-Amino Substituted 7-Aza-isoindolin-1-ones

Heng Zhou, Qunfeng Shi, Xiangchao Liu, Xiaoping Zhan, Zenglu Liu, and Zhenmin Mao*

*School of Pharmacy, Shanghai Jiaotong University , No.800 Dongchuan Road, Minhang District, Shanghai 200240, China

Abstract

A simple and convenient route for the synthesis of a series of 5-amino or 4-amino substituted 7-aza-isoindolin-1-ones is described. Amino substituted pyridine derivatives were cyclized with different amines in alkaline condition to give the desired products.

■ Thermal and Photochemical Rearrangements of 3-Arylamino-2-phenyl-1H-inden-1-ones to N-Arylphthalimides

Masayuki Kawai, Eriko Sakanoshita, Motoko Akita, and Keiji Kobayashi*

*Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

Upon heating to above their melting temperatures, 3-arylamino-2-phenyl-1H-inden-1-ones and 2,2’-diphenyl-3,3’-bis(arylimino)- [2,2’-bi-1H-indene]-1,1’-dione undergo a skeletal rearrangement to afford N-arylphthalimides along with benzoic acid in the presence of atmospheric oxygen. The photoreaction of these compounds in acetonitrile also results in the formation of these products. The mechanism of these reactions, including the formation of a peroxyl radical followed by its conversion to a nitrogen-centered radical, is proposed.

■ Unexpected Behaviour of 6-Cyanopurines Towards Secondary Amines

Amal Al-Azmi* and K. Anita Kumari

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

Abstract

Reaction of 6-cyanopurines with excess dimethylamine and excess piperidine at room temperature or by reflux-respectively-yielded a mixture of 6-purinecarboximidamides and N,N-dialkylpurines or piperidin-1-yl(purin-6-yl)methanimine and (piperidin-1-yl)-9H-purine, respectively. 6-Purinecarboximidamides were initially formed from the reaction, whereas N,N-dialkylpurines were detected in the mixture 30 min afterward. Both purines appeared to be generated from different mechanistic pathways.

■ Synthesis of 2-Sulfanyl-4H-3,1-benzothiazine Derivatives by the Reaction of 2-(Bromomethyl)phenyl Isothiocyanates with Thiols

Kosuke Ezaki, Miyuki Tanmatsu, and Kazuhiro Kobayashi*

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

Abstract

The reaction of 2-(bromomethyl)phenyl isothiocyanates with thiols in the presence of triethylamine gave the corresponding 2-sulfanyl-4H-3,1-benzothiazines. The procedure was successfully applied to the preparation of 1,ω-bis[(4H-3,1-benzothiazin-2-yl)sulfanyl]alkanes using 1,ω-alkanedithiols.

■ Intramolecular [2π+2π]-Photocyclization and Conformational Preference of 5-(2-Benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a,d]cycloheptene

Motoko Akita, Sin-ya Mohri, Mai Takahashi, and Keiji Kobayashi*

*Department of Chemistry, Faculty of Science, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

The photoirradiation of 5-(2-benzo[b]thienyl)-5-ethoxy-5H-dibenzo[a.d]cycloheptene (2) in acetonitrile afforded a cagelike tetracyclic compound (1) via intramolecular [2π+2π]-photocycloaddition. The molecular and crystal structures of 1 and 2 were characterized by a single-crystal X-ray diffraction study. The formation of the cycloadduct is discussed in relation to the preferable conformation of the central C-C bond in 2, which was revealed to be in restricted rotation on the basis of the temperature-dependent 1H NMR spectra.

■ Microwave-Assisted Synthesis of 3-Methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones under Solvent-Free Conditions

Guo-Yu Yang, Jing-Tian Yang, Cai-Xia Wang, Su-Fang Fan, Pu-Hui Xie, and Cui-Lian Xu*

*College of Science, Henan Agricultural University, Zhengzhou 450002, China

Abstract

A novel microwave-assisted method for the synthesis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones by the cyclization of 3-[1-(phenylhydrazono)ethyl]chromen-2-ones with CuO/SBA-15 under solvent-free conditions is described. The reaction gave the corresponding chromenopyrazole products in good to excellent yields in short reaction times.

■ Asymmetric Conversion of (Z)-N-Benzoyl-α-dehydro(9-phenanthryl)alanine N´-Methylamide into Its Cyclization Intermediates via Photoinduced Electron Transfer

Shin-ichi Matsuki, Takayuki Kimura, Shinsaku Hattori, Kaoru Kawai, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

Irradiation of (Z)-N-benzoyl-α-dehydro(9-phenanthryl)alanine N´-methylamide [(Z)-1] in 2-propanol-methanol (4:1 v/v) containing (S)-nicotine afforded the (3S,8aS)-3,8a-dihydro-2-dibenzo[f,h]-quinolinone derivative [(3S,8aS)-2] and (3R,8aS)-2 in 20% and 35% enantiomeric excess (ee), respectively. Analysis of the effects of a chiral amine and solvent on the electron transfer-initiated enantioselective photocyclization of (Z)-1 revealed that the magnitude of the ee is predominantly determined by the ability of this amine to form hydrogen bonds at the two sites of the enol intermediate as the precursor of 2.

■ A FACILE SYNTHESIS OF (5-HYDROXY-4-OXO-4H-PYRAN-2-YL)METHYL CARBOXYLATES AND THEIR ANTIVIRAL ACTIVITY AGAINST HEPATITIS C VIRUS

Tetsuro Shimo,* Yuki Taketsugu, Takuya Goto, Masaaki Toyama, Kohji Yoshimura, and Masanori Baba

*Department of Chemistry, Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890-0065, Japan

Abstract

5-Benzyloxy-2-hydroxymethyl-4H-pyran-4-one (2) was synthesized from kojic acid (1) and subsequently reacted with carboxylic anhydride (3a) and a series of carboxylic acid chlorides (3b–l) to give the corresponding (5-benzyloxy-4-oxo-4H-pyran-2-yl)methyl carboxylates (4a–l). These compounds were then reductively debenzylated to afford the (5-hydroxy-4-oxo-4H-pyran-2-yl)methyl carboxylates (5a-l), which were tested for their inhibitory activities against the hepatitis C virus.