HETEROCYCLES

■ Contents

■ Recent Development in Palladium-Mediated Synthesis of Oxygen Heterocycles

Krishna C. Majumdar,* Buddhadeb Chattopadhyay, Pradip K. Maji, Sudip K. Chattopadhyay, and Srikanta Samanta

*Department of Chemistry, University of Kalyani, Kalyani 741 235, West Bengal, India

Abstract

This review describes the synthesis of oxygen heterocycles by palladium-mediated cyclization published during 2003 to 2007.

■ Synthesis of Metal Complexes with 1-Substituted 3-Hydroxy-2(1H)-pyridinethiones and Their Insulin-Mimetic Activities

Akira Katoh,* Hiroko Yokoyama, Yuriko Matsumura, Yutaka Yoshikawa, Hiroyuki Yasui, and Hiromu Sakurai

*Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, Musashino-shi, Tokyo 180-8633, Japan

Abstract

Eight kinds of 1-alkyl-3-hydroxy-2(1H)-pyridinethiones were synthesized from a commercially available 3-methoxy-2(1H)-pyridinone via 3 steps. Zn(II) and vanadyl complexes were synthesized by treatment with Zn(OAc)2 or ZnSO4, and VOSO4, respectively. Vanadyl complexes were found to exist in VO(S2O2) coordination mode by means of ESR spectroscopy. From in vitro evaluation of the inhibitory effect on FFA release from rat adipocytes treated with epinephrine, it was found that IC50 values of Zn(II) complexes with 1-alkyl-3-hydroxy-2(1H)-pyridinethiones, regardless of the methylene-chain length at N-1 position, were in micromolar levels. In other words, these Zn(II) complexes showed higher insulin-mimetic activities than those synthesized previously. On the other hand, the insulin-mimetic activity of vanadyl complexes unfortunately could not be measured owing to their insolubility in KRB buffer which is used in vitro assay.

■ Reusable Polymer-Supported Terpyridine Copper Complex for [3+2] Huisgen Cycloaddition in Water

Toshimasa Suzuka,* Kazumasa Ooshiro, and Ken’yu Kina

*Department of Chemistry, Biology and Marine Sciences, Faculty of Science, University of Ryukyus, Nishihara-cho, Okinawa 903-0213, Japan

Abstract

A polymer-supported terpyridine copper(I) complex was prepared and found to promote the Huisgen [3+2] cycloaddition reaction between azides and alkynes in water to give the corresponding triazoles with up to 87% isolated yield. This catalyst was recovered and reused several times without any loss in catalytic activity.

■ Synthesis of 3-(Pyrimidinyl)pyrrole Derivatives

Igor Yu. Nestorak, Anton V. Tverdokhlebov,* Andrey A. Tolmachev, and Yulian M. Volovenko

*Enamine Ltd. Co., Alexandra Matrosova Str. 23, 01103 Kiev, Ukraine

Abstract

Alkylation of 4,6-dimethyl-2-pyrimidineacetonitrile and 2,6-dimethyl-4-pyrimidineacetonitrile with chloroacetic acid anilides was shown to give 5-amino-4-(4,6-dimethyl-2-pyrimidinyl)-2,3-dihydro-1-arylpyrrol-2-ones and 5-amino-4-(2,6-dimethyl-4-pyrimidinyl)-2,3-dihydro-1-arylpyrrol-2-ones, respectively. Corresponding isomeric compounds, 5-amino-4-pyrimidinyl-2,3-dihydropyrrol-3-ones were obtained by Claisen condensation of the mentioned pyrimidineacetonitriles with N-Boc α-aminoacids imidazolides followed by removal of the protecting group accompanied with simultaneous ring closure.

■ Absolute Configuration of Sargaol Acetate Using DFT Calculations and Vibrational Circular Dichroism

Marcelo A. Muñoz, Carlos Areche, Juana Rovirosa, Aurelio San-Martín, and Pedro Joseph-Nathan*

*Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, A.P. 14-740, Avenida IPN 2508, Esquina Ticoman, C.P. 07000 México, D.F., Mexico

Abstract

The absolute configuration (AC) of sargaol acetate (2), isolated from the brown alga Stypopodium flabelliforme, was determined using vibrational circular dichroism (VCD) measurements and density functional theory (DFT) calculations. Conformational searches using the Monte Carlo stochastic algorithm for 2 and three model compounds with a smaller side chain (diisoprenyl, isoprenyl and ethyl) provided 2172, 596, 82 and 12 conformations, respectively. In the last two cases the moderate number of conformations allowed conformational distributions assessment using single point energy calculations and considering a Boltzmann behavior. In the larger model molecules a prior selection from the original conformational set was done based on structure diversity as implemented in the Spartan`04 modeling software, keeping only 100 conformations in each case. All final conformers where further subjected to geometry optimizations and vibrational calculations providing weighted theoretical IR and VCD spectra which were compared to the experimental spectrum. In all cases only very weak bands are observed above 1300 cm-1, the strong bands around 1200 cm-1 clearly show that the AC of 2 is R, and only models including isoprenyl units allowed good prediction of bands in the 1000 - 1100 cm-1 spectral region.

■ Iodotrimethylsilane and Catalytic Iodine Promoted Cyclization for the Facile Synthesis of 3-Monoarylated Five-Membered Benzosultams

Yue-Hui Dong, Qiong-Wei Ni, Shu-Tao Ma, and Zhao-Peng Liu*

*Department of Organic Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44, WenHua XiLu, Jinan 250012, China

Abstract

3-Monoarylated five-membered benzosultams with various functional groups were prepared by simple and convenient two-step procedures. N-t-Bu-benzenesulfonamides were lithiated and reacted with substituted aromatic aldehydes to form the corresponding carbinols, which were converted to the cyclic compounds via a sequence of consecutive processes mediated by TMSCl-NaI-MeCN reagent and catalytic amount of iodine. Iodine played a crucial role in the eliminating the reductive side reaction in the cyclization processes.

■ Synthesis and Biological Activity of Mono- and Disubstituted 1,2,4-Triazole Derivatives

Vytautas Mickevičius,* Vida Intaitė, Aušra Voskienė, Kristina Kantminienė, Maryna Stasevych, Olena Komarovska-Porokhnyavets, and Volodymyr Novikov

*Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, Kaunas LT-50254, Lithuania

Abstract

Novel mono- and disubstituted triazole derivatives were synthesized by condensation reactions of 1-aryl-3-hydrazinocarbonyl-5-oxopyrrolidinones with organic and inorganic cyanates, their structures were investigated and antimicrobial activity was evaluated.

■ Effect of Nitro-Substitution on the Photochemistry of 3-Piperidino-1,2-benzisothiazole Derivatives: A Mechanistic Investigation

Hiroharu Tanikawa, Kazuhiro Ishii, Shun Kubota, Takashi Sasanuma, Shiki Yagai, Akihide Kitamura, and Takashi Karatsu*

*Department of Applied Chemistry and Biotechnology, Graduate School and Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522,

Abstract

Photochemical isomerization of 3-piperidino-1,2-benzisothiazole (BIT)–benzothiazole (BT) was investigated. In particular, the effect of nitro-substitution on the benzene ring was selectively examined for the parent, 5-nitro-, and 7-nitro-derivatives. 3-Piperidino-BIT and nitro-3-piperidino-BIT isomerized irreversibly to the corresponding 2-piperidino-BT, and this reaction mechanism was investigated using density-functional theory (DFT) and time-dependent (TD)-DFT calculations. These calculations showed that this isomerization goes through an azirine intermediate. In addition, excitation wavelength effect demonstrates that isomerization occurs from the upper excited state of nitro-derivatives. The HOMO-LUMO transition has charge-transfer and photoinactive characters.

■ Synthesis of Fused Thiopyranthione and Thiophene Derivatives from 4,5-Dihydro-3-thiophene(and -3-furan)carbonitriles Having an Active Methylene Group at C-2 Position

Hiroshi Maruoka,* Fumi Okabe, Keishi Yamasaki, Eiichi Masumoto, Toshihiro Fujioka, and Kenji Yamagata

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

A versatile strategy is described for the synthesis of new fused thiopyranthione and thiophene derivatives. The reaction of heterocyclic α,β-unsaturated nitriles 3a−c, 4a−d, 5a−c, and 6a−d, which were prepared from tetrahydro-2-oxo-3-thiophene- and -3-furan-carbonitriles 1a−c and/or 2a−d and alkylidene phosphoranes such as (triphenylphosphoranylidene)acetonitrile and methyl (triphenylphosphoranylidene)acetate through Wittig reaction, with carbon disulfide in the presence of sodium hydride in THF gave the corresponding 6-thioxothieno[3,2-c]thiopyran and 6-thioxothiopyrano[4,3-b]furan derivatives 7a−c, 8a−d, 9a−c, and 10a−d. On the other hand, treatment of compounds 3a−c, 5a−c, and 6a−d with sulfur powder in the presence of triethylamine in methanol caused Gewald reaction to provide the corresponding thieno[3,4-b]thiophene and -furan derivatives 11a−c, 12a−c, and 13a−d.

■ The First Cerium (IV) Ammonium Nitrate (CAN)-Catalyzed Friedländer Synthesis of Quinolines in Ionic Liquid

Rei-Sheu Hou,* Huey-Min Wang, Iou-Jiun Kang, Hau-Dung Du, and Ling-Ching Chen*

*Department of Cosmetic Science, Chung Hwa University of Medical Technology, Department of Chemistry, National Cheng Kung University, Tainan, 701, Taiwan, R.O.C.

Abstract

A mild and efficient route for the synthesis of quinolines and polycyclic quinolines utilizing cerium (IV) ammonium nitrate (CAN) as a novel catalyst via Friedländer annulation in ionic liquid 1-n-butyl-3-methylimidazolium hexafluorophosphate [Bmim][PF6] under mild conditions was described.

■ Synthesis of 1,2-Dihydro-3-benzoxepins by the Reaction of 2-Lithio-β-methoxystyrenes with Epoxides Followed by Hydriodic Acid Catalyzed Cyclization

Kazuhiro Kobayashi,* Hiroo Hashimoto, Toshiyuki Nagaoka, Yuu Shirai, and Hisatoshi Konishi

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

Abstract

5-Substituted 1,2-dihydro-3-benzoxepins can be prepared in reasonable overall yields from α-substituted 2-bromo-β-methoxystyrenes. Thus, the reaction of α-substituted 2-lithio-β-methoxystyrenes, generated by the bromine-lithium exchange between α-substituted 2-bromo-β-methoxystyrenes and butyllithium, with epoxides gives the corresponding 2-(methoxyvinyl)phenethyl alcohols. These undergo cyclization with a loss of methanol on treatment with a catalytic amount of hydriodic acid to give the desired products.

■ Regioselective Synthesis and Structure of New Spiro-isoquinolinedione Derivatives

Nafâa Jegham, Yakdhane Kacem, and Béchir Ben Hassine*

*Department of Chemistry, Faculty of Sciences, Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, Avenue of the Environment, 5019 Monastir, Tunisia

Abstract

New spiro-isoquinolinoisoxazolines were prepared by regioselective 1,3-dipolar cycloaddition of 4-arylidene-isoquinoline-1,3-dione derivatives 1a-d with arylnitrile oxides 2e-g. In all cases, two regioisomers 3ae-dg and 4ae-dg were isolated with comparable ratios. Regioselectivity was established by unambiguous structural NMR assignments and X-ray diffraction analysis.

■ A Novel Tetra(tetrathiafulvalene-Thiacrown Ether)-Substituted Porphyrazine: Synthesis, Electrochemical, and Control Aggregation in Solution by Complexation of Transition-Metal Ions

Ruibin Hou, Cuiping Jiang, and Bingzhu Yin*

*Key Laboratory of Organism Functional Factor of Changbai Mountain, Ministry of Education, Yanbian University, 977, Park Road, Yanji City, Jilin Prov. 133002, China

Abstract

Synthesis of a novel magnesium porphyrazine 6，peripherally substituted with S4 crown ether-TTF macrocycles was described. Molecular structure has been fully characterized by 1H-NMR, IR, MS, and elemental analysis. Crystal structure of the precursor was determined by X-ray crystallography. Their solution electrochemical data showed two reductive and three oxidative processes within a -1.3 V to -1.5 V potential window. UV/Vis spectroscopy and electron paramagnetic resonance (EPR) measurements revealed the formation of a charge-transfer complex between porphyrazine 6 with F4TCNQ. UV/vis spectroscopy showed that addition of the transition-metal ions led to dimerization of the porphyrazine complexes.