HETEROCYCLES

■ Contents

■ Heterocycles Award

HETEROCYCLES Announcement*

*The Japan Institute of Heterocyclic Chemistry, 1-7-17, Motoakasaka, Minato-ku, Tokyo 107-0051, Japan

■ Recent Advancements in the Synthesis of Half-Esters and Their Applications

Jianjun Shi and Satomi Niwayama*

*Division of Sustainable and Environmental Engineering, Graduate School of Engineering, Muroran Institute of Technology, 27-1, Mizumoto-cho, Muroran, Hokkaido, 050-8585, Japan

Abstract

Half-esters are important building blocks for the synthesis of pharmaceuticals, polymers and natural products. Therefore, synthetic methodologies for both chiral and racemic half-esters have been actively investigated for decades. This short review summarizes recent progress in the synthesis of half-esters and their applications including the studies from our laboratories.

■ Divergent Synthesis of Steroid Analogs from Steroidal β-Formylenamides, Conjugated Enones and β-Formylvinyl Halides

Geetmani S. Nongthombam and Romesh C. Boruah*

*Chemical Science and Technology Division, CSIR-North East Institute of Science & Technology, Jorhat, Assam, India 785006

Abstract

In the past two decades, our laboratory has been actively engaged in the design and synthesis of novel heterosteroidal analogues. Three functional groups namely β-formylenamide, conjugated enone and β-formylvinyl halide were primarily employed in various reactions to afford a library of novel heterosteroids. The synthetic strategies have been concomitantly utilized in the relevant non-steroidal β-formylenamides, conjugated enones and β-formylvinyl halides.

■ Synthesis of 4,4-Dimethyl-2-(2-pyrrolyl)-2-oxazolines

Kentaro Okano,* Kazuki Morii, Daichi Mari, and Atsunori Mori

*Department of Chemical Science and Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan

Abstract

A practical synthesis of 4,4-dimethyl-2-oxazolines on pyrrole was achieved via the cyclization of the corresponding amides, which were derived from the trichloroacetylpyrroles. The established conditions were applicable to pyrroles bearing a ketone or an ester moiety. In addition to pyrroles, the method could be extended to the synthesis of the indole derivative.

■ Ring-Opening Metathesis of N-Alkenyl β-Lactams

Sambasivarao Kotha,* Sunil Pulletikurti, and Yuvaraj Dommaraju

*Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400 076, India

Abstract

We have synthesized a new class of N-alkenylated β-lactam derivatives and studied their metathetic behavior. Here, ring-opening metathesis is more favorable than ring-rearrangement metathesis. Molecular modelling studies revealed that the orientation of two olefinic moieties of β-lactam derivatives are far apart and therefore ring-rearrangement metathesis did not occur and ring-opening metathesis is only feasible.

■ Reaction of 2,3,5,6,7,8-Hexahydroquinoxaline with Thiourea Derivatives: Analysis of the Structure and Conformational State of [4.4.3]Propellane

Kazuhide Nakahara,* Koki Yamaguchi, and Hisao Kansui

*Department of Integrative Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan

Abstract

The reaction of 2,3,5,6,7,8-hexahydroquinoxaline with thiourea derivatives yields a propellane-type tetraazaindene structure, whose conformation was established by 2D NMR analysis and molecular orbital calculations, and verified by single-crystal X-ray diffraction analysis. Further, the result obtained from X-ray analysis of this propellane-type tetraazaindene structure indicated that the crystalline state was stabilized by specific hydrogen bonds; four hydrogen bonds were of the type >C=S•••H–N, four of N–H•••N type between the imidazolidine moieties, and two of >C=S•••H–C type.

■ Divergent Synthesis of 5,6- and 3,6-Dihydropyridin-2(1H)-one via Intramolecular Knoevenagel Condensation

Arturo Bocardo-Bautista, María L. Orea, Jorge R. Juárez, Dino Gnecco, David M. Aparicio,* and Joel L. Terán*

*Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edif. IC9, Complejo de Ciencias, C.U. 72570 Puebla, Pue., México.

Abstract

A simple and friendly strategy for the regioselective synthesis of 5,6- and 3,6-dihydropyridin-2(1H)-one via intramolecular Knoevenagel condensation from a common methyl 3-((2-(1,3-dioxolan-2-yl)ethyl)alkylamino)-3-oxopropanoate under acidic conditions is reported.

■ Synthesis of [1,4]Dithiino[2,3-d]pyrimidine-6-carbonitrile Derivatives via the Reaction of 2-[(4-Chloropyrimidin-5-yl)sulfanyl]acetonitriles with Carbon Disulfide

Kazuhiro Kobayashi,* Kota Yamasaki, Daiki Fujiwara, Kazuma Nozaki, Hidetaka Hiyoshi, and Kazuto Umezu

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

Abstract

An efficient procedure has been developed for the preparation of 7-(alkylsulfanyl)[1,4]dithiino[2,3-d]pyrimidine-6-carbonitrile derivatives from 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP). 2-{[4-Chloro-2-(methylsulfanyl)pyrimidin-5-yl]sulfanyl}acetonitriles are prepared via the reaction of the 5-lithio derivative of DCSMP with sulfur and then 2-bromoacetonitrile. These can be converted into the desired products on treatment with carbon disulfide in the presence of sodium hydride followed by alkyl halides. This is the first construction of the [1,4]dithiino[2,3-d]pyrimidine structure.

■ 4,6-Diacetylresorcinol in Heterocyclic Synthesis Part II: Synthesis of Some Novel 4,6-Bis(azolyl/azinyl/azepinyl)resorcinols

Mohammed A. Assiri, Tarik E. Ali,* Magdy A. Ibrahim, E. M. El-Amin, and I. S. Yahia

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo, Egypt

Abstract

A series of new 4,6-bis(azolyl/azinyl/azepinyl)resorcinols was synthesized in a combinatorial manner besides, (2E,2'E)-4,6-bis[3-(aminophenyl-substituted)prop-2-en-1-oxo-1-yl]resorcinols were also obtained. Heterocyclization of (2E,2'E)-4,6-bis[3-(dimethylamino)prop-2-en-1-oxo-1-yl]resorcinol (2) with nitrogen-containing binucleophiles afforded the target compounds. All the newly synthesized compounds were characterized by spectral tools.

■ Synthesis of 2H-Benzo[b]thietes by TFA-Mediated Cyclization of O-tert-Butyl S-(2-Vinylphenyl) Carbonothioates via 4H-3,1-Benzoxathiin-2-one Intermediates

Kazuhiro Kobayashi* and Takuma Ueyama

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

Abstract

An efficient method for the preparation of 2H-benzo[b]thiete derivatives under mild conditions has been developed. The reaction of 2-(1-arylethenyl)phenyl bromides with butyllithium at –78 ˚C generates 2-(1-arylethenyl)phenyllithiums, which are successively treated with sulfur and Boc2O at the same temperature to afford S-[2-(1-arylethenyl)phenyl] O-tert-butyl carbonothioates. These compounds are then treated with TFA at 0 or 20 ˚C to yield 2-aryl-2-methyl-2H-benzo[b]thietes via formation of the 4-aryl-4-methyl-4H-3,1-benzoxathiin-2-ones followed by decarboxylation.