HETEROCYCLES

■ Contents

■ The Interrupted Pummerer Reaction: Design of Sulfoxides and Their Utility in Organic Synthesis

Kazuhiro Higuchi* and Masanori Tayu

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Acid anhydride-activated sulfoxides can undergo a variety of cascade reactions after reacting with nucleophiles on its sulfur atom. Originally regarded as an abnormal phenomenon that occurs under Pummerer reaction conditions, the reports of the reaction increased gradually, and research regarding sulfoxide reactivity has advanced. In recent years, the term ‘interrupted Pummerer reaction’ has been introduced, and the transformation has been actively incorporated into the development of new research areas. Such studies have yielded numerous valuable sulfoxides, which contribute to the precise reaction control and to the generation of practical products. Notably, the outcome of the interrupted Pummerer reaction is characteristic for each nucleophile.

■ Attractive Organic Cocrystal Materials in Optics

Xiao Han,* Linyu Wang, and Gaiqing Xi

*College of Chemical Engineering & Material, Hebei Key Laboratory of Heterocyclic Compounds, Handan University, Handan 056005, Hebei, China

Abstract

Since the beginning of this century, organic molecule solid material, one of favorable choices for constructing high-performance optoelectronic devices/circuits, has showed the impressive perspective in organic optoelectronics. Especially, because of the long-range order, absent grain boundary and extremely low defect density, organic single-crystal material support a great platform for fundament and application researches. Herein, cocrystal engineering, one simply collaborative strategy, shows offers the unique advantages, involving facile and low-cost synthesis procedure, easily achieving rare and multifunctional properties, tunable structure, morphology and size. It is extremely suitable to construct functional organic molecule solid material, especially novel multifunctional organic single-crystal materials. In this mini review, a overview of organic cocrystal is presented to introduce its attractive future in optics, such as OFET, lasing, nonlinear optics, optical waveguide material, stimuli-responsive material and other potential applications.

■ Purification of High-Purity 2-Mercaptobenzothiazole by Two-Steps

Zengbing Zhao, Bo Chen, Lanxing Cheng,* Yili Zhao, Yongli Chai, and Shucheng Yang

*Henan Chemical Industry Research Institute Co., Zhengzhou, 450052, China

Abstract

High-purity 2-mercaptobenzothiazole (2-MBT) is prepared from crude 2-MBT by aniline method under high pressure by solvent crystallization and deep impurity removal. For the first step of toluene purification, the semi-finished 2-MBT with excellent purity and yield can be obtained when the temperature of toluene solution reaches 100 oC and the content of toluene is about 1.5 times of that of crude 2-MBT. For the second step of deep purification, the by-products of semi-finished 2-MBT could be further removed by Na2SO3 when the mass ratio of water, the 2-MBT and Na2SO3 is 2: 1: 0.12 and the reaction condition is under 100 oC for 0.75 h. As a result, the purity and yield of 2-MBT can reach 99.9% and 97.3%, respectively. The preparation of high-purity 2-MBT would further optimize the market demand and meet the quality standard requirements for the development of other pharmaceutical intermediates or fine chemicals. This strategy solves the current problem of purification 2-MBT, and develops a new process technology route for the production of high-purity 2-MBT.

■ Copper Corrole Catalyzed Esterification of C(sp3)-H with Carboxylic Acids via Cross-Dehydrogenative Coupling Reaction

Zhao-Yang Liu, Wei-Yu Peng, Waseem Akram, Jia-Wei Lai, Hao Zhang, and Hai-Yang Liu

*Department of Chemistry, The Key Laboratory of Fuel Cell Technology of Guangdong Province, South China University of Technology, Guangzhou 510640, China

Abstract

Copper corrole complex was firstly used as catalyst for oxidative esterification of un-reactive C(sp3)-H bond of cyclic ether and carboxylic acid via cross dehydrogenative coupling (CDC) reaction using di-tert-butyl peroxide (DTBP) as oxidant. A wide range of carboxylic acids can react with cyclic ether with good to excellent yields, showing copper corrole is a new kind of promising catalyst for CDC reaction. Under gram-level test, the turnover number (TON) may achieve 8400 with 84% yield at only 0.01% catalyst loading, demonstrating its practical uses.

■ Synthesis, Photochemical Properties, and Cytotoxicity of 10-Alkylphenazin-2(10H)-ones

Haruki Kohatsu, Shogo Kamo, Takuya Hosokai, Shinji Kamisuki, Yutaro Machida, Ryota Kobayashi, Tsuneomi Kawasaki, Kenji Ohgane, and Kouji Kuramochi*

*Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

In the present study, the synthesis of a variety of 10-alkylphenazin-2(10H)-ones by oxidative coupling between N-alkylbenzene-1,2-diamine and 1,2,4-benzenetriol under an oxygen atmosphere was realized, and their photochemical and biological properties were investigated. 10-Methylphenazin-2(10H)-one, a reddish orange pigment, exhibited fluorescence in the visible light region upon exposure to ultraviolet light. Interestingly, the fluorescence from 10-methylphenazin-2(10H)-one consisted of two components. In addition, the cytotoxic evaluation of various synthetic compounds was performed. Among the compounds tested in this study, 10-methylphenazin-2(10H)-one exhibited the most selective cytotoxic activity against human cancer A549 cells compared to normal MRC-5 cells.

■ Secoiridoid Glucosides Esterified with a Phenolic Glucoside from Alstonia macrophylla

Atsuko Itoh, Eri Kawaguchi, Sayo Nishio, Kaori Tani, Misaki Uchigaki, Marina Nakamura, Toru Akita, Toyoyuki Nishi, and Takao Tanahashi*

*Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.

Abstract

Eleven novel secoiridoid glucosides, O-methylfrachinoside (1) and alstomacrosides A–J (2–11) were isolated, together with seventeen known compounds, from the dried twigs of Alstonia macrophylla. The structures of the new compounds were established on the basis of 1D and 2D NMR spectroscopic data. These compounds were commonly characterized as esters of secoxyloganin with a phenolic glucoside.

■ Synthesis and Evaluation of Dendroamide A and Three Regioisomeric Analogs Having a Reversed Azole Ring as P-Glycoprotein Inhibitors

Takuji Magata, Yoshimi Hirokawa, Yuki Rokuhara, Ryota Nakayama, Rina Takahashi, Masashi Nogami, Yasuto Tai, Tomoki Imahori, Takanori Hashizume, and Naoyoshi Maezaki*

*Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-Kita, Tondabayashi, Osaka 584-8540, Japan

Abstract

We have synthesized dendroamide A and three new analogs having a differently oriented azole moiety to reveal the effect of the orientation of the azole rings on the P-glycoprotein inhibitory activity. The appropriate assembly of modified azole units and dimers from natural-type azole units is examined. Although linear trimers including a modified thiazole unit were hard to cyclize compared with a derivative containing a modified oxazole unit, the yields of cyclization were successfully improved by changing the reaction conditions or the position of ring closure. Evaluation of P-glycoprotein inhibitory activity also reported.

■ Synthesis and Cytotoxicity Properties of Some Novel Functionalized 2-{2-[(4-Oxo-4H-chromen-3-yl)methylene]hydrazinyl}-1,3-selenazoles

Tarik E. Ali,* Mohammed A. Assiri, and Hanaa R. Aboelwafa

*Department of Chemistry, Faculty of Science, King Khalid University, Abha, Saudi Arabia

Abstract

A series of novel functionalized 1,3-selenazoles bearing 4-oxo-4H-chromen-3-yl moiety was constructed by Hantzsch-type condensation reaction. The methodology depended on the cyclization of N-[(4-oxo-4H-chromen-3-yl)methylene]selenosemicarbazide with bis-halogen and α-halocarbonyl compounds in DMF. The structures of the synthesized compounds were assigned based on the spectral tools. The cytotoxicity properties of the products were evaluated. Both compounds 9 and 11 showed significant cytotoxic properties against HCT-116, Hep-G2, A-549 and MCF-7 cancer cell lines.

■ One-Pot and Three-Component Synthesis of Some Novel Functionalized Chromonyl Pyrido[2,3-d]pyrimidines as Anticancer Agents

Tarik E. Ali,* Mohammed A. Assiri, Ali A. Shati, Mohammad Y. Alfaifi, Serag Eldin I. Elbehairi, and Attalla F. El-Kott

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

Abstract

A facile and efficient method for the construction of functionalized chromonyl pyrido[2,3-d]pyrimidines via a one-pot, three-component reaction of 6-aminothiouracil and 4,6-diaminopyrimidine-2(1H)-thione with 4-oxo-4H-chromene-3-carboxaldehyde in the presence of different nitrile active methylene compounds in distillated water at 70 oC without using a catalyst was achieved. The methodology displayed excellent yields and simple workup procedure. The targeted compounds were assessed for their in vitro anticancer activity against mammary gland breast cancer cell line (MCF-7), liver cancer (HepG-2), and human colon cancer (HCT-116) by using sulphorhodamine B assay (SRB) method, while doxorubicin, was utilized as standard reference drug. Compounds 4b and 6a were the best potent cytotoxic agents towards liver (HepG-2) and colon (HCT-116) compared with doxorubicin as a reference drug with IC50 values ranging from 1.1 to 1.8 μg/mL.

■ Rhodium(I) N-Heterocyclic Carbene Complexes as Catalysts for the Anti-Markovnikov Hydroaminations of Styrene

Yetkin Gök, Beyhan Yiğit, Özlem Özeroğlu Çelikal, and Murat Yiğit*

*Department of Chemistry and Chemical Process Technologies, Vocational School of Higher Education, Adiyaman University, 02040-Adıyaman, Turkey

Abstract

A series of new rhodium(I) complexes with benzimidazole based N-heterocyclic carbene (NHC) ligand were synthesized by reactions of benzimidazolium salts with [Rh(OMe)COD]2. The characterization of rhodium(I) complexes with the general formula [RhCl(NHC)(η4-1,5-cyclooctadiene)] was done by physicochemical and spectroscopic methods. All the synthesized complexes were tested as catalysts in the intermolecular hydroamination reactions between styrene with aromatic amines in ionic liquid. All of these complexes tested here are catalytically active for the intermolecular hydroamination of styrene with aromatic amines in ionic liquid. The anti-Markovnikov addition products were obtained selectively by using 1 mol% of the rhodium complex.

■ A New Chromone Derivative from Endophytic Fungus Xylaria sp. ECN212

Ken-ichi Nakashima,* Junko Tomida, Yoshiaki Kawamura, and Makoto Inoue

*Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan

Abstract

A new chromone derivative as well as four known polyketides were isolated from cultures of the endophytic fungus Xylaria sp. ECN212. The structure of the new compound was determined by extensive spectroscopic analyses. Furthermore, the absolute configuration of the new compound was established by comparison of experimental and calculated electronic circular dichroism data. The new compound is a related compound of xylariacetal, isolated from Xylaria sp. ECN8 in our previous study.

■ Synthesis and Properties of Fused Triad Donors Composed of Two 1,3-Dithiole[5]radialenes and Extended Tetrathiafulvalene

Kohei Kagawa, Takayuki Higashi, Aya Yoshimura, and Yohji Misaki*

*Department of Applied Chemistry, Graduate School of Science and Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama, Ehime 790-8577, Japan

Abstract

Synthesis of fused triad donors composed of two 1,3-dithiole[5]radialenes and one vinyl-extended or thiophene-inserted teterathiafulvalene (5, 6) have been successfully synthesized. Both donors exhibited simultaneous eight-electron oxidation attributed to simultaneous oxidation of two extended 1,3-dithiole[5]radialene units.