HETEROCYCLES

■ Contents

■ Heterocycles Award

HETEROCYCLES Announcement*

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

■ 1,2,3-Benzotriazin-4(3H)-ones: Synthesis, Reactions and Applications

Zunera Khalid, Hafiz Adnan Ahmad, Munawar Ali Munawar,* Misbah-ul-Ain Khan, and Salman Gul

*Institute of Chemistry, University of the Punjab, Lahore 54590, Pakistan

Abstract

An up-to-date review of 1,2,3-benzotriazin-4(3H)-ones including its synthesis, reactions and applications is presented. The title ring system deserves a special treatment due to its increasing importance in pharmaceuticals, imaging and recording materials.

■ A Simple Approach Synthesis of Benzo[b]Pyrazolo-[3,2-h][1,6]Naphthyridin-1(2H)-Ones

Jian-Nan Yang, Dao-Lin Wang,* and Jian-Hua Qian

*Liaoning Key Laboratory of Synthesis and Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

A simple method for the synthesis of benzo[b]pyrazolo[3,2-h][1,6]- naphthyridin-1(2H)-ones by a tandem addition-elimination-cyclization reaction strategy from α-(dimethylaminomethylene)-2-cyanomethylquinoline-3-carboxylate and hydrazine has been developed.

■ Enantioselective Protecting-Group-Free Synthesis of (+)-9,10-Dihydroecklonialactone B

Asmaa Said Ali Yassen, Jun Ishihara, and Susumi Hatakeyama*

*Medical Innovation Center, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

An enantioselective protecting-group-free route to ecklonialactones, C-18 oxylipins isolated from the brown algae, was demonstrated by the synthesis of (+)-dihydroecklonialactone B from (E)-ethyl hex-3-enoate in 17 steps.

■ Synthesis and Optical Properties Research of Some Novel Trichromophore Compounds Containing Coumarin, Pyrazoline and Naphthalimide Groups

Wu Gongying, Zhao Fang, Hu Yang, and Hu Shengli*

*College of Chemistry and Chemical Engineering, Hubei Normal University, Huangshi 435002, China

Abstract

A series of novel trichromophore compounds containing coumarin, pyrazoline and naphthalimide groups were synthesized and their properties were elucidated using absorption and fluorescence. In chloroform solution, their maximal absorption bands and the maximal emission bands slightly varied from 478 to 485 nm and from 559 to 565 nm, respectively.

■ Efficient and Diastereoselective Synthesis of bis-Quinazolinedione Derivatives via Low-Valent Titanium Reagent

Wei Lin,* Yazhen Wang, Yongxiang Zheng, and Daqing Shi*

*School of Chemistry and Environmental Engineering, Jiangsu Technology of University, Changzhou , Jiangsu 213001, China

Abstract

An efficient and simple method for the synthesis of chiral benzo[5,6][1,3]oxazino[4,3-c]quinoxaline-dione and octahydroquinoxalino- [1,2-c:4,3-c']diquinazoline-dione derivatives using 2-hydroxybenzaldehydes (or 2-nitrobenzaldehydes) and chiral cyclohexane-1,2-diamine as the starting materials promoted by low-valent titanium reagent has been described. The structures of all synthesized products were identified by their IR, 1H NMR, 13C NMR and HRMS analysis, and the structure of compound 8a was confirmed by X-ray diffraction analysis.

■ Efficient Construction of N-heterocycles from Benzylic Ethers/Alcohols and o-Substituted Anilines without Using any Catalyst and Additive

Xiuling Chen, Hongxue Qi, Shaofeng Wu, Leng Liu,* Jianhui Wen, Wanxi Li, Fang Guo, Yongjun Bian, and Jun Li*

*School of Chemistry & Chemical Engineering, Jinzhong Universityu, Shanxi Province Jinzhong University, 030600, China

Abstract

A novel method for the synthesis of N-heterocycles from benzylic ethers/alcohols with o-substituted aniline without using any catalyst and additive is developed. This protocol involves C-O bond cleavage of benzylic ethers, N-benzylation, and benzylic C-H amidation in one pot, the tandem oxidation-cyclization transformation may open the door for the easy generation of N-heterocycles.

■ Three New Isobenzofurans from the Root of Yunnan Local Sun Cured Tobacco and Their Bioactivities

Zhen-Yuan Xia, Li-Fang Zhang, Xiao-Han Mo, Yu-ping Wu, Ling Ye, Dan-Yu Tang, Feng-Mei Zhang, Pei He, Zhi-Hua Liu, Qin-Peng Shen, Chun-Bo Liu, and Tian-fei Li*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, Yunnan Academy of Tobacco Science, Kunming 650106, China

Abstract

Three new isobenzofurans (1-3), together with three known isobenzofurans (4-6) were isolated from the root of Yunnan local sun cured tobacco. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-4 were tested for their anti-tobacoo mosaic virus (TMV) activities and compounds 1-6 were tested for their cytotoxicity activities. The results revealed that compounds 1-4 showed high anti-TMV activity with inhibition rate of 31.4, 35.2 and 38.8, 29.6%. These rates are close to that of positive control. Compounds 1-6 also showed moderate-to- weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 2.6 -9.5 μM.

■ Facile and Convenient Syntheses of Fluorine-Containing Pyrimido[5,4-c]quinolines and Benzo[h][1,6]naphthyridines by Condensation Reaction of 2-Methoxy-3-trifluoroacetyl-4-quinolylamine with Aldehydes and Ketones

Mizuki Hatakenaka and Etsuji Okada*

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

Abstract

2-Methoxy-3-trifluoroacetyl-4-quinolylamine reacted easily with various aldehydes in the presence of aqueous ammonia to afford mainly trifluoromethylated pyrimido[5,4-c]quinoline derivatives in moderate to high yields. In contrast, the use of ketones instead of aldehydes in the presence of pyrrolidine, exclusively gave benzo[h][1,6]naphthyridine derivatives in good to excellent yields.

■ A new Isocoumarin Derivative from an Endophytic Fungus Thielavia sp. Isolated from Crassula ovata

Ken-ichi Nakashima,* Junko Tomida, Takao Hirai, Yuji Morita, Yoshiaki Kawamura, and Makoto Inoue

*Laboratory of Medicinal Resources, Faculty of Pharmaceutical Sciences, Aichi Gakuin University, 1-100 Kusumoto-cho Chikusa-ku Nagoya city 464-8650, Japan

Abstract

Thielavic acid (1), a new isocoumarin derivative, was isolated from an endophytic fungus Thielavia sp. ECN-115, which was obtained from the stems of Crassula ovata. The relative structure of 1 was established by spectroscopic analyses including extensive 2D-NMR experiments. The absolute configuration was identified as (4S)-thielavic acid by comparing the experimental and calculated electronic circular dichroism spectra.

■ One-Pot Palladium-Catalyzed Racemization of (S)-Praziquanamine: A Key Intermediate for the Anthelmintic Agent (R)-Praziquantel

Zhezhou Yang, Xiang Guo, Shanghu Xu, Huirong Jiao, Zhinmin Tan, and Fuli Zhang*

*Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 285 Gebaini Road, Shanghai 201203, China

Abstract

An one-pot palladium-catalyzed procedure for racemization of (S)-praziquanamine, which is the undesired enantiomer and produced during the resolution step for preparing the anthelmintic drug (R)-praziquantel, has been developed through dehydrogenation of (S)-praziquanamine into 6,7-dihydro-4H-pyrazino[2,1-a]isoquinolin-4-one and then hydrogenation of the double bonds. And a superior racemization method was also developed that (S)-praziquanamine was directly treated with Pd/C under H2 atmosphere to obtain a racemic mixture in quantitative yield with 95% chemical purity. Such a concise and efficient approach to the racemization of (S)-praziquanamine can be useful to recycle the waste enantiomer into the resolution process to obtain the (R)-enantiomer on a large scale.

■ Molecular Structure and Spectroscopic Properties of [2,3,9,10,16,17,23,24-Octakis(3-carboxyphenoxy)phthalocyaninato-κ4N](pyridine-κN)zinc(II) Pyridine Octasolvate

Rei Fujishiro, Hayato Sonoyama, Yuki Ide, Shigeki Mori,* Tamotsu Sugimori, Atsushi Nagai, Katsumi Yoshino, Mikio Nakamura, and Takahisa Ikeue*

*Department of Chemistry, Graaduate School of Science and Engineering, Shimane University, 1060 Nishikawatsu, Matsue, Shimane 690-8504, Japan

Abstract

The title complex, [2,3,9,10,16,17,23,24-octakis(3-carboxyphenoxy)- phthalocyaninato-k 4N] (pyridine-kN)zinc(II) pyridine octasolvate abbreviated as [ZnPc(3-CO2H)8(Py)]ˑ8(Py) (2), has been obtained by recrystallization of [ZnPc(3-CO2H)8]·(1) from pyridine. Molecular structure of 2 determined by X-ray crystallography exhibits the anticipated N5 square pyramidal coordination structure around zinc(II) ion, where the average Zn-N(Pc) and Zn-N(Py) bond lengths are 2.027(4) Å and 2.121(4) Å, respectively. The deviation of the zinc(II) ion from the phthalocyanine N4 plane is 0.417 Å. Eight pyridine molecules are involved in the hydrogen bonding with the carboxylic acid moieties of phenoxy rings in a 1:1 mode. Two discrete phthalocyanine molecules in a unit cell are stacked in a back-to-back fashion with an interplanar distance of 3.376 Å. Pyridine solutions of 1 exhibit well-resolved 1H NMR, UV-Vis, and fluorescent spectra, suggesting that 1 exists as pyridine ligated monomeric species.

■ One-Pot Synthesis of Imidazo[1,5-c]pyrimidine Derivatives from a 4,6-Dichloropyrimidine Derivative and Benzyl Isocyanides

Kazuhiro Kobayashi,* Daiki Fujiwara, Yuuho Shigemura, Hidetaka Hiyoshi, and Kazuto Umezu

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

Abstract

A convenient method for the synthesis of imidazo[1,5-c]pyrimidine derivatives has been developed. Thus, benzyl isocyanides are treated with sodium hydride in DMF at 0 ˚C to generate the corresponding benzyl anions, which are allowed to react with 4,6-dichloro-2-(methylsulfanyl)pyrimidine (DCSMP) to afford 1-aryl-7-chloro-5-(methylsulfanyl)imidazo[1,5-c]pyrimidines in one pot in moderate yields.