HETEROCYCLES

■ Contents

■ Diazonaphthoquinones: Synthesis, Reactions and Applications

Dina I. A. Othman and Mitsuru Kitamura*

*Department of Applied Chemistry, Faculty of Engineering, Kyushu Institute of Technology, 1-1 Sensuicho, Tobata, Kitakyushu, 804-8550, Japan

Abstract

This review deals with synthesis and reactions of diazonaphthoquinones during the past 6 years. Various substituted diazonaphthoquinones have been prepared by the reaction of the appropriate naphthol and 2-azido-1,3 dimethyl imidazolinium chloride (ADMC) in short direct pathway. This method is likely to find wide spread uses in organic synthesis and material chemistry such as for preparing photoresists. In this review, different metal catalyzed reactions are investigated and applied successfully to the synthesis of important aromatic compounds. In addition, total synthesis of some natural compounds has been attempted using this recently developed diazo transfer methodology. It is hoped that this compilation, in combination with the previously published literatures on diazo-transfer reaction, will provide useful, up-to-date and comprehensive foundation and reference sources for individuals interested in the same field.

■ Oxidative Dearomatic Cyclization of N-Substituted Benzanilide Derivatives: Conformational Effect of Amide Groups on the Reaction

Kousuke Hayashi, Jun Takayama,* Meiyan Xuan, Misaki Suda, Hiroyuki Teramae, and Takeshi Sakamoto*

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

The synthesis of spirooxindoles with a hypervalent iodine reagent depended on N-substituted benzanilide derivatives as starting materials. Reaction yields of benzanilides containing various N-substituents were discovered to relate to the cis and trans conformations of the amide bond by ab initio molecular orbital calculations at the B3LYP/6-31G(d,p) and MP2/6-31G(d,p) levels, including full geometry optimizations. The relationship between the reaction and conformation of the starting material by quantum chemical calculations was applied to the formal synthesis of SR121463.

■ Synthesis of Nitriles from Aldehydes with Trimethylphenylammonium Tribromide and Ammonium Acetate

Shinsei Sayama*

*Natural Sciences (Chemistry), Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan

Abstract

Various aromatic and heterocyclic aldehydes were easily converted to respective nitriles with the combination of trimethylphenylammonium tribromide and ammonium acetate in good yields at room temperature.

■ Exploring the Synthesis of Deceptively Simple Biginelli Products through N-CN Bond Cleavage

Juan Jesús Nolasco Fidencio, Hulme Ríos-Guerra,* Gilberto González-Villanueva, José Guillermo Penieres-Carrillo, Gustavo Guevara Balcázar, Ma. Inés Nicolás-Vázquez, Hulme Ríos-Guerra, and Francisco Delgado

*Faculty of Higher Cuautitlan Studies, Chemistry Science Department, UNAM, Av. 1° de Mayo s/n Sta. Ma. Gpe. las Torres, Postcode 54740, Cuautitlán Izcalli, Mexico

Abstract

Brønsted-Lowry acid-promoted cleavage of the N-CN bond in 2-cyanoimino-3,4-dihydro-(1H)-pyrimidine is described. Formic acid efficiently activates cyclic N-cyanoguanidines through an O-formylisourea reactive intermediate, leading to chemospecific N-CN bond cleavage of the cyanoimine moiety. This low environmental-load method provides step- and atom-economical access to difficult-to-obtain acid-sensitive Biginelli products in excellent yields.

■ Synthesis of 2-Alk(or Aryl)oxy- and 2-(Alkyl(or Aryl)sulfanyl)-4H-3,1-benzothiazine Derivatives Carrying a (Z)-Halomethylidene Substutuent at the 4-Position

Kazuhiro Kobayashi* and Takashi Nogi

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

Abstract

2-Alk(or aryl)oxy-4-(Z)-(halomethylidene)-4H-3,1-benzothiazines were synthesized by the reaction of 2-(2,2-dihaloethenyl)phenyl isothiocyanates with sodium alk(or aryl)oxides. Similar treatment of the 2-(2,2- dibromoethenyl)phenyl isothiocyanates with sodium thiolates gave the corresponding 2-(alkyl(or aryl)sulfanyl)-4-(Z)-(bromomethylidene)-4H-3,1- benzothiazines. The above 2-aryloxybenzothiazine derivative underwent clean conversion to 2-aryloxy-4-(Z)-[(arylsulfanyl)methylidene]-4H-3,1-benzothiazines on treatment with sodium arenethiolates. 2-(Arylsulfanyl)-4-(Z)- [(arylsulfanyl)methylidene]-4H-3,1-benzothiazines were also synthesized by the reaction of 2-(2,2-dibromoethenyl)phenyl isothiocyanates with two equivalents of sodium arenethiolates.

■ Synthesis of Prodelphinidin Trimer Isolated from Cistus Albidus and its Growth Inhibitory Activity Against Human Prostate Cancer Cell Lines

Masataka Mori, Kiriko Matsumoto, Chisato Ishihara, Koichiro Kawaguchi, Sei-ichi Kawahara, Yasunao Hattori, Hiroshi Fujii,* and Hidefumi Makabe*

*Sciences of Functional Foods, Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa-mura, Kamiina-gun, Nagano 399-4598, Japan

Abstract

First synthesis of prodelphinidin trimer (epigallocatechin-gallocatechin-catechin) isolated from Cistus albidus was accomplished from monomeric epigallocatechin electrophile and dimeric gallocatechin-catechin nucleophile. The condensation was worked using AgOTf as a Lewis acid and condensed product was successfully converted into titled compound in good yield. Synthesized compound showed significant growth inhibitory activity against human prostate PC-3 cell lines. Its activity was little bit stronger than that of prodelphinidin B3.

■ Thiosemicarbazides, Potent Reagents for Synthesis of Some New 1,4-Diphenylbenzo[g]quinoxaline-5,10-dione Based Heterocycles

Islam H. El Azab* and Hosam A. Saad

*Department of Chemistry, Faculty of Science, Aswan University, Aswan 81528, Egypt

Abstract

2-(5,10-Dioxo-1,4-diphenyl-3,4-dihydrobenzo[g]quinoxalin-2(1H,5H, 10H)-ylidene)hydrazinecarbothioamide (4) and 2-((4-oxothiazolidin-2-ylidene)- hydrazono)-1,4-diphenyl-1,2,3,4-tetrahydrobenzo[g]quinoxaline-5,10-dione (5), were prepared and utilized as versatile building blocks, via incorporating in series of conversions including cyclocondensation reactions to afford a series of four and fivepharmacophoricmotif conjugates 10, 13, 18, 20, 21, 25, 30, 31, 32, 33 and 34 in fair yields.

■ Three New Phenylpropanoids from the Leaves of Yunnan Local Sun Cured Tobacco and Their Bioactivities

Feng-Mei Zhang, Jian-Jun Xia, Pei-Song Yang, Qin-Peng Shen, Chun-Bo Liu, Pei He, Jia-Qiang Wang, Zhi-Hua Liu,* and Zhong-Tao Ding*

*Key Laboratory of Tobacco Chemistry of Yunnan Province, China Tobacco Yunnan Industry Company, Hongjin Road 181#, Kunming, 650231, China

Abstract

Three new benzolactones, 5-(hydroxymethyl)-6-(2-oxopropyl)isobenzofuran-1(3H)-one (1), 5-methyl-6-(2-oxopropyl)isobenzofuran-1(3H)-one (2), and 5-methoxy-6-(2-oxopropyl)isobenzofuran-1(3H)-one (3), together with three known benzolactones (4-6) were isolated from the leaves of Yunnan local sun cured tobacco. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-3 were tested for their anti-tobacoo mosaic virus (TMV) activities and compounds 1-6 were tested for their cytotoxicity activities. The results revealed that compound 1-3 showed high anti-TMV activity with inhibition rate of 28.6, 31.2 and 32.7%. 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 2.5-8.5 μM.

■ Microwave-Assisted Efficient Synthesis of 4-Substituted Amino-2-methylquinolines Catalyzed by p-Toluenesulfonic Acid

Xiao-qin Wang,* Yuan-hong Cai, Xiao-yang Xie, Cui-ying Huang, Jia-yu Li, Wen-na Chen, Ming-hua He, and Wen-jia Pan*

*School of Pharmacy, Guangdong Medical University, NO1, Xincheng Road, Songshan Lake, Dongguan 523808, China

Abstract

A series of novel 4-subtituted amino-2-methylquinolines (3a-3o) were readily synthesized via the reaction of 4-chloro-2-methylquinoline with amines catalyzed by p-toluenesulfonic acid (TsOH) at 120 ℃ for 1 h under microwave-assisted organic synthesis (MAOS) condition. The yields of product 3a-3o were in range of 55-89%. This approach has advantages such as higher yield, shorter reaction time, lower costs, more convenience, and higher efficiency compared to the conventional method. The structures of the products were characterized by using 1H NMR, 13C NMR and HRMS. The reactivity of different amines was discussed.

■ Palladium Catalyzed Syntheses of Dibenzothiophenes by Ring-Closure of 2-Iodinated Diaryl Thioether

Ya-Fang Chen, Rui-Yue Ma, Lu-Nan Zhou, Zhen-Ting Du,* and Tao Zhang*

*Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A＆F University, Yangling 712100, Shaanxi Province, China

Abstract

An efficient ring-closure of 2-iodo diaryl thioether at the presence of palladium catalyst to form dibenzothiophene is described. After the best condition was set up as Pd3(dba)2 as the catalyst, anhydrous Cu(OAc)2 as additive, PivONa.H2O as base, DMF as solvent, a series of dibenzothiophenes could be successfully obtained through this protocol in moderate to excellent yields.

■ A New and Practical Synthesis of Tivozanib

Chunping Zhu, Yongjun Mao,* Han Wang, and Jingli Xu

*College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Rd., Songjiang, Shanghai, 201620, China

Abstract

New and improved synthetic route of tivozanib is described on a hectogram scale. An reduction cyclization process to prepare the key intermediate 6,7-dimethoxyquinolin-4-ol from the 3-(dimethylamino)-1-(2-nitrophenyl)prop-2- en-1-one compound at H2/Ni condition is adopted in good result. Commercial available materials, simple reaction and operation are used, including nitration, condensation, hydrogenation, chlorination and so on, to give the final product in 28.7% yield over six steps and 98.9% purity (HPLC).