HETEROCYCLES

■ Contents

■ Dipolar Cycloadditions of Nitrones in Aqueous Media

Giorgio Molteni*

*Department of Organic and Industrial Chemistry, University of Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

1,3-Dipolar cycloadditions of nitrones in aqueous media have been recently exploited as a non-conventional protocol in the synthesis of the fully- or partly-saturated isoxazole ring. Water as the reaction medium can affect positively both cycloaddition rates and yields, while the large array of latent functionalities displayed by the cycloadducts is of interest in their further transformations. A systematic review of literature data is given; improvements with respect to the nitrone cycloaddition carried out in organic solvents will be taken into account.

■ A Facile One-Pot Synthesis of Chromeno[4,3-b][1,5]-Naphthyridines

Dong Wang, Dao-Lin Wang,* Xiao-Ce Shi, 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 and efficient synthesis of chromeno[4,3-b][1,5]naphthyridine derivatives were accomplished in high yields via the one-pot three-component reaction of 4-hydroxycoumarin, arylaldehyde and 3-aminopyridine in aqueous media catalyzed by sulfamic acid.

■ Design, Synthesis, in vitro Antiproliferative Activity Evaluation of 2-Acylaminothiopene-3-carboxamide Derivatives

Jiefeng Zhang, Fengjie Guan, Jiakun Qiu, Yanfen Fang, Lifang Yu, Jingya Li, Fan Yang, Xiongwen Zhang, Jia Li, and Jie Tang*

*Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China

Abstract

A series of 2-alkanoylamidothiophene-3-carboxamide derivatives were synthesized based on the hit compound 1. The anti-proliferative activity of all the compounds in vitro against MGC-803 (stomach) and HCT-116 (colon) cancer cell lines using SRB assays were tested. Several compounds showed improved anti-proliferative activity against MGC-803 and HCT-116. SAR study revealed that chlorine substituent in the 2-acetylamino part was important for anti-proliferative activity. 5a, 11b, 11c and 11d were the most potent compounds against MGC-803 (IC50s = 2.32-2.95 μM), and 5a and 11c also showed good anti-proliferative activity against HCT-116 cells (IC50s = 3.41-3.75 μM). In addition, the anti-proliferative activity of 11b and 11d could be attributed to the apoptosis in HCT116 cells via caspase 3 activation, confirmed by flow cytometry assay and western blot analysis. Meanwhile, 11b and 11d decreased the mitochondrial membrane potential (MMP) in HCT116 cells.

■ Strategic and Tactical Approaches to the Synthesis of 5,6-Dihydro-[1,2,4]oxadiazines

Johan J. N. Veerman,* Yorik B. Bruseker, Bart C. J. van Esseveldt, Rebecca Glen, Bryce A. Harrison, Erik H. Heijne, Andrew J. McRiner, Tommi M. Meulemans, Peter van Rijnsbergen, Wim Zonneveld, Matthew G. Bursavich,* and Duane A. Burnett

*Department of Chemistry, Mercachem B.V., Kerkenbos, 1013, Nijmegen 6546BB, Netherlands

Abstract

Three methods were developed for the synthesis of substituted 5,6-dihydro-4H-[1,2,4]oxadiazines. The desired oxadiazine rings were synthesised via reductive amination, addition to an iminium ion intermediate and by condensation of a diamine with an imidate. For all methods the scope with respect to the substituents that could be introduced was explored. It was found that the imidate condensation route was the most versatile and the products could be isolated in yields up to 91%. This route is also suitable for the introduction of chirality on the C5 and C6 position of the oxadiazine rings.

■ Synthesis of β-Glycosyl Formamides Through N-Glycosylation of Unprotected Carbohydrates

Yoshiyasu Ichikawa,* Akihito Matsukawa, Mitsutoshi Maeda, Yumiko Tomita, Rika Mimura, Ayumi Kitamori, Hiyoshizo Kotsuki, Keiji Nakano, and Toshiya Masuda

*Faculty of Science, Kochi University, 2-5-1, Akebono-cho, Kochi 780-8520, Japan

Abstract

Two new synthetic routes involving N-glycosylation of unprotected carbohydrates were developed for the preparation of β-glycosyl formamides. Using this protocol, D-glucose, D-xylose, D-galactose and D-maltose were transformed to their corresponding β-glycosyl formamides.

■ Synthesis of Quinoline Derivatives by an Improved Döebner-von Miller Reaction Using a Recyclable Ag(I)-Exchanged Montmorillonite K10 Catalyst

Janeeka Jayram and Vineet Jeena*

*School of Chemistry and Physics, University of KwaZulu-Natal, Cnr Golf and Ridge Roads 3209, South Africa

Abstract

The Döebner-von Miller synthesis of quinolines under solvent-free conditions is described, catalyzed by recyclable Ag(I)-exchanged Montmorillonite K10. The desired products are obtained in good to excellent yields and the reaction accommodates both aromatic and aliphatic α,β-unsaturated aldehydes making this process an attractive method for the synthesis of substituted quinolines. In addition, the Ag(I)-exchanged Montmorillonite K10 catalyst can be recovered and reused up to 5 times with excellent activity.

■ An Efficient Synthesis of 3-(Arylsulfanyl)quinolin-4(1H)-ones via Cyclization of N-{2-[2-(Arylsulfanyl)acetyl]phenyl}benzamides with N,N-Dimethylformamide Dimethyl Acetal

Kazuhiro Kobayashi,* Kohei Nishikawa, 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

The reaction of N-[2-(2-chloroacetyl)phenyl]benzamides, readily derived from 2-(2,2-dichloroethenyl)benzenamines, with sodium arenethiolates gives the corresponding N-{2-[2-(arylsulfanyl)acetyl]phenyl}benzamides. These are treated with N,N-dimethylformaide dimethyl acetal (DMF–DMA) to yield 3-(arylsulfanyl)quinolin-4(1H)-ones in generally good yields.

■ An Efficient Synthesis of Functionalized Chromeno[4,3-d]pyrazolo[3,4-b]pyridine Derivatives

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

*College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

Abstract

A series of functionalized chromeno[4,3-d]pyrazolo[3,4-b]pyridine derivatives were synthesized via one-pot three-component reaction of salicylaldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one and pyrazol-5-amines catalyzed by CuSO4 in ethanol. The structures of all synthesized were identified by their IR, 1H NMR, 13C NMR and HRMS analysis, and the structure of compound 4h was confirmed by X-ray diffraction analyses.

■ Methodology to Access Thiazo[3’,2’:2,3]pyrido[4,5-d]thiazolo[3,2-a]pyrimidinones

Dao-Lin Wang,* Dong Wang, Qiao-Min Li, 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 synthesis of model thiazolo[3’,2’:2,3]pyrido[4,5-d]thiazolo[3,2-a] pyrimidin-5-ones (5), based on the classical Pictet-Spengler method, is described. The key intermediate, 7-(3-amino-5-phenylaminothiazol-2-yl)-5H-thiazolo [3,2-a]pyrimidin-5-one (3), was synthesized from 7-chloromethyl-5H-thiazolo [3,2-a]pyrimidin-5-one (1) with potassium N-phenyl-N'-cyanoimidothiocarbonate (2) by Thorpe-Ziegler isomerization. Cyclocondensation of the intermediate amine with aromatic aldehydes, using sulfamic acid under Pictet-Spengler reaction conditions, delivered the target compounds 5a-m. 

■ One-Pot Regioselective Synthesis of Diazaspiro[5.5]undecane-1,5-dione-9-thione Derivatives Catalyzed by Reusable 1-Methylimidazolium Trifluoromethylsulfonate under Solvent-Free Conditions

Zhaohui Xu,* Houfu Zhang, Yunkui Xiong, Deyong Liu, and Qingshui Huang*

*College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330027, China

Abstract

A green and environmentally benign Biginelli-like synthesis of 2,4-dioxa-8,10-diazaspiro[5.5]undecane-1,5-dione-9-thione derivatives by one-pot three-component reaction of aromatic aldehydes with thiourea and 1,3-dioxane-4,6-dione catalyzed by reusable 1-methylimidazolium trifluoromethylsulfonate under solvent-free conditions is described.

■ Synthesis of 1-Aryl-1,3-dihydrobenzo[c]thiophenes by Acid-Mediated Cyclization of 1-[Aryl(methoxy)methyl]-2-[(tert-butylsulfanyl)methyl]benzenes

Kazuhiro Kobayashi* and Yuuho Shigemura

*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 preparation of 1-aryl-1,3-dihydrobenzo[c]thiophenes has been developed using a three-step sequence starting from 2-[aryl(methoxy)methyl]benzyl alcohols. Thus, treatment of the starting materials with thionyl chloride gives the corresponding benzyl chlorides, which are allowed to react with sodium tert-butyl mercaptide to yield 1-[aryl(methoxy)methyl]-2-[(tert-butylsulfanyl)methyl]benzenes. Finally, these compounds undergo cyclization on treatment with concentrated hydrobromic acid to provide the desired products in reasonable yields.

■ Regioselective Bromination of 2-Iodomethyl-2,3-Dihydrothiazolo[3,2-a]pyrimidin-5-one

Renata Studzińska,* Renata Kołodziejska, Tomasz Kosmalski, and Bożena Modzelewska-Banachiewicz

*Department of Organic Chemistry, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Jurasza 2, Bydgoszcz 85-089, Poland

Abstract

The bromination reactions of 2-iodomethyl-2,3- dihydrothiazolo[3,2-a]pyrimidin-5-one were carried out using bromine and NBS as the brominating agent. Depending on the brominating agent used and a solvent two bromo derivatives were obtained: the product of electrophilic substitution in the pyrimidin ring and the product containing two bromine atoms which was formed as a result of two parallel reactions – an electrophilic substitution on the pyrimidine ring and a nucleophilic substitution of iodine. The position of bromine atoms in the obtained compounds was confirmed using 1H NMR spectrum.