HETEROCYCLES

■ Contents

■ Development of Solvent-Driven Iron-Catalyzed Reactions

Toshiyuki Itoh*

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

Abstract

The possibility of solvent-driven iron-catalyzed reactions has been investigated using ionic liquids and acetonitrile as key solvents. Three iron-catalyzed reactions, the intramolecular cyclization of cyclopropane dithioacetals, the [2+2]-cycloaddition of (trans)-anethole, and the [2+3]-type cycloaddition of styrene derivatives with 1,4-benzoquinone, were first developed using acetonitrile as solvent in the presence of 3~5 mol% of Fe(ClO4)3•Al2O3 or Fe(BF4)2•6H2O under air conditions. In particular, we found the rapid cycloaddition of iron-catalyzed [2+3]-type cycloaddition of styrene derivatives with 1,4-benzoquinone when the reaction was carried out in an ionic liquid which contained [PF6] or [Tf2N] anion. Homo-coupling reaction of aryl or alkynyl Grignard reagent was next discovered using 1 mol% of FeCl3 as catalyst and the reaction also proceeded very rapidly in an ionic liquid. We also found that 3~5 mol% of Fe(ClO4)2•Al2O3 or Fe(BF4)2•6H2O-successfully catalyzed Friedel-Crafts type alkylation of indoles or pyrroles with vinyl ketones or α-aryl-β-silylalcohol. In particular, the reaction of chiral α-aryl-β-silylalcohol with indole using Fe(ClO4)3•nH2O as catalyst proceeded with retention of the configuration of stereochemistry of the hydroxyl group. Then, we discovered the first example of iron-catalyzed enantioselective C-S bond formation via Michael addition of thiols to (E)-3-crotonoyloxazolidin-2-one using 10 mol% of Fe(BF4)2/Pybox. We further demonstrated that Fe(ClO4)3•Al2O3-catalyzed the Nazarov type cyclizations of thiophene, pyrrole, indole, benzofuran, and benzo[b]thiophene derivatives using ionic liquids as solvent. Solvents have been recognized as a by-player in chemical reactions in the process of “optimization of reaction conditions”. However, further investigation of the solvent-driven iron-catalyzed reaction will allow discovery of useful reactions for organic syntheses.

■ A Simple and Convenient Synthesis of Isolated Fused Heterocycles Based on: 6-Phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one and 5-Acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one

Mohamed Ahmed Mahmoud Abdel Reheim,* Ibrahim Saad Abdel Hafiz, and Mohamed Ahmed Elian

*Department of Chemistry, Faculty of Science, Suez Canal Univeristy, Arish 45511, Egypt

Abstract

The reaction of 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1 with acetylchloride in acetic anhydride in the presence of sodium acetate afforded 5-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 2 which reacted with bromine, hydrazine hydrate, phenylhydrazine, cyanothioacetamide, aldehydes and (malononitrile/sulfur) to give 2-thioxo-2,3-dihydropyrimidine derivatives 4, 7a,b, 8, 10 and 11 respectively. In the present investigation 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1 was reacted with chloroacetylchloride yielded the corresponding compound 13. Compound 1 was reacted with some electrophilic reagents such as (benzylidene cyanothioacetamide derivatives, 2-cyano-2-cyclopentylethanethioamide, 2-cyano-2-cyclohexylethanethioamide and aromatic diazonium salts) to give compounds 23, 27a,b and 35 respectively. The newly synthesized heterocycles were characterized on the basis of their chemical properties and spectral data.

■ Synthesis, Characterization and Cytotoxicity Evaluation of Some Novel Pyrazole, Pyrimidine and Isoxazoloe Drivatives Containing Benzothiazole Moiety

Khaled. S. Mohamed,* Hala M. Refat, and Nada A. H. Mohamed

*Engineering Chemistry Department, Higher Institute for Engineering and Technology, New Damietta, New Damietta 34518, Egypt

Abstract

The 2-(2-benzothiazolyl)-3-(2-methoxy-1-naphthyl)acrylonitrile (3) was used as precursor for the synthesis of some novel pyrazole, isoxazole, pyrimidine derivatives and other related products containing benzothiazole moiety via the reaction of compound 3 with appropriate chemical reagents. The structures of the newly synthesized products were confirmed by elemental analyses, IR, 1H-NMR, 13C-NMR and mass spectral data. These compounds were screened for their antitumor activities. Compound 7 displayed promising in vitro antitumor activity in the four cell lines assay.

■ One-Pot and Three-Component Synthesis, Characterization and Biological Evaluation of Some New 1,2,4-Triazine-coumarins

Guang-cheng Wang,* Jing Wang, Dian-xiong He, Xin Li, Juan Li, and Zhi-yun Peng

*College of Chemistry and Chemical Engineering, Jishou University, Jishou University, Jishou 416000, China

Abstract

A series of 1,2,4-triazine-coumarins were prepared by a one-pot, three-component condensation of 1,2-diarylethane-1,2-diones, thiosemicarbazide and 2-coumaryloxy-methyloxiranes using K2CO3 as a catalyst in aqueous medium. This three-component reaction offers several advantages such as simple procedure, environmentally friendly and high yields. The resulting products were characterized by 1H NMR, 13C NMR and melting points. Furthermore, all newly synthesized compounds were evaluated for their α-glucosidase inhibitory activity. As a result, the majority of the screened compounds displayed potent inhibitory activity with IC50 values in the range of 32.57±0.21 to 148.77±3.23 μM, when compared to the standard acarbose (IC50 = 876.14±2.46 μM).

■ Preparation and Electrochemical Behavior of N-Substituted Phenothiazine Oxide

Hideki Hayashi* and Take-aki Koizumi

*Organic Materials Laboratory, Nagoya Municipal Industrial Research Institute, 3-4-41, Rokuban, Atsuta-ku, Nagoya 456-0058, Japan

Abstract

The chemical properties of promazine oxide (Prom-O) and promazine (Prom) were compared. Cyclic voltammetry (CV) experiments showed a higher oxidation potential of Prom-O compared to that of Prom. The results of CV measurements also suggested the potential applicability of Prom-O as an n-type semiconductor.

■ DABCO-Catalyzed Green Synthesis of Thiazole and 1,3-Thiazine Derivatives Linked to Benzofuran

Sobhi M. Gomha, Mohamed G. Badrey, and Wael A. A. Arafa*

*Department Of Chemistry, Fayoum University, Fayoum 12975, Egypt

Abstract

An eco-friendly and simple procedure for the reaction of 2-(1-(benzofuran-2-yl)ethylidene)hydrazinecarbothioamide with arylidenemalononitriles and hydrazonoyl halides catalyzed by using sterically hindered organic base, 1,4-diazabicyclo[2.2.2]octane (DABCO) was described. This new protocol has the advantage of good yields and short reaction times. The structure of the newly synthesized compounds was elucidated via elemental analyses and spectral data.

■ Two New 2-Arylbenzofurans from the Stems of Nicotiana tabacum and Their Bioactivities

Pei-Song Yang, Wei Zhang, Xiao-Feng Shen, Xin-Lin Wang, Chao Li, Xiao-Wei Gong, Xu-Dong Zheng, Dong-Lai Zhu, and Jia-Qiang Wang*

*School of Chemical Science and Technology, Yunnan University, Kunming 650091, China

Abstract

Two new 2-arylbenzofurans, 4-(7-methoxy-3,5-dimethyl-benzofuran-2-yl)phenol (1), 4-(6-methoxy-3,5-dimethylbenzofuran-2-yl)-phenol (2), together with two known 2-arylbenzofurans (3 and 4) were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Compounds 1-4 were tested for their anti-TMV and cytotoxicity activities. The results showed that compound 2 exhibited high anti-TMV activities with inhibition rates of 36.4% at the concentration of 20 μM. This rate is higher than that of positive control. Compounds 1-4 showed moderate-to-weak cytotoxicities against some tested human tumor cell lines with IC50 values in the range of 2.2–8.4 μM.

■ Catalyst-Free Synthesis of 1-Phenylnaphtho[2,1-b]furan Derivatives under Microwave Irradiation

Baolong Wang, Jinfu Zhang, Jianhong Liao, Yiyuan Peng, and Hua Zheng*

*School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, 122 Luoshi Road,Wuhan,Hubei 430070, China

Abstract

An environmentally benign and efficient method has been developed for the synthesis of naphtho[2,1-b]furan from (E)-(2-nitrovinyl)benzene and naphthalen-2-ol in brine media under catalyst-free conditions through microwave-assisted technology. The advantages of this process are that it is catalyst-free, has an easy work-up, provides good yields, and uses brine as the solvent which is considered to be relatively environmentally benign.

■ Oxidative Synthesis of Isoxazoline-N-oxide from Optically Active Nitro Alcohols

Takaaki Moriyama, Takuji Kawamoto, Hidemitsu Uno, and Akio Kamimura*

*Department of Applied Molecular Bioscience, Graduate School of Medicine, Yamaguchi University, , Japan

Abstract

Treatment of optically active 6-nitrohex-1-en-3-ols with Ag2O and iodine under basic conditions resulted in an oxidative intramolecular cyclization reaction to give isoxazoline-N-oxide along with bicyclo[3.1.0]hexane. The stereoselectivity and chemoselectivity of the reaction depended on the configuration of the stereogenic center adjacent to the alkenyl group. The structure was determined by X-ray crystallographic analyses as well as coupling constants from NMR data. Stereochemical preferences in the transition structure of the reaction are discussed.

■ Intramolecular 1,3-Dipolar Cycloaddition of Diazido-terminal Dialkynes: Synthesis of New Polyoxyethylene Fused exo-Bis(1,2,3-triazolo-1,4-oxazines)

Nejib Hussein Mekni*

*Organic Structural Chemistry Laboratory, Synthesis and Physico-Chemical Studies, Department of Chemistry, University of Tunis El-Manar, 2092 Tunis, Tunisia

Abstract

The synthesis of new tetraheterocyclic 1,5-disubstituted exo-heterocyclic polyoxyethylene bis(1,2,3-triazolo-1,4-oxazine) is achieved through nucleophilic azide ion ring opening reaction on polyoxyethylene dioxiranes, followed by an O-propargylation, then thermal uncatalyzed 1,3-dipolar intramolecular cycloaddition.

■ A Convenient Synthetic Route for Substituted 1-(Aryldiazenyl)Imidazo[1,5-a]Pyridine

Mustafa M. El-Abadelah,* Hamdallah A. Hodali, Monther S. Zreid, Firas F. Awwadi, Mohammed M. Abadleh, and Wolfgang Voelter

*Department of Chemistry, Faculty of Science, The University of Jordan, Amman 11942, Jordan

Abstract

In the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), model 2-(N'-aryl)picolinohydrazonamides 7, 8 (derived from interaction of the respective ethyl glycinate and (2-pyridyl)methylamine with the particular hydrazonoyl chloride) underwent didehydrogenation with concomitant heterocyclization to deliver the corresponding 1-(aryldiazenyl)imidazo- [1,5-a]pyridines 9, 10. Structures of the latter bicyclic systems are deduced from spectral data and confirmed by X-ray diffraction analysis of the Pd-complex 11, derived from 9.

■ Natural Tetrahydrocurcumin in Multi-Component Synthesis of 1,4-Dihydropyridine Derivatives

Thatsawan Yutthaseri, Anawat Ajavakom, and Vachiraporn Ajavakom*

*Department of Chemistry, Ramkhamhaeng University, 2086 Huamark, Bangkapi, Bangkok 10240, Thailand

Abstract

The mild condition synthesis of tetrahydrocurcumin- (THC-) dihydropyridine (DHP) was achieved by using the multi-component Hantzsch reaction in the presence of the catalytic amount of p-toluenesulfonic acid and 4 Å molecular sieves as a dehydrating agent. The successfully isolated intermediate, enaminone-THC, was the key component to reveal the reaction mechanism of this modified Hantzsch reaction. Due to containing the phenolic diarylheptanoid moiety, these novel heterocycles, THC-DHPs, are expected to exhibit interesting therapeutic properties.