HETEROCYCLES

■ Contents

■ Synthesis of Nitrogen Containing Heterocycles by Using Carbon-Nitrogen Double Bond

Kentaro Okuma*

*Department of Chemistry, Faculty of Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

Recent achievements in the construction of mainly nitrogen containing heterocycles by the intramolecular cyclization of alkenylanilides via activation of unsaturated bonds are reviewed. NIS or ZnX2 activation of 2-alkenylanilines and 2-alkynylanilines gave quinolines or indoles in high yields. Reaction of 2-aminobenzaldehyde with acetophenones under basic conditions gave dibenzonaphthyridines in one-pot operation. Other nitrogen and chalcogene containing heterocycles were also synthesized by the reaction of ketone hydrazones with chalcogen halides.

■ Lewis Acid Promoted Prins Cyclization Using Non-Conjugated Diene Alcohol: Sequential Reactions Terminated by Fluoride Ion

Kouichi Matsumoto,* Rina Yanagi, Kouji Yamaguchi, Erin Hayashi, Eri Yasuda, Kaho Kuriyama, Toshiki Nokami, Keiji Nishiwaki, and Shigenori Kashimura

*Faculty of Science and Engineering, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan

Abstract

The sequential cyclization involving Prins cyclization was successfully demonstrated, in which the various aldehydes bearing the alkyl or aromatic substituent were reacted with the alcohol bearing the non-conjugated diene moiety in the presence of 2 equiv. of BF3·Et2O and 4 mol% of TMSCl at -40 oC to afford the corresponding fluorinated bicyclic compounds in moderate to good yields.

■ Synthesis of Oxazolines from N-Allylamides Using an Electrochemically Generated ArS(ArSSAr)+ Pool

Yu Miyamoto, Naoya Mitani, Rina Yanagi, Shigenori Kashimura, Seiji Suga, Jun-ichi Yoshida,* and Kouichi Matsumoto*

*School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

The reaction of N-allylamides with ArS(ArSSAr)+, which was generated and accumulated by the low-temperature anodic oxidation of ArSSAr, afforded the corresponding ArS-substituted oxazolines in moderate to good yields. In-situ electrochemical oxidation of ArSSAr in the presence of N-allylamides was also applicable. Oxazolines bearing various substituents were successfully synthesized by using the present reactions.

■ Cinchona Alkaloid Thiourea-Catalyzed One-Pot Synthesis and Bioselective Activities of β-Amino Acid Ester Derivatives Containing a Pyrimidine Moiety

Song Bai,* Shan Liu, Yunying Zhu, Xian Wei, Kunhong Zhao, Weihua Li, and Qin Wu*

*School of Chemical Engineering, Guizhou Institute of Technology, 1st, Caiguan Road, Yunyan District, Guiyang City, Guizhou Province 550003, China

Abstract

We have studied the synthesis of enantiomerically pure optically active β-amino acid ester derivatives with good biological activities. Here, we report that both enantiomers of β-amino acid ester derivatives that contain a pyrimidine moiety can be produced in an enantioselective Mannich-type one-pot reaction with good yields and excellent enantiomeric excess (up to >99% ee) by chiral cinchona alkaloid thiourea catalysts. An evaluation of the antiviral activities of our reaction products against tobacco mosaic virus (TMV) was promising with high and selective biological activities. Compound (−)-4h showed an excellent anti-TMV activity (curative activity, 56.1%; inactivation activity, 70.7%; protection activity, 95.7%) at 500 μg/mL. These values exceed those of the commercially available antiviral agent, ningnanmycin (curative activity, 52.6%; inactivation activity, 62.0%; protection activity, 90.2%). These novel chiral compounds could be used as protective agents against TMV disease.

■ 5,11-Diethyl-6-formylindolo[3,2-b]carbazole: Crystal, Interaction with Protein and Theoretial Study

Yingchun Gu, Dayong Lin, Xuening Fei,* Lei Zhang, Cuihong Wang, Qi Yang, Shiyang Liu, Xueling Ren, and Ran Zhang

*School of Science, Tianjin Chengjian University, No.26 Jinjing Road, Xiqing District 300384, China

Abstract

In this work, 5, 11-diethyl-6-formylindolo[3,2-b]carbazole (DEFICZ) was crystallized in a monoclinic crystal system with the space group of P121/n1. Its spectral properties and potential interaction with protein including BSA and HSA were also studied correspondingly. The crystal structure was theoretically investigated using the density functional tight-binding method. In order to address the regioselective associated with the synthesis of DEFICZ, the B3LYP density functional theory (DFT) calculation has been carried out to estimate the relative stability of different active intermediates. In addition, time-dependent density functional theory method was used to unveil the origin of the absorption spectra of DEFICZ as observed experimenta.

■ Benzylic sp3 C-H Functionalization Reaction of 2-Methylazaarenes Catalyzed by Pepsin

Feng Ai, Guo-Qing Chen, Jiu-Jian Ji, Zhi-Qiang Zhu, Zhang-Gao Le,* and Zong-Bo Xie*

*Department of Applied Chemistry, East China University of Technology, Nanchang 330013, China

Abstract

In this work, the addition of 2-methylazaarenes benzylic sp3 C-H to electron-deficient olefins, catalyzed by pepsin from pig gastric mucosa was reported. A series of azaarene derivatives (1 mmol) were obtained in good yields at 60 °C for 60~72 h with 20 mg pepsin as catalyst. This is a facile method and the reaction conditions are mild, which expands the application of biocatalysis in sp3 C-H functionalization of azaarenes.

■ A Facile Synthesis of Indolo[2,3-b]carbazoles from the Reaction of Di(2-indolyl)methane and Aromatic Aldehydes Catalyzed by Oxalic Acid

Chun Li, Xunhua Lu, Yuanyong Yang, and Lin Zhang*

*Department of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Guiyang, 550014, China

Abstract

Oxalic acid catalyzed condensation of di(2-indolyl)methane with aromatic aldehydes has been established. Various indolo[2,3-b]carbazole derivatives were prepared in good isolated yields (up to 94.5%). Compared with literature methods, the present protocol features mild reaction conditions, easily controlled selectivity, good functional group tolerance, and simple operation procedures.

■ A Facile Synthesis of 4-Aryl-1H-2-benzothiopyran-3-carboxylic Acid Derivatives from o-Bromobenzyl Mercaptans

Kazuhiro Kobayashi,* Syunta Furugaki, and Takuma Ueyama

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

Abstract

The synthesis of 4-aryl-1H-2-benzothiopyran-3-carboxylic acid derivatives by a sodium hydride-mediated thiopyran ring formation of 2-[(2-aroylphenyl)methylsulfanyl]acetic acid derivatives is reported. The precursors were prepared by successive treatment of lithium o-lithiobenzyl mercaptides, which were generated by the reaction of o-bromobenzyl mercaptans with two equivalents of butyllithium, with aromatic aldehydes and 2-bromoacetonitrile or tert-butyl 2-bromoacetate, followed by oxidation of the resulting sulfanyl alcohols with pyridinium chlorochromate (PCC).

■ A New Short Synthesis of (±)-Olean through Cross Metathesis

Nektarios S. Kranidiotis, Constantinos E. Grammatoglou, and John K. Gallos*

*Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece

Abstract

A new synthesis of (±)-1,7-dioxaspiro[5.5]undecane (olean), the olive fruit fly pheromone, utilizing the cross-metathesis reaction as the key-step, is reported.

■ An Efficient Construction of 9-(Guaiazulen-1-yl)xanthen-4(9H)-ones via Domino Reaction

Yu Liu, Jiao Xu,* Dao-Lin Wang,* Wei Ma, and Xing-Wei Zhang

*College of Chemistry and Chemical Engineering, Bohai University, 19, Keji Rd., New Songshan District, Jinzhou City, Liaoning Province 121001, China

Abstract

A facile, convenient, and efficient synthesis of 9-(guaiazulen-1-yl)xanthen-4(9H)-one derivatives has been developed by the condensation of guaiazulene with salicylaldehyde, and 1,3-hexanediones in the presence of L-proline as the catalyst via the tandem Knoevenagel–Michael reaction.

■ Synthesis and Bioactivities Evaluation of Novel N-Pyridylpyrazole Derivatives with 1,2,3-Triazole and Quinazolin-4(3H)-one Substructures

Wei Wei, Liangliang Zhu, Yunyun Zhou,* and Zhengming Li*

*State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Songhu Road No. 2005, Shanghai, 200433, China

Abstract

Two series of N-pyridylpyrazole derivatives containing 1,2,3-triazole and quinazolin-4(3H)-one substructures were designed and synthesized. In total, 18 novel compounds were prepared, and all compounds were characterized by 1H NMR, 13C NMR and elemental analysis (EA). Preliminary bioassay results revealed that a few of new compounds with quinazolin-4(3H)-one moiety exhibited good insecticidal activity against the oriental armyworm (Mythimna separata). In addition, the compounds Ia-h with 1, 2, 3-triazole moiety showed broad-spectrum antifungal activities against Fusarium oxysporum f.sp.cucumerinum, Cercospora arachidicola Hori, Botryosphaeria dothidea, Alternaria solani, Gibberella zeae and Phytophthora capsici at 50 μg/mL concentration. The EC50 values of Ib and If against Botryosphaeria dothidea were 13.9 and 11.0 μg/mL, respectively, which were comparable to Chlorothalonil. These results indicated the potential application of N-pyridylpyrazole derivatives as fungicide in further study.