HETEROCYCLES

■ Contents

■ Ring-Substitution, Enlargement, and Contraction by Base-Induced Rearrangements of N-Heterocyclic Ammonium Salts

Eiji Tayama*

*Department of Chemistry, Faculty of Sciences, Niigata University, Ikarasi 2-8050, Niigata 950-2181, Japan

Abstract

An overview of the utility of base-induced Stevens, Sommelet–Hauser, and related sigmatropic rearrangements of N-heterocyclic ammonium salts into various types of N-heterocycles reported after 1970 will be described. The synthetic transformations are classified as N-heterocyclic ring-substitution, ring-enlargement, and ring-contraction.

■ Synthesis, Crystal Structure and Herbicidal Activity of a Series of [1,2,4]Triazolo[1,5-a]pyrimidine-2-sulfonamide Compounds

Yi-Chao Ma, Ying-Hui Yu, Guang-Feng Hou,* Ji-Han Huang, and Jin-Sheng Gao*

*Engineering Research Center of Pesticide, Heilongjiang University, Xuefu Road 74# 150080, China

Abstract

With the aim of obtaining efficient, safe and environmentally friendly green herbicide, a series of [1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide compounds (8a−8f) were synthesized by reacting 2-amino-5,7-(bis-substituted)- 1,2,4-triazolo[l,5-a]pyrimidine (4a and 4b) with 2-substituted-6-trifluoromethyl- benzenesulfonyl chloride (7a−7c). And their structures were characterized by 1H-NMR, 13C-NMR, HRMS, FTIR, single-crystal X-ray diffraction, elemental analysis. Moreover, their herbicidal activities against six species of weeds were evaluated. Three target compounds such as 8a, 8c and 8e, exhibited significant postemergence herbicidal activity against some common dicotyledons and monocotyledons under different concentrations. The structure and activity relationship is discussed based on the herbicidal performances of the compounds with different substituents. The investigation results indicated that the above structures could serve as lead compounds for the development of new herbicides.

■ Synthesis of N,N-Disubstituted 1-Aryl-1,3-dihydro-2H-isoindole-2-carbothioamides

Kazuhiro Kobayashi,* Yuuho Shigemura, and Miyuki Tanmatsu

*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 N,N-disubstituted 1-aryl-1,3-dihydro-2H-isoindole-2-carbothioamides starting from 2-[aryl(methoxy)methyl]phenyl bromides is described. Thus, the reaction of 1-[aryl(methoxy)methyl]-2-(isothiocyanatomethyl)benzenes, derived from the starting materials by an easily operated five-step sequence under mild conditions, with secondary amines provides the corresponding thiourea derivatives, which cyclize on treatment with methanesulfonic acid to afford the desired products.

■ Synthesis of trans-2,6-Piperidinedicarboxamide Using the Ugi Reaction. A Plausible Model for the Biosynthesis of Halichonadin P

Rika Mimura, Ayumi Kitamori, Keiji Nakano, Hiyoshizo Kotsuki, Kenji Matsumoto, Daisuke Kaneno, Toshiya Masuda, and Yoshiyasu Ichikawa*

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

Abstract

The Ugi reaction of isocyanides, glutaraldehyde and glycine methyl ester is found to produce trans-2,6-piperidinedicarboxamides. It is proposed that this multi-component reaction is a plausible model for the biosynthesis of the marine natural product, halichonadin P.

■ Efficient Constructions of the Four Different Thienopyrimidinone Skeletons via Various Cyclocondensation of o-Aminothienonitrile with Carbonyl Compounds

Junjuan Yang, Daxin Shi, Kai Zhang, Zhangtao Zhao, Fadong Qiu, Yujiao Bi, Qi Zhang, and Jiarong Li*

*Department of Chemical Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing Postcode: 100081, China

Abstract

A series of new thienopyrimidinone derivatives were synthesized via a novel, straightforward and efficient tandem cyclocondensation of o-aminothienonitrile 1 and carbonyl compounds 2 in different conditions. The synthesized four thienopyrimidinone skeletons were thieno[2,3-d]pyrimidinone 3, tert-hydroxythieno[2,3-d]pyrimidinone 4, symmetrical tetracycle thienothiophenepyrimidone 5 and thienopyrimidine 6 respectively. Their plausible mechanisms were proposed. The properties of compound 5 were investigated.

■ Studies on the aza-Claisen Rearrangement of 7 to 9-Membered Vinylazacycles

Seok-Ho Kim, Won-Il Lee, Seon-Mi Kim, Jae-Kyung Jung, Jaebong Jang, Jaehoon Sim, Jong-Wha Jung,* and Young-Ger Suh*

*Department of Pharmacy, Kyungpook National University, #411 80 Daehak-ro Buk-gu 41566, Korea

Abstract

A systematic study on the amide enolate-induced aza-Claisen rearrangement (ACR) of 7 to 9-membered vinylazacycles has been carried out, resulting in an efficient synthetic method to prepare 11 to 13-membered macrolactams. Key feature includes introduction of electron-donating substituents at α-position of the amide substrates possessing 7 to 9-membered vinylazacycles to facilitate amide enolate-induced ACR. In addition, substituent effects on ACR has been discussed based on the experimental results. We believe this study would provide experimental evidences for the substituent effects and envision for the synthetic application of ACR-induced ring expansion.

■ Development of Madelung-Type Indole Synthesis Using Copper-Catalyzed Amidation/Condensation Strategy

Masahiro Abe, Charline Denneval, Kanako Nozawa-Kumada, and Yoshinori Kondo*

*Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

A new method for Madelung-type indole synthesis was investigated, and it was found that the amidation of 2-iodophenylacetonitrile with various alkanamides proceeds smoothly in the presence of CuI and a diamine ligand. The subsequent cyclization of the C-N coupling products takes place under the coupling reaction conditions.

■ Microwave Assisted Multi-Component Synthesis of Novel Bis(1,4-dihydropyridines) Based Arenes or Heteroarenes

Sherif M. H. Sanad, Refaie M. Kassab, Ismail A. Abdelhamid,* and Ahmed H. M. Elwahy*

*Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt

Abstract

A synthesis of novel bis-1,4-DHPs was reported. Two possible synthetic approaches for these compounds were investigated. In the first approach the monopodal 1,4-DHPs were used as building blocks for the construction of the target molecules via a simple alkylation. In the second strategy the appropriate bis-aldehydes have been synthesized in a first step followed by reaction with four equivalents of 3-aminobut-2-enenitrile using different catalysts under microwave irradiation as well as under conventional heating to give the corresponding bis-1,4-DHPs in good to excellent yield. The oxidative aromatization of some derivatives of the latter compounds into the corresponding bis-2,6-dimethylpyridine-3,5-dicarbonitrile derivatives was achieved using ceric ammonium nitrate (CAN).

■ Novel Twin-Drug Type C2-Symmetrical Phenylboronic Acid Pinacol Esters

Makoto Furutachi, Ayumi Ejima, Reika Tsuru, Saho Goto, Toshiaki Gondo, Kenta Ako, Saya Fujii, Arisa Okumura, Ayumi Tozuka, Kazumi Yokomizo, Jian-Rong Zhou, Hiroshi Inao, Yutaro Ono, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto*

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

Abstract

We here report the preparation of newly designed bivalent twin-drug type C2-symmetrical cyclic phenylboronic acid derivatives. The synthesis of these C2-symmetrical mid-size molecules 3 was accomplished by an amide bond formation reaction using amino-substituted phenylboronic acid pinacol esters 1 and dicarboxylic acid dichlorides 2 in the presence of Et3N. We confirmed that this procedure is conventionally applicable to the preparation of various C2-symmetrical cyclic boronic acid derivatives 3 in good to excellent yields.

■ Facile Syntheses of Fluorine-Containing 4-Methoxypyrazolo[4,3-c]quinolines and 6-Methoxy-1,4-diazepino[6,5-c]quinolines

Mizuki Hatakenaka, Satoru Adachi, 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

N,N-Dimethyl-2-methoxy-3-trifluoroacetyl-4-quinolylamine underwent chemoselective aromatic nucleophilic N-N exchange reaction with hydrazines followed by cyclocondensation to afford the corresponding novel fluorine-containing 4-methoxy-1H- and 2H-pyrazolo[4,3-c]quinolines in good to high yields. Furthermore, the use of 1,2-ethylenediamine and 1,2-phenylenediamines gave the corresponding fluorine-containing 6-methoxy-1,4-diazepino[6,5-c]quinoline derivatives in good yields.

■ Facile Synthesis of Chiral Benzimidazolium Salts and the Application in Asymmetric Catalytic Borylation

Jie Zhou, Xiaohui Liu, and Zhihua Sun*

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

Abstract

A synthetic method towards chiral benzimidazolium salts is developed. The stereocenter is introduced by direct aromatic substitution of 2-fluoronitrobenzene with optically pure amines. After nitro group reduction, selective arylation of the primary amine is achieved via copper catalyzed Chan-Lam coupling reaction. Finally, cyclization of the diamine with HC(OMe)3 afforded the desired chiral benzimidazolium salts. In situ generated benzimidazole carbenes show potential application for asymmetric catalytic borylation of α,β-unsaturated esters, providing up to 85% ee value with a catalyst loading of only 0.5 mol%.

■ Synthesis of Some Novel Thiazole, Thiadiazole and 1,4-Phenylene-bis-thiazole Derivatives as Potent Antitumor Agents

Sobhi M. Gomha,* Fathy M. Abdelrazek, Aly H. Abdelrahman, and Peter Metz

*Department of Organic Chemistry, Cairo University, Giza-Haram 12613, Egypt

Abstract

A novel series of 2-ethylidenehydrazono-5-arylazothiazoles 5a-h and 2-ethylidenehydrazono-5-arylazothiazolones 9a-d were prepared by cyclocondensation of hydrazonyl halides 3a-h and 7a-d with ethylidenethiosemicarbazide 2. In addition, reaction of 2 with N-phenyl- carbohydrazonyl chloride (14), afforded 1,3,4-thiadiazole derivative 17 as the end product. Moreover, the thiosemicarbazide derivative 2 was reacted with various bromoacetyl compounds 19a-d and 1,1’-(1,4-phenylene)bis(2-bromoethanone) (21) furnished the respective thiazole derivatives 20a-d and 1,4-phenylene-bis-thiazole derivative 22. The structures of the newly synthesized compounds were established on the basis of spectroscopic evidences and their alternative syntheses. The newly synthesized compounds were evaluated for their anti-tumor activities against hepatocellular carcinoma (HepG2) cell line and the results revealed promising activities of compounds 5h, 5d, 5g, 5f and 5e with IC50 equal 2.23 ± 0.28, 2.48 ± 0.34, 2.49 ± 0.24, 4.03 ± 0.11, and 5.32 ± 0.27 μM, respectively.