HETEROCYCLES

■ Contents

■ Iodine-Containing 4,7-Dihalobenzo[b]thiophene Building Blocks and Related Iodobenzo[b]thiophenes: Promising Molecular Scaffolds for Bio-Inspired Molecular Architecture

Kozo Toyota* and Shinichi Mikami

*Department of Chemistry, Graduate School of Science, Tohoku University, Aoba, Sendai, Miyagi 980-8578, Japan

Abstract

This review describes preparations and reactions of 4,7-dihalobenzo[b]thiophenes bearing iodine atom(s). A short survey of typical preparative methods for iodobenzo[b]thiophenes and relatively simple benzo[b]thiophenes is included. Reactions of the iodine-containing 4,7-dihalobenzo[b]thiophenes are shown and their application to α helix-inspired artificial molecular architecture is referred.

■ Recent Advances in 1,2,4-Triazole Ring Construction via Cycloaddition Reactions

Nataliya Korol,* Mikhailo Slivka, and Oksana Holovko-Kamoshenkova

*Organic synthesis laboratory, Faculty of Chemistry, Uzhhorod National University, Uzhhorod 88000, Ukraine

Abstract

The sources, describing cycloaddition reactions that lead to obtaining of substituted 1,2,4-triazoles and their fused derivatives were reviewed. The review article covers the literature data published in the period 2011-2021. Synthetic particularities of cycloaddition products, the optimization of reaction conditions, factors that influence on the direction of the reaction are reasonably mentioned. Cycloaddition reactions are presented as convenient method for obtaining of as functional 1,2,4-triazoles, as well as their fused derivatives.

■ A Simple Route for Synthesis of New Triazole Derivatives via Reaction between Arylglyoxals, Acetylacetone and Sodium Azide

Fereshteh Nejad-Shahrokhabadi and Mohammad Anary-Abbassinejad*

*Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 7718897111, Iran

Abstract

A fast and green way to preparation of a new series of triazole derivatives is reported using the three-component reaction between arylglyoxals, acetylacetone and sodium azide in water as solvent.

■ Ruthenium(II) Complexes with Chelating N-Heterocyclic Carbenes and a Ruthenate(II) Complex as Catalysts for the Anti-Markovnikov Hydroaminations of Styrene

Murat Yiğit,* Yetkin Gök, Özlem Özeroğlu Çelikal, and Beyhan Yiğit

*Department of Chemistry and Chemical Processing Technologies, Vocational School of Technical Sciences, Adiyaman University, 02040-Adıyaman, Turkey

Abstract

New ruthenium chelate and ruthenate complexes were synthesized through the reaction of benzimidazolium salts and [RuCl2(p-cymene)]2 in toluene and characterized by elemental analysis, 1H NMR and 13C NMR spectroscopy. These ruthenium complexes were tested as catalysts in the intermolecular hydroamination reactions between styrene with aromatic amines in ionic liquid. All of these complexes tested here showed good catalytic activity in these reactions. The hydroamination reactions regioselectively produced anti-Markovnikov addition products in moderate to good yields by using 1 mol% of the ruthenium complex.

■ Synthetic Approaches for Construction of Novel 3-Heteroarylchromeno[2,3-b]pyridines and Annulated Chromenopyridopyrazolopyrimidines

Magdy A. Ibrahim* and Youssef A. Alnamer

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy 11757, Cairo, Egypt

Abstract

Hydrazinolysis of ethyl 2,5-dioxo-1,5-dihydro-2H-chromeno[2,3-b]- pyridine-3-carboxylate (2) afforded chromeno[2,3-b]pyridine-3-carbohydrazide 3 which utilized as a precursor for building a diversity of heterocyclic compounds at position 3. Condensation of carbohydrazide 3 with 3-formylchromone produced the condensation product 4, while addition of carbohydrazide 3 to phenyl isothiocyanate gave hydrazinecarbothioamide derivative 5 which upon cyclization afforded 3-thiadiazolylchromeno[2,3-b]pyridine-2,5(1H)-dione 6. Condensation of carbohydrazide 3 with some monoelectrophilic reagents namely ethyl chloroformate, carbon disulfide, acetyl chloride and benzoyl chloride and chromone-3-carboxylic acid gave a variety of novel 3-oxadiazolylchromeno-[2,3-b]pyridines 7-10 and 12. Treatment of carbohydrazide 3 with a variety of 1,3-bielectrophiles such as acetylacetone, ethyl acetoacetate and diethyl malonate yielded 3-(pyrazolyl)carbonylchromeno[2,3-b]pyridines 13-15. Finally, reaction of carbohydrazide 3 with ethyl cyanoacetate and (ethoxymethylene)malononitrile afforded heteroannulated chromeno[2``,3``:6`,5`]pyrido[2`,3`-d]pyrazolo[1,5-a]-pyrimidines 17 and 18. Structures of the synthesized products were confirmed based on their analytical and spectral data.

■ Synthesis, Characterization, Antibacterial and Cytotoxic Evaluation of New 6-(Chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile Derivatives and Their Corresponding Furo[2,3-b]pyridine Derivatives

Ala’a B. Said, Mahmoud Al-Refai,* Armin Geyer, Iman A. Mansi, and Basem Fares Ali*

*Department of Chemistry, Al al-Bayt University, Mafraq 25113, Jordan

Abstract

The synthesis of a new series of 6-(chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile compounds 2 and 5 and their furo[2,3-b]pyridines bearing heteroaryl substituents 3 and 6 in high yield is reported. The 6-(chlorothiophenyl)-2-(2-oxopropoxy)pyridine-3-carbonitrile derivatives (2a-f) and (5a-d) were prepared from the corresponding 3-cyano-(2H)-pyridones (1a-f) and (4a-d) followed by the Thorpe-Ziegler ring cyclization in the presence of sodium methoxide to give the target furo[2,3-b]pyridine derivatives (3a-f) and (6a-d). Proposed structures of the new compounds are based on NMR and mass spectral data. Antibacterial evaluation of (2a-d), (2f), (5a-d), (3a-d), (3f), and (6a-d) derivatives against eight different microorganisms shows no activity towards any of the tested bacteria while compounds (6a) and (6c) showed weak antibacterial activity with inhibition zone of 10 mm. Cytotoxic assessment against MCF7 breast cancer cells reveals that 10 of the derivatives were found to decrease cell viability in a dose dependent manner at concentration of 100 μM, but six of them decreased it to less than 50% and had IC50’s ranging from 23.3 to 41.2 μM.

■ Detection of New 3,4-Dimethylpyrrole Derivatives upon the Incubation of Exogenous Amines with Extract of Onion (Allium cepa) and Crude Alliinase from Garlic (A. sativum)

Taichi Yoneda, Seikou Nakamura,* Shogo Okui, Sayaka Okazaki, Souichi Nakashima, and Hisashi Matsuda

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan

Abstract

Seven new N-substituted 3,4-dimethylpyrroles were obtained in situ through the reaction of an amine ((L)-phenylalanine, (L)-tryptophan, (L)-leucine, (L)-methionine, 1-phenethylamine, aniline or dodecylamine) and a mixture of unstable sulfur-containing compounds derived from the reaction of amino acids in Allium cepa and plant enzyme alliinase. In addition, a plausible reaction mechanism for the synthesis of N-substituted 3,4-dimethylpyrroles was displayed.

■ An Efficient Synthesis of 2-Amino-4-(guaiazulen-1-yl)-4H-chromenes via Cycloaddition of 1-Hydroxy-2-(3-guaiazulenylium)benzenes with Malononitrile/Ethyl Cyanoacetate

Shuang Yang, Xin-Shuang Xiong, and Dao-Lin Wang*

*College of Chemistry and Material Science, Bohai University, Jinzhou, China

Abstract

An efficient two-step method developed for the synthesis of 2-amino-4-(guaiazulen-1-yl)-4H-chromenes is described. The construction of these compounds was achieved by the reaction of guaiazulene and 2-hydroxy-benzaldehydes in the presence of perchloric acid, followed by cycloaddition of the resulting 1-hydroxy-2-(3-guaiazulenylmethylium)benzenes which allowed access to the title heterocycles.

■ Quinoline Alkaloids from the Leaves of Cigar Tobacco and Their Anti-Tobacco Mosaic Virus Activity

Guang-Hui Kong, Guang-Hai Zhang, Zhong-Long Lin, Gao-Kun Zhao, Yin-Ke Li, Heng Yao, Guang-Yu Yang, Qiu-Fen Hu,* and Yu-Ping Wu*

*Yunnan Academy of Tobacco Agricultural Sciences, Kunming, Yunnan 650031, P. R. China

Abstract

Three new (1-3), together with three known (4-6) quinoline alkaloids were isolated from the leaves of cigar tobacco (a variety of Nicotiana tabacum). Their structures were elucidated by spectroscopic methods, including extensive 1H, 13C, and 2D-NMR techniques. Compounds 1-6 were tested for their anti-tobacco mosaic virus (anti-TMV) activity. The results showed that compound 3 exhibited high anti-TMV activity with inhibition rate of 42.2% at the concentration of 20 μM. This rate in higher than that of positive control (with inhibition rate of 32.5% at the concentration of 20 μM). Compounds 1, 2, 4~6 also showed potential anti-TMV activity with inhibition rates of 28.2, 31.0, 22.8, 26.6, and 29.5% at the concentration of 20 μM, respectively. These rates are slightly lower than that of positive control.

■ New Synthesis of Lumateperone Tosylate

Cong Sun, Yongjun Mao,* Bo Li, Zhiyong Xu, Shun Jiang, Linlin Kang, and Han Wang

*College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China

Abstract

A new and practical synthesis of lumateperone tosylate is developed. The intermediate, ethyl (4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido-[4,3-b]indole-2-carboxylate (12), is prepared on kilograms scale in 31% overall yield and >99% ee. (6bR,10aS)-3-Methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline hydrochloride (16-HCl) is obtained through reductamination reaction, palladium catalyzed cyclization and ester hydrolysis in 60% yield over 3 steps and >98% purity. Lumateperone tosylate is produced on 20 g scale in 65% yield over 2 steps and >99% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are developed.

■ Synthesis of Benzimidazoles, Benzoxazoles and Benzothiazole by the Reaction of 2-Amino-4,5-dihydro-3-furancarbonitrile and o-Substituted Anilines in the Catalysis of Trimetylamine Hydrochloride

Fumi Okabe-Nakahara,* Hayate Nagabuchi, Eiichi Masumoto, and Hiroshi Maruoka

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

Abstract

Efficient synthesis of benzimidazoles, benzoxazoles and benzothiazole from the reaction of 2-amino-4,5-dihydro-3-furancarbonitrile with o-substituted anilines in the catalysis of trimethylamine hydrochloride was achieved. The structures of the obtained products were established by spectroscopic data.