HETEROCYCLES

■ Contents

■ Dehydroacetic Acid and Its Derivatives as Starting Synthons for Synthesis of Heterocyclic Compounds

Ranjana Aggarwal,* Chinu Rani, and Swati

*Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India

Abstract

From the last few years, dehydroacetic acid (DHA) has been found to show its immense contribution to the synthesis of various heterocyclic moieties. The present review reveals the various synthetic methods, developed from 2000 to 2015, to heterocyclic scaffolds considering DHA as starter. The present literature ensures the versatility of DHA for the synthesis of heterocyclic compounds, hence considered as versatile synthon.

■ A Facile Access and Computational Studies of Some New 4,5'-Bipyrazole Derivatives

Ahmad M. Farag, Nabila A. Kheder,* Kamal M. Dawood, and Ahmed M. El Defrawy

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

Abstract

4,5'-Bipyrazoline-5-carboxylate ester 4 was regioselectively obtained from 1,3-dipolar cycloaddition reaction of nitrilimine 2 with ethyl 2-cyano-5-phenylpenta-2,4-dienoate (3). The bipyrazoline-5-carboxylate ester 4 underwent thermal elimination of hydrogen cyanide upon heating in DMF to afford bipyrazole 10. Heating the 4,5'-bipyrazole derivative 4 in ethanolic sodium ethoxide solution afforded the bipyrazole 11 via concurrent decarboxylation and hydrogen cyanide elimination. Oxidation of the latter product with tetrachloro-1,4-benzoquinone gave the 4,5'-bipyrazole 12. The regioselectivity of the reaction was studied in the light of some theoretical reactivity indices and the frontier molecular orbital (FMO) theory using the B3PW91/6-31G(d) level of calculation as well as some thermodynamic properties using the PM6 semi-empirical level of calculation. The analysis of the data obtained reveals that the dipolar cycloaddition reactions in the present study can be classified in the normal electron demand category.

■ Synthesis of N-Aryl-2-aminobenzoxazoles from Substituted Benzoxazole-2-thiol and 2-Chloro-N-arylacetamides in KOH-DMF System

Guang-cheng Wang,* Jing Wang, Lu-yao Li, Shan Chen, Ya-ping Peng, Zhen-zhen Xie, Ming Chen, Bing Deng, and Wen-biao Li

*College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, China

Abstract

A simple and novel method for the synthesis of N-aryl-2-aminobenzoxazoles from substituted benzoxazole-2-thiol and 2-chloro-N-arylacetamides in KOH-DMF system has been developed. The present protocol provides an attractive approach to access various N-aryl-2-aminobenzoxazoles in moderate to good yields without using transition metal catalyst under very mild reaction condition.

■ Halogenation of Dimethyl Indole-2,3-dicarboxylates Using PhI(OAc)2 and Alkali Metal Halide

Yasuyoshi Miki,* Yukari Hirata, Noriko Makino, Yuuka Hirose, Misa Nogata, Akira Nakamura, Hiromi Hamamoto, and Tomohiro Maegawa*

*School of Pharmaceutical Sciences, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan

Abstract

We studied selective bromination and iodination of dimethyl indole-2,3-dicarboxylates using phenyliodine diacetate (PIDA), LiBr, and LiI in the presence of Lewis acid. The protective group on the nitrogen of indole is important for selectivity of the halogenation position, and the use of a benzenesulfonyl group as a protective group resulted in preferential halogenation of indole at the 6-position.

■ Inhibitory Activity of Hispidin Derivatives Isolated from Inonotus obliquus on Amyloid β Aggregation

Yukine Aihara, Ayumi Kawaguchi, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, and Hideyuki Shigemori*

*Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8572, Japan

Abstract

Alzheimer’s disease (AD), the most common neurodegenerative disease, is characterized by the aggregation of the 42-mer amyloid β-protein (Aβ42). The inhibition of Aβ aggregation is one of the therapeutic strategies for AD. We recently reported that caffeoylquinic acids and phenylethanoid glycosides possessing two or more catechol moieties strongly inhibit the aggregation of Aβ. We report on the inhibitory effect of hispidin derivatives, which were isolated from Inonotus obliquus, on the aggregation of Aβ42. Hispidin derivatives exhibited anti-aggregation activity in a dose-dependent manner. The structure–activity relation of hispidin derivatives validated that the presence of a catechol moiety is essential for the inhibitory activity.

■ Synthesis and Application of 1,2,3-Triazole Allyl Acetates: Expedient Access to Pyridine Derivatives

Nan Zheng and Wang-Ze Song*

*School of Chemical Engineering, School of Pharmaceutical Science and Technology, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China

Abstract

A series of novel 1,2,3-triazole allyl acetates were prepared by CuTC-catalyzed azide-alkyne cycloaddition (CuAAC) from 3-acyloxy-1,4-enynes and sulfonyl azides. The 1,2,3-triazole allyl acetates could be further transformed to pyridine derivatives through 6π-azaelectrocyclization followed by elimination.

■ Synthesis and Photophysical Property of Methanobenzo[10]annulene-2,3:8,9-bis(dicarboximide) Derivatives

Tatsuya Yanagisawa,* Naoki Kobayashi, Ryuta Miyatake, and Mitsunori Oda*

*Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, 611-0011, Japan

Abstract

Bis(dicarboximide) derivatives possessing methanobenzo[10]annulene skeleton were synthesized. The annulation of another dicarboximide on mono(dicarboximide), namely 1,6-methanobenzo[10]annulene-3,4-dicarboximide, provided the improvement of their molar extinction coefficients and fluorescence quantum yields. The change in photophysical behavior between mono(dicarboximide) and bis(dicarboximide) was explained by collaboration with theoretical calculations.

■ Selectivity of N- Versus O-Alkylation in Mitsunobu Reactions with Various Quinolinols and Isoquinolinols

Ryan E. Hartung,* Mark C. Wall, Sylvain Lebreton, Martin Smrcina, and Marcel Patek

*Icagen, 2090 E. Innovation Park Drive, Oro Valley, AZ 85755, USA

Abstract

Reacting quinolinols and isoquinolinols under Mitsunobu conditions can give rise to N-alkylated products in addition to the normally desired O-alkylated structures. An in-depth study of how the solvent, reagent equivalents, position of the quinoline/isoquinoline nitrogen and type of reacting aliphatic alcohol employed affect the ratio of N- versus O-alkylation is described.

■ Synthesis of Erlenmeyer-Plöchl Azlactones Promoted by 5-Sulfosalicylic Acid

Hamzeh Kiyani* and Shiva Aslanpour

*School of Chemistry, Damghan University, 36719-41167 Damghan, Iran

Abstract

5-Sulfosalicylic acid was found as an efficient catalyst in the synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones by condensation and cyclodehydration of aromatic aldehydes with hippuric acid and acetic anhydride at room temperature. The catalyst was easily recycled from the filtrate via evaporation of solvent and reused. This process is green, simple to handle, commercially available starting materials and catalyst, mild conditions, as well as it does not require to hazardous organic solvents, heating, and microwave and ultrasound irradiations.

■ Tandem Sonogashira-Hagihara Coupling/Cycloisomerization Reactions of Ethynylboronic Acid MIDA Ester to Afford 2-Heterocyclic Boronic Acid MIDA Esters: A Concise Route to Benzofurans, Indoles, Furopyridines and Pyrrolopyridines

Yohji Sakurai*

*Medicinal Chemistry Research Institute, Otsuka Pharmaceutical Co., Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima, 771-0192, Japan

Abstract

A one-pot process that provides direct access to 2-heterocyclic MIDA (N-methyliminodiacetic acid) boronates has been developed. The reaction of 2-iodophenols or 2-iodoanilines with ethynylboronic acid MIDA ester readily afforded 2-substituted heterocyclic compounds. Amidine and phosphazene bases, especially TMG (1,1,3,3-tetramethylguanidine) assumed an important role in the tandem Sonogashira-Hagihara coupling/cycloisomerization reactions.

■ Catalytic Enantioselective Desymmetrization of meso-Aziridines with Fluoromalonates

Seiya Fukagawa, Yingjie Xu, Masahiro Anada, Tatsuhiko Yoshino, and Shigeki Matsunaga*

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Catalytic enantioselective desymmetrization of meso-aziridines with fluoromalonates is described. Optimization studies revealed that the appropriate combination of Brønsted basic metal and Lewis acidic metal is important for promoting the reaction using fluoromalonates. A heterodinuclear Gd(OiPr)3/Y(OTf)3/Schiff base = 1:1:1 was the best catalyst, and ring-opening adducts, synthetic precursors for α-fluoro-γ-amino acids, were obtained in 98%~17% yield and >99.5%~99% ee. Transformation of the ring-opening adduct into α-fluoro-γ-lactam was also demonstrated.

■ Synthesis of Novel Tetracyclic Thieno[3’,2’:2,3]pyrido[4,5-d]pyrido[1,2-a]pyrimidinones via Pictet-Spengler Cyclization

Yi-Xin Tang, Dao-Lin Wang,* and Jian-Hua Qian

*Liaoning Key Laboratory of Synthesis & Application of Functional Compound, College of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121001, China

Abstract

Synthesis of novel thieno[3’,2’:2,3]pyrido[4,5-d]pyrido[1,2-a]pyrimidin-5-one derivatives (5) via Pictet-Spengler cyclization is reported. The key intermediate, 2-(3-amino-4-cyano-5-phenylaminothieno-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3), was readily prepared from 2-chloromethyl-4H-pyrido[1,2-a]pyrimidin-4-one (1) with potassium (2,2-dicyano-1-phenylaminoethen-1-yl)thiolate (2) by Thorpe-Ziegler isomerization. Reaction of the intermediate amine with aromatic aldehydes in the presence of p-TsOH gives tetracyclic thienopyridine-fused pyrido[1,2-a]pyrimidines 5 in good yields.