HETEROCYCLES

■ Contents

■ PEG-OSO3H as an Efficient Catalyst in the Synthesis of N3-Functionalized 3.4-Dihydropyrimidinone and Quinazolinone Derivatives

Liang-Jie Yang, Jin-Ge Luo, and Xi-Cun Wang*

*College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East Road, 967, 730070, China

Abstract

PEG-OSO3H-catalyzed three-component reaction of 3,4-dihydropyrimidones and quinazolinone with paraformaldehyde and various reagents for synthesis of N3-functionalized 3,4-dihydropyrimidone and quinazolinone derivatives is described. 2-Hydroxy-substituted 3,4-dihydropyrimidone reacts with aldehydes giving benzo[e]pyrimido[1,6-c][1,3]oxazines. This paper explores the versatility and effectiveness of polymer bound sulfonic acids as catalysts in different C-N and C-O bonds formation reactions. The reactions were completed in short times, and the products were obtained in good to excellent yields. The catalysts activity and recyclability were investigated completely.

■ Effect of End Groups on the Band Gap of Donor-Acceptor Based Small Molecules Containing Diketopyrrolopyrrole

Jin-Hee Han, Hun-Min Kang, Dong Jin Song, Baji Shaik, Yu Mi Heo, Hye Jin Chung, and Seung-Mann Paek*

*Department of Chemistry, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju daero, Jinju, Gyeongnam 660-701, Korea

Abstract

(Acceptor-donor-acceptor type compounds 5,5'-(4,4'-(2,5-bis(2-octyldodecyl)-3,6-dioxo-2,3,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1,4-diyl)bis(4,1-phenylene))dithiophene-2-carbonitrile (DPPTCN), 4',4''-(2,5-bis(2-octyldodecyl)-3,6-dioxo-2,3,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1,4-diyl)dibiphenyl-4-carbonitrile(DPPPhCN), 2,2'-(5,5'-(4,4'-(2,5-bis(2-octyldodecyl)-3,6-dioxo-2,3,5,6-tetra-hydropyrrolo[3,4-c]pyrrole-1,4-diyl)bis(4,1-phenylene))bis(thiophene-5,2-diyl))-bis(methan-1-yl-1-ylidene)dimalononitrile (DPPT2CN), 2,2'-(4',4''-(2,5-bis(2-octyldodecyl)-3,6-dioxo-2,3,5,6-tetrahydropyrrolo[3,4-c]pyrrole-1,4-diyl)bis(bi-phenyl-4',4-diyl))bis(methan-1-yl-1-ylidene)dimalononitrile (DPPPh2CN) were designed and synthesized. All the compounds have central diketopyrrolopyrrole as common acceptor unit, the donor groups differ either thiophene or phenyl group and the terminal end groups are differ either nitrile or dicyanovinylene groups. In order to study the relationship between chemical structure and properties, their optical, thermal and electrochemical properties were investigated. Thermal properties indicate that all the compounds have high thermal stability. Among them, DPPT2CN with thiophene groups as donor and dicyanovinylene as acceptor has shown lowest LUMO energy level of -3.77 eV and low HOMO-LUMO band gap of 1.86 eV.

■ Microwave-Assisted Synthesis of Benzofuran/Benzothiophene-Fused Naphthyridines via Thorpe-Ziegler Type Heterocyclization

Jiao Xu,* Dao-Lin Wang, Zhen-Peng Liu, Kai-Xue Zhang, Wei Ma, and Bin Liu

*Heilongjiang University of Chinese Medicine, Harbin 150040, China

Abstract

An efficient one-pot domino protocol for the synthesis of novel benzofuran/benzothiophene-fused naphthyridines, benzofuro- and benzothieno- [3,2-h]benzo[b][1,6]naphthyridin-5(6H)-one derivatives 4, was developed, starting from 2-chloromethylquinoline-3-carboxylates (1) with salicylonitriles (2) or 2-mercaptobenzonitrile (3) by microwave-assisted Thorpe-Ziegler type heterocyclization in the presence of cesium carbonate with good yields.

■ Short Synthesis of 5-Substituted-2,3,4,5-tetrahydro-Benzo[f][1,4]thiazepines by Using a Modified Pictet-Spengler Reaction

Toshiaki Saitoh, Michikazu Kitabatake, Yuuko Sugihara, Yuuki Ono, Yoshie Horiguchi, and Kunihiko Mohri*

*Department of Pharmaceutical Sciences, Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

5-Substituted-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepines (6) were synthesized using a modified Pictet-Spengler reaction of N-formyliminium ion (4) as the key step. The cyclization of 4 was found to be affected by the acidity of the reaction media, which depended on the structure of the benzene ring. The cyclization of the substrates (4a-g) lacking an electron-donating substituent at the benzene ring proceeded smoothly by using a mixed acid catalyst of trifluoroacetic acid and a small amount of trifluoromethanesulfonic acid, thus giving N-formylbenzothiazepines (5a-g) in good yields. On the other hand, in the case of substrates (4h-j) with the OMe group at the benzene ring, although the cyclization proceeded by use of trifluoroacetic acid as the sole catalyst to give the products (5h-j), the mixed acid catalyst did not induce the cyclization reaction to any extent. The modified Pictet-Spengler reaction, which constitutes imination of 2-(phenylthio)ethanamine (1a) with aldehydes (2), and formylation of the resulting imines (3), followed by the acid-catalyzed cyclization of N-formyliminium ion (4), could be carried out as a one-pot procedure, thus providing a convenient methodology for synthesizing various 5-substituted-2,3,4,5-tetrahydrobenzo[f][1,4]thiazepines (6).

■ Synthesis and Biological Evaluation of Novel Di- and Trisubstituted Thiazole Derivatives

Irmantas Parašotas, Eglė Urbonavičiūtė, Kazimieras Anusevičius, Ingrida Tumosienė, Ilona Jonuškienė, Kristina Kantminienė,* Rita Vaickelionienė, and Vytautas Mickevičius

*Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Radvilenu rd. 19, LT-50254 Kaunas, Lithuania

Abstract

Novel di- and trisubstituted thiazole derivatives bearing heterocyclic, aromatic, chalcone, and carboxyalkyl-heterocyclic moieties were synthesized. Compounds possessing significant antibacterial activity, comparable to that of commercial antibacterial agent ampicillin, against Rhizobium radiobacter, Xanthomonas campestris, and Escherichia coli were identified. Some of the synthesized compounds exhibited a very high antioxidant activity.

■ An Efficient One-Pot Synthesis of 4-Hydroxyisoquinoline-1,3(2H,4H)-diones from N-Alkylbenzamides and α-Keto Esters

Kazuhiro Kobayashi* and Yuuya Honda

*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

An efficient method for the preparation of 4-substituted 4-hydroxyisoquinoline-1,3(2H,4H)-diones has been developed. Thus, treatment of N-alkyl-2,N-dilithiobenzamides, generated by treating N-alkylbenzamides with two equivalents of butyllithium, with methyl 2-oxoalkanoates resulted in the formation of the desired products in one pot in satisfactory yields.

■ Development of N6-(Heteroarylcarbonyl)adenines as BRD4 Inhibitors

Seika Amemiya, Takao Yamaguchi, Yuichi Hashimoto, and Tomomi Noguchi-Yachide*

*Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan

Abstract

N6-(Heteroarylcarbonyl)adenines were synthesized as candidate BRD4 inhibitors, and their structure-activity relationships were investigated. Among the synthesized compounds, N6-[(3-methoxythiophen-2-yl)carbonyl]adenine (15) showed the most potent BRD4-inhibitory activity.

■ A Green and Highly Efficient Synthesis of 5,5-(Phenylmethylene)bis(1,3-dioxane-4,6-dione) Derivatives In Biobased Gluconic Acid Aqueous Solution

Zhaohui Xu,* Peng Zhou, Yuanhong Tu, Deyong Liu, Weilin Liao, and Chuanwen Liao

*College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330027, China

Abstract

A green and highly efficient synthesis of 5,5-(Phenylmethylene)bis(1,3-dioxane-4,6-dione) derivatives through tandem Knoevenagel condensation and Michael addition of aromatic aldehydes and 1,3-dioxane-4,6-dione in gluconic acid aqueous solution(GAAS) is described. Gluconic acid aqueous solution could be recycled and reused several times without significant loss of its effciency.

■ Stereoselective Encapsulation for a Triarylmethylium o,o-Dimer by Natural γ-Cyclodextrin: Origin of Chiral Recognition for the Axially Chiral Dicationic Guest

Takanori Suzuki,* José P. Cerón-Carrasco, Hitomi Tamaoki, Yusuke Ishigaki, Ryo Katoono, Takanori Fukushima, and Horacio Pérez-Sánchez*

*Department of Chemistry, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan

Abstract

Upon 1:1 complexation with γ-cyclodextrin (CyD) in water, easily interconverting rotational isomers of biphenyl-2,2'-diylbis[bis(4- dimethylaminophenyl)methylium] (R)/(S)-1a2+ were biased to prefer an R configuration (75 : 25 at 25 ºC). Docking and quantum chemical calculations revealed two modes (on-top and botton-side) of encapsulation of γ-CyD, which shed a light on the origin of the first chiral recognition of axially chiral dicationic dyes by using natural CyDs.

■ Conversion of Oxazolines to Cyanomethyl Esters with Pyridinium Hydrobromide Perbromide in Water1

Shinsei Sayama*

*Natural Sciences (Chemistry), Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan

Abstract

Various aromatic and heterocyclic oxazolines were directly converted to respective cyanomethyl esters with pyridinium hydrobromide perbromide in water at room temperature.

■ An Efficient and Multi-Component Synthesis of 5-Imino-3,5-dihydro-2H-chromeno[3,4-c]pyridin-2-one Derivatives

Juxian Wang, Yang Gao, Juanjuan Zhang, Guoning Zhang, Jinfeng Ren, Yue Zhao, Yucheng Wang,* and Daqing Shi*

*College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

Abstract

A facile and efficient one-pot procedure for the synthesis of 5-imino-3,5-dihydro-2H-chromeno[3,4-c]pyridin-2-one derivatives via a four-component reaction of salicylaldehyde, malononitrile, ethyl cyanoacetate and hydrazine hydrate under mild conditions in excellent yield is described. The structures of fused molecules have been unambiguously confirmed by their spectroscopic techniques as well as by single crystal X-ray analysis.

■ Synthesis of 3-Iminobenzo[c]thiophen-1(3H)-one Derivatives Based on the Reaction of 2-Lithio-N,N-dimethylbenzamides with Isothiocyanates

Kazuhiro Kobayashi,* Yuuho Shigemura, and Daiki Fujiwara

*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 facile two-step sequence for the preparation of 3-(Z)-(aryl(or alkyl)imino)benzo[c]thiophen-1(3H)-ones starting from 2-bromo-N,N- dimethylbenzamides has been developed. The starting amides were allowed to react with butyllithium to generate 2-lithio-N,N-dimethylbenzamides, of which reaction with isothiocyanates gave the corresponding N,N-dimethyl-2-(thiocarbamoyl)benzamides. These precursors were treated with p-toluenesulfonic acid monohydrate. The cyclization proceeds in a chemo- and stereo-selective manner to provide the desired product as the sole isolated product in each case.