Investigation of the reactivity of (1H-benzo[d]imidazol-2-yl)acetonitrile and (benzo[d]thiazol-2-yl)acetonitrile as precursors for novel bis(benzo[4,5]imidazo[1,2-a]pyridines) and bis(benzo[4,5]thiazolo[3,2-a]pyridines)

Abstract

Table of Contents 1. Experimental S2 2. 1 H and 13 C NMR spectra for compounds 1a-h; 9; 18 and 19a-d S6 S2 Experimental Materials and methods Melting points were determined in open glass capillaries with a Gallenkamp apparatus. The infrared spectra were recorded in potassium bromide disks on a Pye Unicam SP 3-300 and Shimaduz FTIR 8101 PC infrared spectrophotometer. NMR spectra were recorded using a Varian Mercury VXR-300 NMR spectrometer or Bruker Ultrashield 400 MHz or Ascend 400 MHz (1H: 300 or 400 MHz, 13C: 75 or 100.6 MHz) instruments using DMSO-d6 as solvent. Mass spectra (EI) were obtained at 70 eV using a type Shimadzu GCMQP 1000 EX Spectrometer. Elemental analyses were performed on a Perkin-Elmer 240 micoanalyser at the Micro analytical Center of Cairo University. Compounds 10ai [42] and 13a-i [22] were prepared according to literature. General procedure for the synthesis of compounds 1a-h.Method A. To a mixture of bisaldehydes 10a-h (1 mmole), malononitrile ( 5) (2 mmole) and 2-(1Hbenzo[d]imidazol-2-yl)acetonitrile (11) (2 mmole) in absolute ethanol (25 mL), piperidine (2 mmole) was added. The reaction mixture was heated at reflux for 2 h. The crude solid was isolated and recrystallized from the proper solvent. Method B. To a mixture of appropriate bis(arylidene malononitrile) 13a, 13b or 13f (1 mmole) and 2-(1H-benzo[d]imidazol-2-yl)acetonitrile (11) (2 mmole) in absolute ethanol (15 mL) piperidine (2 mmole) was added. The reaction mixture was heated at reflux for 2 h. The crude solid was isolated and recrystallized from the proper solvent to give 1a, 1b and 1f, respectively. Method C. To a mixture of 3,3'-((alkane-1,3-diylbis(oxy))bis(2,1-phenylene))bis-(2-(1Hbenzo[d]imidazol-2-yl)acrylonitrile) (18) (1 mmole) and malononitrile (5) (2 mmole) in absolute ethanol (15 mL) piperidine (2 mmole) was added. The reaction mixture was heated at reflux for 2 h. The crude solid was isolated and recrystallized from DMF to give 1a. 3,3'-((Propane-1,3-diylbis(oxy))bis(2,1-phenylene))bis(1-aminobenzo-[4,5]imidazo[1,2a]pyridine-2,4-dicarbonitrile) (1a).

Synthesis and DTF studies of novel aminoimidazodipyridines using 2-(3H-imidazo[4,5-b]pyridin-2-yl)acetonitrile as an efficient key precursor

“…Synthesis of compounds 6a-e via reaction of 4 with cinnamonitriles. Route A that affords compounds 12 was approved based on literature similarities 32,33 that indicated the superiority of the nucleophilicity of CH2 over NH group. Further support for the formation of compound 12a was provided by an alternative synthesis via a three component reaction of 2-(3H-imidazo [4,5-b]pyrid-2yl)acetonitrile 10 with both benzaldehyde (18) and malononitrile (19) in EtOH heated at reflux in the presence of catalytic piperidine (Scheme 6, Method B).…”

Design, Synthesis, In silico and In Vitro Anticancer Activity of Novel Bis‐Furanyl‐Chalcone Derivatives Linked through Alkyl Spacers

“…In our endeavor towards the development and discovering of a novel potent anticancer agents, [24][25][26][27][28][29][30][31][32][33][34][35][36] we designed and prepared a novel series of furan-substituted chalcone derivatives, in which the bis-furan units are at the A-or B-rings (Figure 2), utilizing the appropriate bis-aldehydes or bisketones as precursors. To prove the anticancer activity, the newly synthesized chalcones were tested against six human cancer cell lines; A549 (Lung carcinoma), HCT116 (Colon cancer), HePG2 (hepatocellular carcinoma cell line), PC3 (Prostate cancer), A431 (skin cancer) and BJ1 (normal skin fibroblast).…”

Hantzsch reaction with 6-aminouracil: Synthesis of novel tetrakis(6-aminouracil-5-yl)methanes and bis(decahydropyrido[2,3-d:6,5-d']dipyrimidine-tetraones) linked to aliphatic or aromatic cores via ether-amide or ester-amide linkages

“…18,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] Figure 1. Some selected FDA-approved uracil drugs In connection with the importance of both 1,4-dihydropyridine and the dipyrimidine moiety and in continuation to our interest in enamine chemistry, [52][53][54][55][56] the synthesis of bis(heterocycles) 17,[47][48][49][50][51][52][53][54][55][56][57][58][59][60] as well as the C-C bond formation reactions, 52,[71][72][73] we report herein a highly efficient method for the synthesis of bis(pyrido [2,3-d:6,5-d']dipyrimidinetetraones) linked to aliphatic or aromatic core via ether-amide or esteramide linkages through the reaction of bis(aldehydes) with 6-aminouracil.…”