Efficient Synthesis of Pyrrolo[2,1‐a]isoquinoline and Pyrrolo[1,2‐a]quinoline Derivatives via One‐pot Two‐step Metal‐catalyzed Three‐component Reactions

A sequential one‐pot two‐step reaction for efficient synthesis of pyrrolo[2,1‐a]isoquinoline and pyrrolo[1,2‐a]quinoline derivatives in good yields has been successfully developed. The reaction included firstly Cu‐catalyzed three‐component reaction of isoquinoline (quinoline), acetylenedicarboxylate and alkynylbenzene and then Pd‐catalyzed intramolecular C(sp)‐C(sp²) coupling reaction of initially formed 1‐alkenyl‐2‐alkynyl‐1,2‐dihydroisoquinoline (1,2‐dihydroquinoline).     

Regioselective Synthesis of Indolizines,Pyrrolo[2,1-a]isoquinolines,and Quinolines

Convenient and regioselective synthesis of indolizine and pyrrolo[2,1-a]isoquinoline/quinoline derivatives by one-pot multicomponent reaction of N-substituted pyridinium and isoquinolinum/quinolinium salts with alkyl propiolates in the presence triphenylphosphine is described.     

Photocatalytic Oxidative [3+2] Cycloaddition for Pyrrolo[2,1-a]isoquinoline Synthesis Using a Porphyrin-Based Covalent Organic Framework

By using a catalytic amount of a porphyrin-based covalent organic framework (Por-Ad-COF) as the efficient recyclable photocatalyst, the photocatalytic oxidative [3+2] cycloaddition reaction between tetrahydroisoquinolines and N-substituted maleimides was developed under aerobic conditions at room temperature. Various substituted pyrrolo[2,1-a]isoquinolines were obtained in moderate to good yields via the dipolar [3+2] cycloaddition and oxidative aromatization cascade process under visible light irradiation. This was the first example to employ the covalent organic framework as the heterogeneous photocatalyst to perform the photocatalytic dipolar [3+2] cycloaddition reaction for the synthesis of pyrrolo[2,1-a]isoquinolines.     

Synthesis of Novel 1H‐Imidazol[1,2‐a]Indeno[2,1‐e]Pyridine‐6(5H)‐Ones Derivatives via a One‐Pot Four‐Component Condensation Reaction

1H‐imidazol[1,2‐a]indeno[2,1‐e]pyridine‐6(5H)‐ones derivatives were synthesized in a one‐pot four‐component condensation of corresponding aldehydes, 1,3‐indandione, diamine, and nitro ketene dithioacetal using KAl(SO₄)₂·12H₂O (alum) as nontoxic, reusable, inexpensive and easily available catalyst in good to excellent yields. This green protocol provides a powerful entry into fused polycyclic structures related to bioactive heterocycles.     

Synthesis of Novel Disubstituted Pyrazolo[1,5‐a]pyrimidines,Imidazo[1,2‐a]pyrimidines,and Pyrimido[1,2‐a]benzimidazoles Containing Thioether and Aryl Moieties

A series of novel 6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐7‐phenylpyrazolo[1,5‐a]pyrimidines, 5‐phenyl‐6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]imidazo[1,2‐a]pyrimidines, and 2‐phenyl‐3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]pyrimido[1,2‐a]benzimidazoles have been synthesized in four steps starting with 2‐hydroxyacetophenone. The intermediate 3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐4H‐1‐benzopyran‐4‐ones reacted with pyrazol‐3‐amines, 5‐methylpyrazol‐3‐amine, and 1H‐imidazol‐2‐amine, 1H‐benzimidazol‐2‐amine via a cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The approach affords the target compounds in acceptable‐to‐good yields. The new compounds were characterized by their IR, NMR, and HR mass spectra.     

Multicomponent Strategy for the Preparation of Pyrrolo[1,2‐a]pyrimidine Derivatives under Catalyst‐Free and Microwave Irradiation Conditions

A simple and efficient one‐pot procedure has been developed for the construction of pyrrolo[1,2‐a]pyrimidines via the three‐component domino reaction of 5‐aminopyrazoles, acetylenedicarboxylates and malononitrile under catalyst‐free, microwave irradiation conditions. The key step in this transformation is the N? N bond cleavage reaction of the 5‐aminopyrazole substrate, which has been reported in this context for the first time in this study. The advantages of this protocol include readily available starting materials, short reaction times and good regioselectivity.     

3a‐Phenyl‐2,3,3a,4‐tetrahydro‐1H‐benzo[d]pyrrolo[1,2‐a]imidazol‐1‐one,a potential plant‐growth regulator

Molecules of the title compound, C₁₆H₁₄N₂O, a potential plant‐growth regulator, are linked into chains by intermolecular C=O...H—N hydrogen bonds. These chains are weakly interconnected by π–π stacking interactions to form a three‐dimensional framework. A comparison of the geometric parameters of the title molecule and several related benzimidazoles and pyrrolidones is presented.<!?tpb=22pt>     

Superacid‐Promoted Cyclodehydration Leading to the Imidazo[2,1‐a]isoquinoline Ring System

A series of heterocycle‐substituted acetophenones were prepared and reacted with the Brønsted superacid CF₃SO₃H (triflic acid=trifluoromethanesulfonic acid). Cyclodehydration provided aryl‐substituted imidazo[2,1‐a]isoquinolines and related products (28–85%, seven examples). A mechanism is proposed involving dicationic intermediates.     

Synthesis of Novel Isoindolo[2,1‐a]quinazolinedione Derivatives Containing a 1,2,3‐Triazole Ring System

A synthesis of isoindolo[2,1‐a]quinazolinedione derivatives, coupled with a 1,2,3‐triazole ring system, via the reaction of isatoic anhydride, HC?CCH₂NH₂, and 2‐formylbenzoic acid is described, which led to the formation of the isoindolo[2,1‐a]quinazoline‐5,11‐dione scaffold having a C?C bond that participated in a click reaction with various organic azides.     

One‐Pot Synthesis of Novel Pyrrolo[1,2‐a]quinoxaline‐4(5H)‐ones Using Benzene‐1,2‐diamine,Acetylenedicarboxylates, and β‐Nitrostyrene Derivatives

The reaction between a variety of o‐phenylenediamines (=benzene‐1,2‐diamines), dialkyl acetylenedicarboxylates, and derivatives of nitrostyrene (=(E)‐(2‐nitroethenyl)benzene) in the presence of sulfamic acid (SA; H₃NSO₃) as catalyst led to the corresponding pyrrolo[1,2‐a]quinoxaline‐4(5H)‐one derivatives in high yields.     

Synthesis of 9,9‐Disubstituted 9H‐Pyrrolo[1,2‐a]indoles by Hydriodic Acid‐Catalyzed Cyclization of 1‐[2‐(1‐Aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles

A novel method is reported for the synthesis of 9,9‐disubstituted 9H‐pyrrolo[1,2‐a]indoles. Cyclization of 1‐[2‐(1‐aryl(or methyl)ethenyl)phenyl]‐1H‐pyrroles, which can be easily prepared from 2‐(1‐aryl(or methyl)ethenyl)anilines, proceeds smoothly, in general, at 0° in the presence of a catalytic (or an equimolar) amount of HI in MeCN to provide the desired products.     

Diastereoselective Synthesis of 1,10-Dihydropyrrolo [ 1,2-a] [1,10]phenanthroline Derivatives via 1,3-Dipolar Cycloaddition Reaction

The functionalized 1,10-dihydropyrrolo[1,2-a][1,10]phenanthroline derivatives were synthesized in good yields and with high diastereoselectivity by 1,3-dipolar cycloaddition reactions of N-phenacylphenanthrolinium bromides or N-ethoxycarbonylmethylene phenanthrolinium bromide with various nitrostyrenes in acetonitrile at room temperature in the presence of triethvlamine,     

1,4‐Dipolar Cycloaddition Reactions in Ionic Liquids: A Facile Synthesis of 9aH,15H‐[1]Benzopyrano[3′,2′: 3,4]pyrido[2,1‐a]isoquinolines (=9aH,15H‐Benzo[a][1]benzopyrano[2,3‐h]quinolizines)

Ionic liquids were found to be a suitable reaction medium for 1,4‐dipolar cycloaddition reactions of an isoquinoline, an activated alkyne, and a 4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde at room temperature to afford [1]benzopyrano‐pyrido‐isoquinoline (=9aH,15H‐benzo[a][1]benzopyrano[2,3‐h]quinolizine) derivatives selectively in good yields. The ionic liquid can be recovered and recycled in further runs without loss of activity.     

TFAA‐Catalyzed Annulation Synthesis of Spiro Pyrrolo[1,2‐a]quinoxaline Derivatives from 1‐(2‐Aminophenyl)pyrroles and Benzoquinones/Ketones

A metal‐free trifluorosulfonate anhydride (TFAA)‐catalyzed strategy for the synthesis of spiro pyrrolo[1,2‐a]quinoxalines from 1‐(2‐aminophenyl)pyrroles and benzoquinones/ketones has been developed. With this general method, spiro pyrrolo[1,2‐a]quinoxalines have been accessed via nucleophilic addition and cyclization. This reaction exhibits good functional group tolerance, and a wide range of products are obtained in moderate to good yields.     

Synthesis and Antimicrobial,Anticancer and Anti-Oxidant Activities of Novel 2,3-Dihydropyrido[2,3-d]pyrimidine-4-one and Pyrrolo[2,1-b][1,3]benzothiazole Derivatives via Microwave-Assisted Synthesis

In our attempt towards the synthesis and development of effective antimicrobial, anticancer and antioxidant agents, a novel series of 2,3-dihydropyrido[2,3-d]pyrimidin-4-one 7a–e and pyrrolo[2,1-b][1,3]benzothiazoles 9a–e were synthesized. The synthesis of 2-(1,3-benzo thiazol-2-yl)-3-(aryl)prop-2-enenitrile (5a–e) as the key intermediate was accomplished by a microwave efficient method. Via a new variety oriented synthetic microwave pathway, these highly functionalized building blocks allowed access to numerous fused heteroaromatic such as 7-amino-6-(1,3-benzo thiazol-2-yl)-5-(aryl)-2-thioxo-2,3dihydropyrido [2,3-d]pyrimidin-4(1H)-one 7a–e and 1-amino-2-(aryl)pyrrolo[2,1-b][1,3]benzothiazole-3-carbonitrile derivatives 9a–e in order to study their antimicrobial and anticancer activity. The present investigation offers effective and rapid new procedures for the synthesis of the newly polycondensed heterocyclic ring systems. All the newly synthesized compounds were evaluated for antimicrobial, anticancer and antioxidant activity. Compounds 7a,d, and 9a,d showed higher antimicrobial activity than cefotaxime and fluconazole while the remaining compounds exhibited good to moderate activity against bacteria and fungi. An anticancer evaluation of the newly synthesized compounds against the three tumor cell lines (lung cell NCI-H460, liver cancer HepG2 and colon cancer HCT-116) exhibited that compounds 7a, d, and 9a,d have higher cytotoxicity against the three human cell lines compared to doxorubicin as a reference drug. These compounds also exhibited higher antioxidant activity and a great ability to protect DNA from damage induced by bleomycin.     

Multicomponent Transformation of Isoindoline‐1,3‐diimine (=1H‐Isoindole‐1,3(2H)‐diimine), Acetylenic Esters,and Triphenylphosphine to Novel Dihydropyrimido[2,1‐a]isoindole Derivatives

The three‐component reaction of the zwitterions generated from dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates and triphenylphosphine (Ph₃P) with isoindoline‐1,3‐diimine (=1H‐isoindole‐1,3(2H)‐diimine) is described (Scheme 1). This reaction affords the corresponding special type of substituted dihydropyrimido[2,1‐a]isoindole derivatives in good yields without using any catalyst and activation (Table).     

A Novel,Simple and Efficient Synthesis of 3‐Amino‐Benzo[d]imidazo[2,1‐b]Thiazole Derivatives via a Multicomponent Procedure

3‐Amino‐benzo[d]imidazo[2,1‐b]thiazoles were synthesized in moderate to good yields in the presence of NH₄Cl via a one pot procedure. All the products were characterized by ¹H NMR, IR, HRMS.