Microwave‐Assisted One‐Pot Synthesis of Substituted 3‐Bromoimidazo[1,2‐a]pyridines and Imidazoheterocycles

Herein, an efficient, one‐pot microwave‐assisted synthesis of a diverse set of 3‐bromoimidazo[1,2‐a]pyridines is being reported with good yields (40–85%). The method involves electrophilic aromatic bromination using bromodimethylsulfonium ion generated in situ via oxidation of HBr salt by DMSO. This methodology was also applied to the synthesis of related imidazoheterocycles. Copyright © 2014 HeteroCorporation     

Microwave‐Assisted Aqueous Synthesis of 6‐Ferrocenyl Pyridin‐2(1H)‐one Derivative

A clean and green method for synthesizing a series of new ferrocenyl pyridin‐2(1H)‐one derivative was developed via the one‐pot reactions of aldehydes, Meldrum's acid, acetylferrocene, and ammonium acetate using high‐temperature water as a solvent and microwave heating. This method had several advantages such as good yields, reduced environmental impact, and convenient procedure.     

3‐(α‐Chlorobenzyl)quinoxalin‐2(1H)‐ones as Versatile Reagents for the Synthesis of 3‐Benzylquinoxalin‐2(1H)‐ones and Thiazolo[3,4‐a]quinoxalin‐4(5H)‐ones

Facile and efficient methods for the synthesis of 3‐benzylquinoxalin‐2(1H)‐ones and thiazolo[3,4‐a]quinoxalin‐4(5H)‐ones by the reaction of the readily available 3‐(α‐chlorobenzyl)quinoxalin‐2(1H)‐ones and thiourea have been developed, with multiple roles of the latter. Possible mechanisms are discussed. These two‐step sequences can be performed in a one‐pot manner to produce the desired products in moderate to high yields.     

Reactions of 4‐Hydroxyquinolin‐2(1H)‐ones with Acenaphthoquinone: Synthesis of New 1,2‐Dihydroacenaphthylene‐spiro‐tetrakis(4‐hydroxyquinolin‐2(1H)‐ones)

Reaction of four equivalents of 4‐hydroxyquinolin‐2(1H)‐ones with one equivalent of acenaphthoquinone in absolute ethanol, containing catalytic triethylamine, gave 3,3′,3″,3?‐(1,2‐dihydroacenaphthylene)‐1,1,2,2‐tetrayl‐tetrakis(4‐hydroxyquinolin‐2(1H)‐ones) in a good to excellent yields. The structures of the products were elucidated by ¹H NMR, ¹³C NMR, NMR, IR, mass spectra, and elemental analyses.     

Synthesis of Novel 1‐(Benzo[d]thiazol‐2‐yl)‐1H‐pyrrol‐2(5H)‐ones

The titled products comprising of two mutually merged bioactive nucleuses, 2‐aminobenzo[d]thiazole and 2,5‐dihydropyrrole rings, were obtained from the reaction between dialkyl acetylenedicarboxylates and alkyl 2‐(benzo[d]thiazol‐2‐yl)amino‐2‐oxoacetates in the presence of triphenylphosphine at RT.     

Synthesis of 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones and their reactions with nucleophiles

[2‐Alkylthio‐6‐methyl‐4‐oxopyrimidin‐3(4H)‐yl]acetonitriles ( 3‐5 ) treated with sodium methoxide in methanol followed by ammonium chloride were cyclized to 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones ( 6‐8 ). Under acid or base‐catalyzed hydrolysis they were converted to 7‐methyl‐imidazo[1,2‐a]pyrimidine‐2,5‐[1H,3H]‐diones ( 9‐11 ), whereas in the reaction with butyl‐ or benzylamine the corresponding 7‐methyl‐2‐(substitutedamino)imidazo[1,2‐a]pyrimidin‐5(3H)‐ones ( 13‐18 ) were produced. The latter were found to exist in two tautomeric forms in CDCl₃ solution.     

Synthesis of 5,6‐Diarylpyridin‐2(1H)‐ones from Isoflavones

A simple method for the cyclocondensation of substituted isoflavones with cyanoacetamide in the presence of sodium hydroxide to give an array of 3‐cyano‐5,6‐diarylpyridin‐2(1H)‐ones in good yields is reported.     

Microwave‐Assisted Synthesis of Pyrrolo[2,1‐b]thiazoles Linked to a Carbohydrate Moiety

Herein, we describe the synthesis of pyrrolo[2,1‐b]thiazoles substituted on C‐2 or C‐5 with a protected carbohydrate moiety. The new fused bicyclic heterocycles were obtained via thiazole intermediates, and the N‐alkylation step was assisted by microwave irradiation. The new products were completely characterized by physical and spectroscopic techniques. The cytotoxicity and antiviral activity against Junín virus of the methylated derivates was also evaluated.     

Microwave‐assisted synthesis of new regioisomeric 6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones

Novel 11‐amino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e] pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones 4a‐f were prepared regioselectively by the tricomponent reaction of 4,5,6‐triaminopyrimidine 1, 1,3‐indandione 2 and aromatic aldehydes 3a‐f. The bicomponent approach, using 2,4,5,6‐tetraaminopyrimidine 5 and 2‐aryl‐ideneindandiones 6a‐f as reagents, afforded 9,11‐diamino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b]‐[1,4]diazepin‐5(5aH)‐ones 7a‐f in good yields and the regioisomeric 8,10‐diamino derivatives 8a‐c in lower yields. Both, bi‐ and tricomponent approaches were performed by microwave irradiation and all products were fully characterized by detailed NMR measurements.     

One‐Pot Synthesis of Pyrrolo[1,2‐a]quinolin‐1‐ones by the Cyclocondensation of 5‐Hydroxy‐1‐arylpyrrolidin‐2‐ones with Dicarbonyls

A one‐pot synthesis of pyrrolo[1,2‐a]quinolin‐1‐ones has been developed from the reactions of 5‐hydroxy‐1‐arylpyrrolidin‐2‐ones with 1,3‐dicarbonyl compounds under the promotion of H₃PO₄/P₂O₅ or HOAc/H₂SO₄. The pyrrolo[1,2‐a]quinolin‐1‐ones are formed by two‐step reactions, that is, the coupling of N‐acyliminium ion intermediates produced from 5‐hydroxy‐1‐arylpyrrolidin‐2‐ones with 1,3‐dicarbonyls and subsequent Friedel–Crafts reactions of the resulting ketone with the aryl ring.     

Synthesis of 4‐Hydroxy‐3‐(2‐arylimidazo[1,2‐a]pyridin‐3‐yl)quinolin‐2(1H)‐ones in the Presence of DABCO as an Efficient Organocatalyst

The one‐pot, three‐component, synthesis of a new series of 4‐hydroxy‐3‐(2‐arylimidazo[1,2‐a]pyridin‐3‐yl)quinolin‐2(1H)‐ones in the presence of DABCO as a catalyst has been achieved using aryl glyoxal monohydrates, quinoline‐2,4(1H,3H)‐dione, and 2‐aminopyridine in H₂O/EtOH under reflux conditions. The cheapness of organocatalyst, simple workup, operational simplicity, regioselectivity, and high yields are some advantages of this protocol.     

Quinolone analogues 7 [1‐6]. Synthesis of 3‐Heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The 3‐heteroaryl‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐e were synthesized by the oxidative‐hydrolytic ring transformation of the 3‐heteroaryl‐1,2‐diazepino[3,4‐b]]quinoxaline‐5‐carbonitriles 9a‐c , which were obtained by the 1,3‐dipolar cycloaddition reaction of the 2‐(2‐heteroarylmethylene‐1‐methylhydrazino)quinoxaline 4‐oxides with 2‐chloroacrylonitrile. The assignment of the thiophene and furan ring protons was carried out through the data of the NOE, decoupling, and coupling constants.     

Synthesis of [2′‐2H1]‐Ribonucleosides

New syntheses of C(2′)‐deuterated ribonucleosides have been accomplished starting either from 3,5‐di‐O‐benzyl‐1‐O‐methyl‐α,β‐D ‐ribofuranose ( 1b ) or 2,3‐O‐isopropylidene‐D ‐ribose ( 14 ), with >97 atom‐% D incorporation in both cases. The former is suited to the demands of multiple‐site deuteration or uniform ¹³C/multiple ²H double labeling of the ribofuranose moiety, whereas the latter is particularly appropriate for single‐site ²H labeling for mechanistic studies of enzyme reactions.     

Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b , whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d , whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d , respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d , whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d , respectively. Compounds 6a‐d had antifungal activities in vitro.     

First Synthesis of Highly Chemiluminescent Benzo[b]furan‐2(3H)‐ones Bearing a Urea Substructure

A series of benzo[b]furan‐2(3H)‐ones (coumaran‐2‐ones) bearing a urea substructure, namely derivatives of 3‐(aminocarbonylamino)benzo[b]furan‐2(3H)‐one, was prepared for the first time. The accessibility of these compounds through an electrophilic α‐amidoalkylation approach of phenols (Tscherniac–Einhorn reaction) in the key step as well as the chemiluminescence (CL) properties of the desired compounds are strongly dependent on the substitution patterns at the urea moiety. Competing reaction pathways are discussed and an improved one pot synthetical approach of also general interest is presented. In conclusion, especially N,N‐dialkylaminocarbonylamino‐derivatives of benzo[b]furan‐2(3H)‐ones exhibit a strong flash like blue CL upon treatment with bases such as 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in the presence of oxygen or hydrogen peroxide. Comparative physico‐chemical investigations revealed that novel compounds outperform their urethane‐analogues in terms of CL‐intensity and the speed of the decay making them potentially useful as new tools for CL‐based applications on the short time scale.     

Solvent‐Free Microwave‐Assisted Synthesis of Novel 4‐Hetarylpyrazolo[1,5‐a][1,3,5]triazines

A series of novel 4‐hetaryl substituted pyrazolo[1,5‐a][1,3,5]triazines were synthesized by microwave assisted reaction between O,S‐diethyl hetaroylimidothiocarbonates and 5‐amino‐3‐aryl‐1H‐pyrazoles under solvent‐free conditions. This procedure led to the formation of mixtures of two new pyrazolotriazine derivatives in a 1:4 ratio, which were separated by column chromatography being their corresponding structures unambiguously established by spectroscopic and analytical techniques. Comparison of the reactions mediated by microwave irradiation and by conventional heating in solution of DMF showed that both procedures afforded the same mixtures of products, but the first approach required shorter reaction times and gave higher yields than the second one.