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.     

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.     

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 Diastereoselective Synthesis of Densely Functionalized 2H‐Indeno[2,1‐b]furans. Single‐Crystal X‐Ray Structure of Dimethyl 8,8a‐Dihydro‐8‐oxo‐8a‐(2,2,2‐trichloroethoxy)‐2H‐indeno[2,1‐b]furan‐2,3‐di­carboxylate

Highly reactive 1 : 1 intermediates were produced in the reaction of Ph₃P and dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates). Protonation of these intermediates by alcohols (2,2,2‐trichloroethanol, propargyl alcohol (=prop‐2‐yn‐1‐ol), MeOH, benzyl alcohol, and allyl alcohol (=prop‐2‐en‐1‐ol) led to vinyltriphenylphosphonium salts 4 , which underwent a Michael addition reaction with the conjugate base to produce the corresponding stabilized phosphonium ylides 5 (Scheme). Wittig reaction of the stabilized phosphonium ylides with ninhydrin ( 6 ) led to the corresponding densely functionalized 2H‐indeno[2,1‐b]furans 10 in fairly good yields (Table 1). The structures of the final products were confirmed by IR, ¹H‐ and ¹³C‐NMR spectroscopy, and mass spectrometry. The configuration of dimethyl 8,8a‐dihydro‐8‐oxo‐8a‐(2,2,2‐trichloroethoxy)‐2H‐indeno[2,1‐b]furan‐2,3‐dicarboxylate ( 10a ) was established by a single‐crystal X‐ray structure determination, establishing that the one‐pot multicomponent condensation reaction was completely diastereoselective.     

A Novel Route to 1‐Substituted 3‐(Dialkylamino)‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles

Heptalenecarbaldehydes 1 / 1′ as well as aromatic aldehydes react with 3‐(dicyanomethylidene)‐indan‐1‐one in boiling EtOH and in the presence of secondary amines to yield 3‐(dialkylamino)‐1,2‐dihydro‐9‐oxo‐9H‐indeno[2,1‐c]pyridine‐4‐carbonitriles (Schemes 2 and 4, and Fig. 1). The 1,2‐dihydro forms can be dehydrogenated easily with KMnO₄ in acetone at 0° (Scheme 3) or chloranil (=2,3,5,6‐tetrachlorocyclohexa‐2,5‐diene‐1,4‐dione) in a ‘one‐pot’ reaction in dioxane at ambient temperature (Table 1). The structures of the indeno[2,1‐c]pyridine‐4‐carbonitriles 5′ and 6a have been verified by X‐ray crystal‐structure analyses (Fig. 2 and 4). The inherent merocyanine system of the dihydro forms results in a broad absorption band in the range of 515–530 nm in their UV/VIS spectra (Table 2 and Fig. 3). The dehydrogenated compounds 5, 5′ , and 7a – 7f exhibit their longest‐wavelength absorption maximum at ca. 380 nm (Table 2). In contrast to 5 and 5′, 7a – 7f in solution exhibit a blue‐green fluorescence with emission bands at around 460 and 480 nm (Table 4 and Fig. 5).     

A Facile One‐Pot Synthesis of Functionalized 1,5‐Dihydro‐2H‐[1]benzopyrano[2,3‐b]pyridin‐5‐ones

The highly reactive 1 : 1 intermediate generated in the reaction between dialkyl acetylenedicarboxylate (=but‐2‐ynedioic acid dialkyl ester) 4 and triphenylphosphine was trapped by 2‐amino‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes 5 to yield highly functionalized dialkyl‐1,5‐dihydro‐5‐oxo‐1‐phenyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,3‐dicarboxylates in high yield.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

Synthesis of Isoindolo[2,1‐a]quinazoline‐5,11‐dione Derivatives via the Reductive One‐Pot Reaction of N‐Substituted 2‐Nitrobenzamides and 2‐Formylbenzoic Acids

Various isoindolo[2,1‐a]quinazoline‐5,11‐dione derivatives 3 were synthesized in good yields by means of the reductive reaction of N‐substituted 2‐nitrobenzamides 1 and 2‐formylbenzoic acids 2 in the presence of SnCl₂?2 H₂O under reflux in EtOH (Scheme, Table). The procedure needed two steps, the reduction of the nitro group of the 2‐nitrobenzamide and ring closure by nucleophilic addition of the NH₂ group to both the formyl and carboxylic acid C?O groups.     

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).     

Synthesis of 1,3‐Dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates via Intramolecular Cyclization of 2‐[2‐(Dimethoxymethyl)phenyl]‐ 2‐hydroxyalkanoates Followed by Oxidation

A novel and efficient method for the preparation of 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 4 under mild conditions has been developed. Thus, the reaction of [2‐(dimethoxymethyl)phenyl]lithiums, generated easily from 1‐bromo‐2‐(dimethoxymethyl)benzenes 1 , with α‐keto esters gives the corresponding 2‐[2‐(dimethoxymethyl)phenyl]‐2‐hydroxyalkanoates 2 . The TsOH‐catalyzed cyclization of these hydroxy acetals is followed by the oxidation of the resulting cyclic acetals 3 with PCC to give the desired products in satisfactory yields. The reaction of [2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]lithium with (MeOC?O)₂, followed by treatment with NaBH₄ or organolithiums, affords 2‐[2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]‐2‐hydroxyalkanoates 6 , which can similarly be transformed into the corresponding 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 7 in reasonable yields.     

Facile Access to Benzothiazole‐Containing Pyrrolo[1,2‐a]quinolines and Pyrrolo[2,1‐a]isoquinolines via Nitrogen Ylides

Quinoline and isoquinoline react with 2‐(bromoacetyl)benzothiazole ( 1 ) in dry benzene to give the corresponding quinolinium and isoquinolinium salts 2 and 10 which undergo base‐mediated [3+2] 1,3‐dipolar cycloaddition with some acetylene and ethylene derivatives to give the corresponding benzothiazole‐containing pyrrolo[1,2‐a]quinoline and pyrrolo[2,1‐a]isoquinoline derivatives.     

Synthesis of 6‐Aminoindolo[2,1‐a]isoquinoline‐5‐carbonitriles by the Cu‐Catalyzed Reaction of 2‐(2‐Bromophenyl)‐1H‐indoles with CH2(CN)2

A series of 6‐aminoindolo[2,1‐a]isoquinoline‐5‐carbonitriles 4 have been prepared by treatment of 2‐(2‐bromophenyl)‐1H‐indoles 1 , available from 1‐(2‐bromophenyl)ethanones or 1‐(2‐bromophenyl)propan‐1‐ones by using Fischer indole synthesis, with propanedinitrile in the presence of a catalytic amount of CuBr and an excess of K₂CO₃ in DMSO at 100°.     

Diversity‐Oriented Synthesis of Novel 2′‐Aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] Derivatives via a One‐Pot Four‐Component Reaction

A sequential one‐pot four‐component reaction for the efficient synthesis of novel 2′‐aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] derivatives 5 in the presence of AcONH₄ as a neutral, inexpensive, and dually activating catalyst is described (Scheme 1). The syntheses are achieved by reacting ninhydrin ( 1 ) with benzene‐1,2‐diamines 2 to give indenoquinoxalines, which are trapped in situ by malono derivatives 2 and various α‐methylenecarbonyl compounds 4 through cyclization, providing the multifunctionalized 2′‐aminospiro[11H‐indeno[1,2‐b]quinoxaline‐11,4′‐[4H]pyran] analogs 5 . This chemistry provides an efficient and promising synthetic way of proceeding for the diversity‐oriented construction of the spiro[indenoquinoxalino‐pyran] skeleton.     

An Efficient One‐Pot Synthesis of Substituted 1H‐Naphtho[2,1‐b]pyrans and 4H‐1‐Benzopyrans (=Chromenes) under Solvent‐Free Microwave‐Irradiation Conditions

A facile heterogeneous synthesis of 3‐amino‐1‐aryl‐1H‐naphtho[2,1‐b]pyran and 2‐amino‐4‐aryl‐4H‐1‐benzopyran derivatives 3 and 5 , respectively, was carried out efficiently by one‐pot three‐component coupling of an aromatic aldehyde 1 , an active methylene compound 2 , and naphthalen‐2‐ol or a phenol 4 in the presence of 5‐Å molecular sieves under solvent‐free microwave‐irradiation conditions (Scheme 1 and 2, Tables 1 and 2). The catalyst was recovered and recycled (Table 3).     

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.     

Synthesis of 4‐fluoroalkyl‐2H‐pyrido [1, 2‐a] pyrimidin‐2‐ones from 2, 2‐dihydropolyfluoroalkanoic acids

In the presence of N, N′‐dicyclohexylcarbodiimide, 2‐aminopyridine and its derivatives (2) condensed with 2, 2‐di‐hydropolyfluoroalkanoic adds (1) to give the corresponding amides. Subsequent intramolecular Micheal addition‐elimination reactions of the fluorine‐containing amides under basic conditions gave 4‐fluoroalkyl‐2H‐pyrido[1,2‐a]pyrimidin‐2‐ones (3) in good yields.     

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.     

One‐pot Synthesis of Benzamidonaphtho[2,1‐b]furans and Benzamidobenzo[b]furans as Novel Polycyclic Heteroaromatic Compounds

An operationally simple, green and efficient procedure for one‐pot synthesis of novel polycyclic heteroaromatic compounds such as benzamidonaphtho[2,1‐b]furans and benzamidobenzo[b]furans has been developed from the reaction of arylglyoxals, benzamide, and phenols. The reactions were mediated with low amounts of yttrium nitrate hexahydrate as a suitable Lewis acid catalyst without using solvent.     

A Novel and Facile Synthesis of 2‐(Benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic Acid Derivatives

A simple and concise approach for the synthesis of a series of new heterocyclic systems of 2‐(benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic acid derivatives ( 3a–3g ) is described. The synthetic strategy features the one‐pot reaction of ethyl 2‐(chloromethyl)benzo[h]quinoline‐3‐carboxylate ( 2 ) with various substituted salicylaldehydes as well as 2‐hydroxy‐1‐naphthaldehyde as a key step. The substrate 2 was prepared in good yield by a mild, efficient and direct reaction of 1‐naphthylamine ( 1 ) with Vilsmeier‐Haack reagent. The structures of all the new compounds were identified by spectral data and elemental analysis.