A Simple and Facile Synthesis of 4‐Phenylquinoline‐fused Pyrrolidin‐2‐ones

In the present investigation, a simple and facile synthesis of a series of 4‐phenylquinoline‐fused pyrrolidin‐2‐ones, namely, 9‐phenyl‐2‐substituted‐2,3‐dihydro‐1H‐pyrrolo[3,4‐b]quinolin‐1‐ones is described, involving the tandem intermolecular C‐N bond formation reaction between readily available ethyl 2‐(chloromethyl)‐4‐phenylquinoline‐3‐carboxylate and various amines followed by in situ intramolecular C–N bond cyclization process in the presence of EtOH‐AcOH (v/v, 10:1) solvent system as the reaction medium.     

Novel regioselective synthesis of 3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐one containing compounds

A variety of 3″,5″‐diaryl‐3″H,4′H‐dispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]thiadiazol]‐4′‐ones 3a‐c were synthesized regioselectively through the reaction of 4′H,5H‐trispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]oxadithiino[5,6‐c]chromene‐5″,1″′‐cyclohexan]‐4′‐one ( 1 ) with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a‐c ) in refluxing dry toluene. Single crystal X‐ray diffraction studies of 3a,b add support for the established structure. Similarly, 3′,5′‐diaryl‐2,2‐dimethyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5a‐c were obtained in a regioselective manner through the reaction of 2,2,5′,5′‐tetramethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino[5,6‐c]chromen]‐4‐one ( 4a ) with nitrilimines under similar reaction conditions. On the other hand, reaction of 2,5′‐diethyl‐2,5′‐dimethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino‐[5,6‐c]chromen]‐4‐one ( 4b ) with nitrilimines in refluxing dry toluene afforded the corresponding 3′,5′‐diaryl‐2‐ethyl‐2‐methyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5d‐f as two unisolable diastereoisomeric forms.     

Heterocyclization reaction of 2‐(2‐methylaziridin‐1‐yl)‐3‐ureidopyridines under appel's conditions

The reaction of 2‐(2‐methylaziridin‐1‐yl)‐3‐ureidopyridines 12 with triphenylphosphine, carbon tetra‐chloride, and triethylamine (Appel's conditions) led to the corresponding carbodiimides 13 , which underwent intramolecular cycloaddition reaction with aziridine under the reaction conditions to give the pyridine‐fused heterocycles, 2,3‐dihydro‐1H‐imidazo[2′,3′:2,3]imidazo[4,5‐b]pyridines 16 and 12,13‐dihydro‐5H‐1,3 ‐benzodiazepino [2′,3′:2,3] imidazo[4,5‐b]pyridines 17 .     

Synthesis,Docking, and Bioavailability of 2′‐Oxo‐3‐phenylspiro[cyclopropane‐1,3′‐indoline]‐2,2‐dicarbonitriles as Antibacterial Agents In Silico

An efficient method has been developed for the synthesis of N‐alkylated 2′‐oxo‐3‐phenylspiro[cyclopropane‐1,3′‐indoline]‐2,2‐dicarbonitrile from 3‐chloroindolin‐2‐one and 2‐benzylidenemalononitrile by using triethylamine as a base at room temperature and obtained the products in moderate to good yields. In extension, the scope of the reaction has been investigated by stepwise and one‐pot methods. Furthermore, in silico antibacterial activity was carried out in order to understand possible binding modes of novel derivatives with the active site of DNA gyrase A enzyme, and the results were well complemented. Additionally, absorption, distribution, metabolism, and excretion properties of compounds have shown drug likeness with good oral absorption and moderate blood–brain barrier permeability.     

Regiocontrolled syntheses of some new spiro[polycyclic-1′-isothiochroman]-4′-one derivatives

Indan-1-one (1a), 1-tetralone (1b), fluorenone (1c), and anthrone (1d) reacted with mercaptoacetic acid in toluene in the presence of p-toluenesulfonic acid to give spiro[indan-1,2′-[1′,3′]oxathialan]-5′-one (2a), spiro[tetrahydro-naphthalene-1,2′-[1,3′]oxathialan]-5′-one (2b), spiro[fluorene9,2′-[1′,3′]-oxathialan]-5′-one (2c), and spiro[anthracene-9(10H)-2′-[1′,3′]-oxathialan]-5′-one (2d), respectively. Compounds 2a–d reacted with arenes in the presence of aluminum chloride to yield spiro[polycyclic-1′-isothiochroman]-4′-one derivatives 3a–t. The mechanisms of these reactions are discussed. All the synthesized spiroheterocycle derivatives were identified by conventional methods (IR, ¹H-NMR spectroscopy) and elemental analyses. © 1996 John Wiley & Sons, Inc.     

Efficient Preparation of 2, 2′‐Disubstituted‐3, 3′‐(1, 4‐phenylene)bis‐thienopyrimidin‐4‐ones Based on an aza‐Wittig Reaction

Tandem aza‐Wittig reaction of iminophosphorane with 1, 4‐phenylene diisocyanate followed by intramolecular heteroconjugate addition annulation after addition of a nucleophilic reagent (amine, phenol, and alcohol), in the presence of catalytic K₂CO₃ or NaOR, gives selectively the functionalized substituted 2, 2′‐di(alkylamino, aryloxy)‐3, 3′‐(1, 4‐phenylene)bis(thieno[3, 2‐d]pyrimidin‐4(3H)‐ones) and 2, 2′‐di(alkylamino or alkoxy)‐3, 3′‐(1, 4‐phenylene)bis(3, 5, 6, 7‐tetrahydro‐4H‐cyclopenta[4, 5]thieno[2, 3‐d]pyrimidin‐4‐ones).     

New Synthesis of N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a]quinoline‐6‐carbonitrile Derivatives from the Cyclic β‐Enaminones

A facile and convenient synthesis of an interesting N‐(1H‐pyrazol‐5‐yl)‐hexahydroquinoline‐3‐carbonitrile and octahydropyrazolo[4′,3′:5,6]pyrimido[1,2‐a ]quinoline‐6‐carbonitrile derivatives via the versatile readily accessible cyclic enaminones incorporating pyrazole moiety was accomplished.     

On the Reaction of Thiazole‐2,4‐diamines with Isothiocyanates – Preparation and Transformation of 2,4‐Diaminothiazole‐5‐carbothioamides

In the reaction of thiazole‐2,4‐diamines 8 with isothiocyanates 1 , 2,4‐diaminothiazole‐5‐carbothioamides 9, 10, 18 , and 19 as well as thiazolo[4,5‐d]pyrimidine‐7(6H)‐thiones 21 were formed. The carbothioamides 9, 10 , and 18 were transformed by reaction with different types of monofunctional and bifunctional electrophiles into hitherto unknown acceptor‐substituted 4,4′‐([2,5′‐bithiazole]‐2′,4′‐diyl)bis[morpholines] 24 and 29 , the 2′,4′‐bis(dialkylamino)[2,5′‐bithiazol]‐4‐(5H)‐ones 30 , and the 4‐substituted 2′,4′‐bis(dialkylamino)‐2,5′‐bithiazoles 31 . From 30 and 31 new 4‐mono‐ or 4,5‐disubstituted 2′,4′‐bis(dialkylamino)‐2,5′‐bithiazoles 34, 35, 38 , and 39 as well as 5‐substituted 2′,4′‐bis(dialkylamino)[2,5′‐bithiazol]‐4(5H)‐ones 33, 36 , and 37 were prepared.     

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.     

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.     

Synthesis and Reactions of Pyrido[2,1‐a]isoquinolin‐4‐yl Formimidate Derivatives and Antimicrobial Activities of Isolated Products

Treatment of arylidene malononitriles 2A – C with 1‐cyanomethylisoquinoline 1 afforded 4‐amino‐2‐arylpyrido[2,1‐a ]isoquinoline‐1,3‐dicarbonitrile derivatives 5A – C , which converted to formimidates 6A – C via reaction with triethylorthoformate. Treatment of the latter compounds with hydrazine hydrate gave the corresponding amino–imino compounds 7A – C , which underwent Dimroth rearrangement to afford 13‐aryl‐1‐hydrazinylpyrimido[5′,4′:5,6]pyrido[2,1‐a ]isoquinoline‐12‐carbonitrile 8A – C . The latter reacted with aldehyde to give 9a – i . Oxidative cyclization of the latter compounds 9a – i gave [1,2,4]triazolo[4″,3″:1′,6′]‐pyrimido[5′,4′:5,6]pyrido[2,1‐a ]isoquinolines 10a , d , g . Such compounds isomerized to the thermodynamically more stable isomers [1,2,4]triazolo[1″,5″:1′,6′]pyrimido[5′,4′:5,6]‐pyrido[2,1‐a ]isoquinolines 11a , d , g . Antimicrobial activities for some compounds were studied.     

Synthesis and Structure of 2‐Substituted Thieno[3′,2′:5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one Derivatives

A series of new 2‐substituted 3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 8 were synthesized via an aza‐Wittig reaction. Phosphoranylideneamino derivatives 6a or 6b reacted with 4‐chlorophenyl isocyanate to give carbodiimide derivatives 7a or 7b , respectively, which were further treated with amines or phenols to give compounds 8 in the presence of a catalytic amount of EtONa or K₂CO₃. The structure of 2‐(4‐chlorophenoxy)‐3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one ( 8j ) was comfirmed by X‐ray analysis.     

Synthetic Studies Towards the Preparation of 2‐Benzyl‐2‐ hydroxybenzofuran‐3(2H)‐one,the Prototype of Naturally Occurring Hydrated Auronols

Various synthetic approaches were employed to prepare 2‐benzyl‐2‐hydroxybenzofuran‐3(2H)‐one ( 8 ), the prototype of naturally occurring auronols. While the base‐induced ring transformation of 3‐hydroxyflavanone ( 2 ) as well as the hydration of 2‐benzylidenebenzofuran‐3(2H)‐one (=aurone; 6 ) proved to be inappropriate, the hydrogenolytic epoxide‐ring opening of 2′‐phenylspiro[benzofuran‐2(3H),2′‐oxiran]‐3‐one ( 7 ), obtained from 6 , represents an efficient method to afford the auronol 8 .     

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.     

A Facile,Atom‐Economical,and One‐Pot Pseudo Four‐Component Synthesis of Isoxazolylspiro[diindeno[1,2‐b;2′,1′‐e]pyridine‐11,3′‐indoline]‐2′,10,12‐triones Catalyzed by pTSA

A facile, atom‐economical, and one‐pot pseudo four‐component method for the synthesis of isoxazolylspiro[diindeno[1,2‐b ;2′,1′‐e ]pyridine‐11,3′‐indoline]‐2′,10,12‐trione derivatives ( 14 ) is described. Prominent advantages of this new method are operational simplicity, excellent yields with high purity, short reaction time, easy workup, and mild conditions.     

Chemoselective synthesis of thieno[3,2‐c][1,8]naphthyridin‐4(5H)‐ones by tandem cyclization

A number of the thieno[3,2‐c][1,8]‐naphthyridin‐4(5H)‐ones are chemoselectively synthesized from 4‐(4′‐aryloxybut‐2′‐ynylthio)‐1‐phenyl‐1,8‐naphthyridin‐2(1H)‐ones in 82–90% yield by the formation of sulfoxide, followed by [2,3] and [3,3]sigmatropic rearrangement and an intramolecular Michael addition. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:87–92, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20234     

Reaction of 2‐acyl‐6‐methylbenzo[b]furan‐3‐acetic acids derivatives with hydrazine

Reaction of 2‐acyl‐6‐methylbenzo[b]furan‐3‐acetic acids and their derivatives such as amides and esters with hydrazine does not give expected 1‐alkyl‐5H‐benzofuro[2,3‐e]diazepin‐4‐ones ones but results in 2‐amino‐7‐methyl‐2H‐benzo[4,5]furo[2,3‐c]pyridin‐3‐ones or (3‐R‐6‐methylbenzo[b]furan‐2‐yl)alkyl ketone azines.     

Synthesis of Dispiro[indole‐3,2′‐pyrrolidine‐3′,2″‐pyrrolizine]‐1″,2(1H)‐diones via Azomethine Ylide 1,3‐Dipolar Cycloaddition

The 1,3‐dipolar cycloaddition of azomethine ylide generated in situ from isatin and sarcosine to 2‐arylmethylidene‐2,3‐dihydro‐1H‐pyrrolizin‐1‐ones afforded novel 1′‐methyl‐4′‐(aryl)‐1″H‐dispiro[indole‐3,2′‐pyrrolidine‐3′,2″‐pyrrolizine]‐1″,2(1H)‐diones in good yields. The structures of all the products were characterized thoroughly by NMR, infrared spectroscopy, mass spectrum, and elemental analysis.     

Synthesis of tetrahydrobenzo[b]furans via a gold(I)‐catalyzed rearrangement/cycloisomerization sequence of cyclic 1‐aryl‐2‐propargyl‐cyclohex‐2enols

A facile synthesis of tetrahydrobenzo[b]furans via gold(I)‐catalyzed cycloisomerization of 1‐aryl‐2‐propargylcyclohex‐2‐enols is described. The transformation is suggested to proceed through a gold(I)‐catalyzed tertiary allylic alcohol rearrangement to give a secondary allylic alcohol that underwent a 5‐exo‐dig addition of the hydroxyl group onto the gold(I)‐activated alkyne to give a vinylgold species. Protodeauration of the resulting vinylgold intermediate followed by aromatization furnished the tetrahydrobenzo[b]furans.     

Reactions of Imidoyl Isoselenocyanates with Aromatic 2‐Amino N‐Heterocycles and 1‐Methyl‐1H‐imidazole

The reaction of N‐phenylimidoyl isoselenocyanates 1 with 2‐amino‐1,3‐thiazoles 10 in acetone proceeded smoothly at room temperature to give 4H‐1,3‐thiazolo[3,2‐a] [1,3,5]triazine‐4‐selones 13 in fair yields (Scheme 2). Under the same conditions, 1 and 2‐amino‐3‐methylpyridine ( 11 ) underwent an addition reaction, followed by a spontaneous oxidation, to yield the 3H‐4λ⁴‐[1,2,4]selenadiazolo[1′,5′:1,5] [1,2,4]selenadiazolo[2,3‐a]pyridine 14 (Scheme 3). The structure of 14 was established by X‐ray crystallography (Fig. 1). Finally, the reaction of 1‐methyl‐1H‐imidazole ( 12 ) and 1 led to 3‐methyl‐1‐(N‐phenylbenzimidoyl)‐1H‐imidazolium selenocyanates 15 (Scheme 4). In all three cases, an initially formed selenourea derivative is proposed as an intermediate.