Interaction of 3‐(2‐Aminophenyl)‐6‐R1‐1,2,4‐triazin‐5‐ones with Acylating Reagents: An Efficient Method for Preparation of 6‐Substituted 3‐R1‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐ones

The series of 6‐substituted 3‐R¹‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one was prepared via condensation of 3‐(2‐aminophenyl)‐6‐R¹‐1,2,4‐triazin‐5‐ones with acylating reagents. Particularities of ¹H NMR spectra have been also discussed based on the comparison of experimental and theoretical results for 3‐methyl‐6‐phenyl‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one and its 4,3‐isomer.     

One‐pot Two‐step Reaction for Synthesis of Poly‐substituted Pyrano[3,2‐c]pyridones and Spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in Water

An efficient four‐component approach for the synthesis poly‐substituted pyrano[3,2‐c]pyridones and spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in water has been established. During the reaction, the products were readily achieved through one‐pot two‐step reaction using solid acid as catalyst. The advantages of atom and step economy, the recyclability of heterogeneous solid acid catalyst, easy workup procedure, and the wide scope of substrates make the reaction a powerful tool for assembling pyrano[3,2‐c]pyridone skeletons of chemical and medical interest.     

Synthesis and Hypolipidemic Activity of New 6,6‐Disubstituted 3‐R‐6,7‐Dihydro‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐Ones

Presented article describes the synthesis and hypolipidemic activity of previously unknown 6,6‐disubstituted 3‐R‐6,7‐dihydro‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐ones. It was shown, that interaction of 6‐R‐3‐(2‐aminophenyl)‐1,2,4‐triazin‐5(2Н)‐оnes with methylalkylketones in acetic acid resulted the single product, namely, the desired tricyclic derivatives. At the same time, after refluxing of 6‐R‐3‐(2‐aminophenyl)‐1,2,4‐triazin‐5(2Н)‐оnes with methylarylketones in acetic acid the mixture of target compound and insignificant amount of corresponding 3‐substituted 6‐methyl‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐ones were isolated. The mechanism of above‐mentioned mixture formation was discussed. The structures of all synthesized compounds were proven using the appropriate physicochemical methods. The compounds with promising lipid‐lowering activity were identified and the «structure — hypolipidemic activity» correlations were discussed.     

Synthesis of Hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1′‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones] from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione Using Fe3O4@Cu(OH)x as a Nanocatalyst

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione, undergoes three‐component, one‐pot reactions with 1‐aryl‐3‐methylpyrazole‐5‐amines and cyclohexane‐1,3‐diones producing hexacyclic spiro products, hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones]. Comparable spiro condensation products are also obtained using 4‐hydroxy‐2H‐1‐benzopyran‐2‐one in place of cyclohexane‐1,3‐diones.     

Green Synthesis of 1‐(1,2,4‐Triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)indole]‐2′,4′(1′H)‐diones as Potential Insecticidal Agents

One pot green synthesis of 1‐(1,2,4‐triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)‐indole]‐2′,4′(1′H)‐diones was carried out by the reaction of indole‐2,3‐diones,4‐amino‐4H‐1,2,4‐triazole and acetyl chloride/chloroacetyl chloride in ionic liquid [bmim]PF₆ with/without using a catalyst. It was also prepared by conventional method via Schiff's bases, 3‐[4H‐1,2,4‐triazol‐4‐yl]imino‐indol‐2‐one. Further, the corresponding phenoxy derivatives were obtained by the reaction of chloro group attached to azetidine ring with phenols. The synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and FAB mass) data. Evaluation for insecticidal activity against Periplaneta americana exhibited promising results.     

A New Four‐Component Reaction for the Synthesis of Spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles]

A new four‐component synthesis of spiro[4H‐indeno[1,2‐b]pyridine‐4,3′‐[3H]indoles] and spiro[acenaphthylene‐1(2H),4′‐[4H‐indeno[1,2‐b]pyridines] by the reaction of indane‐1,3‐dione, 1,3‐dicarbonyl compounds, isatins (=1H‐indole‐2,3‐diones) or acenaphthylene‐1,2‐dione, and AcONH₄ in refluxing toluene in the presence of a catalytic amount of pyridine is reported.     

Green Synthesis of Spiro[indoline‐3,4′‐pyrazolo[3,4‐b][1,6]naphthyridine]‐2,5′(1′H)‐diones Catalyzed by TsOH in Ionic Liquids

A three‐component reaction of isatin, 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐amine, and piperidine‐2,4‐dione was treated in ionic liquids catalyzed by TsOH and provided an efficient and green method for the synthesis of spiro[indoline‐3,4′‐pyrazolo[3, 4‐b][1,6]naphthyridine]‐2,5′(1′H)‐dione derivatives in high yields.     

A convenient synthesis of novel spiro[benzoxazole-2′,4(1H,3′H)-pyrazolo[5,1-c][1,2,4]triazines] by ring transformation of novel pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzoxazepines

Novel pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzoxazepines 5, 6 and 8 were synthesized, and these compounds were converted into novel spiro[benzoxazole-2′,4(1H,3′H)-pyrazolo[5,1-c][1,2,4]triazines] 7 and 9 by ring transformation.     

Synthesis of 2‐Coumarinyl and Spiroindolyl‐5‐Phenyl‐1,3,4‐Oxadiazoles

The 2H‐1‐benzo/naphthopyran‐2‐one‐4‐yl (un)substituted phenyl‐1,3,4‐oxadiazoles has been synthesized by the oxidative cyclization of benzoic acid hydrazides formed in situ by the condensation of the respective 2H‐1‐benzo/naphthopyran‐2‐one‐4‐carboxaldehyde and (un)substituted monobenzoyl hydrazide in moderate yields. Also, spiro[indoline‐thiozolidine]‐2,4′‐diones has been syhthesized in a similar way from 3‐phenyl‐spiro[3H‐indoline‐3,2′‐thiozolidine]‐2,4′‐(1 H)dione monohydrazide and (un)substituted benzaldehydes.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Synthesis of nitrogen-containing heterocycles. 8. Preparation and ring-opening of spiro[cycloalkane-[1′,2′,4′]triazolo[1′,5′-c]pyrimidine] derivatives

Diaminomethylene- and aminomethylthiomethylenehydrazones [2] of cyclic ketones 1–8 readily reacted with ethoxymethylenemalononitrile to give spiro[cycloalkane-1,2′-[1,2′,4′]triazolo[1,5′-c]pyrimidine-8′-carbonitrile] derivatives 12–19 through the electrocyclic reaction of the initially formed condensation products 26 in moderate to high yields. The spiro[cyclopentanetriazolopyrimidine] derivatives underwent ring-opening at the cycloalkane moiety upon heating in solution to give 2-alkyl-5-substituted-[1,2,4]triazolo[1,5-c]pyrimidine-8′-carbonitriles 20–23 . When an alkyl substituent was introduced into the cyclopentane ring, cleavage of the spiro compounds occurred preferentially at the cyclopentane moiety between the spiro carbon and the more branched one. In contrast, the cyclohexane ring, especially of spiro-5-amino-triazolopyrimidines 17 and 18 strongly resisted to ring-opening under similar conditions, but those of 5-methylthiotriazolopyrimidines 14 gave up to 17 percent of cleavage after prolonged heating in hot ethanol. 2-t-Butyl-5-methylthio-2,3-dihydro[1,2,4]triazolo[1,5-c]pyrimidine-8-carbonitrile 25 [R³ = C(CH₃)₃] was highly susceptible to the cleavage even at room temperature and produced the corresponding 2-unsubstituted triazolopyrimidine 24 with loss of the t-butyl group.     

Synthesis,structure and some reactions of 4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]‐quinazolines]

2′‐Substituted 5′,6′,7′,8′‐tetrahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 3a‐d were synthesized by condensation of 3‐substituted 5‐amino‐1,2,4‐triazoles 1a‐d with 2‐cyclohexylidene cyclohexanone 2 in DMF. The compounds 3 were hydrogenated with sodium borohydride in ethanol to give 2′‐substituted cis‐4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 4a‐d in high yields. The reactions of alkylation, acylation and sulfonylation of the compounds 4 were studied. The structure of the synthesized compounds was determined on the basis of NMR measurements including HSQC, HMBC, NOESY techniques and confirmed by the X‐ray analysis of 6 and 11b . The described synthetic protocols provide rapid access to novel and diversely substituted hydrogenated [1,2,4]triazolo[5,1‐b]quinazolines.     

An Efficient One‐pot Synthesis of Novel Spiro Cyclic 2‐Oxindole Derivatives of Pyrimido[4,5‐b]Quinoline,Pyrido[2,3‐d:6,5‐d′]Dipyrimidine and Indeno[2′,1′:5,6]Pyrido [2,3‐d]Pyrimidine in Water

A novel and facile one‐pot synthesis of spiro cyclic 2‐oxindole derivatives of pyrimido[4,5‐b]quinoline‐4,6‐dione, pyrido[2,3‐d:6,5‐d′]dipyrimidine‐2,4,6‐trione, and indeno[2′,1′:5,6]pyrido [2,3‐d]pyrimidine employing 6‐aminothiouracil (or 6‐aminouracil), isatin, and cyclic 1,3‐diketone (e.g. 1,3‐indanedione, dimedone, or barbituric acid) has been developed.     

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.     

Iodine‐Catalyzed Synthesis of Spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones under Mild Conditions

The I₂‐catalyzed preparation of spiro[1,3,4‐benzotriazepine‐2,3′‐indole]‐2′,5(1H,1′H)‐diones from 2‐aminobenzohydrazide and isatins in MeCN at room temperature in good‐to‐excellent yields is described. The structure of 3 was corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS data). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

One‐Pot,Three‐Component Synthesis of Novel Spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones in an Ionic Liquid as a Reusable Reaction Media

A facile one‐pot, three‐component protocol for the synthesis of novel spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones by condensing 1H‐indole‐2,3‐diones, 4H‐1,2,4‐triazol‐4‐amine and 2‐sulfanylpropanoic acid in [bmim]PF₆ (1‐butyl‐3‐methyl‐1H‐imidazolium hexafluorophosphate) as a recyclable ionic‐liquid solvent gave good to excellent yields in the absence of any catalyst (Scheme 1 and Table 2). The advantages of this protocol over conventional methods are the mild reaction conditions, the high product yields, a shorter reaction time, as well as the eco‐friendly conditions.     

Synthesis of spiro[indoline‐3,3′‐pyrrolizines] by 1,3‐dipolar reactions between isatins,l‐proline and electron‐deficient alkenes

Two spiro[indoline‐3,3′‐pyrrolizine] derivatives have been synthesized in good yield with high regio‐ and stereospecificity using one‐pot reactions between readily available starting materials, namely l ‐proline, substituted 1H‐indole‐2,3‐diones and electron‐deficient alkenes. The products have been fully characterized by elemental analysis, IR and NMR spectroscopy, mass spectrometry and crystal structure analysis. In (1′RS ,2′RS ,3SR ,7a′SR )‐2′‐benzoyl‐1‐hexyl‐2‐oxo‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizine]‐1′‐carboxylic acid, C₂₈H₃₂N₂O₄, (I), the unsubstituted pyrrole ring and the reduced spiro‐fused pyrrole ring adopt half‐chair and envelope conformations, respectively, while in (1′RS ,2′RS ,3SR ,7a′SR )‐1′,2′‐bis(4‐chlorobenzoyl)‐5,7‐dichloro‐2‐oxo‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizine], which crystallizes as a partial dichloromethane solvate, C₂₈H₂₀Cl₄N₂O₃·0.981CH₂Cl₂, (II), where the solvent component is disordered over three sets of atomic sites, these two rings adopt envelope and half‐chair conformations, respectively. Molecules of (I) are linked by an O—H…·O hydrogen bond to form cyclic R ₆⁶(48) hexamers of (S ₆) symmetry, which are further linked by two C—H…O hydrogen bonds to form a three‐dimensional framework structure. In compound (II), inversion‐related pairs of N—H…O hydrogen bonds link the spiro[indoline‐3,3′‐pyrrolizine] molecules into simple R ₂²(8) dimers.     

New Synthetic Approach to Naphtho[1,2‐b]furan and 4′‐Oxo‐Substituted Spiro[cyclopropane‐1,1′(4′H)‐naphthalene] Derivatives

A one‐step synthesis of ethyl 2,3‐dihydronaphtho[1,2‐b]furan‐2‐carboxylate and/or ethyl 4′‐oxospiro[cyclopropane‐1,1′(4′H)‐naphthalene]‐2′‐carboxylate derivatives 2 and 3 , respectively, from substituted naphthalen‐1‐ols and ethyl 2,3‐dibromopropanoate is described (Scheme 1). Compounds 2 were easily aromatized (Scheme 2). In the same way, 3,4‐dibromobutan‐2‐one afforded the corresponding 1‐(2,3‐dihydronaphtho[1,2‐b]furan‐2‐yl)ethanone and/or spiro derivatives 8 and 9 , respectively (Scheme 6). A mechanism for the formation of the dihydronaphtho[1,2‐b]furan ring and of the spiro compounds 3 is proposed (Schemes 3 and 4). The structures of spiro compounds 3a and 3f were established by X‐ray structural analysis. The reactivity of compound 3a was also briefly examined (Scheme 9).     

Alum (KAl(SO4)2·12H2O) Catalyzed Multicomponent Transformation: Simple,Efficient, and Green Route to Synthesis of Functionalized Spiro[chromeno[2,3‐d]pyrimidine‐5,3′‐indoline]‐tetraones in Ionic Liquid Media

The combination of isatin, barbituric acid, and cyclohexane‐1,3‐dione derivatives in the presence of alum (KAl(SO₄)₂·12H₂O) as a catalyst for 15 min was found to be a suitable and efficient method for the synthesis of spiro[chromeno[2,3‐d]pyrimidine‐5,3′‐indoline]‐tetraones.     

A Novel Method for the Synthesis of Spiro[indoline‐Pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine]triones by Alum as a Reusable Catalyst

Synthesis of spiro[indoline‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine]trione derivatives by a cyclo‐condensation reaction of indolin‐2‐ones, barbituric acids, and 1,3‐diphenyl‐1H‐pyrazol‐5‐amines with the ionic liquid as an effective green reaction media and in the presence of Alum as a reusable catalyst was reported. Excellent yields of products, green media, use of a reusable catalyst, and short reaction time are the main advantages of this new method.