Spiro[pyrido[3,2,1‐ij]pyrimido[4,5‐b]quinoline‐7,5′‐pyrrolo[2,3‐d]pyrimidines] and Spiro[pyrimido[4,5‐b]quinoline‐5,1′‐pyrrolo[3,2,1‐ij]quinolines] Derived from 5,6‐Dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

Reaction of 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione ( 1 ) with two equivalents of some 6‐aminouracils (or 6‐amino‐2‐thiouracil) generates spirocyclic tetrahydrobenzo[if]quinolizines ( 7 ). The one‐pot, three‐component reaction of amido ketone ( 1 ) with 6‐aminouracil (or 6‐amino‐2‐thiouracil) and a cyclic six‐membered 1,3‐diketone produces spirocyclic tetrahydropyrrolo[3,2,1‐ij]quinolinones ( 15 ).     

Hexahydrospiro‐pyrazolo[3,4‐b]pyridine‐4,1′‐pyrrolo[3,2,1‐ij]quinolines Derived from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione ( 1 ), reacts with a combination of an aryl cyanomethyl ketone 8 and a 5‐amino‐1‐arylpyrazole 7 to generate spirocyclic products 9 .     

Synthesis and reactions of 11H‐benzo[b]pyrano[3,2‐f]indolizines an pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolines

2‐Methyl‐3H‐indoles 1 cyclize with two equivalents of ethyl malonate 2 to form 4‐hydroxy‐11H‐benzo[b]pyrano[3,2‐f]indolizin‐2,5‐diones 3, whereas 2‐mefhyl‐2,3‐dihydro‐1H‐indoles 9 give under similar conditions regioisomer 8‐hydroxy‐5‐methyl‐4,5‐dihydro‐pyrrolo[3,2,1‐ij]pyrano[3,2‐c]quinolin‐7,10‐diones 10 . The pyrone rings of 3 and 9 can be cleaved either by alkaline hydrolysis to give 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 4 or 5‐acetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo‐[3,2,1‐ij]quinolin‐4‐ones 11 , respectively. Chlorination of 3 and 9 with sulfurylchloride gives under subsequent ring opening 7‐dichloroacetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 5 or 5‐dichloracetyl‐6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 12 . The dichloroacetyl group of 5 can be reduced with zinc to 7‐acetyl‐8‐hydroxy‐10H‐pyrido[1,2‐a]indol‐6‐ones 7. Treatment of the acetyl compounds 4, 7 and 11 with 90% sulfuric acid cleaves the acetyl group and yields 8‐hydroxy‐10H‐pyrido[1,2‐a]‐indol‐6‐ones 6 and 8 , and 6‐hydroxy‐2‐methyl‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 13 . Reaction of dichloroacetyl compounds 12 with sodium azide yields 6‐hydroxy‐2‐methyl‐5‐(1H‐tetrazol‐5‐ylcarbonyl)‐1,2‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinolin‐4‐ones 14 via intermediate geminal diazides.     

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.     

Molecular Iodine Promoted Synthesis of New Pyrido[2,3‐d]pyrimidin‐4‐ols

A highly ef?cient synthesis of novel pyrido[2,3‐d]pyrimidin‐4‐ols was developed via an iodine‐catalyzed tandem oxidative cyclization under focused microwave irradiation. Pyrido[2,3‐d]pyrimidin‐4‐ols were obtained from easily available 2‐amino‐4‐aryl‐6‐arylnicotinamides and benzylic amines with good to excellent yields.     

Iminophosphoranes in Heterocyclic Synthesis: A Facile Synthesis of Pyrido[4,3‐D]Pyrimidine and Pyrido[4,3‐D][1,3]Oxazine Derivatives via Intermolecular aza‐Wittig Reactions

A novel series of pyrido[4,3‐d ]pyrimidine and pyrido[4,3‐d ][1,3]oxazine derivatives were synthesized via tandem aza‐Wittig and annulation reactions with the corresponding iminophosphoranes, aromatic isocyanate, and amines. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Synthesis and reactions of pyrido[3,2,1‐jk]carbazole‐4,6‐diones

Pyrido[3,2,1‐jk]carbazoles 1 , synthesized from carbazoles and alkyl‐ or arylmalonates, gave regioselective electrophilic substitution reactions at position 5 such as chlorination to 5‐chloro derivatives 2 , nitration to 5‐nitro compounds 3 , or hydroxylation to 5‐hydroxy derivatives 4 . 5‐Hydroxy compounds 4 gave on treatment with strong bases ring contraction to 5 , 6 or the ring opening product 7 . Exchange of the chloro group in 2 with azide or amines gave the corresponding azides 8 and the 5‐amino derivatives 9 and 10 . Alkylation of 1 with benzyl chloride or allyl bromide resulted in the formation of 5‐C‐alkylated products 11 together with 4‐alkyloxy derivatives 12 . J. Heterocyclic Chem., 48, 1039 (2011).     

5‐Unsubstituted Pyrido[3,2,1‐jk]carbazol‐6‐ones: Syntheses,Substitution, and Cyclization Reactions

The synthesis of the 5‐unsubstituted pyrido[3,2,1‐jk]carbazol‐6‐one 4 can be achieved by the reaction of carbazole ( 1 ) and malonate derivatives, either in a three‐step synthesis via 5‐acetyl‐pyridocarbazolone 3 or in a one‐step reaction from 1 and malonic acid/phosphoryl chloride. The 5‐acetyl derivative 5 can be transformed via a tosylate intermediate to 4‐azido‐pyridocarbazolone 11 , which cyclizes by thermal decomposition to the isoxazolo‐pyrido[3,2,1‐jk]carbazolone 12 . The thermolysis conditions were investigated by DSC. Nitration of pyridocarbazolone 4 and subsequent introduction of azide leads to azido derivative 23 , which cyclizes on thermolysis to furazan‐oxide derivative 24 . Again, the thermolysis conditions were investigated by DSC. 5‐Chloro‐5‐nitro‐pyrido[3,2,1‐jk]carbazole‐4,6‐dione, obtained from 4 by subsequent nitration and chlorination, forms by exchange of both 5‐substituents 5,5‐dihydroxy‐pyridocarbazoledione 17 , which acylates phenol to give 5‐hydroxy‐5‐(p‐hydroxyphenyl)‐pyridocarbazoledione 20 . Acid‐catalyzed cyclodehydration of 20 forms a highly fused benzofuro‐pyridocarbazole 21 . Another C–C coupling at position 5 starts from 4‐chloro‐5‐nitro‐pyridocarbazolone 22 and diethyl malonate 2a , which forms the diethyl (nitrocarbazolyl)malonate 25 . With dimethyl malonate 2c , the intermediate dimethyl (nitrocarbazolyl)malonate gives on thermolysis the (nitrocarbazolyl)acetate 27 by loss of one ester group.     

Synthesis of Some New [1,8]Naphthyridine,Pyrido[2,3‐d]‐Pyrimidine,and Other Annulated Pyridine Derivatives

2‐Aminopyridine‐3‐carbonitrile derivative 1 reacted with each of malononitrile, ethyl cyanacetate, benzylidenemalononitrile, diethyl malonate, and ethyl acetoacetate to give the corresponding [1,8]naphthyridine derivatives 3 , 5 , 8 , 11 , and 14 , respectively. Further annulations of 3 , 5 , and 8 gave the corresponding pyrido[2,3‐b][1,8]naphthyridine‐3‐carbonitrile derivative 17 , pyrido[2,3‐h][1,6]naphthyridine‐3‐carbonitrile derivatives 18 and 19 , respectively. The reaction of 1 with formic acid, formamide, acetic anhydride, urea or thiourea, and 4‐isothiocyanatobenzenesulfonamide gave the pyridopyrimidine derivatives 20a , b , 21 , 22a , b , and 26 , respectively. Treatment of compound 1 with sulfuric acid afforded the amide derivative 27 . Compound 27 reacted with 4‐chlorobenzaldehyde and 1H‐indene‐1,3(2H)‐dione to give the pyridopyrimidine derivative 28 and spiro derivative 30 , respectively. In addition, compound 1 reacted with halo compounds afforded the pyrrolopyridine derivatives 32 and 34 . Finally, treatment of 1 with hydrazine hydrate gave the pyrazolopyridine derivative 35 . The structures of the newly synthesized compounds were established by elemental and spectral data.     

Preparation of 2,3‐dihydro‐1H,5H‐pyrido[3,2,1‐ij]quinoline‐1,5‐dione derivatives

The 2,3‐dihydro‐7‐methyl‐1H,5H‐pyrido[3,2,1‐ij]quinoline‐1,5‐dione derivatives 9 and 10 were prepared from 3‐(5,7‐dimethoxy‐4‐methyl‐2‐oxo‐2H‐quinolin‐1‐yl)propionitrile ( 6 ). Cyclodehydration of the amide 8 gave 1,2‐dihydro‐7,9‐dimethoxy‐6‐methylpyimido[1,2‐a]quinolin‐3‐one ( 11 ).     

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

In the present investigation, the synthesis of a series of structurally new and interesting tert‐butyl‐ and bromo‐functionalized [1,2,4]triazino[5,6‐b ]indoles ( 6a – f ) and indolo[2,3‐b ]quinoxalines ( 8a – f ) has been achieved, involving the condensation reaction of 7‐bromo‐5‐tert‐butylisatins ( 4a – f ) with thiosemicarbazide ( 5 ) and benzene‐1,2‐diamine ( 7 ). The substrates 4a – f were prepared through bromination reaction of 5‐tert‐butylisatin ( 3 ) with NBS in PEG‐400 followed by alkylation reaction. The molecular structures of these newly synthesized compounds were elucidated on the basis of their elemental analyses and spectral data.     

A Convenient Synthesis of [1,2,3]Triazolo[1,5-a]quinoline

Russian Journal of Organic Chemistry - The reaction of methyl 2-azido-5-bromobenzoate with ethyl 4-(ethylsulfanyl)-3-oxobutanoate was used to synthesize ethyl...     

Synthesis of some [1,2,4]triazino[5,6‐b]quinoline derivatives

By coupling of diazonium salts with ethyl N‐(4‐oxo‐1,4‐dihydroquinolin‐2‐yl)carbamate 4 , the corresponding 3‐arylazocompounds 5 were obtained. These ones were cyclized thermally or in alkaline medium to the corresponding 2‐aryl‐2,3,5,10‐tetrahydro‐[1,2,4]triazino[5,6‐b]quinolin‐3,10‐diones 6 . Compounds 6 were transformed by alkaline hydrolytic splitting to the corresponding 2‐amino‐3‐arylazo‐1,4‐dihydroquino‐lin‐4‐ones 7. Starting carbamate 4 was prepared by a two‐step synthesis from 2‐amino‐1,4‐dihydroquinolin‐4‐one 1.     

An Alternate Synthesis of 6H‐Indolo[2,3‐b]quinoline via One‐Pot Alkylation–Dehydration–Cyclization–Aromatization Approach

A simple, straightforward and efficient synthesis of 6H‐indolo[2,3‐b]quinoline, a natural product isolated from leaves of Justicia betonica, is achieved through a pivalic acid‐assisted one‐pot alkylation–dehydration–cyclization–aromatization approach. This synthesis constitutes a formal approach toward a biologically important alkaloid neocryptolepine.     

Unexpected Approach to the Synthesis of 2‐Phenylquinoxalines and Pyrido[2,3‐b]pyrazines via a Regioselective Reaction

An unexpected approach to the preparation of quinoxaline and pyrido[2,3‐b]pyrazine derivatives 5 is described. The reaction between 1H‐indole‐2,3‐diones 1 , 1‐phenyl‐2‐(triphenylphosphoranylidene)ethanone ( 2 ), and benzene‐1,2‐ or pyridine‐2,3‐diamines 3 proceeds in MeOH under reflux in good to excellent yields (Scheme 1 and Table). No co‐catalyst or activator is required for this multi‐component reaction (MCR), and the reaction is, from an experimental point of view, simple to perform. The structures of 5, 5′ , and 6 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and were confirmed by comparison with reference compounds. A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis and ring closure reactions of pyrido[3,2,1‐jk]carbazol‐6‐ones

4‐Hydroxy‐5‐phenylpyrido[3,2,1‐jk]carbazol‐6‐ones ( 4, 5 ), which were obtained from carbazoles 1 and malonates 2 or 3 , were converted to reactive intermediates such as 4‐chlorides 9 or 4‐tosylates 10 , which gave in turn 4‐azido‐5‐phenyl derivatives 11 . 5‐Alkyl‐4‐azides 11 were not obtained in this manner; however a new one‐pot azidation reaction was developed starting from 4‐hydroxy derivatives 4 which gave azides 11 in good yields. 4‐Azido‐5‐phenyl derivative 11f cyclized on thermolysis to the indole 12 . The thermal behaviour of the azides 11 was studied by thermoanalytical methods (DSC).