A regioselective three-component reaction for synthesis of novel 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione derivatives

A ring opening and regioselective three-component reaction of isatoic anhydride, isatins, and aromatic or aliphatic primary amines in the presence of catalytic amount of KAl(SO₄)₂·12H₂O (alum) to yield a novel series of 1′H-spiro[isoindoline-1,2′-quinazoline]-3,4′(3′H)-dione is described.     

Photo-induced aromatic assembly of benzocycloalka[1,2-b] furan and spiro[furan-2(3H),1′-benzocycloalkane] derivatives

The photo-induced benzannulation of benzocycloalka[1,2-b]furans produced hydrohelicene-type compounds in good yields. A similar photoreaction of the spiro[furan-2(3H),1′-benzocycloalkane]s afforded dihydrophenalene derivatives in moderate yields. Benzo[kl]xanthene was also formed by a similar photoreaction of spiro[furan-2(3H),9′-xanthene]. The reaction pathway was elucidated by the ¹H NMR spectrum of the reaction mixture and the alternative synthesis of the intermediate.     

Synthesis of dihydropyrazolo[3′,4′:3,4]pyrrolo[1,2-a]indoles and spiro-[3H-indole-3,3′-[Δ-1,2,4]-triazolin]-2-ones via intra and intermolecular 1,3-dipolar cycloadditions

A new class of dihydropyrazolo[3′,4′:3,4]pyrrolo[1,2-a]indoles and spiro[3H-indole-3,3′-[Δ²-1,2,4]-triazoline]-2-ones were synthesised via intra and intermolecular 1,3-dipolar cycloaddition reactions in good yields.     

One stone kills four birds: a novel diazaperinone 12H-pyrazino[2′,3′:3,4]pyrrolo[1,2-a]perimidin-12-one recognizes four different metal ions

A novel diazaperinone 12H-pyrazino[2′,3′:3,4]pyrrolo[1,2-a]perimidin-12-one has been successfully synthesized through a one-step condensation. Single crystal X-ray analysis shows that the product is of planar structure with strong π?π interactions and H-bonding. Interestingly, the 12H-pyrazino[2′,3′:3,4]pyrrolo[1,2-a]perimidin-12-one can recognize three different metal cations Cu²⁺, Ag⁺ and Hg²⁺ via naked eye visualization, and shows turn-on fluorescence for Fe³⁺ and Ag⁺ among the 22 metal cations.     

Cascade assembly of N,N′-dialkylbarbituric acids and aldehydes: a simple and efficient one-pot approach to the substituted 1,5-dihydro-2H,2′H-spiro(furo[2,3-d]pyrimidine-6,5′-pyrimidine)-2,2′,4,4′,6′(1′H,3H,3′H)-pentone framework

Cascade assembly of N,N′-dialkylbarbituric acids and aldehydes in the presence of bromine leads to the selective and efficient formation of substituted 1,5-dihydro-2H,2′H-spiro(furo[2,3-d]pyrimidine-6,5′-pyrimidine)-2,2′,4,4′,6′-(1′H,3H,3′H)-pentones in 70-88% yields via a complex cascade process. Spirobarbiturates containing the furo[2,3-d]pyrimidine framework are a class of compounds with interesting pharmacological and physiological activity.     

Facile entry into the 3H,9H-bis[1,2,4]triazolo-[1,5-a:5′,1′-d][1,3,5]triazinium (5/6/5 tricyclic NNN) system

A facile, one-pot reaction between 3,4,5-triamino-1,2,4-triazole (guanazine) and cyanogen bromide provides a new high-nitrogen example of the 3H,9H-bis[1,2,4]triazolo[1,5-a:5′,1′-d][1,3,5]triazinium system, the 2,3,5,6-tetraamino-9-imino derivative (3) as a quaternary bromide salt.     

Facile synthesis of 3H,3′H-spiro[benzofuran-2,1′-isoindole]-3,3′-diones using monobromomalononitrile (MBM) as an efficient organo-brominating agent

An efficient methodology for the synthesis of 3H,3′H-spiro[benzofuran-2,1′-isoindole]-3,3′-diones has been developed where monobromomalononitrile (MBM) has been employed as a non-hazardous brominating agent under ambient reaction condition. The intrinsic advantages of the methodology are the utilization of simple and easily available starting materials and non-toxic reagents, operational simplicity, and good yields of the products with high atom-economy.     

A novel one-pot and efficient procedure for the synthesis of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones

A novel and practical one-pot procedure is described for the preparation of several new of 3H-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′,5′-tetraones based on the addition reaction of ninhydrin and 6-aminouracils followed by oxidative cleavage of their corresponding dihydroxyindenopyrrolopyrimidines.     

A novel tandem cyclization of condensed 2,3-dialkynylpyrazines into [1,2,3]triazolo[1′,5′;1,2]pyrido[3,4-b]pyrazines promoted by sodium azide

6,7-Dialkynyl-1,3-dimethylpteridine-2,4(1H,3H)-diones and 2,3-dialkynylquinoxalines have been shown to react with sodium azide in DMF at room temperature giving rise 9,11-dimethyl-[1,2,3]triazolo[1′,5′;1,2]pyrido[4,3-g]pteridine-8,10(9H,11H)-diones and [1,2,3]triazolo[1′,5′;1,2]pyrido[3,4-b]quinoxalines. A novel tandem cyclization involves 1,3-dipolar cycloaddition of an azide ion to the carbon-carbon triple bond followed by intramolecular nucleophilic addition of the intermediate 1,2,3-triazole N-anion to another CC bond.     

Grignard reagent-promoted 6-endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2-a:3′,4′-d]imidazole

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.     

New iminophosphorane-mediated synthesis of thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones and 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes

Mono(iminophosphorane) 4 was selectively prepared from the reaction of 3,4-diaminothieno[2,3-b]thiophene 3 with excess triphenylphosphine, C₂Cl₆, and Et₃N due to intramolecular double hydrogen bond formation. Mono(iminophosphorane) 4 reacted with aromatic isocyanates to give stable carbodiimides 8, which were further treated with aliphatic secondary or primary amines to give 2-amino substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 10 or 12 in the presence of a catalytic amounts of EtO⁻Na⁺. However, in the presence of a catalytic amounts of potassium carbonate, the carbodiimides 8 were transformed into previously unreported 5H-2,3-dithia-5,7-diaza-cyclopenta[c,d]indenes 13 via direct cyclization in high yields. The reaction of carbodiimides 8 with phenols in the presence of a catalytic amounts of potassium carbonate gave a mixture of 2-aryloxy substituted thieno[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-ones 14 and 13. X-ray structure analysis of 10m supported the structure and the proposed reactivity of amino group.     

Reaction of 1-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones with urea. Synthetic route to novel 3-(3-acylureido)-2,3-dihydro-1H-indol-2-ones, 4-alkylidene-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones, and 3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones

1-Substituted 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with urea in boiling acetic acid to give products depending on the type of substitution in position 3 and at the nitrogen atom of the 3-amino group. Starting compounds bearing a primary amino group in position 3 give 3-(3-acylureido)-2,3-dihydro-1H-indol-2-ones. Starting compounds bearing a secondary amino group in position 3 react according to the character of the other substituent in position 3. If there is a hydrogen atom α to the carbon atom C(3), 4-alkylidene-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones arise. If a hydrogen atom is not present in this position, the reaction leads to 3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones. Reaction mechanisms for these transformations are proposed. All compounds were characterized by their ¹H, ¹³C, IR and atmospheric pressure chemical ionization mass spectra and some of them also by ¹⁵N NMR data.     

Silica sulfuric acid: an efficient reusable heterogeneous solid support for the synthesis of 3H,3′H-spiro[benzofuran-2,1′isobenzofuran]-3,3′-diones under solvent-free condition

A highly efficient protocol for the library synthesis of biologically important 3H,3′H-spiro[benzofuran-2,1′isobenzofuran]-3,3′-diones has been developed by employing silica sulfuric acid (SSA) as solid acid support under solvent-free condition. The dual characteristics of SSA, as an activating agent as well as oxidizing agent, have been well exposed in these syntheses. The intrinsic advantages of the methodology are the use of solvent-free reaction condition without using any toxic reagents or metal catalyst, operational simplicity, recyclability of the solid support, good availability of the starting materials, and excellent yields which make the method attractive, economic, and ‘benign by design’.     

A facile synthesis of pyrrolo[1,2-a]benzimidazoles and pyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazole derivatives

Reaction of 2-cyanomethylbenzimidazole 1 with hydrazonoyl halides 2 led to formation of pyrrolo[1,2-a]benzimidazole derivatives 7. Similar reaction of 1 with halides 3 afforded 5-amino-4-(benzimidazol-2-yl)pyrazole derivatives 11 or 1-amino-2-arylpyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazol-4-one 14 depending on the reaction conditions. The mechanisms of the studied reactions are discussed.     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

Synthesis and tautomeric structure of 6-arylhydrazono 1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepines

A simple synthetic strategy is described for synthesis of the hitherto unreported 6-arylhydrazono-1,3-diphenyl-7-methyl-1H-pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazepin-5(6H)-ones 5a-j. The acid dissociation constants were determined for the series prepared and were correlated by the Hammett equation using the enhanced substituent constants. The results of such a correlation together with the spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric form.     

Pyrazolo[2′,3′:3,4][1,3]oxazino[5,6-b]quinoxaline, a novel tetracyclic ring system

Reaction of 2-chloro-3-(3-chloro-1H-pyrazol-5-yl)quinoxaline and aldehydes does not afford the corresponding N-(α-hydroxyalkylated) derivatives but results in a cyclisation reaction to give a derivative bearing the hitherto undescribed pyrazolo[2′,3′:3,4][1,3]oxazino[5,6-b]quinoxaline system.     

Regioselective synthesis of 1H,3H,6H[2]benzopyrano[4,3-d]pyrimidine-2,4-diones and 12H-benzopyrano[3,2-c][1]benzopyran-5-ones by radical cyclization

5-Hydroxy uracils or 4-hydroxy[1]benzopyran-2-ones were refluxed with 2-bromobenzyl bromides in acetone in the presence of anhydrous potassium carbonate to afford a number of 5-(2′-bromobenzyloxy) pyrimidine-2,4-dione (80-92%) or 4-(2′-bromobenzyloxy) benzopyran-7-ones (70-82%) respectively. These were then refluxed with tri-n-butyltin chloride and sodium cyanoborohydride in the presence of a catalytic amount of azobisisobutyronitrile (AIBN) for 3-4 h to give 1H,3H,6H [2]benzopyrano[4,3-d]pyrimidine-2,4-diones (75-85%) or 12H-benzopyrano[3,2-c][1]benzopyran-5-ones (70-85%) respectively.     

An efficient synthesis of new 1-H-4′-methyl-3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinoline] scaffolds

Efficient synthesis of new 3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinolines] by a four step synthetic route based on 1-benzyl-4-piperidone reactivity is reported.