Synthesis of a Novel Hydrazone of Thieno[2,3-d]pyrimidine Clubbed with Ninhydrin : X-ray Crystal Structure and Computational Investigations

The novel hydrazone-containing thieno[2,3-d]pyrimidine, namely, N′-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)-2-(4-oxo-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazide 4 was synthesized in a very good yield from the reaction of the triketoester 1 or ninhydrin 2 with the exocyclic acetohydrazide 3 in methanol. Good-quality crystals of 4 were obtained by recrystallization of the compound from the DMF/MeOH solvent mixture. The target product 4 crystallized in the triclinic crystal system and P-1 space group. The topology analysis of molecular packing indicated that the H…H (30.4%), O…H (22.0%) and H…C (17.0%) contacts are the most dominant intermolecular interactions in the crystal of 4, while the O…H, N…H, H…C, N…C, O…C, C…C and O…O are the only contacts which have shorter interaction distances than the vdWs radii sum of the interacting atoms. The structure of 4 is optimized and the calculated structure showed good agreement with the experimental one. Additionally, MEP, HOMO, LUMO and the reactivity descriptors were calculated.peerReviewe

Synthesis and X-ray Crystal Structure Analysis of Substituted 1,2,4-Triazolo [4’,3’:2,3]pyridazino[4,5-b]indole and Its Precursor

The hit compound 1,2,4-triazolo[4’,3’:2,3]pyridazino[4,5-b]indole 3 was synthesized from the reflux of 4-amino-5-indolyl-1,2,4-triazole-3-thione 1 with 4′-bromoacetophenone 2 in methanol catalyzed by concentrated HCl and the desired final molecule was obtained by recrystallization from methanol. The suggested structures of compounds 1 and 3 based on the spectral characterizations were confirmed by X-ray single crystal diffraction analysis. Compound 3 crystallized in the triclinic crystal system and P-1 space group with a = 5.9308(2) Å, b = 10.9695(3) Å, c = 14.7966(4) Å, α = 100.5010(10)°, β = 98.6180(10)°, and γ = 103.8180(10)°. On the other hand, the crystal system of 1 is monoclinic, where a = 6.23510(10) Å, b = 26.0156(4) Å, c = 12.4864(2) Å, β = 93.243(2)° and the space group is P21. The triazole and indole rings are found twisted from each other in both compounds. The twist angle is higher in 3 (12.65°) than 1 (4.94–7.22°). In the case of the former, the H…H (39.6%), H…C (22.0%), N…H (12.8%) and Br…H (13.2%) contacts are the most dominant while the C…C, C…H, Br…H, N…H and S…S contacts have the characteristics of strong interactions. In the latter, the C…H, N…H, S…H, S…S, and C…C contacts are the most important. In this case, the percentages of the H…H, C…H, N…H and S…H contacts are in the range of 34.9–37.4, 20.5–24.0, 12.2–13.6, 14.0–15.8, respectively. In both systems, the shape index and curvedness of surfaces confirmed the presence of π–π stacking interactions.peerReviewe

4-Methyl/Phenyl-1,2,5,6-tetraazafluoranthen-3(2<i>H</i>)-ones Synthesis: Mechanistic Pathway Study and Single-Crystal X-ray Analysis of the Intermediates

The synthesis of 4-methyl/phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 4 and 7 has been reported with ninhydrin via a reaction first with ethyl acetoacetate or ethyl benzoylacetate and then a reaction of the resultant esters with hydrazine hydrate. The mechanism of hydrazinolysis and cyclization to obtain tetraazafluoranthen-3(2H)-ones is ambiguous, and the previously proposed mechanism was not based on facts because the actual intermediates were not isolated. Herein, the important intermediates involved in the hydrazinolysis–cyclization mechanistic pathway were isolated and characterized using NMR and X-ray single-crystal analysis. The intermediates demonstrate that the reaction carried out via two hydrazinolysis–cyclization reactions, the first of which includes the condensation of one hydrazine molecule with two ketone groups and the second of which includes the reaction of another hydrazine molecule with the ester and then condensation with the other ketone group. The stability of hydrazide 11 enabled the hydrazine to reduce the carbonyl of the ketone group to form 12 via a Wolff–Kishner-like reduction. The structure of the three intermediates was confirmed using X-ray crystallographic analysis. It was found that the three fused ring systems deviated from planarity to different extents, with their deviation from being coplanar reaching up to 5.3°. The possible non-covalent interactions which control the molecular packing of these intermediates were elucidated with the aid of Hirshfeld analysis

Straightforward One-Pot Synthesis of New 4-Phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one Derivatives : X-ray Single Crystal Structure and Hirshfeld Analyses

A straightforward one-pot route for the synthesis of a new 4-phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one is reported form the direct hydrazinolysis of triketo ester and hydrazine hydrate in ethanol. 4-Phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one was subjected to aza-Michael addition and N-alkylation on reaction with a set of alkylating agents in the presence of K2CO3. Hydrazinolysis of 4-phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one ester to hydrazide and conversion of hydrazide to thiosemicarbazide were successful. X-Ray single crystals analysis and 1H, 13C NMR were used for unambiguous structure confirmation. The O…H, N…H, C…N and C…C in 2, and the N…H, C…N, C…C, C…O and H…H interactions in 6 are the most important in the molecular packing based on Hirshfled analysis. Moreover, the presence of short C…C and C…N contacts in both compounds revealed the presence of π–π stacking interactions.peerReviewe