A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of Pseudo(mono)radical Azomethine Ylides with Phenyl Vinyl Sulphone
The [3+2] cycloaddition (32CA) reaction of an azomethine ylide (AY), derived from isatin and L-proline, with phenyl vinyl sulphone has been studied within Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) level. ELF topological analysis of AY classifies it as a pseudo(mono)radical species with two monosynaptic basins at the C1 carbon, integrating a total of 0.76 e. While vinyl sulphone has a strong electrophilic character, AY is a supernucleophile, suggesting a high polar character and low activation energy for the reaction. The nucleophilic Parr functions indicate that the pseudoradical C1 carbon is the most nucleophilic center. The 32CA reaction presents an activat…
Synthesis, X-ray Structure, Antimicrobial and Anticancer Activity of a Novel [Ag(ethyl-3-quinolate)2(citrate)] Complex
A novel Ag(I) citrate complex with ethyl-3-quinolate (Et3qu) was synthesized. Its structure was confirmed using X-ray single crystal to be [Ag(Et3qu)2(citrate)]. It crystallized in the Triclinic crystal system and P-1 space group with unit cell parameters of a = 8.6475(2) Å, b = 11.4426(3) Å, c = 15.2256(3) Å, α = 73.636(2)°, β = 79.692(2)° and γ = 86.832(2)°, while the unit cell volume was 1422.19(6) Å3. In the unit cell, there are two [Ag(Et3qu)2(citrate)] molecules and one unit as the asymmetric formula. The molecular structure comprised one Ag(I) coordinated with two Et3qu molecules via two almost equidistant Ag-N bonds and one citrate ion acting as a mono-negative monodentate ligand vi…
A novel synthetic approach to pyran-2,4-dione scaffold production: Microwave-assisted dimerization, cyclization, and expeditious regioselective conversion into β-enamino-pyran-2,4-diones
Abstract Here, we report a novel, green, simple, low-cost, and rapid methodology for the high-yield production of pyran-2,4-dione scaffolds under microwave irradiation. Regio- and stereoselective conversions of β-diketone systems into β-enaminones were achieved using 18 primary amines and four amino acid esters. Microwave-assisted further cyclization of 3-(β-substitutedvinyl)-6-phenyl-pyran-2,4-dione into 3-benzoyl-4,7-diphenyl-2H,5H-pyrano[4,3-b]pyran-2,5-dione via reaction with ethyl benzoyl acetate.
Base-Controlled Regiospecific Mono-Benzylation/Allylation and Diallylation of 4-Aryl-5-indolyl-1,2,4-triazole-3-thione : Thio-Aza Allyl Rearrangement
The regiospecific S-benzylation/allylation of two 4-aryl-5-indolyl-1,2,4-triazole-3-thione precursors was carried out using Et3N as a base. Allyl group migration from exocyclic sulfur to the triazole nitrogen (N3) was successfully achieved in a short time via thermal fusion without the need for any catalyst. The allylation of indole nitrogen, along with exocyclic sulfur or triazole nitrogen (N3), was carried out using K2CO3 as stronger base. S,N-Diallylated products were converted to N,N-diallylated analogues using a simple fusion approach. Structural analyses of the two newly synthesized hybrids 2b and 5b investigated via the X-ray diffraction of a single crystal combined with Hirshfeld ca…
Synthesis, X-ray Structure of Two Hexa-Coordinated Ni(II) Complexes with s-Triazine Hydrazine Schiff Base Ligand
The hydrazine s-triazine ligand (E)-4,4’-(6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine-2,4-diyl)dimorpholine (DMPT) was used to synthesize two new Ni(II) complexes via a self-assembly technique. The two complexes were synthesized by a one-pot synthesis strategy and characterized by elemental analysis, FTIR and single-crystal X-ray diffraction analysis to be [Ni(DMPT)(H2O)3](NO3)2.3H2O (1) and [Ni(DMPT)(H2O)3](NO3)2.H2O (2). The structures of both complexes were very similar regarding the coordination sphere and counter anions, but differ only in the number of the crystal water molecules. In the case of complex 1, there are three water molecules instead of one H2O molecu…
Synthesis, Structure and Antimicrobial Activity of New Co(II) Complex with bis-Morpholino/Benzoimidazole-s-Triazine Ligand
A new Co(II) perchlorate complex of the bis-morpholino/benzoimidazole-s-triazine ligand, 4,4′-(6-(1H-benzo[d]imidazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine (BMBIT), was synthesized and characterized. The structure of the new Co(II) complex was approved to be [Co(BMBIT)2(H2O)4](ClO4)2*H2O using single-crystal X-ray diffraction. The Co(II) complex was found crystallized in the monoclinic crystal system and P21/c space group. The unit cell parameters are a = 22.21971(11) Å, b = 8.86743(4) Å, c = 24.38673(12) Å and β = 113.4401(6)°. This heteroleptic complex has distorted octahedral coordination geometry with two monodenatate BMBIT ligand units via the benzoimidazole N-atom and four water …
Design, Construction, and Characterization of a New Regioisomer and Diastereomer Material Based on the Spirooxindole Scaffold Incorporating a Sulphone Function
The 1,3-dipolar cycloaddition reaction is one of the most rapid, and efficient protocols to access, and construct highly divergent heterocycle chiral auxiliaries. Free catalyst synthesis of spirooxindole scaffold incorporating sulphone moiety via one pot&ndash
Acetic Acid Mediated for One-Pot Synthesis of Novel Pyrazolyl s-Triazine Derivatives for the Targeted Therapy of Triple-Negative Breast Tumor Cells (MDA-MB-231) via EGFR/PI3K/AKT/mTOR Signaling Cascades
Here, we described the synthesis of novel pyrazole-s-triazine derivatives via an easy one-pot procedure for the reaction of β-dicarbonyl compounds (ethylacetoacetate, 5,5-dimethyl-1,3-cyclohexadione or 1,3-cyclohexadionone) with N,N-dimethylformamide dimethylacetal, followed by addition of 2-hydrazinyl-4,6-disubstituted-s-triazine either in ethanol-acetic acid or neat acetic acid to afford a novel pyrazole and pyrazole-fused cycloalkanone systems. The synthetic protocol proved to be efficient, with a shorter reaction time and high chemical yield with broad substrates. The new pyrazolyl-s-triazine derivatives were tested against the following cell lines: MCF-7 (breast cancer); MDA-MB-231 (tr…
Synthesis of Unexpected Dimethyl 2-(4-Chlorophenyl)-2,3-dihydropyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate via Hydrolysis/Cycloaddition/Elimination Cascades: Single Crystal X-ray and Chemical Structure Insights
Hydrolysis/[3 + 2] cycloaddition/elimination cascades employed for the synthesis of unexpected tricyclic compound derived from isoquinoline. Reaction of ethylene derivative 1 with the isoquinoline ester iminium ion 2 in alkaline medium (MeOH/NEt3) under reflux for 1 h resulted in the formation of the fused pyrrolo[2,1-a]isoquinoline derivative 3. Its structure was elucidated by X-ray single crystal and other spectrophotometric tools. Hirshfeld calculations for 3 and its crystal structure analysis revealed the importance of the short O…H (19.1%) contacts and the relatively long H…C (17.1%), Cl…H (10.6%) and C…C (6.1%) interactions in the molecular packing. DFT calculations were used to compu…
Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent
A new series of spirooxindoles based on ethylene derivatives having furan aryl moiety are reported. The new hybrids were achieved via [3 + 2] cycloaddition reaction as an economic one-step efficient approach. The final constructed spirooxindoles have four contiguous asymmetric carbon centers. The structure of 3a is exclusively confirmed using X-ray single crystal diffraction. The supramolecular structure of 3a is controlled by O···H, H···H, and C···C intermolecular contacts. It includes layered molecules interconnected weak C–H···O (2.675 Å), H···H (2.269 Å), and relatively short Cl···Br interhalogen interactions [3.4500(11)Å]. Using Hirshfeld analysis, the percentages of these intermolecul…
A novel synthetic approach to pyran-2,4-dione scaffold production : microwave-assisted dimerization, cyclization, and expeditious regioselective conversion into β-enamino-pyran-2,4-diones
Here, we report a novel, green, simple, low-cost, and rapid methodology for the high-yield production of pyran-2,4-dione scaffolds under microwave irradiation. Regio- and stereoselective conversions of β-diketone systems into β-enaminones were achieved using 18 primary amines and four amino acid esters. Microwave-assisted further cyclization of 3-(β-substitutedvinyl)-6-phenyl-pyran-2,4-dione into 3-benzoyl-4,7-diphenyl-2H,5H-pyrano[4,3-b]pyran-2,5-dione via reaction with ethyl benzoyl acetate. peerReviewed
Synthesis and Solid-State X-ray Structure of the Mononuclear Palladium(II) Complex Based on 1,2,3-Triazole Ligand
Herein, we described the synthesis and X-ray crystal structure of the new [Pd(3)2Cl2] complex with 1,2,3-triazole-based ligand (3). In the unit cell, there are two [Pd(3)2Cl2] molecules, and the asymmetric unit comprised half of this formula due to the presence of an inversion symmetry element at the Pd(II) center. The monoclinic unit cell volume is 1327.85(6) Å3, with crystal parameters of a = 10.7712(2) Å, b = 6.8500(2) Å, and c = 18.2136(6) Å, while β = 98.851(2)°. The structure comprised two trans triazole ligand units coordinated to the Pd(II) ion via one of the N-atoms of the triazole moiety. In addition, the Pd(II) is further coordinated with two tran…
Cu(ii)-thiophene-2,5-bis(amino-alcohol) mediated asymmetric Aldol reaction and Domino Knoevenagel Michael cyclization : a new highly efficient Lewis acid catalyst
The highly efficient Lewis acid-catalytic system Cu(II)-thiophene-2,5-bis(amino-alcohol) has been developed for enantioselective Aldol reaction of isatin derivatives with ketones. The new catalytic system also proved to be highly enantioselective for the one pot three-component Domino Knoevenagel Michael cyclization reaction of substituted isatin with malononitrile and ethylacetoacetate. The chiral ligand (2S,2′S)-2,2′-((thiophene-2,5-diylbis(methylene))bis(azanediyl))bis(3-phenylpropan-1-ol) (L1) in combination with Cu(OAc)2·H2O employed as a new Lewis acid catalyst, furnished 3-substituted-3-hydroxyindolin-2-ones derivatives (3a–s) in good to excellent yields (81–99%) with high enantiosel…
Design, Synthesis, Chemical and Biochemical Insights Into Novel Hybrid Spirooxindole-Based p53-MDM2 Inhibitors With Potential Bcl2 Signaling Attenuation
The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized…
Intramolecular Hydrogen Bond, Hirshfeld Analysis, AIM; DFT Studies of Pyran-2,4-dione Derivatives
Intra and intermolecular interactions found in the developed crystals of the synthesized py-ron-2,4-dione derivatives play crucial rules in the molecular conformations and crystal stabili-ties, respectively. In this regard, Hirshfeld calculations were used to quantitatively analyze the different intermolecular interactions in the crystal structures of some functionalized py-ran-2,4-dione derivatives. The X-ray structure of pyran-2,4-dione derivative namely (3E,3′E)-3,3′-((ethane-1,2-diylbis(azanediyl))bis(phenylmethanylylidene))bis(6-phenyl-2H-pyran-2,4(3H)-dione) was determined. It crystallized in the monoclinic crystal system and C2/c space group with unit cell parameters: a = 14.0869(4) …
X-ray Crystal Structure and Hirshfeld Analysis of Gem-Aminals-Based Morpholine, Pyrrolidine, and Piperidine Moieties
The gem-aminals of 1,2-dimorpholinoethane (1) and 1-morpholino-3-morpholinium bromide propane (2) were synthesized by reaction of two molar ratio of morpholine with the halogenating agents in the presence of basic condition (K2CO3) in acetone at room temperature (RT) overnight. The structures of the centro-symmetric compound 1 and the morpholinium salt derivative 2 were assigned unambiguous by single crystal X-ray diffraction analysis and compared with the 1,2-di(pyrrolidin-1-yl)ethane 3 and 1,2-di(piperidin-1-yl)ethane 4. The 1,2-dimorpholinoethane molecule has a center of symmetry at the midpoint of the C-C bond of the ethyl moiety leading to two equivalent halves. It crystallized in mono…
X-ray Single Crystal Structure, Tautomerism Aspect, DFT, NBO, and Hirshfeld Surface Analysis of a New Schiff Bases Based on 4-Amino-5-Indol-2-yl-1,2,4-Triazole-3-Thione Hybrid
Four different new Schiff basses tethered indolyl-triazole-3-thione hybrid were designed and synthesized. X-ray single crystal structure, tautomerism, DFT, NBO and Hirshfeld analysis were explored. X-ray crystallographic investigations with the aid of Hirshfeld calculations were used to analyze the molecular packing of the studied systems. The H···H, H···C, S···H, Br···C, O···H, C···C and N···H interactions are the most important in the molecular packing of 3. In case of 4, the S···H, N···H, S···C and C···C contacts are the most significant. The results obtained from the DFT calculations indicated that the thione tautomer is energetically lower than the thiol one by 13.9545 and 13.7464 kcal…
Supramolecular Structure and Antimicrobial Activity of Ni(II) Complexes with s-Triazine/Hydrazine Type Ligand
The two complexes, [Ni(DPPT)2](NO3)2*1.5H2O (1) and [Ni(DPPT)(NO3)Cl].EtOH (2), were synthesized using the self-assembly of (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine (DPPT) with Ni(NO3)2*6H2O in the absence and presence of NiCl2*6H2O, respectively. In both cases, the neutral tridentate DPPT ligand is found coordinated to the Ni(II) via three N-atoms from the hydrazone, pyridine and s-triazine rings. Hence, the homoleptic complex 1 has a NiN6 hexa-coordination environment while two NO3− are counter anions in addition to one-and-a-half crystallized hydration water molecules are found acting as an outer sphere. The heteroleptic complex 2 has a NiN3O…
Synthesis, X-Ray Structure, Tautomerism Aspect, and Chemical Insight of The 3-(1H-Indol-2-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-ol
The 3-(1H-indol-2-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-ol 2 was obtained exclusively in the enol configuration starting from triazolyl-indole derivative 1 and alkyl halo-esters in the presence of K2CO3. Chemical structure elucidations with the aid of physicochemical characterizations were used to predict its molecular structure while single crystal X-ray diffraction technique was used to shed the light on the supramolecular structure of 2. DFT calculations agreed very well with the reported X-ray structure where the most stable form thermodynamically is the enol form. Its optimized geometry agreed very well with the experimental structure where the correlation coefficients betwe…
Efficient Consecutive Synthesis of Ethyl-2-(4-Aminophenoxy) Acetate, a Precursor for Dual GK and PPARγ Activators, X-ray Structure, Hirshfeld Analysis, and DFT Studies
Herein, we report a facile synthesis of ethyl-2-(4-aminophenoxy)acetate 4 as a building synthon for novel dual hypoglycemic agents. This building template was synthesized by alkylation of 4-nitrophenol with ethyl bromo-acetate followed by selective reduction of the nitro group. This reduction methoddoes not require nascent hydrogen or any reaction complexity; it goes easily via consecutive reaction in NH4Cl/Fe to yield our target synthon as very pure crystals. This product was characterized by 1HNMR, 13CNMR, COSY, NOESY NMR spectroscopy, and elemental analysis. Additionally, its structure was studied and approved by X-ray single crystal structure determination. The unit cell parameters are …
Stereoselective Synthesis of New 4-Aryl-5-indolyl-1,2,4-triazole S- and N-β-Galactosides: Characterizations, X-ray Crystal Structure and Hirshfeld Surface Analysis
5-(1H-Indol-2-yl)-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 1a and 4-(4-chlorophenyl)-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1b were galactosylated in the presence of NaHCO3 in ethanol to produce S-galactosides 3,4, whereas, in the presence of K2CO3 in acetone they produced a mixture of S- and N-galactosides 3-6 with a higher yield of S-galactosides over the respective N-galactosides. Improvement in the yields of N-galactosides was produced by thermal migration of the galactosyl moiety from sulfur to nitrogen using fusion. β-Stereoselectivity of galactosylation was determined using the coupling constant value 3J1,2, which exceeded 9.0 Hz in all prepared galactos…
Synthesis, Characterization and Single Crystal X-ray Diffraction Analysis of Fused Triazolo/Thiadiazole Clubbed with Indole Scaffold
The present synthetic strategy involves the synthesis of indolyl-triazolo-thiadiazole heterocyclic ring systems 8–13 from the condensation of 4-amino-5-(1H-indol-2-yl)-3H-1,2,4-triazole-3-thione 1 with the aromatic carboxylic acid derivatives 2–7 in presence of POCl3 for 1 h. All compounds were obtained in very good yields and have been well-characterized using spectroscopic techniques. Exclusively, good quality crystals from the target organic hybrid 8-(1H-indol-2-yl)-5-(p-tolyl)-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazole 9 were obtained and found suitable for X-ray single crystal diffraction measurement, which is used to confirm and analyze the molecular and supramolecular stru…
Synthesis of Enaminones-Based Benzo[d]imidazole Scaffold: Characterization and Molecular Insight Structure
(E)-1-(1H-Benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one 2 was synthesized by one-pot synthesis protocol of 2-acetyl benzo[d]imidazole with dimethylformamide dimethylacetal (DMF-DMA) in xylene at 140 °
Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes : Synthesis and Application in Cu-Catalyzed Friedel–Crafts Asymmetric Alkylation
Five new C2-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)2 catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for …
Synthesis and X-ray Crystal Structure of New Substituted 3-4′-Bipyrazole Derivatives. Hirshfeld Analysis, DFT and NBO Studies
A new compounds named 3-4′-bipyrazoles 2 and 3 were synthesized in high chemical yield from a reaction of pyran-2,4-diketone 1 with aryl hydrazines under thermal conditions in MeOH. Compound 2 was unambiguously confirmed by single-crystal X-ray analysis. It crystalizes in a triclinic crystal system and space group P-1. Its crystal structure was found to be in good agreement with the spectral characterizations. With the aid of Hirshfeld calculations, the H…H (54.8–55.3%) and H…C (28.3–29.2%) intermolecular contacts are the most dominant, while the O…H (5.8–6.5%), N…H (3.8–4.6%) and C…C (3.0–4.9%) are less dominant. The compound has a polar nature with a net dipole moment of 6.388 Debye. The …
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 i…
Synthesis of C2-Symmetrical Bis-(β-Enamino-Pyran-2,4-dione) Derivative Linked via 1,6-Hexylene Spacer: X-ray Crystal Structures, Hishfeld Studies and DFT Calculations of Mono- and Bis-(Pyran-2,4-diones) Derivatives
The synthesis of C2-symmetrical bis(β-enamino-pyran-2,4-dione) derivative 3 connected via 1,6-hexylene linker was reported for the first time. X-ray structures and Hirshfeld studies of the new bis- β-enamino-pyran-2,4-dione derivative 3 along with two structurally related pyran-2,4-dione derivatives 2a,b were discussed. A comparative analysis of the different intermolecular contacts affecting the crystal stability was presented. Generally, the H…H, O…H, and H…C interactions are common in all compounds and are considered the most abundant contacts. In addition, DFT calculations were used to compute the electronic properties as well as the 1H and 13C NMR spectra of the studied systems. All co…
Synthesis, X-ray structure, Hirshfeld analysis, and DFT studies of a new Pd(II) complex with an anionic s-triazine NNO donor ligand
A new Pd(II) complex, [Pd(Triaz)Cl], with the hydrazono-s-triazine ligand, 2,4-di-tert-butyl-6-((2-(4-morpholino-6-(phenylamino)-1,3,5-triazin-2-yl)hydrazono)methyl)phenol, was synthesized by the reaction of PdCl2 with the organic ligand (1:1) in acetone under isothermal conditions. The molecular structure of the [Pd(Triaz)Cl] complex was determined using FTIR and 1H NMR spectroscopic techniques, and single-crystal X-ray diffraction. Moreover, using Hirshfeld surface analysis, the percentages of the intermolecular interactions were determined. The obtained values were 60.6%, 11.6%, 8.1%, 3.6%, and 5.0% for the H⋯H, C⋯H, O⋯H, N⋯H, and Cl⋯H interactions, respectively. Among them, the O⋯H, C⋯H…
A New Pt(II) Complex with Anionic s-Triazine Based NNO-Donor Ligand: Synthesis, X-ray Structure, Hirshfeld Analysis and DFT Studies
The reaction of PtCl2 with s-triazine-type ligand (HTriaz) (1:1) in acetone under heating afforded a new [Pt(Triaz)Cl] complex. Single-crystal X-ray diffraction analysis showed that the ligand (HTriaz) is an NNO tridentate chelate via two N-atoms from the s-triazine and hydrazone moieties and one oxygen from the deprotonated phenolic OH. The coordination environment of the Pt(II) is completed by one Cl−1 ion trans to the Pt-N(hydrazone). Hirshfeld surface analysis showed that the most dominant interactions are the H···H, H···C and O···H intermolecular contacts. These interactions contributed by 60.9, 11.2 and 8.3% from the…
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, …
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, whe…
Synthesis, X-ray structure, Hirshfeld analysis, and DFT studies of a new Pd(II) complex with an anionic s-triazine NNO donor ligand
Abstract A new Pd(II) complex, [Pd(Triaz)Cl], with the hydrazono-s-triazine ligand, 2,4-di-tert-butyl-6-((2-(4-morpholino-6-(phenylamino)-1,3,5-triazin-2-yl)hydrazono)methyl)phenol (HTriaz), was synthesized by the reaction of PdCl2 with the organic ligand (1:1) in acetone under isothermal conditions. The molecular structure of the [Pd(Triaz)Cl] complex was determined using FTIR and 1H NMR spectroscopic techniques, and single-crystal X-ray diffraction. Moreover, using Hirshfeld surface analysis, the percentages of the intermolecular interactions were determined. The obtained values were 60.6%, 11.6%, 8.1%, 3.6%, and 5.0% for the H⋯H, C⋯H, O⋯H, N⋯H, and Cl⋯H interactions, respectively. Among …
X-Ray structure, Hirshfeld analysis and DFT studies of two new hits of triazolyl-indole bearing alkylsulfanyl moieties
Two new hits of triazolyl-indole containing two different alkylsulfanyl analogues named tert-butyl 2-((4-amino-5-(1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetate 2, and ethyl 2-((4-amino-5-(1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetate 3 were synthesized via reaction of 4-amino-5-(1H-indol-2-yl)-1,2,4-triazol-3(2H)-thione 1 with tert-butyl bromoacetate and ethyl chloroacetate in the presence of base (Et3N). The molecular structure of 2, and 3 was confirmed by single-crystal X-ray diffraction and 1H/13C- NMR spectroscopic techniques. In compound 2, the molecular packing depends on significant O...H (9.3%), N...H (12.4%) and S...H (3.1%) as well as relatively weak C...H (14.1%), S...C (…
s ‐Triazine pincer ligands: Synthesis of their metal complexes, coordination behavior, and applications
Synthesis and Antiproliferative Activity of a New Series of Mono- and Bis(dimethylpyrazolyl)-s-triazine Derivatives Targeting EGFR/PI3K/AKT/mTOR Signaling Cascades
Here, we synthesized a newseries of mono- and bis(dimethylpyrazolyl)-s-triazine derivatives. The synthetic methodology involved the reaction of different mono- and dihydrazinyl-s-triazine derivatives with acetylacetone in the presence of triethylamine to produce the corresponding target products in high yield and purity. The antiproliferative activity of the novel mono- and bis(dimethylpyrazolyl)-s-triazine derivatives was studied against three cancer cell lines, namely, MCF-7, HCT-116, and HepG2. N-(4-Bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-morpholino-1,3,5-triazin-2-amine 4f, N-(4-chlorophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine 5c, and 4,6-bis(3,5-dimethy…
Synthesis and characterization of a new spirooxindole grafted pyrrolidino/piperidine moiety
In this text, we synthesized and characterized a new spirooxindole grafted pyrrolidino/piperidine moieties. The new hit obtained via one-pot reaction of the chalcone based cyclohexanone with the isatin and (R)-piperidine-2-carboxylic acid in MeOH under reflux for 48 h. The compound exclusively obtained in regio-selective and diastereo-selective manner. The chemical feature of the target compound is confirmed by 1H NMR and 13C NMR spectroscopy. In addition, we reported for the first time the X-ray single crystal structure of isatin. Its molecular packing depends mainly on strong O…H hydrogen bonds and π-π stacking interactions as well as weak H…H and H…C contacts. Using DFT calculations, is…
Regio- and stereoselective synthesis of spiro-heterocycles bearing the pyrazole scaffold via [3+2] cycloaddition reaction
Abstract Herein we reported the utility of one-pot multicomponent based [3+2] cycloaddition reaction transformation to prepare a new two hybrids of spirooxindoles engrafted with pyrazole skeleton. Upon treatment of the electron-deficient olefins based pyrazole motif with in situ the generated azomethine ylides (AY) of sarcosine with the 6-chloro-isatin afforded spiroadducts. To enlighten the regio- and diastereo-selectivity of these spiroheterocycles, single crystal X-ray diffraction analysis was presented. Using Hirshfeld calculations, many short distance contacts such as O…H, Cl…H, N…H, H…C, C…C and Cl…S have a great impact on the molecular packing and the crystal stability of 8a and 8b. …
Straightforward Regio- and Diastereoselective Synthesis, Molecular Structure, Intermolecular Interactions and Mechanistic Study of Spirooxindole-Engrafted Rhodanine Analogs
Straightforward regio- and diastereoselective synthesis of bi-spirooxindole-engrafted rhodanine analogs 5a–d were achieved by one-pot multicomponent [3 + 2] cycloaddition (32CA) reaction of stabilized azomethine ylide (AYs 3a–d) generated in situ by condensation of L-thioproline and 6-chloro-isatin with (E)-2-(5-(4-chlorobenzylidene)-2,4-dioxothiazolidin-3-yl)-N-(2-morpholinoethyl)acetamide. The bi-spirooxindole-engrafted rhodanine analogs were constructed with excellent diastereo- and regioselectivity along with high chemical yield. X-ray crystallographic investigations for hybrid 5a revealed the presence of four contiguous stereocenters related to C11, C12, C19 and C22 of the spiro struct…
[3 + 2] Cycloadditions in Asymmetric Synthesis of Spirooxindole Hybrids Linked to Triazole and Ferrocene Units: X-ray Crystal Structure and MEDT Study of the Reaction Mechanism
Derivatization of spirooxindole having triazole and ferrocene units was achieved by the [3 + 2] cycloaddition (32CA) reaction approach. Reacting the respective azomethine ylide (AY) intermediate generated in situ with the ethylene derivative produced novel asymmetric cycloadducts with four contiguous asymmetric carbons in an overall high chemical yield with excellent regioselectivity and diastereoselectivity. X-Ray single-crystal structure analyses revealed, with no doubt, the success of the synthesis of the target compounds. The 32CA reaction of AY 5b with ferrocene ethylene 1 has been studied within MEDT. This 32CA reaction proceeds via a two-stage one-step mechanism involving a high asyn…
A Novel Na(I) Coordination Complex with s-Triazine Pincer Ligand: Synthesis, X-ray Structure, Hirshfeld Analysis, and Antimicrobial Activity
The pincer ligand 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-methoxy-1,3,5-triazine (bpmt) was used to synthesize the novel [Na(bpmt)2][AuCl4] complex through the self-assembly method. In this complex, the Na(I) ion is hexa-coordinated with two tridentate N-pincer ligands (bpmt). The two bpmt ligand units are meridionally coordinated to Na(I) via one short Na-N(s-triazine) and two slightly longer Na-N(pyrazole) bonds, resulting in a distorted octahedral geometry around the Na(I) ion. In the coordinated bpmt ligand, the s-triazine core is not found to be coplanar with the two pyrazole moieties. Additionally, the two bpmt units are strongly twisted from one another by 64.94°. Based on Hirshf…
New Bioprecursor Prodrugs of Sulfadiazine: Synthesis, X-ray Structure and Hirshfeld Analysis
Sulphonamide motif is found extensively in numerous chemotherapeutic drug candidates, it acts by stopping the production of folate inside the bacterial cell. Current research has established the synthesis and characterization of new bioprecursor prodrugs of sulfadiazine. The first prodrug, 3, was synthesized via the coupling of diazonium salt of sulfadiazine with ethyl acetoacetate in AcONa at 0 °C. The second prodrug, sulfadiazine-pyrazole, 5, was furnished via cyclocondensation of the hydrazono derivative, 3, and 2-pyridyl hydrazine, 4. The generated data from the X-ray analysis is interpreted and refined to obtain the crystal structure of the target compound, 5. Density functional th…
Synthesis and Structure Elucidation of Novel Spirooxindole Linked to Ferrocene and Triazole Systems via [3 + 2] Cycloaddition Reaction
In the present work, a novel heterocyclic hybrid of a spirooxindole system was synthesized via the attachment of ferrocene and triazole motifs into an azomethine ylide by [3 + 2] cycloaddition reaction protocol. The X-ray structure of the heterocyclic hybrid (1″R,2″S,3R)-2″-(1-(3-chloro-4-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carbonyl)-5-methyl-1″-(ferrocin-2-yl)-1″,2″,5″,6″,7″,7a″-hexahydrospiro[indoline-3,3″-pyrrolizin]-2-one revealed very well the expected structure, by using different analytical tools (FTIR and NMR spectroscopy). It crystallized in the triclinic-crystal system and the P-1-space group. The unit cell p…
[3+2] Cycloaddition Reaction for the Stereoselective Synthesis of a New Spirooxindole Compound Grafted Imidazo[2,1-b]thiazole Scaffold : Crystal Structure and Computational Study
A new spirooxindole hybrid engrafted imidazo[2,1-b]thiazole core structure was designed and achieved via [3+2] cycloaddition reaction approach. One multi-component reaction between the ethylene derivative based imidazo[2,1-b]thiazole scaffold with 6-Cl-isatin and the secondary amine under heat conditions afforded the desired compound in a stereoselective manner. The relative absolute configuration was assigned based on single-crystal X-ray diffraction analysis. Hirshfeld calculations for 4 revealed the importance of the H . . . H (36.8%), H . . . C (22.9%), Cl . . . H (10.4%) and S . . . H (6.6%), as well as the O . . . H (4.7%), N . . . H (5.3%), Cl . . . C (1.6%), Cl . . . O (1.0%) and N …
Construction of Spirooxindole Analogues Engrafted with Indole and Pyrazole Scaffolds as Acetylcholinesterase Inhibitors
Twenty-five new hits of spirooxindole analogs 8a–y engrafted with indole and pyrazole scaffolds were designed and constructed via a [3+2]cycloaddition (32CA) reaction starting from three components: new chalcone-based indole and pyrazole scaffolds 5a–d, substituted isatins 6a–c, and secondary amines 7a–d. The potency of the compounds were assessed in modulating cholinesterase (AChE) activity using Ellman’s method. Compounds 8i and 8y showed the strongest acetylcholine esterase inhibition (AChEI) with IC50 values of 24.1 and 27.8 μM, respectively. Molecular docking was used to study their interaction with the active site of hAChE. peerReviewed
Synthesis and Characterizations of Novel Isatin-s-Triazine Hydrazone Derivatives : X-ray Structure, Hirshfeld Analysis and DFT Calculations
A novel series of isatin-s-triazine hydrazone derivatives has been synthesized and reported herein. The synthetic methodology involved the reaction of s-triazine hydrazine precursors with isatin derivatives in the presence of CH3COOH as a catalyst and EtOH as solvent to afford the corresponding target products 6a-e in high yields and purities. The characterization data obtained from elemental analysis, FT-IR, NMR (1H- and 13C-) were in full agreement with the expected structures. Furthermore, an X-ray single crystal diffraction study of one of the target s-triazine hydrazone derivatives, 6c confirmed the structure of the desired compounds. It crystallized in the triclinic crystal system and…
Molecular, Supramolecular Structures Combined with Hirshfeld and DFT Studies of Centrosymmetric M(II)-azido {M=Ni(II), Fe(II) or Zn(II)} Complexes of 4-Benzoylpyridine
The supramolecular structures of the three metal (II) azido complexes [Fe(4bzpy)4(N3)2]
Synthesis, and Molecular Structure Investigations of a New s-Triazine Derivatives Incorporating Pyrazole/Piperidine/Aniline Moieties
In this work, we synthesized two new s-triazine incorporates pyrazole/piperidine/aniline moieties. Molecular structure investigations in the light of X-ray crystallography combined with Hirshfeld and DFT calculations were presented. Intermolecular interactions controlling the molecular packing of 4-(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5a and N-(4-bromophenyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazin-2-amine; 5b were analyzed using Hirshfeld calculations. The most dominant interactions are the H...H, N...H and H...C contacts in both compounds. The N...H and H...C interactions in 5a and the N...H, Br...H and H...H interacti…
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