Spiro Heterocycles Research Articles

Density functional theory study of a mechanism of formation of a spiro heterocycle with the Ge spiroatom from dimethylgermylidene germylene (Me2Ge=Ge:) and ethylene

The B3LYP/6-311++G** study of the mechanism of the cycloaddition of singlet 2,2-dimethyl-1,2-digermavinylidene (Me2Ge=Ge:) to ethylene was performed. [2+2] Cycloaddition of the reactants first produced four-membered cyclic germylene, then the interaction of unoccupied 4p orbital of the Ge atom with the π orbital of another ethylene molecule yielded intermediate with the π → p donor-acceptor bond. Isomerization of this intermediate via low-laying transition state resulted in spirocyclic compound with the sp3 hybridized Ge spiroatom.

Iron(III) Chloride Catalyzed Synthesis of Functionalized Spiropyrimidines

Potentially bioactive pyrimidine-annulated spiroheterocyclic compounds are synthesized in good to excellent yields using readily available, cheap and environmentally friendly iron(III) chloride (FeCl3) as the catalyst. The process is straightforward and provides a diverse range of spiropyrimidine derivatives via the 5-endo-dig mode of cyclization, starting from simple and easily available starting materials.

An Extraction of the Isatin from the <i>Couroupita guianesis</i> (Cannon Ball Tree) and a Novel Synthesis of the N,N'-(2-oxo-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazole]-3',5'-diyl]diacetamidefrom the Isatin

Isatins are synthetically versatile substrates, where they can be used for the synthesis of a large variety of Isatins and heterocyclic compounds. In this, the isatin were extracted from the floral material of Couroupita guianesis commonly known as an Cannon ball tree. After that, a novel heterocyclic spiro derivative having an IUPAC name N,N’-(2-oxo-3’H-spiro[indoline-3,2’-[1,3,4] thiadiazole]-3’5’-diyl)diacetamide were synthesized , which may be used as raw material for drug synthesis. A spiro compound N,N’-(2-oxo-3’H-spiro[indoline-3,2’-[1,3,4] thiadiazole]-3’5’-diyl)diacetamide were synthesise by refluxing Isatin and thiosemicarbazone in ethanol and then on heating with acetic anhydride underwent to cyclization into intermediate that on acetylation of the NH and NH2 groups afforded the spiro compound.

Microwave-Induced Solvent-Free Synthesis and Antifungal Screening of Novel Spiro Heterocyclic Systems Containing 3,5-Diphenyl-7H-thiazolo[3,2-a]pyrimidine and Indolin-2-one

A microwave-induced technique has been developed for the synthesis of a series of novel spiro indoline-based heterocycles (7a–g) at atmospheric pressure in an open vessel using an environmentally benign procedure. This rapid method produces pure products in good yields within a few minutes in comparison to the conventional procedure developed for the synthesis of these heterocycles. The synthesized compounds have been screened in vitro for antifungal activity against two fungal strains (i.e., Aspergillus niger and Aspergillus flavus). All compounds have shown significant activity against these pathogens. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]

An Extraction of the Isatin from the <i>Couroupita guianesis</i> (Cannon Ball Tree) and a Novel Synthesis of the N,N'-(2-oxo-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazole]-3',5'-diyl]diacetamidefrom the Isatin

Isatins are synthetically versatile substrates, where they can be used for the synthesis of a large variety of Isatins and heterocyclic compounds. In this, the isatin were extracted from the floral material of Couroupita guianesis commonly known as an Cannon ball tree. After that, a novel heterocyclic spiro derivative having an IUPAC name N,N’-(2-oxo-3’H-spiro[indoline-3,2’-[1,3,4] thiadiazole]-3’5’-diyl)diacetamide were synthesized , which may be used as raw material for drug synthesis. A spiro compound N,N’-(2-oxo-3’H-spiro[indoline-3,2’-[1,3,4] thiadiazole]-3’5’-diyl)diacetamide were synthesise by refluxing Isatin and thiosemicarbazone in ethanol and then on heating with acetic anhydride underwent to cyclization into intermediate that on acetylation of the NH and NH2 groups afforded the spiro compound.

ChemInform Abstract: Spiro Heterocycles as Potential Inhibitors of SIRT1: Pd/C‐Mediated Synthesis of Novel N‐Indolylmethyl Spiroindoline‐3,2′‐quinazolines.

AbstractA series of novel spiro‐indolinequinazoline derivatives (III) (14 examples) are designed and synthesized via a Pd‐C/Cu‐mediated tandem coupling‐cyclization strategy.

Studies on the conversion of ketones of heterocyclic spiro compounds having barbituric acid moieties into oxime derivatives

Five oxime derivatives 7, 11-bis-(4-chlorophenyl)-3-thioxo-2,4-diazaspiro[5,5]undecane-1,5,9-trione-9-oxime (2a), 7,11-bis-(4- methoxyphenyl)-2,4-diazaspiro[5,5]undecane-1,3,5,9-tetraone-9-oxime (2b), 7,11-diphenyl-2,4-diazaspiro[5,5]undecane-1,3,5,9-tetraone- 9-oxime (2c), 7,11-bis-(4-methoxyphenyl)-3-thioxo-2,4-diazaspiro[5,5]undecane-1,5,9-trione-9-oxime (2d), 7,11-diphenyl-3-thioxo-2,4- diazaspiro[5,5]undecane-1,5,9-trione-9-oxime (2e) were synthesized from the corresponding 7,11-diaryl-2,4-diazaspiro[5,5]undecane-3- oxo (or thioxo)-1,5,9-triones (1a-e) with hydroxylaminehydrogenchloride in presence of pyrimidine in absolute alcohol. The structures of the compounds 2a-e were confirmed by their UV, IR, 1H NMR, 13C NMR and mass spectral data and elemental analyses. DOI: http://dx.doi.org/10.3329/bjsir.v48i1.15383 Bangladesh J. Sci. Ind. Res. 48(1), 7-12, 2013

ChemInform Abstract: Synthesis and Biological Applications of Some Novel Spiro Heterocycles Containing 1,3,4‐Thiadiazine, Thiazole, and Oxazole Derivatives.

AbstractMost of the novel spiro‐heterocycles show significant activity against gram‐positive as well as gram‐negative bacteria.

ChemInform Abstract: Chemistry of Dimedone for Synthesis of Oxygen‐, Nitrogen‐, and Sulfur‐Containing Heterocycles from 2‐(3‐Hydroxy‐5,5‐dimethylcyclohex‐2‐enylidene)malononitrile.

AbstractAn efficient route for the synthesis of a wide range of new O‐, N‐, and S‐containing spiro heterocycles via reactions of readily available malononitrile (III) with active methylene or bidentate compounds is presented.

Density functional theory study of mechanism of forming a spiro-Ge-heterocyclic ring compound from Me2Ge=Ge: and acetone

The H2Ge=Ge: and its derivatives (X2Ge=Ge:, X = H, Me, F, Cl, Br, Ph, Ar……) is a new species. Its cycloaddition reactions is a new area for the study of germylene chemistry. The mechanism of the cycloaddition reaction between singlet Me2Ge=Ge: and acetone has been investigated with the B3LYP/6-31G* method in this article. From the potential energy profile, it can be predicted that the reaction has only one dominant reaction pathway. The reaction rule presented is that the two reactants firstly form a four-membered Ge-heterocyclic ring germylene through the [2 + 2] cycloaddition reaction. Because of the 4p unoccupied orbital of Ge: atom in the four-membered Ge-heterocyclic ring germylene and the π orbital of acetone forming a π → p donor–acceptor bond, the four-membered Ge-heterocyclic ring germylene further combines with acetone to form an intermediate. Because the Ge: atom in the intermediate produces sp3 hybridization after a transition state, then the intermediate isomerizes to a spiro-Ge-heterocyclic ring compound via a transition state. The research result indicated the laws of cycloaddition reaction between Me2Ge=Ge: and acetone, and laid the theory foundation of the cycloaddition reaction between H2Ge=Ge: and its derivatives (X2Ge=Ge:, X = H, Me, F, Cl, Br, Ph, Ar……) and asymmetric π-bonded compounds, which is significant for the synthesis of small-ring and spiro-heterocyclic ring compounds involving Ge. The study extends the research area and enriches the research content of germylene chemistry.

A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole–pyrrolizine–piperidine hybrids

A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13μM, respectively.

Theoretical study of mechanism of cycloaddition reaction between 2,2-dimethyl(2-germavinylidene) [(CH3)2Ge=C:] and formaldehyde

The mechanism of the cycloaddition reaction between singlet 2,2-dimethyl(2-germavinylidene) [(CH3)2Ge=C:] and formaldehyde has been investigated with CCSD(T)//MP2/6-311G** method. From the potential energy profile, it could be predicted that the reaction has two competitive dominant reaction pathways. The first pathway consist of the transfer of formaldehyde oxygen π-electrons to the 2p unoccupied orbital of the C: atom in 2,2-dimethyl(2-germavinylidene) with a formation of intermediate which then isomerizes to a four-membered heterocyclic ring carbene (Ge and O in the 1,3-position). The second pathway is a direct [2 + 2] cycloaddition reaction in which the interaction of two π-bonds in 2,2-dimethyl(2-germavinylidene) and formaldehyde generates another four-membered heterocyclic ring carbene (Ge and O in 1,2-position). Because of the unsaturated property of the C: atom in the two four-membered heterocyclic ring carbenes, the two four-membered heterocyclic ring carbenes could further react with formaldehyde, generating two spiro-heterocyclic ring compounds.

Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2′-quinazolines

Novel N-indolylmethyl substituted spiroindoline-3,2′-quinazolines were designed as potential inhibitiors of SIRT1. These compounds were synthesized in good yields by using Pd/C–Cu mediated coupling-cyclization strategy as a key step involving the reaction of 1-(prop-2-ynyl)-1′H-spiro[indoline-3,2′-quinazoline]-2,4′(3′H)-dione with 2-iodoanilides. Some of the compounds synthesized have shown encouraging inhibition of Sir 2 protein (a yeast homologue of mammalian SIRT1) in vitro and three of them showed dose dependent inhibition of Sir 2. The docking results suggested that the benzene ring of 1,2,3,4-tetrahydroquinazolin ring system of these molecules occupied the deep hydrophobic pocket of the protein and one of the NH along with the sulfonyl group participated in strong H-bonding interaction with the amino acid residues.

Synthesis and Biological Applications of Some Novel Spiro Heterocycles Containing 1,3,4‐Thiadiazine, Thiazole, and Oxazole Derivatives

2‐Ethoxy carbonylcyclopentanone (1) has been brominated to yield 2‐bromo‐2‐ethoxy carbonylcyclopentanone (2) which on further reaction with substituted thiosemicarbazones, thiocarbohydrazones, thiocarbamides and carbamides has furnished 1‐thia‐3,4‐diaza‐5,7‐dioxo‐2‐[(substituted benzylidine)‐amino]spiro[4.5]dec‐2‐ene (3a–e), 1‐thia‐3,4‐diaza‐5,7‐dioxo‐2‐[(substituted benzylidine)‐hydrazino] spiro[4.5]dec‐2‐ene (4a–e), 1‐thia‐3‐aza‐2‐(substituted imino)‐4,6‐dioxo‐spiro[4.4]nonane (5a–f) and 1‐oxa‐3‐aza‐2‐(substituted imino)‐4,6‐dioxo‐spiro[4.4]nonane (6a–g) respectively. The structures of the compounds have been elucidated on the basis of spectral analysis.

Chemistry of Dimedone for Synthesis of Oxygen-, Nitrogen-, and Sulfur- Containing Heterocycles from 2-(3-Hydroxy-5,5-dimethylcyclohex-2-enylidene)malononitrile

A series of new oxygen-, nitrogen- and sulfur- containing spiro heterocycles was synthesized by reactions of 2-(3-hydroxy-5,5-dimethylcyclohex-2-enylidene)malononitrile with some active methylene and bidentate compounds.

ChemInform Abstract: Direct Spiro Heterocyclization of Methyl 3‐Aroyl‐1‐aryl‐4,5‐dioxo‐4,5‐dihydro‐1H‐pyrrole‐5‐carboxylate by the Action of 3‐Amino‐1H‐inden‐1‐one.

ChemInform Abstract: Direct Spiro Heterocyclization of Methyl 3‐Aroyl‐1‐aryl‐4,5‐dioxo‐4,5‐dihydro‐1H‐pyrrole‐5‐carboxylate by the Action of 3‐Amino‐1H‐inden‐1‐one.

Theoretical study on the mechanism of cycloaddition reaction between silylene silylene(H2Si=Si:) and acetaldehyde

The mechanism of the cycloaddition reaction between singlet silylene silylene (H₂Si=Si:) and acetaldehyde has been investigated with CCSD(T)//MP2/6-31G* and CCSD(T)//MP2/6-31G** method, from the potential energy profile, we could predict that the reaction has three competitive dominant reaction pathways. The present rule of this reaction is that the 3p unoccupied orbital of the Si: atom in silylene silylene (H₂Si=Si:) inserts on the π orbital of acetaldehyde from oxygen side, resulting in the formation of an intermediate. Isomerization of the intermediate further leads to the generation of a four-membered ring silylene (the H₂Si-O in the opposite position). In addition, the [2 + 2] cycloaddition reaction of the two π-bonds in silylene silylene and acetaldehyde generates another four-membered ring silylene (the H₂Si-O in the syn-position). Because of the unsaturated property of Si: atom in the two four-membered ring silylenes, they could further react with acetaldehyde, resulting in the generation of two spiro-heterocyclic ring compounds with Si. Simultaneously, the ring strain of the four-membered ring silylene (the H₂Si-O in the syn-position) makes it isomerize to a twisted four-membered ring product.

Molecular drug design, synthesis and pharmacophore site identification of spiroheterocyclic compounds: Trypanosoma crusi inhibiting studies

Synthesis and evaluation of the bioactivity of spiroheterocycles (STC) against Trypanosoma cruzi are described. Selectivity indices were improved for two compounds versus the leads 17 and 20, the spiro-thiochromanone (STC) derivatives 17–26, thus increasing the therapeutic interest of our family. As our previous studies conducted on the structure of pharmacophore sites of our compounds made us hypothesize the existence of original sites, STC can be considered as promising tools further anti-trypanosoma studies, as probes for affinity chemotherapy. Compounds 17 and 20 are more potent and more selective than benznidazole and nifurtimox. The highest anti-trypanosoma cruzi (TC) activity is obtained for compounds 17 and 20 which exhibited low IC50 values (1.5 and 3.78 μM), up to sixfold lower than clinical drugs, nifurtimox (Nfx) or up to fourfold lower than benznidazole (Bdz).

Direct spiro heterocyclization of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-5-carboxylate by the action of 3-amino-1H-inden-1-one

Direct spiro heterocyclization of methyl 3-aroyl-1-aryl-4,5-dioxo-4,5-dihydro-1H-pyrrole-5-carboxylate by the action of 3-amino-1H-inden-1-one

ChemInform Abstract: NaCl as a Novel and Green Catalyst for the Synthesis of Biodynamic Spiro Heterocycles in Water under Sonication.

AbstractThe advantages of the presented method are a high yield, an easy handling and purification of the product is not necessary.