Closure Reaction Research Articles

Synthesis of Novel Fluorine Substituted Isolated and Fused Heterobicyclic Nitrogen Systems Bearing 6-(2’-Phosphorylanilido)-1,2,4-Triazin-5-One Moiety as Potential Inhibitor towards HIV-1 Activity

Novel 6-(5’-fluoro-2’-diphenylphosphorylanilido)-3-hydrazino-1,2,4-trizin-5 (2H) one (3) is achieved from hydrozinolysis of the corresponding 3-thioxo-analoges 2. Compound 2 is also obtained from phosphorylation of 6-(5’-fluoro-2’-aminophenyl)-3-thioxo-1,2,4-triazin-5(2H) one (1). Novel fluorine substituted isolated and/or fused heterobicyclic nitrogen systems bearing and/or containing, 6-phosphoryl anilido-1,2,4-trizin-5 (2H) one moiety (4 - 22) have been synthesized from ring closure reactions of compound 3 with π-acceptors activated carbon compounds in different medium and conditions. Structures of the products are characterized by MS, IR, UV-VIS, CH, N, and 1H/13CNMR spectral data. The new products have been evaluated as potential inhibitors towards HIV-1 activity.

Synthesis of Some New Fluorine Substituted Thiobarbituricacid Derivatives as Anti HIV1 and Cyclin-Dependent Kinase 2 (CDK2) for Celltumer Division-Part II

In search for new potential inhibitors some new fluorine substituted thiobarbituric acid derivatives (2-4, 7, 8) and their fused/isolated heterobicyclic nitrogen systems (5, 6, 9, 10, 11, 12) have been synthesized from heterocyclization of fluorinated 1,3-diketoamine (1) with CS2 followed by ring closure reactions with primary nitrogen reagents. Structures of the targets have been established from elemental analysis and spectral data. Some synthesized systems have been evaluated as anti-HIV-1 and of cyclin-dependent kinase 2 (CDK2) for cell tumor division.

Construction of 3,5-substituted 1,2,4-oxadiazole rings triggered by tetrabutylammonium hydroxide: a highly efficient and fluoride-free ring closure reaction of O-acylamidoximes

Tetrabutylammonium hydroxide (TBAH) is an efficient and mild alternative to tetrabutylammonium fluoride (TBAF) for base catalyzed cyclizations of 1,2,4-oxadiazoles from O-acylamidoximes. For most 3,5-substituted 1,2,4-oxadiazoles the reactions were dramatically accelerated by addition of 0.1 equiv of TBAH at room temperature. This method was also more generally applicable allowing for a wider range of substrates. Additionally, due to the absence of fluoride, TBAH will not result in corrosion of reactor vessels and therefore is better suited for large-scale synthesis.

Recent Developments of Cascade Reactions Involving ω-Transaminases

Enzymatic cascade reactions experience tremendous attention by cutting short conventional step-by-step synthesis in a highly efficient and elegant fashion. Focusing on ω-transaminases, this review provides an overview of different biocatalytic strategies to afford a variety of (chiral) amines employing diverse cascade systems: Cascades to shift the reaction equilibrium as well as cascades for the amination of alcohols and nonactivated C–H bonds are discussed. Cascades enable the deracemization of rac-amines, other ones involve biocatalyzed C–C bond formation and C–C bond hydrolysis. Finally, the potential of spontaneous ring closure reactions initiated by ω-transaminases is illustrated.

Regio- and Stereocontrol in the Michael-Initiated Ring-Closure Reactions of γ,δ-Epoxy-α,β-unsaturated Esters, Ketones, Sulfones, and Amides

Organozincates or Grignard reagents in the presence of zinc catalysts undergo Michael initiated ring closure (MIRC) reactions with γ,δ-epoxy-α,β-enoates, enones, enesulfones, and enamides to afford 1,2,3-trisubstituted cyclopropanes. The direction of diastereoselectivity is solvent dependent for alkyl Grignard reagents reacting with epoxy enoates, ensulfones, and enamides but solvent independent for the enones. Excellent diastereoselectivity can be achieved for the epoxy enoates, enones, and ensulfones, while the enamides afford modest diastereoselectivity under optimal conditions. The MIRC reaction can be achieved with phenylmagnesium chloride and these substrates under reaction conditions designed to minimize biphenyl formation.

Synthesis of novel pyrano[3,2-f]quinoline, phenanthroline derivatives and studies of their interactions with proteins: An application in mammalian cell imaging

A series of tri-cyclic pyrano[3,2-f]quinoline and phenanthroline derivatives have been synthesized by a HCl-mediated 6-‘endo-trig’ Michael type ring closure reaction of 6-amino-5-(3-hydroxy-3-methylbut-1-ynyl)-2H-chromen-2-one in excellent yields. The process is very simple, facile and inexpensive and can provide a diverse range of substituted quinoline derivatives from simple and easily available starting materials. Moreover, the synthesized derivatives exhibit staining property to the cultured HeLa cells after fixing and can be used as fluorophores which can bind with protein molecule.

A Straightforward and Highly Diastereoselective Access to Functionalized Monofluorinated Cyclopropanes via a Michael Initiated Ring Closure Reaction

The synthesis of highly functionalized monofluorinated cyclopropanes based on a Michael Initiated Ring Closure (MIRC) reaction has been developed. The addition of quaternary ammonium salts derived from ethyl bromofluoroacetate on a panel of electron deficient alkenes followed by cyclization gave rise to an efficient access to monofluorinated cyclopropanes with good yields and remarkable diastereoselectivity.

ChemInform Abstract: Synthesis of Substituted Diazino[c]quinolin‐5(6H)‐ones, Diazino[c]isoquinolin‐6(5H)‐ones, Diazino[c]naphthyridin‐6(5H)‐ones and Diazino[c]naphthyridin‐5(6H)‐ones

Abstractvia one‐pot cross‐coupling/cyclization or two‐step cross‐coupling/KOH‐mediated anionic ring closure reactions

Synthesis of 1H-pyrazolo[3,4-d]pyrimidines via solid-phase Aza-Wittig/electrocyclic ring closure reaction

An elegant solid-phase synthetic route of pyrazolo[3,4-d]pyrimidine derivatives via Aza-Wittig/electrocyclic ring closure reaction was developed and validated. By manipulating the R group from the primary amine building block, one can easily prepare the library of pyrazolo[3,4-d]pyrimidine derivatives.

A Two‐Step Sequence to Ethyl α‐Fluorocyclopropanecarboxylates Through MIRC Reaction of Ethyl Dichloroacetate and Highly Regioselective Fluorination

AbstractA two‐step sequence to ethyl α‐fluorocyclopropanecarboxylates has been developed. Ethyl α‐chlorocyclopropanecarboxylates were first obtained through a Michael‐initiated ring closure reaction of terminal electron‐deficient olefins with ethyl 2,2‐dichloroacetate under mild basic conditions. Subsequent smooth conversion into the corresponding monofluorinated analogues in good yields was through a halogen exchange reaction with potassium bifluoride. Further investigation clearly demonstrated that potassium bifluoride in this reaction system played a dual role of base and nucleophilic reagent. This is the first successful example reported hitherto for producing ethyl α‐fluorocyclopropanecarboxylate directly through fluorination of its chlorinated analogue with alkali bifluoride.

ChemInform Abstract: Synthesis of 2‐Amino 3‐Substituted Quinazolin‐4(3H)‐one Derivatives via Iodine‐Mediated Guanidinylation of Pbf‐Activated Thiourea.

AbstractTitle compounds are prepared using the Pbf‐activated thiourea moiety as guanidinylating reagent in the ring closure reaction step.

ChemInform Abstract: Stereoselective Cyclopropanation of α‐Bromochalcone with Diethyl Malonate Promoted by K2CO3.

AbstractBesides good yields for the exclusive formation of the trans‐isomers (III), this Michael‐initiated ring closure reaction also provides the first access to the cis‐isomers (IV) of the depicted densely substituted cyclopropanes.

Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2

SUMMARYMononuclear non-haem iron (NHFe) enzymes catalyse a wide variety of oxidative reactions including halogenation, hydroxylation, ring closure, desaturation, and aromatic ring cleavage. These are highly important for mammalian somatic processes such as phenylalanine metabolism, production of neurotransmitters, hypoxic response, and the biosynthesis of natural products.1–3 The key reactive intermediate in the catalytic cycles of these enzymes is an S = 2 FeIV=O species, which has been trapped for a number of NHFe enzymes4–8 including the halogenase SyrB2, the subject of this study. Computational studies to understand the reactivity of the enzymatic NHFe FeIV=O intermediate9–13 are limited in applicability due to the paucity of experimental knowledge regarding its geometric and electronic structures, which determine its reactivity. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes of Fe on the nature of the FeIV=O active site.14–16 Here we present the first NRVS structural characterisation of the reactive FeIV=O intermediate of a NHFe enzyme. This FeIV=O intermediate reacts via an initial H-atom abstraction step, with its subsquent halogenation (native) or hydroxylation (non-native) rebound reactivity being dependent on the substrate.17 A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate is able to direct the orientation of the FeIV=O intermediate, presenting specific frontier molecular orbitals (FMOs) which can activate the selective halogenation versus hydroxylation reactivity.

ChemInform Abstract: Electrocatalytic and Chemical Methods in MHIRC Reactions: The First Example of the Multicomponent Assembly of Medicinally Relevant Spirocyclopropylbarbiturates from Three Different Molecules.

AbstractElectrolysis of barbituric acids, malononitrile and aromatic aldehydes in an undivided cell in the presence of sodium bromide results in a Michael halogenation initiated ring closure (MHIRC) reaction yielding spirocyclopropylbarbiturates (IV).

Effective synthesis of 3,5-diaryl-(1H)-pyrazin-2-ones via microwave mediated ring closure

Abstract In this study we report on a flexible straight forward synthesis toward novel 3,5-diaryl-(1 H )-pyrazin-2-ones. Our synthetic strategy involved an acyclic di-keto derivative as key intermediate. The final pyrazin-2-one ring closure reaction was yield-optimized by using a microwave mediated procedure and ammoniumacetate as nitrogen source. Our method is a suitable alternative to palladium-catalyzed coupling reactions for the 3,5-diaryl decoration of the (1 H )-pyrazin-2-one scaffold. Since the (1 H )-pyrazin-2-ones is present as scaffold in a number of biologically active compounds the reported synthetic platform is a useful approach to generate a set of highly diverse 3,5-diaryl-(1 H )-pyrazin-2-one compounds.

Synthesis of dihydrobenzo[1,4]oxazines using copper catalyzed intramolecular ring closure reaction

The synthesis of dihydrobenzo[1,4]oxazines has been accomplished efficiently by copper catalyzed intramolecular cyclization of the adducts formed by the treatment of 1,2-cyclic sulfamidates with 2-halo phenols. The products (except two) are new and their yields are high. The catalyst is easily available and less expensive.

Unified Azoline and Azole Syntheses by Optimized Aza‐Wittig Chemistry

AbstractIntramolecular aza‐Wittig ring closures were applied to synthesize thiazolines, oxazolines, and imidazolines from β‐azido thioester, ester, and amide precursors. The cyclization precursors were obtained from amino acid derivatives. Optimized conditions for diazo transfer with a fast rate and racemization suppression, (thio)esterification, and amide coupling reactions are described. The ring closure reaction can be executed with PPh3 under neutral conditions and was found to be highly chemoselective for five‐membered rings. If amide groups were activated with tosyl groups, smooth intramolecular ring closure of iminophosphoranes furnished enantiopure imidazoline products with position‐specific tosyl protection. This aza‐Wittig‐based azoline synthesis was then extended to double azoline ring closures to furnish catenated azoline building blocks common to peptide natural product building blocks and their analogues.

ChemInform Abstract: Synthesis and Photoluminescent Properties of New Aza‐Indenofluorene Derivatives.

AbstractSeveral new carbazole derivatives (VII), (IX) are synthesized via Suzuki coupling of boronic acid (I) with 1‐bromo‐2‐nitrobenzene (II), followed by the Cadogan ring closure reaction.

Syntheses and properties of 3,4-diaryldithieno [2,3-b;3′,2′-d]thiophenes

Dithieno[2,3-b;3′,2′-d]thiophenes (DTT), having substituted phenyl groups at 3- and 4-carbons, have been synthesized, applying 2,5-diketone ring closure reaction using P4S10. Cyclic voltammetry studies indicated that all the DTTs had the oxidation potentials between 1.19 and 1.70 V. Computational calculations displayed positive radical spin densities at C2 positions for DTTs and negative for their dimers.

Oxidation of Neat Synthetic Paraffinic Kerosene Fuel and Fuel Surrogates: Quantitation of Dihydrofuranones

Thermal stressing experiments on a modified surrogate fuel and synthetic paraffinic kerosene (SPK) have been carried out under both static and dynamic conditions at 140 °C. In order to characterize the oxidation products, some key degradation compounds were monitored throughout the stressing experiment. Products resulting from ring closure reactions were also identified in the surrogate fuel and the SPK, with the identification of iso-benzofuranone and alkyldihydrofuranones. Furanones were quantified using gas chromatography–mass spectrometry (GC-MS) with high-performance liquid chromatography (HPLC) prefractionation. The formation of these furanones indicates that dynamic stressing promotes a reactivity that has only been reported at either higher temperatures or longer residence times.