Closure Reaction Research Articles

Synthesis of New Fluorine Substituted Heterocyclic Nitrogen Systems Derived from p‐Aminosalicylic Acid as Antimycobacterial Agents

Some new fluorine substituted heterocyclic nitrogen systems 2–17 have been synthesized from ring closure reactions of substituted p‐amino salicylic acids (PAS). The Schiffs base of PAS was cyclized with chloroacetyl chloride and mercaptoacetic acid to give azetidinone 2, thiazolidinone 3, and spiro‐fluoroindolothiazoline‐dione 10. However, PAS when reacted directly with 4‐fluorobenzoyl chloride and 5‐oxazolinone yielded derivatives 4, 5, and 7. Aminomethylation of PAS using formaldehyde and piperidine or piperazine formed N‐alkyl and N,N′‐dialkyl derivatives (11 and 12 respectively) upon fluorinated benzoylation gave compounds 13 and 14. Similarly, treatment of PAS with thiosemicarbazide 15 and subsequent cyclization with diethyl oxalate yielded the fluorinated heterocycle 17. The structures of the fluorinated heterocyclic systems have been established on the basis of elemental analysis, 1H NMR, 13C NMR, and MS spectral data. Some of the targets exhibited a high inhibition towards Mycobacterium strain with favorable log P values.

Synthesis and Photoluminescent Properties of New Aza‐Indenofluorene Derivatives

ABSTRACTThe carbazole derivatives 5a–h were synthesized by four steps involving Suzuki coupling of boronic acid 1 with 1‐bromo‐2‐nitrobenzene, followed with the Cadogan ring closure reaction. Their UV and photoluminescence properties are also reported, and the compounds showed medium‐to‐strong photoluminescence between 370 and 446 nm at the concentration of 1 × 10−5 M CH2Cl2. Also, the X‐ray structure of the carbazole derivative 6 was elucidated by an X‐ray diffractometer. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 24:18–24, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21058

3‐aryl‐6‐methoxy‐2‐oxo‐1,2‐dihydroquinoline‐4‐carbonitriles as Solvent and pH Independent Green Fluorescent Dyes

Highly fluorescent and stable 3‐aryl‐6‐methoxy‐2‐oxoquinoline‐4‐carbonitriles 6 (λexc = 408 nm and λem = 510 nm) were synthesized starting from appropriate arylmalonates 2. Ring closure reaction with p‐anisidine gave 4‐hydroxyquinolones 3, which could be bis‐chlorinated to yield quinolines 4. Regioselective hydrolysis produced reactive 4‐chloroquinolones 5, which were converted to green fluorescent 4‐cyano quinolones 6 using toluenesulfinates as catalysts.

Chiral Cyclopentadienyl Ligands as Stereocontrolling Element in Asymmetric C–H Functionalization

Metal complexes coordinated by a single cyclopentadienyl (Cp) ligand are widely used, versatile catalysts, but their application to asymmetric reactions has been hindered by the difficulty of designing Cp substituents that effectively bias the coordination sphere. Here, we report on a class of simple C(2)-symmetric Cp derivatives that finely control the spatial arrangement of the transiently coordinated reactants around the central metal atom. Rhodium(III) complexes bearing these ligands proved to be highly enantioselective catalysts for directed carbon-hydrogen (C-H) bond functionalizations of hydroxamic acid derivatives.

Biotinylated Rh(III) Complexes in Engineered Streptavidin for Accelerated Asymmetric C–H Activation

Enzymes provide an exquisitely tailored chiral environment to foster high catalytic activities and selectivities, but their native structures are optimized for very specific biochemical transformations. Designing a protein to accommodate a non-native transition metal complex can broaden the scope of enzymatic transformations while raising the activity and selectivity of small-molecule catalysis. Here, we report the creation of a bifunctional artificial metalloenzyme in which a glutamic acid or aspartic acid residue engineered into streptavidin acts in concert with a docked biotinylated rhodium(III) complex to enable catalytic asymmetric carbon-hydrogen (C-H) activation. The coupling of benzamides and alkenes to access dihydroisoquinolones proceeds with up to nearly a 100-fold rate acceleration compared with the activity of the isolated rhodium complex and enantiomeric ratios as high as 93:7.

Molecular Model of the Ring-Opening and Ring-Closure Reaction of a Fluorinated Indolylfulgide

A combination of experimental and theoretical techniques is used to study the photoinduced ring-opening/closure of a trifluoromethyl-indolylfulgide. Time-resolved UV/vis pump and IR probe measurements are performed in the subpicosecond to 50 ps time range. Probing in the mid-IR between 1200 and 1900 cm(-1) provides mode-specific dynamics and reveals photochemical reaction dynamics as well as the presence of a noncyclizable conformer. Ring-opening occurs with about 3 ps. Experiments on the open isomer confirm that the ring-closure occurs on the subpicosecond time scale. They also show a 10 ps transient that can be assigned to internal conversion of a noncyclizable conformer. Quantum chemical calculations with multireference methods are used to explore the complex potential energy landscape in the excited electronic state showing paths for ring-opening and closure reactions as well as for competing side-reactions. The calculations reveal that photoexcitation induces a charge transfer from the indole to the anhydride. The same charge transfer drives the system toward a low-energy conical intersection seam spreading from the closed to the open ring side and is responsible for the ultrafast relaxation to the ground state. The ultrafast photoreactivity comes at the expense of selectivity.

ChemInform Abstract: The Thriving Chemistry of Ketenimines

AbstractReview: ca. 100 refs.

Biomimetic Synthesis of the Apoptosis-Inducing Thiazinoquinone Thiaplidiaquinone A

A concise total synthesis of the apoptosis-inducing, marine metabolite thiaplidiaquinone A is described. The key ring forming steps are both based on biosynthetic considerations and involve the construction of the central benzo[c]chromene quinone unit by an extremely facile oxa-6π-electrocyclic ring closure reaction of an ortho-quinone intermediate, derived by tautomerization of a bis-benzoquinone, readily accessed from two simple phenolic precursors. This is followed by the installation of the 1,4-thiazine-dioxide ring by reaction of the benzo[c]chromene quinone with hypotaurine.

ChemInform Abstract: Thieno[3,2‐b]thiophene‐2‐carboxylic Acid Derivatives as GPR35 Agonists.

AbstractThe title derivatives are obtained from dibromo‐ and perbromothiophene (I) and (XIII) via a ketone‐based ring closure reaction and subsequent introduction of substituents into the thienothiophene core by Hiyama or Suzuki cross‐coupling.

Synthesis of 1-acetyl-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives and evaluation of their anticancer activity

In the present study, 1-acetyl-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives (1–6) were synthesized via the ring closure reaction of 1-(2-thienyl)-3-aryl-2-propen-1-ones with hydrazine hydrate in acetic acid. The chemical structures of the compounds were elucidated by IR, 1H-NMR, 13C-NMR and mass spectral data and elemental analyses. MTT assay, analysis of DNA synthesis and caspase-3 activation assay were carried out to determine anticancer effects of the compounds on A549 and C6 cancer cell lines. They exhibited dose-dependent anticancer activity against A549 and C6 cancer cell lines. Anticancer activity screening results revealed that compounds 1, 2 and 4 were the most potent derivatives among these compounds. But anticancer effects of these compounds may result from different death mechanisms in A549 and C6 cell lines.

Photoinduced Cyclization Reactions in Aqueous Media

This account intends to cover recent literature on photoinduced cyclization reactions in water or aqueous media. The reactions covered do not proceed by the assistance of metals, or through electron transfer reactions mediated by metallic species or complexes. Radical cyclization of perfluoroalkyl-substituted compounds is neither the subject of this article, since these examples have been reviewed recently. Instead, photomacrocyclization and photoelectrocyclic ring closure reactions are the aims of this article, as well as the syntheses of lactones and 5-methyleneoxazolidin-4-ones, showing the scope of these reactions carried out in an environmentally-friendly media. These cyclization reactions will be shown to enable the syntheses of important synthetic targets, with relevancy in biochemistry and medicinal chemistry. Keywords: Photocyclization in aqueous media, Electrocyclic ring closure, Oxazolidinones, Photocyclization of phthalimides, 1-ethylpiperidine, benzopyrrolizidine, trimellitic acid substrates, H2O/Me2CO mixtures, X-ray structures, (silylalkyl)phthalimide, N-alkylphthalimide.

Concise Syntheses, Polymers, and Properties of 3-Arylthieno[3,2-b]thiophenes

Thieno[3,2-b]thiophenes (TT), having para-substituted phenyl groups at C-3, have been synthesized through a ring closure reaction, using P4S10, in moderate to high yields. Their absorbance studies displayed that the TT, having nitrophenyl group had the most red shift absorbance at 365 nm, which also showed the lowest optical band gap of 2.92 eV; the rest of the TTs had the absorbance between 300 and 302 nm. Cyclic voltammetry studies indicated that while all the TTs had the oxidation potentials above 1.0 V, the TT with dimethylaminophenyl group had the lowest oxidation potential of 1.33 V. The rest had the oxidation potentials between 1.6 and 1.99 V. The TTs were both electropolymerized and copolymerized with thiophene through Suzuki coupling reaction. Electropolymerized polymers indicated that while the polymer having strong electron donating dimethylaminophenyl group had the lowest oxidation potential of 0.97 V, the rest of the polymers displayed the potentials between 1.09 and 1.39 V. Their electronic ...

Asymmetric Synthesis of Cyclopropanes with a Monofluorinated Quaternary Stereocenter

New chiral fluorinated reagents (N-(dibromofluoroacetyl)oxazolidinones) were easily synthesized and used in an asymmetric cyclopropanation process. The Michael initiated ring closure reaction provided chiral cyclopropanes bearing a fluorinated quaternary stereocenter. Various electron-deficient alkenes can be used to efficiently obtain chiral polysubtituted fluorinated cyclopropanes in good yields. Moderate to very good cis/trans ratios were obtained with a high level of diastereoselectivity for each isomer.

ChemInform Abstract: Polycyclic N‐Heterocyclic Compounds. Part 69. Synthesis of 5‐Amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and Their Transformations to Related Compounds.

AbstractRing closure reaction of 1,6‐dinitriles (I) in the presence of strong base proceeds via Thorpe—Ziegler pathway to give oxepine derivatives (II), and via Truce—Smiles rearrangement to give difuropyridines (III).

FeCl3-Catalyzed Stereoselective Construction of Spirooxindole Tetrahydroquinolines via Tandem 1,5-Hydride Transfer/Ring Closure

An efficient FeCl(3)-catalyzed stereoselective intramolecular tandem 1,5-hydride transfer/ring closure reaction was developed. The method allows for the formation of structurally diverse spirooxindole tetrahydroquinolines in high yields (up to 98%) with good to excellent levels of diastereoselectivity (up to 99:1 dr). The catalytic enantioselective variant of this process was also investigated preliminarily with a chiral BINOL-derived phosphoric acid.

Study on the scope of tert‐amino effect: new extensions of type 2 reactions to bridged biaryls

Thermal isomerization of aminomethyl‐ or oxygen‐bridged biphenyl systems possessing dicyanovinyl and sec‐amino groups in ortho‐ and ortho′‐positions was investigated. Both systems underwent cyclization via tert‐amino effect. Thus, 2‐(2‐{[2‐(sec‐amino)benzyl]‐N‐methylamino}benzylidene)malononitriles gave tetrahydroquinolines, whereas a 2‐[2‐(sec‐amino)phenoxy]benzylidenemalononitrile isomerized to dibenzoxazonine derivative. The ring closure reaction was studied by differential scanning calorimetry measurements. Copyright © 2012 John Wiley & Sons, Ltd.

One-step synthesis, characterization and X-ray analysis of benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-ones

Two isomeric compounds of methoxy substituted benzo[de]benzo[4,5]imidazo[2,1-a] -isoquinolin-7-one were obtained from the one-step ring closure reaction of 2-(2-acetamino-5-methoxyphenyl)benzo[de]isoquinoline-1,3-dione under acidic condition. Their structures were characterized by using HRMS, NMR spectra analyses together with single crystal X-ray diffraction. Compound 2 crystallizes in the monoclinic P2 (1)/n space group with the crystal cell parameters a=8.3311(11)Å, b=7.6646(10)Å, c=21.201(2)Å, α=90.00°, β=95.7380(10)°, γ=90.00°, V=1347.0(3)Å3 and Z=4. Compound 3 crystallizes in the monoclinic space group P2 (1)/c with the crystal cell parameters a=3.8270(3)Å, b=15.8361(14)Å, c=28.559(3)Å, α=90.00°, β=94.1090(10)°, γ=90.00°, V=1726.4(3)Å3 and Z=4. X-ray results indicated that it exist non-classically intermolecular interactions in the molecules of the two compounds. The substitution position of methoxy group has no obvious influence on the whole molecular planarity, but results in great different formation modes of their intermolecular interactions and structural stabilization.

Synthesis and antibacterial activity of some new 4-anilino-5-phenyl-4H-1,2,4-triazole-3-thiol derivatives

4-Anilino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) reacted with formaldehyde and different amines to give Mannich bases 2a–i. Treatment of compound 1 with formaldehyde afforded the corresponding 2-hydroxymethyl derivative 3, which upon its reaction with thionyl chloride yielded the corresponding chloromethyl derivative 4. Treatment of compound 4 with some thiols gave the corresponding sulfides 5a–f. The ring closure reaction of chloromethyl derivative 4 with hydrazine hydrate, phenyl hydrazine, hydroxylamine, urea and thiourea afforded triazolo-, oxadiazolo- and triazinotriazoles 6–10, respectively.

The Asymmetric Formal Hetero‐Diels–Alder Reaction of Methyl (E)‐4‐Aryl‐2‐oxo‐3‐butenoates Catalyzed by [Sc(OTf)3/pybox] Complexes

AbstractThe complex between scandium triflate and pybox is a good enantioselective catalyst for the reaction between methyl (E)‐4‐aryl‐2‐oxo‐3‐butenoates (1) and enol silyl ethers (2). The main products with (4′S)‐isopropyl‐, (4′S)‐phenyl‐, and (4′S,5′S)‐4‐TIPS‐pybox are methyl (4S,4aS,8aS)‐4‐aryl‐8a‐trialkylsiloxy‐hexahydro‐4H‐chromen‐2‐carboxylates (7), which are obtained in good yield and enantioselectivities of more than 95 % ee. Because the reaction gives products with a trans ring junction that cannot derive from a conventional concerted hetero‐Diels–Alder pathway, the mechanism involved in the enantioselective catalytic cycle and the origin of the stereoinduction were investigated. The structures of two desilylated products, 8b and 9b, were determined by X‐ray crystal analysis. Their absolute configuration was then related to that of 7 by stereospecific isomerization and/or desilylation reactions. If aryl‐butenoates 1 are coordinated to the catalyst, forming reacting complexes characterized by the five‐membered structure 11, these rigid reacting intermediates give a face discrimination that is determined by the configuration of the pybox 4′‐substituent. The resulting face‐selective attack of enol silyl ethers to coordinated 1 gives an enantioselective tandem Mukaiyama–Michael addition/intramolecular ring closure reaction, which is an enantioselective formal hetero‐Diels–Alder reaction, which rationalizes the absolute configuration of the reaction products.

A Novel Pathway to Imidazo[1,2-a]pyridines. Access through Imino Pyridinium Salts

A new synthetic strategy for the preparation of imidazo[1,2-a]pyridines 10 is reported, which is based on the electrocyclization reaction of imino pyridinium salts 7 upon treatment with a strong base. The starting materials are easily prepared from 2-aminopyridine (3) by imine condensation and subsequent alkylation at the pyridine nitrogen atom. The ring closure reaction of the zwitterionic intermediate 8 to give a five-membered ring proceeds in low yield forming first the dihydro compound 9, which under the reaction conditions is transformed into the corresponding aromatic compounds 10 and 11 by air oxidation. The mechanism of the electrocyclization reaction is interpreted in detail by quantum-chemical calculations.