Ortho Carbonyl Group Research Articles

NiH-Catalyzed Proximal-Selective Hydroamination of Unactivated Alkenes with Anthranils.

The regioselective hydroamination of unactivated alkenes is a long-standing challenge in organic synthesis. Herein, we report a NiH-catalyzed proximal-selective hydroamination of unactivated alkenes with 8-aminoquinoline (AQ) as a bidentate auxiliary and anthranils as aminating reagents. A wide range of primary aryl amines bearing an ortho-carbonyl group were installed in both terminal and internal unactivated alkenes, delivering a variety of valuable β- and γ-amino acid building blocks, respectively, with excellent regiocontrol. The utility of this transformation was further demonstrated by the conversion of the multifunctionalized aryl amines into useful N-heterocycles.

Coupling-to-diazonium role-convert strategy for 1,3-dimethylbarbituric acid-based dyes and configurational confirmation via NMR/UV–vis spectra

5-Amino-1,3-dimethlybarbituric acid (5-amino-diMeBA), prepared form 1,3-dimethlybarbituric acid (diMeBA) via the functional group transformation strategy, is first used as the diazonium component to produce heterocyclic dyes, in order to expand the existing research objects in this area. Role-convert synthesis has been successfully achieved from a general coupling component diMeBA to a corresponding diazonium unit 5-amnio-diMeBA, and three pyrazolone/pyridone coupled bi-heterocyclic dyes were yielded. There are multiple possible azo/hydrazone tautomers for them since three ortho-carbonyl groups could serve as the protonated sites for active protons. The configurational confirmation depends on the precise location of heterocyclic hydroxyl groups, which could be deduced by comparing the alterations of two characteristic methyl single peaks in diMeBA moiety in the 1H NMR spectra before and after deprotonation. Our results reveal that three bi-heterocyclic dyes adopt the monohydrazone form in pyrazolone with 4-OH-diMeBA and the monohydrazone form in diMeBA with 6-OH-pyridone, respectively. Further UV–Vis spectra have been carried out to compare the delocalized π-conjugated system for them, together with three BA coupled heterocyclic dyes. In addition, solvatochromic and acid-base titration experiments were performed to verify the strength of intramolecular charge transfer within the whole molecules and the monohydrazone configuration for every bi-heterocyclic dye.

FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1/AMPK/\u03b21-integrin pathway

Highly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS. FR58P1a activates AMPK in a Sirt1-dependent fashion. Although the activation of Sirt1/AMPK axis by FR58P1a has a cyto-protective role, selectively inhibits fibronectin-dependent adhesion and migration in TNBC cells but not in non-tumoral MCF10A cells by decreasing β1-integrin at the cell surface. Prolonged exposure to FR58P1a triggers a metabolic reprograming in TNBC cells characterized by down-regulation of OXPHOS-related genes that promote cell survival but comprise their ability to migrate. Taken together, our results show that TNBC cell migration is susceptible to mitochondrial alterations induced by small molecules as FR58P1a, which may have therapeutic implications.

A Study about Regioisomeric Hydroquinones with Multiple Intramolecular Hydrogen Bonding.

A theoretical exploration about hydrogen bonding in a series of synthetic regioisomeric antitumor tricyclic hydroquinones is presented. The stabilization energy for the intramolecular hydrogen bond (IHB) formation in four structurally different situations were evaluated: (a) IHB between the proton of a phenolic hydroxyl group and an ortho-carbonyl group (forming a six-membered ring); (b) between the oxygen atom of a phenolic hydroxyl group and the proton of an hydroxyalkyl group (seven membered ring); (c) between the proton of a phenolic hydroxyl group with the oxygen atom of the hydroxyl group of a hydroxyalkyl moiety (seven-membered ring); and (d) between the proton of a phenolic hydroxyl group and an oxygen atom directly bonded to the aromatic ring in ortho position (five-membered ring). A conformational analysis for the rotation around the hydroxyalkyl substituent is also performed. It is observed that there is a correspondence between the conformational energies and the IHB. The strongest intramolecular hydrogen bonds are those involving a phenolic proton and a carbonyl oxygen atom, forming a six-membered ring, and the weakest are those involving a phenolic proton with the oxygen atom of the chromenone, forming five-membered rings. Additionally, the synthesis and structural assignment of two pairs of regioisomeric hydroquinones, by 2D-NMR experiments, are reported. These results can be useful in the design of biologically-active molecules.

ChemInform Abstract: Directing Group Assisted Copper‐Catalyzed Chemoselective O‐Arylation of Phenols and Enols Using Alkylbenzenes.

AbstractThe ortho carbonyl group in hydroxyarenes (I) is essential for the oxidative aroylation of the OH‐group with alkylbenzenes in the presence of tBu‐OOH as oxidant.

A novel synthesis of coumarins employing triphenyl(α-carboxymethylene)phosphorane imidazolide as a C-2 synthon

A novel one-pot synthesis of coumarins via intramolecular Wittig cyclization from the reaction of phenolic compounds containing ortho-carbonyl group and triphenyl(α-carboxymethylene)phosphorane imidazolide is described.

Novel Rh Catalysis in Cross-Coupling between Alkyl Halides and Arylzinc Compounds Possessing ortho-COX (X = OR, NMe2, or Ph) Groups

[reaction: see text] Rh-dppf was found to be an efficient catalyst for the cross-coupling between primary alkyl halides bearing beta-hydrogens and arylzinc compounds possessing carbonyl groups such as ester, amide, or ketone at the ortho position. Various functional groups such as ester, nitrile, or acyloxylate moieties on the halides were tolerated under the catalysis conditions. Arylzinc compounds free of ortho-carbonyl groups reacted well with ethyl 3-iodopropanoate, suggesting that the essential intramolecular interaction between carbonyl groups and Rh promotes the reductive elimination.

Redox cycling of o-naphthoquinones in yrypanosomatids : Superoxide and hydrogen peroxide production

β-Lapachone and structurally related lipophilic o-naphthoquinones, namely, CG 8-935, CG 9-442, CG 10-248 and mansonones A, C, E, and F, were investigated for redox cycling, production of reactive oxygen species, and cytotoxicity in the trypanosomatids Crithidia fasciculata and Leptomonas seymouri. Structural analysis of the assayed quinones indicated that a tricyclic structure, including a naphthalene ring, a 1,2 b or l,8 bc pyran ring, and two ortho-carbonyl groups were required for quinone activities. The contribution of oxygen radical production to quinone cytotoxicity was supported by: (a) spectroscopic observation of quinone redox cycling; (b) production of the semiquinone radical; (c) H 2O 2 and O 2 − production; (d) the effect of β-lapachone on thiol pools in C. fasciculata; (e) the effect of quinones on cell respiration; (f) Superoxide dismutase inactivation after incubation of C. fasciculata with CG 8-935; and (g) the effect of quinones on cell growth.

Pyrolysis of Aryl Azides. XIII. Conformational Effects on the Ability of Carbonyl as a Neighbouring Group

Our previous claim, that locking an ortho carbonyl group into a favourable conformation causes very large increases in the rate of thermolysis of aryl azides , has been reexamined. In 8-azido-5-methoxy-1-tetralone the rate advantage over an azide with a rotatable ortho acetyl group is estimated to be only 18-fold. Nevertheless, this factor is large enough to invalidate attempts to explain relative neighbouring group abilities on simple electronic effects alone. The very large rate increases we reported previously for 1-azidoacridin-g(10H)-one and 1-azidoanthracene-9,10-dione are partly due to favourable retention of conjugation in the transition state.

On the regioselectivity of the condensation of stabilized phosphoylids with 3-substituted phthalic anhydrides

Condensations of stabilized phosphorane 1 with 3-substituted phthalic anhydrides were investigated. The importance of various effects influencing regio- and stereoselectivity of these reactions is discussed. It is proposed that the oxygen atom on the substituents in position 3 can act as a Lewis base toward the electron-deficient phosphorus of the ylid. The resulting complexation stabilizes the transition state for the reaction at the ortho carbonyl group, thus offsetting the usual steric and "push" effects, which favour attack at the meta carbonyl function. Keywords: Wittig condensations, phthalic anhydrides, regioselectivity, stereoselectivity.

Fluorescence and Phosphorescence of Wool Keratin Excited by UV-A Radiation

Corrected fluorescence and phosphorescence spectra of wool keratin excited by UV-A radiation are presented. Some of the observed luminescence is believed to originate from N-formylkynurenine residues, which are photo-oxidation products of tryptophan residues. The positions of the spectral maxima of the fluorescence and phosphorescence arising from N-formylkynurenine residues indicate that there is hydrogen bonding between the ortho carbonyl group of N-formylkynurenine and the N-H group of a protein peptide linkage. The N-formylkynureninine residues also appear to be located principally in regions of low polarity.

Pyrolysis of aryl azides. IV. Neighbouring group effects by ortho carbonyl groups

The question of the mechanism by which ortho carbonyl groups enhance the rate of pyrolysis of aryl azides is examined. Rate measurements on sterically hindered 1-(2-azidophenyl)ethan-1-ones are consistent with the pericyclic mechanism proposed by Dyall and Kemp1 but not with the intramolecular 1,3-dipolar addition route put forward by Hall, Behr and Reed.2 A definitive test of mechanism is also provided by 1- azidoanthraquinone and 1-(2-azidophenyl)-2,2-dimethylpropan-1-for both of which the formation of a 1,3-dipolar adduct is precluded on steric grounds but the pericyclic process is not. At 393.2 K, these two azides pyrolyse 7385 and 61.7 times faster than phenyl azide, respectively.

Hydrogen Bonding in Organic Compounds. VIII. Aromatic Primary Amines with ortho-Carbonyl Groups

The NH stretching frequencies of the amine group in a number of aromatic primary amines with o-carbonyl groups have been studied as the fundamental and first overtone absorption bands, both before and after deuteration. Several correlations are established between functions of the vibration frequencies which seem to be related to the strengths of the hydrogen bonds that have been formed. These correlations, established for carbonyl as the acceptor, extend to some other classes of hydrogen bond acceptor. When bilateral hydrogen bonds are formed to two o-carbonyl groups the NH2 stretching frequencies do not conform to the equation of Bellamy and Williams. Further evidence in favour of the interpretation of the spectrum of 1-aminoanthraquinone given by Hambly and Bonnyman is offered. The preparation of 5-chloro-2-t-butylaniline is described and some further details of the spectra of anilines with tertiary butyl substituents are given.