Α-methyl Group Research Articles

Copper-promoted site-selective carbonylation of sp3 and sp2 C-H bonds with nitromethane.

Copper-promoted direct carbonylation of unactivated sp3 C-H and aromatic sp2 C-H bonds of amides was developed using nitromethane as a novel carbonyl source. The sp3 C-H functionalization showed high site-selectivity by favoring the C-H bonds of α-methyl groups. The sp2 C-H carbonylation featured high regioselectivity and good functional group compatibility. Kinetic isotope effect studies indicated that the sp3 C-H bond breaking step is reversible, whereas the sp2 C-H bond cleavage is an irreversible but not the rate-determining step. Control experiments showed that a nitromethyl intermediate should be involved in the present reaction.

ChemInform Abstract: Glycerol: A More Benign and Biodegradable Promoting Medium for Catalyst‐Free One‐Pot Multi‐Component Synthesis of Triazolo[1,2‐a]indazole‐triones.

The one-pot three component synthesis of triazolo[1,2-a]indazole-triones was conducted successfully under catalyst-free conditions in glycerol as a benign, nontoxic and biodegradable promoting medium. A broad range of substrates including aromatic aldehydes are condensed with carbonyl compounds possessing a reactive α-methylene group and urazole derivatives. All reactions are completed in short times and the products are obtained in good to excellent yields. Moreover, presented method was applied successfully to the large scale synthesis of title compounds.

Local Structure Contributions to Surface Tension of a Stereoregular Polymer.

We have used all-atom molecular dynamics (MD) simulations to calculate the surface tension of melt poly(methyl methacrylate) (PMMA) as a function of tacticity. Computation of surface tension using the Kirkwood-Buff approach required hundreds of nanoseconds of equilibration. The computed slopes of surface tension versus temperature are in very good agreement with reported experimental values. Using a rigorous treatment of the true interface, which takes into account the molecular roughness, we find that isotactic PMMA, in comparison to syndiotactic and atactic PMMA, shows a larger surface concentration of polar ester-methyl and carbonyl groups on the surface versus nonpolar α-methyl groups. A mechanistic hypothesis based on the helical nature of the isotactic PMMA chains, their relative flexibility, and their reported conformational energies is proposed to explain the trends in composition near the surface. We highlight here how surface composition and surface tension are controlled by both polarity and steric constraints imposed by tacticity.

Evaluating Ketoreductase Exchanges as a Means of Rationally Altering Polyketide Stereochemistry.

Modular polyketide synthases (PKSs) are multidomain multienzymes responsible for the biosynthesis in bacteria of a wide range of polyketide secondary metabolites of clinical value. The stereochemistry of these molecules is an attractive target for genetic engineering in attempts to produce analogues exhibiting novel therapeutic properties. The exchange of ketoreductase (KR) domains in model PKSs has been shown in several cases to predictably alter the configuration of the β-hydroxy functionalities but not of the α-methyl groups. By systematic screening of a broad panel of KR domains, we have identified two donor KRs that afford modification of α-methyl group stereochemistry. To the best of our knowledge, this provides the first direct in vivo evidence of KR-catalyzed epimerization. However, none of the introduced KRs afforded simultaneous alteration of methyl and hydroxy configurations in high yield. Therefore, swapping of whole modules might be necessary to achieve such changes in stereochemistry.

Dual stimuli-responsive homopolymers: Thermo- and photo-responsive properties of coumarin-containing polymers in organic solvents

Thermoresponsive properties of poly(7-methacryloyloxycoumarin) (P1a) and its derivatives as homopolymers containing a photoreactive coumarin unit were systematically investigated. P1a showed a lower critical solution temperature (LCST)-type phase separation in dichloromethane, chloroform, and 1,1,2-trichloroethane. The temperature producing a 50% transmittance (Tc) of 0.1wt% P1a in distilled chloroform was 26°C, while the Tc value decreased to 21°C in deuterated chloroform i.e., the deuterium isotope effect. The Tc values in chloroform were adjustable from 28 to 57°C by the introduction of the ethyleneoxy spacer and the substitution of α-methyl group by hydrogen. While the polymers containing 4-substituted coumarins were soluble in chloroform and dichloromethane from 0°C to their boiling points. In the distilled chloroform solution, the coumarin units in P1a underwent a [2+2] cycloaddition and the transmittance at 500nm decreased from 98% to 29% at 25°C by a 180-s photoirradiation (326mJ/cm2, emission band at 365nm).

Direct Aerobic Carbonylation of C(sp²)-H and C(sp³)-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source.

The direct carbonylation of aromatic sp(2) and unactivated sp(3) C-H bonds of amides was achieved via nickel/copper catalysis under atmospheric O2 with the assistance of a bidentate directing group. The sp(2) C-H functionalization showed high regioselectivity and good functional group compatibility. The sp(3) C-H functionalization showed high site-selectivity by favoring the C-H bonds of α-methyl groups over those of the α-methylene, β- or γ-methyl groups. Moreover, this reaction showed a predominant preference for functionalizing the α-methyl over α-phenyl group. Mechanistic studies revealed that nickel/copper synergistic catalysis is involved in this process.

Pyridine-enabled copper-promoted cross dehydrogenative coupling of C(sp2)-H and unactivated C(sp3)-H bonds.

The pyridine-enabled cross dehydrogenative coupling of sp2 C-H bonds of polyfluoroarenes and unactivated sp3 C-H bonds of amides was achieved via a copper-promoted process with good functional group compatibility. This reaction showed great site-selectivity by favoring the sp2 C-H bonds ortho to two fluoro atoms of arenes and the sp3 C-H bonds of α-methyl groups over those of the α-methylene, β- or γ-methyl groups of the aliphatic amides. Mechanistic studies revealed that sp3 C-H bond cleavage is an irreversible but not the rate-determining step, and the sp2 C-H functionalization of arenes appears precedent to the sp3 C-H functionalization of amides in this process.

Reactions of N-alkylhydrazones of aliphatic ketones

For the first time data concerning the reactions of N-alkylhydrazones of aliphatic ketones have been systematized. The possible reaction centres of hydrazones and the main lines of attack for electrophilic and nucleophilic reagents have been distinguished. Differences in the reactivity of N-alkyl and N-arylhydrazones have been studied. The types of tautomerism of hydrazones and their impact on the reactivity of these compounds have been considered. Most reactions occurring on the sp2-hybridized carbon atom lead to formation of azocompounds, which are generally aliphatic radical sources or initiators of radical processes. The interaction of hydrazones with oxidising reagents leading to the corresponding bisazocompounds has been studied. For a number of N-acylation hydrazones the ring-chain tautomerism has been described, as a result these compounds exist in cyclic and acyclic forms. The general methods for construction of heterocyclic compounds based on N-alkylhydrazones of aliphatic ketones due to cyclization of hydrazones with bis-functional reagents on both nitrogen atoms, as well as the nitrogen atom and the carbon atom have been considered. Hydrazone-enhyidrazine tautomerism is inherent to hydrazones of aliphatic ketones with the α-methylene group; it causes a simultaneous attack of dielectrophiles on the sp3-hybridized carbon atom and the nitrogen atom of hydrazone and can be used to construct derivatives of pyridazine and pyrazole, and the use of compounds of phosphorus and of silicon as dielectrophiles results in formation of phosphodiazoles and silapyrazolines, respectively. Reduction reactions for C=N bond of N-alkylhydrazones of aliphatic ketones have been studied.

Molecular structure of poly(methyl methacrylate) surface II: Effect of stereoregularity examined through all-atom molecular dynamics.

Utilizing all-atom molecular dynamics (MD), we have analyzed the effect of tacticity and temperature on the surface structure of poly(methyl methacrylate) (PMMA) at the polymer-vacuum interface. We quantify these effects primarily through orientation, measured as the tilt with respect to the surface normal, and the surface number densities of the α-methyl, ester-methyl, carbonyl, and backbone methylene groups. Molecular structure on the surface is a complex interplay between orientation and number densities and is challenging to capture through sum frequency generation (SFG) spectroscopy alone. Independent quantification of the number density and orientation of chemical groups through all-atom MD presents a comprehensive model of stereoregular PMMA on the surface. SFG analysis presented in part I of this joint publication measures the orientation of molecules that are in agreement with MD results. We observe the ester-methyl groups as preferentially oriented, irrespective of tacticity, followed by the α-methyl and carbonyl groups. SFG spectroscopy also points to ester-methyl being dominant on the surface. The backbone methylene groups show a very broad angular distribution, centered along the surface plane. The surface number density ratios of ester-methyl to α-methyl groups show syndiotactic PMMA having the lowest value. Isotactic PMMA has the highest ratios of ester- to α-methyl. These subtle trends in the relative angular orientation and number densities that influence the variation of surface structure with tacticity are highlighted in this article. A more planar conformation of the syndiotactic PMMA along the surface (x-y plane) can be visualized through the trajectories from all-atom MD. Results from conformation tensor calculations for chains with any of their segments contributing to the surface validate the visual observation.

The role of cations in homogeneous succinoylation of mulberry wood cellulose in salt-containing solvents under mild conditions

The role of two cations [tetraethylammonium+ (TEA+) and tetrabutylammonium+ (TBA+)] in the homogeneous succinoylation of mulberry wood (MW) cellulose in dimethyl sulfoxide (DMSO)/tetraethylammonium chloride (TEACl) and DMSO/tetrabutylammonium fluoride (TBAF) was investigated using the intrinsic viscosity and two-dimensional nuclear Overhauser effect NMR spectroscopy (2D NOESY). The intrinsic viscosity of MW cellulose solution strongly depends on the salt dosage for both TEACl and TBAF, indicating that the increase in the hydrodynamic size of cellulose chains was caused by the interactions between salts and cellulose, which promotes the solvation process of cellulose in solution. Two-dimensional NOESY spectra reveal that cations bind to cellobiose in DMSO by the interactions between α-methylene groups of TEA+ (or TBA+) and C1/C1′ groups of cellobiose, and the intensities of the respective crosspeaks increase with increasing TEACl dosage from 5 to 10 mg/ml, but no change was present with TBAF at the same concentration range. Taking cellobiose as a model compound for cellulose, it can be expected that TEA+ (or TBA+) and cellulose form polyelectrolyte-like complexes. The degree of substitution (DS) of homogeneous succinoylation of MW cellulose benefits from the interactions between TEA+ (or TBA+) and cellulose evidenced by FT-IR spectra and CP/MAS 13C NMR spectra. The DS of the succinylated cellulose declines at TBAF concentrations higher than 11 wt% probably because of the steric hindrance effects of TBA+.

Molecular structure of poly(methyl methacrylate) surface. I. Combination of interface-sensitive infrared-visible sum frequency generation, molecular dynamics simulations, and ab initio calculations.

The chemical composition and molecular structure of polymeric surfaces are important in understanding wetting, adhesion, and friction. Here, we combine interface-sensitive sum frequency generation spectroscopy (SFG), all-atom molecular dynamics (MD) simulations, and ab initio calculations to understand the composition and the orientation of chemical groups on poly(methyl methacrylate) (PMMA) surface as a function of tacticity and temperature. The SFG spectral features for isotactic and syndiotactic PMMA surfaces are similar, and the dominant peak in the spectra corresponds to the ester-methyl groups. The SFG spectra for solid and melt states are very similar for both syndiotactic and isotactic PMMA. In comparison, the MD simulation results show that both the ester-methyl and the α-methyl groups of syndiotactic-PMMA are ordered and tilted toward the surface normal. For the isotactic-PMMA, the α-methyl groups are less ordered compared to their ester-methyl groups. The backbone methylene groups have a broad angular distribution and are disordered, independent of tacticity and temperature. We have compared the SFG results with theoretical spectra calculated using MD simulations and ab initio calculations. Our analysis shows that the weaker intensity of α-methyl groups in SFG spectra is due to a combination of smaller molecular hyperpolarizability, lower ordering, and lower surface number density. This work highlights the importance of combining SFG spectroscopy with MD simulations and ab initio calculations in understanding polymer surfaces.

ChemInform Abstract: Reactions of Enaminones and Related Compounds with N,N‐Dimethylacetamide Dimethyl Acetal. A Simple One‐Pot Metal‐Free Synthesis of Polysubstituted Benzene Derivatives.

Abstract Herein a simple one-pot metal-free synthesis of alkyl-, aryl-, heteroaryl- and alkoxycarbonyl substituted 1,3-bis(dimethylamino)benzene derivatives is described. The products were prepared from the corresponding methyl ketones or compounds with an α-methylene group in regard to the carbonyl group, using N,N-dimethylacetamide dimethyl acetal (DMADMA) as the reagent.

Synthesis of aromatic carbamates derivatives with a chromen-2-one fragment

Condensation of methyl N-(3-hydroxyphenyl)carbamate with ethyl trifluoromethylacetoacetate, 2-methoxyethyl acetoacetate in the presence of conc. sulfuric acid, and also with acetonedicarboxylic acid formed in situ from citric acid under the action of conc. sulfuric acid afforded chromene derivatives. The esterification of 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}acetic acid with methanol in the presence of TsOH provided the corresponding ester. The oxidation of its α-methylene group with selenium dioxide led to the formation of methyl 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}-2-oxo-acetate entering into a condensation with o-phenylenediamine resulting in a derivative with a dihydroquinoxaline fragment. The reaction of phenyl N-(4-formylphenyl)carbamate with 3-acetyl-2H-chromen-2-one in butanol in the presence of catalytic quantity of piperidine and acetic acid furnished 4-[(E)-3-oxo-2H-chromen-3-yl)-1-propenyl]phenyl N-phenylcarbamate.

Peptidophospholipids: Synthesis, phospholipase A2 catalyzed hydrolysis, and application to development of phospholipid prodrugs

New phospholipid analogues incorporating sn-2-peptide substituents have been prepared to probe the fundamental structural requirements for phospholipase A2 catalyzed hydrolysis of PLA2-directed synthetic substrates. Two structurally different antiviral oligopeptides with C-terminal glycine were introduced separately at the sn-2-carboxylic ester position of phospholipids to assess the role of the α-methylene group adjacent to the ester carbonyl in allowing hydrolytic cleavage by the enzyme. The oligopeptide-carrying phospholipid derivatives were readily incorporated into mixed micelles consisting of natural phospholipid (dipalmitoyl phosphatidylcholine, DPPC) and Triton X-100 as surfactant. Hydrolytic cleavage of the synthetic peptidophospholipids by the phospholipase A2 occurred slower, but within the same order of magnitude as the natural substrate alone. The results provide useful information toward better understanding the mechanism of action of the enzyme, and to improve the design and synthesis of phospholipid prodrugs targeted at secretory PLA2 enzymes.

Investigation of a Nanocomposite of 75 wt % Poly(methyl methacrylate) Nanoparticles with 25 wt % Poly(ethylene oxide) Linear Chains: A Quasielatic Neutron Scattering, Calorimetric, and WAXS Study

We have investigated the thermal behavior, local structure, and dynamics in a system where 25 wt % PEO [poly(ethylene oxide)] linear chains are mixed with 75 wt % PMMA [poly(methyl methacrylate)] soft nanoparticles. Calorimetric and wide-angle X-ray scattering experiments point to a weak penetration of the PEO chains in the nanoparticles, qualifying the mixture as a nanocomposite. Quasi-elastic neutron scattering (QENS) experiments on partially deuterated samples has selectively revealed the component dynamics in the system. The α-methyl group dynamics of PMMA, which fall within the QENS time scale in the temperature range investigated, are hardly affected by the presence of PEO except for hints of a more heterogeneous environment in the nanocomposite than in bulk PMMA. The effects on the dynamics of PEO are more interesting. The observation of dynamics in the microseconds range for the PEO component of the nanocomposite at temperatures at which the calorimetric experiments indicate the freezing of its segmental relaxation provides evidence for confined dynamics below the main glass transition of the mixture—attributable to the effective glass transition of the slow component. A parallel study on an equivalent blend of PEO and linear PMMA chains shows that these effects are independent of the topology of the PMMA. However, well above the effective glass transition of the slow component, the dynamics of PEO differ in both systems. In the linear blend, PEO segments move with the typical features of supercooled polymers in metastable equilibrium, while in the nanocomposite PEO dynamics exhibit an anomalously strong deviation from Gaussian behavior. This deviation grows with increased mobility of the nanoparticles. PEO segments are seemingly trapped in effective cages imposed by the nanoparticles for a very long time—more than 2 orders of magnitude longer than in bulk or when surrounded by linear PMMA chains—before the subdiffusive process leading to segmental relaxation sets in. We speculate that local loops in the surface of the nanoparticles may play an important role in this trapping mechanism.

ChemInform Abstract: Discovery and Exploitation of AZADO: The Highly Active Catalyst for Alcohol Oxidation

AbstractReview: 67 refs.

Effect of Acrylate Constituent Units on the COD Removal Rates of Acrylate Copolymers for Warp Sizing

The aerobic biodegradability of acrylate copolymers for warp sizing was studied using the shaking-bottle incubating method for their COD removal rates after being cultivated for 30 days. Influences of acrylate unit chemical structure, including the alkyl chain length of the ester group, α-methyl group, and molar content of acrylate units, on the biodegradability of the sizes were investigated. The acrylate copolymers were prepared via free radical copolymerization of acrylates with acrylic acid in ethanol. The biodegradability of acrylate copolymers strongly depended on the structure and molar content of the acrylate units. After being cultivated for 30 days, poly(MA-co-AA) was biodegraded substantially and the COD removal rate exceeded 50%. However, the biodegradability of poly(BMA-co-AA) was poor and the removal rate was 10%.

Reactions of enaminones and related compounds with N,N-dimethylacetamide dimethyl acetal. A simple one-pot metal-free synthesis of polysubstituted benzene derivatives

Herein a simple one-pot metal-free synthesis of alkyl-, aryl-, heteroaryl- and alkoxycarbonyl substituted 1,3-bis(dimethylamino)benzene derivatives is described. The products were prepared from the corresponding methyl ketones or compounds with an α-methylene group in regard to the carbonyl group, using N,N-dimethylacetamide dimethyl acetal (DMADMA) as the reagent.

α-Alkyl cysteine-coated gold nanoparticles: effect of Cα-tetrasubstitution on colloidal stability

In this work, we report the synthesis of new α-methyl l-cysteine-coated gold nanoparticles (average core diameter ca. 3 nm) and the remarkable enhancement of their aqueous stability against aggregation in comparison with the nanoparticles capped with unmodified l-cysteine under the same experimental conditions. Atomistic molecular dynamics simulations of model gold surfaces capped with l-cysteine or α-methyl l-cysteine revealed important differences in both the organization of the amino acids with respect to the surface and their spontaneous assembly with neighboring molecules. These differences, which are originated by the introduction of the α-methyl group in the amino acid, could be associated with the observed increase in stability and dispersibility of the composites in aqueous solutions at different pH values and ionic concentrations.

Microscopic Dynamics in Nanocomposites of Poly(ethylene oxide) and Poly(methyl methacrylate) Soft Nanoparticles: A Quasi-Elastic Neutron Scattering Study

We have selectively studied the component dynamics in a nanocomposite where 25 wt % of PMMA [poly(methyl methacrylate)] soft nanoparticles (SNPs) are dispersed in PEO [poly(ethylene oxide)] by means of quasi-elastic neutron scattering (QENS) experiments on partially deuterated samples. We have covered a time range from subpico to nanosecond regime and a momentum transfer range 0.5 ≤ Q ≤ 1.8 Å–1 by combining three different spectrometers. Complementary diffraction measurements with polarization analysis have facilitated the data analysis, by providing the coherent and incoherent contributions to the scattered intensities. Regarding the SNPs, the α-methyl group dynamics of PMMA—to which the QENS experiments are most sensitive in the temperature range investigated—turn to be faster than in bulk PMMA. This could be due to the plasticization effect induced by the fast PEO chains. In fact, calorimetric measurements show the coexistence of two glass-transition temperatures in the system, associated with each of the components, but modified with respect to those in the neat materials. The QENS results on the PEO component for large length scales reveal Rouse-like dynamics slowed down by the presence of the SNPs with respect to that in the bulk. With decreasing temperature indications for distributed chain mobilities are found, probably due to the enhancement of the concentration fluctuations. At local scales, deviations from Rouse-like dynamics occur, that could be attributed to an extra-friction related to the local potentials, and also to non-Gaussian effects arising from the discrete character of the elementary processes underlying the subdiffusive dynamics in the polymer. The deviations take place in a very similar way as in bulk PEO.