Ortho Alkylation Research Articles

N-Chlorophthalimide as a mild and efficient chlorination reagent in the Gassman ortho alkylation of aromatic amines. Synthesis of 3-(methylthio)oxindoles

A practical modification of the Gassman 3-(methylthio)oxindole synthesis is reported. In our method, substituted anilines and 2-(methylthio)acetamide were reacted under mild reaction conditions, in the presence of N-chlorophthalimide as a chlorinating agent to give α-amidosulfides, which, in the next step of the process, were cyclized to give 3-(methylthio)oxindoles. The method was successfully applied for the synthesis of the key intermediate, 2-(2-amino-3-benzoylphenyl)-2-(methylthio)acetamide, in the process of the preparation of nepafenac, a commonly used ophthalmic drug.

Effect of the ortho alkylation of perylene bisimides on the alignment and self-assembly properties.

The effect of the ortho alkylation of perylene bisimides on the alignment and self-assembly properties has been studied. It was found that the dichroic properties of perylene bisimides in a liquid crystal host can be reversed with a single synthetic step by ortho alkylation. Furthermore, a solvent-induced growth of ultralong organic n-type semiconducting fibrils from non-ortho-alkylated perylene bisimide was observed. Ortho substitution of the perylene bisimide core alters the mode of fibrillar growth, leading to isotropic crystallization.

ChemInform Abstract: Cobalt‐Catalyzed ortho Alkylation of Aromatic Imines with Primary and Secondary Alkyl Halides.

AbstractThe stereochemical outcome of the reaction of secondary alkyl halides like (IX) suggest that the present reaction involves single‐electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical.

Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives

Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and 1H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the ΔG≠ values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond- related conformations.

Catalytic alkylation of cresols with propanol-1

Study of the reaction of alkylation of ortho-, meta-, and para-cresols with propanol-1 in the presence of ferrite cobalt and manganese catalysts is reported. The effect of the catalyst composition and reaction conditions on the yield and isomeric composition of the resulting propyl derivatives of cresol was examined and the main and side conversions occurring in the catalysis were determined.

Electron impact, electron capture negative ionization and positive chemical ionization mass spectra of organophosphorus flame retardants and plasticizers

Phosphate esters are important commercial products that have been used both as flame retardants and as plasticizers. To analyze these compounds by gas chromatographic mass spectrometry, it is important to understand the mass spectra of these compounds using various ionization modes. This paper is a systematic overview of the electron impact (EI), electron capture negative ionization (ECNI) and positive chemical ionization (PCI) mass spectra of 13 organophosphate esters. These data are useful for developing and optimizing analytical measurements. The EI spectra of these 13 compounds are dominated by ions such as H4 PO4 (+) , (M - Cl)(+) , (M - CH2 Cl)(+) or (M)(+) depending on specific chemical structures. The ECNI spectra are generally dominated by (M - R)(-) . The PCI spectra are mainly dominated by the protonated molecular ion (M + H)(+) . The branching of the alkyl substituents, the halogenation of the substituents and, for aromatic phosphate esters, ortho alkylation of the ring are all significant factors controlling the details of the fragmentation processes. EI provides the best sensitivity for the quantitative measurement of these compounds, but PCI and ECNI both have considerable qualitative selectivity.

Cobalt-Catalyzed Ortho Alkylation of Aromatic Imines with Primary and Secondary Alkyl Halides

We report here cobalt-N-heterocyclic carbene catalytic systems for the ortho alkylation of aromatic imines with alkyl chlorides and bromides, which allows the introduction of a variety of primary and secondary alkyl groups at room temperature. The stereochemical outcomes of the reaction of secondary alkyl halides suggest that the present reaction involves single-electron transfer from a cobalt species to the alkyl halide to generate the corresponding alkyl radical. A cycloalkylated product obtained by this method can be transformed into unique spirocycles through manipulation of the directing and cycloalkyl groups.

Energetics of Nonbonded Ortho Interactions in Alkylbenzenes

The gas-phase enthalpies of formation for a set of ortho-substituted alkylbenzenes were obtained from CCSD(T*)-F12 and W1-F12 calculations. Most values are in keeping with available experimental data. The gas-phase enthalpies of formation of 1-ethyl-2-propylbenzene, 1-ethyl-2-isopropylbenzene, 1,2-diisopropylbenzene, 1,2,4-triethylbenzene, and 1,2,4,5-tetraethylbenzene, for which no experimental data are available, were determined as -46.0, -46.8, -68.7, -76.9, and -116.8 kJ mol(-1), respectively (estimated error bar ±4 kJ mol(-1)). The whole set of experimental and theoretical values are in good agreement with the estimates obtained using the extended Laidler bond additivity (ELBA) method. This agreement supports the approximation used in ELBA that interactions between ortho alkyl groups (other than tertiary alkyl groups) have roughly the same magnitude as a methyl-methyl interaction.

Mechanistic Investigation on Scandium-Catalyzed C–H Addition of Pyridines to Olefins

This paper reports computational studies on the ortho alkylation of pyridines via C–H addition to olefins catalyzed by cationic half-sandwich rare-earth alkyl species. A detailed mechanism concerning the generation of catalytically active species and C–H addition has been computationally investigated at the molecular and electronic levels. The results support the mechanism based on experiments, which involves the initial generation of a metal pyridyl active species, followed by the coordination and insertion of an olefin and the subsequent pyridine C–H activation by a metal–carbon bond. The o-methyl sp3 C–H activation product of α-picoline has been also calculated, and the results suggest that the sp3 C–H activation product mainly results from the conversion of the sp2 C–H activation product of α-picoline rather than from the direct reaction of the cationic species (η5-C5Me5)Sc(CH2C6H4NMe2-o)+ with α-picoline, and such a conversion is reversible. The reaction rate of the whole process is controlled by the...

ChemInform Abstract: Cobalt—Phenanthroline Catalysts for the ortho Alkylation of Aromatic Imines under Mild Reaction Conditions.

AbstractCobalt—phenanthroline catalysts are successfully applied in the ortho‐alkylation of aromatic imines with various olefins.

Cobalt–Phenanthroline Catalysts for the ortho Alkylation of Aromatic Imines under Mild Reaction Conditions

Mild mannered: Cobalt catalysts complexed with phenanthroline-type ligands and activated with Grignard reagents serve as inexpensive and effective catalysts for the ortho alkylation of aromatic imines with a variety of olefins (see scheme). The new catalytic systems feature remarkably mild reaction conditions for CH bond activation and functionalization.

Steric Effect on the Formation of 3H-Azepine Derivatives from o-Alkylphenylnitrene and Alcohol as a Nucleophilic Media

The steric influence of the ortho-alkyl group of the nitrobenzene substrate and the nucleophile on the reaction pathway is investigated.

ChemInform Abstract: Symmetrical and Unsymmetrical 2,6-Dialkyl-1,1′-biaryls by Combined Catalysis of Aromatic Alkylation via Palladacycles and Suzuki-Type Coupling.

The title compounds are made readily accessible by a catalytic procedure, occurring under mild conditions, based on palladium-mediated ortho alkylation of aromatic iodides with alkyl bromides followed by reaction with arylboronic acids.

Tampering with Molecular Cohesion in Crystals of Hexaphenylbenzenes

Hexaphenylbenzene (HPB) and analogous compounds have properties of broad utility in science and technology, including conformationally well-defined molecular structures, high thermal stability, high HOMO-LUMO gaps, little self-association, inefficient packing, and high solubilities. Previous structural studies of HPB and its analogues have revealed persistent involvement of the central aromatic ring in strong C-H...pi interactions. These interactions can be blocked by adding simple ortho alkyl substituents to the peripheral phenyl groups. Comparison of the structures of HPB and a series of ortho-substituted derivatives has shown systematic changes in molecular cohesion and packing, as measured by packing indices, densities, solubilities, temperatures of sublimation, melting points, and ratios of H...H, C...H, and C...C contacts. These results illustrate how crystal engineering can guide the search for improved materials by identifying small but telling molecular alterations that thwart established patterns of association.

Salicylaldiminato-based cobalt(III)-, iron(III)-, and chromium(III)/methyl aluminoxane catalyst systems for polymerization of t-butyl acrylate

A new series of penta-coordinated Co(III)-, Fe(III)-, and Cr(III)- complexes (6–10) bearing N-salicylidineisopropylaniline and sodium N-(4-sulfonitsalicylidineisopropyl-aniline) ligands has been synthesized and utilized, after activation with methyl aluminoxane, as catalysts for the polymerization of tert-butylacrylate (t-BA). High molar mass P(t-BA) polymers with very low molecular weight distributions were produced (M w/M n = 1.06–1.09). Cobalt- and chromium-based precatalysts showed higher activity towards the polymerization reaction than those of the iron complexes. The presence of sulfonated groups on the para position of the aryl group in the backbone of the ligand decreases the catalytic activity of the complexes. The ortho alkyl substituents on the aryl groups of the ligand have a favorable influence on the polymerization activity compared to the alkyl-free analogue (11).

Kinetics of reductive alkylations of phenylenediamines: Influence of substrates isomeric structure

Reductive alkylation of ortho-, meta- and para-phenylenediamines (PDAs) with methyl ethyl ketone (MEK) has been studied in a semi-batch slurry reactor in the presence of a commercial 3% Pt/Al 2O 3 catalyst. It was observed that the PDA isomers differ remarkably from each other in their activity in reductive alkylation and product distribution. The activity was found to decrease in the following order: PPDA>OPDA>MPDA. To understand the substrate structure–activity correlation, the homogeneous equilibrium reactions involved in the alkylation step and the overall catalytic reactions were studied separately. Kinetics of reductive alkylation of PDAs with MEK as a solvent and alkylating agent with 3% Pt/Al 2O 3 catalyst was studied in a semi-batch slurry reactor over a temperature range of 373–453 K and pressure range of 2.07–6.21 MPa. Semi-batch slurry reactor models were developed and kinetic parameters were estimated by fitting the integral batch reactor data at different temperatures to understand the influence of different reaction steps on the activity and selectivity of different products.

A Study of Dynamic Interfacial Properties as Related to Foaming Properties of Sodium 2,5-dialkyl Benzene Sulfonates

In this article, foaming properties and dynamic interfacial properties of a series of sodium 2,5-dialkyl benzene sulfonates in aqueous solutions were carried out to elucidate the relationship between foaming properties and dynamic interfacial properties. The properties of foams generated from bubbling air through different surfactant solutions were measured using a modified Bikerman device. The dynamic surface tension and surface dilational elasticity were obtained from an image analysis technique based on the oscillating bubble method. The surfactants molecular adsorption at the air/water interface was introduced with Rosen empirical equation and the rate of adsorption was determined from measurements of the dynamic surface tension. The surfactant with the longest alkyl chain shows the lowest dynamic surface activity, which lead to the lowest foam volume. The short ortho straight alkyl chain has little effect on the arrangement of molecules at the interface and the foam stability changes a little with the changing of the ortho alkyl chain length. The foam stability is correlated with both the higher surface dilational elasticity and the larger surface monolayer strength.

Changes in the Isotropic Shielding of the17O Nucleus upon Torsion in Terminal Oxygen Systems: A Computational Study on Their Origin

We are presenting a computational study on the isotropic shielding, charge, and orbital contributions to the shielding of oxygen in benzaldehydes (Ar-CHO), nitrobenzenes (Ar-NO2), phenyl isocyanates (Ar-NCO), anilides (Ar-NHCOCH3), and N-sulfinylamines (Ar-NSO). In particular, changes upon ortho substitution of the aromatic ring and upon torsion of the unsubstituted parent molecules are examined. The experimentally observed changes in (17)O chemical shift, be they upfield or downfield, upon substitution by ortho-alkyl groups are reproduced well by the calculations. Relaxed torsional scans of the parent systems reveal that (a) charges change as expected from resonance arguments and (b) changes in isotropic shielding are monotonic and in line with changes upon substitution, with N-sulfinylaniline as an exception. In general, the changes in isotropic shieldings are explained in terms of changes in molecular orbitals, their energies, and relative alignments, whose mixing is magnetically active. Thus, for example, the observed deshielding of (17)O upon methyl substitution and upon torsion of benzaldehyde is mainly caused by a contribution from the pi-type oxygen lone pair, yet how these contributions change is fundamentally different. As a consequence, the experimentally observed downfield shift upon methyl substitution cannot be interpreted to imply a change in torsion angle between the phenyl ring and the aldehyde group. For N-sulfinylaniline, the consecutive downfield shifts upon methyl and tert-butyl substitution and the associated changes in torsion angle are in contrast to the 45 degrees maximum in isotropic shielding that is determined from a relaxed torsional scan.

An RCM Based Approach to (.+‐.)‐Herbertene‐1,14‐diol and (.+‐.)‐Tochuinyl Acetates.

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Cyclodimerization of Alkynes with Phosphine-Free Ruthenium Carbene Complexes: Carbene Consumption by a Shunted Alkyne Oligomerization

A new cyclodimerization of ruthenium carbenes and alkynes is reported. The cyclodimerization produces substituted cyclopentadienes and consumes the carbene complex. Cyclodimerization of alkynes is predominant at low alkene concentrations and was found to be competitive with enyne metathesis. The presence of the ortho alkyl ether in the ruthenium carbene complex appears to be a critical determinant for the formation of cyclopentadienes. At higher alkene concentration, the observed cyclodimerization can be suppressed, favoring enyne metathesis.