Ethyl Substituents Research Articles

First‐principles based group additivity values for thermochemical properties of substituted aromatic compounds

A set of 7 Benson group additive values (GAV) together with 15 correction terms for non‐nearest neighbor interactions (NNI) is developed to calculate the gas phase standard enthalpies of formation, entropies and heat capacities of monocyclic aromatic compounds containing methyl, ethyl, vinyl, formyl, hydroxyl, and methoxy substituents. These GAVs are obtained through least squares regression of a database of thermodynamic properties of 143 molecules, calculated at the post‐Hartree–Fock G4 composite method. Out of the 15 NNIs, which account for several well‐known substituent effects in aromatic molecules, 13 have been determined for the first time. All but two group additively calculated standard enthalpies of formation agree within 4 kJ mol−1. The entropies and the heat capacities generally deviate less than 4 J mol−1 K−1 from the ab initio results. Natural bond orbital analysis is utilized to identify the underlying causes of the observed NNIs. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3858–3870, 2015

Active-Site Engineering of ω-Transaminase for Production of Unnatural Amino Acids Carrying a Side Chain Bulkier than an Ethyl Substituent

ω-Transaminase (ω-TA) is a promising enzyme for use in the production of unnatural amino acids from keto acids using cheap amino donors such as isopropylamine. The small substrate-binding pocket of most ω-TAs permits entry of substituents no larger than an ethyl group, which presents a significant challenge to the preparation of structurally diverse unnatural amino acids. Here we report on the engineering of an (S)-selective ω-TA from Ochrobactrum anthropi (OATA) to reduce the steric constraint and thereby allow the small pocket to readily accept bulky substituents. On the basis of a docking model in which L-alanine was used as a ligand, nine active-site residues were selected for alanine scanning mutagenesis. Among the resulting variants, an L57A variant showed dramatic activity improvements in activity for α-keto acids and α-amino acids carrying substituents whose bulk is up to that of an n-butyl substituent (e.g., 48- and 56-fold increases in activity for 2-oxopentanoic acid and L-norvaline, respectively). An L57G mutation also relieved the steric constraint but did so much less than the L57A mutation did. In contrast, an L57V substitution failed to induce the improvements in activity for bulky substrates. Molecular modeling suggested that the alanine substitution of L57, located in a large pocket, induces an altered binding orientation of an α-carboxyl group and thereby provides more room to the small pocket. The synthetic utility of the L57A variant was demonstrated by carrying out the production of optically pure L- and D-norvaline (i.e., enantiomeric excess [ee]>99%) by asymmetric amination of 2-oxopantanoic acid and kinetic resolution of racemic norvaline, respectively.

Crystal structure of trans-1-{2-[4-(di-methyl-amino)-phen-yl]eth-yl}-4-[2-(pyren-1-yl)eth-yl]cyclo-hexa-ne.

The title compound, C34H37N, is a pyrene derivative in which the pyrene ring system is linked to an ethyl­cyclo­hexane unit which, in turn, carries a [4-(di­methyl­amino)­phen­yl]ethyl substituent in the para position. The central cyclo­hexane ring has a chair conformation, with the exocyclic C—C bonds in equatorial orientations. The benzene ring is inclined to the mean plane of the pyrene ring system [maximum deviation = 0.038 (4) Å] by 14.84 (15)°. In the crystal, mol­ecules are linked by C—H⋯π inter­actions, forming chains propagating along [010]. The crystal was refined as a non-merohedral twin [domain ratio = 0.9989 (4):0.0011 (4)].

Synthesis of traditional and ionic polymethacrylates by anion catalyzed group transfer polymerization

ABSTRACTThe hydrophobic ionic liquid 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide was successfully used as solvent in group transfer polymerization of traditional methacrylates (methyl methacrylate, n‐butyl methacrylate, and benzyl methacrylate) and of ionic liquid methacrylates (ILMAs). This demonstrates that this ionic liquid makes reaction conditions, which do not require the use of ultra‐dried solvents. The ILMAs were N‐[2‐(methacryloyloxy)ethyl]‐N,N‐dimethyl‐N‐alkylammonium bis(trifluoromethylsulfonyl)imides bearing methyl, ethyl, propyl, butyl, or hexyl substituents. Increasing size of the alkyl substituent at the cation results in decreasing glass transition temperature in case of both ionic liquid methacrylates and polymers derived of them. Furthermore, the glass transition temperature is significantly higher for these polymers compared with the ionic liquid methacrylates, and the effect of glass transition temperature reduction with increasing size of the alkyl substituent is stronger for the polymers. A mechanism was proposed explaining the catalytic function of the ionic liquid used as solvent for polymerization. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2849–2859

All Poly(ionic liquid)-Based Block Copolymers by Sequential Controlled Radical Copolymerization of Vinylimidazolium Monomers

The organometallic-mediated radical polymerization (OMRP) of N-vinyl-3-alkylimidazolium-type monomers, featuring the bis(trifluoromethylsulfonyl)imide counteranion (Tf2N–), in the presence of Co(acac)2 as controlling agent, is reported. Polymerizations of monomers with methyl, ethyl, and butyl substituents are fast, reaching high monomer conversion in ethyl acetate as solvent at 30 °C, and afford structurally well-defined hydrophobic poly(ionic liquid)s (PILs) of N-vinyl type. Block copolymer synthesis is also achieved by sequential OMRP of N-vinyl-3-alkylimidazolium salts carrying different alkyl chains and different counteranions (Tf2N– or Br–). These block copolymerizations are carried out at 30 °C, either under homogeneous solution in methanol or in a biphasic medium consisting of a mixture of ethyl acetate and water. Unprecedented PIL-b-PIL block copolymers are thus prepared under these conditions. However, anion exchange occurs at the early stage of the growth of the second block. Finally, diblock c...

Effect of alkyl chain on the NLO property of nonylphenol isomers: a DFT study

Density functional theory (DFT) method was employed to study the nonlinear optical (NLO) response of the nonylphenol isomers with different alkyl substituents (methyl, ethyl, propyl, and isopropyl). The linear alkyl chain (hyperpolarizability, β T) and alkyl group aggregation (Hyper Rayleigh scattering hyperpolarizability, β HRS) in nonylphenol isomer has a strong positive influence on the NLO property. Among all the substituents, the methyl dominated alkyl chain nonylphenol isomers are strong NLO materials due to their large polarizability and hyperpolarizability values compared to that of urea/phenol. The absorption spectra obtained from TD-DFT study suggest that the absorption bands are shifted towards the UV–Vis region, dominated by π–π* transitions. The C–H···π intramolecular interactions are a blue shift in nature; however, their function and influence on the NLO property is insignificant. The Rayleigh scattering is dominant for methyl and ethyl substituent, while in the Rayleigh activity is controlled by the natural light.

Crystal structure of (E)-4-ethyl-2-(4-meth-oxy-benzyl-idene)-3,4-di-hydro-naphthalen-1(2H)-one.

In the title compound, C20H20O2, the exocyclic C=C double bond has an E conformation. The ethyl substituent on the cyclo­hexa­none ring is in an axial orientation. The cyclo­hexa­none ring adopts a screw-boat conformation, with the methyl­ene C atom and the C atom bearing the 4-meth­oxy­benzyl­idene group displaced from the other atoms by 0.812 (1) and 0.334 (1) Å, respectively. The dihedral angle between the planes of the benzene rings is 42.20 (8)°. In the crystal, no directional inter­actions beyond van der Waals contacts are observed.

Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists.

We synthesized derivatives of the δ opioid receptor (DOR) antagonists naltrindole (NTI) and compound 1 that were modified with small alkyl or fluorinated ethyl substituents on the 17-nitrogen. Although the derivatives showed decreased binding affinities for the opioid receptors, their selectivities for the DOR were higher than the parent compounds NTI and compound 1. Surprisingly, 17-fluoroethyl NTI derivatives exerted DOR inverse agonistic activities. The DOR inverse agonism of compounds 4c-e was less efficacious but significant, as compared with a standard DOR inverse agonist ICI-174864. On the other hand, compound 1 and its derivatives with small alkyl or monofluoroethyl substituents were partial agonists, but the derivatives having di- or trifluoroethyl group showed neither agonistic nor inverse agonistic activities.

Fragmentation patterns of boron-dipyrromethene (BODIPY) dyes by electrospray ionization high-resolution tandem mass spectrometry.

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene derivatives (BODIPYs) are fluorescent organic dyes that are widely used as non-radioactive labels in biological analyses. The fragmentation behaviour of ten structurally related BODIPYs was studied using tandem mass spectrometry (MS/MS), to support the structural elucidation process during synthesis. The BODIPYs were investigated by electrospray ionization (ESI)-MS/MS, utilizing collision-induced dissociation (CID) data from triple quadrupole MS and high-resolution, accurate mass CID data from Fourier transform ion cyclotron resonance (FTICR) experiments. Unusual radical molecular cations ([M](+•)) were formed directly during the ESI process. These radical species dissociated into a large range of product ions during the subsequent CID experiments. Superimposed dissociations originating from parallel [M](+•) and [M+H](+) decompositions significantly complicated the interpretation of the MS/MS spectra. Detailed dissociation mechanisms were proposed in this study for BODIPY dyes. The elemental formulae of CID product ions were unambiguously assigned using FTICR-MS and unique fragment ions were discovered for the rapid identification of methyl, ethyl, butyl, tert-butyl, and phenyl substituents of individual dyes in BODIPY synthesis mixtures by low-resolution MS.

Crystal structure of (E)-2-[1-(1,3-benzodioxol-5-yl)ethyl-idene]-N-ethyl-hydra-zine-1-carbo-thio-amide.

In the title compound, C12H15N3O2S, the 1,3-benzdioxole fragment is nearly planar [the maximum deviation being 0.0515 (14) Å], the N—N—C(=S)—N fragment is also nearly planar [the maximum deviation being 0.0480 (10) Å], and the dihedral angle between their mean planes is 23.49 (10)°. In the crystal, mol­ecules are linked by pairs of N—H⋯S hydrogen bonds, forming inversion dimers. The dimers are stacked along the a axis with neighbouring columns having the same direction; however, the mol­ecules show different orientations leading to a centrosymmetric arrangement. In the crystal, the methyl­ene group of the ethyl substituent and the terminal methyl H atoms are disordered over two sets of sites and were refined using a split model with an occupancy ratio of 0.5:0.5.

ChemInform Abstract: Diphenylprolinol Silyl Ether Catalyzed Asymmetric Michael Reaction of Nitroalkanes and β,β‐Disubstituted α,β‐Unsaturated Aldehydes for the Construction of All‐Carbon Quaternary Stereogenic Centers.

The asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β-substituents such as β-aryl and β-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.

Synthesis of Multiring Azo-Benzoic Acid Liquid Crystalline Molecules and Their Special Photosensitive Property

10 new rod-like azo benzoic acid liquid crystals belonged to three series have been prepared, in which trans-cyclohexyl benzene, biphenyl or bi-trans-cyclohexyl carboxylic acid mesogenic cores with ethyl, n-propyl, n-butyl or n-pentyl substituents were connected with azo benzoic acid. Meantime, a simple method was developed in synthesizing compounds bearing both ester and carboxyl groups in one-step reaction. All these compounds have been characterized on the basis of their spectral data, differential scanning calorimeter (DSC) and hot stage polarizing optical microscope (HS-POM). All these compounds have higher thermo-stability. 8 of these compounds have liquid crystalline properties. Their temperature ranges of mesophase have not been obtained, resulting from all the compounds decomposed before their clearing points. Although these compounds are photosensitive in solution under illumination of UV light (365nm), they can't do trans-cis isomerization in their mesophses, indicating the super stabilities of the trans isomer in mesophase.

Total Synthesis of Indolizidine Alkaloids (–)‐167B, (–)‐209I, and (–)‐223A by Using a Common Tricyclic Lactone

AbstractHighly stereocontrolled total synthesis of dart frog indolizidine alkaloids (–)‐167B, (–)‐209I, and (–)‐223A was accomplished, with a common tricyclic lactone intermediate as the starting compound, in overall yields of 17 %, 14 %, and 17 %, respectively. The C7–C8 bond of the 167B, without a C8 chiral substituent, was formed through ring closure metathesis followed by hydrogenation. In 209I and 223A, which have a C8 chiral substituent, highly substrate‐controlled asymmetric radical cyclization was used to form the C7–C8 bond, and the correct stereochemistry of the C8 substituents was obtained in both molecules. Ethyl substituent at the C6 position of 223A was obtained with correct stereochemistry through asymmetric alkylation/epimerization sequences of the tricyclic lactone. Cleavage of the excess carbon on the C5 position of all three indolizidines was performed by using a Barton decarboxylation protocol. Reduction of the corresponding indolizidin‐3‐ones by LAH completed the total synthesis of (–)‐167B, (–)‐209I and (–)‐223A.

Alkyne hydroacylation: switching regioselectivity by tandem ruthenium catalysis.

By using tandem Ru-catalysis, internal alkynes can be coupled with aldehydes for the synthesis of β,γ-unsaturated ketones. The catalyst promotes alkyne transformations with high regioselectivity, with examples that include the differentiation of a methyl vs ethyl substituent on the alkyne. Mechanistic studies suggest that the regioselectivity results from a selective allene formation that is governed by allylic strain.

Crystal structure of di-chlorido-bis-(4-ethyl-aniline-κN)zinc.

The title compound, [ZnCl2(C8H11N)2], was synthesized by the reaction of zinc dichloride and 4-ethyl­aniline. The Zn2+ cation is coordinated by two Cl− anions and the N atoms of two 4-ethyl­aniline ligands, forming a distorted Zn(N2Cl2) tetra­hedron. The dihedral angle between the two benzene rings is 85.3 (2)° The Zn atom lies on a twofold rotation axis. The ethyl substituents are disordered over two sets of sites in a 0.74 (2):0.26 (2) ratio. In the crystal, N—H⋯Cl hydrogen bonds link the mol­ecules into sheets perpendicular to the a axis. C—H⋯Cl inter­actions also occur.

Antimycobacterial activity of rhodamine 3,4-HPO iron chelators against Mycobacterium avium: analysis of the contribution of functional groups and of chelator's combination with ethambutol

ChelatorMRH7(thiourea linkage; ethyl substituents) and its co-administration with ethambutol are the best choices for a higher antimycobacterial effect.

Microwave-assisted synthesis of dialkylphosphinic acids and a structure–reactivity study in rare earth metal extraction

Dialkylphosphinic acids were synthesized efficiently under microwave irradiation. The extractants with ethyl or propyl substituents at the β-position showed higher separation efficiency.

Palladium/Imadazolium Salt Mediated Cyclisations for the Synthesis of Heterocyclic Compounds

The use of intramolecular reactions involving palladium/imidazolium salts to synthesize hetero-cyclic compounds is described. Reactivity of phenyl, ethyl and methyl substituents leading to isolation of various isomeric products is also illustrated. Rearrangement of phenyl intermediates to furnish benzoxazoles is also mentioned.

Crystal structure of 2-ethyl-3-(4-fluoro-phenyl-sulfin-yl)-5,7-dimethyl-1-benzo-furan.

In the title compound, C18H17FO2S, the dihedral angle between the planes of the benzo­furan ring system (r.m.s. deviation = 0.004 Å) and the 4-fluoro­phenyl ring is 86.38 (6)°. The terminal C atom of the ethyl substituent is displaced by 1.444 (3) Å from the benzo­furan ring system to the same side of the mol­ecule as the 4-fluoro­phenyl ring. In the crystal, mol­ecules are linked via pairs of C—H⋯π inter­actions into inversion-related dimers. These dimers are further linked by π–π inter­actions between the benzene rings of neighbouring mol­ecules [centroid–centroid distance = 3.715 (3) Å] and between the furan rings of neighbouring mol­ecules [centroid–centroid distance = 3.598 (3) Å]. The mol­ecules are stacked along the a-axis direction. In the sulfinyl group, the S and O atoms are disordered over two sets of sites, with site-occupancy factors of 0.797 (3) and 0.213 (3).

Diphenylprolinol silyl ether catalyzed asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes for the construction of all-carbon quaternary stereogenic centers.

The asymmetric Michael reaction of nitroalkanes and β,β-disubstituted α,β-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for β-substituents such as β-aryl and β-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of α,β-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.