Tert-butyl Moiety Research Articles

Improved synthesis of mercapto C-nucleoside possessing p-phenyl thiol as base using a lithiated coupling reaction

We have developed a new route for synthesizing mercapto C-nucleoside possessing a phenyl thiol group, using organometallic reagents. Duplexes incorporating redox-active nucleobase analogues display a high melting temperature under oxidation condition. Originally, we had anticipated the production of mercapto C-nucleoside using a Friedel–Crafts coupling reaction via bis(toluoyl) protected ribose and tert-butyl phenyl sulfide in the presence of Lewis acid. However, an undesired coupling compound was formed by cleavage of the S-tert-butyl group of S-tert-butyl phenyl sulfide by Lewis acids (BF3 Et2O, SnCl4). The highly stereoselective synthesis of mercapto C-nucleoside was, however, achieved by the addition of p-(tert-butyl)thiophenyllithium to a disiloxane-protected 2-deoxyribonolactone. This route showed moderately good yield at all steps. The tert-butyl moiety coupled to the sulfur atom at the phenyl group was converted to a 2-nitrophenylsulfenyl (Nps) group, and the Nps group was easily cleaved by ethanethiol to afford the desired compound and its disulfide dimer.

Sorption of Eu(III) on Merrifield resin modified with thiacalix[4]arenes

We have studied the sorption of Eu(III) ions on Merrifield resin (chloromethylated polystyrene) impregnated and covalently modified with tetrahydroxythiacalix[4]arenes that contain hydrogen atoms, tertbutyl, and dialkoxyphosphonylmethyl moieties on the macrocyclic upper rim. The resulting materials have a sorption capacity of up to 70 mg/g and allow one to extract up to 99% of Eu(III) from aqueous solutions with medium mineral content at pH 5.5–6.

Heat revolution on photophysical properties and electroluminescent performance of Ir(ppy)3-doped bipolar host of oxadiazole derivatives attaching with inert group of tert-butyl moiety

Two bipolar materials, 2,5-bis(2-(9H-carbazole-9-yl)phenyl)-1,3,4-oxadiazole (o-CzOXD) and 2,5-bis(2-(3′,6′-di-tert-butyl-9H-carbazole-9-yl)phenyl)-1,3,4-oxadiazole (tBu-o-CzOXD), were synthesized according to reported methods. In parallel study, it was demonstrated that introduction of inert tert-butyl group improved material thermal stability, even though this modification only had a slight influence to the photophysical and electrochemical properties of these materials. A comparative study focusing on effects of heat treatment was carried out on the quartz glass substrates with vacuum deposited films containing one of the bipolar host doped with 6 wt% fac-tris(2-phenylpyridinato-N,C2′)iridium (Ir(ppy)3). Results show that when the two samples were heated, the absorption, emission, and photo images of the host:dopant system changed, with the o-CzOXD suffering more severe degradation under high temperature, which is consistent with their thermal stability. In addition, it was proved that the high temperature-annealed host:dopant system can enhance the emission of the dopant. This finding was used as a guideline to improve our device performance. We fabricated two types of phosphorescent organic light-emitting devices (PhOLEDs), one was based on o-CzOXD, the other was based on tBu-o-CzOXD. They had analogous structure. We investigated the effect of heat on device performance by selectively annealing. Although these two freshly prepared devices exhibited similar performance, when annealed at 90 °C for 10 minutes, the OLEDs based on tBu-o-CzOXD showed significant performance enhancement, which can be attributed to the observation that annealing Ir(ppy)3 doped host can change film morphology and enhance the dopant emission. The maximum efficiencies of the freshly prepared tBu-o-CzOXD device were 25.8 cd A−1, 23.1 lm W−1, and 9.3%; whereas those for annealed device were 47.0 cd A−1, 42.2 lm W−1, and 13.4%.

Gas transport properties of aromatic polyamides containing adamantyl moiety

In this work we report the synthesis of a new diamine monomer, 1-adamantylmethyl[3,5-bis-{2′-trifluoromethyl-4′-(4″-aminophenyl)phenoxy}]benzoate and its polymerization with four different diacids. The monomer and the prepared poly(ether amide)s (PAs) were characterized by elemental analyses, NMR, and FTIR techniques. The polymers were further characterized by GPC and thermal techniques and the mechanical properties of the films prepared from these polymers are also reported. The permeability of CH4, N2, O2 and CO2 through these PA membranes was investigated at three different temperatures (35, 45 and 55°C) under an applied upstream pressure of 3.5bar. The PA 9B containing hexafluoroisopropylidene moiety exhibited highest permselectivity in the series (for, O2/N2=8.2 and CO2/CH4=41.7) whereas PA 9A containing tert-butyl moiety exhibited highest gas permeability (PCO2=34 and PO2=9.5). The gas transport properties have been correlated with the polymer structures with respect to their glass transition temperature, chain packing and dielectric constant values. The activation energies of the permeation and diffusion processes were calculated.

Preparation of Unconventional Dendrimers that Contain Rigid NHTriazine Linkages and Peripheral tert‐Butyl Moieties for CO2‐Selective Adsorption

Three unconventional dendrimers that contained rigid NH-triazine linkages and peripheral tert-butyl moieties were prepared by using a convergent approach and characterized by (1)H and (13)C NMR spectroscopy, mass spectrometry, and elemental analysis. Based on a thermogravimetric analysis study, these dendrimers were observed to display thermal stability at about 300 °C. The NH-triazine moiety, which possessed protonated and proton-free nitrogen sites (like the imidazole unit), displayed the capture of polarizable CO2 molecules through hydrogen-bond and/or dipole-quadrupole interactions. In addition, the adsorption of various amounts of CO2 and N2 at different pressures suggests that the dendritic pores, which arise from the stacking of the middle co-planar and rim protuberant dendrimers, Gn -N∼N-Gn (n=1-3), either swell or shrink at high pressure, thus indicating that these dendrimers may have a breathing ability.

Synthesis and Characterization of Dye-Labeled Poly(methacrylic acid) Grafted Silica Nanoparticles

The synthesis of dye-labeled poly(methacrylic acid) (PMAA) grafted silica nanoparticles was studied. Surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization of tert-butylmethacrylate (tBuMA) was conducted on dye-labeled CPDB coated silica nanoparticles followed by sequential removal of the thiocarbonylthio end groups and the tert-butyl moieties. Additionally, as a more straightforward strategy, direct polymerization of methacrylic acid on silica nanoparticles with a diameter size as small as 15 nm was conducted via the RAFT polymerization technique. A variety of PMAA brushes with different lengths and densities were prepared on nanoparticle surfaces via surface-initiated RAFT polymerization with excellent control and surface grafting densities as high as 0.65 chains/nm2. The grafted PMAA was methylated by trimethylsilyldiazomethane to conduct organic phase GPC characterization. The dye-labeled PMAA grafted nanoparticles provide a platform to bind biomolecules and to track the movement of the nanoparticles in biological systems.

Syntheses and evaluation of the antioxidant activity of novel methoxypsoralen derivatives

A series of 5- and 8-methoxypsoralen (MOP) analogs, suitable for structure-antioxidative/anti-inflammatory activity relationship studies, were synthesized using as key-reactions the selective monobromination of MOPs with N-bromosaccharin and either a Heck reaction or a Suzuki coupling or a Suzuki coupling followed by a Wittig reaction to install side-chains of the acrylate- or benzoate- or cinnamate-type, respectively. The 8-MOP analogs 19 and 24, incorporating at position 5 of the psoralen nucleus a butyl acrylate or a tert-butyl cinnamate moiety, were the most powerful inhibitors of soybean LOX and inhibited effectively lipid peroxidation. Analog 19 was a more potent anti-inflammatory agent than the reference compound indomethacin and of comparable cytocompatibility to 8-MOP whereas analog 24 was a weaker inhibitor of inflammation than indomethacin and significantly more cytotoxic than 8-MOP. The results of the biological tests are discussed in terms of structural characteristics.

Intrachain Folding and Interchain Association of Hyperbranched Chains with Long Uniform Subchains Made of Amphiphilic Diblock Copolymers

Combining atom transfer radical polymerization and copper-catalyzed azide–alkyne “click” chemistry, hyperbranched copolymers with uniform poly(tert-butyl acrylate-b-styrene-b-tert-butyl acrylate) triblock copolymer subchains, denoted as hyper-(PtBA-PS-PtBA)n, were successfully prepared and characterized by size exclusion chromatography (SEC), FT-IR, and 1H NMR. Using laser light scattering, we first studied the intrachain contraction of ultralarge hyper-(PtBA36-PS55-PtBA36)600 chains in cyclohexane, a solvent selectively poor for PS at lower temperatures. We found that at temperatures lower than 34 °C each PS block collapses into a small globule that was stabilized by its three neighboring PtBA blocks with no intrachain or interchain association in a dilute solution. Further, after hydrolyzing those tert-butyl (tBA) moieties into acrylic acids (AA), we comparatively studied the interchain association of linear triblock PAA23-PS14-PAA23 and its resultant hyper-(PAA23-PS14-PAA23)n with different overall mol...

Cunninghamella as a Microbiological Model for Metabolism of Histamine H3 Receptor Antagonist 1-[3-(4-tert-Butylphenoxy)propyl]piperidine

The aim of the study was to analyze the ability of the microorganism Cunninghamella to carry out the biotransformation of 1-[3-(4-tert-butylphenoxy)propyl]piperidine (DL76) and to compare the obtained results with in silico models. Biotransformation was carried out by three strains of filamentous fungus: Cunninghamella echinulata, Cunninghamella blakesleeana, and Cunninghamella elegans. Most probable direction of DL76 metabolic transition was the oxidation of the methyl group in the tert-butyl moiety leading to the formation of the metabolite with I° alcohol properties. This kind of reaction was conducted by all three strains tested. However, only in the case of C. blakesleeana that biotransformation product had a structure of carboxylic acid. CYP2C19 was identified by Metasite software to be the isoform of major importance in the oxidation process in the tert-butyl moiety of DL76. In silico data coincide with the results of experiments conducted in vitro. It was confirmed that Cunninghamella fungi are a very good model to study the metabolism of xenobiotics. The computational methods and microbial models of metabolism can be used as useful tools in early ADME-Tox assays in the process of developing new drug candidates.

Bacterial Acyl-CoA Mutase Specifically Catalyzes Coenzyme B12-dependent Isomerization of 2-Hydroxyisobutyryl-CoA and (S)-3-Hydroxybutyryl-CoA

Coenzyme B(12)-dependent acyl-CoA mutases are radical enzymes catalyzing reversible carbon skeleton rearrangements in carboxylic acids. Here, we describe 2-hydroxyisobutyryl-CoA mutase (HCM) found in the bacterium Aquincola tertiaricarbonis as a novel member of the mutase family. HCM specifically catalyzes the interconversion of 2-hydroxyisobutyryl- and (S)-3-hydroxybutyryl-CoA. Like isobutyryl-CoA mutase, HCM consists of a large substrate- and a small B(12)-binding subunit, HcmA and HcmB, respectively. However, it is thus far the only acyl-CoA mutase showing substrate specificity for hydroxylated carboxylic acids. Complete loss of 2-hydroxyisobutyric acid degradation capacity in hcmA and hcmB knock-out mutants established the central role of HCM in A. tertiaricarbonis for degrading substrates bearing a tert-butyl moiety, such as the fuel oxygenate methyl tert-butyl ether (MTBE) and its metabolites. Sequence analysis revealed several HCM-like enzymes in other bacterial strains not related to MTBE degradation, indicating that HCM may also be involved in other pathways. In all strains, hcmA and hcmB are associated with genes encoding for a putative acyl-CoA synthetase and a MeaB-like chaperone. Activity and substrate specificity of wild-type enzyme and active site mutants HcmA I90V, I90F, and I90Y clearly demonstrated that HCM belongs to a new subfamily of B(12)-dependent acyl-CoA mutases.

Effects of alkyl substitution on the physical properties and gas transport behavior in selected poly(R-phenoxyphosphazenes)

A systematic preparation of alkyl substituted phenoxyphosphazene polymers was performed and their gas transport properties determined. In this study, phosphazenes substituted with 4-methylphenol, 4-ethylphenol, and 4-isopropylphenol are reported. An additional polymer substituted with 4-tert-butylphenoxy-1-ethanol also was synthesized in this work. Data derived for these materials, including chemical, thermal and gas transport characterization, were compared to previous reports discussing poly[bis-phenoxyphosphazene] and its analog with tert-butyl substitution: poly[bis-(4-tert-butylphenoxy)phosphazene]. The tert-butyl moiety influences orderly chain packing, presumably through steric hindrance that can influence aromatic π-stacking. For the new poly[(alkylphenoxy)phosphazenes], semicrystallinity is maintained and the added steric bulk serves to decrease the polymer glass transition temperature (Tg) and increase both permeability and selectivity for the gas pairs: O2/N2 and CO2/CH4. Removal of the tert-butyl moiety from the immediate vicinity of the backbone through a flexible spacer serves to depress the Tg as compared to poly[bis-(4-tert-butylphenoxy)phosphazene], but provides no performance enhancement for gas transport.

Poly(Acrylic Acid-b-Styrene) Amphiphilic Multiblock Copolymers as Building Blocks for the Assembly of Discrete Nanoparticles.

In order to expand the utility of current polymeric micellar systems, we have developed amphiphilic multiblock copolymers containing alternating blocks of poly(acrylic acid) and poly(styrene). Heterotelechelic poly(tert-butyl acrylate-b-styrene) diblock copolymers containing an α-alkyne and an ω-azide were synthesized by atom transfer radical polymerization (ATRP), allowing control over the molecular weight while maintaining narrow polydispersity indices. The multiblock copolymers were constructed by copper-catalyzed azide-alkyne cycloaddition of azide-alkyne end functional diblock copolymers which were then characterized by (1)H NMR, FT-IR and SEC. The tert-butyl moieties of the poly(tert-butyl acrylate-b-styrene) multiblock copolymers were easily removed to form the poly(acrylic acid-b-styrene) multiblock copolymer ((PAA-PS)(9)), which contained up to 9 diblock repeats. The amphiphilic multiblock (PAA-PS)(9) (M(n) = 73.3 kg/mol) was self-assembled by dissolution into tetrahydrofuran and extensive dialysis against deionized water for 4 days. The critical micelle concentration (CMC) for (PAA-PS)(9) was determined by fluorescence spectroscopy using pyrene as a fluorescent probe and was found to be very low at 2 × 10(-4) mg/mL. The (PAA-PS)(9) multiblock was also analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter of the particles was found to be 11 nm. Discrete spherical particles were observed by TEM with an average particle diameter of 14 nm. The poly(acrylic acid) periphery of the spherical particles should allow for future conjugation of biomolecules.

Computational prediction of selectivities in nonreversible and reversible hydroformylation reactions catalyzed by unmodified rhodium-carbonyls

The regio- and stereoselectivities of the hydroformylation reaction catalyzed by an unmodified Rh catalyst have been investigated at the B3P86/6-31G* level with Rh described by effective core potentials in the LANL2DZ valence basis set for a number of either mono- or (1,1-, 1,2-, 1,3-) di-substituted substrates and compared with a variety of earlier results of ours, supplemented with free energy results when not already available. The computational prediction of regio- and stereoselectivities in nonreversible hydroformylations performed under mild reaction conditions is seemingly possible provided a careful conformational search for TS structures is carried out and all the low energy conformers are taken into account. The internal energy can be used to compute both the regio- and stereoselectivities in the hydroformylation of 1,1- and 1,3-substituted substrates with satisfactory results, whereas for 1,2-substituted substrates the regioselectivity determined from the internal energy is in good agreement with the experiment in the case of aliphatic olefins just for the lowest terms in the series (i.e., methyl and ethyl substituents), while the ratios are only qualitatively correct for the slightly bulkier iso-propyl and tert-butyl moieties. The theory/experiment agreement becomes decidedly better using the free energy differences instead.

Thermal transformations of 4-tert-butylbiphenyl

The thermal stability of 4-tert-butylbiphenyl was studied in the range of 703–763 K. The competition of the cracking and isomerization reactions of alkyl substituents on the aromatic ring of the reactant and its products has been revealed. The kinetic characteristics of the complex of transformations occurring in the system have been determined. Recommendations are provided regarding the conditions for the determination of the critical parameters of 4-tert-butylbiphenyl and for the processing and use of compounds with a tert-butyl moiety in the molecule.

Asymmetric synthesis of bicyclo[ n.1.0]alkanes by the enantioselective 1,3-CH insertion reaction of chiral magnesium carbenoids

Treatment of enantiomerically pure 1-chlorovinyl p-tolyl sulfoxides, derived from cyclic ketones and ( R)-chloromethyl p-tolyl sulfoxide, with the lithium enolate of tert-butyl carboxylates gave adducts in quantitative yields as single diastereomers. The adducts were treated with i-PrMgCl in toluene to afford optically active bicyclo[ n.1.0]alkanes bearing a tert-butyl carboxylate moiety in up to 99% enantiomeric excess through the enantioselective 1,3-CH insertion reaction of the generated chiral magnesium carbenoids. This is the first example of the enantioselective 1,3-CH insertion reaction of magnesium carbenoid.

Morphologically and electrochemically stable bipolar host for efficient green electrophosphorescence

A new host tBu-o-CzOXD is facilely synthesized through a simple aromatic nucleophilic substitution reaction between 3,6-di-tert-butyl-9H-carbazole and 2,5-bis(2-fluorophenyl)-1,3,4-oxadiazole. Its thermal, electrochemical, electronic absorption and photoluminescent properties are fully investigated. A high glass transition temperature (T(g)) of 149 degrees C is observed for tBu-o-CzOXD due to the introduction of bulky tert-butyl moiety, significantly higher than 97 degrees C of o-CzOXD without tert-butyl substituent. Moreover, encapsulation of tert-butyl on the 3- and 6-positions of carbazole greatly enhances the electrochemical stability as compared to o-CzOXD. Green phosphorescent OLEDs hosted by tBu-o-CzOXD show a maximum luminance of 48293 cd m(-2) at 17.1 V, a maximum current efficiency of 38.4 cd A(-1) and a maximum power efficiency of 34.7 lm W(-1). Furthermore, the devices exhibit a slow current efficiency roll-off. The device merits, together with the excellent morphological and electrochemical stability, make the new compound an ideal host material for phosphorescent emitters.

Regio-selective synthesis of novel 1- tert-butyl-4-nitro-1 H-pyrrole-3-carboxylic acid building block

A convenient, regio-selective synthesis of novel 1- tert-butyl-4-nitro-1 H-pyrrole-3-carboxylic acid was developed, utilizing the bulky tert-butyl moiety of 1- tert-butyl-1 H-pyrrole to direct selective, un-symmetrical substitutions to the desired 3 and 4 positions.

Characterization of New PPARγ Agonists: Benzimidazole Derivatives – the Importance of Position 2

Probing SAR: The 1-(biphenyl-4-ylmethyl)-1H-benzo[d]imidazole moiety is known to be an essential structural component of telmisartan for PPARgamma activation. This study focused on the substituents at position 2 of the benzimidazole in an attempt to optimize PPARgamma activation. In particular, the elongation of the alkyl chain and the introduction of an aromatic ring system were studied (shown).The relevance of substituents at C-2 of the central benzimidazole of telmisartan for PPARgamma activation has recently been demonstrated, and the most active compound identified in our previous work, 4'-[(2-propyl-1H-benzo[d]imidazol-1-yl)methyl]biphenyl-2-carboxylic acid (4 a), is used as lead structure in the present study. Modifications at C-2 included butyl (4 b), iso-butyl (4 c), tert-butyl (4 d), phenyl (4 e), benzyl (4 f), phenethyl (4 g), 4-chlorobenzyl (4 h), 4-methoxyphenyl (4 i), and 4-hydroxyphenyl (4 j) moieties. The compounds were tested in a differentiation assay using 3T3-L1 preadipocytes and a luciferase assay with COS-7 cells, transiently transfected with pGal4-hPPARgammaDEF, pGal5-TK-pGL3 and pRL-CMV, as established models for the assessment of cellular PPARgamma activation. The activity in the luciferase assay increased in the alkyl series: propyl (4 a) <iso-butyl (4 c) <or= tert-butyl (4 d) <butyl (4 b). A phenyl group at C-2 led to the most active compound (4 e) in this study with an EC(50) value of 0.27 microM. 4-Hydroxylation of the C-2 phenyl group (4 j) drastically decreased the activity (EC(50)=5.8 microm) presumably due to hydrophilic repulsion. This assumption was verified by O-methylation to give compound 4 i, which maintained activity (EC(50)=0.29 microM). The weak effect of the benzyl derivative 4 f (EC(50)=1.4 microM) was abolished by an additional hydrophobic 4-chloro substituent (4 h; EC(50)=0.55 microM) or an elongation of the alkyl chain between the phenyl and the benzimidazole core (4 g; EC(50)=0.31 microM).

Synthesis of 2,2-functionalized benzo[1,3]dioxoles

Highly functionalized catechol ketals exhibiting either a tert-butyl moiety or a spiro center in position 2 are synthesized by ketalization and functionalized in a sequence of subsequent transformations. By a specific ketalization protocol catechol ketals of enolizable β-keto esters can be prepared. With the succeeding steps these compounds incorporate moieties, which are not compatible and accessible by direct ketalization of catechol.

Atomic Force Microscopy Based Thermal Lithography of Poly(tert-butyl acrylate) Block Copolymer Films for Bioconjugation

In this paper, we report on the local thermal activation of thin polymer films for area-selective surface chemical modification on micrometer and nanometer length scales. The thermally induced activation of tert-butyl ester moieties in polystyrene- block-poly(tert-butyl acrylate) (PS- b-PtBA) block copolymer films leads to the formation of pending carboxylic acid groups, which are among the versatile functionalities for subsequent bioconjugation. From Fourier transform infrared (FTIR) spectroscopic analyses, the apparent activation energy (Ea) for the tert-butyl ester deprotection in thin films was calculated to be 93 +/- 12 kJ/mol, which is in good agreement with values reported for the bulk. The availability of the deprotected carboxylic acid groups in subsequent wet chemical grafting reactions on neat thermolyzed films was confirmed by covalently immobilizing fluoresceinamine and amino end-functionalized poly(ethylene glycol) (PEG-NH2) using established 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) chemistry. Local thermal deprotection on micrometer and sub-micrometer length scales was achieved by scanning thermal microscopy using an atomic force microscope with heatable probe tips. Passivating PEG and fluoresceinamine layers were selectively covalently coupled to locally deprotected areas as small as 370 nm x 580 nm.