Tert-butyl Benzoic Acid Research Articles

A 1,4-benzoquinone with counteracting inductive donor and acceptor substituents

Investigation of a published route to produce 3,5-di- tert-butylphenol, starting from commercial 3,5-di- tert-butylbenzoic acid via 3,5-di- tert-butylanlinium hydrogen sulfate, unexpectedly yielded 2,6-dintitro-3,5-di- tert-butylphenol. Attempts to increase the yield of the latter resulted, instead, in the previously unreported 2,6-dinitro-3,5-di- tert-butylcyclohexa-2,5-dien-1,4-dione. Single-crystal X-ray diffraction structures are reported for the anilinium salt, the nitrated phenol, and the quinone. Voltammetry of the quinone shows two chemically reversible reductions in anhydrous solution and the radical anion produced from the first reduction step has been characterized by electron paramagnetic resonance spectroscopy. This compound fits well to the middle range of electron-poor quinones, indicating that the inductive effects of the tert-butyl and nitro groups counteract each other. This conclusion is also supported by the infrared spectroscopic data where the ν(C=O) and ν(C=C) bands are of very similar energy to those of 2,3,5,6-tetrachloro-1,4-benzoquinone.

Lysmeral Exposure in Children and Adolescences Participating in the German Environmental Survey (2012-2015): Integrating Sex/Gender into Analysis.

Comprehensive consideration of the biological and social diversities of sex and gender as well as their interdependencies is mostly missing in human biomonitoring (HBM) studies. Using the INGER sex/gender concept as theoretical background, we analyzed differences in exposure to lysmeral, a compound commonly found as a fragrance in cosmetics, personal care, and household products, in 2294 children and adolescents in Germany using decision tree, regression, and mediation analysis. The variables "sex assigned at birth" and "age", as well as well as use of personal care products and fabric conditioner proved to have the highest explanatory value. Mediating effects of behaviour associated with societal gender expectations were observed, as the use of cosmetics correlated highly with lysmeral metabolites concentrations in girls between 6 and 17 years, with the strongest effect in adolescents between 14 and 17 years old. In the youngest age group (3-5 years) boys showed higher concentration of the metabolite tert-butylbenzoic acid (TBBA) compared to girls of the same age but only if TBBA urine concentrations were normalized on creatinine. Our study offers the first retrospective sex/gender assessment of HBM data. It demonstrates the possibilities to rethink and broaden sex/gender analysis in existing HBM-studies and highlights the need for inclusion of new sex/gender concepts in the design of new studies.

Human biomonitoring in urine samples from the Environmental Specimen Bank reveals a decreasing trend over time in the exposure to the fragrance chemical lysmeral from 2000 to 2018

2-(4-tert-butylbenzyl)propionaldehyde (trade names, e.g. lysmeral or lilial) is a fragrance chemical frequently used in cosmetic products where it is labelled as Butylphenyl methylpropional. A recently developed LC-MS/MS method for the analysis of four lysmeral metabolites (tert-butylbenzoic acid (TBBA), lysmerol, lysmerylic acid, and hydroxy-lysmerylic acid) was applied to 329 urine samples from the Environmental Specimen Bank collected between 2000 and 2018. The two major metabolites TBBA and lysmerol were found in quantifiable concentrations in almost all samples in this study and correlated significantly. Hence, both analytes proved to be specific biomarkers indicating the broad exposure to lysmeral. A significant decline was found for TBBA and lysmerol for the monitored years with the most pronounced decrease from 2012 to 2015. The daily intake (DI) was used to evaluate potential health risks with respect to the derived no-effect level (DNEL) as a threshold for exposure of the general population. The median DI (1.63 μg/kg bw/d) and the 95th percentile (4.69 μg/kg bw/d) corresponded to 2.6% and 7.5% of the lowest DNEL (62.5 μg/kg bw/d for oral administration), respectively. Even though a decreasing trend in exposure was observed the data still calls for efforts to reduce the exposure towards lysmeral since metabolites of lysmeral were detected in nearly all samples and adverse effects cannot be excluded. Clearly, these results need to be substantiated by HBM campaigns in population representative samples like the German Environmental Survey in adults (GerES VI) to provide more robust data for the adult population.

Metabolites of the fragrance 2-(4-tert-butylbenzyl)propionaldehyde (lysmeral) in urine of children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

The synthetic fragrance 2-(4-tert-butylbenzyl)propionaldehyde, also known as lysmeral, butylphenyl methylpropional, lilial, or lily aldehyde, is widely used in cosmetics, personal care products, laundry detergents, and air fresheners. It is classified as suspected to be harmful to fertility and possibly endocrine disrupting. Its maximum concentration in cosmetics is limited. First-morning void urine samples (N=2133) were analysed for several metabolites of lysmeral (Chemical Abstract Service (CAS) No.: 80-54-6). Samples were collected in the population-representative German Environmental Survey for Children and Adolescents 2014-2017 (GerES V) from German residents aged 3-17 years. Four main metabolites tert-butylbenzoic acid, lysmerol, lysmerylic acid, and hydroxy-lysmerylic acid were found in quantifiable amounts in 100%, 99%, 40%, and 23% of the samples, respectively, with geometric mean concentrations of 10.21μg/L (8.658 μg/gcrea) for tert-butylbenzoic acid, 1.528μg/L (1.296 μg/gcrea) for lysmerol, and below the limit of quantification of 0.2μg/L and 0.4μg/L for lysmerylic acid and hydroxy-lysmerylic acid, respectively. Girls had higher urinary concentrations of lysmeral metabolites than boys. Usage of fragrances, fabric softener, and personal care products, especially perfume, was positively associated with urinary concentrations of lysmeral metabolites. Source identification builds a basis to derive proposals for reduction of exposure. These results can also provide the foundation for developing reference values for urinary metabolite concentrations of lysmeral in children and adolescents in Germany that will facilitate recognising future exposure trends.

Comment on “Measurement and Modeling of Solubility of para-tert-Butylbenzoic Acid in Pure and Mixed Organic Solvents at Different Temperatures” and “Determination of Solubility and Thermodynamic Properties of Benzophenone in Different Pure Solvents”

Errors are discovered in the tabulated thermodynamic properties for dissolution of tert-butylbenzoic acid and benzophenone dissolved in organic monosolvents. The thermodynamic properties of dissolution were reported in two recently published papers. Specifically, the dissolution properties that were reported by Aniya et al. and by Ouyang et al. do not obey the standard thermodynamic relationship of ΔdissG = ΔdissH – TΔdissS, where ΔdissG, ΔdissH, and ΔdissS are respectively the Gibbs energy of dissolution, the enthalpy of dissolution, and the entropy of the dissolution of crystalline organic compounds in the organic solvent at the solution temperature, T.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the human biomonitoring of non-occupational exposure to the fragrance 2-(4-tert-butylbenzyl)propionaldehyde (lysmeral)

2-(4-tert-Butylbenzyl)propionaldehyde also known as lysmeral, lilial, or lily aldehyde (CAS No. 80-54-6) is a synthetic odorant mainly used as a fragrance in a variety of consumer products like cleaning agents, fine fragrances, cosmetics, and air fresheners. Due to its broad application in various fields, lysmeral was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). A method based on ultra-high pressure liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of potential biomarkers of lysmeral in human urine samples. Sample cleanup was performed by liquid-liquid extraction (LLE). Quantification was achieved by standard addition using stable isotope-labeled, authentic reference standards. The method is characterized by its robustness, reliability, and excellent sensitivity as proven during method validation according to approved standard guidelines. The following five lysmeral metabolites were identified as potential biomarkers of exposure for lysmeral in human urine samples: lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, tert-butylbenzoic acid (TBBA), and tert-butylhippuric acid (TBHA). The determination of lysmerol required derivatization with 3-nitrophthalic acid anhydride and showed the lowest limit of detection (LOD) and limit of quantification (LOQ) in urine (0.035 and 0.10μg/L, respectively). LOD and LOQ for the other metabolites were in the range of 0.12-0.15 and 0.36-0.45μg/L, respectively. Accuracy for all analytes was in the range of 90-110%. Intra- and inter-day precision was in the range of 5-10%, except for TBHA, for which the coefficient of variation was unacceptably high (>20%) and therefore excluded from the method. The method was applied to urine samples of 40 adult volunteers. The four remaining lysmeral metabolites were detectable in most of the 40 urine samples in the following order according to quantity excreted: TBBA >> lysmerol ≈ lysmerylic acid > hydroxy-lysmerylic acid. In conclusion, we successfully developed a biomonitoring method for the assessment of the exposure to lysmeral in the general population. The method is characterized by its precision, robustness, and accuracy. The metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, and TBBA turned out to be suitable biomarkers of exposure to lysmeral, either alone or in combination with one or more of the other metabolites. Sensitivity was found to be sufficient for assessing the background exposure to this chemical in the general population.

Layer‐by‐layer coating of textile with two oppositely charged cyclodextrin polyelectrolytes for extended drug delivery

The coating of a nonwoven textile by polyelectrolyte multilayer film (PEM) issued from cationic and anionic β-cyclodextrin (βCD) polyelectrolytes according to the layer-by-layer (LbL) technique was successfully attempted. The tert-butyl benzoic acid (TBBA) was used as drug model to evaluate the loading capacity and sustained release properties of this PEM system. The build-up of the multilayer assembly was monitored in situ by optical waveguide lightmode spectroscopy (OWLS) on the one hand, and was assessed by gravimetry on the other hand when applied onto the textile substrate. In parallel, the complexation study of TBBA with both CD polyelectrolytes was also investigated by nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). The influence of thermal crosslinking of the multilayered coating on its stability and on TBBA release kinetics in phosphate buffered saline (PBS) at 37°C was studied. Finally, biological and microbiological tests were performed to investigate the cytocompatibility and the intrisic antibacterial activity of multilayer assemblies. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1408-1424, 2016.

Reactions of [(Me 3Si) 3CAlMe 2] with substituted benzoic acids. Isolation of a rare organoalumoxane carboxylate

The reactivity of bulky tris(trimethylsilyl)methyl group substituted aluminum trialkyl [(Me 3Si) 3CAlMe 2·THF] ( 1) with a series of substituted benzoic acid derivatives has been investigated. An equimolar reaction of 4-methyl benzoic acid or 4- tert-butyl benzoic acid with 1 in toluene at 50 °C leads to the formation of cyclic dimeric aluminum carboxylates [(Me 3Si) 3CAl(Me)(μ-O 2CC 6H 4R)] 2 (R = Me 2; t Bu 3). Reaction of 3,5-di- iso-propylsalicylic acid (H 2dipsa) with 1 leads to the exclusive isolation of a trimeric organoaluminum carboxylate [(Me 3Si) 3CAl(μ-dipsa)] 3 ( 4), in which each aluminum is bound to two carboxylates, a phenoxide, and an alkyl group and produce a 12-membered macrocycle. Deliberate, but controlled, introduction of water in the form of 3,5-di- tert-butyl salicylic acid monohydrate (H 2dtbsa·H 2O) in the reaction with 1 in toluene leads to the isolation of carboxylate [(Me 3Si) 3CAl(μ-O)(μ-Hdtbsa)} 2] ( 5) with a bicyclic structure. Compound 5 represents a rare example of an organoalumoxane carboxylate that simultaneously possesses alkyl, oxo, and carboxylate moieties on aluminum.

Molecular recognition in Mn-catalyzed C-H oxidation. Reaction mechanism and origin of selectivity from a DFT perspective.

Experimental studies have shown that the C-H oxidation of Ibuprofen and methylcyclohexane acetic acid can be carried out with high selectivities using [(terpy')Mn(OH(2))(mu-O)(2)Mn(OH(2))(terpy')](3+) as catalyst, where terpy' is a terpyridine ligand functionalized with a phenylene linker and a Kemp's triacid serving to recognize the reactant via H-bonding. Experiments, described here, suggest that the sulfate counter anion, present in stoichiometric amounts, coordinates to manganese in place of water. DFT calculations have been carried out using [(terpy')Mn(O)(mu-O)(2)Mn(SO(4))(terpy')](+) as a model catalyst, to analyze the origin of selectivity and its relation to molecular recognition, as well as the mechanism of catalyst inhibition by tert-butyl benzoic acid. The calculations show that a number of spin states, all having radical oxygen character, are energetically accessible. All these spin states promote C-H oxidation via a rebound mechanism. The catalyst recognizes the substrate by a double H bond. This interaction orients the substrate inducing highly selective C-H oxidation. The double hydrogen bond stabilizes the reactant, the transition state and the product to the same extent. Consequently, the reaction occurs at lower energy than without molecular recognition. The association of the catalyst with tert-butyl benzoic acid is shown to shield the access of unbound substrate to the reactive oxo site, hence preventing non-selective hydroxylation. It is shown that the two recognition sites of the catalyst can be used in a cooperative manner to control the access to the reactive centre.

Spectroscopic properties of lanthanoid benzene carboxylates in the solid state: Part 1

Europium and terbium complexes of benzoic acid (HBA), 9-anthracene carboxylic acid (9-HACA), 1-naphthoic acid (1-HNA), 2-naphthoic acid (2-HNA), cinnamic acid (HCA), o-phenylbenzoic acid ( o-HPhBA), p-phenylbenzoic acid ( p-HPhBA), o-methylbenzoic acid ( o-HMeBA), m-methylbenzoic acid ( m-HMeBA), p-methylbenzoic acid ( p-HMeBA), p- tert-butylbenzoic acid ( p- tert HBuBA), phthalic acid (H 2Phth), isophthalic acid (H 2-IsoPhth) and terephthalic acid (H 2-TerePhth) were synthesised by aqueous metathesis reactions. The compositions were determined by microanalysis, DTA, and EDTA volumetric methods. Structural conclusions were drawn from powder XRD patterns and IR spectra. The optoelectronic properties were determined in the solid state, including reflectance, excitation, emission, and excitation efficiency, complemented by considering triplet state energies, which were derived from phosphorescence spectra of the corresponding gadolinium complexes. Besides the emission efficiencies, the splitting pattern of the 5D 0 → 7F J transitions of Eu 3+ were used to derive structural information and the intensities relative to the 5D 0 → 7F J were used to gain information about the mechanism, adding electronic allowed dipole character to the forbidden emissions.

Enantioselective inclusion of chiral alkyl aryl sulfoxides in a supramolecular helical channel consisting of an enantiopure 1,2-amino alcohol and an achiral carboxylic acid

The enantioselective clathrate formation of alkyl aryl sulfoxides 4 was achieved with dissymmetric one-dimensional helical channels created in two-component hosts consisting of (1 R,2 S)-2-amino-1,2-diphenylethanol 1 and an achiral carboxylic acid, p- tert-butylbenzoic acid 2, or 2-anthraquinonecarboxylic acid 3. X-ray crystallographic analyses showed that the host framework (1 R,2 S)- 1· 3 in the single crystal of a clathrate with methyl p-methylphenyl sulfoxide 4n [(1 R,2 S)- 1· 3· 4n (single)] maintained a supramolecular helical array as those of the solvent-included single crystals (1 R,2 S)- 1· 3· EtOH(single) and (1 R,2 S)- 1· 3· H 2 O· THF(single), while the guest 4n molecules were highly disordered. Moreover, the X-ray powder diffraction pattern of (1 R,2 S)- 1· 3· 4n(clathrate) obtained through the clathrate formation demonstrated that the molecular arrangements of (1 R,2 S)- 1, 3, and 4n were not the same as those which appeared in (1 R,2 S)- 1· 3· 4n(single); the channel was enlarged. These results are consistently explained by assuming the dynamic motion of the framework (1 R,2 S)- 1· 3 to achieve widely applicable clathrate formation.

Structure of host-guest assemblies involving interaction of cyclen with diphenylphosphinic and 4- tert-butylbenzoic acid

The synthesis and characterisation by single crystal X-ray diffraction of 1:2 host-guest assemblies formed between the tetra-amine macrocycle 1,4,7,10-tetraazacyclododecane (cyclen) and diphenylphosphinic acid or 4- tert-butylbenzoic acid are reported. In each case strong hydrogen bonds associated with proton transfer from the acid species to two (trans) amino groups in the cyclen ring are observed. Both adducts are also associated with complex hydrogen bonded networks involving the secondary amines and water molecules, with each crystal structure containing five water molecules per asymmetric unit.

Determination of endocrine-disrupting compounds in cereals by pressurized liquid extraction and liquid chromatography–mass spectrometry: Study of background contamination

A sensitive method based on pressurized liquid extraction (PLE) and liquid chromatography–electrospray ionization mass spectrometry (LC–ESI-MS) has been developed for the determination in cereal samples of seven endocrine-disrupting compounds: bisphenol A (BPA), 4- tert-butylbenzoic acid (BBA), 4-nonylphenol (NP), 4- tert-butylphenol ( t-BP), 2,4-dichlorophenol (DCP), 2,4,5-trichlorophenol (TCP) and pentachlorophenol (PCP). For the PLE procedure, methanol was selected as the extraction solvent. An experimental design approach was applied to optimize other PLE parameters. The recoveries achieved for the all seven compounds were in the 81–104% range, with relative standard deviations of 4–9%. An additional preconcentration step, based on solid-phase extraction (SPE), after the PLE step proved to be a successful way for obtaining a more sensitive method. The detection limits achieved in corn breakfast cereals were in the 0.003–0.013 μg g −1 range, except for BPA, with a detection limit of 0.043 μg g −1, for a sample size of 2.5 g. These values are similar to or even lower than currently legislated limits for pesticides in cereals and cereal-based foodstuffs. We also investigated possible contamination during the experimental process by the target compounds released from purified water, plastics, syringes, peristaltic pump tubes, glassware and other laboratory materials in contact with the samples along the analytical process.

Inhibition of the activity of mushroom tyrosinase by alkylbenzoic acids

The inhibition kinetics of alkylbenzoic acids on the diphenolase activity of mushroom tyrosinase have been investigated. The results show that the alkylbenzoic acids assayed can lead to reversible inhibition of the enzyme; furthermore, o-toluic acid and m-toluic acid are mixed-type inhibitors and p-alkylbenzoic acids are uncompetitive inhibitors. The inhibition constants have been determined. For these p-alkylbenzoic acids, the inhibition strength follows the order: p-toluic acid < p-ethylbenzoic acid < p-propylbenzoic acid < p-isopropylbenzoic acid < p- tert-butylbenzoic acid < p-butylbenzoic acid < p-pentylbenzoic acid < p-hexylbenzoic acid < p-heptylbenzoic acid < p-octylbenzoic acid, indicating that the hydrophobic p-alkyl group played an important role in the inhibition of the enzyme. The inhibitory effects were potentiated with increasing lengths of the hydrocarbon chains. The inhibitory effects of o-toluic acid and p-isopropylbenzoic acid on the monophenolase activity have also been studied. The results show that both o-toluic acid and p-isopropylbenzoic acid can lengthen the lag time and decrease the steady-state activity of the enzyme.

Determination of weakly acidic endocrine-disrupting compounds by liquid chromatography–mass spectrometry with post-column base addition

A sensitive analytical method based on liquid chromatography–electrospray ionisation mass spectrometry (LC–ESI-MS) has been developed for the determination of seven endocrine-disrupting compounds: 4- n-nonylphenol (NP), 4- tert-butylphenol ( t-BP), bisphenol A (BPA), 2,4-dichlorophenol (DCP), 2,4,5-trichlorophenol (TCP), pentachlorophenol (PCP) and 4- tert-butylbenzoic acid (BBA) in water samples. To achieve a good LC separation, acidification of the LC mobile phase was necessary, but this led to MS signal suppression for the less acidic compounds. In order to enhance the sensitivity for these analytes, post-column addition of different bases such as ammonia, trimethylamine, and 1,8-diazabicyclo-(5,4,0)undec-7-en (DBU) was evaluated. The post-column addition of base is proposed here to raise effluent pH, helping in the ionisation process of the compounds with higher p K a values ( t-BP, BPA, DCP and NP). The use of DBU, diluted in MeOH, proved to be the most efficient post-column reagent for enhancing the MS signal. The signal-to-noise ratios for t-BP and NP increased by more than 200-fold and 35-fold, respectively, whereas for DCP and BPA an increase of about 10-fold was achieved. This strategy permitted direct determination of the seven compounds at low ppb levels. For application to real water samples, an extraction and preconcentration step using the solid-phase extraction (SPE) technique was carried out. The applicability of three solid-phase materials—Bond Elut C 18, and two polymeric sorbents: LiChrolut EN and Oasis HLB—and the optimization of other SPE parameters such as the elution solvent and sample volume used, were studied in order to maximize extraction efficiency. Oasis HLB provided the best results, obtaining—with the proposed SPE procedure—satisfactory percentage recoveries for all compounds (70–110%) with the exception of NP, for which a recovery of 54% was achieved. Application of the whole method, SPE–LC–(ESI)-MS, to natural waters permitted low nanogram-per-liter determination of all seven compounds.

Aerial oxidation of substituted aromatic hydrocarbons catalyzed by Co/Mn/Br − in water-dioxane medium

Aerial oxidation of substituted aryl aromatic hydrocarbons were carried out using Co/Mn/Br − catalyst system in water-dioxane medium in the range 14–56 bar air and temperature 383–423 K. The combination of optimum catalyst concentration of salts Co(OAc) 2, Mn(OAc) 2 and NaBr (1:3:10 molar ratio) in water-dioxane (1:2 mole ratio) is found catalyze aerial oxidation of substituted aryl aromatic to give corresponding oxygenated products. Under the optimized conditions, p-cymene gave p-isopropyl benzaldehyde (33.1%), p-isopropylbenzyl alcohol (54.7%) and p-isopropyl benzoic acid (3.3%), respectively, at p-cymene conversion 40.2%. Similarly, oxidation of p-methoxy toluene gave p-methoxy benzaldehyde (87.4%), benzyl alcohol (5.5%), and p-methoxy benzoic acid (6%), while oxidation of p- tert-butyl toluene yielded p- tert-butyl benzaldehyde (87%), p- tert-butyl benzyl alcohol (5.7%) and p- tert-butyl benzoic acid (6.1%), at conversions 16.4% and 36.1%, respectively. It is found that Co/Mn/Br −catalyst system in water-dioxane medium is effective in the aerial oxidation of substituted aromatic hydrocarbons to get corresponding alcohol and aldehydes in greater yields.

An integrated optical Mach–Zehnder interferometer functionalized by β-cyclodextrin to monitor binding reactions

We demonstrate an integrated optical Mach–Zehnder interferometer for the monitoring of guest–host reactions on immobilized β-cyclodextrin (β-CD). Adamantanecarboxylic acid, 4- tert-butylbenzoic acid and methyl orange were investigated as guest molecules. The binding constants of the three guests into the two-dimensionally arranged immobilized cyclodextrins could be determined and are a quarter to a third smaller than the values measured in the three-dimensional environment of a solution.

The crystal structure of the inclusion complex of cyclomaltoheptaose (β-cyclodextrin) with 4- tert-butylbenzoic acid

The crystal of the 1:1 complex of cyclomaltoheptaose (β-cyclodextrin, βCD) with 4- tert-butylbenzoic acid is triclinic P1 with a = 18.244(3), b = 15.476(3), c = 15.417(2) A ̊ ; α = 102.94(1), β = 113.08(1), γ = 99.69(2)°; V = 3740(1) A ̊ 3 ; and Z = 2. The final R was determined to be 0.0932 for 8111 observed reflections (Mo Kα radiation). Two independent molecules of βCD form a dimer, via hydrogen bonds involving the O-3 n atoms, that encloses two molecules of 4- tert-butylbenzoic acid. The guest molecules penetrate the βCD cavities to different depths. There are 26.8 water molecules, distributed over 30 sites, which form a dense water network surrounding the dimers.