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Indole ring is widely represented in natural compounds, as well as in a great variety of drugs. In this paper, the synthesis of a 5-hydroxybenzoindole derivative carrying a pyridyl substituent on position 1 is reported. The method involved no chromatography for purification and used solvents and catalysts of very low toxicity. [ABSTRACT FROM AUTHOR]

This paper reports a new sustainable protocol for the microwave‐assisted catalytic conversion of levulinic acid into N‐substituted pyrrolidones over tailor‐made mono (Pd, Au) or bimetallic (PdAu) catalysts supported on either highly mesoporous silica (HMS) or titania‐doped HMS, exploiting the advantages of dielectric heating. MW‐assisted reductive aminations of levulinic acid with several amines were first optimized in batch mode under hydrogen pressure (5 bar) in solvent‐free conditions. Good‐to‐excellent yields were recorded at 150 °C in 90 min over the PdTiHMS and PdAuTiHMS, that proved recyclable and almost completely stable after six reaction cycles. Aiming to scale‐up this protocol, a MW‐assisted flow reactor was used in combination with different green solvents. Cyclopentyl methyl ether (CPME) provided a 99 % yield of N‐(4‐methoxyphenyl) pyrrolidin‐2‐one at 150 °C over PdTiHMS. The described MW‐assisted flow synthesis proves to be a safe procedure suitable for further industrial applications, while averting the use of toxic organic solvents. [ABSTRACT FROM AUTHOR]

Aryl and heteroaryl iodides have been efficiently converted into the corresponding thioacetates in cyclopentyl methyl ether (CPME), a green solvent, under Cu catalysis. The chemoselectivity of the reaction is mainly controlled by electronic factors, enabling the conversion of both electron-rich and electron-deficient substrates into the corresponding thioacetates in good to excellent yields. The products can be easily deprotected to the corresponding thiolates to carry out additional synthetic transformations in situ. Surprisingly, despite CPME's relatively low dielectric constant, the reaction rate significantly increased when conducted under microwave irradiation conditions. This synthetic methodology exhibits a remarkable tolerance to functional groups, mild reaction conditions, and a wide substrate scope, utilizing a safe and inexpensive CuI pre-catalyst in the green solvent CPME. A non-aqueous workup allowing for the complete recovery of both catalyst and solvent makes this approach an environmentally sustainable protocol for C(sp2) sulfur functionalization. Additionally, the reaction shows selective cross-coupling with iodides in competition with chlorides and bromides, allowing its use in multistep syntheses. To demonstrate the potential of this methodology, it was applied to the high-yield synthesis of a photochromic dithienylethene, where a selective synthesis had not been reported before. [ABSTRACT FROM AUTHOR]

Indole ring is widely represented in natural compounds, as well as in a great variety of drugs. In this paper, the synthesis of a 5-hydroxybenzoindole derivative carrying a pyridyl substituent on position 1 is reported. The method involved no chromatography for purification and used solvents and catalysts of very low toxicity.

A new, improved 2nd generation route for the synthesis of 3‐ethyl‐4‐hydroxy‐5‐methylbenzonitrile has been developed. The original route started from 2‐ethyl‐6‐methylaniline, which was converted by a classical sequence of para‐bromination, cyanation and Sandmeyer hydroxylation into the desired phenol. This route was used on multi‐kg scale and delivered the product with the desired purity. However, the route was not ideal, as it featured safety critical steps (cyanation), employed undesirable solvents (DMF), included laborious workup and isolation procedures, and suffered from a low overall yield (40–45 %) and suboptimal green metrics (PMI: 210). We envisioned a new, non‐classical approach to the product by introducing the nitrile through a para‐selective formylation, followed by transformation of the intermediate aldehyde into the nitrile with hydroxylamine‐O‐sulfonic acid (HOSA). The new sequence of Sandmeyer hydroxylation, Duff formylation and HOSA‐promoted nitrile formation was thoroughly optimized and finally scaled up to 400 g. This novel 3‐step sequence delivered 3‐ethyl‐4‐hydroxy‐5‐methylbenzonitrile in 69 % overall yield with excellent purity (99.3 % a/a) and a vastly improved PMI of 81. [ABSTRACT FROM AUTHOR]

Reaction of glycerol with aldehydes and ketones is a strategy widely studied in literature to valorize this bioproduct. A Brønsted or Lewis acid is normally used to activate the carbonyl function and various strategies adopted to drive the equilibrium to the products. In this study ammonium salts as catalysts, and removal of water by azeotropic distillation of cyclopentyl methyl ether, permit the conversion of glycerol into acetals obtained as mixture of dioxanes and dioxolanes determined by 1H‐NMR. Under the optimized conditions, the products could be obtained in excellent yield without using excess of reactants and the solvent was recycled efficiently. [ABSTRACT FROM AUTHOR]

Aryl and heteroaryl iodides have been efficiently converted into the corresponding thioacetates in cyclopentyl methyl ether (CPME), a green solvent, under Cu catalysis. The chemoselectivity of the reaction is mainly controlled by electronic factors, enabling the conversion of both electron-rich and electron-deficient substrates into the corresponding thioacetates in good to excellent yields. The products can be easily deprotected to the corresponding thiolates to carry out additional synthetic transformations in situ. Surprisingly, despite CPME’s relatively low dielectric constant, the reaction rate significantly increased when conducted under microwave irradiation conditions. This synthetic methodology exhibits a remarkable tolerance to functional groups, mild reaction conditions, and a wide substrate scope, utilizing a safe and inexpensive CuI pre-catalyst in the green solvent CPME. A non-aqueous workup allowing for the complete recovery of both catalyst and solvent makes this approach an environmentally sustainable protocol for C(sp2) sulfur functionalization. Additionally, the reaction shows selective cross-coupling with iodides in competition with chlorides and bromides, allowing its use in multistep syntheses. To demonstrate the potential of this methodology, it was applied to the high-yield synthesis of a photochromic dithienylethene, where a selective synthesis had not been reported before.

A general catalytic protocol for the Pd‐catalyzed intramolecular arylations of N‐(2‐halogenoaryl) amides in eco‐friendly medium was successfully developed by using rationally designed acenaphthoimidazolylidene‐ligated chiral oxazoline palladacycles. Under the optimal reaction condition, a broad scope of substrates with various functional groups were well tolerated, leading to desired 3,3′‐disubstituted oxindoles in excellent yields (up to 98% yield). [ABSTRACT FROM AUTHOR]

Though foot and ankle surgery fellowships have been around for decades, contributing factors for long-term research productivity remain unreported. Along with enhancing surgical training, the American College of Foot and Ankle Surgeons (ACFAS) tasked programs with fostering research in effort to continue post-fellowship investigations. As the number of fellowship programs and fellows continues to increase, this study attempts to identifies factors associated with postfellowship research success. A PubMed search of peer-reviewed literature authored by ACFAS recognized 1-year fellowship graduates from 2000-2018 was conducted. Demographic data including current practice type and location was collected. Research activity at the 3, 5, and 10-year postfellowship period was investigated between publication history and current practice type. Statistical significance was set at p ≤.05. Among the 37 fellowships assessed, 132 fellows were eligible for analysis. Most fellows maintained hospital-based employment 46 (34%) followed by private 44 (33%) and orthopedic group 30 (22%) practices. The proportion of fellows that published 5 and 10 years postfellowship was associated with research productivity 3 and 5 years postfellowship (p ≤.03). The odds of publishing 3 years post-fellowship in orthopedic groups and university-based practices were 1.62 and 4.42 times higher compared to hospital-based graduates, respectively. The odds of publishing 5 years post-fellowship in orthopedic group and university based practices were 3.5 and 6.63 times higher than hospital-based practices, respectively. Despite the growing number of fellowships, a small proportion of fellows continue publishing postfellowship. These findings support the need to provide resources to engage graduates if retaining young practitioners in scholarly activity is desired. [ABSTRACT FROM AUTHOR]

In this work, a novel capsule phase microextraction (CPME) method coupled to high performance liquid chromatography with diode array detection (HPLC-DAD) was developed and validated for the determination of coumarin in bakery products, in accordance with the European Commission Regulation (EC) 1334/2008. The CPME extraction protocol was optimized after examining the following critical parameters: a) selection of the CPME membrane, b) sample loading time c) type of elution solvent, and d) desorption time. The optimum extraction parameters involved the use of a sol-gel CPME capsule (1 cm length), 1 mL of sample loading volume, elution with 3 mL of methanol, the stirring was set at 350 rpm, while the absorption time was 20 min and the desorption time was 15 min. The developed CPME-HPLC-DAD method was validated in terms of selectivity, linearity, accuracy, and precision and showed satisfactory results. The LOD and LOQ were equal to 0.18 µg/g and 0.48 µg/g, respectively. Trueness was assessed by means of relative percentage of recovery and ranged between 83 to 91% for intra-day experiments, and between 81-86% for inter-day experiments, respectively. The green character of the proposed method was examined using complexGAPI index. The method was successfully applied in the analysis of coumarin in bakery products.

In this work, mild Lewis acids and low environmental impact solvents were investigated for Nenitzescu synthesis. Cyclopentyl methyl ether can be used at room temperature in substitution of halogenated solvents with zinc, iron and magnesium salts as homogeneous catalysts to give 5‐hydroxyindoles in fair to good yields. The reaction features a straightforward workup and excellent solvent recycle. [ABSTRACT FROM AUTHOR]

The simplest way to prepare the tosylate salts of amino acid benzyl esters, whose enantiomers are very important synthetic intermediates, is treatment of amino acid with benzyl alcohol and p-toluenesulfonic acid in a refluxing water-azeotroping solvent (Fischer-Speier esterification). However, to this day, the literature proposes only hazardous solvents, such as benzene, carbon tetrachloride, and chloroform, which must be absolutely avoided, or solvents, such as toluene and benzyl alcohol, which cause racemization because of too high boiling water azeotropes. On the other hand, the alternative successful use of cyclohexane, which we have recently reported for several amino acid benzyl esters, is inapplicable or not very efficient for ‘problematic’ amino acid such as tryptophan, arginine, and methionine, for which, indeed, the simple Fischer-Speier esterification is not described or poorly exemplified in the literature. Therefore, more polar solvents, in particular the green ethers CPME, TAME, and Me-THF, were selected and first considered for the preparation of methionine benzyl ester, previously accomplished in cyclohexane with modest yield. After discarding CPME and TAME, because causing racemization and decomposing under acidic conditions, respectively, we focused on Me-THF. In this ether, the benzyl esters of Met, Arg, and Trp could be obtained in good yield and, as proved by chiral HPLC or H NMR analysis, enantiomerically pure. The procedure was successfully extended to proline benzyl ester, which could be prepared enantiomerically pure and in quantitative yield both in cyclohexane and in Me-THF, thus avoiding the recently reported use of carbon tetrachloride. [ABSTRACT FROM AUTHOR]

This work presents densities, dynamic viscosities, surface tensions, and refractive indices of three methyl ethereal solvents: cyclopentyl methyl ether (CPME), tert-amyl methyl ether (TAME), and tert-butyl methyl ether (MTBE). CPME and TAME were chosen as methyl alternatives of the common but environmentally problematic MTBE. The highest density, viscosity, surface tension, and refractive index were observed for CPME and the lowest for MTBE. The results are in good agreement with other authors’ data. Based on the experiments, the critical temperature and the critical pressure of CPME were estimated. The parachor, molar refraction, and critical compressibility factor were calculated from experimental data. Parameterisations of the experimental data using corresponding correlative models are presented. [ABSTRACT FROM AUTHOR]

Cyclopentyl methyl ether (CPME) has been used in chemical synthesis as an alternative to hazardous solvents. According to some earlier investigation by others, CPME has low acute or subchronic toxicity with moderate irritation and negative mutagenicity and negative skin sensitization (Local Lymph Node Assay). Calculated Permitted Daily Exposure (PDE) value of CPME obtained by our 28-day oral toxicity test is 1.5 mg/day, and CPME is thus assumed to be a class 2 equivalent solvent in the ICH (International Conference on Harmonization) Harmonized Tripartite Guideline Q3C (R5). Wide synthetic utility and a detailed toxicity study suggest CPME as a green and sustainable solvent of choice for modern chemical transformations.

[Display omitted] • The oil extraction from sewage sludge was studied using two methods for biodiesel production. • The efficiency of both organic and green solvents in oil extraction methods was examined. • Response surface methodology (RSM) was employed to model and optimize the oil extraction process. • Folch method using CPME solvent is a more efficient way for oil extraction from sewage sludge. • Biodiesel was produced using the NaOH/Clinoptilolite-Fe 3 O 4 catalyst via the electrolysis method. A comparative study of oil extraction from secondary dry sludge was performed via Reflux and Folch methods by cyclopentyl methyl ether (CPME) and hexane as green and organic solvents, respectively. Response surface methodology based on Box-Behnken design (RSM-BBD) was utilized to optimize and predict the impact of influential factors, including sludge amount (4–6 g), the volume of solvent (12–16 mL), and extraction time (2–6 h). The maximum oil extraction efficiency was 8.078 % and 4.076 % under the optimal conditions: 5.15 g, 16 mL, 2 h for CPME, and 4.22 g, 11 mL, 2 h for hexane. The raw sludge was characterized by FESEM and XRF analyses, while the extracted oil characteristics were determined by GC-Mass and FTIR methods. As a result, the Folch method by CPME solvent was a more efficient way to extract oil from sewage sludge. Finally, biodiesel was produced via the transesterification double-step process (TDSP) using NaOH/Clinoptilolite-Fe 3 O 4 magnetic catalyst. The production efficiency of biodiesel from the oil extracted by CPME and hexane is 6.94 % and 4.1 %, respectively. The maximum yield of biodiesel production was 6.94 % under the optimum reaction conditions: methanol to oil molar ratio of 10:1, catalyst weight of 0.45 wt%, and reaction time of 2.5 h with the help of the electrolysis method. [ABSTRACT FROM AUTHOR]

Cyclopentyl methyl ether (CPME) has been used in chemical synthesis as an alternative to hazardous solvents. According to some earlier investigation by others, CPME has low acute or subchronic toxicity with moderate irritation and negative mutagenicity and negative skin sensitization (Local Lymph Node Assay). Calculated Permitted Daily Exposure (PDE) value of CPME obtained by our 28-day oral toxicity test is 1.5 mg/day, and CPME is thus assumed to be a class 2 equivalent solvent in the ICH (International Conference on Harmonization) Harmonized Tripartite Guideline Q3C (R5). Wide synthetic utility and a detailed toxicity study suggest CPME as a green and sustainable solvent of choice for modern chemical transformations. [ABSTRACT FROM AUTHOR]

An appropriate solvent to perform the original Simmons-Smith reaction was reinvestigated. Among available solvents, cyclopentyl methyl ether (CPME), a recently commercialized ethereal solvent, was found to be the best so far. Compared with Et2O under reflux - the commonest conditions - reaction completion in CPME at 50 °C was about 10 times faster. The product yields and selectivities were mostly identical to those with Et2O, but were better in some cases; e.g. 13-56% with 2-cyclohexenol. The good performance of CPME should be mainly due to its moderate polarity and high boiling point. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

An appropriate solvent to perform the original Simmons-Smith reaction was reinvestigated. Among available solvents, cyclopentyl methyl ether (CPME), a recently commercialized ethereal solvent, was found to be the best so far. Compared with Et2O under reflux - the commonest conditions - reaction completion in CPME at 50 °C was about 10 times faster. The product yields and selectivities were mostly identical to those with Et2O, but were better in some cases; e.g. 13-56% with 2-cyclohexenol. The good performance of CPME should be mainly due to its moderate polarity and high boiling point. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The classical Pinner reaction has been improved by the utilization of 4N-HCl solution in cyclopentyl methyl ether (CPME) as a solvent, wherein direct isolation of the product was possible by a simple filtration. [ABSTRACT FROM AUTHOR]

• Experimental vapor liquid equilibria for ethanol + hexane + cyclopentyl methyl ether mixture. • Experimental surface tension for ethanol + hexane + cyclopentyl methyl ether mixture. • Theoretical modeling of phase equilibria and surface tension for ethanol + hexane + cyclopentyl methyl ether mixture. • Square Gradient Theory for ethanol + hexane + cyclopentyl methyl ether mixture. Vapor-liquid equilibrium (VLE) and surface tension (ST) for the hexane + ethanol + cyclopentyl methyl ether mixture have been measured and modeled. VLE determinations are carried out in a dynamic Guillespie type cell at the isobaric condition of 94 kPa, whereas the dependence of ST on concentration is measured in a maximum differential bubble pressure tensiometer at atmospheric pressure and 298.15 K. The thermodynamical consistent VLE data exhibit positive deviation from ideal behavior without ternary azeotropy and are well correlated by Redlich–Kister expansion and predicted by the binary nonrandom two-liquid, Wilson and universal quasichemical activity coefficient models. The ST data exhibit negative deviation from the linear behavior and are smoothed using the Myers-Scott expansion, showing no ternary aneotropic behavior. The experimental data of VLE and ST are accurately characterized by applying the square gradient theory to the Peng–Robinson Stryjek–Vera equation of state (EoS) appropriately extended to mixtures employing the modified Huron–Vidal mixing rule. This theoretical framework shows that experimental VLE and ST data can be fully predicted by only using binary contributions within a global average absolute deviation of 1.25% for VLE and 6.1% for ST. The theoretical approach also provides a route to explore the concentration distribution of species in the interfacial region, where it is possible to conclude that hexane exhibits both adsorption and desorption; ethanol displays strong positive adsorption whereas CPME does not exhibit surface activity. [ABSTRACT FROM AUTHOR]

Abstract: New and effective method for the Beckmann rearrangement of indanone oxime mesylate is described, in which a selective and controlled production of the isomeric isocarbostyrils is achieved. [Copyright &y& Elsevier]

β-Barrel shaped membrane proteins are attractive hosts for hybrid catalysts in which reactions are controlled through space. Production and extraction of β-barrel shaped membrane proteins in gram scale is challenging due to their hydrophobicity. Solvent mixtures such as chloroform/methanol (CM) are widely used for membrane protein extraction but toxicity and mutagenicity were reported in several cases. 2-Methyltetrahydrofuran (2-MeTHF) and cyclopentylmethylether (CPME) are two green (reduction of solvent-related environmental damage in chemical production) and potentially efficient solvents for membrane protein purification. On the example of the ferric hydroxamate uptake protein component A (FhuA) a 4-Step method was developed to provide gram amounts of highly purified FhuA: cell disruption (Step 1), removal of membrane protein impurities with n-octyl-poly-oxyethylene (oPOE) (Step 2), dissolution of membranes and FhuA precipitation (Step 3), and refolding using urea and dialysis with polyethylene-polyethyleneglycol (PE-PEG; Step 4) resulted in high FhuA purity (95% 2-MeTHF, 80% CPME; 70mg FhuA per liter fermenter broth). Structural integrity of FhuA protein was confirmed by circular dichroism (CD) and a translocation functionality assay., (Copyright © 2013 Elsevier B.V. All rights reserved.)