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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]

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]

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]

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]

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]