Nicolas Duguet

Glycerol Ether Synthesis: A Bench Test for Green Chemistry Concepts and Technologies

and Technologies Marc Sutter,† Eric Da Silva,† Nicolas Duguet,† Yann Raoul,‡ Estelle Met́ay,† and Marc Lemaire*,† †Equipe Catalyse Synthes̀e Environnement, Institut de Chimie et Biochimie Molećulaires et Supramolećulaires, UMR-CNRS 5246, Universite ́ de Lyon, Universite ́Claude Bernard-Lyon 1, Bat̂iment Curien, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne Cedex, France ‡Organisation Nationale Interprofessionnelle des Oleágineux, 11 rue de Monceau, CS 60003, 75378 Paris Cedex 08, France

Amidation of phenol derivatives: a direct synthesis of paracetamol (acetaminophen) from hydroquinone

A direct synthesis of paracetamol (acetaminophen) from hydroquinone has been developed using ammonium acetate as an amidating agent. The reaction proceeds in acetic acid at elevated temperatures without any metallic catalyst. Under these conditions, paracetamol was obtained with high yield and selectivity (>95%). The reaction has also been carried out on the multi-gram scale (44 g of hydroquinone) and a potential process has been proposed based on the recycling of the solvent and by-products. This amidation protocol has also been extended to other phenol derivatives.

Preparation of amphiphilic sorbitan monoethers through hydrogenolysis of sorbitan acetals and evaluation as bio-based surfactants

Amphiphilic sorbitan acetals have been prepared from sorbitan by acetalisation using linear aliphatic aldehydes or by transacetalisation starting from the corresponding aldehyde diethylacetals. A series of sorbitan acetals has been obtained with 29–81% isolated yields. It has been shown that these sorbitan acetals exist as a mixture of five-membered and six-membered regioisomers. Hydrogenolysis of the mixtures gave the corresponding sorbitan ethers as a mixture of 3 regioisomers with 55–85% isolated yields. A one-pot two-step procedure was also optimized from sorbitan giving similar results. The amphiphilic properties of sorbitan acetals and ethers were evaluated and both families exhibit interesting surfactant properties.

Catalytic reductive cleavage of methyl α-D-glucoside acetals to ethers using hydrogen as a clean reductant

The palladium-catalysed reductive cleavage of methyl glucoside acetals has been studied using hydrogen as a clean reducing agent. The reaction proceeds at 120 °C in cyclopentyl methyl ether (CPME) without acid co-catalyst. Under these conditions, the corresponding methyl glucoside monoethers were obtained with poor to good isolated yields (37–81%) and high selectivities (86–99%).

Thiazolylidene-catalyzed cleavage of methyl oleate-derived α-Hydroxy ketone to the corresponding free aldehydes

The thiazolylidene-catalyzed cleavage of the α-hydroxy ketone derived from methyl oleate gave the corresponding aldehydes under nonoxidative conditions through a retro-benzoin process. The aldehydes produced are in equilibrium with their corresponding acyloins. To illustrate the synthetic utility of this protocol, the aldehydes were recovered by distillation.

Homogeneous and heterogeneous catalytic (dehydrogenative) oxidation of oleochemical 1,2-diols to α-hydroxyketones

Herein, the preparation of methyl oleate α-hydroxyketone from the corresponding 1,2-diol was investigated using both homogeneous and heterogeneous systems. Homogeneous conditions using a Pd(OAc)2/neocuproine complex were first developed using oxygen as a sole oxidant under mild conditions (MeOH, 50 °C). Under these conditions, the conversion of diol reached 95%, and α-hydroxyketone was obtained with 97% selectivity. The access to α-hydroxyketone has also been studied by dehydrogenation using a range of heterogeneous catalysts under solvent-free conditions at high temperatures (160–180 °C). Dehydrogenation using activated Ru/C under vacuum provided α-hydroxyketone with 93% conversion and 82% GC yield. The optimized conditions were applied to a range of oleochemical diols, including a vegetable oil derivative, to obtain the corresponding α-hydroxyketones with up to 74% isolated yields.

Dodecyl sorbitan ethers as antimicrobials against Gram-positive bacteria

A range of amphiphilic sorbitan ethers has been synthesized in two steps from sorbitan following an acetalization/hydrogenolysis sequence. These sorbitan ethers and the acetal intermediates have been evaluated as antimicrobials against Gram-negative and Gram-positive bacteria. No antimicrobial activity was observed for Gram-negative bacteria. However, the compounds bearing a linear dodecyl chain exhibit antimicrobial activity (MIC as low as 8μg/mL) against Gram-positive bacteria such as Listeria monocytogenes, Enterococcus faecalis and Staphylococcus aureus. Encouraged by these preliminary results, dodecyl sorbitan was tested against a range of resistant strains and was found to be active against vancomycin-, methicillin- and daptomycin-resistant strains (MIC=32-64μg/mL).

Solvent-free direct α-alkylation of ketones by alcohols catalyzed by nickel supported on silica–alumina

The α-alkylation of acetophenone with benzyl alcohol through borrowing hydrogen has been studied using nickel catalysis. Ni/SiO2-Al2O3 was found to be the best catalyst for this transformation and the corresponding alkylated acetophenone was obtained with 93% isolated yield. Following the objectives of clean and sustainable chemistry, the reaction occurs under solvent-free conditions and requires only a catalytic amount of base. This protocol was next applied to a wide range of ketones and alcohols and the desired products were isolated with 18–86% yields (26 examples). The recovery and recyclability of the nickel catalyst was also investigated and it was found to be active over 5 runs without significant loss of activity. Surprisingly, the active catalyst appears to include an amorphous nickel hydroxide layer.

Robust Organocatalysts for the Cleavage of Vegetable Oil Derivatives to Aldehydes through Retrobenzoin Condensation

A series of thiazolium salts was prepared and tested for the cleavage of the α-hydroxyketone derived from methyl oleate. The robustness of these precatalysts was determined by dynamic thermogravimetric analyses (TGA). It has been shown that the stability of these species is mainly governed by the nature of the counter-anion and some of them were found to be stable until 350-400 °C. The α-hydroxyketone derived from methyl oleate was cleaved under reactive distillation conditions using optimized, thermally robust N-butylthiazolium triflate to give the cleavage product, namely, nonanal and methyl azelaaldehydate, with 85 and 70 % yields. A range of α-hydroxyketones derived from several fatty acids was cleaved to give the corresponding bio-based aldehydes with up to 98 % isolated yields. Finally, this protocol was successfully applied to a high-oleic sunflower oil derivative.