Reaction of Glycerol with Trimethyl Orthoformate: Towards the Synthesis of New Glycerol Derivatives

The reactivity of glycerol with trimethyl orthoformate is here described with an emphasis on developing a reliable synthetic approach for glycerol valorization. The glycerol based orthoester 4-(dimethoxymethoxy)methyl)-2-methoxy-1,3-dioxolane (3) was synthesized, under catalytic as well as catalyst-free conditions, by taking advantage of the thermodynamically controlled equilibrium between intermediates. Both Brønsted and Lewis acid catalysts accelerated the attainment of such an equilibrium, particularly Brønsted acidic ionic liquids BSMImHSO4 and BSMImBr were the most effective compounds for this reaction. The kinetic profiles allowed the proposal of a mechanism that accounts for the selectivity of the reaction

Intensifying organic processes: a \u201cgreen\u201d toolbox for the synthesis of benign-by-design chemicals from waste feedstocks

This Ph.D. thesis is centered on developing greener methodologies for the synthesis of bio-based compounds starting from waste or low-value feedstock. The work is divided in two main chapters based on output, one dealing with the synthesis of cyclic organic carbonates (Chapter 2), the other with the synthesis of glycerol derivatives (Chapter 3). In Chapter 2 a novel class of tungstate ionic liquids (TILs) was studied. Different synthetic routes were followed, some already published, others that exploit a green halide-free protocol developed in this thesis. The TILs were initially investigated for the CO2 fixation reaction into epoxides. Once established their potential use in this field, the TILs were investigated for the tandem direct oxidative carboxylation (DOC) of olefins to give cyclic organic carbonates. Tandem catalysis is a way to achieve process intensification by using the same catalyst for two or more sequential reaction steps having different mechanisms. TILs are demonstrated as effective tandem catalysts for the direct synthesis of COCs from olefins. In the first step, the TILs promote epoxidation of the olefin, while in the second step they catalyse insertion of CO2 into the epoxide, without any intermediate work-up. The procedure is greener than current protocols from several standpoints: H2O2 is used as oxidant, atmospheric pressure of CO2 is sufficient to achieve yields >90% in COCs and product recovery occurs by simple phase separation. Additionally, simple alkali metal halide salts (e.g., NaBr, NaI, KBr, KI) are sufficient to promote CO2 insertion into epoxides in place of traditional costlier (for their environmental burden and resource use) ammonium halides. The simple alkali metal halide salt NaBr is also used as catalysts in a new CO2 insertion process run in continuous flow. In this case, NaBr is activated by diethylene glycol (DEG) that acts as an inexpensive and largely available complexing agent for Na+ as well as a hydrogen-bond donor that promotes the ring- opening of the epoxides. An in-depth study of the continuous-flow conditions allowed to obtain COCs with high yields from terminal epoxides, and with a higher overall productivity compared to the batch process. A simple method for the recycling of the catalytic system was also developed. In Chapter 3, focus is on the synthesis of high value-added glycerol derivatives, i.e., esters, acetals and orthoesters of glycerol. Initially, the acetylation of glycerol and glycerol acetals with esters (in lieu of the commonly used acetic acid and acetic anhydride) in continuous flow was developed. A thermal, catalyst- free, continuous flow protocol allowed to reach high conversions of the substrates. Among the different esters that were tested, isopropenyl acetate (iPAc) showed the highest performance, affording quantitative yields in marketable products such as Solketal acetate and triacetin. The better performance of iPAc is due to the fact that it promotes an irreversible esterification process caused by the release of acetone. Next, tandem acetalization of glycerol with the acetone released in situ was studied. This reaction did not proceed satisfactorily under catalyst-free conditions. The direct synthesis of Solketal acetate by tandem acetalization-acetylation reactions of glycerol with isopropenyl acetate was therefore explored using Amberlyst-15 as acid catalyst. By addition of acetic acid and/or acetone as co-reactant, the selective synthesis of Solketal acetate or of a 1:1 mixture of Solketal acetate and triacetin was attained. Finally, new bio-based glycerol derivatives by reaction with orthoesters were investigated. The reactions of glycerol with this class of compounds \u2013 only scarcely explored in the 60s \u2013 yielded the first regioselective synthesis of 5-membered ring diastereoisomeric derivatives of glycerols through a catalyst-free procedure

Direct oxidative carboxylation of terminal olefins to cyclic carbonates by tungstate assisted-tandem catalysis

Tungstate catalysts are well established for olefin epoxidation reactions, while their catalytic activity for CO2 insertion in epoxides is a more recent discovery. This dual reactivity of tungstate prompted the present development of a catalytic tandem process for the direct conversion of olefins into the corresponding cyclic organic carbonates (COCs). Each of the two steps was studied in the presence of the ammonium tungstate ionic liquid catalyst - [N-8,N-8,N-8,N-1](2)[WO4] - obtained via a benign procedure starting from ammonium methylcarbonate ionic liquids. The catalytic epoxidation first step was optimised on 1-decene as model substrate, using H2O2 as benign oxidant, [N-8,N-8,N-8,N-1](2)[WO4] as catalyst and phosphoric acid as promoter affording quantitative conversion with 92% selectivity towards decene oxide. Unfortunately, the addition of CO2 from the start (auto-tandem catalysis) gave low yields of decene carbonate (<10%). On the contrary, the addition of 1 atm CO2 and tetrabutyl ammonium iodide after completion of the epoxidation first step without any intermediate work-up (assisted-tandem catalysis) afforded a 94% yield in decene carbonate. The protocol could be scaled up to a 10 gram scale. The scope of the reaction was demonstrated for primary aliphatic olefins with different alkyl chain lengths (C-6-C-16), while cyclic and aromatic activated olefins such as cyclohexene and styrene suffered from the formation of undesired overoxidation products in the first step

Diethylene Glycol/NaBr catalyzed CO2 insertion into terminal epoxides: from batch to continuous flow

CO2 insertion reactions on terminal epoxides (styrene oxide, 1,2-epoxyhexane and butyl glycidyl ether) were performed in a binary homogeneous mixture comprising NaBr as the nucleophilic catalyst and diethylene glycol (DEG) as both solvent and catalyst activator (cation coordinating agent). The reaction protocol was initially studied under batch conditions either in autoclaves and glass reactors: quantitative formation of the cyclic organic carbonate products (COCs) were achieved at T=100 degrees C and p(0)(CO2)=1-40 bar. The process was then transferred to continuous-flow (CF) mode. The effects of the reaction parameters (T, p(CO2), catalyst loading, and flow rates) were studied using microfluidic reactors of capacities variable from 7.85 . 10(-2) to 0.157 cm(3). Albeit the CF reaction took place at T=220 degrees C and 120 bar, CF improved the productivity and allowed catalyst recycle through a semi-continuous extraction procedure. For the model case of 1,2-epoxyhexane, the (non-optimized) rate of formation of the corresponding carbonate, 4-butyl-1,3-dioxolan-2-one, was increased up to 27.6 mmol h(-1) equiv.(-1), a value 2.5 higher than in the batch mode. Moreover, the NaBr/DEG mixture was reusable without loss of performance for at least 4 subsequent CF-tests