Marco Noè

Ionic Liquids Made with Dimethyl Carbonate: Solvents as well as Boosted Basic Catalysts for the Michael Reaction

This article describes 1) a methodology for the green synthesis of a class of methylammonium and methylphosphonium ionic liquids (ILs), 2) how to tune their acid-base properties by anion exchange, 3) complete neat-phase NMR spectroscopic characterisation of these materials and 4) their application as active organocatalysts for base-promoted carbon-carbon bond-forming reactions. Methylation of tertiary amines or phosphines with dimethyl carbonate leads to the formation of the halogen-free methyl-onium methyl carbonate salts, and these can be easily anion-exchanged to yield a range of derivatives with different melting points, solubility, acid-base properties, stability and viscosity. Treatment with water, in particular, yields bicarbonate-exchanged liquid onium salts. These proved strongly basic, enough to efficiently catalyse the Michael reaction; experiments suggest that in these systems the bicarbonate basicity is boosted by two orders of magnitude with respect to inorganic bicarbonate salts. These basic ionic liquids used in catalytic amounts are better even than traditional strong organic bases. The present work also introduces neat NMR spectroscopy of the ionic liquids as a probe for solute-solvent interactions as well as a tool for characterisation. Our studies show that high catalytic efficacy of functional ionic liquids can be achieved by integrating their green synthesis, along with a fine-tuning of their structure. Demonstrating that ionic liquid solvents can be made by a truly green procedure, and that their properties and reactivity can be tailored to the point of bridging the gap between their use as solvents and as catalysts.

Carbonate phosphonium salts as catalysts for the transesterification of dialkyl carbonates with diols. The competition between cyclic carbonates and linear dicarbonate products

At 90-120 °C, in the presence of methylcarbonate and bicarbonate methyltrioctylphosphonium salts as catalysts ([P8881][A]; [A] = MeOCO2 and HOCO2), the transesterification of non-toxic dimethyl- and diethyl-carbonate (DMC and DEC, respectively) with 1,X-diols (2 ≤ X ≤ 6) proceeds towards the formation of cyclic and linear products. In particular, 1,2-propanediol and ethylene glycol afford propylene- and ethylene-carbonate with selectivity and yields up to 95 and 90%, respectively; while, the reaction of DMC with higher diols such 1,3-butanediol, 2-methyl-1,3-propanediol, 1,3-propanediol, 2,2-dimethyl, 1,3-propanediol, 1,4-butanediol and 1,6-hexanediol produce linear C8-C10 dicarbonates of general formula MeOC(O)O∼∼∼OC(O)OMe as the almost exclusive products. Of note, these dicarbonate derivatives are not otherwise accessible in good yields by other conventional base catalyzed methods. Among 1,3-diols, the only exception was 2-methyl 2,4-pentandiol that yields the corresponding cyclic carbonate, i.e. 4,4,6-trimethyl-1,3-dioxan-2-one. In no one case, polycarbonates are observed. Such remarkable differences of product distributions are ascribed to the structure (branching and relative position of OH groups) of diols and to the role of cooperative (nucleophilic and electrophilic) catalysis which has been proved for onium salts. The investigated carbonate salts are not only effective in amounts as low as 0.5 mol%, but they are highly stable and recyclable.

Methylcarbonate and bicarbonate phosphonium salts as catalysts for the nitroaldol (Henry) reaction.

Phosphonium ionic liquids exchanged with bicarbonate and methylcarbonate anions (CILs) exhibit catalytic performances comparable to those of sterically hindered (non nucleophilic) organosuperbases such as DBU. At 25-50 °C, under solventless conditions, CILs efficiently catalyze the Henry addition of different aldehydes and ketones to nitroalkanes: not only they allow the selective formation of nitroaldols but they unlock a novel high-yielding access to dinitromethyl derivatives of ketones.

Upgrading of glycerol acetals by thermal catalyst-free transesterification of dialkyl carbonates under continuous-flow conditions

At 250–300 °C and 30–50 bar, a continuous-flow (CF) transesterification of different dialkyl and alkylene carbonates (dimethyl-, diethyl-, dibenzyl-, and propylene carbonate, respectively) with two glycerol derived acetals (glycerol formal and solketal) was investigated without any catalyst. An unprecedented result was obtained; not only the desired process occurred, but also the formation of the corresponding mono-transesterification products took place with an excellent selectivity (up to 98%) in all cases. Under isothermal conditions, a study on the effect of pressure allowed us to optimize the conversion of acetals (up to 95%) for the reactions of dimethyl- and diethyl-carbonate (DMC and DEC, respectively). This proved that an abrupt progress of the reaction occurred for very small increments of pressure. For example, at 250 °C, the thermal transesterification of DMC with glycerol formal showed a sharp increase of the conversion from 1–2% at 30 bar to ∼85% at 37 bar. The lower the temperature, the lower the pressure interval at which the onset of the reaction is achieved. The absence of catalysts allowed us to run CF-reactions virtually indefinitely and with a very high productivity (up to 68 mg min−1) compared to the capacity (1 mL) of the used CF-reactor. Products of the transesterification of DMC and DEC were isolated in good-to-almost quantitative yields. In the case of heavier carbonates, steric reasons were responsible for the considerably lower reactivity of propylene carbonate (PC) with respect to DMC and DEC, while the transesterification of dibenzyl carbonate (DBnC, solid at room temperature) with glycerol formal required the presence of acetone as an additional solvent/carrier. Although the reactions of both PC and DBnC were not optimized, results offered a proof-of-concept on the extension of thermal transesterification processes to higher homologues of linear and alkylene carbonates.

A flexible Pinner preparation of orthoesters: the model case of trimethylorthobenzoate

In the absence of additional solvents, a novel procedure was implemented for the synthesis of trimethylorthoesters through the Pinner reaction. At 5 °C, the reaction of both aliphatic and aromatic nitriles (RCN; R = Et, Bu, Ph) with a moderate excess of MeOH and gaseous HCl gave the corresponding imidate hydrochlorides [RC(NH)OR′·HCl] in excellent yields (>90%). At 25–65 °C, the methanolysis of alkyl imidate salts provided trimethylortho-propionate and valerate, while only traces of trimethylorthobenzoate (TMOB) were observed. However, the aromatic hydrochloride could be readily converted into the hydrogenphosphate salt [PhC(NH)OR′·H3PO4] which, in turn, underwent a selective (>80%) reaction with MeOH to produce TMOB in a 62% isolated yield. This allowed for an unprecedented Pinner-type synthesis of TMOB starting from benzonitrile, rather than from the highly toxic trichloromethylbenzene. Overall, remarkable improvements in safety and process intensification were achieved.

Selective Nitroaldol Condensations over Heterogeneous Catalysts in the Presence of Supercritical Carbon Dioxide

At 40-60 degrees C, in the presence of heterogeneous catalysts based on Al2O3, supercritical carbon dioxide not only acts as a good solvent for the reaction of aromatic and aliphatic aldehydes with 1-nitroalkanes but, most importantly, it also allows the selectivity to be tuned between the competitive formation of beta-nitroalcohols and nitroalkenes (from the Henry reaction and the nitroaldol condensation, respectively). In particular, when the pressure (and the density) of the supercritical phase is enhanced from 80 to 140 bar, the nitroalkenes selectivity increases, on average, from approximately 60 to >90%. Experiments show that, in the same pressure range, a steep increase of the concentration profiles of reactant aldehydes takes place. By contrast, under solvent-free conditions, the reaction usually proceeds with a higher conversion, but nitroalkanols are the major products.

Improved synthesis of tadalafil using dimethyl carbonate and ionic liquids

An improved synthesis of tadalafil, a drug for the treatment of male erectile dysfunction, involves the use of safer solvents and reagents as well as a reduced number of steps.

Phosphonium nitrate ionic liquid catalysed electrophilic aromatic oxychlorination

Trioctylmethylphosphonium nitrate (P8,8,8,1NO3), an ionic liquid made via a green synthesis, catalyses electrophilic aromatic chlorination of arenes with HCl and air at 80 °C. The aromatic oxychlorination is truly catalytic in nitrate, proceeds without added solvents, and uses atmospheric oxygen as oxidant. The extent of chlorination can be controlled to yield selectively mono or dichlorinated products, and the ionic liquid catalyst can be recycled. Dependence of the chlorination rate on HCl and nitrate concentrations as well as on the rate of re-oxidation of the nitrogen intermediates by air, allowed us to propose a reaction mechanism.

Synthesis of the Fatty Esters of Solketal and Glycerol-Formal: Biobased Specialty Chemicals.

The caprylic, lauric, palmitic and stearic esters of solketal and glycerol formal were synthesized with high selectivity and in good yields by a solvent-free acid catalyzed procedure. No acetal hydrolysis was observed, notwithstanding the acidic reaction conditions.

Methyltriphenylphosphonium Methylcarbonate, an All‐In‐One Wittig Vinylation Reagent

The methyltriphenylphosphonium methylcarbonate salt [Ph3 PCH3 ][CH3 OCO2 ], obtained directly by quaternarization of triphenylphosphine with dimethylcarbonate, is a latent ylide that promotes Wittig vinylation of aldehydes and ketones. Alkenes are obtained simply by mixing [Ph3 PCH3 ][CH3 OCO2 ] and the carbonyl and heating in a solvent (no base, no halides, and no inorganic byproducts). Deuterium exchange experiments and the particularly short anion-cation distance measured by XRD in [Ph3 PCH3 ][CH3 OCO2 ] allowed to explain the nature and reactivity of this species. Green chemistry metrics (atom economy, mass index, environmental factor) indicate that this vinylation procedure is more efficient than comparable ones. Deuterated [Ph3 PCD3 ][CH3 OCO2 ] promoted the synthesis of deuterated olefins.