In 1979 I needed to synthesize for my personal thesis work a particular alkene, accessible certainly by Wittig reaction in homogeneous anhydrous medium or in transfer of liquid liquid phase, I substitute for convenience the medium water / benzene by 1,4-dioxane , the soda remaining in solid form. The result was staggering since the alkene was obtained selectively with a quantitative yield. Traces of water present at the solid / liquid interface, by modifying the nature of the interactions between anions and cations of the solid base, were in fact at the origin of this result. One of the first solid / liquid phase transfer reactions in a weakly hydrated organic medium had just emerged.
Functionalized alkenes and functionalized epoxies
Furfural chosen as the model molecule was thus quantitatively converted into 2-vinyl furan or corresponding functionalized alkenes in the presence of a solid alkali metal hydroxide or carbonate, an organic phase constituted by the solvent, the reagents under consideration and traces of water in carefully quantified quantities. This reaction, generalized to the whole of the carbonyl function, proceeds according to an original reaction mechanism which favors, thanks to the specific solvation of the intermediate species at the solid / liquid interface, a preferential orientation towards the alkene Z or E.
It also allows the conversion of phenolic aldehydes to corresponding alkenes and in particular the first direct synthesis from p-hydroxy-benzaldehyde of 2-vinyl phenol or p-hydroxystyrene, a monomer of great interest in macromolecular chemistry.
In addition, the possible modulation of acid-base interactions makes it possible for the first time to obtain, by promoting the formation of ylide at the expense of the aldolisation reaction, the conversion of aliphatic aldehydes to the corresponding alkenes with high yields.
The transformation of a carbonyl derivative into epoxides using a heterogeneous solid-liquid medium weakly hydrated was developed with furfural and then generalized to various aldehydes and ketones: aromatic, heteroaromatic and aliphatic.
This study demonstrated the good performance of brominated alkylated sulfonium salts and powdered potassium hydroxide as a base. The use of thiolanium salt allowed for the first time the stereoselective obtaining of epoxy-esters.
The need to use a solid base, in some cases different from potassium hydroxide, has made clear the importance of acid-base and molecular interactions between the sulfonium salt and the basic agent.
Infra-Red analysis and a crystallographic study show that the formation of the sulphonium ylide and thus that of the epoxide requires :
- a basic power of the base sufficient to tear the proton from the sulphonium salt,
- a structure of the crystalline mesh of the basic agent compatible with that of the sulphonium salt so that it can allow the approach of the salt towards its active sites and ensure the ylide a stability and a sufficient nucleophilic power to attack the carbonyl function.
Moreover, it appears that the water molecules introduced at the beginning of the reaction in a controlled quantity and localized on the surface of the base play a determining role in :
- the formation of the sulphonium ylide by modifying the surface of the crystal lattice
- betaine rearrangement by decreasing the interactions of oxyanion with the base.
Finally, a study of the kinetics of the furfural epoxidation reaction and the conditions of treatment of the reaction medium enabled us, by liquid-liquid extraction, to isolate 95% of 2-furyl oxirane with a purity of 96%.
Functionalized ethylenic esters and formylation of phenolic aldehydes
The condensation of alkyl diethylphosphonoacetate with furfural, hydroxymethylfurfural, and a very large number of ketones and aldehydes in heterogeneous medium solid / liquid weakly hydrated, leads selectively and quantitatively to the corresponding ethylenic esters. A successive transesterification reaction in protic medium allows access depending on the nature of the alcohol used to a new class of esters.
The spectroscopic characterization of the intermediate species located at the solid-liquid interface shows that these reactions proceed according to a reaction mechanism characterized by :
- a decisive influence of intermediate carbanionic structures,
- the need for compatibility between the microcrystalline structure of the base and the phosphonate considered,
- the existence of a monoadsorbed interfacial process with the carbonyl compound in solution,
- the role of water which allows the solid base to present a microcrystalline structure compatible with the substrates in the presence and which promotes the final decomposition of the intermediate oxaphosphetane,
- the regeneration of the active centers of the solid base assisted by the phosphate generated at the end of the reaction in the form of acid.
The use of solid sodium hydroxide in the presence of carefully quantified water traces allows the phenol formylation by chloroform and thus the synthesis with high yields of parahydroxybenzaldehyde and salicylaldehyde.
Formylation is governed by the generation and subsequent reactivity of the solid-liquid interface of dichlorocarbene and phenate. The formation of the dialdehydes essentially proceeds by simultaneous double formylation of the phenol by the stabilization of a chlorocarbon intermediate by the alcohol at the solid-liquid interface. The generalized synthesis method with different substituted phenols leads to remarkable results. Thus guaïcol is converted for the first time quantitatively into vanillin, orthovanillin and 2,4-diformyl 6-methoxy phenol.
Thiirans and unsaturated nitriles
Another illustration of the effectiveness of the weakly hydrated solid-liquid heterogeneous medium in organic syntheses is the conversion of epoxides to thiiranes.
Indeed, a new method for obtaining these sulfur derivatives has been proposed by involving a solid sulfur agent (thiourea or potassium thiocyanate) in the presence of a small amount of water.
Two access routes are studied. They make use of the exceptional performances of anionic activation in heterogeneously weakly hydrated medium. The cyano agents are diethylphosphonacetonitrile and acetonitrile. Depending on the aldehydes or ketones, they lead to the corresponding substituted acrylonitriles.
Remarkable results have been obtained with furan aldehydes whose reactivity remained poorly controlled until then with conventional techniques.