Solvent-free Claisen condensation

As with ketone enolate anions (see 16-34), the use of amide bases under kinetic control conditions (strong base with a weak conjugate acid, aprotic solvents, low temperatures), allows the mixed Claisen condensation to proceed. Self-condensation of the lithium enolate with the parent ester is a problem when LDA is used as a base, ° but this is minimized with LICA (lithium isopropylcyclohexyl amide).Note that solvent-free Claisen condensation reactions have been reported. ° ... 

Chalcones (123) are commonly prepared by Claisen-Schmidt or aldol condensation. An important way to synthesize chalcones (123) is the Friedel-Crafts acylation involving treatment of acid chlorides (121) with arenes (122). Such a protocol for the synthesis of chalcones (123) was developed by More et al. (2012) using nano-ZnO heterogeneous catalyst under solvent-free conditions at room temperature (Scheme 9.38). Arenes (122) of all sorts, activated as well as unactivated, reacted smoothly to afford the chalcones (123) in excellent yield. High regioselectivity was observed during the course of reaction, which occurred selectively at the para-position of OMe, Br, Me, and Cl. 

The most conunonly used solvents for the study of the laser action are a 2 1 1 mixture of jS-ethoxypropionitrile, j8-ethojgfethanol and acetonitrile (EAA), a 1 1 1 mixture of proprion-itrile, butyronitrile and isobutyronitrile ( nitrile solvent ), a 3 1 ethanol-methanol mixture, a 3 1 ethanol-DMF mixture, and acetonitrile. Some of the mixed solvent systems remain liquid to temperatures as low as -150 °C. However, the /3-diketonate complexes are not always stable for a long time in such solutions. For instance, Schimitschek et al. (1965b) mention that emopimn(III) j8-diketonate complexes degrade in the 3 1 ethanol methanol mixture. Fry and Pirie (1965) foimd that in this alcohol mixture, [Eu(bzac)3(H20)] decomposed upon heating the solution to 70 °C or upon irradiation with ultraviolet radiation. The main decomposition products were ethyl acetate and acetophenone, which indicates that benzoylacetonate underwent a reverse Claisen condensation. Brecher et al. (1965) discussed the dissociation in solution of the tetrakis complexes into mixtures of non-lasing tris complexes and free jS-diketonate anions. 

The synthetic pathways developed to access the target pyridazinone arrays are based on the assembly of the exocyclic a,P-unsaturated framework through either Knoevenagel (chemotype A) or Claisen-Schmidt (chemotypes B and C) condensations (Scheme 1.11) with silica-supported aluminum chloride anployed as a catalyst. In comparison with conventional aluminum chloride, the silica-supported equivalent offers several advantages over the free catalyst (milder acidity, superior shelf Ufe, and the ability to condnct nonaqueous workups) and the polystyrene-supported version (no swelling and ability to carry out reaction in polar solvents). 

---