Optimization of Nazarov Cyclization of 2,4-Dimethyl-1,5-diphenylpenta-1,4-dien-3-one in Deep Eutectic Solvents by a Design of Experiments Approach

Abstract

The unprecedented Nazarov cyclization of a model divinyl ketone using phosphonium-based Deep Eutectic Solvents as sustainable non-innocent reaction media is described. A two-level full factorial Design of Experiments was conducted for elucidating the effect of the components of the eutectic mixture and optimizing the reaction conditions in terms of temperature, time, and substrate concentration. In the presence of the Deep Eutectic Solvent (DES) triphenylmethylphosphonium bromide/ethylene glycol, it was possible to convert more than 80% of the 2,4-dimethyl-1,5-diphenylpenta-1,4-dien-3-one, with a specific conversion, into the cyclopentenone Nazarov derivative of 62% (16 h, 60 °C). For the reactions conducted in the DES triphenylmethylphosphonium bromide/acetic acid, quantitative conversions were obtained with percentages of the Nazarov product above 95% even at 25 °C. Surface Responding Analysis of the optimized data furnished a useful tool to determine the best operating conditions leading to quantitative conversion of the starting material, with complete suppression of undesired side-reactions, high yields and selectivity. After optimization, it was possible to convert more than 90% of the model substrate into the desired cyclopentenone with cis percentages up to 77%. Experimental validation of the implemented model confirmed the robustness and the suitability of the procedure, leading to possible further extension to this specific combination of experimental designs to other substrates or even to other synthetic processes of industrial interest.

Promising Technological and Industrial Applications of Deep Eutectic Systems

“…Surface Responding Analysis (SRA) confirmed the synergic effect between the former components of the DES, which increases the expected performances of the system. Thus, conversions >90% with high chemoselectivity were reached under mild conditions (43 • C) [158].…”

A Phenylpropanoid Compound from the Seeds of Sterculia quadrifida and its Cytotoxic Activity

“…The results of the 13 C-NMR spectrum analysis (Figure 4), DEPT 135 (Table 1), and HSQC (Table 1) ). 16 COSY and HMBC analyses were performed to verify the proposed structure (Figure 5). The COSY analysis observed correlations between the protons H2-H3-H4, H-2'-H3', H5'-H6', H2''-H3'', and H5''-H6'', supporting the presence of a benzene structure and an α,β-unsaturated carbonyl (Table 1).…”

Deep Eutectic Solvents and Multicomponent Reactions: Two Convergent Items to Green Chemistry Strategies

“…The Nazarov cyclization of the model substrate 2,4‐dimethyl‐1,5‐diphenylpenta‐1,4‐dien‐3‐one has been optimized in deep eutectic mixtures containing triphenylmethylphosphonium bromide (TPMPBr) and acetic acid or ethylene glycol as hydrogen bond donors. [144] This reaction has been extended using NDES formed from choline chloride and carboxylic acids [145] (Scheme 21 ).…”