The Use of Switchable Polarity Solvents for the Synthesis of 16‐Arylidene Steroids via Claisen–Schmidt Condensation

Abstract

Switchable polarity recyclable solvent mixtures were applied as reaction medium and catalyst to replace the conventional base catalysts in the Claisen–Schmidt condensation of 17‐oxo steroids with aromatic aldehydes. Reversibility between ionic and nonionic forms of the new 2‐n‐butyl‐1,1,3,3‐tetramethylguanidine (nBu‐TMG)/ethylene glycol/CO2 and 2‐tert‐butyl‐1,1,3,3‐tetramethylguanidine (tBu‐TMG)/ethylene glycol/CO2 systems were proved by conductivity measurements. The structure of the ionic form was established by 1H NMR and IR measurements and by quantum chemical calculations. The steroidal products with androstane and estrane skeleton were characterised with spectroscopic methods (NMR, IR, MS).

Claisen‐Schmidt Condensation and Domino Claisen‐Schmidt Condensation ‐ Michael Addition of 16‐Formyl Steroids in the Presence of Switchable Polarity Solvents

“…The structure of 18 a is supported by 1 H-and 13 C NMR measurements (Figure 2). Similarly to the nBu-TMG/ethylene glycol system reported before, [18] the signals of the nonequivalent methylene protons of alkylcarbonate 18 a appeared as two multiplets between 3.84-3.87 ppm and 3.55-3.57 ppm. The presence of these nonequivalent groups proves that the anion is not symmetric, only one of the hydroxyl groups of ethylene glycol was converted to a carbonate.…”

“…The two peaks collapse again into one broad signal after introduction of CO 2 .This phenomenon can be explained by the charge resonance within the guanidinium ion. [35] The IR spectrum of the ionic liquid 18 a shows similar features observed before for the nBu-TMG + ethylene glycol + CO 2 system, [18] such as the splitting of the C=N band around 1600 cm À 1 and the appearance of the δ(CO 2 ) vibration at 1284 cm À 1 (Figure S2). Unfortunately, all attempts to convert the ionic liquid 18 a back to the molecular solvent without some loss of the components failed.…”

“…The alcohol component had been shown to accelerate the condensation reaction. [18] Besides, at the end of the reaction the presence of the alcohol is necessary to form the alkylcarbonate ionic liquid to facilitate product separation (Scheme 2). Although relatively few information exists on the toxicity on guanidinium-based ionic liquids, tetramethylguanidinium cations with benzoate, salicylate, lactate, dihydrogen phosphate, nitrate, formate, acetate, propanoate, butanoate and valerate anions were found to be easily biodegradable.…”

“…Recyclability of the catalyst was also demonstrated. [18] In continuation of this work, the synthesis of other 16substituted derivatives was attempted starting from 16-formyl steroids (Figure 1) by the application of the same methodology.…”

Microwave-Assisted Stereoselective Heterocyclization to Novel Ring d-fused Arylpyrazolines in the Estrone Series

“…During preliminary experiments to synthesize novel ring d -fused pyrazolines in the estrone series, 16-benzylidene-estrone 3-methyl ether ( 2 ) [36], obtained from its precursor ( 1 ) by MW-assisted Claisen-Schmidt condensation, was reacted with hydrazine hydrate in acetic acid (Scheme 1).…”