Mechanochemical synthesis and cycloaddition reactions of fluoro nitrone under solvent‐free conditions and potential antimicrobial activities of the cycloadducts

Abstract

Synthesis and cycloaddition reactions of fluoro nitrone under solvent‐free conditions using ball‐milling technique have been reported. Significant change in rate and yields of the cycloadducts have been noticed compared with solvent‐free microwave‐induced reactions of fluoro nitrones. The present study reports synthesis of N‐benzyl fluoro nitrone and its cycloaddition reactions with maleimides and few electron deficient alkynes under solvent‐free conditions. The synthesized fluoro cycloadducts were found to exhibit potential antimicrobial activities.

The Kinetic Solvent Effect on 1,3‐Dipolar Cycloaddition of 2,2,5,5‐Tetramethyl‐3‐imidazoline‐3‐oxide‐1‐oxyl

“…1,3-Dipolar cycloaddition (1,3DC) reaction is a widely used synthetic tool in organic chemistry. [1][2][3][4][5][6][7] In general, the rate of 1,3DC is weakly dependent on solvent, [8][9][10] however, in several studies [11][12] a large solvent effect of up to two-three orders of magnitude is reported. The solvent effect on the 1,3DC rate coefficient is strongly dependent on the structures of dipoles: acceleration of reaction with an increase in solvent polarity was observed for azides [9] and azomethine ylides; [13] rate enhancement is also found for nitrile N-oxides in a protic solvent; whereas nitrones react faster in non-polar solvents and slower in protic ones.…”

“…1,3‐Dipolar cycloaddition (1,3DC) reaction is a widely used synthetic tool in organic chemistry [1–7] . In general, the rate of 1,3DC is weakly dependent on solvent, [8–10] however, in several studies [11–12] a large solvent effect of up to two‐three orders of magnitude is reported.…”

Sustainable Synthesis of a Potent and Selective 5-HT7 Receptor Antagonist Using a Mechanochemical Approach

“… 14 − 16 Interestingly, an increasing number of mechanochemical procedures for generating pharmaceutically relevant fragments and functionalities have been reported thus far. 17 − 19 This novel mechanochemical application led to coining the term “medicinal mechanochemistry.” 20 , 21 …”

“…In particular, mechanochemistry has been used to produce various families of compounds. − The primary driving force underlying the rediscovery of mechanochemistry is green chemistry, − in particular, the need of chemical and pharmaceutical industries for the development of more sustainable synthetic protocols characterized by the energy efficiency of chemical transformations and reduction of solvent use. The use of such approaches offers additional advantages of mechanosynthesis over classical organic chemistry, in terms of excellent selectivity and the possibility to perform previously unknown reactions. − Interestingly, an increasing number of mechanochemical procedures for generating pharmaceutically relevant fragments and functionalities have been reported thus far. − This novel mechanochemical application led to coining the term “medicinal mechanochemistry.” , …”

Efficient and Sustainable Synthesis of a Potent and Selective 5-HT7 Receptor Antagonist Using a Mechanochemical Approach

“…[14][15][16] Interestingly, an increasing number of mechanochemical procedures for generating pharmaceutically relevant fragments and functionalities has been reported thus far. [17][18][19] This novel mechanochemical application led to coining the term "medicinal mechanochemistry." 20,21 We have recently developed a novel class of potent and selective 5-HT 7 receptor (5-HT 7 R) antagonist, namely arylsulfonamide derivative of (aryloxy)alkyl alicyclic amine, and identified several lead structures that exhibit significant in vivo antidepressant and pro-cognitive properties in rodents (Figure 1).…”