A greener and efficient access to substituted four- and six-membered sulfur-bearing heterocycles

Abstract

The regioselective functionalization of four- and six-membered cyclic sulfones was investigated using a lithiation/electrophile trapping strategy. The protocol features an interesting eco-compatibility profile because of the use of 2-MeTHF as a solvent (more eco-friendly than other organic solvents) and n-hexyllithium as a lithiating agent safer than other alkyllithium compounds. Several derivatives were prepared with different stereochemistry and substitution patterns. A number of selected derivatives, spanning a range of 5 log P units, were characterized for their lipophilicity through RP-HPLC. A good linear correlation, with a slope close to 1.0, was observed between the experimentally determined RP-HPLC lipophilicity parameters (log k') and calculated log P (clog P) values, whereas a systematic difference in absolute values between the chromatographic parameters and in silico lipophilicity descriptors can be attributed mainly to silanophilic interactions between the H-bond acceptor SO group and free silanol groups on silica-based C18 columns, which results in increased retention times.

Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One Derivatives for Their Multitarget Activity on β-Amyloid Aggregation and Neurotoxicity

“…Log k’ w values resulted reasonably correlated, over a range of about five log units, with CLOGPs from ACDLabs software ( r 2 = 0.805; Supplementary Materials Figure S1 ). The linear equation correlating log k’ w and CLOGP has a slope close to one (+1.03) and an intercept of about +0.70, the latter revealing a systematic positive deviation from linearity, likely due to the so-called “silanophilic” interactions on the silica-based C18 stationary phase [ 36 , 37 , 38 ].…”

Away from Flatness: Unprecedented Nitrogen-Bridged Cyclopenta[a]indene Derivatives as Novel Anti-Alzheimer Multitarget Agents

“…In an attempt to examine the effect of lipophilicity on the enzyme selectivity and inhibitory potency of these molecules, experimental lipophilicity parameters were measured in RP-HPLC through a previously reported method . A relative lipophilicity scale of log k ′ w (i.e., the so-called polycratic capacity factor of the capacity factor extrapolated to 100% water mobile phase), spanning a range of more than two log units from 3.10 ( 28 ) to 5.35 ( 18 ) was determined (Table ).…”

Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

“…The 2-MeTHF was shown to improve regioselectivity considerably over THF. 351 A wide range of benzylic and aliphatic electrophiles were utilized, and varying degrees of electrophile dependent stereocontrol were observed.…”

“…Similarly, Schwartz’s reagent can be utilized to reduce isothiocyanates to thioformamides. 351 Electron withdrawing groups attached to the aromatic isocyanates were also well tolerated including reactive functional groups such as azo and azide motifs. 353 The use of 2-MeTHF and the use of an in situ generated Schwartz reagent as the hydride source were crucial for obtaining high chemocontrol.…”