Synthesis and Physicochemical Properties of 3‐Fluorocyclobutylamines. Issue 29 (25th August 2015)

• Record Type: Journal Article
• Authors: Chernykh, Anton V.; Radchenko, Dmytro S.; Chernykh, Alla V.; Kondratov, Ivan S.; Tolmachova, Nataliya A.; Datsenko, Olexandr P.; Kurkunov, Maxim A.; Zozulya, Sergey X.; Kheylik, Yuri P.; Bartels, Katharina; Daniliuc, Constantin G.; Haufe, Günter
• Is Part Of: European journal of organic chemistry. Issue 29(2015)
• Page Start: 6466
• Page End: 6471
• Publication Date: 2015-08-25
• Subjects: Fluorine -- Small ring systems -- Basicity -- Lipophilicity -- Rearrangement; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201500746
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: Hitherto unknown cis ‐ and trans ‐3‐alkyl‐ and 3‐aryl‐3‐fluorocycobutylamines have been synthesised selectively from 3‐oxocyclobutane carboxylic acid in six or seven steps. Comparison of their p K a and log D values with those of the fluorine‐free parent compounds showed acidification by about 0.8 units, irrespective of the stereochemistry. This indicates that there are no through‐space interactions between fluorine and the amino function – a conclusion that was supported by the results of X‐ray analysis. Fluorinated trans ‐compounds were found to be more lipophilic (Δ log P ≈ 1) compared with the non‐fluorinated analogues, whereas the difference was marginal for cis isomers. Abstract : Hitherto unknown cis ‐ and trans ‐3‐alkyl and 3‐aryl‐3‐fluorocycobutylamines have been synthesised. Comparison of their p K a values with those of the fluorine‐free parent compounds showed acidification by about 0.8 units, independent of the stereochemistry, indicating that no through‐space interactions occur between fluorine and the amino function.