biostudies-literatureNeumann CNNIBIB NIH HHSNCRR NIH HHSNIGMS NIH HHS369-73https://www.ebi.ac.uk/biostudies/studies/S-EPMC4911285biostudies-literatureUnknown534(7607)Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain (18)F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a 'leaving group' leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr subNatureConcerted nucleophilic aromatic substitution with (19)F(-) and (18)F(-).PMC4911285R01 EB013042GM088237R01 GM0882371S10RR017208Ritter THooker JMNeumann CNfalseConcerted nucleophilic aromatic substitution with (19)F(-) and (18)F(-).Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain (18)F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a 'leaving group' leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr sub2016-01-01T00:00:00Z2016 Jun2026-05-05T05:39:09.545Z2019-03-27T02:16:15ZS-EPMC49112852728122110.1038/nature17667