Abstract
We present a quantum chemical analysis of the 18F-fluorination of 1,3-ditosylpropane, promoted by a quaternary ammonium salt (tri-(tert-butanol)-methylammonium iodide (TBMA-I) with moderate to good radiochemical yields (RCYs), experimentally observed by Shinde et al. We obtained the mechanism of the SN2 process, focusing on the role of the –OH functional groups facilitating the reactions. We found that the counter-cation TBMA+ acts as a bifunctional promoter: the –OH groups function as a bidentate ‘anchor’ bridging the nucleophile [18F]F− and the –OTs leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition states of a very compact configuration for facile SN2 18F-fluorination.
Highlights
IntroductionThe 18 F-fluorination [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] of organic compounds is gaining considerable importance for synthesizing chemicals that can be employed as radiotracers for the diagnosis of various diseases [21,22,23] by the highly sensitive imaging technique of positron emission tomography (PET) [24,25]
Scheme 1 presents the structure of TBMA-I, which is transformed to TBMA-18 F by Shinde and co-workers’ procedure [13], along with the 18 F-fluorination of the model substrate 1,3-ditosylpropane 1
In Shinde and co-workers’ experiments, TBMA-18 F is recovered from QMA cartridges after treatment with methanolic TBMA-I, and the counter-cation TBMA+ accelerates the 18 F-fluorination, the reaction given in Scheme 1 would be the key process
Summary
The 18 F-fluorination [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] of organic compounds is gaining considerable importance for synthesizing chemicals that can be employed as radiotracers for the diagnosis of various diseases [21,22,23] by the highly sensitive imaging technique of positron emission tomography (PET) [24,25]. We present the analysis of the 18 Ffluorination of 1,3ditosylpropane (1), finding that the counter-cation TBMA+ acts as a bifunctional promoter: the –OH groups in TBMA+ act as a bidentate ‘anchor’ by forming hydrogen bonds with the nucleophilic [18 F]fluoride and the tosylate (–OTs) leaving group or the third –OH. These electrostatic interactions cooperate for the formation of the transition state (TS) of a very compact configuration for facile SN 2 18 F-fluorination. Structure of TBMA-I and the 18 F-fluorination of 1,3-ditosylpropane [13]
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