Rationale: 3-Aroylbenzofurans and their 2-nitrophenyl derivatives constitutefundamental intermediates for the synthesis of target compounds withpharmaceutical properties. However, their preparation via the Friedel–Craftsacylation of 2-phenylbenzofurans, using Lewis acid as catalyst, often leads tomixtures of regioisomeric aroylbenzofurans that can be challenging to distinguish,thus preventing the reaction characterization.Method: We report a method for the unambiguous identification and differentiationof the desired 3-benzoyl isomers from their 4- and 6-regioisomers in a crude reactionmixture using gas chromatography coupled to multiple-stage mass spectrometric(GC/MSn) analysis performed in collision-induced dissociation (CID) mode.Results: Upon electron ionization, each set of isomers displayed nearly identical massspectra. MSnrevealed fragmentation patterns that varied in the location ofthe benzoyl group on the benzofuran scaffold: CID experiments performed on themolecular ion allowed the distinction of the 3-acyl isomers from the 4- and6-regioisomers; CID experiments on the [M − Ar]+ion allowed the distinction ofthe 4-benzoyl from the 6-benzoyl regioisomer, when the nitro group is located onthe 2-phenyl ring. Moreover, the unusual loss of OH•radical allowed ascertaining theposition of the nitro group in 3-acyl regioisomers bearing the NO2group. The originof the diagnostic OH•loss was investigated through MSnexperiments using18O-labelled 3-benzoyl derivatives.Conclusions: The method allows the rapid characterization of crude reactionmixtures of benzoylbenzofurans using solely GC/MSnanalysis, simplifying theworkflow of extensive isolation and purification for structure elucidation.

Begala, M., Mancinelli, M., Quezada, E., Delogu, G.L. (2021). GC/MSn analysis of the crude reaction mixtures from Friedel–Crafts acylation: Unambiguous identification and differentiation of 3‐aroylbenzofurans from their 4‐ and 6‐regioisomers. RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 35(11), 1-8 [10.1002/rcm.9082].

GC/MSn analysis of the crude reaction mixtures from Friedel–Crafts acylation: Unambiguous identification and differentiation of 3‐aroylbenzofurans from their 4‐ and 6‐regioisomers

Mancinelli, Michele
Membro del Collaboration Group
;
2021

Abstract

Rationale: 3-Aroylbenzofurans and their 2-nitrophenyl derivatives constitutefundamental intermediates for the synthesis of target compounds withpharmaceutical properties. However, their preparation via the Friedel–Craftsacylation of 2-phenylbenzofurans, using Lewis acid as catalyst, often leads tomixtures of regioisomeric aroylbenzofurans that can be challenging to distinguish,thus preventing the reaction characterization.Method: We report a method for the unambiguous identification and differentiationof the desired 3-benzoyl isomers from their 4- and 6-regioisomers in a crude reactionmixture using gas chromatography coupled to multiple-stage mass spectrometric(GC/MSn) analysis performed in collision-induced dissociation (CID) mode.Results: Upon electron ionization, each set of isomers displayed nearly identical massspectra. MSnrevealed fragmentation patterns that varied in the location ofthe benzoyl group on the benzofuran scaffold: CID experiments performed on themolecular ion allowed the distinction of the 3-acyl isomers from the 4- and6-regioisomers; CID experiments on the [M − Ar]+ion allowed the distinction ofthe 4-benzoyl from the 6-benzoyl regioisomer, when the nitro group is located onthe 2-phenyl ring. Moreover, the unusual loss of OH•radical allowed ascertaining theposition of the nitro group in 3-acyl regioisomers bearing the NO2group. The originof the diagnostic OH•loss was investigated through MSnexperiments using18O-labelled 3-benzoyl derivatives.Conclusions: The method allows the rapid characterization of crude reactionmixtures of benzoylbenzofurans using solely GC/MSnanalysis, simplifying theworkflow of extensive isolation and purification for structure elucidation.
2021
Begala, M., Mancinelli, M., Quezada, E., Delogu, G.L. (2021). GC/MSn analysis of the crude reaction mixtures from Friedel–Crafts acylation: Unambiguous identification and differentiation of 3‐aroylbenzofurans from their 4‐ and 6‐regioisomers. RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 35(11), 1-8 [10.1002/rcm.9082].
Begala, Michela; Mancinelli, Michele; Quezada, Elias; Delogu, Giovanna Lucia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/831905
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