Synthetic approaches to regiospecifically mono‐ and dilabelled arenes

Abstract

A variety of methods for the preparation of selectively mono-, di-or tri-labelled arenes are reviewed. The review concentrates on those for which the application to labelled synthesis has been demonstrated. Further methods, the application of which to labelled synthesis appears viable but which have not been reduced to practise, are included also. The available methods provide a range of substitution patterns.

A method for the preparation of [13C6]‐labelled 2‐substituted naphthalenes

“…Generation of naphthalenes with one or two labels in the ring that is being built up is well precedented, 1 and a very similar sequence to that illustrated has been used to prepare 1,4-dilabelled 1-tetralone from 1,4-dilabelled succinic anhydride. 5 In our case, Friedel-Crafts acylation of [ 13 C 6 ]-bromobenzene with succinic anhydride, followed by HuangMinlon reduction of the keto acid (4), gave [benzene-13 C 6 ]-4-(4-bromophenyl)butanoic acid (5).…”

“…The aqueous phase was re-extracted twice with ether and the combined organic phases were dried (MgSO 4 ) and evaporated. [naphthalene-4a,5,6,7,8,8a-13 C 6 ]-2-(2-Bromoethyl)naphthalene (1) A suspension of 10 (1.913 g, 11 mmol.) in 48% hydrobromic acid (27 ml) was stirred at reflux for 18.5 h, cooled, and extracted three times with toluene.…”

“…Many of the methods described are somewhat limited in scope, 2 but there is one convenient and reliable approach that appears consistently in the literature, involving annulation of a second ring onto an existing benzene framework, and has been used for the generation of both singly and multiply labelled naphthalenes. 1,3 In this paper, we report the adaptation of this sequence to the synthesis of 2-substituted [ 13 C 6 ]-naphthalenes, exemplified by [naphthalene-1,2,3,4,4a,8a-…”

“…A variety of routes to a number of singly and multiply 13 C-labelled arenes, 1 and specifically to naphthalenes with defined labelling patterns, 2,3 have been described in the literature in recent years. Many of the methods described are somewhat limited in scope, 2 but there is one convenient and reliable approach that appears consistently in the literature, involving annulation of a second ring onto an existing benzene framework, and has been used for the generation of both singly and multiply labelled naphthalenes.…”

Late-Stage Carbon-14 Labeling and Isotope Exchange: Emerging Opportunities and Future Challenges

“…Of course, even more sophisticated precursors can be prepared such as mono- or multilabeled aromatic rings ( Scheme 1 , top). 51 , 52 …”