708-48-5Relevant academic research and scientific papers
Metalations utilizing aryllithiums; ortho-functionalization of p-bromoanisole (pBrA)
Slocum,Reece, Troy L.,Sandlin, Rebecca D.,Reinscheld, Thomas K.,Whitley, Paul E.
, p. 1593 - 1595 (2009)
An ortho-metalation protocol has been developed, which permits the survival of a bromine substituent in p-bromoanisole. Eight derivatives of the generated ortho-lithiated intermediate have been prepared. A neglected metalation concept is being explored here; one which proposes that minimizing the pKa difference between the aryl substrate and the conjugate acid of the metalating agent will lead to a regiospecific and selective metalation process.
Focused ortho-Lithiation and Functionalization of p-Bromo- and p-Iodoanisole
Slocum,Jennings, John A.,Reinscheld, Thomas K.,Whitley, Paul E.
, p. 4400 - 4406 (2018/09/10)
By use of the strategy for ortho-lithiation (DoM) that conceptually diminishes the pKA difference between the ortho-H of the substrate and the conjugate acid of the metalating agent, effective metalation of bromine and iodine bearing aryl substrates can be carried out. As a set of prototypes, p-bromoanisole (p-BrA) and p-iodoanisole (p-IA) have been successfully ortho-metalated in promoted hydrocarbon media using ortho-lithiodimethylbenzylamine (o-LiDMBA) as the metalating agent. No hint of exchange of either halogen was noted using these conditions. These studies add to the emerging evidence of a hitherto unidentified acidifying effect on the proton(s) ortho- to a directing metalation group (DMG) by both a p-iodo and a p-bromo substituent.
Near-ambient temperature halogen-lithium exchange of p-bromoanisole and related substrates: Flow/batch studies
Slocum,Reinscheld, Thomask.,Austin, Nickd.,Kusmic, Damir,Whitley, Paule.
experimental part, p. 2531 - 2536 (2012/09/22)
With the advent of flow chemistry, the norm has been reactions executed on the laboratory scale with flow rates of only a few mL/min. We bring to the community's attention our investigation of the halogen-lithium (X-Li) exchange in a continuous flow reactor, the Synthetron. This novel reactor is capable of orders of magnitude greater rates of flow than current microreactors. This paper details a problematic X-Li exchange using our promoted hydrocarbon media formulated batch studies as well as the comparative derived flow studies. All of these studies have the additional feature of being performed at ambient or near-ambient temperatures. From the initial discoveries of Wittig and Gilman in the late 1930s, it has been known that X-Li exchange of p-bromoanisole (p-BrA) is plagued by a secondary ortho-lithiation. Fine-tuning of promoted hydrocarbon media batch studies can increase the ratio of p-LiA/o-Li-p-BrA; results from the Synthetron studies afford a much superior ratio of >100:1. Gram quantities of derivatives from this exchange (employing two reactors) can be prepared in a few seconds. Rationales for these observations will be presented as well as initial studies and discussion for bromobenzene (PhBr), m-bromoanisole (m-BrA), and p-iodoanisole (p-IA). Georg Thieme Verlag Stuttgart · New York.
