Resolving Bromonitromethane Sourcing by Synthesis: Preparation at the Decagram Scale

Abstract

The accessibility of bromonitromethane has declined in recent years, limiting its viability as a reagent for chemical synthesis. The reinvestigation and optimization of a variety of preparations, and the development of safe operating principles, are described. The reproducible protocol described here leverages the effectiveness of hydroxide for nitromethane bromination while respecting its incompatibility with the product it forms. This careful balance was achieved at scales up to 56 g, resulting in a reproducible procedure that provides straightforward, sustainable, and affordable access to this critical reagent.

Backbone-Determined Antiarrhythmic Structure–Activity Relationships for a Mirror Image, Oligomeric Depsipeptide Natural Product

“…Conversion of hexanal to α-amido sulfone 14 ( 23 ) preceded elimination to the N-Boc imine substrate ( 15 ) 23b for the aza-Henry reaction. 24 Catalyzed addition of bromonitromethane 25 using the chiral proton catalyst ( S , S )-PBAM·HOTf 26 furnished β-amino nitroalkane 16 in 91% ee as a 1:1 mixture of diastereomers. These diastereomers converged to a single terminal nitroalkane ( 17 ) in 90% ee upon treatment with stannous chloride.…”

Copper(I) Photocatalyzed Bromonitroalkylation of Olefins: Evidence for Highly Efficient Inner‐Sphere Pathways

“…We started our investigation by irradiating bromonitromethane [9] ( 1 a ) and styrene ( 2 a ) in the presence of [Cu I (dap) 2 ]Cl with a blue or green LED (455 or 530 nm, Table 1, entries 1–2). The ATRA product 4 a was exclusively obtained in 87–90 % yield.…”

“…in [Cu(dap) 2 ]Cl [8a] E 1/2 (Cu II /Cu I = 0.62 V vs. saturated calomel electrode (SCE)) having lower oxidizing power such as [Ir(tbppy) 3 ] + E 1/2 (Ir IV /Ir III = 0.69 V vs. SCE) [7] or [Ir(ppy) 3 ] E 1/2 (Ir IV /Ir III = 0.77 V vs. SCE) [8b] should also result in 3 unless Cu II could successfully compete with the cyclization to C. Indeed, Iwasaki et al already had shown that the related thermal reaction between 1 e (R = Ph) and 2 a initiated by Cu(OH) 2 (50 mol %) exclusively leads to isoxazoline-N-oxide of type 3 in 84 % yield. [6c] We started our investigation by irradiating bromonitromethane [9] (1 a) and styrene (2 a) in the presence of [Cu I (dap) 2 ]Cl with a blue or green LED (455 or 530 nm, Table 1, entries 1-2). The ATRA product 4 a was exclusively obtained in 87-90 % yield.…”

Kupfer(I) Photokatalysierte Bromnitroalkylierung von Olefinen: Hinweise für effizienten Inner‐Sphären Mechanismus

“…Tatsächlich hatten Iwasaki et al bereits gezeigt, dass die thermische Reaktion zwischen 1 e (R = Ph) und 2 a, initiiert durch Cu(OH) 2 (50 Mol-%), ausschließlich zu Isoxazolin-N-Oxid 3 in 84 %iger Ausbeute führt. [6c] Unsere Untersuchungen begannen mit der Bestrahlung von Bromnitromethan [9] (1 a) und Styrol (2 a) in Gegenwart von [Cu I (dap) 2 ]Cl mit einer blauen oder grünen LED (455 oder 530 nm, Tabelle 1, Einträge 1-2), welche ausschließlich zu ATRA-Produkt 4 a in 87-90 % Ausbeute führten. [Cu II -(dap)Cl 2 ], welches unter photochemischen Bedingungen durch Homolyse der CuÀ Cl-Bindung [10] leicht zu Cu I (dap)Cl reduziert wird, konnte ebenfalls erfolgreich eingesetzt werden (Tabelle 1, Eintrag 3).…”