A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

Abstract

Chloramines are an important class of reagents, providing a convenient source of chlorine or electrophilic nitrogen. However, the instability of these compounds is a problem which makes their isolation and handling difficult. To overcome these hazards, a continuous-flow approach is reported which generates and immediately reacts N-chloramines directly, avoiding purification and isolation steps. 2-Chloramines were produced from the reaction of styrenes with N-alkyl-N-sulfonyl-N-chloramines, whilst N-alkyl or N,N’-dialkyl-N-chloramines reacted with anisaldehyde in the presence of t-BuO2H oxidant to afford amides. Primary and secondary imines were produced under continuous conditions from the reaction of N-chloramines with base, with one example subsequently reduced under asymmetric conditions to produce a chiral amine in 94% ee.

On-Demand Generation and Use in Continuous Synthesis of the Ambiphilic Nitrogen Source Chloramine

“…Additionally, 1 is toxic in high concentrations and has been reported as an intermediate in the synthesis of hydrazine. , The use of continuous-flow systems to employ hypochlorite in oxidation and halogenation reactions has also seen much recent application . For these reasons, we hypothesized that a continuous-flow apparatus would be uniquely successful not only in generating 1 but also in directly employing this reagent in subsequent synthetic transformations, as has been accomplished for N -alkyl chloramines and in a recent remdesivir syntheis. , To this end, NH 2 Cl was prepared in flow via aqueous ammonia and sodium hypochlorite, with ammonium chloride as a pH buffer. The reactor was cooled to 0 °C to attenuate thermal decomposition.…”

“…6 For these reasons, we hypothesized that a continuous-flow apparatus would be uniquely successful not only in generating 1 but also in directly employing this reagent in subsequent synthetic transformations, as has been accomplished for N-alkyl chloramines and in a recent remdesivir syntheis. 7,8 To this end, NH 2 Cl was prepared in flow via aqueous ammonia and sodium hypochlorite, with ammonium chloride as a pH buffer. The reactor was cooled to 0 °C to attenuate thermal decomposition.…”

Practical N-Hydroxyphthalimide-Mediated Oxidation of Sulfonamides to N-Sulfonylimines

“…Several other user-friendly oxidants were tried, and only trichloroisocyanuric acid (TCCA) and N -Bromosuccinimide (NBS) could generate products with a pretty low yield (Table 1, entry 9–15). Both TCCA and N -Chlorosuccinimide (NCS) would give N -chlorinated amides as major product, especially in the case of NCS [33,34]. At last, the necessity of NHPI and PhI(OAc) 2 was investigated by control experiment.…”

Continuous Flow Z‐Stereoselective Olefin Metathesis: Development and Applications in the Synthesis of Pheromones and Macrocyclic Odorant Molecules**

“…With this in mind we opted for a reactor design consisting of a serial array of CSTRs. [26] Incorporating this into a semi-continuous process targeting Civetone, we began with a larger scale self-metathesis of the bio-sourced ethyl 9-decenoate 5 catalyzed by cyclometalated Ru-4. Pleasingly, after 3 hours inside the 3 mL tube-in-tube reactor, 6 was isolated in good yield (71 %; 1.27 g) and excellent 96 % Z-selectivity (Scheme 5 a).…”