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

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• 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. Keywords: continuous flow; CSTR; N-chloramine; synthetic methods

• ]. Whilst Cl2 gas is atom efficient it is difficult to handle, with associated toxicity, and the acid byproduct which leads to N-chloramine hydrolysis [16]. On the other hand, N-chlorosuccinimide or chloramine-T are commonly employed, being commercially available, stable and straightforward to handle

• , though both exhibit poor atom economy [17][18][19][20][21]. Sodium hypochlorite (NaOCl) solutions are less widely used, yet readily available, economic and provide an atom efficient reagent for N-chloramine formation [22][23][24]. A continuous-flow process for the oxidation of alcohols using NaOCl as a

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• . Mal and co-workers reported a metal free, solvent-free and room temperature synthesis of amide bonds at 62–75% yield under ball-milling (21 Hz) from aromatic aldehydes and N-chloramine in presence of 20 mol % of tetrabutylammonium iodide (TBAI) and 2.0 equiv of TBHP (Scheme 16) [79]. Aromatic

• acids [78]. Mechanochemical amidation reaction from aromatic aldehydes and N-chloramine [79]. Mechanochemical CDC between benzaldehydes and benzyl amines [81]. Mechanochemical protection of -NH2 and -COOH group of amino acids [85]. Mechanochemical Ritter reaction [87]. Mechanochemical synthesis of

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• reactivity, since the partition coefficient is similar to that of dibutylamine. The productivities of N-chloramine formation are in the range of 0.04–0.06 mol/h. Green metrics A key driver within the chemical industry is the need for greener, more sustainable processes. In order to assess the sustainability

• of the continuous process for chloramine formation described in this publication, the metrics of the reaction were assessed and compared with existing literature procedures [35]. The results are summarised in Table 3. The yields of the continuous N-chloramine process were high, and comparable to

• . The mass efficiency remains low, but is comparable to literature procedures. Whilst increasing the reactant concentrations is possible, the safe removal of the heat of reaction must be considered, moreover the flow process is much more productive than batch. Nevertheless the N-chloramine solution that

Synthesis of crispine A analogues via an intramolecular Schmidt reaction

• Ajoy Kapat,
• Ponminor Senthil Kumar and
• Sundarababu Baskaran

Beilstein J. Org. Chem. 2007, 3, No. 49, doi:10.1186/1860-5397-3-49

• developed for the synthesis of crispine A. [20][21][22][23][24][25][26][27][28] Interestingly, Schell and Smith reported the first synthesis of crispine A, even before its isolation, using the N-chloramine rearrangement reaction as a key step.[25] In order to understand the structure activity relationship