Mechanistic Understanding of a Robust and Scalable Synthesis of Per(6-deoxy-6-halo)cyclodextrins, Versatile Intermediates for Cyclodextrin Modification was written by Zultanski, Susan L.;Kuhl, Nadine;Zhong, Wendy;Cohen, Ryan D.;Reibarkh, Mikhail;Jurica, Jon;Kim, Jungchul;Weisel, Lauren;Ekkati, Anil R.;Klapars, Artis;Gauthier, Donald R. Jr.;McCabe Dunn, Jamie M.. And the article was included in Organic Process Research & Development in 2021.Electric Literature of C42H63Br7O28 This article mentions the following:
Cyclodextrin (CD) perfunctionalization reactions are challenging to study because they proceed through a number of regioisomeric intermediates, thus warranting creative approaches to understanding the reaction mechanism. Particularly useful perfunctionalization targets are per(6-deoxy-6-halo)cyclodextrins. Their standard synthesis entails selective SN2 halogenation at their primary alcs. using a Vilsmeier reagent, but this requires a strongly basic quench to unmask the Vilsmeier-capped secondary alcs. Herein we present an alternative and simple acidic hydrolytic quench that utilizes existing HX in the end-of-reaction solution and requires only the addition of water. We performed a detailed mechanistic investigation of the new quench, and a central feature was the use of proton sponge to develop an 1H NMR titration method for HX in organic solvent. This method was used to both quantify and remove HX in the prequenched reaction solution The HX-free prequenched solution enabled us to (1) identify sensitive intermediates during the quench, (2) quantify all of the reaction byproducts, and (3) determine that HX is critical for hydrolysis. We then studied the halogenation reaction, wherein the new acidic quench facilitated high-throughput experimentation, using mass spectrometry as well as Design of Experiments with automated reaction profiling. Through this, we were able to establish robustness and understand the complex effects of Vilsmeier equivalent and temperature on the reaction outcome. In the experiment, the researchers used many compounds, for example, Heptakis(6-Bromo-6-Deoxy)-β-Cyclodextrin (cas: 53784-83-1Electric Literature of C42H63Br7O28).
Heptakis(6-Bromo-6-Deoxy)-β-Cyclodextrin (cas: 53784-83-1) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Electric Literature of C42H63Br7O28
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary