Inexpensive, One-Pot Synthesis of Unsymmetrical Disulfides Using 1-Chlorobenzotriazole

Abstract

A new synthesis of unsymmetrical disulfides is described. The reaction of a thiol R1SH with 1-chlorobenzotriazole (BtCl) at -78 degrees C in DCM affords a high-yielding conversion to R1SBt without appreciable formation of the symmetrical disulfide R1SSR1. R1SBt is then reacted with R2SH to form the unsymmetrical disulfide in a one-pot sequence with green character that avoids the use of toxic and harsh oxidizing agents. The methodology has been developed for synthesis of various types of disulfides.

One-pot synthesis of unsymmetrical disulfides using 1-chlorobenzotriazole as oxidant: Interception of the sulfenyl chloride intermediate

“…The R 1 SBt derivative could be isolated by flash column chromatography but rapidly degraded over time in solution, and is thus better suited to a one-pot procedure. Thus, keeping it in solution and reacting it at À20 C with a second thiol as n-PrSH 19 (1.5 equiv) resulted in rapid (30 min) nucleophilic substitution to afford the desired unsymmetrical disulfide in 67% isolated yield after chromatography (Scheme 3).…”

“…The work-up involved an extraction using aqueous basic sodium thiosulfate to remove any traces of BtCl as well as HCl, which, following evaporation of solvent in the normal fashion furnished a residue that could be chromatographically separated into homodisulfide, heterodisulfide and BtH. However, as mentioned previously, 19 one could alternatively use an acid-base extraction to recover the BtH separately, which is something that holds promise for large-scale work. In such a way, we thus consider our new methodology to have a degree of greenness in view of the fact that BtCl is prepared from BtH (recoverable) and bleach as a benign oxidant.…”

“…Electron-deficient heteroaromatic rings also worked well in the reaction, and both the pyridyl (entry 10) and benzothiazolyl (entry 12) products offer possibilities as precursors for exchange reactions with other thiols for accessing other unsymmetrical disulfides. A small library of fluoroalkyl aryl disulfides (entries [13][14][15][16][17][18][19] were also prepared as potential precursors for garlic allicin mimics, 22 following a report by Brace 23 that fluorine substitution in the allicin chain enhanced thiosulfinate stability. Their chemoselective oxidation gave a family of aryl fluoroalkylthiosulfinates, whose stability and anti-microbial activity will be reported elsewhere.…”

“…In response to this overall limitation, we have recently introduced a new methodology 19 involving 1-chlorobenzotriazole as the oxidant in a one-pot transformation that minimizes the formation of homodimer 1. 1-Chlorobenzotriazole (BtCl) was introduced as a novel oxidant in 1968 by Rees 20 and may be cheaply and readily prepared in multigram quantities by the oxidation of benzotriazole (BtH) with bleach in aqueous acetic acid.…”

Enhancement of ruthenium-promoted Co/CNT nanocatalyst performance using microemulsion technique

“…In most of chemical synthesis of DSA is done by oxidation of suitable thiols. To serve for this purpose, reagents such as H 2 O 2 , MoO 2 Cl 2 , metal halides and metals with exchange resin are used [16][17][18][19][20]. The disadvantages of these methods are a very time-consuming process and required maintenance of drastic conditions (either very high temperature or low temperature below zero degrees centigrade).…”