Neopentylidenephosphorodithioic Acid in Organic Synthesis
Dr. Janusz Rachon
Gdansk University of Technology in Poland
Wednesday, August 28, 2013
C2-361 (Reading Room)
Abstract: Easily available acyl dithiophosphates are not stable and isomerize reversibly to O-thioacyl monothiophosphates and much slower but probably irreversibly to S-thioacyl monothiophosphates. But treatment of mixture of isomeric anhydrides with the excess of dithiophosphoric acid leads to formation of S-thioacyl dithiophosphates exclusively. They appeared to be excellent thioacylating agents; relatively stable, inert towards water and oxygen and therefore easy to handle. Reaction with nitrogen or sulfur nucleophiles proceeds very fast at ambient conditions yielding respective thioacyl derivatives. Isolation of the product is very simple. Due to low reactivity of S-thioacyl dithiophosphates towards oxygen nucleophiles they can be used for direct thioacylation of multifunctional nucleophiles possessing unprotected hydroxyl groups. They can be used to obtain thiohydroxamic acids directly from hydroxylamines nonprotected on oxygen.
However in case of sterical hindrance O-thioacylhydroxylamines are formed. We found out that O-thioacyl hydroxylamines reacts with dithiophosphoric acids leading to the N-O bond cleavage and acyl thiophosphoryl disulfides formation. Our research strongly suggests that in this new type of reaction a single electron transfer process is involved.
Disulfides are important compounds for both chemical and biological processes. There are many biologically active peptides and peptide mimetics possess unsymmetrical disulfide bonds. Disulfides are applied for preparation of self-assembled monolayers (SAMs) and monolayer-protected clusters (MPCs) with the interesting properties.
A new and versatile synthesis of unsymmetrical disulfides as well as trisulfides based on the readily available 5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl sulfenyl bromide will be presented. The developed procedure is very rapid (15 min) and proceeds under mild conditions and excellent yields (90-100%). Unsymmetrical disulfides can be prepared from thiols bearing neutral, aromatic, basic or acidic functionalities with variable length of carbon chain.