Designing new routes to pharmaceutical reagents via the acid-base reaction of copper(I) oxide with a weak acid in the presence o

Tris(triphenylphosphine) copper(I) phenolate, (Ph₃P)₃CuOPh, is a possible intermediate in the synthesis of tris(triphenylphosphine) (trifluoromethyl) copper(I), (Ph₃P)₃CuCF₃, which is an
important compound in medicinal chemistry. (Ph₃P)₃CuOPh is synthesized by reacting a copper-containing base (copper(I) oxide, Cu₂O) with a weak acid (phenol, PhOH) in the presence of a ligand (triphenylphosphine, PPh₃). We have been altering the conditions of the acid-base reaction to make our phenolate complex in a timelier and more cost-efficient manner, in high purity. So far, we have experimented with sulfuric, hydrobromic and hydrochloric acids as catalysts in our reactions. Currently, we have lowered the synthesis time to 8 hours from 72 hours and have obtained (Ph₃P)₃CuOPh in acceptable purity with an average of 98% yield. We have also attempted to synthesize a very similar nitromethanide complex, which would serve the same purposes as the phenolate, i.e., as an intermediate in the synthesis of our target compound, (Ph₃P)₃CuCF₃. The current yield is around 80%, and we are trying to improve the purity of this intermediate produced by our method.
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Abstract/Description: Tris(triphenylphosphine) copper(I) phenolate, (Ph₃P)₃CuOPh, is a possible intermediate in the synthesis of tris(triphenylphosphine) (trifluoromethyl) copper(I), (Ph₃P)₃CuCF₃, which is an important compound in medicinal chemistry. (Ph₃P)₃CuOPh is synthesized by reacting a copper-containing base (copper(I) oxide, Cu₂O) with a weak acid (phenol, PhOH) in the presence of a ligand (triphenylphosphine, PPh₃). We have been altering the conditions of the acid-base reaction to make our phenolate complex in a timelier and more cost-efficient manner, in high purity. So far, we have experimented with sulfuric, hydrobromic and hydrochloric acids as catalysts in our reactions. Currently, we have lowered the synthesis time to 8 hours from 72 hours and have obtained (Ph₃P)₃CuOPh in acceptable purity with an average of 98% yield. We have also attempted to synthesize a very similar nitromethanide complex, which would serve the same purposes as the phenolate, i.e., as an intermediate in the synthesis of our target compound, (Ph₃P)₃CuCF₃. The current yield is around 80%, and we are trying to improve the purity of this intermediate produced by our method.
Subject(s): Nitromethanide complex
Undergraduate Research
Phenolate complex
Date Issued: 2021