Williamson serendipitously discovered (1851) a new and efficient way to produce ethers using ethyl iodide and potassium salts and in doing so elucidated the molecular mechanism behind ether formation. Before Williamson, the direct reaction between alcohol and acids was the only method of generating the elusive “ethers”. This tedious and low yield approach eventually led to Voegeli's synthesis of the first organophosphate ever, triethyl phosphate (TEP) in 1848. Based on the landmark work of Williamson, however, over the next thirty years or so numerous chemists managed to produce TEP and tetraethyl pyrophosphate (TEPP) using synthetic pathways of increasingly higher yield. With the “wood spirit” (methyl-alcohol) easily available attempts were also made during the same period to synthesize methyl ester analogues (TMP and TMPP). The synthesis of TMP was reported 1887 by Hall in a paper dealing with vanadium esters; he acknowledges his inability to synthesize methyl vanadate and states that “methyl phosphate had not been described” and goes on to briefly mention the synthesis of methyl phosphate by the Wiliamson method. Hall was however mistaken; the synthesis of TMP had previously been reported by Weger in 1883 and achieved even earlier by Lossen. Tetramethyl pyrophosphate (TMPP) was only recently (1949) synthesized by Toy. This report attempts to identify the pharmacists and chemists involved in the quest for phosphoric and pyrophosphoric acid methyl esters.
A Tue, study studied this question.