Bryce Assink of W.R. Grace has been a loyal reader of the PTC Tip of the Month since about 15 years ago when he very actively participated in the 2-day PTC course in Chicago.
Bryce provided excellent insight in response to our call last month for an explanation about the identity or composition of tetrabutylammonium pyrophosphate. Shown below is Bryce’s unedited input.
Great thanks to Bryce Assink for investing his time and expertise to educate us!
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“Ok, you just made me pull out my thesis from 1999. Here’s what I have.
In 1959, Cramer and Bohm reported reaction conditions suitable for phosphorylating geraniol and farnesol to their respective diphosphates by condensation with bis(triethylammonium) phosphate, trichloroacetonitrile, and substrate alcohol in acetonitrile at rt. Reaction times were 4-24h. Diphosphate yields varied from 15-25%. (Cramer, F.; Bóhm, W. Angew Chem. 1959, 71, 775).
In 1988, Danilov modified the Cramer reaction by using Bu4NH2PO4 as a phosphate source. This reaction took 10-30 minutes, and gave ~45% yields of diphosphate for primary alcohols, and 20-30% for secondary alcohols. This was the method I used in my thesis. (Danilov, L.; Mal’tsev, S.; Shibaev, V. Soviet J. Bioorg. Chem. 1988, 14, 712).
In 1985, Poulter introduced another modification that used SN2 displacement of a tosylate or halide with tris-tetrabutylammonium pyrophosphate (ie: diphosphate) in acetonitrile. Yields were 60-90%, with no monophosphate or polyphosphate byproducts. This procedure was only useful for primary alcohols (secondary/tertiary gave elimination and/or rearrangement). (Davisson, V.; Woodside, A.; Neal, T.; Stremler, K.; Muehlbacher, M.; Poulter, C. J. Org. Chem. 1986, 51, 4768).
It looks like the patent you reference is based off of the Poulter method. My guess is that they are making the mono-quat-trihydrogen reagent themselves in the presence of 6 equivalents of water (7 after the reaction) using pyrophosphoric acid and tetrabutylammonium hydroxide. Pyrophosphoric acid is available in 94% purity. The sticky part is that this would require 73% tetrabutylammonium hydroxide (2.8 M), which does not appear to be readily available.
I hope this gives you some insight.”
