[81236-11-5] · C16H35N3 · 1,1,2,3,3-Pentaisopropylguanidine · (MW 269.54)
(hindered amine base; used in oxidations of ketone hydrazones, and in eliminations of hydrogen iodide and p-toluenesulfonic acid)
Preparative Method: the reagent is not commercially available, but is easily prepared in two steps. First, Thiophosgene is slowly added to Diisopropylamine to give N,N,N´,N´-tetraisopropylthiourea, as a pale yellow liquid, in 44% yield. A Vilsmeier salt is then formed from the reaction of tetraisopropylthiourea with Phosgene, and subsequently treated with isopropylamine to give 1,1,2,3,3-pentaisopropylguanidine (69% yield) as a liquid, bp 60 °C/0.01 mmHg (eq 1).1 The compound solidifies on storing at -20 °C under argon.
Handling, Storage, and Precautions: Use in a fume hood.
Ketone hydrazones are oxidized to vinyl iodides when treated with Iodine in the presence of a base. Yields of vinyl iodides improve significantly with the use of strong guanidine bases under anhydrous conditions (eq 2).2
The base-induced elimination of hydrogen iodide from b-iodo-a,b-unsaturated ester (1) is effected by reaction with pentaisopropylguanidine in methylene chloride at -35 °C to give alkynic ester (2) in 70% yield (eq 3).3 Likewise, reaction of b-iodo-a,b-unsaturated ester (3) with pentaisopropylguanidine in chloroform at -30 °C affords alkynic ester (4) in 69% yield (eq 4).4
Pentaisopropylguanidine is also used in the elimination of sulfonic acids from the corresponding esters to afford alkenes. For example, heating cholestan-3b-yl p-toluenesulfonate (5) with pentaisopropylguanidine at 120 °C for 26 h gives a mixture of cholest-2-ene (6) and cholest-3-ene (7) in 85% yield (eq 5).1 This compares favorably with the literature method involving 2,4,6-Collidine (170 °C, 6 h, 63% yield).5 The same reaction performed using 1,5-Diazabicyclo[4.3.0]non-5-ene (DBN) only gives 31% of the mixed alkenes but at a lower temperature (80-90 °C).
R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA