1,1,2,3,3-Pentaisopropylguanidine

[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.

Oxidation of Ketone Hydrazones.

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

Eliminations.

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).

Related Reagents.

1,1,3,3-Tetramethylguanidine.


1. Barton, D. H. R.; Elliott, J. D.; Géro, S. D. JCS(P1) 1982, 2085.
2. Barton, D. H. R.; Bashiardes, G.; Fourrey, J.-L. TL 1983, 24, 1605.
3. Corey, E. J.; Jardine, P. D.; Mohri, T. TL 1988, 29, 6409.
4. Corey, E. J.; Jardine, P. D. TL 1989, 30, 7297.
5. Beard, C. C. In Organic Reactions in Steroid Chemistry; Fried, J., Edwards, J. A., Eds.; Van Nostrand Reinhold: New York, 1972; Vol. 1, p 344.

Lorraine Scott

R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA



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