A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1990, 68, 243
DOI: 10.15227/orgsyn.068.0243
Submitted by J. H. Munch1 and C. D. Gutsche2.
Checked by Daniel T. Daly and James D. White.
1. Procedure
A slurry prepared from 100 g (0.67 mol) of p-tert-butylphenol, 35 g (ca. 1.1 mol) of paraformaldehyde (Note 1), and 2.0 mL (0.02 mol) of 10 N sodium hydroxide (Note 2) in 600 mL of xylene is placed in a 2-L, round-bottomed, three-necked flask fitted with a Dean–Stark water collector and a mechanical stirrer. The air in the flask is replaced with nitrogen, and the stirred contents of the flask are heated to reflux by means of a heating mantle. After 30 min a homogeneous solution is obtained, and after 1 hr a white precipitate begins to form. The reaction mixture is refluxed for 4 hr, the heating mantle is removed, the mixture is allowed to cool to room temperature, and the precipitate is removed by filtration. The crude product is washed, in succession, with 400-mL portions of toluene, ether, acetone, and water and is then dried under reduced pressure. It is dissolved in ca. 1600 mL of boiling chloroform. The chloroform is concentrated to ca. 1200 mL, the solution is cooled to room temperature, and the precipitate is collected by filtration to yield 67–70 g (62–65%) of a colorless powder, dec 418–420°C (Note 3) and (Note 4).
2. Notes
1. p-tert-Butylphenol from Aldrich Chemical Company, Inc., mp 98–101°C, and paraformaldehyde from Fisher Chemical Company, Certified ACS grade, were used.
2. Other bases, including KOH, RbOH, and CsOH, also work with approximately the same results, but LiOH is considerably inferior.
3. The (solvated) product can be obtained in crystalline form but, on standing in air for a few minutes, the colorless, glistening needles change to a white powder as the result of loss of solvent of crystallization. Considerable variation in the melting point of this material is noted. The product generally melts above 400°C, but sometimes the melting point falls to ca. 395°C or even lower. Undoubtedly, this is due to impurities such as metal ions and/or other cyclic oligomers that are incompletely removed in the recrystallization (see (Note 4)).
4. Evaporation of the xylene filtrate and trituration of the residue with methylene chloride yields ca. 11 g of solid that consists mainly of cyclic hexamer and cyclic tetramer. The methylene chloride contains, inter alia, cyclic pentamer, cyclic heptamer, and bishomo compound, and these can be obtained as pure samples in low yield by fractional crystallization procedures. The composition of the reaction mixtures can be qualitatively established by TLC by means of the following Rf values in 9 : 1 petroleum ether/acetone and 1 : 1 petroleum ether/methylene chloride, respectively: (a) cyclic octamer—0.54, 0.85, (b) cyclic heptamer—0.40, 0.78, (c) cyclic hexamer—0.54, 0.76, (d) cyclic pentamer—0.74, 0.68, (e) cyclic tetramer—0.63, 0.66, and (f) bishomooxa compound—0.66, 0.56.
3. Discussion
This method for preparing p-tert-butylcalix[8]arene was first described in the patent literature3 by chemists of the Petrolite Corporation, St. Louis, MO and, therefore, is often referred to as the "Petrolite procedure." It was introduced into journal literature by Gutsche et al.4 Although the procedure is restricted to phenols substituted in the p-position with electronically neutral groups, it is more general in its application than the accompanying procedures for the calix[4]arenes and calix[6]arenes and has been used with p-isopropylphenol,5 p-tert-pentylphenol,5 p-(1,1,3,3-tetramethylbutyl)phenol,6 and p-phenylphenol.7

References and Notes
  1. Petrolite Corporation, St. Louis, MO 63119;
  2. Department of Chemistry, Washington University, St. Louis, MO 63130.
  3. Buriks, R. S.; Fauke, A. R.; Munch, J. H. U.S. Patent 4 259 464, 1981; Chem. Abstr. 1981, 94, P209, 722x.
  4. Gutsche, C. D.; Dhawan, B.; No, K. H.; Muthukrishnan, R. J. Am. Chem. Soc. 1981, 103, 3782.
  5. Dhawan, B.; Chen, S. I.; Gutsche, C. D. Makromol. Chem. 1987, 188, 921.
  6. Cornforth, J. W.; D'Arcy Hart, P.; Nicholls, G. A.; Rees, R. J. W.; Stock, J. A. Br. J. Pharmacol. 1955, 10, 73.
  7. Gutsche, C. D.; Pagoria, P. F. J. Org. Chem. 1985, 50, 5795.

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

petroleum ether


ether (60-29-7)

sodium hydroxide (1310-73-2)

chloroform (67-66-3)

nitrogen (7727-37-9)

acetone (67-64-1)

toluene (108-88-3)

xylene (106-42-3)

methylene chloride (75-09-2)

p-phenylphenol (92-69-3)

p-tert-butylphenol (98-54-4)

p-isopropylphenol (99-89-8)

p-tert-pentylphenol (80-46-6)

p-(1,1,3,3-tetramethylbutyl)phenol (140-66-9)

paraformaldehyde (30525-89-4)