p-tert-Butylcalix[4]arene has been chemically modified in a regioselective manner at the 1,3-(distal) phenolic groups of the lower rim using electrophiles such as ethyl bromoacetate, chloroacetone, bromopinacolone, chloroacetonitrile, and prop-2-ynyl bromide. X-Ray diffraction analysis of one of these 1,3-derivatives reveals that it exists in a highly distorted cone conformation. Crystals of the dinitrile 7 are triclinic, space group P, with two molecules in a cell of dimensions a= 13.191 (3), b= 16.755(3), c= 10.424(1)Å; α= 100.32(1), β= 93.23(1), γ= 84.89(2)°. The structure was solved by direct methods and refined by full-matrix least squares calculations; R= 0.066 for 4155 observed reflections. The two phenolic rings (A and C) are tilted (interplanar angle 102.3°) so as to place the hydroxy groups inside the cavity, whereas rings B and D bearing OCH₂CN moieties are almost parallel to each other (interplanar angle 13.3°). This arrangement allows for relatively facile intramolecular hydrogen bond formation between proximal hydroxy and ether functional groups [O(H)⋯ O 2.941(3) and 2.903(3)Å]. These products are useful precursors of other 1,3-disubstituted derivatives including double calixarenes and of a variety of tetrasubstituted calix[4]arenes with dual functionality on the lower rim.