Journal of Chemical Crystallography, Vol. 29, No. 2, 1999
Conversion of 2,4-dihydroxybenzaldehyde to 2-benzoyloxy-
4-hydroxybenzaldehyde and structural characterization of
both precursor and product
Zhiyong Hu,(1) Michaele J. Hardie,(2) Pannee Burckel,(2) A. Alan Pinkerton,(2)*
and Paul W. Erhardt(1)*
Received January 4, 1999
2,4-Dihydroxybenzaldehyde can be acylated at the 2 position if the more reactive 4 position
is first protected as the methylmethoxy ether. Deprotection permits isolation of 2-benzoyloxy-
4-hydroxybenzaldehyde. 2,4-Dihydroxybenzaldehyde, C7H6O3, crystallizes in P21/c, with a ϭ
˚
7.3762(6), b ϭ 11.7455(9), c ϭ 7.3149(6) A, ͱ ϭ 90.533(2)Њ, Z ϭ 4, and DX ϭ 1.448 g
cmϪ3. The individual molecules are characterized by an intramolecular hydrogen bond. The
molecules form sheets with additional intermolecular hydrogen bonds. 2-Benzoyloxy-4-hy-
droxybenzaldehyde, C14H10O2, crystallizes in Pca21, with a ϭ 24.2629(14), b ϭ 3.8445(2),
Ϫ3
˚
c ϭ 12.3727(8) A, Z ϭ 4, and DX ϭ 1.394 g cm . The molecules consist of two planar halves
twisted by 51.63(5)Њ about the ester linkage. Intermolecular hydrogen bonding joins the
molecules into ribbons approximately parallel to c.
KEY WORDS: 2-Benzoyloxy-4-hydroxybenzaldehyde; 2,4-dihydroxybenzaldehyde; hydrogen bonding;
x-ray structure.
Introduction
Experimental
As part of a medicinal chemistry program to
Potassium carbonate, 1.38 g (10 mmol), was
added to a solution of 1.38 g (10 mmol) of 2,4-dihy-
droxybenzaldehyde in 70 ml of anhydrous acetone.
The mixture was stirred at room temperature for 15
min and then cooled to 5–10ЊC. A solution of 0.81 g
(10 mmole) of chloromethyl methyl ether in 2 ml of
ethyl acetate was added dropwise and the mixture
stirred for 2 h at 5–10ЊC followed by an additional
15 h at room temperature. Water, 50 ml, was added to
the reaction medium and the new mixture extracted
three times with 70-ml portions of ethyl ether. The
organic phases were combined, washed once with 70
ml of saturated aqueous sodium chloride, once with
70 ml of water, and then dried for several hours over
anhydrous magnesium sulfate at 2ЊC. Filtration of
the combined organic phase followed by evaporation
provided a light yellow oil which displayed a 2 spot
prepare novel anticancer agents, we required 2-ben-
zoyloxy-4-hydroxybenzaldehyde, 1, as a key synthetic
intermediate. Toward this end, the commercial avail-
ability of 2,4-dihydroxybenzaldehyde, 2, affords an
appropriately substituted benzene ring. However, ‘in-
tramolecular hydrogen bonding of the 2-hydroxy
group to the adjacent aldehyde function minimizes
reaction at this site’1 compared to the more reactive
4-position hydroxy group such that 1 is difficult to
obtain by direct acylation of 2. 2-Hydroxy-4-
(methoxymethoxy)benzaldehyde, 3.
(1) Center for Drug, Design and Development, University of To-
ledo, Toledo, Ohio 43066.
(2) Department of Chemistry, University of Toledo, Toledo,
Ohio 43606.
* To whom correspondences should be addressed.
185
1074-1542/99/0200-0185$16.00/0 1999 Plenum Publishing Corporation
Hu, Zhiyong
