Question

Using the Chemical Structure of Naproxen, circle or highlight all polar regions of the molecule. Make a reasonable prediction about whether your molecule will be soluble in water or not. Explain your reasoning. If it seems to be borderline in molecular polarity, making it difficult to predict solubility, explain your reasoning and the difficulty involved. Compare your predictions with the solubility information in the literature.

PLEASE HELP!!

Answer 1

Naproxen can be considered as a derivative of napthalene.

Polar regions in napthalene (Image uploaded):

1. ether functionality (Ar-O-CH₃): the carbon - oxygen bonds are polar due to high electronegativity of oxygen; and there are two lone electron pairs on oxygen. these two factors contribute to net polarity of the functional group. The oxygen atom can potentially form hydrogen bonds with hydrogens of water molecules.

2. carboxylic acid (-COOH): it is an acidic functional group. Both C=O group and -OH group are highly polar. -COOH group can furnish H+ ions and form carboxylate (-COO-). Both the oxygen atoms have potential to form hydrogen bonds with hydrogens of water molecules. The hydrogen of -COOH group can also participate in hydrogen bonding with oxygen of water molecule.

The two polar functional groups can impart water solubility of naproxen.

​The -COOH group is much more polar than ether functionality. It is the -COOH group that contributes mainly for any solubility of naproxen.

However, naproxen also has large hydrophobic group, the naphthalene ring system (and also the methyl groups), that lowers the solubility. Overall we can predict that the solubility of naproxen in water will be low.

Further support for above explanation:

Benzoic acid which has only one benzene ring and -COOH group, has low solubility in water.

Solubility of benzoic acid is only 3.44 g per litre of water at 25^oC.

Anisole (Ph-O-CH₃) has one benzene ring and a -O-CH₃ (ether) group and is insoluble in water.

p-Toluic acid (p-CH₃-Ph-COOH) has a benzene ring, a methyl group and a -COOH group but is sparingly soluble in water.

Hence, we can predict that naproxen which has -COOH and ether functionality that make it polar, but also large non-polar napthalene ring system, will be sparingly soluble in water.

​This is in agreement with information available in literature that naproxen is practically insoluble in water (solubility of naproxen is only few milligrams per litre of water).