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Solutions For An Introduction to Medicinal Chemistry Chapter 13 Problem 14Q

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Solution 1

Hydrogen bonding requires a donor group and an acceptor group. The donor group consists of a hydrogen atom bound to an electronegative atom, whereas the acceptor group consists of an electron-rich atom with a lone pair.

For the first structure, the oxygen atom does not have a very good electron density. The atom is bound to a carbonyl carbon atom and an alkyl group, both of which exert an electron-withdrawing effect on the atom and dissipate its electron density.

For the second structure, the oxygen atom is subjected to an electron-withdrawing effect due to its covalent bond with an aromatic ring, whose resonance structure has a detrimental effect on the electron density of the atom.

Additionally, the oxygen atom is bound to another alkyl or aryl group, which is denoted by the “R” letter. Both of the potential groups, but the aryl group in particular, would have a highly detrimental effect on the electron density of the atom.

For the third structure, the oxygen atom is a part of an aromatic ring, with four carbon atoms making up the remainder of the ring. The resonance effect of this ring greatly dissipates the electron density of the atom, inhibiting its potency as a hydrogen bond acceptor.

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