Nucleophilic Acyl Substitution (Carboxylic Acid Derivatives)

Problem # 730

N,N-dimethylformamide (DMF) is shown below. Based on its structure, you might expect to see only one -CH₃ signal in the ¹H NMR spectrum. But instead DMF shows two different -CH₃ signals. Explain.

Solution

DMF appears to have two identical methyl groups. Since these six protons are all equivalent, its ¹H NMR should only show one methyl signal (singlet, 6H).

So why is that the real life the ¹H NMR of DMF shows two methyl signals? (two singlets with integration of 3H).

Because DMF is an amide.Recall that the "real" structure of molecule is the a mixture of its resonance forms. DMF doesn't look like either of the two resonance forms below. In real life, its somewhere in between.

For most carboxylic acid derivatives (such as esters), the resonance form is only a minor contributor and so the real "picture" looks very close to the carbonyl Lewis structure.

But for amides, its resonance form is fairly stable (it's common for nitrogen atoms to be positively charged), and so is a major resonance contributor.

In an amide, the bond between the carbonyl carbon and the nitrogen atom has a high degree of double bond character. (This also explains why it's harder to rotate the C-N "single bond" than you would expect from its Lewis structure- it's sort of like a double bond).

Because the C-N "single bond" is closer to a double bond, the two methyls are not equivalent. One methyl is cis, and the other is trans, and so they show two signals in the ¹H NMR.

Problem Details

MendelSet practice problem # 730 submitted by Matt on July 24, 2011.

Subject: Organic Chemistry

Subject Topic(s): Nuclear Magnetic Resonance Spectroscopy (NMR), Nucleophilic Acyl Substitution (Carboxylic Acid Derivatives), Amino Acids, Peptides, and Proteins

Question Type: Concept (explain why this is so..)

Keyword(s): proton NMR, amides

Problem # 729

The ester below was dissolved in a solution of water, a small amount of which was isotopically labeled with O-18, denoted with an asterisk.

After a few hours, some isotopically labeled oxygen was found in the ester. Where was it found in the ester? Can you explain why?

Solution

To answer this problem, you must be familiar with the nucleophilic acyl substitution mechanism. (see problem 725)

Water reacts with an ester to form a carboxylic acid. This is what happens here.

If there is only trace amounts of water, it's possible that the water reacts with the ester to form a carboxylic acid, and then goes back to reform the ester. But, in this process, leaves an isotopically labeled oxygen in the carbonyl position.