Nitrogen Inversion in regards to Stereochemistry Topic Outline

• Nitrogen as a Stereocenter • What is Nitrogen Inversion? • How do you know whether a Nitrogen atom has Nitrogen Inversion? • How does Nitrogen Inversion affect the stereochemistry of a molecule? • Practice Problems and solutions

Nitrogen as a Stereocenter A stereocenter is an atom with three or more different substituents where interchanging two of them will lead to a different stereoisomer. Usually a stereocenter is a tetravalent carbon with four different substituents. However it can also be a Nitrogen. Examples:

Stereocenter Not a Stereocenter

Has 4 different attachments Has only two different attachments

Just as in carbon, it is important to make sure there are at least three different substituents. If a nitrogen has three attachments and a lone pair, one might assume that this could also be a stereocenter. Example:

Non-superposable mirror images of ethyl methyl amine. It appears as though they are two different enantiomers. The one on the left would be the R conformation. The one on the right would be the S conformation.

HCl

H

H

H

ClCH2CH3

CH3

However, due to a special case of inversion called nitrogen inversion, this nitrogen is not considered a stereocenter. What is Nitrogen Inversion? Nitrogen inversion is when the lone pair on a Nitrogen oscillates from one side of the plane of the three atoms attached to it to the other side of that plane.

The green lobe represents the lone pair. It is constantly moving from one side of the nitrogen atom to the other side. It goes through a transition state in which the three substituents are planar and the lone pair is in a p orbital.

The other substituents invert like an umbrella:

These two inversions act more like conformational changes and are in equilibrium. The energy required for inversion of simple amines to take place is about 25 kJ/mol. The equilibrium constant is 1. How do you know whether Nitrogen can have inversion? Characteristics of a Nitrogen atom that can go through inversion

• Must have a lone pair available to undergo inversion o Lone pair cannot be delocalized due to resonance

• Must not be involved in strain that will prevent inversion o Strain can be caused by a nitrogen in a ring.

CH3CH3

CH2CH3CH2CH3 H

H

N

..N

..

How does Nitrogen Inversion affect the stereochemistry of a molecule? Whennitrogeninversionistakingplace,thereisnostereocenterbecausethestereochemistryisrapidlychangingbetweenRandSconfigurations.DuetothisinversionthedifferentRandSconfigurationsactmorelikeconformationalchanges.Anitrogenwithinversionisnotconsideredastereocenter.

Practice Problems For each molecule decide which Nitrogens are stereocenters and explain why or why not.

1. Epibatidine

2. Coniine

3. Tetraethylamine

4.

Solutions

Noneofthemarestereocenters.Innumber1thenitrogenontherightisundergoinginversion.Althoughitisinsortofaring,thehydrogenandthelonepairarestillfreetoswitcharound.

Innumber2thenitrogenisalsogoingthroughinversion.

Innumber3thenitrogenisattachedtofouridenticalsubstituents.

AdditionalPractice:

Practiceproblem10onpg96ofthethinkbookisagreatproblemtopracticerecognizingNitrogenstereocenters.

WorksCited:

OrganicChemistryStructuerandFunctionVollhordtandSchore

Dr.Hardinger’sThinkbookandIllustratedGlossary.

Imagesofumbrellas,coniine,epibatidine,andtetraethylaminearefromgoogleimages.

OrganicChemistryWilliamH.Brown