Lecture notes, lecture 1 - Tautomerism PDF

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Tautomerism...

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Tautomerism: This important phenomenon arises in the general class of compounds represented by the structure shown below:

H

Y

Y

Z

Z

X

H

X

Z = C usually but can be N Y = O, or N Z = C usually, can be N, P Tautomerism in carbonyl compounds Carbonyl compounds fall into this category (Z, X = C, Y = O) provided there is a proton on one of the α-carbons. For example 3-pentanone exists as a mixture of tautomeric forms. These are referred to as the keto form and the enol form.

H O C C CH2 CH3 H3 C

H

H

O H C C

H3 C

keto tautomer

CH2 CH3 enol tautomer

Tautomerism in non-carbonyl compounds Many non-carbonyl systems, also exist as mixtures of tautomers, three common examples are:

H NH C C Imine

H C C N Nitrile

H O C N Nitroso

C C

NH2

Enamine

C C NH Ketenimine

OH C N Oxime

As will become clear for the carbonyl compounds, the phenomenon of tautomerism has a huge impact on the chemical properties of the compound You should practise drawing enol and enol-like tautomers for both Carbonyl, and nonCarbonyl compounds. See the tutorial problems, and also McMurry Chapter 22, problem 22.1. or Clayden (online problems) Restricting our attention to Carbonyl compounds The position of the Keto – Enol equilibrium. Simple carbonyl compounds For simple carbonyl-containing molecules, the contribution that the enol-form makes to equilibrium is very small (generally ca. 0.01%). Despite this, enolisable carbonyl compounds, display chemical properties of both these tautomers.

H O

O H3 C

C

H CH3

C H

acid or base

99.9999

C

CH3

0.0001

O C

O C

H

acid or base 99.999

0.001

Mechanisms for interconversion between Keto and Enol tautomers The conversion of the Keto-form, into the Enol-form, can be catalysed by both acids and bases. But also occurs in the absence of acid or base. Base-Catalysed Enolisation

B- :

H B

H O C C CH2 CH3 H3 C H

keto tautomer

.. O

H

H C C

C C H3 C

O H

CH2 CH3

enolate anion

H3 C

CH2 CH3 enol tautomer

Acid-Catalysed Enolisation

.. H A O

H C C CH2CH3 H3C H

AH OH+ H C C CH2CH3 H3C

H

O H

+ H-A C C CH2CH3 H3C

keto tautomer

enol tautomer

Tautomerisation in the absence of acid or base catalysts

O C C H

H C C O

O H C 2x C

Therefore tautomerisation between the keto-form and the enol-form cannot be avoided. Tautomeric forms for unsymmetrical Ketones

α -Hydrogen on both sides of the carbonyl. Whereas symmetrical ketones have only one enol tautomer (e.g. as for 3-pentanone above), unsymmetrical ketones can have two; they can enolise on both sides (provided αH is present). For example 2-butanone, which has α-H on both sides of the carbonyl, gives rise to two enol forms:

H

OH C C

H3 C

CH3 enol 2

H O C C CH3 H3 C H

H OH C C CH2 H3 C H

enol 1

The situation becomes even more complex if we also consider geometrical isomers (e.g. enol 2 above has E and Z stereoisomers possible, only one is shown ((E) here for simplicity).

While the double-bond geometry of the enol tautomer (enol 2) can have some important consequences, for the purposes of this course we will not be dealing with this.

Another example is 2-methylcyclohexanone, illustrating again that unsymmetrical ketones have two different enol forms

OH

O

OH

Unsymmetrical ketones with α -Hydrogen on only one side of the carbonyl. Unsymmetrical ketones with an α-H on one side only, however will have only one enol form. Acetophenone (below) provides an example:

α-Hydrogens absent OH

O

CH2

CH3 Acetophenone α-Hydrogens

This situation, of course also applies to esters and aldehydes, which cannot have α-H on both sides of the carbonyl:

O H

CH3

H

CH2

Tautomerism in Ethanal

OH

O

OH CH3O

CH3

CH3O

CH3

Tautomerism in Methyl acetate

Non-Enolisable Carbonyl Systems: Aldehydes, ketones and esters without α-H’s have no enol forms. Examples include:

O O H

O O

H H

RO

C(CH3 )3

Exceptions arise when H’s are α to a carbon-carbon double bond, which is itself conjugated with a carbonyl group:

H+ .. B

O H CH2

This is an example of conjugate enolisation.

OH CH2...