Why is the carbonyl group in tert-butoxycarbonyl group (tBOC) less susceptible to attack from nucleophiles than the carbonyl group in esters such as ethyl acetate?
Is this something to do with conjugation?
Yes, the difference in reactivity between the carbonyl group in a tert-butoxycarbonyl (tBOC) group and the carbonyl group in esters such as ethyl acetate can be attributed to conjugation effects.
To understand this, let's first define conjugation. Conjugation occurs when there is a continuous sequence of alternating single and multiple bonds (such as in a π system) that facilitates the delocalization of electrons. In organic molecules, conjugation can have a significant impact on the reactivity and stability of functional groups.
In tert-butoxycarbonyl (tBOC) groups, the carbonyl group (C=O) is conjugated with the adjacent carbon-carbon double bond (C=C) in the tert-butyl moiety:
O
│
R'-C=C-C(=O)-R
│
R
The presence of conjugation allows for delocalization of the π-electrons between the carbonyl carbon and the adjacent double bond carbon atoms. This delocalization spreads out the electron density and stabilizes the carbonyl group. As a result, the electrons associated with the carbonyl carbon are less available for attack by nucleophiles, making the carbonyl group less susceptible to nucleophilic attack.
On the other hand, in esters like ethyl acetate, there is no conjugation between the carbonyl group (C=O) and any adjacent double bonds:
O O
│ │
R-C(=O)-O-CH2-CH3 R-C(=O)-O-CH2-CH3
│ │
R R
In the absence of conjugation, the electron density on the carbonyl carbon atom is localized within the carbonyl group. This makes the carbonyl group more exposed and reactive towards nucleophilic attack.
In summary, the conjugated carbonyl group in tert-butoxycarbonyl (tBOC) groups is less susceptible to attack by nucleophiles compared to the non-conjugated carbonyl group in esters like ethyl acetate. This is due to the electron delocalization provided by the adjacent double bond in tBOC groups, which stabilizes the carbonyl carbon and reduces the electron density available for nucleophilic attack.