The silyl ether protecting group is cleaved off with fluoride ion using tetrabutylammonium fluoride ( TBAF) Bu 4N +F –. However, silicon being in the 3 rd row of the periodic table is larger, and the Si-C bond is longer than the C-C bond which reduces the steric effects making the S N2 mechanism possible on a tertiary atom: Have you noticed the arrows indicating an S N2 mechanism in the first step of installing the protecting group? And do you remember that S N2 reactions are not possible with tertiary substrates? Well, that is true for the substrates with the leaving group on the carbon. The reaction with alcohols is carried out in the presence of a base such as triethylamine (TEA) or Imidazole to deprotonate the oxygen: We take a silyl chloride, do a substitution using the alcohol as a nucleophile and then the alcohol converted into a silyl ether can be used in the presence of any strong base including the Grignard reagent. The most common protecting groups for alcohols are the silyl ethers. The term protecting group is usually abbreviated as “PG” in chemical structures: So, for our molecule, we need something to block the alcohol from the attack, perform the Grignard and then remove this blocking unit at the end: A protecting group is a compound that temporarily converts a given functional group into another allowing for performing reactions that are otherwise incompatible with that functional group. Therefore, remember that the Grignard reaction should be carried out in a “proton-free” environment, meaning no acidic functional groups and no protic solvents can be present.Īnd this is where the protecting groups become needed.
The acid-base reaction quenches the ethyl magnesium bromide not allowing the desired Grignard reaction to take place. However, this reaction is slower, and the Grignard reagent first deprotonates the alcohol: And, even the α-hydrogens next to the carbonyl can be attacked by the Grignard reagent since they have a p Ka of ~ 20. Looking at your p Ka table (or better without looking) you can see that the most acidic proton in this molecule is the alcohol (p Ka = 16). Now, with this said, can you identify a proton in the starting material which is acidic enough to be attacked by the ethylmagnesium bromide? Remember that acid-base reactions are among the fastest and will occur before substitution reactions. Grignard reagents are excellent nucleophiles but at the same time, they are also strong bases since there is an extremely polar C-Mg covalent bond which leaves the carbon electron-rich. Let’s, for a moment, forget about the protecting group and try to figure out what will happen if we mix the Grignard reagent with an alcohol: These are the questions we are going to address in today’s article.
Predict the molecular formula of hexanol.Why do you think the following Grignard reaction is impossible to carry out without having a protecting group on the alcohol? Predict the molecular formula of decanol and explain your answer. The general formula for the alcohols is C n H 2n+1 OH (where n is the number of carbon atoms in the molecule). Take care not to confuse the –OH group with the hydroxide ion, OH–. It is responsible for the typical reactions of alcohols. The functional group in the alcohols is the hydroxyl group, –OH. show a gradual variation in physical properties, such as their boiling points.differ by CH2 in molecular formulae from neighbouring compounds.Like all homologous series, the alcohols:
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