nucleophilic acyl addition

When enolates attack, the arrow is drawn from the double bond to the electrophile, and NOT from the negatively charged oxygen! The enolate's carbonyl reforms, and a new bond is created at the alpha position.

But Aldehydes and ketones react differently than ester and acid chlorides.

a) Aldehydes and ketones are oxidation state II carbonyls (the carbonyl has carbon-heteroatom bonds- the double bonded oxygen counts twice).

They do not have a built-in leaving group, and so undergo nucleophilic acyl addition reactions. The carbonyl on the electrophile becomes an alcohol.

So the product from this reaction is a beta hydroxyl carbonyl. If this β-hydroxyl carbonyl is heated up, the hydroxyl will eliminate to from an alpha, beta unsaturated carbonyl.

The mechanism for a) is very similiar to that of an aldol condensation reaction.

b) Esters (and acid chlorides) are oxidation state III carbonyls (the carbonyl carbon has three carbon-heteroatom bonds). They have a built-in leaving group (^-OR in the case of an ester, and Cl^- for an acid chloride), and so undergo nucleophilic acyl substitution reactions. ("up, down, kick"). The carbonyl on the electrophile is reformed.

So the product from this reaction is a beta keto carbonyl.

The mechanism for b) is very similiar to that of a Claisen condensation reaction.

This reaction takes place under acidic conditions, so oxygen should never be negative (only neutral or positively charged). 

Acidic mechanisms tend to be a bit of pain, because you have to include many proton transfer steps (protonation and deprotonation).

The interconversion between a carbonyl (sp² carbon) and a tetrahedral intermediate (sp³ carbon) is the most common mechanism you will encounter in second semester organic chemistry.

You should be familiar drawing it under both acidic (this problem) and basic (problem 705) conditions.

In a), the carbonyl "goes up" to form a tetrahedral intermediate.

In b), an oxygen "comes back down" to reform the carbonyl and kick off a leaving group.

You will see this "up, down, kick" pattern in most mechanisms that involve attack at the carbonyl carbon, which is most of the reactions in second semester orgo!

a) Carbonyl to Hydrate (acidic) "UP"

Because this reaction takes place under acidic conditions, the carbonyl must protonate before the nucleophile attacks, to prevent oxygen from ever being negative (ROH instead of RO^-).

b) Hydrate to Carbonyl (acidic) "DOWN"

The leaving group must protonate before it leaves, so it doesn't leave as a negative molecule (H₂O instead of HO^-).

The mechanisms in this problem and problem 706 are the most common mechanisms you will draw during second semester organic chemistry, and so it's a good idea to draw them out a few times.

In a), the nucleophile attacks the carbonyl carbon, and the double bond goes "up" to form a tetrahedral (sp³) carbon.

In b), one of the oxygen atoms acts as leaving group, and a lone pair on the other oxygen comes "down" to reform the double bond (and the sp² carbon).

You will see this "up, down, kick" pattern in most mechanisms that involve attack at the carbonyl carbon, which is most of the reactions in second semester orgo!

a) Carbonyl to Hydrate (basic conditions) "UP"

b) Hydrate to Carbonyl (basic conditions) "DOWN"

This carbonyl has two leaving groups attached to it- each of those oxygens can take part in a nucleophilic acyl substitution reaction and form a new carbonyl product.

First the Grignard attacks the oxidation state IV carbonyl carbon (4 oxygen bonds, so oxidation state 4). The carbonyl itself will act as a leaving group and form a tetrahedral intermediate. But tetrahedral intermediates don't last if there are any leaving groups attached to the carbon, so the ^-O will "come back down again", kick off an oxygen leaving group, and reform the carbonyl.

Then a second equivalent of Grignard will attack that carbonyl (an ester), and we will do another nucleophilic acyl substitution reaction to form yet another carbonyl.

Finally, the third carbonyl doesn't have any leaving groups built in (it's a ketone), so when the third equivalent of Grignard attacks it, it will do a nucleophilic acyl addition reaction, and the product will be an alcohol.

Notice that as the reaction progresses the oxidation state of the carbonyl carbon (number of oxygen bonds attached to it) goes down form 4 to 3 to 2 and then to 1.

Oxidation state III carbonyls (esters, acid chlorides) contain a built-in leaving group (such as ^-OR or ^-Cl) and so undergo nucleophilic acyl substitution reactions. The product is another carbonyl.

Oxidation state II carbonyls (aldehydes and ketones) do not contain a built-in leaving group and so undergo nucleophilc acyl addition reactions (instead of substitution). The product is an alcohol.

Because Grignards react with all carbonyls- esters and aldehydes/ketones- esters and acid chlorides will react twice with Grignards: once in a Nuc Acyl Sub mechanism to form a ketone, which will then react with another equivalent of Grignard in a Nuc Acyl Add mechanism to form an alcohol.