Alcohols react with the carbonyl groups of aldehydes and ketones to produce compounds called hemiacetals. These react further with another molecule of the alcohol to make a new compound called an acetal. Water is produced in the latter reaction. Here's the reaction.
Let's look first at the first part of the overall reaction, the formation of the hemiacetal.
If we imagine that the OH bond of the alcohol breaks, we see that the H+ is a Lewis acid. The RO- is a Lewis base. Looking at the reaction, we see that the Lewis acid part of the molecule (the H+) adds to the oxygen of the C=O group and the Lewis base part of the alcohol molecule adds to the carbon of the C=O. This is as we expect, and it helps us to connect this reaction to the pattern of additions to C=O groups we developed earlier.
That pattern doesn't tell us what the order of steps (the mechanism) is, though. Our best clues to that are the fact that the reaction is acid catalyzed and our understanding of the addition of HBr to alkenes. These tell us to start the reaction with H+ bonding to the C=O oxygen. This step is just like the first step in addition of HBr to an alkene C=C bond and it also forms a carbocation.
Since there is much more ROH than RO- around, the next step is for the ROH to react with the carbocation. Notice that ROH has unshared pairs of electrons on the oxygen and is a Lewis base. To finish off the reaction, we return an H+ to the solution to replenish the catalyst.
The next process conversion of the hemiacetal to the acetal, has some new features. It is a substitution reaction, a type we haven't seen before. [We've seen additions and eliminations (dehydrations, for example).] Our clue is that the we know how to add ROH to a carbocation and then drop off an H+. So let's work backwards from the acetal and see what we need to have for a carbocation.
That leaves us with the question. "How do we get from the hemiacetal to the acetal?" We have to lose an OH-. Since we know how to put an alcohol on a carbocation (making the hemiacetal), perhaps the way to lose a water is to just reverse the reaction that puts an ROH on a carbocation. If we do that, we see that what we have to do is to put an H+ on the OH of the hemiacetal. If that molecule drops a water molecule off, we have the carbocation we need.
The major application of these reactions is in sugar (carbohydrate) chemistry. The following reaction shows the conversion of a polysaccharide (starch, a polymer of glucose -- notice the acetal functional group) to glucose, first in a ring (cyclic) form (notice the hemiacetal functional group), and then to an open form (notice the aldehyde and alcohol functional groups). We'll look at these in more detail later.
The next reaction (the aldol reaction) we'll look at is one which makes a carbon-carbon bond. Such reactions are important in many contexts. One example is the photosynthetic conversion of CO2 to glucose, C6H12O6. In this process, which is fundamental to life on earth, six new carbon-carbon bonds are formed. Let's see what happens in the aldol reaction.
If we work back from the product and use our understanding that Lewis bases add to carbonyl carbons, we are forced to the conclusion that the Lewis base is an aldehyde minus an H+ from a carbon adjacent to the C=O group. This must mean that the hydrogen on that carbon (let's call it the alpha carbon) is acidic enough to be taken off, at least from a few molecules at a time, by the OH- catalyst we notice as part of the reaction. We won't explain why just now, but that turns out to be correct: hydrogens on a carbon in the alpha position relative to a carbonyl group are weakly acidic.
If we have a solution which contains an aldehyde and OH-, we should expect products of the aldol condensation to occur. We can imagine the structure of the product if we join the alpha carbon of one aldehyde molecule to the carbonyl carbon of the other. The hydrogen goes on what was the oxygen of the carbonyl group added to. The other carbonyl group is unchanged.
An aldol reaction important in the biochemistry of metabolism is step 5 of glycolysis (pp 311-312). In photosynthesis (not covered in this course) and gluconeogenesis (p 322) this reaction makes a carbon-carbon bond, as did the aldol reaction above. In glycolysis it operates in the opposite direction to break the same bond.
