Organic Chemistry Text Book (CHEM 3401 and 3402)

Virtually all of the organic chemistry that you will see in this course takes place in the solution phase. In the organic laboratory, reactions are often run in nonpolar or slightly polar solvents such as toluene (methylbenzene), dichloromethane, or diethylether. In recent years, much effort has been made to adapt reaction conditions to allow for the use of ‘greener’ (in other words, more environmentally friendly) solvents such as water or ethanol, which are polar and capable of hydrogen bonding. In biochemical reactions the solvent is of course water, but the 'microenvironment' inside an enzyme's active site - where the actual chemistry is going on - can range from very polar to very non-polar, depending on which amino acid residues are present.

You probably remember the 'like dissolves like’ rule you learned in general chemistry, and even before you took any chemistry at all, you probably observed at some point in your life that oil does not mix with water. Let’s revisit this rule, and put our knowledge of covalent and noncovalent bonding to work.

When considering the solubility of an organic compound in a given solvent, the most important question to ask ourselves is: how strong are the noncovalent interactions between the compound and the solvent molecules? If the solvent is polar, like water, then a smaller hydrocarbon component and/or more charged, hydrogen bonding, and other polar groups will tend to increase the solubility. If the solvent is non-polar, like hexane, then the exact opposite is true.

Imagine that you have a flask filled with water, and a selection of substances that you will test to see how well they dissolve in the water. The first substance is table salt, or sodium chloride. As you would almost certainly predict, especially if you’ve ever inadvertently taken a mouthful of water while swimming in the ocean, this ionic compound dissolves readily in water. Why? Because water, as a very polar molecule, is able to form many ion-dipole interactions with both the sodium cation and the chloride anion, the energy from which is more than enough to make up for energy required to break up the ion-ion interactions in the salt crystal.

The end result, then, is that in place of sodium chloride crystals, we have individual sodium cations and chloride anions surrounded by water molecules – the salt is now in solution. Charged species as a rule dissolve readily in water: in other words, they are very hydrophilic (water-loving).

Now, we’ll try a compound called biphenyl, which, like sodium chloride, is a colorless crystalline substance.

Biphenyl does not dissolve at all in water. Why is this? Because it is a very non-polar molecule, with only carbon-carbon and carbon-hydrogen bonds. It is able to bond to itself very well through nonpolar van der Waals interactions, but it is not able to form significant attractive interactions with very polar solvent molecules like water. Thus, the energetic cost of breaking up the biphenyl-to-biphenyl interactions in the solid is high, and very little is gained in terms of new biphenyl-water interactions. Water is a terrible solvent for nonpolar hydrocarbon molecules: they are very hydrophobic (water-fearing).

Next, you try a series of increasingly large alcohol compounds, starting with methanol (1 carbon) and ending with octanol (8 carbons).

You find that the smaller alcohols - methanol, ethanol, and propanol - dissolve easily in water, at any water/alcohol ratio that you try. This is because the water is able to form hydrogen bonds with the hydroxyl group in these molecules, and the combined energy of formation of these water-alcohol hydrogen bonds is more than enough to make up for the energy that is lost when the alcohol-alcohol (and water-water) hydrogen bonds are broken up. When you try butanol, however, you begin to notice that, as you add more and more to the water, it starts to form a layer on top of the water. Butanol is only sparingly soluble in water.

The longer-chain alcohols - pentanol, hexanol, heptanol, and octanol - are increasingly non-soluble in water. What is happening here? Clearly, the same favorable water- alcohol hydrogen bonds are still possible with these larger alcohols. The difference, of course, is that the larger alcohols have larger nonpolar, hydrophobic regions in addition to their hydrophilic hydroxyl group. At about four or five carbons, the influence of the hydrophobic part of the molecule begins to overcome that of the hydrophilic part, and water solubility is lost.

Now, try dissolving glucose in the water – even though it has six carbons just like hexanol, it also has five hydrogen-bonding, hydrophilic hydroxyl groups in addition to a sixth oxygen that is capable of being a hydrogen bond acceptor.

We have tipped the scales to the hydrophilic side, and we find that glucose is quite soluble in water.

We saw that ethanol was very water-soluble (if it were not, drinking beer or vodka would be rather inconvenient!) How about dimethyl ether, which is a constitutional isomer of ethanol but with an ether rather than an alcohol functional group? We find that diethyl ether is much less soluble in water. Is it capable of forming hydrogen bonds with water? Yes, in fact, it is –the ether oxygen can act as a hydrogen-bond acceptor. The difference between the ether group and the alcohol group, however, is that the alcohol group is both a hydrogen bond donor and acceptor.

The result is that the alcohol is able to form more energetically favorable interactions with the solvent compared to the ether, and the alcohol is therefore much more soluble.