Cold and Flu Season

 

Recognize these items? These are common items that can be found around this time of year…disinfectants. What are some of the active structures that can be found in these products? Let’s take a look…

 

 

Now, how do these work to disinfect?

 

The long chain is nonpolar; therefore, it can slip between the bilayer and interact with the inner nonpolar portion of the lipid bilayer. The polar amine (positively charged) can interact with the outer polar portion of the bilayer.

This interaction disrupts the bilayer thereby allowing molecule and ions to freely move between the inside and the outside of the cell. Without any control over this movement, the cell will eventually die.

 

 

Now, let’s talk about the main functional group present in these structures, the amine. How would we go about making these active compounds in a research laboratory? Could we put one alkyl group on the amine at a time?

 

Unfortunately, this will not work. After we place the first alkyl group on the nitrogen, the compound now becomes more basic (more reactive than ammonia). Immediately, the primary alkyl amine would grab another alkyl group, producing a secondary amine. Now, the secondary amine is even more reactive than the primary amine. Once again, there would be a very rapid alkylation, producing the tertiary amine; this will continue until the quaternary ammonium salt is formed.

Therefore, we need to be a bit more creative in our synthetic efforts. Luckily, organic chemists over the years have discovered ways around this dilemma. First, we need to find a way to synthesize a primary amine. One of the more famous reactions is called the Gabriel synthesis. This reaction involves reacting potassium pththalimide (the nucleophilic nitrogen source) with an alkyl halide followed by removal with either aqueous sodium hydroxide or hydrazine. The case below involves liberation of the amine using hydrazine:

Here are a couple of alternate ways to synthesize primary amines:

 

 

Once we have synthesized the primary amine, we need a way of adding an additional alkyl group to produce a secondary amine. One common way is shown below, which is called a reductive amination:

The first step involves reacting the primary amine with a carboxylic acid derivative (acid chloride in this case). The second step involves reducing the carbonyl group with a strong reducing agent.