Can Organic Synthesis Products Alleviate Seasonal Allergies?

              Around this time every year, millions of allergy sufferers around the country are impacted by the effects of seasonal allergies. Stuffy noses, sneezing, and watery eyes are all symptoms of the common allergy nuisance. Thankfully, long ago scientists developed antihistamines which can be taken by allergy sufferers to alleviate their symptoms. One of the most common taken antihistamines is Zyrtec, commonly cetirizine. 

The recognized IUPAC name of cetirizine is (+-)-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy] acetic acid.1 The molecular formula is somewhat large at C₁₂H₂₅ClO₂N_3. A figure of the molecule is below:

             As can be seen above, there are several functional groups in the molecule. They have been 

color coded as described for easy recognition: two phenyl groups (red), a cyclic diammine 

group (yellow), an ether (green), carboxylic acid (blue) and halogen (purple). 


              A synthesis was prepared for cetirizine which may be found at the website http://chemistrybydesign.oia.arizona.edu/app.php and selecting “Zyrtec.”³ The given synthesis has five main steps that can be viewed by clicking the above link; briefly described, the steps are:^{4, 5}

Step 1: This step converted a carbonyl group of a ketone to a 2° alcohol. This is mainly completed using the reagent NaBH_4. In Organic Chemistry class lectures, the reduction of ketones to alcohols by NaBH₄ was discussed in the textbook in Chapter 20, page 728.

Step 2: Step 2 uses thionyl chloride, SOCl₂, to convert a 2° alcohol to a chloride substituent. This process was also discussed in the textbook in Chapter 9, page 335.

Step 3: Here, a nucleophilic substitution reaction occurs where Cl^- is a leaving group and is replaced with the given reagent. Nucleophilic substitution reactions were discussed in Chapter 7.

Step 4: This is another substitution reaction, but here OH^- is the leaving group.

Step 5: This step converts an amide to a carboxylic acid. This conversion has not been greatly discussed as of yet in the author of this post’s current organic chemistry class.

Several of the reagents needed to perform this synthesis are readily commercially available. These include NaBH₄, SOCl₂, toluene, NaOH, sodium methoxide. Some of the more specific reagents used in the substitution reactions may need to be custom prepared.

The following mechanism shows by curved arrow notation the conversion of the carbonyl functional group from Step 1 to a 2° alcohol:⁵ The borohydride anion attacks the carbonyl carbon and leaves a new hydrogen bond on that carbon, while electrons are pushed onto the elctronegative oxygen atom. The negatively charged oxygen then abstracts a hydrogen from water to form the alcohol.

So if you find that your eyes are watering after reading this, and you have a tickle in your throat, you may just need to take a personal evaluation of the effectiveness of the synthesized compound you just learned about.

References:
1) RxList. Zyrtec. <http://www.rxlist.com/zyrtec-drug.htm>. (Accessed April 13, 2013).
2) Wikipedia. Cetirizine. <http://en.wikipedia.org/wiki/File:Cetirizine_structure.svg> (Accessed April 13, 2013).

3) Arizona.edu. Chemistry By Design. <http://chemistrybydesign.oia.arizona.edu/app.php> (Accessed April 13, 2013).

4) Reiter, J.; Trinka, P.; Bartha, F.; Pongo, L.; Volk, B.; Simig, G. New Manufacturing Procedure of Cetirizine. Journal of the American Chemical Society. 2012, 16, 1279-1282.
5) Smith, J. Organic Chemistry, 3rd ed.; McGraw-Hill: New York, 2011.