Current Topics in Chemistry - Bruice

Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 9. Reactions at an sp³ Hybridized Carbon I: Substitution Reactions of Alkyl Halides.

For each of the following questions, please refer to the following article:

BAN IS SOUGHT ON 5 PESTICIDES TO PROTECT KIDS
by Steve Yozwiak (The Arizona Republic, January 29, 1998)

Editorial Comments

While working on these web pages for chapter 9, I was reading with a particularly great interest the section 9.11 on "Biological Methylating Reagents. There one reads that biological methylating reagents contain methyl groups that are attached to very good leaving groups so that methylation can take place at a reasonable rate. In other words: If a methyl compound Me-X enters the body and X is a very good leaving group, then this compound can alkylate cellular materials and it may cause damage. In fact, many chemicals are toxic just for that reason and highly methylating reagents have to be avoided.

Shortly after I had read that section 9.11, I came across the above article on pesticides. About halfway into the article I read the sentence "The chemicals environmentalists propose banning are methyl parathion, dimethoate, chlorpyrifos, pirimiphos methyl and azinphos methyl". I have a PhD in chemistry but I had no idea what these compounds are. Could these pesticides be dangerous because they are methylating reagents? Well, to answer that question, I need to know what their structures are. So, I went to a the ChemFinder, entered the name of the compound and immediately received information about the structure and the physical properties of the compound. Now we know that methyl parathion is, by its IUPAC name, dimethyl O-p-nitrophenyl thiophosphate. The other four compounds mentioned in the article contain the same or similar alkylthiophosphate groups. Now we can answer the original question as to whether the methyl groups is attached to a good leaving group and the answer is yes. Phosphates are rather good leaving groups because they can delocalize the negative charge.

Now that we deciphered the commercial names and were able to recognize the alkylating potential of these compounds, we would have to start looking into whether they actually realize this potential and to what extent. Only lots of testing over the course of many years can fully answer our concerns. In the meantime, should we use the pesticides?

Pertinent Text References
Chapter 9. Reactions at an sp³ Hybridized Carbon I: Substitution Reactions of Alkyl Halides.
Section 9.11. Biological Methylating Reagents.
Chapter 11. Reactions at an sp³ Hybridized Carbon III: Substitution and Elimination Reactions of Compounds with Leaving Groups Other than Halogen. Organometallic Compounds.
Chapter 16.18. Box on "Nerve Impulses, Paralysis and Insecticides"

Questions

Question 1: Use ChemFinder to find out about the structures of the five pesticides mentioned in the article.

Answer 1: Execute the ChemFinder search to obtain answer.

Question 2: Learn about the mode of action of these organophosphate pesticides in the Introduction to Insecticides by George Ware. What are the structures of cholin and acetylcholin? What is the function of cholinesterase? What is the effect of cholinesterase inhibition?

Answer 2: Use the ChemFinder to find the structures of cholin and acetylcholin. Cholinesterase cleaves acetylcholin. The inhibition results in the accumulation of acetylcholine (ACh) in the synapses, causing rapid twitching of voluntary muscles and finally paralysis.

Question 3: Organophosphate insecticides and pesticides permanently inhibit cholinesterase by a reaction of an enzyme-OH group with the organophosphate. Using structural formula, describe this reaction.

Answer 3: Nucleophilic attack at the phosphorus results in the substitution of the phenoxy group.

Question 4: Consider the SN2 reaction of methyl parathion with a nucleophile such as an alkoxide (use ethoxide). Draw the structures of the products of this reaction and write down all the resonance forms of the leaving group that is released in this reaction.

Answer 4: Ethyl methyl ether (Et-O-Me) is formed upon cleavage of the phosphate anion. The negative charge is delocalized over the oxygen atoms and (to a lesser degree) over the sulfur atom.

Chemistry & Society.
Question 5: In the article, a person named Cook is quoted as saying "We have the right to remain silent about risks in the food supply." Do you think that is an ethical attitude?