The following molecule is chloroethane

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The following molecule is chloroethane.
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It is unreactive towards hydroxide and most nucleophiles under
normal conditions, i.e., the chlorine-carbon bond is not a very good
electrophilic center, hence 1 is not a good alkylating agent and does not
transfer the CH3CH2group
easily.

On the other hand, there is a class of drugs that contain a
chloroethyl group which are good alkylating agents and have been used
clinically to treat cancer. An example of this class of drugs is melphalan.

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The reason melphalan, is a good alkylating agent, and 1 is not, is
due to the formation of the intermediate 3 caused by the close proximity of a
basic nitrogen to the carbon-chlorine bond in 2. Reaction of 3 with a
nucleophile (Nuc) gives the alkylated nucleophile, 4.
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In vivo, in a therapeutic setting, the Nuc is specifically a
nitrogen or oxygen on a purine in a DNA strand, which once alkylated cleaves
from the DNA strand to create errors in reading the DNA code and ultimately
death of a cancer cell. The alkylation takes place in two steps defined by the
rate constants k1 and k2.
1. If k1 > k2, is the overall reaction of molecule 2àmolecule 4 an SN1 or SN2 reaction?
2. Conversely, if k2 > k1 is the overall reaction SN1
or SN2? Explain why.
3. If the basic pKa of the nitrogen in the -N-(CH2CH2Cl)2in molecule 2 is 1.5 and the basic pKa
in the -N-(CH2CH2Cl)2in Molecule 5 is 6.5, which drug,
(molecule 2 or molecule 5) is more likely to go by an SN1 reaction
with the nucleophile and why? Note that the rate or ease of reaction k1 for 2à3 will depend on how basic is the nitrogen in -N-(CH2CH2Cl)2.

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Assignment Two:
The following molecule, atracurium, is a very complex drug. It is
aneuromuscular blocking agent
and is related to the natural product tubocurarine.Atracuriumexhibits a very short half-life
(20-min). The products of the fastest inactivation process are shown below.
Explain what mechanism is responsible for the formation of the
products.
Hint:The acidic pKa of CH3(C=O)CH3àCH3(C=O)CH2- is 20.
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