Transcript Aprotic Solvent

Nucleophilic Reactions and Cancer Drugs
By the end of this chapter, you’ll know enough to explain how these
drugs work!
SN2 Orbital Timeline
Hughes (left) and Ingold (right) worked
Out the mechanism for SN2 reactions
SN2 Movie
General YouTube comments: “Poor carbonyl keeps getting attacked by nasty Mr Grignard”
“that halogen is a creeper” “INVERTED PRODUCT!” “This is the best movie I’ve ever seen”
Predict the SN2 Products
NO SN2 Rxn (3o Carbon)
Higher-Row Nucleophiles in the SN2 Reaction
Down a column of the periodic
table: nucleophiles become
larger and more polarizable, but
less solvated and less basic.
Polarizability means that the
loosely held electron cloud of
iodide is readily distorted
The tightly held electron cloud of
fluoride is less polarizable.
5
Because of their small size, second-row nucleophiles are
solvated by polar solvents hindering back-side attack:
Therefore water and alcohol
solvents are not suitable for SN2
reactions with second-row
nucleophiles.
Larger, more polarizable groups, like Iodine,
do not have this effect.
SN2 reactions with second-row nucleophiles are carried out in
polar aprotic solvents:
Includes DMSO, DMF, and acetonitrile (CH3CN)
Consequently, the anionic
nucleophile is unsolvated and
reactive
Pick the Best Nucleophile for SN2
More Polarizable
(Protic Solvent)
Bulky
Neg charge
Stronger Base
(Aprotic Solvent)
Stronger Base
(Aprotic Solvent)
More Polarizable
(Protic Solvent)
More Polarizable
(Protic Solvent)
Stronger Base
Stronger Base
(Aprotic Solvent)
Bulky
Note:
This table
will be included
on your tests
Determine the Direction of the SN2 Reaction
HBr (pKa = -9)
HCl
(pKa = -7.0)
NH4
(pKa = 9.4)
H2S
(pKa = 7.0)
In equilibrium
Methyl Bromide – Effective at Putting Bugs to
Sleep … for good (aka Insecticide)
X
Proteins perform
reactions in cells to
keep an organism alive.
Proteins contain Amino Acid
Which can do SN2 reactions w/methyl
bromide
Methyl Bromide used to kill all kinds of
insects
Is still frequenly sprayed on crops
Once reacted, the proteins
function in the cell is
destroyed
Alternative Methods are being
developed
SN1 Reaction
General YouTube comments: “lol” “This rocks ,dudez.” “very n1”
Predict the Product for the Following Reactions
SN1 or SN2?
1o
3o benzyl
Vinyl
Neither
3o
Strong
1o benzyl (look at solvent + Nu)
Strong
Polar Aprotic
Weak
Polar Aprotic
2o (look at solvent + Nu)
Polar Protic
2o (look at solvent + Nu)
3o benzyl
Neither
Benzyl
Keep in mind that
the reaction may not
proceed due to heavy
SN2 Condions
Good Polar
Protic
Solvents
Good Polar
AProtic
Solvents
Predict the Intramolecular Product
SAM, a Biological Methylating Agent
S-Adenosyl methionine (SAM)
A sulfide leaving group
Methyltetrahydrofolate, Another Biological
Methylating Agent
An amine
leaving group
Nucleophilic Reactions and Cancer Drugs
By the end of this chapter, you’ll know enough to explain how these
drugs work!
Mechlorethamine, a Nitrogen Mustard
Mustard: refers to odor and color of the impure warfare agent.
Now used to treat lymphomas, breast and lung cancers.
Crosslinks DNA, which triggers cell to kill
itself. This affects only rapidly dividing
cells, both normal and cancerous.