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Notes 14D SN2 Chemistry
Notes 14D SN2 Chemistry
Substitution
Reactions
Chem 14D
Winter 2005
- Concerted reaction because nucleophile attacks and leaving group leaves simultaneously. No intermediates
are formed.
More often molecules collide, the faster the reaction.
Gedunker experiment:
Example: 1. Cars on a freeway. The more cars, the
- Kinetics factors that effect reaction rate
more accidents. 2. Recall throwing molecule balls in
HO + CH3Cl
reaction
class.
collision
Audi
Benz
More likely!
Moment of Collision
HO- + CH3-Cl
Cadillac
collision
HOCH3 + CL
Trigonal bipyramidal is the best way to arrange 5 atoms around a central atom.
Uh ohpentavalent carbon? No, central C still has 8 e-, so the rule is not violated.
-
In Backside Attack, the nucleophile attacks from the backside of the carbon-leaving group
bond) due to:
o Electrostatics (Negative charges on nucleophile and leaving group repel)
o Sterics, steric hindrance (Crowding; leaving group blocks approach of nucleophile to
the front)
o Hughes, Ingold noticed that the stereocenter will change (wont happen in front side
attack)
front
Retention of
Stereochemistry
back
Inversion of
Stereochemistry
99% SR or RS,
but not always true
See virtually 100% Inversion of stereochemistry (also called a Walden inversion, this is good
and bad
o When a chiral alkyl halide undergoes an SN2 reaction, only one substitution product is
formed
Bruice, p. 366
o Good: says backside attack is an accurate model
o Bad: questions the 2 reasons above. There must be another factor.
-
Greatest stabilization occurs when orbitals overlap end to end. The overlap between the
orbital containing the pair of donated e- by the nucleophile and the _* carbon-leaving
group antibonding orbital is maximized.
Bruice, p. 364
Answer:
SN2 Energetics
o _G = _H-T_S
Gibbs free energy (_G) energy of whole system
Enthalpy (_H) differences energy due to bond changes (usually tens of
kcal/mol)
Entropy (_S)- freedom of the system, molecules like to be floppy or more
molecules; entropy is a small factor (perhaps only one cal/mol), and even
when multiplied by T (temperature in Kelvin), it is still smaller than _H
o At reasonable temperatures, _G _H; Products and reactants arent the only thing
that matter, the transition state has its own energy (really important).
o Energy Profile:
CH3Cl
HO
Energy
_G
_G
Reaction Coordinate
CH3OH
Cl
_G is negative, so it wants to
spontaneously go to products
- Transition state (TS): the highest energy point in the energy reaction profile (due to partial bonds)
- Energy of Activation (_G): Energy needed to reach transition state; controls the rate of a reaction
- 2 partial bonds dont make up for 1 full bond
- 2 partial bonds in is energetically expensive
- Breakfast metaphor: Rate of room emptying is a function of:
1) Energy of the students
2) Height of the hill of stairs leading up to the doors
- _G: influences the position of the equilibrium, but not the rate
- _G: influences rate of reaction, but not equilibrium
- Example: Cells amino acids
Cant wait for years for a reaction to complete, so enzymes make the [TS] more stable.
This
_G, so reactions go faster.
k = A0e-_G/RT
rate
SN2 Variables:
R
Nuc------------------C-----------------LG
R
R
Role of nucleophile in partial bonds:
- Share electrons (its making the partial bond)
- The more complete the bond is, the more stable the [TS]
The single most important factor which controls the nucleophilicity or basicity of any molecule or ion is the ability,
desire, or driving force to share an e- pair.
- Nucleophilicity: ability to share e- pairs with electrophile
- Basicity: ability to share e- pair with H
- Stronger bases are better nucleophiles
* When comparing molecules with attacking atoms that vary greatly in size, the polarizability (ability to skew the
electron cloud) of the atom and the reaction conditions determine whether the greater polarizability of the larger
atoms makes up for their decreased basicity.
* The relationship between basicity and nucleophilicity becomes inverted when the reaction is carried out in a
protic solvent (the solvent molecules have a hydrogen bonded to a nitrogen or oxygen). This will be explained in
the solvents section.
4 Factors influencing Nucleophilicity (similar to basicity factors because both nucleophiles and bases share e-):
1) Resonance (can increase or decrease e- density at the atom that shares e- with the electrophile, but
generally decreases nucleophilicity)
CH3OMethoxide
Stronger nuc. b/c neg charge
more concentrated
vs.
Weaker nuc. b/c neg charge spread out
over 2 oxygens
No res. no res.
Loses res. when reacts so more hesitant to do so.
Doesnt want to lose resonance, its stabilizing like $
2) Atomic Size (refers to size of atomic radius of atom doing e- sharing, not molecule as a whole, just the
business end - the end that forms a new bond with electrophiles):
CH3Ovs.
CH3SO is smaller so charge is more concentrated, greater drive to share e-, better nuc.
O and S both have the same # of valence e- and formal charge of -1, but O has a smaller atomic radius.
Smaller atoms are better nucleophiles because they have a more concentrated e- density, and thus a stronger
driving force to share e-.
3) Electronegativity measure of e- greediness, think of it as anti-nucleophilicity
Higher electronegativity means lower nucleophilicity, because the role of a nucleophile is to share e-. If the atom
is more electronegative it is less willing to share its e- and wants to hold onto them.
Fvs.
HOEN: 4.0
3.5
Poorer nucleophile
better nucleophile
4) Inductive Effect the electronic effect of atoms other than the atom that is sharing e- density; can increase
or decrease e- density on the atom sharing e- with the carbon
Electron withdrawing groups decrease nucleophilicity.
Electron donating groups increase nucleophilicity.
CH3CH2Ovs.
CF3CH2OSince F is very EN, it draws e- density away from O-, making for a poorer nucleophile
X-Factor (doesnt consistently fit into this sequence of decreasing importance)
Formal Charge: If you have more e- density, better nucleophile
HOvs.
H2O
More e- density (formal neg. charge)
neutral
Better nucleophile
FMore e- density
But high EN
vs.
NH3
stronger nucleophile
(A Toss Up)
No res.
No res.
2) Atomic Size:
O is smaller
S is larger
Has res.
(Least nucleophilic, least willing to share)
Medium nuc.
Poorest nuc.
CH3CO2-,
acetate
CH3Omethoxide
Answer:
Has res.
No res.
Poorest nucleophile because res. reduces e- density
No res.
- Leaving Group portion of molecule that leaves with the pair of e- that was the bond between the leaving
group and some other atom; role of leaving group is to accept e- and leave, the more easily the leaving group
can accept and spread out e- density, the better it is
R
Nuc--------------------C-------------------LG
R R
*Relatively good leaving groups make alkyl halides convenient to study for substitution reactions.
*Cells of plants and animals exist in mostly aqueous environments. Since alkyl halides are insoluble in water,
biological systems use compounds in which the group that is replaced is more polar than a halogen and thus
more soluble in water.
Bruice, p. 367
Since basicity and leaving group ability are inversely related (weaker conjugate bases = better leaving groups),
alkyl fluorides are least reactive while alkyl iodides are the most reactive of the alkyl halides.
Bruice, p. 367
1) Resonance: acetate is a better LG b/c it accommodates e- density better due to res.
vs.
acetate
2) Atomic Size: the larger the size of the business atom, the better the LG because its e- shell is less
concentrated and can accept more e- more readily and leave.
*Alkyl iodides are least basic, while halide fluorides are most basic because larger atoms are better able to
stabilize their negative charge.
3) Electronegativity: the higher the EN, the better the LG, because it has a higher affinity for e4) Inductive Effect: can be e- withdrawing (usually) or e- donating, so can work either way
Withdraws e-: better LG
Donates e-: worse LG
X Factor: Formal Charge
R-LG+ LG
Best leaving group, charge being quenched
R-LG LG-
H20, ROH
+
R---CH2
Bad Leaving Groups: (not leaving groups unless special circumstances)
FToo Small
HO , CH3O
O- not stabilized by resonance
Never Leaving Groups:
H:H3C:- (carbon anion)
CH3CO2-
2 res. contributors
e- donation by CH3
Worst e- dispersion
Poorest
3 res. contributors
e- donation by CH3
Medium e- dispersion
Middle
Steric Effects: results from repulsion by two or more atoms or atom groups; decreases reactivity when groups
are in the way at the reaction site
*Note: Steric effects affect nucleophilicity, but not basicity. (Strength of a base only depends on its willingness to
share its electrons). A bulky nucleophile cannot approach the back side of a carbon as easily as a less sterically
hindered nucleophile.
R3C:
SN2 Rate: SN2 reactions are sensitive to increasing steric hindrance at the electrophilic carbon
H3C-LG > RCH2-LG > R2CH-LG >>> R3C-LG
Methyl
1
2
3 (no reaction)
Fastest slowest
- Tertiary alkyl halides cannot undergo SN2 reactions because the three alkyl groups make it impossible for the
nucleophile to come within bonding distance of the tertiary carbon.
- The larger the group attached to the C attached to the LG, the more hindrance (harder for nucleophile to reach
electrophilic carbon), the slower the reaction.
Figure 10.3 Reaction coordinate diagrams for a) the SN2 reaction of methyl bromide with hydroxide ion; b) an
SN2 reaction of a sterically hindered secondary alkyl bromide with hydroxide ion.
Bruice, p.365
Lecture Supplement, Hardingers Thinkbook, p. 5:
a)
OR b)
Answer:
Reaction a) is more sterically hindered at the electrophilic carbon, so it is slower than reaction b).
Solvent Effects:
What is the role of a solvent in a reaction?
- Serve as buffer, absorb heat in reaction so temp doesnt rise too quickly
- Dissolve stuff in solution so particles can react with each other. Can very significantly influence the rate of an
SN2 reaction
+ H2O
KF
K+ (aq) + F- (aq)
Solid
F- is a nucleophile.
H bonding decreases ability of F- to share e-,
solvent occupies some of its e- density.
OR
Answer:
CH3OH is a protic solvent. Because of hydrogen bonds, protic solvents decrease nucleophilicity. Therefore,
CH3S- is a better nucleophile than CH3O- because smaller atoms have more concentrated electron density, so
they hydrogen bond better. As a result, the reaction involving CH3O- is slower.
30) Consider this reaction:
b)
c)
F is a poorer leaving group than Br, so this reaction is slower. You can also increase steric hindrance at the
carbon undergoing substitution to make the reaction slower.
d)
Iodide does less hydrogen bonding than methanethiolate, so iodide a better nucleophile, making for a faster
reaction. *Changing the solvent doesnt change the nucleophile itself, although it may alter nucleophilicity.
How do you decide if a reaction is a reasonable SN2 reaction? (Really asking about rate, which is asking about
TS)
R
Nuc---------------------------C---------------------------LG
R
R
TS is energetically expensive
because of partial bonds.
OCH3
OCH3
so overall OK
CH3CH2I + Br-
- Le Chateliers principle: If an equilibrium is disturbed, the system will adjust to offset the disturbance, so you
can drive a reversible reaction toward desired products by removing one of the products as it is formed.
A+B
C+D
Keq = [C][D]
[A][B]
To maintain the value of the equilibrium constant, if [C] is decreased, A and B will react to form more C and D.