ALKYL HALIDE
SN2 Reaction
- Concerted
- Simultaneous
- Backside attack
- One step
stereospecificity - Inversion of
configuration
Substrate (alkyl halide) - Most reactive on
effect on rate primary
- Unreactive on
tertiary
Nucleophilic Strength - Needs strong Factors that affect
nucleophile nucleophilicity
1. Negative charge -
more nucleophilic
2. Polarizability (more
important than the
charge) - directly
related to size of
List of Strong Nucleophile atom
1. I-
2. Br-
3. Cl-
4. HS-
5. RS-
6. HO-
7. RO-
8. CN-
List of Weak Nucleophile
1. H2O
2. ROH
Solvent Effects - Polar aprotic
solvents
List of Polar Aprotic
Solvents
- Acetone
- DMSO
(dimethylsulfoxide)
- DMF
(dimethylformanide)
- HMPA
(Hexamethyphospho
ramide)
- Acetonitrile
E2 Reaction
- use of bases, rather
than nucleophiles
- Beta elimination
- 1, 2 - elimination -
proton removed in
the beta position and
halide is ejected as a
leaving group in the
alpha position, and a
double bond is
formed between beta
and alpha carbon.
- Dehydrohalogenatio
n, X and H is
removed from the
substrate
Mechanism - One step
- Concerted
Substrate - Compared to SN2,
E2 can undergo
reaction with tertiary
alkyl halide
Regioselectivity - can produce more - Zaitsev product
than one possible - More
product substituted
- Zaitsev product alkene
- Steric hindered base - Hoffman product
affects the major - Less
product - favors less substituted
substituted alkene
List of Bases
- NaOEt
Some Sterically Hindered
bases
- t-BuOK
- Diisopropylamine
- Triethylamine
-
Stereospecifity - Anti coplanar
- Prefer trans
- Only possible
between alpha
carbon and beta
carbon with at least
1 hydrogen
- If 2 hydrogen atoms
are present in the
beta 2 possible
product with trans as
the major product
- If 1 hydrogen atom is
present one possible
product draws new
man projection
(cyclic)
- If wedge si X sa
alpha carbon, we
need dashed H in
beta carbon
Solvolysis - Solvolysis is the chemical breaking of bonds in the presence of a solvent
SN1
- Two-step
Solvolysis - Resonance
stabilized is faster
Stereochemistry - Produce racemic
mixture (equal
mixture of inversion
and retention)
E1
- two-step
Solvolysis - Resonance
stabilized is faster
Regiochemical - No control unlike E2
- More possible
product
PREDICTING PRODUCTS: SUBSTITUTION VS. ELIMINATION
1. Determine the Substitution Nucleophilicity
function of the - the reagent functions - is a kinetic
reagent. as a nucleophile phenomenon and
refers to the rate of
reaction.
- Is determined by the
factors
- High electron
density
- polarizability
Elimination Bacisity
- the reagent functions - is a thermodynamic
as a base phenomenon and
refers to the position
of equilibrium.
- is determined by the
stability of the base
2. Analyze the
substrate and
determine the
expected
mechanism.
3. Consider any
relevant
regiochemical and
stereochemical
requirements.
W/ Other Substrates
1. Tosylates - Sulfonate ion
(RSO3-) → excellent
leaving groups
- commonly used and
prepared by treating
the corresponding
alcohol (ROH) with
tosyl chloride
(TsCl) in the
presence of
pyridine (pyr)
Alcohols Substitution - No reaction with a
- Substrate → ROH strong nucleophile
- Reagent → HBr
Elimination
- Substrate - ROH
- Reagent - Concen.
H2SO4
Summary
ADDITION REACTION
Addition - reverse of
elimination
- two molecules are
joining together to
produce one
molecule
REGIOSELECTIVITY Markovnikov Addition the halogen is generally
installed at the more
substituted position
(Carbon)
Anti-Markovnikov the halogen is installed at
Addition the less substituted carbon
Hydrohalogenation - H and X (X = Cl, Br,
I)
Regioselectivity Markovnikov Addition
Anti-Markovnikov Addition if
alkyl peroxide is present
(ROOR)
Stereochemistry
With Carbocation - the mechanism for
rearrangements HX addition involves
the formation of
intermediate
carbocation →
subject to
carbocation
rearrangement.
→ only possible if
there is a methyl
group adjacent
ACID-CATALYZED - adding water (H and - Reagent
HYDRATION OH) - H3O+
Catalyst
- Enclosed in a [],
normally H2SO4
- Markovnikov addition - Tertiary carbocation
→ rapid reaction
- uses an equilibrium
arrow rather than a
single ( → )
Oxymercuration-demercur - Mercuric cation is a (Reagent → substituent)
ation powerful electrophile H-Z
and is subject to - H2O → OH
attack by a - EtOH → OEt
nucleophile, such as - EtNH2 → NHEt
the pi bond of the
alkene.
- the more substituted
bears a partial
charge
- MARKOVNIKOV
ADDITION
- after attack of the
nucleophile, the
mercury can be
removed through a
process called
demercuration with
sodium borohydride
HYDROBORATION - - Anti-Markovnikov - Installs the OH group
OXIDATION Addition of water at the less
- Syn addition substituted position
Reagents
CATALYTIC - addition of molecular - Metal catalyst
HYDROGENATION hydrogen (H2) across - Pt
a double bond in the - Pd
presence of a metal - Ni
catalyst
- Syn Addition
HALOGENATION - involves the addition
of X2 (Br2 or Cl2)
- Anti addition
HALOHYDRIN - addition of X (Br and Example:
Cl) and OH
- OH group is
generally installed at
the more substituted
position
- Anti addition
DIHYDROXYLATION - addition of OH and
OH across an alkene
ANTI DIHYDROXYLATION Reagent
- 1. RCO3H
- 2. H3O
SYN DIHYDROXYLATION Reagent
- OsO4
OZONOLYSIS
Predicting the Products of an Addition Reaction
ALKYNES
ALCOHOLS
- R-OH
- Contain a hydroxyl
group (-OH) bonded
to sp3 hydridized
carbon
NAMING suffix -ol
- In cyclic, OH
substituent is the
priority
PREPARATION
1. Substitution
SN2
- Starting
material:
Alkyl halide
- Reagent:
(strong
nucleophile)
-OH
SN1
- Starting
material: alkyl
halide
- Reagent:
H2O, ROH
2. Addition Reaction
3. Grignard Reaction
REACTIONS 1. Substitution Reaction
2. Elimination Reaction
E1
E2
3. Oxidation Reaction
Tertiary Alcohol and Phenol → no reaction (no alpha
proton)
ETHER
- R-O-R
- Contains 2 alkyl
group bonded to an
oxygen atom
- Can either be
symmetrical (Same
R groups attached)
or unsymmetrical
(different groups)
- Organic derivative of
water
NAMING 1. Name both alkyl
groups and add
ether
PREPARATION 1. The Williamson Ether Synthesis
2. Alkoxymercuration - Demercuration
REACTIONS 1. Acidic Cleavage
- when heated with a concentrated solution of a
strong acid (HX), an ether will undergo acidic
cleavage
2. Claisen Rearrangement
- specific to
- allyl aryl ether (H2C=CHCH2-O-Ar)
- allyl vinyl ether (H2C=CHCH2-O-CH=CH2)
- occurs in a single step through a pericyclic
mechanism
- allyl vinyl ether (H2C=CHCH2-O-CH=CH2)
- allyl aryl ether (H2C=CHCH2-O-Ar)
EPOXIDE
- also called oxiranes
- Ethers having the
oxygen in the
three-membered ring
- have angle strain,
making them more
reactive than other
ether
NAMING Epoxyalkanes
-
Oxiranes
-
Alkene oxides
-
PREPARATION
REACTIONS
ALCOHOL, ETHER, EPOXIDE
Physical Properties
