Orgo I - Unit 2 Study Guide

Stereochemistry
Chirality of conformers
Mobile conformations vs. conformationally locked/sterically hindered
Allene (R-C=C=C-R) chirality: Depends on substituents
Fischer Projections
To and from perspective drawings
Carbon @ top = most oxidized C
R/S rules compared to perspective drawings
How rotation affects molecule
Diastereomers and meso compounds
2n rule
Absolute vs. relative configuration
Resolution of enantiomers
Racemic mixture+ chiral resolving agent pair of seperatable diastereomers
1.
2. Pass racemic mixture through column lined with chiral compound; enantiomers +
chiral compound -> diastereomers; enantiomers will elute at separate times
Alkyl Halides & Reaction/Mechanism Intro
Alkyl Halides
Naming
o IUPAC: halo- prefix
o Common: Name carbon chain as alkyl, halogen as halide, -> alkyl halide
CH2X2 = methylene halide
CHX3 = haloform
CX4 = carbon tetrahalide
Geminal dihalide: Both X on same carbon
Vicinal dihalide: X are on adj. carbons
Halothane (anesthetic): CF3CHClBr
Common uses: Solvents, reagents, anesthetics, freons (CFCs; Freon 22 replaced
Freon 12), pesticides (DDT banned)
Bond dipoles ( = *d); is directly proportional to EN
o EN: F > Cl > Br > I
o Bond length: C-F < C-Cl < C-Br < C-I (reverse of EN)
o Bond : C-Cl > C-F > C-Br > C-I
Soluble in organic solvents, not H2O (no hydrogen bonding)
Alkyl fluorides and monochlorides are less dense than H2O, dichlorides and bromides
and iodides are more dense
Reaction types
1. Substitution
2. Elimination: Most common when X = H, Y = heteroatom more electronegative
than C
3. Addition
Reaction Mechanisms
Concerted vs. step-wise

Homolysis (radical cleavage) vs. heterolysis (ionic cleavage)

o Bond cleavage is endothermic
Reactive intermediates
o More stable = easier to form, stays around longer so it can react to further the
reaction
1. Carbocations: sp2, electrophilic, stabilized by alkyl groups (Methyl < 1o < 2o <
3o), hyperconjugation (alkyl bonds overlap w/ empty p orbital) and
resonance, destabilized by electron-withdrawing groups
2. Free radicals: Electrophilic, stabilized by alkyl groups (Methyl < 1o < 2o < 3o)
and resonance, destabilized by electron-withdrawing groups
a. Radical inhibitors eg. BHA
3. Carbanions: sp3, nucleophilic, destabilized by alkyl groups (Methyl > 1o > 2o
> 3o), stabilized by electron-withdrawing groups and resonance
4. Carbenes: sp2, can be either nucleophilic (lone pair) or electrophilic (empty p
orbital)
Free-radical reactions: Initiation, propagation, termination
Alkane halogenation (free radical halogenation): 1st method of preparing alkyl halides
o Initation (requires h and/or )
o Propagation chain reaction (first part = rate-determining step)
o Termination (@ low [X2]): consumes radicals
o Thermodynamics: Fluorination and chlorination are exothermic, bromination
and iodination are exothermic
o Kinetics: Fluorination (explosive) >> chlorination > bromination (requires
heat) > iodination (essentially inactive)
o Bromination is more selective than chlorination (larger 2o:1o product ratio) due
to its resembling products and a larger Ea between 2o and 1o radical
formation
Allylic bromination: 2nd method of preparing alkyl halides (also free radical)
o Radicals are more stable due to resonance
o Produces alkyl halides
o Avoids Br2 excess by using NBS to generate Br2 as HBr is formed
NBS + Br2 -> HBR + succinimide
Thermodynamics
Keq, favoring of products vs. reactants
Free energy change (Go)
o
Go =RTln ( K eq ) ; R = 8.314 J*mol-1*K-1
o Go < 0 = spontaneous reaction
o A smaller G is favored (indicates stability)
o Go = Ho - TSo
In organic reactions (even @ high T): TSo << Ho so Go Ho
Heat/enthalpy of reaction (Ho): Approximated by BDE (reactants) BDE (products)
o BDE decreases as you go down a periodic column
o A longer bond has a lower BDE because its weaker than a shorter bond

o Only represents overall change in energy; doesnt reflect kinetics or

mechanism; calculated for gaseous reactions (organic rxns occur in (l)
solvents
Kinetics
Effect of [reactants] and T on rate
Rate law: rate = k[reactants]order
o Rate law for concerted (single-step) vs. stepwise (rate-determining step and
fast step(s)) reactions
Arrhenius equation: k =A eE / RT ; R = 8.314 J*mol-1*K1
Energy diagrams: Intermediate = local minimum, (transition state(s)) = local
maxima
o Ea = energy difference b/n and reactants (step w/ highest Ea = RDS)
o Hammonds postulate: a is closest in structure to the stage of a reaction it is
closest to energetically
Exothermic: closest to reactants
Endothermic: closest to products
Nucleophilic Substitution (SN2 & SN1) Reactions
Reactions of Alkyl Halides
Polar C-X bond makes C an electrophile, X a leaving group
Nucleophilic Substitution
Negatively charged nucleophiles used as salts w/ positive spectator ions
Using a neutral nucleophile creates a substitution product with a positive charge
o A positively charged product where the nucleophile contained O-H or N-H
can act as a B-L acid and become neutral
SN2: Concerted reaction
Inversion of configuration at C* (Walden inversion)
Can be used to make alkyl fluorides and iodides through halide exchange
Rate=k [ Nucleophile ] [substrate ]

SN2 Affecting Factors

I.
Nucleophile Strength
a. For 2 nucleophiles w/ the same nucleophilic atom, the one thats a stronger
base is the stronger nucleophile eg. OH- is stronger than H2O
b. A negatively charged Nuc is always stronger than its conjugate acid
c. Nucleophilicity increases down the periodic table due to increasing
size/polarizability (both make nucleophile hold electrons less tightly),
decreasing EN
d. From left to right across the periodic table, nucleophilicity and basicity are
directly proportional
e. When a possible nucleophile is sterically hindered, it is a poor nucleophile
but basicity is not affected (non-nucleophilic base)
f. NaBr used as nucleophile source: Na+ solvated by ion-dipole, Br- solvated
by H-bonding w/ H2O
g. Weak nucleophile: No negative charge (neutral) eg. H2O
a

h. Moderate nucleophile: Stabilized negative charge eg. resonance-stabilized

or halides
i. Strong nucleophile: Unstable negative charge eg. OR-, NR2II.
Solvent
a. Polar protic solvent: Nucleophilicity increases down a periodic column
(less energy needed to strip solvent off a larger anion than a smaller anion)
b. Polar aprotic solvents: Anions are poorly solvated; stronger base =
stronger nucleophile (basicity dec. down a periodic column, so
nucleophilicity does too); F- is more nucleophilic than I- in an aprotic
solvent
c. SN2 prefers polar aprotic solvents because nucleophiles are stronger if
poorly solvated
III.
Leaving group: Should be electron-withdrawing, stable once its left (not a strong
base), polarizable to stabilize the
a. The better of two LG is the weaker base (accepts electrons more readily)
b. Left to right across the PT: basicity decreases so LG ability increases
c. Down a periodic column: basicity decreases so LG ability increases
d. Excellent LG: Neutral (able to accept electrons)
e. Good LG: Very stable ie. delocalized negative charge
f. Poor LG: Unstable negative charge
IV. Substrate
a. As N(R on C*) increases, rate decreases
i. Rate: Me C* > 1o C > 2o C (3o C is so hindered it does not react
under SN2)
V. Any factors that increase Ea decrease rate
SN2 Stereochemistry: Inversion of configuration at C8 (Walden inversion) due to
back-side attack by nucleophile
Important in lab synthesis of many drugs and in biological systems
CH

+
o Adrenal glands:
+

Norepi+
SN1: Multistep Reaction
Racemization: No inversion of configuration
Carbocation intermediate; prefers polar protic solvents
Rate=k [ substrate]

Possibility of hydride or CH3- rearrangement to yield a more stable C+

SN1 vs. SN2
SN1
SN2
o
o
Substrate
Methyl, 1 , 2
2o. 3o
Nucleophile Strength
Weak (Nuc may be solvent)
Strong
Leaving Group
Better LG = higher rate
Better LG = higher rate
Solvent
Polar protic (ionic
Polar aprotic (poor solvation = stronger Nuc)
intermediate)

Kinetics
Stereospecific?
Rearrangement?

rate=k [substrate]
No (racemization)
Yes (H- or CH3-)

rate=k [ substrate ] [Nuc ]

Yes (Walden inversion)
No

Organic synthesis backtrack from products of nucleophilic substitution

Carbon atoms come from alkyl halide, functional group comes from nucleophile

Mechanisms
1. Free-Radical Chlorination of CH4

2. Allylic Bromination

3. SN2: 2nd Order Nucleophilic Substitution

4. SN1: 1st Order Nucleophilic Substitution

a. Hydride (H-) Rearrangement

b. Methyl (CH3-) Rearrangement

Reactions

ROH
+ X
I.
Ether Synthesis:
R X +OH
II.
Halide Exchange:

RI +X
A.
R X + I
,CH 3 CN RF + KX
B. R X + KF 18crown6

'

III.
Ether Synthesis: ROR + X
R X+ R ' O

IV. Thioether Synthesis: RSR ' + X

RX + R' S

NH

+ X
V. Amine Synthesis:
)

+ X NH 3 RNH 2 +

RNH 3
R X + NH 3 ( excess )

VI.
VII.

Nitrile Synthesis: RC N + X
R X +C N

'
'

Alkyne Synthesis: + R X RC CR + X
RC C