Chapter 3 Mechanisms of Organic Reactions

3.1 Reaction Thermodynamics nd Kinetics

Net Reaction and Mechanism net reaction starting materials

R O OH + HO R'

catalyst
H H2O

products
+ R O O R'

acid
+H OH OH

alcohol

water

ester
H

reaction mechanism
+ HO R' OH H R O OH R' ~H H O H R O OH R' H2O

O R' OH

elementary steps

net reaction describes the starting materials and the products of a reaction reaction mechanisms describes the individual elementary steps of the reaction catalyst takes part in the reaction mechanism but is retained unchanged
Organic Reaction Mechanisms 91

Thermodynamics of Chemical Reactions (1)

thermodyamics are concerned with the energy balance of chemical reactions

R O OH + HO R' H2O + R O O R'

G R = G R + RT ln

[RCOOR][H2 O] [RCOOH][ROH]

G R > 0 G R = 0 G R < 0

endergonic reaction, runs from right to left reaction is in equilibrium exergonic reaction, runs from left to right

Gibbs free reaction energy G determines whether and in which direction the reaction runs standard Gibbs free reaction energy G at standard conditions (1 bar, 25C, reactants 1 mol/L)
R R
Organic Reaction Mechanisms 92

Thermodynamics of Chemical Reactions (2)

thermodyamics are concerned with the energy balance of chemical reactions

R O OH + HO R' H2O + R O O R'

G R = G R + RT

ln

[RCOOR]eq [H2 O]eq [RCOOH]eq [ROH]eq

=0

KR =

[RCOOR]eq [H2 O]eq [RCOOH]eq [ROH]eq

pK R = log K R
pK R
G R

= RT ln K R G R

RT

equilibrium constant K is the ratio of reactant concentrations in equilibrium standard free reaction enthalpy G determines the position of the equilibrium (at given temp.)
R R
Organic Reaction Mechanisms 93

Thermodynamics of Chemical Reactions (3)

thermodyamics are concerned with the energy balance of chemical reactions

R O OH + HO R' H2O + R O O R'

= HR T S R G R <0 HR >0 HR <0 S R >0 S R

Gibbs-Helmholtz Equation

exothermic reactions, sum of all bond energy changes negative endothermic reactions, sum of all bond energy changes positive exotropic reactions, disorder, degrees of freedom decrease endotropic reactions, disorder, degrees of freedom increase

standard reaction enthalpy H is negative (advantageous) if bonds in products are stronger standard reaction entropy S is positive (advantageous) if the disorder increases
R R
Organic Reaction Mechanisms 94

Kinetics of Chemical Reactions

reaction kinetics refers to how fast reactions proceed, i.e., the reaction rates rate laws describe the relation between substrate concentrations and reaction rates
rst order
r 1f = k 1f [ A ]

monomolecular
A

monomolecular
B

rst order
r 1r = k 1r [B ]

second order
r 2f = k 2f [ A ][B ]

bimolecular
A+B

bimolecular
C+D

second order
r 2r = k 2r [C ][D ]

third order
r 3f = k 3f [ A ][B ][C ]

trimolecular
A+B+C

monomolecular
D

rst order
r 3r = k 3r [D ]

third order
r 4f = k 4f [ A ]2 [C ]

trimolecular
2A+B

bimolecular
2C

second order

r 4r = k 4r [C ]2

reaction rates r are proportional to the product of the concentrations of all reactants rate constants k are the proportionality factors reaction order is the sum of all exponents of the concentrations of all reactants in the rate law molecularity is the number of molecules actually involved in an elementary reaction for simple, single-step reactions, the molecularity determines the reaction order
Organic Reaction Mechanisms 95

Relation of Theromdynamics and Kinetics

in thermodyamic equilibrium, concentrations of reactants do not change anymore forward and reverse reaction are equally fast
r 2f = k 2f [ A ][B ]
A+B C+D

r 2r = k 2r [C ][D ]

r 2f = r 2r

k 2f [ A ][B ] = k 2r [C ][D ]
k 2f k 2r = [C ][D ] =K [ A ][B ]

the ratio of rate constants of forward and reverse reactions determines equilbrium constant K the faster the forward reaction (relative to reverse), the larger is K the faster the forward (relative to reverse) reaction, the more the equilibrium is on product side
Organic Reaction Mechanisms 96

Reaction Proles (1)

reaction proles are simplied energy diagrams of chemical reactions, following the lowest
energy path from the starting materials to the products in the energy hypersurface
Br + H H Br H + H

S P

S dHH dHBr
Rkt

starting materials (S) and products (P) are stable compounds, i.e., energetic minima transition states () are saddle points in the energy hypersurface, maxima in the reaction prole
Organic Reaction Mechanisms 97

Reaction Proles (2)

reaction proles are simplied energy diagrams of chemical reactions, following the lowest
energy path from the starting materials to the products in the energy hypersurface
Br + H H Br H + H

S P

S dHH dHBr
Rkt

starting materials (S) and products (P) are stable compounds, i.e., energetic minima transition states () are saddle points in the energy hypersurface, maxima in the reaction prole
Organic Reaction Mechanisms 98

Relation of Reaction Proles, Thermodynamics, and Kinetics

Boltzmann distribution of molecular thermal energies

E A , f G = RT ln k f f
E A ,r G r = RT ln k r

exergonic reaction
Gf < Gr

endergonic reaction
Gf > Gr Gf = Gr > 0

Gf = Gr < 0

fast slow

slow fast
Rkt

Rkt
= G G G R r f

KR =
Organic Reaction Mechanisms

kf

r f = rr

kf kr

k f [S]eq = k r [P]eq

kr

[P]eq [S]eq

= KR
99

Hammond Postulate and Polanyi Principle

Polanyi Principle and Hammond Postulate for mechanistically similar, single-step reactions
late transition state higher activation energy early transition state lower activation energy
S
G3f > G2f = G2r > G3f G3f > G2f = 0 > G3f

E 1

3 2 P3 P2 P1

endergonic

exergonic
Rkt

Polanyi Principle: Dierence in activation energies proportional to dierence in free enthalpies Hammond Postulate: Energetically more similar states are also geometrically more similar
Organic Reaction Mechanisms 100

Multistep Reactions

elementary reactions are steps between the minima in the reaction prole, i.e., between starting
materials (S), intermediates (I), and products (P), seprated by transition states ().
E
elementary step 1 elementary step 2

1
G1f > G
1r

2
G2f < G2r

slow

fast

Gf = Gr < 0

P Rkt

overall reaction rate and molecularity are controlled by slowest, rate-determining step typically, the generation of the reactive intermediate is the rate-determining step intermediate is a good approximation for the transition state of the rate-determining step
Organic Reaction Mechanisms 101

Reaction Proles: Thermodynamics and Kinetics

= RT ln K R G R

less exergonic reaction equilibrium less on product side

more exergonic reaction equilibrium more on product side

S
Gf = Gr < 0

Gf = Gr < 0

P Rkt

P Rkt

change in standard Gibbs free reaction energy G leads to change of equilibrium concentrations in reality, even more drastic because ln K ~ G
R R
Organic Reaction Mechanisms 102

Reaction Proles: Thermodynamics and Kinetics

and G G = RT ln k f r = RT ln k r f

higher energy transition state forward/reverse reactions slower

lower energy transition state forward/reverse reactions faster

Gf

Gr Gf

Gf = Gr < 0

S P Rkt

Gr

Gf = Gr < 0

P Rkt

change in Gibbs free energy of transition state G leads to change in reaction rates in reality, even more drastic because ln k ~ G

Organic Reaction Mechanisms 103

Reaction Proles: Thermodynamics and Kinetics

higher energy transition state forward/reverse reactions slower

very high energy transition state metastable

Gf Gr Gf

Gf = Gr < 0

S P Rkt

Gr

Gf = Gr < 0

equilibrium cannot be established

Rkt

Organic Reaction Mechanisms

104

Reaction Proles: Thermodynamics and Kinetics

lower temperature forward/reverse reactions slower

higher temperature forward/reverse reactions faster

E
Gf Gr

E S
Gf = Gr < 0

Gf = Gr < 0

P
for endotropic reaction (S>0): equilbrium less on the product side

P Rkt
for endotropic reaction (S>0): equilbrium more on the product side

Rkt

change in temperature changes equilbrium (due to Gibbs-Helmholtz equation G = H T S) change in temperature also causes reaction rates because of thermal energy of molecules
Organic Reaction Mechanisms 105

3.2 Classi cation of Organic Reactions

Classication of Organic Reactions (1)

classication according to reaction type, i.e., the type of changes to molecular topology
R1 X R2 R3

Substitution
+ Y X +

R1 R2 R3

Substitution Addition
+X +Y R2 R1 X Y R R4 3

R1 R2

R3 R4

Elimination Addition
+ Y

R1 R2

R3 R4

Y R1 R R2 R4 3

Elimination
R2 X

Rearrangement
Y R3

R1

R2 X

Rearrangement

Y R1

R3

Organic Reaction Mechanisms

107

Classication of Organic Reactions (2)

classication according to reactive intermediate

bond heterolysis
H R R R R X R R R

bond homolysis
Y R R

R1

C R3 R2

R1 C R2 R3

R1 C R3 R2

carbanion sp3 pyramidal

carbocation sp2 planar

carbon radical sp2 or sp2 or in between planar or pyramidal radical mechanisms radical starters

polar mechanisms nucleophiles or electrophiles

Organic Reaction Mechanisms

108

3.3 Nucleophilic Substitutions (SN Reactions)

Nucleophilic Substitutions (SN Reactions) SN1 Mechanism: leaving group leaves rst (and allows nucleophile to come in subsequently intermediate
LG R1 R3 R2 + Nu

nucleophile
Nu + R1 C LG R2 R3

leaving group nucleophilic substitution transition state

R1 Nu R3 R2 LG Nu C R R3 2 R1 + LG

electrophilic center

SN2 Mechanism: nucleophile attacks (and forces leaving group to leave simultaneously)

a nucleophile is an electron pair donor, an electrophile is an electron pair acceptor

Organic Reaction Mechanisms 110

SN1 Mechanism: Rate-Determining Step is Unimolecular

sp3 R1 C LG R2 R3 sp2 LG R1 R3 or + Nu R2 sp3 R1 Nu C R R3 2 sp3 R1 C Nu R2 R3

pure enantiomer
1
G1f > G
1r

planar, achiral
2
G2f < G2r fast

racemic mixture

slow

Gf = Gr < 0

Rkt the departure of the leaving group generates a carbokation as a true intermediate the formation of the intermediate is energetically disfavorable, rate-determining good leaving group, stabilized carbocation will decrease energy of the intermediate (favorable)
111

Organic Reaction Mechanisms

Leaving Group Quality

leaving group quality is approximately inverse to the basicity of the obtained anion scale by pK values of the corresponding acids
A
O O S H O CF3 15 > O O S H O Me 10 > O O S H O 7 O > H O 1 CF3 > H O 5 O Me

H I 10

>

H Br 9

>

H Cl 7

>

H F 3

H F 3

>

H OH 16

>

H NH2 38

>

H CH3 48

[H+ ][LG ] pK A = log K A = log HLG

residues with corresponding pK < 0 are good leaving groups residues with corresponding pK < 10 are moderate leaving groups residues with corresponding pK < 20 are poor leaving groups residues with corresponding pK > 20 are not leaving groups at all
A A A A
Organic Reaction Mechanisms 112

Trivial Names and Abbreviations of Important Leaving Groups

O O S R O CF3 R OTf

>

O O S R O Me R OMs

>

O O S R O R OTs

O > R O CF3 > R O

O Me

R OTFA

R OAc

tri uoromethanesulfonate tri ate

methanesulfonate mesylate

4-toluenesulfonate tosylate

tri uoroacetate

acetate

Organic Reaction Mechanisms

113

Stabilization of the Carbocation Intermediate (1)

carbocations are electron-decient, must be stabilized by electron-donating groups

R R Sn R

> >
R H H H H H R Si R H R R H R H

> >
R R R

>

>

> >

> >

>

>

>> >

triphenylmethyl trityl

diphenylmethyl

phenylmethyl ethenylmethyl tertiary benzyl allyl carbon

secondary carbon

primary carbon

phenyl (sp2)

S 1 reactions very favorable in benzyl or allyl position S 1 reactions also observed on highly substituted sp carbons S 1 reactions never observed in phenyl position (or other sp or sp carbons)
N N N 3 2
Organic Reaction Mechanisms 114

Stabilization of the Carbocation Intermediate (2)

stabilization by resonance (+M eect)

H H H C H H HC H H CH H H
H H

compare to phenyl cation

the more delocalization (donor groups, larger aromatic systems), the better stabilization
H H RO RO H C H H RO C H H RO H H RO H CH H

Organic Reaction Mechanisms

115

Stabilization of the Carbocation Intermediate (3)

stabilization by inductive eects (+I eect); conceptual explanation by hyperconjugation

H! R H< C < C ! R H !+
< <

H H C H

R R

H H C H

R R

H H C H

R R

H H C H

R R

the more alkyl groups (the higher substituted), the better stabilized is carbocation stabilization by decreasing electronegativity (and size) of cationic center
R R Sn R > R R Si R > R R C R

EN 1.9

EN 1.9

EN 2.5

Organic Reaction Mechanisms

116

Examples of SN1 Reactions

good leaving group

Cl + MeOH Cl

moderate nucleophile
+ MeOH Me O H H OMe

trityl chloride

methanol

excellently stabilized cation

excellent leaving group

OTf + NaOAc Br TfO Br

moderate nucleophile
CH2 + Na O O CH3 Na Br OAc

benzylbromotri ate

sodium acetate

well-stabilized cation

Organic Reaction Mechanisms

117

SN2 Mechanism
sp3 R1 C LG R2 R3 R1 Nu R3 R2 LG sp3 R1 Nu C R R3 2

LG

Nu

pure enantiomer
E
Nu R1 C R2 R3 LG *

pure enantiomer stereoinversion

E
Nu R1 C R2 R3 LG

Nu (S) (P) Nu *

C R R3 2

R1

LG

C R R3 2

R1

LG

nucleophile interacts with antibonding * orbital of the CLG bond back-side attack and concerted departure of leaving group under stereoinversion good nucleophile (and good leaving group) will favor S 2 reaction
N
Organic Reaction Mechanisms 118

Nucleophilicity

there is no simple, rational nucleophilicity scale! No relation to basicity! nucleophilicity is a kinetic parameter, basicity is a thermodynamic parameter determination of nucleophilicity n according to Pearson:
Nu + H3C I

kNu

Nu CH3

MeOH

H3C I

kMeOH

MeO CH3

H I

k Nu n = log k MeOH
R2P RS R3C > > > > R2N RO R2N > > > > R3P R2S RO > > > > R3N R2O F I H H C O H > Br > Cl > F

H > R C O H

H > R C O R

R > R C O R

Organic Reaction Mechanisms

Pearson et al., J. Am. Chem. Soc. 1968, 90, 3319.

119

Examples for Nucleophilic Substitutions

Br Br

+ EtO Br Br

OEt

OMe Br Br Br

+ EtO Br EtO Br EtO

OMe

+ EtO Br

Cl

OTf

+ EtO TfO Cl

OEt

Cl

Si

Cl

+ EtO Cl Cl Si

OEt

Organic Reaction Mechanisms

120

Nucleophilic Reactions on Carbonyl Compounds

carbonyl carbon atoms are inherently very reactive electrophilic centers

R O C R R O C R R R O R R O

(HOMO)

* (LUMO)

electrophilicity controlled by M eect and I eect

O R Hal > O R O O R > O R R' > O R H > O R OR' > O R' NR'2 > O R OH > O R O

acid halides

acid anhydrides

ketones

aldehydes

esters

amides

acids

carboxylates

aldehydes (H) and ketones (R) have no leaving groups amides (NR ), acids (OH), and carboxylates have very poor leaving groups acid halides, anhydrides (and some esters) have good (or at least moderate) leaving groups reminder: leaving group quality strictly controlled by basicity of the leaving group anion!
2
Organic Reaction Mechanisms 121

Nucleophilic Substitution on Carbonyl Compounds: AdditionElimination Mechanism (SAE)

carbonyl carbons are very reactive electrophilic centers carbonyl carbons are sp hybridized, coordinatively unsaturated
2

sp2 O C LG + Nu

sp3 O C Nu LG R +

sp3 O C LG Nu R LG

sp2 O C LG

R or + Nu

E 1
G1f > G1r slow

2
G2f < G2r

fast

Gf = Gr < 0

P Rkt

addition of the nucleophile prior to cleavage of the leaving group is possible, advantageous!
Organic Reaction Mechanisms 122

Active Acid Derivatives

O R Cl Cl

acid chlorides
O R O O R O

pKA (HCl) = 7
O R O O R

O Cl
H3C

O O S Cl

benzoyl chloride (BzCl)

O

tosyl chloride (TsCl)

O O S H3C Cl

acid anhydrides
F O R F O F F F F O

pKA (RCOOH) 4
F F F F F O F C F F F etc.
H3C

Cl

acetyl chloride (AcCl)

O H3C O O CH3

mesyl chloride (MsCl)

O OO O S S F3C O CF3

per uorophenyl esters

O R O O N O

pKA (PfpOH) 6
O O N O O O N

active ester

etc. O

acetic anhydride (AcOAc, Ac2O)

Tri ic anhydride (TfOTf, Tf2O)

N-succinyl esters

pKA (SuOH) 10 active ester

Organic Reaction Mechanisms

123

Examples for Nucleophilic Substitutions on Carbonyl Carbons

O O S Cl OH TsCl NEt3 HNEt3 Cl CH3

CH3

S O O O

OTs

tosylation

O OH NH2 H3C

O HO HN

O CH3 Ac2O

CH3 O OH NHAc

NEt3 HNEt3 AcO

acetylation

Organic Reaction Mechanisms

124

Example: Peptide Coupling Reactions

no amide (peptide) formation between carboxylic acid and amine:

O R OH + H2N R' O R O + H3N R'

solution: peptide coupling reagents

O R OH NEt3 HNEt3 O N O C R NH H2N R' R O O

dicyclohexylcarbodiimide (DCC)
N C N

+ HNEt3 NEt3

O R N H R' + N H

O C

N H

peptide

Organic Reaction Mechanisms

125

3.4 Electrophilic Additions to Ole ns (AE Reactions)

Reactions of Olens with Electrophiles

olens are (weak) nucleophiles and react with electrophiles to form carbocations
H R H H El H R El HH + Nu RH Nu El HH

reactivity order
R OR > R R R > R R > Ph > R R > R > COOH > Cl

decreasing electron density (M or I eect)

Organic Reaction Mechanisms

127

Examples

hydrohalogenation of olens
H Br

Br H

hydration of olens
H HSO4 H2O

OH H

halogen addition to olens

Br Br

Br Br

Organic Reaction Mechanisms

128

Mechanism of Electrophilic Additions to Olens

El El R3 H El C + Nu R2 R R3 C C 1 Nu H El

R3 C H

C R 1

R2

C R 1

R2

backside attack

* (LUMO)
R4 3 C H R C R 2 1

E
G1f > G

R4 3 H

R C R 2 1

(HOMO)
R4 3 C H C R 1 R2
1r

1
slow

2
G2f < G2r

fast

Gf = Gr < 0

electrophile adds to double bond so that more stable cation is formed nucleophile attacks from the other side
Organic Reaction Mechanisms

Rkt

129

Regioselectivity of Electrophilic Additions: Markovnikov-Rule

H H H Ph H Br H

H H Br

H H H Ph H

E 2
G2f < G2r fast

Ph H Br

H Ph H Br

Ph H Br

1 I
G1 > G1 slower slow

1 2
G2f < G2r

fast

S P
Gf < Gr

P Rkt

electrophile adds to double bond so that more stable cation is formed IMarkovnikov rule: in HX addition, X is added to the higher substituted carbon (the more you
have, the more you get)
Organic Reaction Mechanisms 130

Stereoselectivity of Electrophilic Additions

electrophilic additions are trans-additions

Br H C (E) C H Ph Br Br H Me Me H
+

Ph H Br Ph H

Br H Me Me H

(S) (R)

Ph H Br Br Ph H

Me

+
(R) (S)

Br

Br

Br H C (Z) H C Ph Br Br H Me Me H
+

H Ph Br H Ph

Br H Me Me H

(R) (R)

H Ph Br Br H Ph

Me

+
(S) (S)

Br

Br

electrophilic additions are diastereospecic, i.e., an olen with a given conguration (E or Z) will
specically be transformed into one diastereomer of possible adducts (a pair of enantiomers)
Organic Reaction Mechanisms 131

3.5 Electrophilic Substitutions on Aromatic Compounds

Multiple Bonds Aromatic Compounds Do Not React Like Olens

Elelctrophilic Addition
+ Nu Nu H H El

H H

El

H El H H El

Elelctrophilic Substitution

electrophilic addition leads to loss of aromaticity, energetically disfavorable electrophilic Substitution re-establishes aromatic system
Organic Reaction Mechanisms 133

Examples

bromination
H Br Br + FeCl3 Br + FeBrCl3 !+ ! Br Br FeCl3

Friedl-Crafts alkylation and acylation

H R Br R + AlCl3 O H R Cl + AlCl3 O R + AlCl4 ! O !+ Cl AlCl3 R + AlBrCl3 !+ R ! Br AlCl3

sulfonation and nitration

H H

H2SO4 H2O

SO3H

HSO3 HSO4

HNO3 / H2SO4 H2O

NO2

NO2 H3O

2 HSO4

Organic Reaction Mechanisms

134

Mechanism of Electrophilic Aromatic Substitutions

El H El H H H H El

H El

complex

complex

E 1
G1f > G1r slow

2
G2f < G2r fast

0 S

P
Gf = Gr < 0

addition product

substitution product

Rkt

in electrophilic aromatic substituions, the most acidic hydrogen is replaced with an electrophile
Organic Reaction Mechanisms 135

Regioselectivity in Electrophilic Aromatic Substitutions

RO

RO HC

RO CH

RO

H C

RO

RHN

>

RO

>

>

Br

>

Cl

> >

Br Br RO + FeCl3 RO

Br + RO Br + RO Br

para major

meta none

ortho minor

substituents with +M eect direct the electrophile into ortho or para-positions substituents with +M eect increase electron density, nucleophilicity, reactivity
Organic Reaction Mechanisms 136

Regioselectivity in Electrophilic Aromatic Substitutions

O RO RO

O RO HC

O RO CH

H C RO

O O S RO

>

O N

O > RO > RN H

O > HO

O > > O

sulfonate

nitro

carboxylic esters
Br Br

carboxylic amides
Br +

carboxylic acids

carboxylates

O2N

+ FeCl3

+ O2N Br O2N Br

O2N

para traces

meta major

ortho traces

substituents with M eect direct the electrophile into meta-positions substituents with M eect decrease electron density, nucleophilicity, reactivity
Organic Reaction Mechanisms 137

3.6 Elimination Reactions

-Hydrogen Eliminations

most common are eliminations of hydrogen (H) and leaving group (LG) on adjacent carbons
E1 mechanism: leaving group leaves rst, hydrogen leaves subsequently
LG H R3 H C C R H 1 R2 H

H # " R2 R R3 C C 1 LG H

Base ! + ! H ! !+ R 2 R R3 C C 1 H ! LG

R3

R4 C

R C R 2 1

ole n

E2 mechanism: concerted reaction

+ Base H Base R2 R R3 C C 1 LG H LG

E1cb mechanism: base rst removes hydrogen and generates conjugate base, then leaving group leaves

-hydrogen eliminations are reverse reactions of electrophilic additions to olens

Organic Reaction Mechanisms 139

Competition of SN1 and E1 Reactions

E1 Elimination
H (base) R2 H R R3 C C 1 LG H LG H R3 H C R C R 2 H 1 + Nu R2 H H Nu R R3 C C R2 + R3 C C 1 Nu H H R1 R3 R4 C R C R 2 1

SN1 Substitution

E1 eliminations are inevitable side reactions of S 1-type substitution reactions! Factors: both: good leaving group, stabilized carbocation (identical intermediate!) E1: absence of a nucleophile, non-nucleophilic base (if any), many or acidic -hydrogens S 1: presence of a (good, not too basic) nucleophile, few or non-acidic -hydrogens
N N
Organic Reaction Mechanisms 140

Competition of SN2 and E1cb/E2 Reactions

E1cb Elimination
+ Base H Base R2 H R R3 C C 1 LG H + Nu H R2 R3 C C R 1 H LG Nu H Nu C C R3 R2 H R1 R2 R R3 C C 1 LG H LG R3 R4 C R C R 2 1

SN2 Substitution

eliminations are often-observed side reactions of S 2-type substitution reactions! however, they do not share the same intermediate E1 /E2: moderate/poor leaving group, strong non-nucleophilic base, acidic -hydrogens S 2: good, non-basic nucleophile (e.g., I , RS , PR , H O), few or non-acidic -hydrogens
N cb N 3 2
Organic Reaction Mechanisms 141

Non-Nucleophilic Bases

N Li

Si

Si Li

lithium diisopropylamide LDA, pKA 40

lithium hexamethyldisilazide LHMDS, pKA 40

N N

diisopropylethylamine DIEA, pKA 10

triisopropylamine TIPA, pKA 10

1,8-bis(dimethylamino)naphthalene proton sponge, pKA 12

N N

N N

N N

1,4-diazabicyclo[2.2.2]octane DABCO, pKA 12

1,5-diazabicyclo[4.3.0]non-5-ene DBN, pKA 12

1,8-Diazabicyclo[5.4.0]undec-7-ene DBU, pKA 12

non-nucleophilic bases have a high pK (of BH) but are strongly sterically hindered!
A
Organic Reaction Mechanisms 142

3.7 Radical Substitutions and Additions

Radical Substitution Reactions (SR)

initiation

Cl Cl

2 Cl

propagation

CH3 + Cl

CH2 + H Cl

CH2 + Cl Cl

CH2Cl

+ Cl

product

termination reactions

2 Cl

Cl Cl

CH2 + Cl

CH2Cl

product

CH2

CH2 CH2

side product

Organic Reaction Mechanisms

144

Radical Addition Reactions (AR)

initiation

Br Br

2 Br

propagation
H C

+ Br

H C Br

Br

Br + Br Br

Br + Br

product

termination reactions
H C

2 Br

Br Br Br

Br + Br H C BrH2C CH

Br

product

Br

CH2Br CH

side product

Organic Reaction Mechanisms

145