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Organic Chemistry 2 (Oc 2) : Reactivity and Mechanism of Organic Compounds Chapter 5: Nucleophilic Substitution (At SP)

Chapter 5 of the Organic Chemistry 2 document covers nucleophilic substitution reactions. It discusses key concepts like nucleophiles and electrophiles, and how the hardness/softness of each influences reaction favorability based on orbital interactions. The chapter also examines factors that determine reaction mechanism (SN1 vs SN2), stereochemistry, carbocation stability, and strategies for activating less reactive functional groups to undergo substitution. Specific reaction types are explored, including substitutions using carbon, nitrogen, oxygen, phosphorus and other nucleophiles.

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107 views38 pages

Organic Chemistry 2 (Oc 2) : Reactivity and Mechanism of Organic Compounds Chapter 5: Nucleophilic Substitution (At SP)

Chapter 5 of the Organic Chemistry 2 document covers nucleophilic substitution reactions. It discusses key concepts like nucleophiles and electrophiles, and how the hardness/softness of each influences reaction favorability based on orbital interactions. The chapter also examines factors that determine reaction mechanism (SN1 vs SN2), stereochemistry, carbocation stability, and strategies for activating less reactive functional groups to undergo substitution. Specific reaction types are explored, including substitutions using carbon, nitrogen, oxygen, phosphorus and other nucleophiles.

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Allalann
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ORGANIC CHEMISTRY 2 (OC 2)

Reactivity and Mechanism of Organic Compounds


Chapter 5: Nucleophilic Substitution (at sp3)

Prof. Dr. Tanja Gulder


Department of Chemistry and Catalysis Research Center TUM

[email protected]

www.biomimeticcatalysis.ch.tum.de
Chapter 5

Goals of chapter 5

Nucleophiles/Electrophiles (concept)
Important reactions besides simple SN1 and SN2
What is a Substitution?
Rules for Nucleophilicity

E
Reactions of hard Nuc + hard E and
E+ soft Nuc + soft E are favored.
LUMO

HOMO
soft Nuc
good O bi al interactions
HOMO bad C l mb interations
hard Nuc Orbital control
bad O bi al interactions
good C l mb interactions
electrostatic control

Example:
Hard and Soft Acids and Bases (HSAB)

Electrophiles (Acids) Nucleophiles (Bases)

Hard Borderline Soft Hard Borderline Soft

H+ Cu+, Ag+, OH–


NO+ H–
Hg+, R-Hg+
– – –
Li+, Na+, K+ Hg2+, Pd2+, F , AcO , Cl I–, SCN–, CN–,
Be2+, Ca2+, Mn2+ Fe2+, Co2+, Pt2+ , NO3– N3–, Br–, NO2– HS–,
Ni2+, Cu2+, 2–, CO 2–
, HSO3–
3+ 3+
Al , Fe , Cr 3+ BH3, GaCl3 SO 4 3
Zn2+, Sn2+ S2O32–
Ti4+, Sn4+ PO43–
X2, X–Y
BX3, AlX3, AlR3 quinones, H2O, NH3, N2 R3P, (RO)3P, CO
BR3 carbenes N2H4
SO3, CO2 SO2 aniline,
ROH, RNH2, pyridine R2S, alkenes,
+ +
RS , I , Br +
HX R2O arenes
C6H5+, OH+
R-CO+ R3C+ RS–, R–
C-radicals RO–
Relative Nucleophilicity vs Basicity
Solvent Effects on Nucleophilicity
Quality of Leaving Groups/Electrophiles
Neutral Leaving Groups
Steric Effects on the Reaction Rate in SN2 Reactions
Reactions at Bridge-Head Positions

SN2 at Bridgeheads: backside-attack is essentially impossible, hence no reaction takes place!

SN1 at Bridgeheads: attack is difficult, if not impossible, since the carbocation needs to
assume a planar configuration (sp2)

illustration:
1 >> 10 7 >> 10 13
krel (SN1)
Mechanistic Types of Substitution
a) Bond-breaking occurs before bond-making:

b) Simultaneous bond-making and bond-breaking

c) Bond-making precedes bond-breaking

not observed at carbon!


SN1 Substitution
Carbocation Watching

H. F. Schaller, H. Mayr, Angew. Chem. 2008, 120, 4022.


Stable Carbocations as Pigments (Triphenylmethane Dyes)
Stereochemistry of the SN1-Reaction
Substitution by the SN2 Mechanism
Stereochemistry of SN2: Inversion of Configuration
Orbital-Interaction in the SN2 Substitution
SN1 vs SN2: Which Mechanism is Preferred?
Carbon Nucleophiles
Nitrogen Nucleophiles
Nitrogen Nucleophiles
Nitrogen Nucleophiles
Phosphor Nucleophiles
Phosphor Nucleophiles
Oxygen and Sulfur Nucleophiles
Activation of Alcohols for SN Reactions
Further Activation Methods for Alcohols
Further Activation Methods for Alcohols
6. Appel-Reaktion

CCl4 (CH3)3CCl CBr4


Mitsunobu Method
6. Mitsunobu Reaktion
Mitsunobu Reaction
Epoxides and other strained Rings as Electrophiles
Epoxides and other strained Rings as Electrophiles
Neighboring Group Effects
Neighboring Group Effects

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