Sections 6.9, 6.10, and 6.11 briefly introduce three significant categories of chemical reactions. Remember, however, that you can categorize most organic reactions as acid-base reactions. Thus, you need to learn as many ways as possible to tell which reactant is the acid and which is the base. You can also classify reagents in organic reactions as either electrophiles or nucleophiles. An electrophilic reagent reacts with electron-rich substrates. That is, an electrophile is a Lewis acid that reacts with a substrate that is a Lewis base. A nucleophilic reagent reacts with an electron-poor substrate and is a Lewis base. Table 6.1 lists representative nucleophiles and electrophiles.
Nucleophiles Electrophiles
c- OH, CH3Oc- , CH3CH2Oc- ,
c- SH, CH3Sc- , CH3CH2Sc- ,
c- CN, Ic- , Brc- , NH3, c- CH3, CH3NH2
H⊕, Cl⊕, Br⊕, ⊕CH3, BF3,
⊕NO2
Table 6.1. Representative nucleophilic and electrophilic reagents.
6.8 Writing Reaction Mechanisms
This book presents organic chemical reactions according to their reaction mechanism type. The mechanism of a reaction is a visual description of the pathway that reacting molecules follow as they are transformed from starting materials to products. That is, as molecules react, they move directly to the product or through one or more intermediate steps. These steps may involve changes that either convert one functional group to another or rearrange the carbon skeleton. A reaction mechanism is a step-by-step written representation of those structural changes. Writing a reaction mechanism is like taking a series of snapshots of each intermediate
A mechanism shows the flow of electrons as reactants are
transformed to products.
step. Understanding organic reactions depends on being able to visualize the structural changes that take place along the reaction pathway and being able to write out the steps helps in the visualization process. By knowing the specific mechanisms that are representative of broad categories of reactions, you can develop a feeling for the essential details of the organic reactions, enabling you to predict the outcome of unfamiliar ones.
When writing a reaction mechanism for an organic reaction, you must show how the electron pairs flow in the reaction. The overall flow of electron pairs in a reaction can be broken down into five general operations and are discussed in this section. These five operations help you to link the reactant structure with the product structure. If you keep these five operations in mind when writing mechanisms, you will find it much easier to understand the electron flow in the reactions.
Using Sections 6.8 to 6.11
Do not attempt to memorize all of the reactions and reaction mechanisms in Sections 6.8 through 6.11. Many of the reactions in these sections are unfamiliar to you, and you do not have enough information to fully understand them. That understanding will come in later chapters. The goal for these sections is to give you the tools to understand and work with the various types of mechanisms. Pay particular attention to the electron flow in the examples given to develop your skills in writing mechanisms. So step back looking for trends and ideas, not for details. You will develop an understanding of the details in future chapters.
The first general operation used in mechanism writing is the heterolytic bond cleavage operation. Heterolytic bond cleavage takes place when the bond between two atoms breaks. One atom takes both electrons and becomes negatively charged while the other atom loses electrons and becomes positively charged.
The heterolytic bond cleavage operation breaks a bond in such a way that one atom takes both electrons.
A B A + B••
Here are some examples of the heterolytic bond cleavage operation:
•• + Cl H
H Cl•••••• ••••••
•• + H
••
O
H H
••
O
H H
H
H + ••
O H
CH3C O
O CH3C
O
••
••
••
••
The second general operation is the heterogenic bond forming operation, which is the reverse of the heterolytic bond cleavage operation. An atom with a pair of electrons reacts with another atom having an empty orbital. The atom with the electrons becomes more positively charged while the atom with the empty orbital becomes more negatively charged.
The heterogenic bond forming operation involves the formation of a bond between one atom with an empty orbital and another with a pair of
nonbonding electrons.
•• +
B A A B
Here are some examples of the heterogenic bond forming operation:
Cl
••
••
••
•• + CH3 CH3Cl
••
••
••
••
••
••
H Br Br•• + H
N F F
F
B H
H H
•• + N
F F
F H
H H B
The third general operation is the 1,3-electron pair displacement operation. This reaction involves an electron flow covering three atoms: an initiating electron-donating atom, the central atom, and an electron-accepting atom. Unlike the first two operations, there is no change in the net charge of the reacting system. However, the initiating atom becomes more positive and the displaced atom becomes more negative. The initiating electron-donor atom is normally called a nucleophile.
In a 1,3-electron pair displacement operation, one atom with a pair of nonbonding electrons forms a bond with a second atom and displaces a pair of bonding electrons to a third atom.
+ B C A B + C••
••
A Nucleophile
In addition to the bond-forming and bond-breaking process shown above, this general operation also fits the addition of a nucleophile to a double bond.
+ B C A B C••
••
A Nucleophile
Some examples of the 1,3-electron pair displacement operation are shown below:
I + I
O•• + ••
••
••
••
••
••
••
••
O ••
••
••
O
+ H
••
••
•• O
H
••••
••
N C C Cl
H H H
N C C
H
HH+ Cl
The fourth general operation is the 1,3-electron pair abstraction operation. In this case, an electron-deficient species draws an electron pair from an electron-rich species, making another atom electron-deficient. The initiating atom becomes less positive, and the displaced atom becomes more positive. The initiating electron- acceptor atom is normally called an electrophile.
In a 1,3-electron pair abstraction operation, one atom with an empty orbital forms a bond with a second atom and removes a bond from a third atom.
A + B C A B + C
Electrophile
In addition to the bond-forming and bond-breaking process shown above, this fourth general operation also fits the addition of an electrophile to a double bond.
A + B C A B C Electrophile
Following are some examples of the 1,3-electron pair abstraction operation:
+ H
H
The fifth general operation is the 1,5-electron pair displacement operation. This operation involves an electron flow covering five atoms: an initiating electron-donor atom, three central atoms, and an electron-acceptor atom. There is no change in the net charge of the reacting system. However, the initiating atom, the nucleophile, becomes more positive and the displaced atom becomes more negative.
In a 1,5-electron pair displacement operation, one atom with a pair of nonbonding electrons forms a bond with a second atom and displaces a bonding electron pair to a third atom and then another to a fifth atom.
+ A B + C D + E••
•• B C D E
A Nucleophile
In addition to the bond-forming and bond-breaking process shown above, the fifth general operation also fits the addition of the electrophile (D) to a double bond.
B C
A + D E A B C D + E••
••
Electrophile
Some examples of the 1,5-electron pair displacement operation are as follows:
Br
H
HO + H2O + +Br
N
O
CH3 Br +
•• N
O
CH3
+ Br
Other operations are possible, but they do not occur in the reaction systems discussed in this book. Most organic reaction mechanisms, no matter how complex, can be written using these five operations. The next Sections 6.9, 6.10, and 6.11 use some specific reactions as examples to preview the three categories of reaction mechanisms covered in more detail in later chapters. In these sections, you will see how the five operations are used in some actual mechanisms.
A Tip for Using Curved Arrows
When the mechanism of a reaction requires the use of multiple arrows, the tail of one arrow follows the head of the previous one. A common mistake of beginners is showing multiple arrows originating from or terminating at a single atom. Remember, the tail of a second arrow follows the head of the first and shows the direction of electron flow.
When drawn this way, your arrow sequence will more likely be correct.
Solved Exercise 6.2
Identify the operations used in the following reaction mechanisms.
a)
H
Cl
••
••
•• ••
••
••
•• H Cl
H Cl
Solution
This mechanism has two steps. The first step is a 1,3-electron pair displacement operation. Compare it to the general operation description.
A•• + B C A B + C••
The second step is a heterogenic bond formation operation. Compare it to the general operation description.
•• +
B A A B
b)
••
••
••
••
OCH3
O •• ••
••
Cl••
••
••
••
OCH3
O
H
••
••
••
••
••
••
••
Cl O
OCH3
H
••
HOCH•• 3
••
••
••
••
••
Cl O
Solution
All three steps are 1,3-electron pair displacement operations.
A
•• + B C A B + C••
Exercise 6.7
Identify the general operation used in each step in the following mechanisms.
a)
H OH
CN CN H
O H
H CN
H O
•• ••
•• ••
••
••
••
••
••
b) Br
H c)
OH O OCH3
O
OH OH
OCH3
•O
• •• ••
••
••
••
•• ••
••
••
••
••
••
••
••
••
••
••
d)
+ + +
••
••
••
••
•• Br
••
O C
CH3
CH3
CH3
H
••
••
••
••
••
••
O C
CH3
CH3
CH3
Br
H
e)
F
NO2
O2N O2N NO2
F NHCH3
H
••
••
••
••
CH3NH2
••
NHCH3
NO2
O2N
H NHCH3
NO2
O2N
••
••
••
F
••
••
••
••
••
Sample solution
b) The first step is a heterolytic bond cleavage operation; the second step is a 1,3-electron pair abstraction operation.