Substitution

In a substitution reactionA chemical reaction in which one atom or a group of atoms in a substance is replaced by another atom or a group of atoms from another substance., one atom or a group of atoms in a substance is replaced by another atom or group of atoms from another substance. A typical substitution reaction is reacting the hydroxide ion with methyl chloride:

Methyl chloride has a polar C–Cl bond, with the carbon atom having a partial positive charge. In Equation 24.1, the electronegative Cl atom is replaced by another electronegative species that is a stronger nucleophile, in this case OH⁻. Reactions of this sort are called nucleophilic substitution reactions. For this type of reaction to occur, the nucleophilic reactant must possess a pair of electrons and have a greater affinity for the electropositive carbon atom than the original substituent.

One type of nucleophilic substitution reaction is shown in Equation 24.1. It proceeds by a mechanism in which the lone pair of electrons on the entering nucleophile (OH⁻) attacks the partially positively charged carbon atom of the polar C–Cl bond, causing the C–Cl bond to weaken and break:

Figure 24.12

 

The convention for writing such a mechanism is to draw arrows showing the direction of electron flow—that is, from the electron-rich center (the nucleophile) to the electron-poor center (the electrophile). The intermediate species, enclosed by square brackets, represents a transient arrangement of atoms that is only postulated to exist. If the atom under attack (in this case, the partially positively charged carbon atom) had –CH₃ groups bonded to it rather than H atoms, the bulky methyl groups would interfere with the attack by OH⁻, making the reaction sterically hindered. The reaction would then proceed in two discrete steps in a second type of substitution reaction: the C–Cl bond would break, forming the (CH₃)₃C⁺ carbocation (the electrophile), which would then react with hydroxide (the nucleophile) in a separate step to give the product, (CH₃)₃COH.

Mustard gas.

An example of a nucleophilic substitution reaction involves the chemical warfare agent known as mustard gas [(ClCH₂CH₂)₂S], which caused about 400,000 casualties during World War I. Mustard gas is toxic because it contains a chloride that can be displaced by nucleophilic amino groups in proteins, thereby allowing the molecule to irreversibly bond to a protein. Because the other product of the reaction is HCl, mustard gas causes severe burns to mucous membranes in the respiratory tract. If mustard gas reacts with DNA (deoxyribonucleic acid), cross-linking of the DNA strands through sulfur occurs, which results in coding errors, the inhibition of replication, and disruption of other DNA functions. If mustard gas reacts with RNA (ribonucleic acid), protein synthesis is altered (see Section 24.6 "The Molecules of Life").

Elimination

Some reactions involve the removal, or “elimination,” of adjacent atoms from a molecule. This results in the formation of a multiple bond and the release of a small molecule, so they are called elimination reactionsA chemical reaction in which adjacent atoms are removed, or “eliminated,” from a molecule, resulting in the formation of a multiple bond and a small molecule.. They have the general form

Figure 24.13

 

and are similar to cleavage reactions in inorganic compounds. (For more information on cleavage reactions, see Chapter 3 "Chemical Reactions", Section 3.5 "Classifying Chemical Reactions".) A typical example is the conversion of ethyl chloride to ethylene:

Much of the approximately 26 million tons of ethylene produced per year in the United States is used to synthesize plastics, such as polyethylene. In Equation 24.2, the A–B molecule eliminated is HCl, whose components are eliminated as H⁺ from the carbon atom on the left and Cl⁻ from the carbon on the right. When an acid is produced, as occurs here, the reaction is generally carried out in the presence of a base (such as NaOH) to neutralize the acid.

Addition

A reaction in which the components of a species A–B are added to adjacent atoms across a carbon–carbon multiple bond is called an addition reactionA chemical reaction in which the components of a species A–B are added to adjacent atoms across a carbon-carbon multiple bond.. An example is the reverse of the reaction shown in Equation 24.2, reacting HCl with ethylene to give ethyl chloride:

Although a multiple bond is stronger than a single bond, the π bonds of the multiple bond are weaker than the σ bond. The high electron density located between multiply bonded carbon atoms, however, causes alkenes and alkynes to behave like nucleophiles, where nucleophilic attack occurs from the more weakly bound π electrons. Hence alkenes and alkynes are regarded as functional groups. Nucleophilic attack occurs on the H^δ+ atom of the polar HCl bond, initially producing a species with a carbon that has only three bonds, a carbocation. In a second nucleophilic attack, Cl⁻, the electrophile in Equation 24.3, attacks the carbocation:

Alcohols, an important class of organic compounds, are often produced by addition reactions. Initial attack by the π bond of an alkene on a H^δ+ of H₃O⁺ produces a carbocation. The carbocation then undergoes nucleophilic attack by a lone pair of electrons from H₂O followed by elimination of H⁺ to form the alcohol.

Radical Reactions

Many important organic reactions involve radicals, such as the combustion of fuels. Probably the best known is reacting a saturated hydrocarbon, such as ethane, with a halogen, such as Br₂. The overall reaction is as follows:

Radical chain reactions occur in three stages: initiation, propagation, and termination. (For more information on radicals, see Chapter 14 "Chemical Kinetics", Section 14.6 "Reaction Rates—A Microscopic View".) At high temperature or in the presence of light, the relatively weak Br–Br bond is broken in an initiation step that produces an appreciable number of Br atoms (Br·). During propagation, a bromine atom attacks ethane, producing a radical, which then reacts with another bromine molecule to produce ethyl bromide:

The sum of the two propagation steps corresponds to the balanced chemical equation for the overall reaction. There are three possible termination steps: the combination of (1) two bromine atoms, (2) two ethyl radicals, or (3) an ethyl and a bromine radical:

Because radicals are powerful nucleophiles and hence highly reactive, such reactions are not very selective. For example, the chlorination of n-butane gives a roughly 70:30 mixture of 2-chlorobutane, formed from the more stable radical by reacting a secondary carbon and 1-chlorobutane.

Oxidation–Reduction Reactions

Oxidation–reduction reactions, which are common in organic chemistry, can often be identified by changes in the number of oxygen atoms at a particular position in the hydrocarbon skeleton or in the number of bonds between carbon and oxygen at that position. An increase in either corresponds to an oxidation, whereas a decrease corresponds to a reduction. Conversely, an increase in the number of hydrogen atoms in a hydrocarbon is often an indication of a reduction. We can illustrate these points by considering how the oxidation state of the carbon atom changes in the series of compounds, which is shown in part (a) in Figure 24.14 "The Oxidation State of Carbon in Oxygen- and Nitrogen-Containing Functional Groups". (For a review of oxidation states and formal changes, see Chapter 3 "Chemical Reactions", Section 3.5 "Classifying Chemical Reactions", and Chapter 8 "Ionic versus Covalent Bonding", Section 8.5 "Lewis Structures and Covalent Bonding"). The number of oxygen atoms or the number of bonds to oxygen changes throughout the series. Hence the conversion of methane to formic acid is an oxidation, whereas the conversion of carbon dioxide to methanol is a reduction. Also, the number of hydrogen atoms increases in going from the most oxidized to least oxidized compound. As expected, as the oxidation state of carbon increases, the carbon becomes a more potent electrophile. Thus the carbon of CO₂ is a stronger electrophile (i.e., more susceptible to nucleophilic attack) than the carbon of an alkane such as methane.

Figure 24.14 The Oxidation State of Carbon in Oxygen- and Nitrogen-Containing Functional Groups

(a) In a hydrocarbon, oxidation is indicated by an increase in the number of oxygen atoms or carbon–oxygen bonds or a decrease in the number of hydrogen atoms. (b) In nitrogen-containing compounds, the number of carbon–nitrogen bonds changes with the oxidation state of carbon.

Similarly, in compounds with a carbon–nitrogen bond, the number of bonds between the C and N atoms increases as the oxidation state of the carbon increases (part (b) in Figure 24.14 "The Oxidation State of Carbon in Oxygen- and Nitrogen-Containing Functional Groups"). In a nitrile, which contains the –C≡N group, the carbon has the same oxidation state (+2) as in a carboxylic acid, characterized by the –CO₂H group. We therefore expect the carbon of a nitrile to be a rather strong electrophile.