23.4 Reactions of Alcohols

Gregory Anderson; Caryn Fahey; Adrienne Richards; Samantha Sullivan Sauer; David Wegman; Jen Booth

23.4 Reactions of Alcohols

Learning Objectives

By the end of this section, you will be able to:

Learn about the major types of reactions of alcohols.
Describe the result of the oxidation of a primary and secondary alcohols.
Draw the products from dehydration of alcohols.
Understand the production of alcohols from esters.

Organic functional groups can be converted into other functional groups through reactions. A map of some of the more common reactions to convert functional groups can be found in Section 19.6 – General Reactions of Carbon in Infographic 19.6a.

Chemical reactions in alcohols occur mainly at the functional group, but some involve hydrogen atoms attached to the OH-bearing carbon atom or to an adjacent carbon atom. We will be discussing three major kinds of alcohol reactions – substitution, elimination and oxidation.

The versatility of the alcohol functional group is well defined as it can be transformed into many other functional groups. Figure 23.4a. highlights the formation of aldehydes, ketones, carboxylic acids, ethers, alkenes, and esters.

A flow diagram of three possible reactions of an alcohol. The final products of the reactions are also shown at the end of the flow diagram. — **Figure 23.4a.** Reactions of Alcohols. (Credits: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

Oxidation

Primary and secondary alcohols are readily oxidized. We saw earlier how methanol and ethanol are oxidized by liver enzymes to form aldehydes. Because a variety of oxidizing agents can bring about oxidation, we can indicate an oxidizing agent without specifying a particular one by writing an equation with the symbol [O] above the arrow. For example, we write the oxidation of ethanol, a primary alcohol, to form acetaldehyde or ethanal, an aldehyde, as shown in Figure 23.4b.

Formula of ethanol reacting to form acetaldehyde with an O in a bracket above the right pointing arrow. — **Figure 23.4b.** Oxidation of ethanol to ethanal (acetaldehyde). (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

We shall see that aldehydes are even more easily oxidized than alcohols and yield carboxylic acids. Secondary alcohols are oxidized to ketones. The oxidation of propan-2-ol (isopropyl alcohol) by potassium dichromate (K₂Cr₂O₇) gives propanone (acetone), the simplest ketone (Figure 23.4c.).

Oxidation of propan-2-ol (isopropyl alcohol) to propanone (acetone) using potassium dichromate as the catalyst. — **Figure 23.4c.** Oxidation of propan-2-ol (isopropyl alcohol) to propanone (acetone) (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0).

Unlike aldehydes, ketones are relatively resistant to further oxidation, so no special precautions are required to isolate them as they form. Note that in oxidation of both primary (RCH₂OH) and secondary (R₂CHOH) alcohols, two hydrogen atoms are removed from the alcohol molecule, one from the OH group and other from the carbon atom that bears the OH group.

Alcohol oxidation is important in living organisms. Enzyme-controlled oxidation reactions provide the energy cells need to do useful work. One step in the metabolism of carbohydrates involves the oxidation of the secondary alcohol group in isocitric acid to a ketone group (Figure 23.4d.). The overall type of reaction is the same as that in the conversion of isopropyl alcohol to acetone.

Oxidation of isocitrate to oxalosuccinate using an enzyme as a catalyst. — **Figure 23.4d.** Oxidation of isocitrate to oxalosuccinate. (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0).

Tertiary alcohols (R₃COH) are resistant to oxidation because the carbon atom that carries the OH group does not have a hydrogen atom attached but is instead bonded to other carbon atoms. The oxidation reactions we have described involve the formation of a carbon-to-oxygen double bond. Thus, the carbon atom bearing the OH group must be able to release one of its attached atoms to form the double bond. The carbon-to-hydrogen bonding is easily broken under oxidative conditions, but carbon-to-carbon bonds are not. Therefore tertiary alcohols are not easily oxidized.

The process of oxidation of alcohols is highlighted in Infographic 23.4a.

**Infographic 23.4a.** Read more about “A Guide to Oxidation Reactions of Alcohols” by Andy Brunning / Compound Interest, CC BY-NC-ND, or access a text-based summary of infographic 23.4a [New tab].

Example 23.4a

Write an equation for the oxidation of each alcohol. Use [O] above the arrow to indicate an oxidizing agent. If no reaction occurs, write “no reaction” after the arrow.

3 images from left to right: a) a 5 carbon chain with an OH group at the end; b) a 4 carbon chain with an OH group and a methyl group at the 2nd carbon and lastly; c) a 6 carbon chain with an OH group at the 2nd carbon. — (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

Solution

The first step is to recognize the class of each alcohol as primary, secondary, or tertiary.

This alcohol has the OH group on a carbon atom that is attached to only one other carbon atom, so it is a primary alcohol. Oxidation forms first an aldehyde and further oxidation forms a carboxylic acid.

(Credit: Introduction to Chemistry: GOB (V. 1.0)., CC BY-NC-SA 3.0.)
This alcohol has the OH group on a carbon atom that is attached to three other carbon atoms, so it is a tertiary alcohol. No reaction occurs.

(Credit: Introduction to Chemistry: GOB (V. 1.0)., CC BY-NC-SA 3.0.)
This alcohol has the OH group on a carbon atom that is attached to two other carbon atoms, so it is a secondary alcohol; oxidation gives a ketone.

(Credit: Introduction to Chemistry: General, Organic, and Biological (V. 1.0)., CC BY-NC-SA 3.0.)

Spotlight on Everyday Chemistry: Chemistry of a Hangover

The process of alcohol oxidation is key to the effects of alcohol in the human body. Infographic 24.3b. highlights some of the chemistry of a hangover.

**Infographic 23.4b.** Read more about “What causes hangovers? A biochemical mystery” by Andy Brunning / Compound Interest, CC BY-NC-ND, or access a text-based summary of infographic 23.4b [New tab].

Ethanol: Chemical, Drug & Poison

Ethanol is classified medically as a central nervous system (CNS) depressant. Its effects—that is, being drunk—resemble the human response to anesthetics. There is an initial excitability and increase in sociable behavior, but this results from depression of inhibition rather than from stimulation. At a blood alcohol concentration of 0.1% to 0.3%, motor coordination is affected, accompanied by loss of balance, slurred speech, and amnesia. When blood alcohol concentration rises to between 0.3% and 0.4%, nausea and loss of consciousness occur. Above 0.6%, spontaneous respiration and cardiovascular regulation are affected, ultimately leading to death. The LD₅₀ of ethanol is 10.6 g/kg.

The passage of ethanol through the body begins with its absorption in the stomach and small intestine, followed by rapid distribution to all body fluids and organs. In the pituitary gland, ethanol inhibits the production of a hormone that regulates urine flow, causing increased urine production and dehydration. In the stomach, ethanol stimulates production of acid. Throughout the body, ethanol causes blood vessels to dilate, resulting in flushing of the skin and a sensation of warmth as blood moves into capillaries beneath the surface. The result is not a warming of the body, but an increased loss of heat at the surface.

Ethanol metabolism occurs mainly in the liver and proceeds by oxidation in two steps, first to acetaldehyde (CH₃CHO) and then to acetic acid (CH₃CO₂H). When continuously present in the body, ethanol and acetaldehyde are toxic, leading to the devastating physical and metabolic deterioration seen in people with chronic alcohol use disorder. The liver usually suffers the worst damage since it is the major site of alcohol metabolism.

Approximately 17,000 people are killed each year in the United States in alcohol-related automobile accidents. Thus, all 50 states have made it illegal to drive with a blood alcohol concentration (BAC) above 0.08%. Fortunately, simple tests have been devised for measuring blood alcohol concentration. The original breath analyzer test measured alcohol concentration in expired air by the colour change occurring when the bright-orange oxidizing agent potassium dichromate (K₂Cr₂O₇) reduced to blue-green chromium(III). Current consumer devices use a conductivity sensor, and tests used by law-enforcement agencies use IR spectroscopy to measure blood-alcohol levels in expired air. Just breathe into the machine, and let the spectrum tell the tale.

Source: “Ethanol: Chemical, Drug & Poison” is adapted from “Ch. 17 Chemistry Matters—Ethanol: Chemical, Drug, and Poison” In Organic Chemistry (OpenStax), CC BY-NC-SA 4.0.

Exercise 23.4a

Write an equation for the oxidation of each alcohol. Use [O] above the arrow to indicate an oxidizing agent. If no reaction occurs, write “no reaction” after the arrow.

3 images from left to right: a) a 6 carbon chain with an OH and a methyl group at the 3rd carbon; a 4 carbon chain with an OH at the 1st carbon and a methyl group at the 3rd carbon and lastly; c) a 6 carbon chain with an OH group at the 3rd carbon and a methyl group at the 2nd carbon. — (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

Check Your Answers:^[1]

Source: Exercise 23.4a is adapted from Introduction to Chemistry: GOB (V. 1.0)., CC BY-NC-SA 3.0 with solution images by Samantha Sullivan Sauer using Biovia Draw.

Elimination – Dehydration Reactions

Formation of Alkenes

As noted in Figure 24.3a., an alcohol undergoes dehydration in the presence of a catalyst to form an alkene and water or an ether and water. It all depends on the conditions.

To form an alkene, the reaction requires a higher temperature and limited supply of alcohol. The reaction removes the OH group from the alcohol carbon atom and a hydrogen atom from an adjacent carbon atom in the same molecule (Figure 24.3e.):

Structural formula of ethanol dehydrating under excess concentrated sulfuric acid at 180 degrees celsius. The products are ethylene and a side product of a water molecule. — **Figure 23.4e.** Elimination of water (dehydration) from an alcohol to form an alkene. (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

The required dehydration reaction temperature is dependent on the classification of the starting alcohol. The needed temperature decreases with increasing substitution of the hydroxy-containing carbon:

1° alcohols: 170° – 180°C
2° alcohols: 100°– 140 °C
3° alcohols: 25°– 80°C

If the reaction is not sufficiently heated, the alcohols do not dehydrate to form alkenes, but react with one another to form ethers.

Example 23.4b

Draw the product of the dehydration of cyclohexanol.

Solution:

Cyclohexene is formed. The dehydration of cyclohexanol to produce a cyclohexene and water in the presence of phosphoric acid and a temperature between 373-384 Kelvin. .

Example and image source: Supplemental Modules (Organic Chemistry), CC BY 4.0

Zaitsev’s Rule

When an unsymmetrical alcohol undergoes dehydration to form an alkene, Zaitsev’s rule applies. According to Zaitsev’s rule, formulated in 1875 by the Russian chemist Alexander Zaitsev, elimination reactions generally (although not always) give the more stable alkene product—that is, the alkene with more alkyl substituents on the double-bond carbons. Another way to say this is the more highly-substituted double bond isomer is favoured among the products.

Dehydration of unsymmetrical secondary alcohol (2-methyl, 3-pentanol) showing major product (2-methyl-2-pentene) and minor product (2-methyl, 3-pentene) according to Zaitsev's rule. — **Figure 23.4f.** Dehydration of unsymmetrical secondary alcohol showing major and minor product according to Zaitsev’s rule. (credit: *Supplemental Modules (Organic Chemistry)*, CC BY-NC-SA 4.0)

Exercise 24.3b

Draw the major product of the given reactions.

The dehydration of secondary alcohols using acid as a catalyst. From top to bottom a) a 6 carbon chain with a dimethyl at the 2nd carbon and an OH at the 3rd carbon; b) a 5 carbon chain with an OH at the 2nd carbon; and lastly c) a 3 carbon chain with an OH at the 2nd carbon.

Check Your Answers:^[2]

Source: Exercise 24.3b is adapted from Organic Chemistry (Wade), images created by Samantha Sullivan Sauer using Biovia Draw, licensed under CC BY-NC-SA 4.0.

Formation of Ethers

Under the proper conditions (lower temperature and excess alcohol), it is possible for the dehydration to occur between two small primary alcohol molecules. The entire OH group of one molecule and only the hydrogen atom of the OH group of the second molecule are removed. The two ethyl groups attached to an oxygen atom form an ether molecule (Figure 23.4g.). Only symmetrical ethers can be prepared this way.

Two molecules of ethanol are dehydrated under concentrated sulfuric acid at 140 degrees celsius and excess ethanol to give a diethyl ether and a water molecule. — **Figure 23.4g.** Elimination of water from two alcohol molecules to form an ether. (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

Example 23.4c

Write the two potential reactions from the dehydration of ethanol.

Solution:

The success of the dehydration reaction is dependent on the temperature and the amount of alcohol present. The two possible reactions are shown. You are not responsible for knowing the temperatures required.

Both reactions are dehydration reactions using sulfuric acid and result in a by-product of water. The first reaction (at lower temperature) combines two ethanol molecules to form diethyl ether (ethoxyethane). The second reaction (at higher temperature and limited alcohol) dehydrates intramolecularly resulting in ethene.

The first reaction (at lower temperature) combines two ethanol molecules to form diethyl ether (ethoxyethane). The second reaction (at higher temperature and limited alcohol) dehydrates intramolecularly resulting in ethene.

Example and image source: Synthesis of Ethers, CC BY-NC-SA 4.0

Both dehydration and hydration reactions occur continuously in cellular metabolism, with enzymes serving as catalysts and at a temperature of about 37°C. The following reaction occurs in the “Embden–Meyerhof” pathway (Figure 23.4h.).

Structural formula of 2 phosphoglycerate forming phosphoenolpyruvate and a water molecule with the aid of enzymes. — **Figure 23.4h.** Dehydration of 2-phosphoglycerate into phosphoenolpyruvate. (Credit: *Introduction to Chemistry: GOB (V. 1.0).*, CC BY-NC-SA 3.0.)

Although the participating compounds are complex, the reaction is the same: elimination of water from the starting material. The idea is that if you know the chemistry of a particular functional group, you know the chemistry of hundreds of different compounds.

Esterification

Carboxylic acids can react with alcohols to form esters in a process called Fischer esterification. An acid catalyst is required and the alcohol is also used as the reaction solvent. The oxygen atoms are colour-coded in the reaction below to help understand the reaction mechanism.

For example, butanoic acid reacts with methanol to synthesize methyl butanoate. It is important to note that any proton source can be used as the catalyst. Sulfuric acid is shown in the example (Figure 23.4j.).