Organic Chemistry 101: Alcohols

“-ol”

For example, ethanol is an ethane chain with a single hydroxyl group replacing one hydrogen. “Ethane-ol” gives us its name, ethanol.

“-diol”

For example, methanediol is a methane molecule with two hydroxyl groups replacing two hydrogens. “Methane-diol” gives us its name, methanediol.

An alcohol is designated by the prefix “hydroxy.”

For example, 1-hydroxypropanone is a propane chain with a carbonyl group on its central carbon (a ketone) and a hydroxyl group on its first carbon. “1-hydroxyl-propane-ketone” gives us its name, 1-hydroxypropanone.

A terminal hydroxyl group is called a primary alcohol.

Primary alcohols are bound to primary carbons, which are carbons that are attached to only one other carbon atom.

For example, 1-propanol consists of a propane chain with one hydroxyl group bound to its first carbon.

A non-terminal hydroxyl group in the middle of a straight carbon chain must be bound to a secondary carbon. For this reason, it is called a secondary alcohol.

For example, 2-propanol consists of a propane chain with one hydroxyl group bound to its second carbon.

A hydroxyl group at the intersection of three carbon chains must be bound to a tertiary carbon. For this reason, it is called a tertiary alcohol.

For example, 2-methylbutanol consists of a butane chain with one hydroxyl group bound to its second carbon, which is also attached to a methyl group.

This molecule is 1-propanol, a primary alcohol.

This molecule is 2-butanol, a secondary alcohol.

This molecule is 1,3-butanediol. As a diol, it contains two hydroxyl groups, one of which is primary and one of which is secondary.

This molecule is 2-methyl-2-butanol, a tertiary alcohol.

Alcohols are able to undergo hydrogen bonding.

Remember that any molecule that contains a hydrogen attached to F, N, or O is able to hydrogen bond. While hydrogen bonding is stronger than dipole-dipole or London dispersion forces, it is much weaker than any intramolecular bond.

The alcohol has a higher boiling point.

Alcohols undergo hydrogen bonding, while alkanes can only exert London dispersion forces. When molecular size is similar, intermolecular attractive forces determine the relative boiling point difference between two molecules.

The alcohol will have a higher boiling point.

Alcohols undergo hydrogen bonding, while aldehydes can only exert dipole-dipole interactions. When molecular size is similar, intermolecular attractive forces determine the relative boiling point difference between two molecules.

Methanol has a lower boiling point than water.

Both water and methanol can undergo hydrogen bonding. However, each water molecule has two hydrogens bound to its oxygen atom, allowing it to possess twice as many hydrogen bonds than methanol per molecule. More hydrogen bonding always increases the intermolecular attractive forces, which causes the boiling point to rise.

Increased branching decreases the boiling point of an alcohol.

Branching decreases boiling point in general, not just for alcohols. The added branches reduce the surface area available for attractive intermolecular forces.

From lowest to highest:

1. tert-butyl alcohol (83°C)

2. isobutanol (108ºC)

3. n-butanol (118ºC).

Increased branching decreases the boiling point of any carbon-based organic compound. The highly branched tert-butyl alcohol, then, must have a significantly lower boiling point than the unbranched n-butanol.

From lowest to highest:

1. 2,3-dimethyl-2-butanol (119ºC)

2. 3-methyl-2-pentanol (134ºC)

3. 1-hexanol (158ºC).

Increased branching decreases the boiling point of any carbon-based organic compound. The highly branched 2,3-dimethyl-2-butanol, then, must have a significantly lower boiling point than the unbranched 1-hexanol.

While you should be able to draw the structures of molecules like this given the names, those structures are included below for reference.

Between already-branched alcohols, increased branching tends to increase the melting point, as long as the branching creates a more compact structure.

Branching increases melting point in general, not just for alcohols. The added branches makes the molecule’s shape more compact and easier to stack into a solid.

Tert-buyl alcohol

Branching tends to increase the melting point, since the added branches make the shape more compact and easier to fit into a solid structure. Straight-chain (unbranched) molecules are not included in this general rule.

The alcohol group will be protonated.

If an environment is sufficiently acidic, it will add an additional proton to the alcohol’s oxygen atom, turning the -OH group into an -OH2+ group. As a water molecule, this protonated alcohol is an effective leaving group. For this reason, protonation is the first step in many reactions that involve alcohols.

tertiary substituted product

For example, if the nucleophile was Br-, the product will be a tertiary alkyl bromide.

The acidic environment protonates the -OH group, turning it into -OH2+, which is an effective leaving group. Since the leaving group is bound to a tertiary carbon, it must dissociate spontaneously via an SN1 reaction. This generates a carbocation, which is later attacked by the nucleophile, forming a tertiary substituted product.

2-bromo-tert-butane

Since the leaving group is bound to a tertiary carbon, this reaction must occur via an SN1 mechanism; SN2 reactions do not occur with tertiary reactants. Bromine, the nucleophile, will simply substitute in for the -OH group.

Rate = kobs [C4H9OH]

Since the leaving group is bound to a tertiary carbon, this must be an SN1 reaction. SN1 reactions are unimolecular, meaning that they depend only on the original substrate (tert-butanol), not the nucleophile (Br-).

primary substituted product

For example, if the nucleophile was Br-, the product will be a primary alkyl bromide.

The acidic environment protonates the -OH group, turning it into -OH2+, which is an effective leaving group. The electrophilic carbon bound to this group is attacked by the nucleophile, and the -OH2+ is displaced via an SN2 reaction mechanism. Note that primary substrates cannot undergo SN1 reactions.

1-bromopropane

Since the leaving group is bound to a primary carbon, this reaction must occur via an SN2 mechanism; SN1 reactions do not occur with primary reactants. Bromine, the nucleophile, will simply substitute in for the -OH group.

Rate = kobs [C3H7OH] [HBr]

Since the leaving group is bound to a primary carbon, this must be an SN2 reaction. SN2 reactions are bimolecular, meaning that they depend on both the original substrate (1-propanol) and the nucleophile (the Br- in HBr).

Common oxidizing agents include:

• the chromium reagents (CrO3, CrO42-, Cr2O72-)

• permanganate (MnO4-) and manganate (MnO42-)

• nitric acid (HNO3)

• pyridinium chlorochromate (PCC)

Remember that oxidizing agents generally contain many oxygen atoms. Reducing agents usually contain many hydrogen atoms.

• aldehyde

• carboxylic acid

Broadly, oxidation involves the gain of bonds to oxygen or the loss of bonds to hydrogen. Weak oxidizing agents like PCC will only convert a primary alcohol to an aldehyde, while strong oxidizing agents like dichromate will oxidize one step further to a carboxylic acid.

ketone

Broadly, oxidation involves the gain of bonds to oxygen or the loss of bonds to hydrogen. Here, two bonds on the central carbon are already used to connect to other carbons; even a very strong oxidizing agent will not be able to break these. A carboxylic acid group cannot be produced from this starting material.

None. The initial tertiary alcohol will remain unreacted.

Broadly, oxidation involves the gain of bonds to oxygen or the loss of bonds to hydrogen. Here, three bonds on the central carbon are already used to connect to other carbons; even a very strong oxidizing agent will not be able to break these.

Pentanal, an aldehyde.

As a comparatively weak oxidizing agent, PCC only converts primary alcohols to aldehydes, not to carboxylic acids.

Pentanoic acid, a carboxylic acid.

Like most of the chromium reagents (but unlike PCC), CrO42- is a strong oxidizing agent. It will convert primary alcohols all the way to carboxylic acids, which are as oxidized as possible.

Pinacol rearrangement

In a Pinacol rearrangement, whichever -OH group that will yield a more stable carbocation (tertiary or secondary) is protonated and leaves. One of the alkyl chains then rearranges to take its place. This allows the remaining -OH group to form a double bond to carbon (creating a carbonyl) and lose its proton to solution.

3,3-methyl-butan-2-one

Since the original molecule is a diol with hydroxyl groups on adjacent carbons, this reaction proceeds via a Pinacol rearrangement. The final product results from one of the methyl groups shifting to replace the protonated hydroxyl group that left. The remaining hydroxyl has been converted to a ketone.

A protecting group must be added to modify the reactive functional group. This group will then be removed in a final work-up step.

For example, the reducing agent LAH converts carbonyls into alcohols. Imagine a case where an ester must be reduced without removing its carbonyl group. If the carbonyl is first converted into an acetal (a protecting group), then it will not react with LAH. The acetal can later be removed by reacting it with aqueous acid.

protection step

Protection is the conversion of a highly reactive substituent into a more stable and less reactive group, allowing the original substituent to be recovered later.

deprotection step

Deprotection is the final work-up in which the protected group is converted back into the original substituent.

Alkyl halide (specifically, an alkyl chloride). In such a molecule, the -OH group is replaced with -Cl.

HCl and SO2 are side products in this reaction.

• The main product is ethyl chloride.

• The side products include HCl and SO2.

When an alcohol is reacted with thionyl chloride, the -OH group will be replaced with -Cl, creating hydrochloric acid and sulfur dioxide as side products.

Alkyl halide (specifically, an alkyl bromide). In such a molecule, the -OH group is replaced with -Br.

HBr and HP(O)(OH)2 are side products in this reaction. Note that three alcohol molecules are necessary to fully react with one PBr3 molecule.

• The main product is ethyl bromide

• The side product is HP(O)(OH)2.

When an alcohol is reacted with phosphorus tribromide, the -OH group on three alcohol molecules will be replaced with -Br, creating HP(O)(OH)2 as a side product.

This reaction results in an alkyl halide, which is very reactive. For this reason, it can be a useful initial step to perform instead of directly converting an alcohol to a different group.

Alkyl halides are especially reactive because Cl-, Br-, and I- are excellent leaving groups. Note that F-, due to its small size, is a much poorer leaving group than the other halogens.

A mesylate ester will form. In this molecule, the -H of the -OH group is replaced with -CH3SO2.

Side products include the Cl- ion and the conjugate acid of the base used.

• The main product is ethyl mesylate.

• The side products include Cl- and the conjugate acid of the base used.

When an alcohol is reacted with methanesulfonate, a mesylate ester is formed. In such a molecule, the -OH group is replaced with -CH3SO2.

A tosylate ester will form. In this molecule, the -OH group is replaced with -CH3C6H4SO2.

HCl will also form as a side product.

• The main product is ethyl tosylate.

• The side product is also formed as HCl.

When an alcohol is reacted with toluenesulfonyl chloride, a tosylate ester is formed. In such a molecule, the alcohol -OH group is replaced with -CH3C6H4SO2.

These reactions result in either a tosylate or a mesylate, respectively. Both compounds are very reactive, so this can be a useful initial step to perform instead of directly converting an alcohol to a different group.

These products are especially reactive because the large, stable structures of mesylates and tosylates make them excellent leaving groups.

The reactants are an alcohol and a carboxylic acid in the presence of a dehydrating agent. The products are an ester and water.

This reaction can be favored by using the alcohol in excess, by using a strong dehydrating agent (such as sulfuric acid), or by physically removing water from the solution.

• The major product is ethyl ethanoate.

• Water is also formed as a side product.

When an alcohol is reacted with a carboxylic acid and a dehydrating agent, an ester is formed. The alcohol -OH group attacks the carbonyl carbon; the proton from the alcohol is then transfered to the hydroxyl group on the carboxylic acid, which leaves as water.

Esters can be formed from acyl chlorides or acid anhydrides. These reactions occur as follows:

• An alcohol is reacted with an acyl chloride, ideally in anhydrous conditions. This produces an ester and HCl.

• An alcohol is reacted with an acid anhydride, ideally in anhydrous conditions. This produces an ester and a carboxylic acid.

Anhydrous conditions are preferred because both acyl chlorides and acid anhydrides also react with water.

• The main product is propyl ethanoate.

• HCl is also formed as a side product.

Remember that an alcohol reacted with an acyl chloride in an anhydrous environment will produce an ester and HCl.

• The main product is propyl propanoate.

• Propanoic acid is also formed as a side product.

Remember that an alcohol reacted with an acid anhydride in an anhydrous environment will produce an ester and a carboxylic acid.

• Inorganic esters form from inorganic acids.

• Organic esters form from organic acids.

In general, esters form from the condensation of an acid and an alcohol.

Specifically, an inorganic ester is an oxo compound in which the oxygen is double-bound to a heteroatom such as phosphorus, sulfur, or nitrogen.

This molecule is an inorganic ester, or more specifically, a phosphoric acid ester.

"Ester" is a general term for the condensation product of an acid and an alcohol. An inorganic ester simply has its "carbonyl" oxygen double-bonded to a heteroatom such as phosphorus, sulfur, or nitrogen.

• The main product is triphenyl phosphate ester.

• Water is also formed as a side product.

"Ester" is a general term for the condensation product of an acid and an alcohol. The -OH groups on phosphoric acid are protonated by the attacking alcohol and leave as water. This process repeats for each of the three -OH groups, until three phenyl groups have been added to form this inorganic ester.

Alcohols are more acidic than esters, aldehydes, and ketones, but less acidic than carboxylic acids.

This general trend assumes that other factors, like size and inductive effect, are similar.

Note that the most acidic hydrogen atom on esters, aldehydes, and ketones is the alpha proton.

From least to most acidic: C, B, A.

In general, and assuming similar size/structure/induction, esters are the least acidic, followed by aldehydes/ketones and alcohols. Carboxylic acids are the most acidic of the compounds shown.