Ch 13- Alcohols.pdf

Chapter 13

13.1 Alcohols and Phenols

• Alcohols possess a hydroxyl group (-OH)

13.1 Alcohols and Phenols

• Phenols possess a hydroxyl group directly attached to an aromatic ring

13.1 Alcohols Nomenclature

• Alcohols are named using the same procedure we used in Chapter 4 to name alkanes with minor modifications 1. Identify the parent chain, which should include the carbon

that the –OH is attached to

2. Identify and Name the substituents

3. Assign a locant (and prefix if necessary) to each substituent.

Give the carbon that the –OH is attached to the lowest number possible

13.1 Alcohols Nomenclature

13.1 Alcohols Nomenclature

• Alcohols are named using the same procedure we used

in Chapter 4 to name alkanes with minor modifications

3. Assign a locant (and prefix if necessary) to each substituent.

Give the carbon that the –OH is attached to the lowest

13.1 Alcohols Nomenclature

• Alcohols are named using the same procedure we used

in Chapter 4 to name alkanes with minor modifications

5. The –OH locant is placed either just before the parent name or just before the -ol suffix

13.1 Alcohols Nomenclature

• For cyclic alcohols, the –OH group should be on carbon 1, so often the locant is assumed and omitted

13.1 Alcohols Nomenclature

• Like halides, alcohols are often classified by the type of carbon they are attached to

13.1 Alcohols Nomenclature

13.1 Alcohols Nomenclature

• Name the following molecule

13.1 Commercially Important Alcohols

• Methanol (CH₃OH) is the simplest alcohol

• With a suitable catalyst, about 2 billion gallons of

methanol is made industrially from CO₂ and H₂ every year

• Methanol is poisonous, but it has many uses

1. Solvent

2. Precursor for chemical syntheses

13.1 Commercially Important Alcohols

• Ethanol (CH₃CH₂OH) has been produced by fermentation for thousands of years. HOW?

• About 5 billion gallons of ethanol is made industrially from the acid-catalyzed hydration of ethylene every year

• Ethanol has many uses

1. Solvent, precursor for chemical syntheses, fuel

13.1 Commercially Important Alcohols

• Isopropanol is rubbing alcohol. Draw its structure

• Isopropanol is made industrially from the acid-catalyzed hydration of propylene

• Isopropanol is poisonous, but it has many uses

1. Industrial solvent

2. Antiseptic

13.1 Physical Properties of Alcohols

• The –OH of an alcohol can have a big effect on its physical properties

• Compare the boiling points below

• Because they can H-bond, hydroxyl groups can attract water molecules strongly

• Alcohols with small carbon chains are miscible in water (they mix in any ratio). WHY?

• Alcohols with large carbon chains do not readily mix with water

• Do hydrophobic groups repel or attract water?

• WHY are molecules with large hydrophobic groups generally insoluble in water?

• Alcohols with 3 or less carbons are generally water miscible

• An alcohol’s potency as an anti-bacterial agent depends on the size of the hydrophobic group

13.1 Physical Properties of Alcohols

• To kill a bacterium, the alcohol should have some water solubility. WHY?

• Hexylresorcinol is used as an antibacterial and as an antifungal agent

• It has a good combination of hydrophobic and hydrophilic regions

– It has significant water solubility

• A strong base is usually necessary to deprotonate an alcohol

• A preferred choice to create an alkoxide is to treat the alcohol with Na, K, or Li metal. Show the mechanism for such a reaction

• Recall from chapter 3 how ARIO is used to qualitatively assess the strength of an acid

• Lets apply these factors to alcohols and phenols

– Atom

• Lets apply these factors to alcohols and phenols

– Resonance

– Explain why phenol is 100 million times more acidic than cyclohexanol

– Show all relevant resonance contributors

• Given the relatively low pK_a of phenols, will NaOH be a strong enough base to deprotonate a phenol?

• Lets apply these factors to alcohols and phenols

– Induction: unless there is an electronegative group nearby, induction won’t be very significant

– Orbital: in what type of orbital do the alkoxide electrons reside? How does that effect acidity?

• Solvation is also an important factor that affects acidity

• Water is generally used as the solvent when measuring pK_a values

• Which of the alcohols below is stronger?

• ARIO cannot be used to explain the difference

• Solvation explains the difference in acidity

• Draw partial charges on the solvent molecules to show how solvation is a stabilizing effect

• Use ARIO and solvation to rank the following molecules in order of increasing pK_a

• We saw in chapter 7 that substitution reactions can yield an alcohol

• What reagents did we use to accomplish this transformation?

• The S_N1 process generally uses a weak nucleophile (H₂O), which makes the process relatively slow

• In chapter 9, we learned how to make alcohols from alkenes

• Recall that acid-catalyzed hydration proceeds through a carbocation intermediate that can possibly rearrange

• A third method to prepare alcohols is by the reduction of a carbonyl. What is a carbonyl?

• Reductions involve a change in oxidation state

• Oxidation state are a method of electron bookkeeping

• Recall how we used formal charge as a method of electron bookkeeping

– Each atom is assigned half of the electrons it is sharing with another atom

– What is the formal charge on carbon in methanol?

• For oxidation states, we imagine the bonds breaking heterolytically, and the electrons go to the more

electronegative atom

• Each of the carbons below have zero formal charge, but they have different oxidation states

• Calculate the oxidation number for each

• Is the conversion from formic acid  carbon dioxide an oxidation or a reduction?

• The reduction of a carbonyl requires a reducing agent

• Is the reducing agent oxidized or reduced?

• If you were to design a reducing agent, what element(s) would be necessary?

• Would an acid such as HCl be an appropriate reducing agent? WHY or WHY NOT?

• There are three reducing agents you should know

1. We have already seen how catalyzed hydrogenation can reduce alkenes. It can also work for carbonyls

• Reagents that can donate a hydride are generally good reducing agents

2. Sodium borohydride

• Reagents that can donate a hydride are generally good reducing agents

3. Lithium aluminum hydride (LAH)

• Note that LAH is significantly more reactive that NaBH₄

• LAH reacts violently with water. WHY?

•

• Hydride delivery agents will somewhat selectively reduce carbonyl compounds

• The reactivity of hydride delivery agents can be fine-tuned by using derivatives with varying R-groups

– Alkoxides

– Cyano

– Sterically hindered groups

• LAH is strong enough to also reduce esters and carboxylic acids, whereas NaBH₄ is generally not

• To reduce an ester, 2 hydride equivalents are needed

•

• Predict the products for the following processes

• Diols are named using the same method as alcohols, except the suffix, “diol” is used

• If two carbonyl groups are present, and enough moles of reducing agent are added, both can be reduced

• Recall the methods we discussed in chapter 9 to convert an alkene into a diol

• Grignard reagents are often used in the synthesis of alcohols

• To form a Grignard, an alkyl halide is treated with Mg metal

• The electronegativity difference between C (2.5) and Mg (1.3) is great enough that the bond has significant ionic character

• The carbon atom is not able to effectively stabilize the negative charge it carries

• If the Grignard reagent reacts with a carbonyl compound, an alcohol can result

• Note the similarities between the Grignard and LAH mechanisms

• Because the Grignard is both a strong base and a strong nucleophile, care must be taken to protect it from

exposure to water

• If water can’t be used as the solvent, what solvent is appropriate?

• Grignard examples

• With an ester substrate, excess Grignard reagent is required. WHY? Propose a mechanism

• Design a synthesis for the following molecules starting from an alkyl halide and a carbonyl, each having 5

carbons or less

• Consider the reaction below. WHY won’t it work?

• The alcohol can act as an acid, especially in the

presence of reactive reagents like the Grignard reagent

• A three-step process is required to achieve the desired overall synthesis

• One such protecting group is trimethylsilyl (TMS)

• The TMS protection step requires the presence of a base. Propose a mechanism

• Evidence suggests that substitution at the Si atom occurs by an S_N2 mechanism

• Because Si is much larger than C, it is more open to backside attack

• The TMS group can later be removed with H₃O+ _{or F}

-• TBAF is often used to supply fluoride ions

• 2 million tons of phenol is produced industrially yearly

• Acetone is a useful byproduct

• Phenol is a precursor in many chemical syntheses

– Pharmaceuticals

– Polymers

• Recall this S_N1 reaction from section 7.5

• The S_N2 reaction also occurs with ZnCl₂ as the reagent

• Recall from section 7.8 that the –OH group can be

converted into a better leaving groups such as a tosyl group

• SOCl₂ can also be used to convert an alcohol to an alkyl chloride

• PBr₃ can also be used to convert an alcohol to an alkyl bromide

• Note that the last step of the SOCl₂ and PBr₃ mechanisms are S 2

• In section 8.9, we saw that an acid (with a non-nucleophilic conjugate base) can promote E1

• Why is E2 unlikely?

• Recall that the reaction generally produces the more substituted alkene product

• If the alcohol is converted into a better leaving group, then a strong base can be used to promote E2

• E2 reactions do not involve rearrangements. WHY?

• When applicable, E2 reactions also produce the more substituted product

• We saw how alcohols can be formed by the reduction of a carbonyl

• The reverse process is also possible with the right reagents

• Oxidation of primary alcohols proceed to an aldehyde and subsequently to the carboxylic acid

– Very few oxidizing reagents will stop at the aldehyde

• Oxidation of secondary alcohols produces a ketone

• Tertiary alcohols generally do not undergo oxidation. WHY?

• There are two main methods to produce the most common oxidizing agent, chromic acid

• When chromic acid reacts with an alcohol, there are two main steps

• Chromic acid will generally oxidize a primary alcohol to a carboxylic acid

• PCC (pyridinium chlorochromate) can be used to stop at the aldehyde

• PCC (pyridinium chlorochromate) is generally used with methylene chloride as the solvent

• Both oxidizing agents will work with

secondary alcohols

• Nature employs reducing and oxidizing agents

• They are generally complex and selective. WHY?

• NADH is one such reducing agent

• The reactive site of NADH acts as a hydride delivery agent

• This is one way nature converts carbonyls into alcohols

• NAD+ _{can undergo the reverse process}

• The NADH / NAD+

interconversion plays a big role in metabolism

• Recall that tertiary alcohols do not undergo oxidation, because they lack an alpha proton

• You might expect phenol to be similarly unreactive

• Yet, phenol is even more readily oxidized than primary or secondary alcohols

• Phenol oxidizes to form benzoquinone, which in turn can be reduced to hydroquinone

• Quinones are found everywhere in nature

• They are ubiquitous

• Ubiquinones act to catalyze the conversion of oxygen into water, a key step in cellular respiration

• Where in a cell do you think unbiquinones are most likely found?

• Ubiquinone catalysis:

13.13 Synthetic Strategies

13.13 Synthetic Strategies

13.13 Synthetic Strategies

• What if you want to convert an aldehyde into a ketone?

Additional Practice Problems

• Name the following molecule

• Use ARIO and solvation to rank the following molecules in order of increasing pK_a

• Design a synthesis for the following molecule starting from an alkyl halide and a carbonyl, each having 5

carbons or less

• Give necessary reagents for the multi-step synthesis below