Chapter 12 - Alcohols and Phenols Flashcards
What is the medical term for a hangover?
Veisalgia
What are common symptoms of a hangover?
- Headache
- Nausea
- Vomiting
- Fatigue
- Heightened sensitivity to light and noise
What are some factors that contribute to hangovers?
- Dehydration
- Loss of vitamin B
- Production of acetaldehyde
What is acetaldehyde?
A product of the oxidation of ethanol
What is the general structure of alcohols?
Compounds that possess a hydroxyl group (OH) connected to an sp3-hybridized carbon atom
How are alcohols typically named?
By replacing the suffix ‘e’ in the parent name with ‘ol’
What is a phenol?
A compound that exhibits an OH group connected directly to a phenyl ring
What is the naming rule for cyclic alcohols?
Cyclic alcohols are numbered starting at the position bearing the hydroxyl group
What differentiates primary, secondary, and tertiary alcohols?
The number of alkyl groups attached directly to the alpha (α) position
What is the systematic name for n-propyl alcohol?
1-propanol
What is the simplest alcohol?
Methanol (CH3OH)
What is ethanol commonly known as?
Grain alcohol
What process is used to prepare ethanol industrially?
Acid-catalyzed hydration of ethylene
What is the boiling point of ethanol?
78°C
Why does ethanol have a higher boiling point than ethane and chloroethane?
Due to hydrogen-bonding interactions between ethanol molecules
What does miscible mean in relation to alcohols?
Alcohols can be mixed with water in any proportion without separating into layers
What is the difference between soluble and miscible?
Soluble refers to the ability to dissolve in a specific amount, while miscible means mixing in any proportion
What happens to the solubility of alcohols as the size of the hydrophobic region increases?
Solubility in water decreases
What is the antibacterial property trend for primary alcohols?
Antibacterial potency increases with molecular weight up to eight carbon atoms
Which alcohol is used as rubbing alcohol?
Isopropanol
What is the common name for 1-butanol?
n-butyl alcohol
What are the four steps required to name alkanes, alkenes, and alkynes?
- Identify and name the parent
- Identify and name the substituents
- Assign a locant to each substituent
- Assemble the substituents alphabetically
When naming alcohols, how should the position of the hydroxyl group be indicated?
Using a locant placed before the parent name
What is the importance of the hydroxyl group in alcohol nomenclature?
It indicates the presence of the hydroxyl group by changing the suffix to ‘ol’
What is the common name for 2-propanol?
Isopropyl alcohol
How does the presence of a chiral center affect alcohol nomenclature?
The configuration must be indicated at the beginning of the name
What distinguishes n-propyl from isopropyl alcohol?
n-propyl is linear while isopropyl is branched
What is the potency of n-nonanol compared to n-octanol?
n-nonanol is less potent than n-octanol
n-dodecanol (12 carbon atoms) has very little potency.
How does chain branching affect the potency of alcohols?
Chain branching decreases the ability of an alcohol to penetrate cell membranes, making isopropanol less potent than n-propanol.
Why is isopropanol used over n-propanol despite its lower potency?
Isopropanol is less expensive to produce than n-propanol.
What is the optimal chain length for antibacterial agents?
The optimal chain length is found to be between five and nine carbon atoms.
What effect does a larger alkyl chain have on an alcohol’s ability to penetrate microbial membranes?
A larger alkyl chain increases the ability to penetrate microbial membranes.
What happens to the potency of alcohols as their alkyl chain becomes larger than eight carbon atoms?
Potency decreases steeply as alkyl chain length exceeds eight carbon atoms.
What is hexylresorcinol and its properties?
Hexylresorcinol is a bactericidal and fungicidal agent used in throat lozenges.
What is the role of resonance in the acidity of alcohols?
Resonance stabilizes the conjugate base, making phenol more acidic than cyclohexanol.
What is the pKa value range for most alcohols?
The pKa for most alcohols falls in the range of 15–18.
What is the conjugate base of an alcohol called?
The conjugate base of an alcohol is called an alkoxide ion.
What are two common ways to deprotonate an alcohol?
- Use a strong base like sodium hydride (NaH)
- Treat with Li, Na, or K.
What is the effect of induction on the acidity of alcohols?
Induction can stabilize the conjugate base, increasing acidity, as seen in trichloroethanol compared to ethanol.
How does steric hindrance affect the acidity of tert-butanol compared to ethanol?
tert-Butanol is less acidic than ethanol due to steric hindrance, which reduces solvation of the conjugate base.
What is the relationship between acidity and pKa?
A strong acid has a low pKa value.
What type of reactions can produce alcohols?
Alcohols can be prepared by substitution or addition reactions.
What is the effect of alkyl branching on the acidity of ethanol and tert-butanol?
Ethanol is more acidic than tert-butanol due to greater solvation of the ethoxide ion.
What are the reagents used in acid-catalyzed hydration to produce alcohols?
Dilute H2SO4 and water.
What is the purpose of oxymercuration-demercuration in alcohol synthesis?
It allows Markovnikov addition without carbocation rearrangement.
What is an example of a compound with three acidic hydroxyl groups?
Naringenin.
What is the effect of resonance on the acidity of phenols compared to alcohols?
Resonance in phenols makes them significantly more acidic than alcohols.
What is the relationship between oxidation states and formal charges?
Oxidation states refer to electron bookkeeping, while formal charges treat bonds as purely covalent.
What is an oxidation state?
A method of electron bookkeeping that treats all bonds as purely ionic.
How is formal charge calculated?
By treating all bonds as purely covalent and breaking them homolytically.
What are the two extreme methods of electron bookkeeping?
- Formal charge * Oxidation state
What is the oxidation state of a carbon atom with four bonds?
Can range from −4 to +4.
When is a reaction called oxidation?
When there is an increase in the oxidation state of a carbon atom.
When is a reaction called reduction?
When there is a decrease in the oxidation state of a carbon atom.
What is a reducing agent?
A substance that donates electrons in a reduction reaction.
What is the common reducing agent used to reduce ketones or aldehydes?
Sodium borohydride (NaBH4).
What is the mechanism of action for sodium borohydride?
Involves hydride transfer to the carbonyl group followed by proton transfer.
What happens to the geometry of a carbon atom during nucleophilic attack by hydride?
Changes from sp2-hybridized with trigonal planar geometry to sp3-hybridized with tetrahedral geometry.
What is lithium aluminum hydride commonly abbreviated as?
LAH.
What is the main difference between NaBH4 and LiAlH4?
LiAlH4 is a much stronger reducing agent and reacts violently with protic solvents.
What type of reaction does NaBH4 not typically reduce?
Esters under mild conditions.
Fill in the blank: A reaction involving an increase in the oxidation state of a carbon atom is called _____
[oxidation]
Fill in the blank: A reaction involving a decrease in the oxidation state of a carbon atom is called _____
[reduction]
What is the product of reducing a ketone or aldehyde with NaBH4?
An alcohol.
True or False: Both NaBH4 and LiAlH4 can reduce ketones or aldehydes.
True.
What is the result of reducing an unsymmetrical ketone with NaBH4?
A racemic mixture of enantiomers.
What happens during the workup step when using LiAlH4?
A proton source is added to protonate the alkoxide ion.
What does the mechanism of LiAlH4 reduction involve?
- Nucleophilic attack * Loss of a leaving group * Proton transfer
What type of bond does NaBH4 selectively reduce in the presence of a C=C bond?
Only the carbonyl group.
What is the role of the solvent in the reduction reaction with sodium borohydride?
Functions as the source of a proton (H+).
What is the significance of the electronegativity in calculating oxidation states?
Electrons are assigned to the more electronegative atom.
What is the oxidation state of carbon in formaldehyde?
0.
What is the oxidation state of carbon in methanol?
-2.
What happens to the carbonyl group during the reduction process?
It is attacked by hydride and then protonated to form an alcohol.
What is produced when the alkoxide ion is protonated?
An alcohol.
What does LiAlH4 deliver to the carbonyl group?
Hydride.
What is the nature of the intermediate after the first attack of hydride?
High-energy and exhibits a negatively charged oxygen atom.
Why can methoxide function as a leaving group in this reaction?
The intermediate is high in energy, allowing for the ejection of methoxide.
What type of mixture is produced during the reduction of a ketone?
A racemic mixture of enantiomers.
What are the two steps in the mechanism of hydride reductions?
- Nucleophilic attack
- Proton transfer
What is the suffix added to the name of diols?
diol.
What are two common names for simple diols?
- Ethylene glycol
- Propylene glycol
How can diols be prepared from diketones?
Via reduction using reducing agents.
What is the role of antifreeze in automobiles?
To prevent damage caused by overheating.
What is a Grignard reagent formed from?
The reaction between an alkyl halide and magnesium.
What characterizes a Grignard reagent?
The presence of a C–Mg bond.
What happens when a Grignard reagent reacts with water?
It is destroyed.
What type of proton source is typically used in the workup of a Grignard reaction?
H3O+ or H2O.
What is a limitation of Grignard reagents with respect to carboxylic acids?
They cannot attack the carbonyl group of a carboxylic acid.
What happens when a Grignard reagent reacts with an ester?
It produces an alcohol with the introduction of two R groups.
What is the mechanism when a Grignard reagent reacts with a ketone or aldehyde?
- Nucleophilic attack
- Proton transfer
What is the expected product when a ketone is reduced by a Grignard reagent?
An alcohol.
What is the effect of the electronegativity difference between carbon and magnesium in a Grignard reagent?
The bond can be treated as ionic.
What type of products are formed from the reduction of a chiral compound with a carbonyl group?
Diastereomeric products.
Fill in the blank: Diols are compounds with two _______ groups.
hydroxyl
What is the significance of the ‘e’ in the naming of diols?
It appears between the parent and the suffix.
What must be avoided when working with Grignard reagents?
Presence of water.
What happens during the workup step of a Grignard reaction?
The alkoxide ion is protonated.
What is an electrophile?
An electrophile is a species that accepts an electron pair from a nucleophile during a chemical reaction.
What is a nucleophile?
A nucleophile is a species that donates an electron pair to an electrophile in a chemical reaction.
What role does the α carbon play in the reaction involving a carbonyl group?
The α carbon in the target molecule has an attached OH group, indicating it used to be a carbonyl carbon.
In the context of Grignard reactions, what is the significance of the carbonyl group?
The carbonyl group serves as the electrophilic component in the desired C-C bond-forming reaction.
What is a Grignard reagent?
A Grignard reagent is an organomagnesium compound that acts as a nucleophile in reactions.
What are the three possible retrosyntheses revealed in the analysis?
The retrosyntheses involve starting with a ketone and introducing a third group as a Grignard reagent.
True or False: Synthesis problems often have only one correct answer.
False. Synthesis problems often have more than one correct answer.
When reacting a Grignard reagent with an ester, how many equivalents are typically required?
Typically, two equivalents of a Grignard reagent are required when reacting with an ester.
Why might three equivalents of a Grignard reagent be required in certain reactions?
A third equivalent may be needed due to the presence of multiple functional groups that react with the Grignard reagent.
What is the purpose of protecting an alcohol group in a Grignard reaction?
The alcohol group is protected to prevent it from reacting with the Grignard reagent.
Define a protecting group.
A protecting group is a moiety that replaces an acidic proton to prevent reaction during a chemical process.
What is the trimethylsilyl group abbreviated as?
TMS.
How is an alcohol’s OH group converted into an OTMS group?
The conversion is achieved by treatment with trimethylsilyl chloride (TMSCl).
What is a notable characteristic of the SN2-like process involving TMS?
The hydroxyl group behaves as a nucleophile attacking the silicon atom, expelling a chloride ion.
What is tetrabutylammonium fluoride (TBAF) used for?
TBAF is commonly used as a source of fluoride ion to remove protecting groups.
How is phenol industrially prepared?
Phenol is prepared via a multistep process involving the formation and oxidation of cumene.
Which compounds are commonly derived from phenol?
- Synthetic polymers
- Pharmaceuticals
- Adhesives for plywood
- Antioxidant food additives (BHT and BHA)
What mechanism do tertiary alcohols undergo when treated with a hydrogen halide?
Tertiary alcohols undergo an SN1 mechanism.
What is the outcome of an SN1 mechanism involving alcohols?
The outcome is the formation of a carbocation intermediate.
What type of alcohols typically undergo SN2 reactions?
Primary and secondary alcohols.
What reagent can convert a hydroxyl group into a tosylate?
Tosyl chloride (TsCl) in the presence of pyridine.
What is the effect of converting an alcohol into a tosylate during SN2 reactions?
It results in an excellent leaving group that enables nucleophilic attack.
What reagents can be used to convert alcohols into alkyl halides?
- SOCl2
- PBr3
- TsCl with pyridine
What is the expected stereochemical outcome when an SN2 reaction occurs at a chiral center?
Inversion of configuration is expected.
Identify the first step in converting an alcohol into an alkyl halide via SN2.
Convert the hydroxyl group into a better leaving group.
What is a common issue when using HCl with alcohols in substitution reactions?
HCl is not effective for alcohols that are not water-soluble.
What type of reaction mechanism do primary alcohols undergo with HBr?
Primary alcohols undergo an SN2 process.
What are tunicates commonly referred to as?
Sea squirts
What is lepadi- formine?
A cytotoxic agent isolated from a marine tunicate
What is drug metabolism?
The set of reactions by an organism that converts drugs into other compounds
What is glucuronidation?
A common metabolic pathway where a bad leaving group is converted into a good leaving group followed by nucleophilic attack
What does UDPGA stand for?
Uridine-5’-diphospho-α-D-glucuronic acid
What is the role of UDP in glucuronidation?
UDP is a good leaving group formed from UDPGA
Which enzyme is required for the glucuronidation process?
UDP-glucuronyl transferase
What type of compounds commonly undergo glucuronidation?
Alcohols and phenols
What are three examples of drugs metabolized via glucuronidation?
- Morphine * Acetaminophen * Chloramphenicol
What is the E1 mechanism?
A mechanism where the core steps are loss of a leaving group followed by proton transfer
What type of alcohols undergo E1 elimination reactions?
Tertiary alcohols
What is the main product of oxidizing a primary alcohol?
A carboxylic acid
What is the oxidation product of a secondary alcohol?
A ketone
What happens to tertiary alcohols during oxidation?
They generally do not undergo oxidation
What common oxidizing reagent is used for oxidizing alcohols?
Chromic acid (H2CrO4)
How can aldehydes be selectively produced from primary alcohols?
Using pyridinium chlorochromate (PCC)
What are the two stages in the mechanism of chromic acid oxidations?
- Formation of a chromate ester * E2 process to form a carbon-oxygen π bond
What are the by-products of chromium-based oxidations?
Chromium salts that are hazardous
What is the Swern oxidation?
An oxidation method using dimethyl sulfoxide (DMSO) and oxalyl chloride
What is the Dess–Martin periodinane (DMP) oxidation?
An oxidation method that converts primary alcohols into aldehydes and secondary alcohols into ketones
What conditions does DMP-based oxidation operate under?
Nonacidic conditions and can be achieved at room temperature
What is the significance of the α position in alcohol oxidation?
It determines how many times an alcohol can be oxidized
Fill in the blank: Alcohols can be formed via a _______ process.
Reduction
True or False: Tertiary alcohols can be oxidized to form ketones.
False
What is the first step in predicting the product of an oxidation reaction involving an alcohol?
Identify whether the alcohol is primary or secondary.
What is the outcome when a primary alcohol is oxidized with chromium trioxide in acidic conditions?
Carboxylic acid.
Which two reagents can be used to stop oxidation at the aldehyde stage?
- PCC
- Swern oxidation
- DMP-based oxidation
What are two greener alternatives to chromium-based oxidations?
- Swern oxidation
- DMP-based oxidation
What is a significant disadvantage of Swern oxidation?
Produces a foul-odored by-product (dimethyl sulfide, DMS).
What is the reactive center in NADH responsible for?
Functions as a hydride delivery agent.
What happens when NADH is oxidized?
It is converted to NAD+.
What role do NADH and NAD+ play in the citric acid cycle?
NAD+ is converted to NADH, storing energy.
What is the process of converting ADP to ATP called?
ATP synthesis.
What is methanol oxidized to in the body?
- Formaldehyde
- Formic acid
What enzyme catalyzes the oxidation of methanol?
Alcohol dehydrogenase.
What is the consequence of a methanol overdose?
Buildup of formic acid can lead to blindness and organ failure.
What does ethanol oxidize to during metabolism?
- Acetaldehyde
- Acetic acid
What are the unpleasant effects of binge drinking primarily caused by?
Buildup of acetaldehyde.
What product is formed from the oxidation of phenol?
Benzoquinone.
What is hydroquinone derived from?
Reduction of benzoquinone.
What is the significance of quinones in cellular respiration?
They are involved in converting molecular oxygen into water.
Who proposed the idea that ATP synthesis could be driven by a battery-like force?
Peter Mitchell.
What are the two main issues to consider when proposing a synthesis?
- A change in the carbon skeleton
- A change in the functional group
What is an example of a reagent that can convert an alcohol into an aldehyde?
PCC.
Fill in the blank: The process that uses NADH and NAD+ in biological systems is called ______.
redox reactions.
True or False: Acetic acid is toxic.
False.
What is the relationship between the citric acid cycle and ATP synthesis?
Energy from the citric acid cycle is used to convert ADP to ATP.
What is the classification of functional groups based on oxidation state?
Functional groups are classified into high oxidation state and low oxidation state categories.
What type of reaction is converting an alkane to an alkyl halide?
Oxidation reaction.
Does converting an alcohol to an alkyl halide involve a change in oxidation state?
No, it does not involve a change in oxidation state.
Which functional groups can interconvert without oxidation or reduction?
Alkenes, alcohols, and alkyl halides.
What is the significance of Figure 12.11 in the context of functional group interconversion?
It summarizes key reactions that allow the interconversion of functional groups.
What is a one-step conversion example in functional group interconversion?
Conversion of an alcohol into a ketone.
What does the term ‘synthetic toolbox’ refer to in this context?
A collection of methods and reagents for synthesizing various functional groups.
Fill in the blank: A Grignard reaction with an aldehyde followed by oxidation converts an aldehyde into a _______.
ketone.
How many steps are typically required to convert an alkane into a ketone?
Multiple steps.
What reducing agent is more selective than LiAlH4 but less selective than NaBH4?
Lithium borohydride (LiBH4).
What happens when an ester reacts with two equivalents of a Grignard reagent?
It forms an alcohol and two new C–C bonds.
True or False: The addition of HBr to an alkene allows for controlled regiochemistry.
False.
What is the result of a Grignard reaction with an aldehyde?
Formation of an alcohol.
List possible starting materials for making an alkyl bromide.
- Alkene
- Alcohol
What is the role of PCC in functional group transformation?
It is used to oxidize alcohols to aldehydes or ketones.
What are the methods for preparing alcohols highlighted in this chapter?
- Reduction of ketones
- Reduction of aldehydes
Identify the functional group transformation when an alcohol is oxidized.
Formation of ketones, aldehydes, or carboxylic acids.
What is the final product when an alkyne reacts with H2 in the presence of Lindlar’s catalyst?
Cis-alkene.
Fill in the blank: The conversion of an alcohol to an alkyl halide can be achieved using _______.
PBr3.
What is the effect of using DMP in functional group transformations?
It oxidizes alcohols to aldehydes or ketones.
What does retrosynthetic analysis involve?
Working backward to identify starting materials for a desired product.
What is a critical flaw in proposing a synthesis involving an alkene intermediate?
Lack of control over the regiochemistry of reactions.
What is the purpose of a ‘synthetic toolbox review’?
To summarize and integrate methods learned for functional group transformations.
What is the utility of drawing structures in synthesis problems?
To visualize intermediates and clarify the steps in the synthesis process.
What is the effect of using Na2Cr2O7 in the functional group transformation?
It oxidizes alcohols to carbonyl compounds.
