scoresvideos
Organic Chemistry
Table of Contents
Unit 17 Overview: Alcohols and Phenols
17.1 Naming Alcohols and Phenols
17.2 Properties of Alcohols and Phenols
17.3 Preparation of Alcohols: A Review
17.4 Alcohols from Carbonyl Compounds: Reduction
17.5 Alcohols from Carbonyl Compounds: Grignard Reaction
17.6 Reactions of Alcohols
17.7 Oxidation of Alcohols
17.8 Protection of Alcohols
17.9 Phenols and Their Uses
17.10 Reactions of Phenols
17.11 Spectroscopy of Alcohols and Phenols

Alcohols are versatile compounds that undergo various transformations. They can be converted to halides, tosylates, and alkenes through different mechanisms. Understanding these reactions is crucial for predicting product formation and stereochemistry in organic synthesis.

Alcohols also participate in esterification reactions, both in the lab and in biological systems. These processes are essential for creating important compounds like fats, oils, and certain hormones. Knowing the mechanisms and conditions for these reactions helps in designing efficient synthetic routes.

Reactions of Alcohols

Conversion of alcohols to halides

  • Primary and secondary alcohols undergo $S_N2$ mechanism
    • Strong acid (HCl, HBr, HI) protonates alcohol
    • Protonated alcohol leaves as water forming carbocation intermediate
    • Halide ion attacks carbocation forming alkyl halide product
  • Tertiary alcohols react via $S_N1$ mechanism
    • Increased carbocation stability favors $S_N1$ pathway
  • Conversion of alcohols to tosylates
    • Alcohols react with p-toluenesulfonyl chloride (TsCl) in presence of base (pyridine)
    • Base deprotonates alcohol forming alkoxide ion
    • Alkoxide ion attacks sulfur atom of TsCl displacing chloride forming tosylate product
    • Tosylates are good leaving groups used in subsequent substitution reactions

Dehydration of alcohols to alkenes

  • Acid-catalyzed dehydration (example of acid-catalyzed reactions)
    • Strong acid (H2SO4, H3PO4) and heat
    • Tertiary alcohols follow E1 mechanism
      • Protonation of alcohol, formation of carbocation intermediate, loss of proton forms alkene
    • Primary and secondary alcohols follow E2 mechanism
      • Protonation of alcohol, simultaneous loss of water and proton from adjacent carbon forms alkene
    • Zaitsev's rule predicts major product: most stable (highly substituted) alkene formed
  • Dehydration with POCl3 or SOCl2
    • Milder conditions compared to acid-catalyzed dehydration
    • Alcohol converted to alkyl chloride intermediate which undergoes elimination forming alkene
  • Cyclic alcohols can also undergo dehydration forming cycloalkenes

Alcohol to ester conversion methods

  • Laboratory methods
    • Fischer esterification: alcohol reacts with carboxylic acid in presence of acid catalyst (H2SO4, HCl) and heat
      1. Protonation of carboxylic acid
      2. Nucleophilic attack by alcohol
      3. Loss of water
      4. Deprotonation forms ester product
    • Steglich esterification: alcohol reacts with carboxylic acid in presence of DCC (dicyclohexylcarbodiimide) and DMAP (4-dimethylaminopyridine)
      • Milder conditions compared to Fischer esterification
      • DCC activates carboxylic acid forming O-acylisourea intermediate
      • Alcohol attacks intermediate forming ester
  • Biological methods
    • Esterification reactions catalyzed by enzymes called esterases
    • Esterases lower activation energy allowing esterification under physiological conditions
    • Biologically important esters: triglycerides (fats and oils), waxes, some hormones and pheromones
    • Esterases also involved in hydrolysis of esters important for digestion and metabolism of dietary fats

Reaction Mechanisms and Kinetics

  • Understanding reaction mechanisms helps predict product formation and stereochemistry
  • Reaction kinetics influence the rate and yield of alcohol reactions
  • Regioselectivity determines the preferred site of reaction in molecules with multiple functional groups
  • Alcohol structure-reactivity relationships affect the ease and products of reactions

Key Terms to Review (41)

Nucleophilic substitution reactions: Nucleophilic substitution reactions are a class of chemical reactions in organic chemistry where an electron-rich nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms to replace a leaving group. The reaction is characterized by the substitution of a nucleophile for a leaving group, which can occur via different mechanisms (SN1 or SN2).
Anti stereochemistry: Anti stereochemistry describes the spatial arrangement in a chemical reaction where two substituents are positioned on opposite sides of a double bond or ring structure after the reaction. It is particularly relevant in the halogenation of alkenes, resulting in products where the added atoms are located across from each other.
Elimination reactions: Elimination reactions are a type of organic reaction where two atoms or groups are removed from a molecule, resulting in the formation of a double bond. These reactions often involve the loss of small molecules like water or hydrogen halides from larger organic molecules.
Fischer esterification reaction: A Fischer esterification reaction is a chemical process where a carboxylic acid reacts with an alcohol in the presence of an acid catalyst to form an ester and water. It is an equilibrium process that is often driven to completion by removing the water formed during the reaction.
Stereochemistry: Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects the chemical and physical properties of the substance. It examines the spatial orientation of atoms and their relationship to one another, which is crucial in understanding many organic chemistry concepts.
Sulfuric Acid: Sulfuric acid (H2SO4) is a highly corrosive, dense, and oily liquid that is one of the most important and widely used industrial chemicals. It is a strong mineral acid that plays a crucial role in various chemical reactions and processes.
Carbocation: A carbocation is a positively charged carbon atom that is part of an organic molecule. These reactive intermediates play a crucial role in various organic reactions, including electrophilic additions, nucleophilic substitutions, and elimination reactions.
Pyridine: Pyridine is a heterocyclic aromatic organic compound with the chemical formula C₅H₅N. It is a colorless, volatile liquid with a distinctive unpleasant odor, and it is widely used in the production of various chemicals and pharmaceuticals.
Esterification: Esterification is a chemical reaction that involves the formation of an ester compound from the reaction between a carboxylic acid and an alcohol. This process is crucial in various areas of organic chemistry, including the properties of functional groups, polar reactions, the behavior of alcohols and phenols, the reactions of carboxylic acids, the chemistry of esters, and the reactions of monosaccharides.
Reaction Kinetics: Reaction kinetics is the study of the rates and mechanisms of chemical reactions. It examines the factors that influence the speed and efficiency of a reaction, such as temperature, pressure, and the presence of catalysts. This concept is crucial in understanding organic reactions, as the rate and pathway of a reaction can have a significant impact on the products formed and the overall efficiency of the process.
SN2: SN2 is a type of nucleophilic substitution reaction in organic chemistry where a nucleophile attacks the backside of a carbon atom bearing a good leaving group, resulting in the displacement of that leaving group and the inversion of stereochemistry at the carbon center.
Elimination Reactions: Elimination reactions are a class of organic reactions where two atoms or groups are removed from a molecule, typically resulting in the formation of a new carbon-carbon double bond. These reactions are an important aspect of organic chemistry, as they allow for the conversion of various functional groups and the synthesis of alkenes and other unsaturated compounds.
Dehydration: Dehydration is a chemical process in which water is removed from a compound, typically resulting in the formation of a new compound with fewer hydrogen and oxygen atoms. This term is particularly relevant in the context of various organic reactions and transformations, where dehydration plays a crucial role in the preparation and interconversion of different functional groups.
E1: E1 is a type of organic reaction mechanism in which the first step involves the unimolecular elimination of a good leaving group from a substrate, resulting in the formation of a carbocation intermediate. This is then followed by the removal of a proton from an adjacent carbon, leading to the formation of a new carbon-carbon double bond.
Nucleophilic Substitution: Nucleophilic substitution is a fundamental organic reaction where a nucleophile (a species that donates electrons) replaces a leaving group attached to a carbon atom, resulting in the formation of a new carbon-nucleophile bond. This process is central to many organic transformations and is particularly relevant in the context of alkyl halides, alcohols, carboxylic acids, and amines.
Reaction Mechanisms: Reaction mechanisms describe the step-by-step process by which a chemical reaction occurs, including the rearrangement of atoms, the formation and breaking of chemical bonds, and the movement of electrons. Understanding reaction mechanisms is crucial for predicting the products of a reaction, explaining experimental observations, and designing new synthetic routes in organic chemistry.
Regioselectivity: Regioselectivity refers to the preference of a chemical reaction to occur at a specific site or region of a molecule, leading to the formation of one regioisomeric product over another. This concept is particularly important in the context of electrophilic addition reactions of alkenes, electrophilic aromatic substitution, and other organic transformations.
Cycloalkenes: Cycloalkenes are a class of organic compounds that consist of a cyclic ring structure with at least one carbon-carbon double bond. These molecules are closely related to both cycloalkanes and alkenes, combining the cyclic nature of the former with the unsaturated character of the latter.
Hydride Shift: A hydride shift is a type of rearrangement reaction in organic chemistry where a hydride ion (H-) moves from one carbon atom to an adjacent carbon atom within a molecule. This process is often observed in the context of carbocation intermediates and plays a crucial role in various organic reactions.
Oxidation: Oxidation is a fundamental chemical process in which a substance loses electrons, resulting in an increase in its oxidation state. This term is central to understanding various reactions and transformations in organic chemistry, from the hydration of alkenes to the oxidation of alcohols and aldehydes.
Zaitsev's Rule: Zaitsev's rule is a principle in organic chemistry that predicts the major product of an elimination reaction. It states that the major alkene product will be the one with the most substituted (most stable) double bond.
PCC: PCC, or Pyridinium Chlorochromate, is a versatile oxidizing agent used in organic chemistry for the selective oxidation of alcohols to aldehydes and ketones. This powerful reagent is widely employed in various reactions across multiple topics, including the hydration of alkynes, the oxidation of alcohols, and the preparation and oxidation of aldehydes and ketones.
Alkoxide: An alkoxide is a functional group consisting of an alkyl group (R-) bonded to an oxygen atom (O-). Alkoxides are important intermediates in many organic chemistry reactions, including Grignard reactions, elimination reactions, and carbonyl condensation reactions.
Swern Oxidation: The Swern oxidation is a chemical reaction used to convert primary and secondary alcohols into aldehydes and ketones, respectively. It is a mild and selective method for the oxidation of alcohols without over-oxidation to carboxylic acids.
SOCl2: SOCl2, or thionyl chloride, is a highly reactive and versatile organic reagent commonly used in various chemical reactions, particularly in the context of nucleophilic substitution reactions and the reactions of alcohols.
O-acylisourea: O-acylisourea is an important reactive intermediate that arises in various organic reactions, particularly in the context of alcohol reactions, acid anhydride chemistry, and peptide synthesis. It serves as a key coupling agent, facilitating the formation of new bonds and enabling the transformation of starting materials into desired products.
Triglycerides: Triglycerides are a type of lipid molecule composed of three fatty acid chains attached to a glycerol backbone. They are the primary form of fat storage in the body and a major component of dietary fat. Triglycerides are an important consideration in the contexts of reactions of alcohols and soap production.
H3PO4: H3PO4, or phosphoric acid, is a chemical compound composed of one phosphorus atom and four oxygen atoms. It is a key player in various organic chemistry reactions, particularly those involving alcohols as described in section 17.6 Reactions of Alcohols.
Esterases: Esterases are a class of enzymes that catalyze the hydrolysis (breaking down) of ester bonds, which are chemical bonds formed between an alcohol and a carboxylic acid. These enzymes play a crucial role in various biological processes, including the metabolism of drugs, the breakdown of fats, and the regulation of neurotransmitter levels in the body.
Acid-Catalyzed Reactions: Acid-catalyzed reactions are chemical transformations that are accelerated by the presence of an acidic catalyst. These reactions are commonly observed in the context of organic chemistry, particularly in the reactions of alcohols, where acids facilitate the activation and transformation of alcohol functional groups.
Lucas Test: The Lucas test is a chemical test used to distinguish primary, secondary, and tertiary alcohols. It is a simple and reliable method for identifying the type of alcohol based on its reactivity with certain reagents.
Fischer Esterification: Fischer esterification is a chemical reaction that involves the formation of an ester compound from a carboxylic acid and an alcohol, typically in the presence of an acid catalyst. This reaction is a key process in the synthesis and interconversion of various organic compounds, particularly esters, which have a wide range of applications in the fields of chemistry, biology, and industry.
Leaving Group Ability: Leaving group ability refers to the propensity of a functional group or atom to depart from a molecule during a chemical reaction. The ease with which a leaving group can be displaced is a critical factor in determining the reactivity and mechanism of various organic reactions.
P-Toluenesulfonyl chloride: p-Toluenesulfonyl chloride, also known as tosyl chloride, is an organic compound commonly used as a protecting group and a reagent in organic synthesis, particularly in the context of reactions involving alcohols.
DMAP: DMAP, or 4-Dimethylaminopyridine, is a nucleophilic catalyst commonly used in organic chemistry reactions, particularly in the context of reactions involving alcohols. It serves as a powerful acylation catalyst, enhancing the reactivity of acyl groups and facilitating various transformations of alcohols.
POCl3: POCl3, or phosphorus oxychloride, is a colorless, volatile liquid compound that is commonly used as a reagent in organic chemistry reactions, particularly in the context of reactions involving alcohols.
Tosylates: Tosylates, also known as p-toluenesulfonates, are organic compounds derived from the reaction of alcohols with p-toluenesulfonyl chloride. They are widely used as versatile leaving groups in organic synthesis, particularly in nucleophilic substitution reactions.
Jones Reagent: Jones reagent is a powerful oxidizing agent used in organic chemistry to selectively oxidize primary alcohols to aldehydes or carboxylic acids, and secondary alcohols to ketones. It is a crucial reagent in the context of reactions involving alcohols.
DCC: DCC, or dicyclohexylcarbodiimide, is a coupling agent commonly used in organic chemistry for the activation and coupling of carboxylic acids and alcohols, as well as in peptide synthesis and the preparation of acid anhydrides. It plays a crucial role in various reactions by facilitating the formation of new carbon-carbon or carbon-heteroatom bonds.
Steglich Esterification: Steglich esterification is a method for the synthesis of esters from carboxylic acids and alcohols, facilitated by the use of a coupling agent and a catalyst. It is a versatile reaction that allows for the formation of esters under mild conditions, making it particularly useful in the context of organic chemistry reactions involving alcohols.
Alcohol Structure-Reactivity Relationships: Alcohol structure-reactivity relationships refer to the connections between the molecular structure of alcohols and their chemical reactivity. This term encompasses how the specific structural features of alcohols, such as the length and branching of the carbon chain, the position of the hydroxyl group, and the presence of other functional groups, influence the alcohol's ability to undergo various chemical reactions.