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Organic Chemistry
Table of Contents
Unit 8 Overview: Alkenes
8.1 Preparing Alkenes: A Preview of Elimination Reactions
8.2 Halogenation of Alkenes: Addition of X2
8.3 Halohydrins from Alkenes: Addition of HO-X
8.4 Hydration of Alkenes: Addition of H2O by Oxymercuration
8.5 Hydration of Alkenes: Addition of H2O by Hydroboration
8.6 Reduction of Alkenes: Hydrogenation
8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation
8.8 Oxidation of Alkenes: Cleavage to Carbonyl Compounds
8.9 Addition of Carbenes to Alkenes: Cyclopropane Synthesis
8.10 Radical Additions to Alkenes: Chain-Growth Polymers
8.11 Biological Additions of Radicals to Alkenes
8.12 Reaction Stereochemistry: Addition of H2O to an Achiral Alkene
8.13 Reaction Stereochemistry: Addition of H2O to a Chiral Alkene

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8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation

Citation:

Alkenes undergo fascinating transformations when exposed to oxygen-containing reagents. Epoxidation creates three-membered cyclic ethers, while hydroxylation forms vicinal diols. Both reactions add oxygen across the double bond in a syn fashion, preserving the alkene's original geometry.

These oxidation reactions showcase the versatility of alkenes in organic synthesis. From peroxyacids for epoxidation to osmium tetroxide for hydroxylation, various reagents can be employed. Understanding the mechanisms and stereochemistry is key to predicting and controlling product structures.

Epoxidation and Hydroxylation of Alkenes

Epoxidation and hydroxylation of alkenes

  • Epoxidation adds an oxygen atom to an alkene forming a three-membered cyclic ether called an epoxide (a heterocyclic compound)
    • Peroxyacids like meta-chloroperoxybenzoic acid (mCPBA) commonly used as reagents
    • Proceeds through a concerted mechanism with oxygen added to the same face of the alkene
    • Stereochemistry of the alkene retained in the epoxide product (syn addition)
  • Hydroxylation adds a hydroxyl group (-OH) to an alkene forming a vicinal diol
    • Osmium tetroxide ($OsO_4$) commonly used as reagent along with a co-oxidant (N-methylmorpholine N-oxide, NMO)
    • Proceeds through a cyclic osmate ester intermediate which is hydrolyzed to give the vicinal diol
    • Stereochemistry of the alkene retained in the diol product (syn addition)

Halohydrins for epoxide synthesis

  • Halohydrins contain both a halogen and a hydroxyl group on adjacent carbons
    • Prepared by addition of a halogen (X2) to an alkene in the presence of water
  • Halohydrins converted to epoxides through an intramolecular $S_N2$ reaction
    • Treatment with a strong base like sodium hydroxide (NaOH) leads to epoxide formation
    • Proceeds with inversion of stereochemistry at the carbon bearing the halogen
  • Compared to direct epoxidation using peroxyacids:
    • Halohydrin formation followed by epoxide synthesis is a two-step process vs direct epoxidation in a single step
    • Stereochemistry of epoxide product may differ between the two methods due to inversion in the halohydrin route
    • Direct epoxidation with peroxyacids often preferred for simplicity and predictable stereochemical outcome

Osmium tetroxide in alkene hydroxylation

  • Catalytic cycle for alkene hydroxylation using osmium tetroxide ($OsO_4$):
    1. $OsO_4$ reacts with alkene to form an osmate ester intermediate
      • Concerted [3+2] cycloaddition step
    2. Osmate ester hydrolyzed to give vicinal diol product and regenerate $OsO_4$ catalyst
      • Hydrolysis typically slow and requires a co-oxidant to proceed efficiently
  • Role of co-oxidants like N-methylmorpholine N-oxide (NMO):
    • Regenerate active $OsO_4$ catalyst from osmate ester intermediate
    • NMO oxidizes osmate ester, releasing vicinal diol product and forming reduced $OsO_4$
    • Reduced $OsO_4$ re-oxidized by NMO, regenerating active catalyst allowing cycle to continue
  • Co-oxidants enable hydroxylation with catalytic amounts of expensive and toxic $OsO_4$, making process more efficient and economical

Oxidation Reactions and Stereochemistry

  • Epoxidation and hydroxylation are examples of oxidation reactions, where alkenes gain oxygen atoms
  • These reactions are classified as addition reactions, as they involve the addition of new atoms to the alkene
  • Stereochemistry plays a crucial role in these reactions:
    • Syn addition in both epoxidation and hydroxylation preserves the original alkene geometry
    • Stereospecific nature of these reactions is important for predicting and controlling product structures
  • Transition metal catalysts, such as osmium tetroxide, are often employed to facilitate these oxidation reactions

Key Terms to Review (26)

Glycol: Glycol, in the context of organic chemistry, specifically refers to a diol, which is a chemical compound containing two hydroxyl (-OH) groups attached to different carbon atoms. These compounds are often formed through the oxidation of alkenes, resulting in the addition of hydroxyl groups across the double bond.
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.
Sharpless epoxidation: Sharpless epoxidation is a chemical reaction that selectively transforms primary and secondary allylic alcohols into their corresponding epoxy alcohols using titanium tetraisopropoxide, tert-butyl hydroperoxide, and diethyl tartrate. It is noteworthy for its stereospecificity, predominantly producing molecules with a specific three-dimensional arrangement.
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.
Addition Reaction: An addition reaction is a type of chemical reaction where two or more reactants combine to form a single product. In the context of organic chemistry, addition reactions typically involve the addition of atoms or molecules to an alkene or alkyne, resulting in the formation of a new compound with a different structure and properties.
Halohydrin: A halohydrin is a compound containing both a halogen atom (such as chlorine, bromine, or iodine) and a hydroxyl group (-OH) on adjacent carbon atoms. These compounds are formed through the addition of a hydrogen halide (HX, where X is a halogen) to an alkene, resulting in the incorporation of both the halogen and the hydroxyl group.
Syn Addition: Syn addition is a type of organic reaction where two substituents are added to the same side of a carbon-carbon double bond, resulting in the formation of a new stereocenter with a specific stereochemical configuration. This term is particularly relevant in the context of various organic chemistry topics, including electrophilic addition reactions of alkenes, hydration of alkenes, reduction of alkenes, and oxidation of alkenes.
Epoxidation: Epoxidation is a chemical reaction that converts alkenes (carbon-carbon double bonds) into cyclic ethers called epoxides. This process involves the addition of an oxygen atom across the double bond, creating a three-membered ring structure. Epoxidation is an important transformation in organic chemistry, with applications in the synthesis of various compounds and the production of polymers.
Epoxide: An epoxide is a cyclic ether compound containing a three-membered ring consisting of one oxygen atom and two carbon atoms. Epoxides are important intermediates in organic chemistry, particularly in the context of alkene oxidation, cyclic ether formation, and various ring-opening reactions.
Peroxyacids: Peroxyacids, also known as peracids, are a class of organic compounds that contain a peroxide group (-O-O-) attached to a carboxyl group (-COOH). These compounds are powerful oxidizing agents and play a crucial role in the oxidation of alkenes, particularly in the processes of epoxidation and hydroxylation.
Hydroxylation: Hydroxylation is the process of introducing a hydroxyl group (-OH) into an organic compound. This reaction is particularly important in the context of the oxidation of alkenes, where it can occur alongside the epoxidation reaction.
Osmium Tetroxide: Osmium tetroxide is a colorless, volatile, and highly toxic compound with the chemical formula OsO4. It is a powerful oxidizing agent that plays a significant role in various organic chemistry reactions, particularly in the context of the oxidation of alkenes, the cleavage of alkynes, and the preparation of alcohols.
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.
Transition Metal Catalyst: A transition metal catalyst is a type of catalyst that contains a transition metal element, which can facilitate chemical reactions by providing an alternative pathway with lower activation energy. These catalysts are widely used in various organic reactions, including the reduction of alkenes and the oxidation of alkenes.
NMO: NMO, or N-Methylmorpholine N-oxide, is an organic compound that serves as a versatile oxidizing agent in various chemical reactions, particularly in the context of the oxidation of alkenes, including epoxidation and hydroxylation.
Sodium Hydroxide: Sodium hydroxide, also known as caustic soda or lye, is a highly alkaline and corrosive chemical compound that plays a crucial role in various organic chemistry processes, including the oxidation of alkenes, the nucleophilic addition of water, and the production of soap.
Intramolecular $S_N2$ Reaction: An intramolecular $S_N2$ reaction is a type of nucleophilic substitution reaction where the nucleophile and the electrophilic carbon center are part of the same molecule, leading to the formation of a cyclic product. This process is particularly relevant in the context of the oxidation of alkenes, specifically in the reactions of epoxidation and hydroxylation.
Heterocyclic Compound: A heterocyclic compound is a cyclic compound that contains atoms of at least two different elements as members of its ring structure. These compounds are widely found in nature and play crucial roles in various organic chemistry reactions, including the oxidation of alkenes through epoxidation and hydroxylation.
Vicinal Diol: A vicinal diol is a type of organic compound that contains two hydroxyl (-OH) groups attached to adjacent carbon atoms on a carbon chain. These diols are important in the context of the oxidation of alkenes and the preparation of alcohols.
MCPBA: mCPBA, or meta-Chloroperoxybenzoic acid, is an organic compound commonly used as an oxidizing agent in various organic chemistry reactions, particularly in the context of the oxidation of alkenes, including epoxidation and hydroxylation.
Meta-Chloroperoxybenzoic acid: meta-Chloroperoxybenzoic acid, also known as mCPBA, is an organic compound used as an oxidizing agent in various chemical reactions, particularly in the context of organic chemistry. It is a peroxycarboxylic acid derivative that plays a crucial role in the oxidation of alkenes, specifically in the processes of epoxidation and hydroxylation.
Co-oxidant: A co-oxidant is a chemical species that assists in the oxidation of another compound, typically in the context of organic chemistry reactions. It plays a crucial role in facilitating and enhancing the efficiency of oxidation processes, particularly in the context of the oxidation of alkenes, which is the focus of topics 8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation.
Concerted Mechanism: A concerted mechanism refers to a reaction that occurs in a single, continuous step without the formation of any discrete intermediates. In a concerted mechanism, the bonds that are being formed and broken happen simultaneously, leading to the product in a single, coordinated process.
Cyclic Osmate Ester: A cyclic osmate ester is a type of organic compound that forms during the oxidation of alkenes through a process called epoxidation. It is a cyclic ester containing an osmium atom bonded to two oxygen atoms, creating a heterocyclic ring structure.
N-methylmorpholine N-oxide: N-methylmorpholine N-oxide is a chemical compound commonly used as an oxidizing agent in organic chemistry. It plays a key role in the oxidation of alkenes through epoxidation and hydroxylation reactions, as well as in the preparation of alcohols.
[3+2] Cycloaddition: [3+2] Cycloaddition is a type of organic reaction in which a 3-membered ring and a 2-membered ring combine to form a new 5-membered ring. This process is an important tool in the synthesis of complex organic molecules, particularly in the context of alkene oxidation reactions like epoxidation and hydroxylation.