Slide 1 - Alcohols - Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is a reaction in which a pinacol undergoes rearrangement in the presence of an acid to form a ketone.
• The reaction involves the migration of a hydride ion from the carbon atom bonded to the OH group to the adjacent carbon atom.
• The resulting ketone is called a pinacolone.
• The pinacol pinacolone rearrangement is an important reaction in organic synthesis, as it allows for the conversion of a diol (pinacol) to a ketone (pinacolone).
• The rearrangement reaction is commonly performed using an acid catalyst, such as sulfuric acid or hydrochloric acid.

Slide 2 - Conditions required for Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement requires the presence of an acid catalyst, typically sulfuric acid or hydrochloric acid.
• The reaction is typically carried out at elevated temperatures, ranging from 100 to 150 degrees Celsius.
• The reaction can also be catalyzed by Lewis acids, such as aluminum chloride or zinc chloride.
• In some cases, a solvent is required, such as acetone or tetrahydrofuran, to facilitate the reaction.
• The reaction proceeds through a carbocation intermediate, which is stabilized by resonance and neighboring group effects.

Slide 3 - Mechanism of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement proceeds through a carbocation intermediate.
• Step 1: Protonation of the hydroxyl group of pinacol by the acid catalyst.
• Step 2: Hydride ion migration from the carbon bonded to the hydroxyl group to the adjacent carbon atom, leading to the formation of a carbocation intermediate.
• Step 3: Deprotonation of the carbocation by a base, such as water or the conjugate base of the acid catalyst.
• Step 4: Rearrangement of the carbocation to a more stable carbocation through hydride shift or alkyl shift.
• Step 5: Deprotonation of the more stable carbocation to form the pinacolone product.

Slide 4 - Example: Pinacol to Pinacolone

• Starting material: Pinacol (2,3-dimethyl-2,3-butanediol)
• Acid catalyst: Sulfuric acid
• Conditions: Elevated temperature, typically 100-150 degrees Celsius
• Mechanism:
  1. Protonation of the hydroxyl group of pinacol by sulfuric acid.
  2. Hydride ion migration from the carbon bonded to the hydroxyl group to the adjacent carbon atom, forming a carbocation intermediate.
  3. Deprotonation of the carbocation by water, leading to the rearrangement of the carbocation to a more stable carbocation through a hydride shift.
  4. Deprotonation of the more stable carbocation to form the product pinacolone.

Slide 5 - Applications of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is a useful reaction in organic synthesis for the conversion of diols to ketones.
• It can be used to synthesize a variety of ketones by controlling the structure of the starting diol.
• The reaction is especially useful for the synthesis of cyclic ketones, as it allows for the ring closure of open-chain diols.
• The pinacol pinacolone rearrangement has applications in the synthesis of natural products and pharmaceuticals.
• It is also used in the production of fragrances and flavors.

Slide 6 - Limitations of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is generally not suitable for the conversion of primary or secondary alcohols to ketones, as it leads to low yields and undesirable side reactions.
• The reaction is more effective for the conversion of 1,2-diols (pinacols) to ketones (pinacolones).
• Steric hindrance around the hydroxyl groups can hinder the reaction and decrease the yield of the desired product.
• The rearrangement may not occur if the reaction conditions are not optimized or if the starting material is not suitable for the reaction.
• The presence of other functional groups, such as carbonyl groups or halogens, can also affect the rearrangement reaction.

Slide 7 - Synthetic Applications of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement can be used in the synthesis of complex organic molecules.
• It can be employed for the construction of carbon-carbon bonds and the formation of cyclic structures.
• The reaction can be used for the synthesis of natural products and pharmaceutical intermediates.
• The pinacol pinacolone rearrangement is often used in multi-step synthesis sequences to introduce ketone functional groups.
• It offers an efficient and selective method for the transformation of 1,2-diols to ketones.

Slide 8 - Pinacol pinacolone Rearrangement vs. Other Rearrangement Reactions

• The Pinacole pinacolone rearrangement is similar to other rearrangement reactions, such as the Wagner-Meerwein rearrangement and the Beckmann rearrangement.
• The Wagner-Meerwein rearrangement involves the migration of a carbon skeleton, whereas the Pinacole pinacolone rearrangement involves the migration of a hydride ion.
• The Beckmann rearrangement involves the migration of a nitrogen atom.
• The Pinacole pinacolone rearrangement is specific to the conversion of diols to ketones, while the other rearrangement reactions have different substrates and products.
• Each rearrangement reaction has its own specific conditions and mechanisms.

Slide 9 - Summary

• The Pinacole pinacolone rearrangement is a reaction in which a pinacol undergoes rearrangement in the presence of an acid catalyst to form a ketone.
• The reaction proceeds through a carbocation intermediate and involves the migration of a hydride ion from the carbon bonded to the hydroxyl group to the adjacent carbon atom.
• The Pinacole pinacolone rearrangement has applications in organic synthesis for the conversion of diols to ketones and the synthesis of complex organic molecules.
• The reaction conditions and starting materials need to be carefully considered to achieve high yields and desired products.
• The Pinacole pinacolone rearrangement is a useful tool in the preparation of natural products, pharmaceuticals, fragrances, and flavors.

Slide 10 - References

1. Smith, M.B., & March, J. (2007). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.). John Wiley & Sons.

2. Wade, L.G. (2013). Organic Chemistry (8th ed.). Pearson Education.

3. Clayden, J., Greeves, N., & Warren, S. (2012). Organic Chemistry (2nd ed.). Oxford University Press.

11. Definition of Alcohols

• Alcohols are a class of organic compounds that contain a hydroxyl functional group (-OH) attached to a carbon atom.
• Alcohols can be classified into three types: primary (1°), secondary (2°), and tertiary (3°), based on the number of carbon atoms bonded to the carbon atom bearing the hydroxyl group.
• The general formula for alcohols is R-OH, where R represents an alkyl or aryl group.
• Alcohols are commonly used as solvents, disinfectants, antiseptics, and in the production of various chemicals.

12. Nomenclature of Alcohols

• Alcohols are named by replacing the final -e of the corresponding alkane with the suffix -ol.
• For example, methane becomes methanol, ethane becomes ethanol, and so on.
• If the hydroxyl group is attached to a substituted carbon atom, the prefix hydroxy- is used to indicate the hydroxyl group’s position.
• Alcohols with more than one hydroxyl group are called diols, triols, and so on. They are named using numerical prefixes such as ethane-1,2-diol (or ethylene glycol).

13. Physical Properties of Alcohols

• Alcohols have higher boiling points compared to corresponding hydrocarbons due to intermolecular hydrogen bonding.
• The boiling points increase with increasing molecular weight of the alcohol.
• Alcohols are generally soluble in water due to the formation of hydrogen bonds with water molecules.
• The solubility decreases with increasing molecular weight and branching of the alcohol.
• Alcohols have lower density compared to water.
• Alcohols exhibit acidic or basic behavior depending on the reaction conditions.

14. Preparation of Alcohols: Substitution Reactions

• Alcohols can be prepared by the substitution reactions of haloalkanes (alkyl halides) with nucleophiles such as water or hydroxide ion.
• The reaction is called nucleophilic substitution, where the halogen atom is replaced by the hydroxyl group.
• The reaction can be carried out in the presence of a base or by heating the haloalkane with water.
• Example:
  • RX + NaOH → R-OH + NaX
  • CH3Br + OH- → CH3OH + Br-

15. Preparation of Alcohols: Reduction Reactions

• Alcohols can be prepared by the reduction of carbonyl compounds such as aldehydes or ketones.
• The reduction is typically carried out using reducing agents like sodium borohydride (NaBH4) or lithium aluminum hydride (LiAlH4).
• The reaction results in the conversion of the carbonyl group to a hydroxyl group.
• Example:
  • RCHO + 2[H] → RCH2OH (Reduction of aldehydes to primary alcohols)
  • R2C=O + 4[H] → R2CHOH (Reduction of ketones to secondary alcohols)

16. Reactions of Alcohols: Acid-Base Reactions

• Alcohols can act as both acids and bases depending on the reaction conditions.
• In acidic conditions, alcohols can donate a proton from the hydroxyl group and act as a weak acid.
• In basic conditions, alcohols can accept a proton and act as a weak base.
• The acid-base reactions of alcohols are important in determining their reactivity in other chemical reactions.

17. Reactions of Alcohols: Dehydration

• Alcohols can undergo dehydration reactions to form alkenes or ethers.
• Dehydration is the elimination of water molecule from the alcohol molecule.
• The reaction is typically carried out in the presence of an acid catalyst, such as concentrated sulfuric acid or phosphoric acid.
• The resulting alkene is obtained as the major product if the reactant alcohol is a primary or secondary alcohol.
• Example:
  • CH3CH2CH2OH → CH2=CHCH3 + H2O (Dehydration of 1-propanol to form propene)

18. Reactions of Alcohols: Oxidation

• Alcohols can undergo oxidation reactions to form aldehydes, ketones, or carboxylic acids.
• The oxidation depends on the type of alcohol and the oxidizing agent used.
• Primary alcohols are oxidized to aldehydes by mild oxidizing agents like pyridinium chlorochromate (PCC) or chromic acid (H2CrO4).
• Further oxidation of aldehydes or primary alcohols leads to the formation of carboxylic acids using strong oxidizing agents like potassium permanganate (KMnO4).
• Example:
  • RCH2OH → RCHO (Oxidation of primary alcohols to aldehydes)
  • RCH2OH → RCOOH (Oxidation of primary alcohols to carboxylic acids)

19. Reactions of Alcohols: Esterification

• Alcohols can react with carboxylic acids to form esters in the presence of an acid catalyst.
• The reaction is an example of condensation reaction, where water is eliminated to form the ester.
• Esterification reactions are reversible, and the equilibrium can be shifted to favor either the reactants or the products by adjusting the reaction conditions.
• Example:
  • RCOOH + R’OH → RCOOR’ + H2O (Esterification of carboxylic acids with alcohols)

20. Reactions of Alcohols: Oxidation to Alkyl Halides

• Alcohols can be converted to alkyl halides (haloalkanes) by reaction with a hydrogen halide (HCl, HBr, or HI) or with phosphorus halides (PCl5, PCl3, PBr3, or PI3).
• The reaction involves the substitution of the hydroxyl group by a halogen atom.
• The reaction with hydrogen halides proceeds via a nucleophilic substitution reaction, while the reaction with phosphorus halides proceeds via an SN2 mechanism.
• Example:
  • R-OH + HX → R-X + H2O (Substitution of hydroxyl group by halogen atom)

Slide 21 - Alcohols - Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is a reaction in which a pinacol undergoes rearrangement in the presence of an acid to form a ketone.
• The reaction involves the migration of a hydride ion from the carbon atom bonded to the OH group to the adjacent carbon atom.
• The resulting ketone is called a pinacolone.
• The pinacol pinacolone rearrangement is an important reaction in organic synthesis, as it allows for the conversion of a diol (pinacol) to a ketone (pinacolone).
• The rearrangement reaction is commonly performed using an acid catalyst, such as sulfuric acid or hydrochloric acid.

Slide 22 - Conditions required for Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement requires the presence of an acid catalyst, typically sulfuric acid or hydrochloric acid.
• The reaction is typically carried out at elevated temperatures, ranging from 100 to 150 degrees Celsius.
• The reaction can also be catalyzed by Lewis acids, such as aluminum chloride or zinc chloride.
• In some cases, a solvent is required, such as acetone or tetrahydrofuran, to facilitate the reaction.
• The reaction proceeds through a carbocation intermediate, which is stabilized by resonance and neighboring group effects.

Slide 23 - Mechanism of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement proceeds through a carbocation intermediate.
• Step 1: Protonation of the hydroxyl group of pinacol by the acid catalyst
• Step 2: Hydride ion migration from the carbon bonded to the hydroxyl group to the adjacent carbon atom, leading to the formation of a carbocation intermediate
• Step 3: Deprotonation of the carbocation by a base, such as water or the conjugate base of the acid catalyst
• Step 4: Rearrangement of the carbocation to a more stable carbocation through hydride shift or alkyl shift
• Step 5: Deprotonation of the more stable carbocation to form the pinacolone product

Slide 24 - Example: Pinacol to Pinacolone

• Starting material: Pinacol (2,3-dimethyl-2,3-butanediol)
• Acid catalyst: Sulfuric acid
• Conditions: Elevated temperature, typically 100-150 degrees Celsius
• Mechanism:
  1. Protonation of the hydroxyl group of pinacol by sulfuric acid
  2. Hydride ion migration from the carbon bonded to the hydroxyl group to the adjacent carbon atom, forming a carbocation intermediate
  3. Deprotonation of the carbocation by water, leading to the rearrangement of the carbocation to a more stable carbocation through a hydride shift
  4. Deprotonation of the more stable carbocation to form the product pinacolone

Slide 25 - Applications of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is a useful reaction in organic synthesis for the conversion of diols to ketones.
• It can be used to synthesize a variety of ketones by controlling the structure of the starting diol.
• The reaction is especially useful for the synthesis of cyclic ketones, as it allows for the ring closure of open-chain diols.
• The pinacol pinacolone rearrangement has applications in the synthesis of natural products and pharmaceuticals.
• It is also used in the production of fragrances and flavors.

Slide 26 - Limitations of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement is generally not suitable for the conversion of primary or secondary alcohols to ketones, as it leads to low yields and undesirable side reactions.
• The reaction is more effective for the conversion of 1,2-diols (pinacols) to ketones (pinacolones).
• Steric hindrance around the hydroxyl groups can hinder the reaction and decrease the yield of the desired product.
• The rearrangement may not occur if the reaction conditions are not optimized or if the starting material is not suitable for the reaction.
• The presence of other functional groups, such as carbonyl groups or halogens, can also affect the rearrangement reaction.

Slide 27 - Synthetic Applications of Pinacole pinacolone Rearrangement

• The Pinacole pinacolone rearrangement can be used in the synthesis of complex organic molecules.
• It can be employed for the construction of carbon-carbon bonds and the formation of cyclic structures.
• The reaction can be used for the synthesis of natural products and pharmaceutical intermediates.
• The pinacol pinacolone rearrangement is often used in multi-step synthesis sequences to introduce ketone functional groups.
• It offers an efficient and selective method for the transformation of 1,2-diols to ketones.

Slide 28 - Pinacol pinacolone Rearrangement vs. Other Rearrangement Reactions

• The