Organic Chemistry Review Part II

Oxidation & Reductions Organic Reactions Addition Esterification Elimination Hydrolysis Substitution Oxidation & Reductions Rearrangement Combustion Condensation

Addition Reactions The components of an organic molecule A–B are added to the carbon atoms in a C=C bonds. Involve the conversion of a π bond into 2 σ bonds. General form: A + B → C

Addition Reactions Symmetrical alkenes produce one product. Unsymmetrical alkenes produce racemic mixtures.

Addition Reactions Alcohols are often produced by addition reactions. Initial attack by the π bond of an alkene on a Hδ+ of H3O+ produces a carbocation. The carbocation then undergoes nucleophilic attack by a lone pair of electrons from H2O. This is followed by elimination of H+ to form the alcohol.

Addition Reactions

Addition Reactions With symmetrical alkenes, addition of hydroxyl group produces one type of alcohol.

Addition Reactions With unsymmetrical alkenes, addition of hydroxyl group produces different types of alcohols depending on the location of the double bond +

Addition Reactions Formation of hemiketals & hemiacetals: Reactions between an acohol and either a ketone or aldehyde.

Elimination Reactions The removal or “elimination” of adjacent atoms from a molecule. Two σ bonds are lost, replaced by a new π bond. The dehydration reaction of alcohols to generate alkene proceeds by heating the alcohols in the presence of a strong acid, such as sulfuric or phosphoric acid, at high temperatures. 

Elimination Reactions The required range of reaction temperature decreases with increasing substitution of the hydroxyl carbon: 1° alcohols: 170° - 180°C 2° alcohols: 100°– 140 °C 3° alcohols: 25°– 80°C

Elimination Reactions If the reaction is not sufficiently heated, the alcohols do not produce alkenes, but they react with one another to form ethers (Williamson Ether Synthesis).

Elimination Reactions General form: A → B + C

Elimination Reactions 1⁰ Alcohols

Elimination Reactions 2⁰ Alcohols

Elimination Reactions In dehydration reactions of alcohols, hydride or alkyl shifts relocate the carbocation to a more stable position. The dehydrated products are a mixture of alkenes, with and without carbocation rearrangement.

Elimination Reactions Hydride or alkyl shifts are the result of hyperconjugation. The interaction between the filled orbitals of neighboring carbons and the singly occupied p orbital in the carbocation stabilizes the positive charge in carbocation. The tertiary cation is more stable than a secondary cation, which is more stable than a primary cation.

Elimination Reactions Hydride shift:

Elimination Reactions Alkyl shift:

Substitution Reactions Nucleophilic substitution reactions. An electronegative atom is replaced by another more electronegative atom, called a stronger nucleophile. The stronger nucleophile must possess a pair of electrons and have a greater affinity for the electropositive carbon atom than the original electronegative atom. A σ bond is replaced by another σ bond .

Substitution Reactions General form: A + B → C + D Non-polar reactions:

Substitution Reactions Polar reactions:

Rearrangement Reactions Are isomerisation reactions. An organic molecule changes structure. Constitutional change in carbon skeleton. Reaction may involve changes in bond type. General form: A → B

Rearrangement Reactions

Condensation Reactions Two molecules combine to form one single molecule with the loss of a small molecule. When this small molecule is water, it is known as a dehydration reaction. Other possible small molecules lost include hydrogen chloride, methanol, or acetic acid.

Condensation Reactions When two separate molecules react, their condensation is termed intermolecular. The condensation of two amino acids to form a peptide bond (red) with expulsion of water (blue).

Condensation Reactions When a condensation is performed between different parts of the same molecule, the reaction is termed intramolecular condensation. In some cases this leads to ring formation.

Condensation Reactions

Esterification Reactions Esters are obtained by refluxing a carboxylic acid with an alcohol in the presence of an acid catalyst. The reaction is driven to completion by using an excess of either the alcohol or the carboxylic acid, or by removing the water as it forms. Alcohol reactivity order :  CH3OH > 1o > 2o > 3o (steric effects).

Esterification Reactions A carboxylic acid and an alcohol react together under acidic conditions to form an ester and lose water.

Esterification Reactions Esters can also be made from other carboxylic acid derivatives, especially acyl halides and anhydrides, by reacting them with the appropriate alcohol in the presence of a weak base. If a compound contains both hydroxy- and carboxylic acid groups, then cyclic esters or lactones can form via an intramolecular reaction. Reactions that form 5- or 6-membered rings are particularly favorable.

Esterification Reactions Pericyclic esters

Hydrolysis A reaction in which water is a reactant, and becomes part of the reaction product. A number of organic compounds undergo hydrolysis with water, such as amides, esters, halogenoalkanes and acyl halides.

Hydrolysis Reactions require a catalyst. The catalyst is either an acid (H+ ions) or alkali (OH- ions). Hydrolysis might involve refluxing in the presence of dilute hydrochloric acid or sodium hydroxide solution.

Hydrolysis In the overall reaction, a bond in an organic molecule is broken. A water molecule also breaks into ions. The -OH group from water is added to one end of the organic molecule and the remaining H atom is added to the other.

Hydrolysis of an Ester: The addition of a strong acid, such as dilute hydrochloric acid, is required to free the carboxylic acid molecule. In the base-catalyzed, the carboxylic acid molecule loses a proton to a hydroxide ion.

Hydrolysis of Amides & Nitriles: Amide acid catalyzed - HCl Nitrile acid catalyzed – HCl or H2SO4

Hydrolysis of Halogenalkanes:

Hydrolysis of Aromatics

Summary of Hydrolysis Reactions The hydrolysis of a primary amide: RCONH2 + H2O    →    RCOOH + NH3 The hydrolysis of a secondary amide: RCONHR' + H2O    →    RCOOH + R'NH2

Summary of Hydrolysis Reactions The hydrolysis of an ester: RCOOR' + H2O    →    RCOOH + R'OH The hydrolysis of a halogenoalkane: RBr + H2O    →    ROH + H+ + Br-

Reduction & Oxidation (REDOX) Reactions Oxidation States Oxidations Reductions

Definitions Oxidation-Reduction reactions: Involve changes in oxidation state at one or more atoms. Can often be identified by changes in the number of oxygen atoms at a particular position in the hydrocarbon skeleton or in the number of bonds between carbon and oxygen at that position. It is not consider an oxidation or reduction reaction: Addition or loss of H+, H2O, HX.

Definitions Oxidation: The oxidation state increases Loss of H2 Loss of a C-H bond Addition of O or O2 Formation of a C-O bond or equivalent (C-Cl, CΞN, C-S) Addition of X2 (halogens)

Definitions Reduction: The oxidation state decreases Addition of H2 or H- Formation of a C-H bond Loss of O or O2 Loss of a C-O bond or equivalent Loss of X2. An increase in the number of hydrogen atoms in a hydrocarbon is often an indication of a reduction.

Oxidation States Carbon oxidation states are assigned on the basis of the electronegativity of attached atoms. For each bond to a more electronegative atom give +1. For each bond to a less electronegative atom (even H) give –1. For each bond to carbon give 0.

Oxidation States

Oxidation States In nitrogen-containing compounds, the number of carbon–nitrogen bonds changes with the oxidation state of carbon.

Oxidation States

Assign oxidation states to all atoms in the following structure: HO C C H H H H

Assign oxidation states to all atoms in the following structure: -2 O +1 H -2 C +1 HO +3 H+1 H+1 -2 -3 C C H +1H +1 H +1

Problem Identify if the following reactions are oxidation-reduction reactions. For any that are, identify the atoms that are oxidized and reduced. Br I + NaI + NaBr + H2 OH O + KMnO4 + MnO2 + H2O +K-O

Problem + H2 No, both Br and I are more electronegative than C -2 Yes, the carbon atoms are reduced, the H2 molecule is oxidized

Problem

Summary of Oxidation States

REDOX Reactions of Alcohols Alcohols can undergo either oxidation or reduction type reactions. Oxidation is a loss of electrons. Reduction is a gain of electrons.

Oxidation of Alcohols 1⁰ and 2⁰ alcohols are easily oxidized by a variety of reagents. The most common reagents used: Pyridinium chlorochromate (PCC) Potassium permanganate Thermal dehydrogenation

Oxidation of Alcohols The most common reagent used for oxidation of 2⁰ alcohols to ketones is chromic acid, H2CrO4. 3⁰ alcohols are resistant to oxidation because they have no hydrogen atoms attached to the oxygen bearing carbon (carbinol carbon).

Oxidation of 1⁰ Alcohols 1⁰ alcohols are easily oxidized just like 2⁰ alcohols. The product of oxidation is an aldehyde. The aldehyde is easily oxidized to an acid as a result of “over-oxidation”. A reagent that selectively oxidizes a 1⁰ alcohol to an aldehyde is pyridinium chlorochromate, PCC.

Oxidation of 2⁰ Alcohols The alcohol and chromic acid produce a chromate ester, which then reductively eliminates the Cr species. The Cr is reduced (VI  IV), the alcohol is oxidized to a ketone.

Summary of Oxidation of Alcohols

Reduction of Alcohols Normally an alcohol cannot be directly reduced to an alkane in one step. The –OH group is a poor leaving group and hydride displacement cannot happen. Instead, the hydroxyl group is easily converted into other groups that are better leaving groups, and allow reaction to move forward.

Reduction of Alcohols Commons reagents are tosyl chloride and lithium aluminum hydride (LiAlH4). The reaction involves the formation of a tosylate. The tosylates can undergo either substitution or elimination reactions.

Reduction of Alcohols The tosylate reduces to cyclohexane very easily with lithium aluminum hydride.

Reduction of Carboxylic Acids Carboxylic acids are reduced to 1⁰ alcohols.

Reduction of Esters Esters are reduced to 1⁰ alcohols.

Reduction of Amides Amides are reduced to 1⁰, 2⁰, or 3⁰ amines.

Reduction of Aldehydes Aldehydes and ketones are reduced to 1⁰ and 2⁰ alcohols respectively.

Summary REDOX Reactions

Combustion Reactions The reaction of an organic molecule with oxygen to form carbon dioxide, heat/energy and water.

Combustion Reactions Alkanes: Alkenes: Alcohols