13 - MED-108 Aldehydes and Ketones PPT 2024 90 min.pdf

MED-108 Organic Chemistry Aldehydes & Ketones LOBs covered Describe methods of preparation of aldehydes and ketones Identify reagents and products of a wide variety of aldehyde and ketone reactions Aldehydes and Ketones Methods of Preparation Preparation of aldehydes and ketones Most of the reaction...

MED-108 Organic Chemistry Aldehydes & Ketones LOBs covered Describe methods of preparation of aldehydes and ketones Identify reagents and products of a wide variety of aldehyde and ketone reactions Aldehydes and Ketones Methods of Preparation Preparation of aldehydes and ketones Most of the reactions employed to prepare aldehydes and ketones from other compounds have already been covered in this course We will review these reactions, as well as introduce a few new reactions Preparation of aldehydes (a) (b) (c) (d) Partial oxidation of primary alcohols Ozonolysis of appropriate alkenes Partial reduction of an ester (NEW) Hydroboration-oxidation of alkynes - Only terminal alkyne can be used here Preparation of aldehydes (a) Partial oxidation of primary alcohols Here, we need to use a milder oxidizing agent because a strong oxidizing agent will oxidize the primary alcohol all the way to a carboxylic acid The appropriate oxidizing agent to carry out a partial oxidation is PCC (pyridinium chlorochromate) Preparation of aldehydes (a) Partial oxidation of primary alcohols Preparation of aldehydes (b) Ozonolysis of appropriate alkenes An aldehyde will form if the alkene C atoms are connected to H atoms Preparation of aldehydes (c) Partial reduction of an ester (NEW) DIBAH = diisobutylaluminium hydride Preparation of aldehydes (d) Hydroboration-oxidation of alkynes - Only terminal alkynes can be used here - Internal alkynes will form a mixture of ketones Preparation of ketones (a) Oxidation of secondary alcohols (b) Ozonolysis of appropriate alkenes (c) Hydroboration-oxidation of alkynes - Only internal alkynes (d) Mercury(II)-catalyzed hydration of alkynes (oxymercuration) - Both terminal and internal alkynes Preparation of ketones (a) Oxidation of secondary alcohols Preparation of ketones (b) Ozonolysis of appropriate alkenes Preparation of ketones (c) Hydroboration-oxidation of alkynes Only internal alkynes Preparation of ketones (d) Mercury(II)-catalyzed hydration of alkynes Both terminal and internal alkynes Here, we see an example of a reaction with a terminal alkyne. This forms a methyl ketone Preparation of ketones (d) Mercury(II)-catalyzed hydration of alkynes Below, we see reaction with an internal alkyne 5-Minute Break Aldehydes and Ketones Chemical Reactions Oxidation of aldehydes and ketones Aldehydes are easily oxidized to carboxylic acids using a wide variety of oxidizing agents Ketones are resistant to oxidation, but under very harsh conditions they will produce carboxylic acids However, for this course, we will always assume that ketones do not undergo oxidation Oxidation of aldehydes Oxidizing agents are usually KMnO4 in hot HNO3, or CrO3 in strongly acidic conditions, or Na2Cr2O7 (K2Cr2O7) in acid The problem with these oxidizing agents is that they work under highly acidic conditions and this may damage other parts of a sensitive molecule Oxidation can also be carried out in alkaline conditions by using Ag2O in aqueous ammonia solution (NH4OH(aq)) This is known as Tollens’ reagent Oxidation of aldehydes Oxidation of aldehydes Alkaline conditions – Tollens’ test (silver mirror test) Further Details for Revision Alkaline conditions – Tollens’ test (silver mirror test) In the above reaction, which is a classic redox reaction, the aldehyde is oxidized to a carboxylic acid. If something is oxidized, something else must be reduced. The reduction taking place is the silver: in Ag2O the silver has an oxidation number of +1. At the end of the reaction, silver atoms (oxidation number = 0) are formed. This is a reduction, forming elemental silver, which deposits on the walls of the test tube in which the reaction takes place. WATCH: https://www.youtube.com/watch?v=7U69JXm0rPM Carbonyl Group Structure The carbonyl group is polarized because of the difference in electronegativities between C and O This means that the C atom can be attacked by electron-rich nucleophiles Nucleophilic Addition If a nucleophile attacks the partially positive C, it will form a single bond with it Here, then, we have addition of a nucleophile NOTE: The O- ion can be easily protonated with an acid, forming an –OH group Nucleophilic Addition Nucleophiles can be fully negative ions OH-, CN-, H- Or they can be neutral but polar (electron-rich) H2O, R-OH Nucleophilic Addition of Water Hydration Hydration of Aldehydes/Ketones The product is a 1,1-diol (geminal diol) as opposed to a 1,2-diol (vicinal diol) Nucleophilic Addition of HCN Cyanohydrin formation Cyanohydrin Formation Reagents Reversible reaction Examples 5-Minute Break Transformations of Cyanohydrins Cyanohydrins themselves are not very useful However, they can be transformed to very useful compounds First Transformation Reduction of -CN group to -CH2NH2 Second Transformation Hydrolysis of –CN to –COOH Summary of Transformations Grignard Reagents How do we make a Grignard reagent? Characteristics of Grignard Reagent Electronic structure is important Alcohols from Grignard Reagents Nucleophilic Addition of Hydrazine Wolff-Kishner reaction Hydrazine = NH2NH2 = N2H4 (Early rocket fuel) Converts a carbonyl group (C=O) to -CH2(Reduction) Wolff-Kishner Reaction Summary for Revision Aldehydes can be prepared by partial oxidation of primary alcohols, ozonolysis of appropriate alkenes, partial reduction of an ester, and hydroboration of a terminal alkyne. Ketones can be prepared by oxidation of secondary alcohols, ozonolysis of appropriate alkenes, hydroboration of internal alkynes, and mercury(II)-catalyzed hydration of terminal/internal alkynes. Aldehydes can be oxidized to carboxylic acids readily. Ketones are resistant to oxidation although they can react under very harsh conditions forming carboxylic acids. Aldehydes can be oxidized under acidic conditions, or under alkaline conditions (Tollens’ reagent). Since carbonyl groups involve a δ+ carbon atom, they can readily be attacked by electron-rich nucleophiles. Nucleophiles can be fully negative, or highly polar molecules. This leads to what is known as a nucleophilic addition reaction. Nucleophilic addition of water leads to the formation of a 1,1-diol (geminal diol). Nucleophilic addition of HCN leads to the formation of a cyanohydrin. Cyanohydrins are not useful compounds themselves, but they can be converted to other more useful organic compounds. Reduction of the CN group forms a primary amine, whereas hydrolysis of a CN group forms a carboxylic acid group. Grignard reagents have been extensively covered in the section on alcohols, as a useful method of preparation of alcohols. The Grignard reagent can be reacted with carbonyl compounds to form alcohols. Using formaldehyde gives a primary alcohol, using any other aldehyde forms a secondary alcohol, and using a ketone gives a tertiary alcohol. Grignard reagent have limitations, as discussed previously. The Wolff-Kishner reaction involves the use of hydrazine, NH2NH2, in KOH and converts a carbonyl group (C=O) into a -CH2- group.