Chemical Tests for Aldehydes Fehling s Test Tallen s Test Chapter 19 20 Carboxylic Acids and Derivatives Acidity and Basicity Resonance stabilized by conjugate base Increased acidity with presence of EWG e withdrawing group Formic Acid Synthesis Acetic Acid Synthesis via Ethene Oxidation Acetic Acid Synthesis via Carbonylation Synthesis of COOHs Oxidation of primary alcohols and aldehydes CrO3 KMnO4 see above dilute HNO3 Addition of organometallics to CO2 s Hydrolysis of Nitriles H or B Substitution at the Carbonyl via addition elimination mechanism Base catalyzed add elim mechanism H catalyzed mechanism Carboxylic Acid Derivatives Acyl Halides forming acyl halides mechanism Anhydrides COOH acyl halide Esters h catalyzed addition to COOH Fischer esteri cation mechanism Amides COOH amine heat mechanism H catalyzed pathway is di cult Carboxylic Acid Chart the conversion of one carboxylic acid derivative to another can be summarized in the chart below You can travel down the chart converting one derivative into another directly however you cannot travel up the chart directly To travel up you must rst convert the derivative into carboxylic acid then you may convert it into the desired derivative Other Reactions of COOHs Reduction with LAH mechanism Hell Vollard Zelinsky Reaction HVZ bromonation alpha to acid proceeds through an acyl halide enol precursor Basicity of COOH Derivatives more resonance means more stability and more Basicity Acidity of Alpha Hydrogens pKa Value to Know Alkanenitriles Hydrolysis acid catalyzed mechanism base catalyzed mechanism reaction with alkyl nucleophiles Reduction Chapter 18 Enols and Enolates Acidity at the Alpha C alpha hydrogens are acidic due to resonance stabilization Aldehydes are more acidic than ketones Formation of Enolates weak moderate bases only partially promote enolate formation stronger bases completely promote enolate formation also works with KH NaH and t BuLi Enolates are ambident can attack from C and O Keto Enol Equilibria Tautomerization rapid equilibrium between keto and enol forms keto form is thermodynamically favorable base catalyzed enol formation acid catalyzed Halogenation alpha monohalogenation occurs under acidic conditions base mediated process produces polyhaolgenated products Alkylation of Aldehydes and Ketones base mediated alkylation is di cult to control aldehydes alkylate faster than ketones but su er from side reactions unsymmetrical ketones more stable enolates occur at higher T thermodynamic control less stable enolates occur at lower T kinetic control Fastest formed and least substituted side monoalkylations with enamines enamines are nucleophiles Aldol Addition Aldol Condensation protonated by heat Direct Dehydration Intramolecular Aldol Reactions 5 and 6 membered rings favored Enones enones are more stable than the saturated species because of resonance nonconjugated enones will walk into conjugation undergo typical reactions of alkenes and carbonyls nucleophilic addition to an enone weak nucleophiles and organocuprates add 1 4 thermodynamic control makes most stable species amines alcohols CN enolates alkoxides strong nucleophiles add 1 2 kinetic control usually forms unstable products organolithiums RMgX add both hydrides add 1 2 with aldehydes The Michael Addition enolate addition to enones forms 1 5 dicarbonyls compounds The Robinson Annulation ring forming Michael addition aldol condensation intramolecular Chapter 23 Claisen Condensations Claisen Condensations ester enolate NAS Retro Claisen reverse mixed Claisen only one zero enolizable Hs Intramolecular Claisens Dieckmann Retrosynthesis Analysis Aldols give beta keto alcohols Michael Additions give 1 5 dicarbonyls Claisens give beta keto esters 1 3 dicarbonyls Beta Dicarbonyl Anions are Nucleophiles Decarboxylation mechanism Acetoacetic Ester Synthesis synthesis of substituted ketones Malonic Ester Synthesis synthesis of substituted COOHs Michael Additions Acyl Anion Equivalents acyl anions cannot be made Dithianes cyclic thioacetals Thioazolium Salts aldehyde coupling mechanism Chapter 21 Amines Nucleophilicity and Basicity amines are good nucleophiles and bases the lone pair on N can act as a nucleophile by attacking the electrophile or it can act as a base by grabbing a proton more steric hinderance leads to greater basicity except tertiary aryl amines are less nucleophilic and less basic than alkyl amines because the lone pair is delocalized around the aromatic ring Alkylation of Amines direct alkylation through SN2 leads to polyalkylations because the product is still nucleophilic and reactive towards the electrophile indirect alkylation is required for monoalkylations Cyanide Displacement Reduction Azide Displacement Reduction Gabriel Synthesis mechanism works best with primary alkyl halides as it relies on SN2 Secondary alkyl halides will work but not as well as primary Will not work with tertiary alkyl halides and aryl halides Reductive Amination forming an amine from an imine via reduction Preparation of Amines from Carboxylic Acids reduction with LAH Ho man Rearrangement involves the loss of one carbon atom useful because it gives us a way to make an amine from any carboxylic acid derivative Acylation of Amines converting an amine into an amide Ho man Elimination gives least stable alkene because it goes through an anti zaitsev TS Mannich Reaction enol Imminium mechanism Nitrosation amines react with nitrosyl cation NO nitrosyl cation formation secondary amines lead to N nitrosamines