Nucleophilic Addition to Aldehydes and Ketones: Mechanisms and Applications - Prof. Robert, Study notes of Chemistry

Download Nucleophilic Addition to Aldehydes and Ketones: Mechanisms and Applications - Prof. Robert and more Study notes Chemistry in PDF only on Docsity! 1 Chapter 21. Addition of Soft Nucleophiles to Aldehydes and Ketones. 1. Nomenclature. a) Aldehydes. i) Systematic. Alkanal. Ethanal, hexanal, propenal. ii) Trivial. Formaldehyde, acetaldehyde, acrolein, benzaldehyde. b) Ketones. i) Systematic. Alkanone. Propanone, 2-butanone, 5-hexen-3-one, 1-phenyl-1-ethanone. 3- Oxobutanoic acid. ii) Trivial. Acetone, acetophenone, benzophenone. 2. Relative stability of aldehydes and ketones. Sterically and electronically, aldehydes more reactive. 3. Nucleophilic addition to aldehydes and ketones. a) Under basic conditions, nucleophiles (usually anionic, except for amines) add to neutral carbonyl compounds. After the addition, the former carbonyl O is protonated to give the product. i) Lone pair nucleophiles. HO–, RO–, RC≡C–, –C≡N, H3N, RNH2. ii) Already talked about sigma bond nucleophiles. b) Under acidic conditions, nucleophiles (always neutral) add to protonated carbonyl compounds. H2O, ROH, H3N, RNH2. After the addition, the nucleophilic atom is deprotonated to give the product. 4. Reversible nucleophilic addition to aldehydes and ketones. a) Carbonyl + H2O + (acid or base) →← hydrate. Slow in pure H2O! Equilibrium favors hydrate only for carbonyl compounds with electron-withdrawing groups on α-C’s, e.g. Cl3CCHO (chloral). b) Carbonyl + ROH + (acid or base) →← hemiacetal. Slow in pure ROH! Equilibrium favors hemi- acetal only for carbonyl compounds with electron-withdrawing groups on α-C’s, e.g. carbo- hydrates. c) Carbonyl + HC≡N + cat. base →← cyanohydrin. Equilibrium favors product in aldehydes. Ketones are more iffy, but can buy acetone cyanohydrin. Another way to make C–C bond! E.g., almonds make mandelic acid from benzaldehyde in this way. 5. Nucleophilic addition followed by substitution. Acetal formation. a) RCHO or R2CO + R'OH + cat. H+ →← RCH(OR')2 or R2C(OR')2 + H2O. i) Proceeds through hemiacetal. Equilibrium toward acetal by removal of H2O, pushed toward carbonyl by addition of H2O. ii) Most convenient with diols such as ethylene glycol. Entropy favors second reaction. iii) Can be selective for aldehydes over ketones! Thermodynamically controlled. iv) Does not work well for esters or acids! b) Who cares? i) Polysaccharides are made and broken down in this way. Glucose + 4-OH of glucose → maltose →→ starch. Glucose + fructose (anomeric centers linked) → sucrose.