Hydration of Ketones and Aldehydes H H H O O H H H H HO OH H2O O O HO OH O a hydrated ketone H H O HO OH H2O Keq = 2000 uncrowded H H H H Aldehydes exist as partial hydrates in aqueous solution: O HO OH H2O Keq = 1 more crowded Me H Me H O H O HO OH Ketones generally do not favor hydration: 2 Keq = 0.002 very crowded Me Me Me Me Nucleophilic Addition of "O–" to Carbonyl Groups Na O O OH H+ (workup) O HO Na + H2O Me Me Me Me Me Me OH OH Me Me A hydrated ketone Starting material! pKa of H2O: approx. 16 pKa of alkoxide: 16-20 Na O O OH H+ (workup) O MeO Na + MeOH Me Me Me Me Me Me OMe OMe Me Me A hemiacetal Starting material! (usually unstable) pKa of MeOH: approx. 15 pKa of alkoxide: 16-20 Hydration of Ketones and Aldehydes 18 O 18 O H2 O + Me Me H cat. Me Me H H H 18O 18O H H H Me Me H H Me 18 18 O O H O OH O H H Me 18O Me Me H H H18O OH H Me Me 18 H O a hydrated ketone Me Me H 18 H O OH2 18 O 18O Me Me Me Me Addition of Alcohols to Carbonyl Groups: Acetal Formation O ROH, H+ RO OR Me Me Me Me An acetal MeOH H+ Me Me H H Me O O MeO OH H+ Me MeOHMe Me MeO OH MeOH Me Me a hemiacetal MeO OMe H Me Me Me MeO OH2 Me Me MeO OMe O Me Me Me An acetal Me MeOH H2O Acetals as Carbonyl Protecting Groups O OH MeMgCl Me Me Me Me Me MeO OMe MeMgCl No reaction Me Me O Br O Li–Bu O P(Ph)3 Br (Ph)3P X (Ph)3P Me Me Me Butyllithium will react with the ketone, and the reagent will react with itself! O MeO OMe MeOH, H+ MeO OMe (Ph) P Br Br 3 Me Me Me A stable reagent O O MeO OMe + H2O, H Me Me Cyclic Hemiacetals MeOH H+ Me H Me MeOH Me H MeO OH O O MeO OH Me Me Me Me MeOHMe a hemiacetal (usually unstable for ketones, sometimes stable for aldehydes) O + O catalytic H O H HO HO H H H H OH OH OH O O solvent a cyclic hemiacetal H (usually stable for 5- and 6-membered rings) Cyclic Hemiacetals in Biological Systems: Carbohydrates OH OH OH OH OH H + catalytic H H HO HO HO OH (not necesary, but OH OH O accelerates formation) OH OH O OH H HO D-glucose (linear form) O H OH H CH2OH HO H O OH HO OH HO O H OH HO H OH a hemiacetal β-D-glucose (cyclic form) Cyclic Hemiacetals in Biological Systems: Mutarotation in Carbohydrates H OH CH2OH H O HO HO OH OH HO H OH O H H HO OH OH β-D-glucose (cyclic form) HO OH OH OH H2O H OH HO HO OH OH O O OH H D-glucose (linear form) H CH2OH H HO O HO H OH HO O H OH H OH HO OH α-D-glucose (cyclic form) The process of equlibration (epimerization) at the hemiacedtal (anomeric) carbon is called mutarotation. The Nitrogen-Equivalent of a Carbonyl Group: Imines and Hydrazones H O NH3 N Me Me Me Me an imine NHR O H2N–NHR N Me Me Me Me a hydrazone Basic conditions: H proton transfer H H O NH H N OH OH N 3 H3N O (via solvent molecules) 2 N Me Me Me Me Me Me Me Me Me Me a carbinolamine Acidic conditions: H H proton transfer H H O NH H N OH2 NH N 3 H3N OH (via solvent molecules) 2 N 3 Me Me Me Me Me Me Me Me Me Me a carbinolamine The Nitrogen-Equivalent of a Carbonyl Group: Imines and Hydrazones O OH N an oxime hydroxylamine H2N OH NH2 N hydrazine H2N NH2 a hydrazone Ph H phenylhydrazine H2N N NH N a phenylhydrazone NO2 H 2,4-dinitrophenylhydrazine (2,4-DNP) H2N N NO2 a 2,4-dinitrophenylhydrazone NO2 NH O2N N O NH2 O H semicarbazide H2N N NH a semicarbazone N NH2.