Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl ..., Study notes of Organic Chemistry

Download Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl ... and more Study notes Organic Chemistry in PDF only on Docsity! 115 Chapter 17: Aldehydes and Ketones: Nucleophilic Addition to the Carbonyl Group 17.1: Nomenclature (please read) suffix: –al for aldehydes –one for ketone 17.2: Structure and Bonding: The Carbonyl Group: Carbonyl groups have a significant dipole moment C O δ + δ - Aldehyde 2.72 D Ketone 2.88 Carboxylic acid 1.74 Acid chloride 2.72 Ester 1.72 Amide 3.76 Nitrile 3.90 Water 1.85 C O C O Carbonyl carbons are electrophilic sites and can be attacked by nucleophiles. The carbonyl oxygen is a basic site. 116 17.3: Physical Properties (please read) 17.4: Sources of Aldehydes and Ketones (Table 17.1, p. 693) 1. Oxidation of Alcohols a. Oxidation of 1° and 2° alcohols (Chapter 15.9) b. From carboxylic acids and esters (Chapter 15.3) c. Ketones from aldehydes 117 2.  Ozonolysis of alkenes (Chapter 6.12) 3.  Hydration of alkynes (Chapter 9.12) 4.  Friedel-Crafts Acylation – aryl ketones (Chapter 12.7) 118 17.5: Reactions of Aldehydes and Ketones: A Review and a Preview Reactions of aldehydes and ketones (Table 17.2, p. 695)- Review: 1.  Reduction to hydrocarbons (Chapter 12.8) a. Clemmenson reduction (Zn-Hg, HCl) b. Wolff-Kishner (H2NNH2, KOH, Δ) 123 17.8: Reaction with Alcohols: Acetals and Ketals Acetals are geminal diethers - structurally related to hydrates, which are geminal diols. R RC O OHC OH R R + H2O - H2O hydrate (gem-diol) aldehyde hemi-acetal acetal (gem-diether) ketone hemi-ketal ketal (gem-diether) R HC O OR'C OH R H + R'OH - R'OH + R'OH - R'OH OR'C OR' R H + H2O R RC O OR'C OH R R + R'OH - R'OH + R'OH - R'OH OR'C OR' R R + H2O 124 Mechanism of acetal (ketal) formation is acid-catalyzed (p. 705) The mechanism for acetal/ketal formation is reversible. How is the direction of the reaction controlled? Dean-Stark Trap 125 Dioxolanes and dioxanes: cyclic acetal (ketals) from 1,2- and 1,3-diols R RC O HO OH+ OO R R H+, - H2O H3O+ R RC O HO+ R R H+, - H2O H3O+ OH OO 1,3-dioxolane 1,3-dioxane 1,2-diol 1,3-diol 126 17.9: Acetals and Ketals as Protecting Groups Protecting group: Temporarily convert a functional group that is incompatible with a set of reaction conditions into a new functional group (with the protecting group) that is compatible with the reaction. The protecting group is then removed giving the original functional group (deprotection). O OCH3 O NaBH4 OH OCH3 O keto-ester O OH cannot be done directly 127 O a) NaNH2 b) H3C-I O CH3 The reaction cannot be done directly, as shown. Why? Aldehyde or ketone hemi-acetal or hemi-ketal acetal or ketal 17.10: Reaction with Primary Amines: Imines (Schiff base) Aldehyde or ketone carbinolamine Imine O C RR + R'OH - R'OH OH C OR'R R + R'OH - R'OH OR' C OR'R R – H2O + H2O OR' C RR + O C RR + R'NH2 - R'NH2 OH C NHR'R R + R'NH2 - R'NH2 NHR' C NHR'R R – H2O + H2O N C RR R' 128 Mechanism of imine formation (p. 709): See Table 17.4 (p. 712) for the related carbonyl derivative, oximes, hydrazone and semicarbazones (please read) O N N-C6H5 H2NOH N OH phenylhydrazoneoxime C6H2NHNH2 N H2NHNCONH2 N H NH2 O semicarbazidesemicarbazone" 133 • There will be two possible Wittig routes to an alkene. • Analyze the structure retrosynthetically, i.e., work the synthesis out backwards. • Disconnect (break the bond of the target that can be formed by a known reaction) the doubly bonded carbons. One becomes the aldehyde or ketone, the other the ylide. R3 CC R2 R1 R4 Disconnect this bond C R2 R1 O R3 C R4 Ph3P+ C R2 R1 PPh3 R3 C R4 O+- OR - C C CH3CH2CH2 H CH3 CH2CH3 134 17.13: Stereoselective Addition to Carbonyl Groups (please read) 17.14: Oxidation of Aldehydes Increasing oxidation state C C C C C C C OH C O C O OR CO2 C NH2 C NH C N C Cl C Cl Cl C Cl Cl Cl C Cl Cl Cl Cl 135 RCH2-OH R H O R H HO OH R OH O hydrationH3O+, acetone H2Cr2O7 1° alcohol H3O+, acetone H2Cr2O7 H2O CH2Cl2 PCC OH CO2HCHO 1° alcohol H3O+, acetone H2Cr2O7 Carboxylic AcidAldehyde Aldehydes are oxidized by Cr(VI) reagents to carboxylic acids in aqueous acid. The reactions proceeds through the hydrate See Chapter 15.9 136 Baeyer-Villiger Oxidation of Ketones. Oxidation of ketones with a peroxy acid to give as esters (p. 732) R R' O O O Cl OH + R O O R' ester OH O Cl + Oxygen insertion occurs between the carbonyl carbon and the more substituted α-carbon CH3 O H3C O mCPBA mCPBA O O O O H3C 137 17.15: Spectroscopic Analysis of Aldehydes and Ketones Infrared Spectroscopy: highly diagnostic for carbonyl groups Carbonyls have a strong C=O absorption peak between 1660 - 1770 cm-1 Aldehydes also have two characteristic C–H absorptions around 2720 - 2820 cm-1 Butanal 2-Butanone C=O (1730 cm-1) C=O (1720 cm-1) C-H C-H 2720, 2815 cm-1 O CH 138 C=O stretches of aliphatic, conjugated, aryl and cyclic carbonyls: Conjugation moves the C=O stretch to lower energy (right, lower cm-1) Ring (angle) strain moves the C=O stretch to higher energy (left, higher cm-1) H O H O CH3 O H3C CH3 O aliphatic aldehyde 1730 cm-1 aliphatic ketone 1715 cm-1 conjugated aldehyde 1705 cm-1 conjugated ketone 1690 cm-1 H O aromatic aldehyde 1705 cm-1 CH3 O aromatic ketone 1690 cm-1 O O O O 1715 cm-1 1750 cm-1 1780 cm-1 1815 cm-1