Nucleophilic Addition to Carbonyl Group: Synthesis & Reactions - Prof. Janice Phillips, Study notes of Organic Chemistry

Download Nucleophilic Addition to Carbonyl Group: Synthesis & Reactions - Prof. Janice Phillips and more Study notes Organic Chemistry in PDF only on Docsity! Chapter 16 Aldehydes and Ketones I Nucleophilic Addition to the Carbonyl Group The general structure of the carbonyl group is C=O H R : : O C The general formula for an aldehyde is And that for a ketone is C=O R' R : : C=O H H : : There is also the unique aldehyde, formaldehyde, in which there are two hydrogen atoms attached to the carbonyl group. The R groups can be either alkyl or aryl. O C O C - + 120o The polarization of the double bond of the carbonyl group arises from the difference in electronegativities between C (2.5) and O (3.5). General Features of the Carbonyl Group C=O R R' δ-δ+ μ = 2.3-2.8 D The contributing resonance structures are: The carbon and oxygen atoms are both sp2 hybridized. The C O bond polarization is clearly evident in this map of electrostatic potential for the simplest ketone, acetone (CH3COCH3). IUPAC systematic names for ketones are based on these rules: (1) The name of the longest alkane chain present that contains the carbonyl group is used as the parent. (2) Replace the "e" in the alkane name with the suffix "one" and indicate the carbonyl position by a number. Number from the end that gives the lower number to the ketone position. (3) Designate the substituents and their positions in the usual way. 2-Pentanone 2-Methyl-4-phenyl-3-pentanone O O Note use of alphabetical order. O (E)-3-Penten-2-one Note provision for C C bond. Physical Properties of Aldehydes and Ketones Because of the polar carbonyl group (μ ~ 2.3-2.8 D), aldehydes and ketones have higher boiling points than hydrocarbons of comparable size. However, they have lower boiling points than alcohols of comparable size because only the latter have intermolecular hydrogen bonds. CH3CH2CH2CH3 CH3CH2CH CH3CCH3 CH3CH2CH2OH O= O= Butane Propanal Acetone 1-Propanol MW 58 58 58 60 BP -0.5 oC 49.0 oC 56.1 oC 97.2 oC Aldehydes and ketones form hydrogen bonds to water molecules and consequently the lower MW ones are soluble in water up to about C6. The smallest ones (formaldehyde and acetone) are miscible with water. O H O H H O H Synthetic Methods for Aldehydes Because aldehydes are between 1o alcohols and carboxylic acids in the oxidation-reduction sequence, they can be synthesized by either selective oxidation of 1o alcohols or by selective reduction of carboxylic acid derivatives. RCH2OH RCH O= RCOOH[O] [H] [O] [H] or RCOX Selective Oxidation with Pyridinium Chlorochromate (PCC) PCC CH2Cl21-Heptanol Heptanal (78%) PCC is It is a unique Cr +6 oxidant. Other oxidants carry oxidation on to the carboxylic acid stage because aldehydes are more easily oxidized than alcohols. OH H O N H Cl CrO3 Hydride Transfer Mechanism RC-Cl :O:= H-Al-OC(CH3)3 OC(CH3)3 OC(CH3)3 -Li + RC-Cl :O: : - H H:- is a nucleophile RC-Cl :O: : - H RCH O= + Cl- Cl- is a good leaving group CCl O= NO2 p-Nitrobenzoyl chloride (1) LiAlH(O-t-Bu)3, -78 oC (2) H2O CH O= NO2 p-Nitrobenzaldehyde Note selective reduction of acyl chloride in presence of nitro group. A specific example: Reduction of Esters with DIBAL-H Esters are selectively reduced to aldehydes with DIBAL-H when one equivalent of the reducing agent is used at low temperature. RCOR' O= Ester (1) 1.0 eq (i-Bu)2AlH, -78 oC (2) H2O RCH O= Aldehyde A Proposed Mechanism DIBAL-H is a trivalent aluminum species and is coordinatively unsaturated (i.e., a Lewis acid). The aluminum complexes with a nonbonding electron pair of the carbonyl oxygen: R-C :O-R': :O:= Al i-Bu i-Bu H R-C :O-R': :O= Al H i-Bu i-Bu + - (Lewis complex) A hydridoaluminate Hydride Transfer: Nucleophilic Addition to the Carbonyl hydride transfer reductionR-C :O-R': :O= Al H i-Bu i-Bu + - H2O R-C-H :O-R': :O : Al(i-Bu)2 R-C- :O:= H AldehydeR-C-H O : Al(i-Bu)2 - RO- At higher temperature and with excess reagent, the aldehyde products are reduced to primary alcohols. Ketones from Nitriles Reaction of a nitrile with either a Grignard or organolithium reagent, followed by hydrolysis, yields a ketone. R-C N: Nitrile (R = alkyl or aryl) + R'-M ether R-C-R' N-M= Imine salt R-C-R' O=H3O+ H2O The nitrile is a polar function similar to a carbonyl. The carbanionic center of an organometallic reagent adds to the electropositive carbon of the nitrile producing the salt of an imine. δ- δ+ During aqueous workup, the imine is hydrolyzed to a ketone. R-C=N-M : + H-O-H R-C=N- R' H : Imine hydrolysis R-C=O: R' : R' δ- δ+ δ- δ+ Examples Butanenitrile (1) ether (2) H3O+ + O Butyrophenone (Phenyl propyl ketone) MgBr N Benzonitrile +N: Li (1) ether (2) H3O+ Ketones by Hydration of Alkynes Alkynes, like alkenes, add water in the presence of electrophilic catalysts such as H+ or Hg2+. Hydration of alkynes is conducted in aqueous solutions of sulfuric acid with mercuric sulfate as catalyst. It follows Markovnikov's rule, with the hydrogen attaching to the carbon with the greater number of hydrogens. -C C- Alkyne + H2O HgSO4 H2SO4 -C=C- H OH "Enol" (or vinylic alcohol) fast -C-C- H H O= The "enol" rapidly rearranges to the ketone. The enol and ketone constitutional isomers actually are connected by an equilibrium which usually lies heavily on the side of the ketone. This process called tautomerization is catalyzed by acid. -C=C- H :OH: O H H+ H2O + -C C- H H :OH = + Conjugate acid of ketone Enol form (less stable) + H -C C- H H :O: = H3O++ Keto form (more stable)