318-12 - Textbook Assignment: Chapter 16 Homework (for...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Textbook Assignment: Chapter 16 Homework (for credit): POW 5 posted Today’s Topics: Aldehydes/Ketones-reactions Exam 1: Grading in Progress Aldehydes And And Ketones Ketones Addition of Alcohols to Carbonyls • Addition of one molecule of alcohol to the C=O group of an aldehyde or ketone gives a hemiacetal • Hemiacetal: a molecule containing an OH and an -OR or -OAr bonded to the same carbon O + H-OEt acid or base OH OEt A he m i ace tal Formation of a hemiacetal-- base catalyzed – Step 1: proton transfer from HOR gives an alkoxide B - + H OR fas t and reversib le BH+ - OR – Step 2: attack of RO- on the carbonyl carbon O CH3 -C-CH3 + – :O-R O:– CH3 -C-CH3 OR – Step 3: proton transfer from the alcohol to O- gives the hemiacetal and generates a new base catalyst O:– CH3 -C-CH3 + H OR OR OH CH3 -C-CH3 + OR - OR Formation of a hemiacetal --acid catalyzed Step 1: proton transfer to the carbonyl oxygen O CH3 -C-CH3 + H-A +H O CH3 -C-CH3 + H-O-R fas t and reversib le + O H A - CH3 -C-CH3 + Step 2: attack of ROH on the carbonyl carbon O-H CH3 -C-CH3 O+ H R Step 3: proton transfer from the oxonium ion to A- gives the hemiacetal and generates a new acid catalyst OH CH3 -C-CH3 + O H R OH CH3 -C-CH3 + H-A OR A - Addition of Alcohols to Carbonyls • Hemiacetals react with alcohols to form acetals Acetal: a molecule containing two -OR or -OAr groups bonded to the same carbon + OH OEt A h emiacetal Psst… He will ask this + H- OEt H OEt OEt A d iethyl acetal + H2 O Step 1: proton transfer from HA gives an oxonium ion HO R-C-OCH3 + H A H H +H O R-C-OCH3 H A n o xo n i u m i on + A:- Step 2: loss of water gives a resonancestabilized cation H + H O R-C OCH3 H + R-C OCH3 + R-C OCH3 + H2 O H H A re so nan ce -stabi l i z e d cati on Step 3: reaction of the cation (an electrophile) with methanol (a nucleophile) gives the conjugate acid of the acetal H + CH3 -OH + R-C OCH3 H + CH 3 O R-C OCH3 H A p rotonated acetal Step 4: proton transfer to A- gives the acetal and generates a new acid catalyst H + CH3 O A: + R-C OCH3 H (4) OCH3 R-C-OCH3 + H-A H An ac e tal Addition of Alcohols to Carbonyls – with ethylene glycol and other glycols, the product is a five-membered cyclic acetal – this a method of “protecting” ketones O + HO OH H + O O Cyclic acetal + H2 O Dean-Stark Trap Acetals as Protecting Groups • How to bring about a Grignard reaction between these compounds: O H Benzald ehyde + Br O H ?? OH O H 5-Hydroxy-5-phen ylpen tanal (racemic) 4-Bromobutanal O BrMg This Grignard cannot be made!! H Acetals as Protecting Groups • a Grignard reagent prepared from 4-bromobutanal will self-destruct (decompose). – first protect the -CHO group as an acetal: O Br H + HO OH H + O Br O A cyclic acetal + H2 O – then prepare the Grignard reagent: O- MgBr+ O O Br O 1 . Mg, ether 2 . C6 H5 CHO A chiral magnesiu m alk oxide (produced as a racemic mixtu re) O – hydrolysis (not shown) gives the target molecule Acetals as Protecting Groups • Tetrahydropyranyl (THP) protecting group THP group RCH2 OH + O Dihydropyran H+ RCH2 O O A tetrahydropyranyl ether – the THP group is an acetal and, therefore, stable to neutral and basic solutions, and to most oxidizing and reducting agents – it is removed by acid-catalyzed hydrolysis Addition of Nitrogen Nucleophiles Addition Nucleophiles • Ammonia, 1°aliphatic amines, and 1°aromatic amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases) imines • Water is removed by Dean-Stark trap or chemical dehydration (e.g. molecular sieves) O CH3 CH + H2 N Acetaldehyde Aniline H + CH3 CH =N An imine (a Schiff base) + H2 O O Cyclohexanone + N H3 Ammonia H + N H + H2 O An imine (a Schiff base) Addition of Nitrogen Nucleophiles Addition Nucleophiles • Formation of an imine occurs in two steps Step 1: carbonyl addition followed by proton transfer O C + H2 N-R O: C - H + N-R H O C H N-R H Step 2: loss of H2O and proton transfer to solvent H H + OH+ O H H + H O C N-R H C N-R H O H H + C N-R + H O + H2 O H A n imin e H Addition of Nitrogen Nucleophiles Addition Nucleophiles – a value of imines is that the carbon-nitrogen double bond can be reduced to a carbonnitrogen single bond H+ - H2 O O+ H2N Cyclohexanone Cyclohexylamine H N (An imine) H2 / Ni N Dicyclohexylamine Does not have to isolated Addition of Nitrogen Nucleophiles Addition Nucleophiles • Secondary amines react with the C=O group of aldehydes and ketones to form enamines (alkene and amine) enamines O Cyclohexanone + H-N H + N An enamine + H2 O Piperidine (a secondary amine) – the mechanism of enamine formation involves formation of a tetrahedral carbonyl addition compound followed by its acid-catalyzed dehydration O H H O N H P ro to n a te d K e to n e H HO N A m in o -a lco h o l HO H N N -P ro to n a te d A m in o -a lco h o l H H HO N H HO N HO N H H A m in o -a lc o h o l O -P ro to n a te d A m in o -a lc o h o l 2 o C a rb o c a tio n N H E n a m in e P ro d u c t Addition of Nitrogen Nucleophiles – the carbonyl group of aldehydes and ketones reacts with hydrazine and its derivatives in a manner similar to its reactions with 1°amines O + H2 NNH2 Hydrazine Reagen t, H 2N -R H2 N-OH H2 N-NH H2 N-NH O2 N O H2 N-NHCNH2 S emicarbazid e Semicarbazone NNH2 + H2 O A hydrazone N ame of D erivative Formed Oxime Ph enylhyd razone N ame of Reagen t Hydroxylamine Phen ylh yd razine NO2 2,4-D initroph enyl- 2,4-D initrop henylhydrazon e hydrazine Acidity of α-Hydrogens Acidity Hydrogens alpha to a carbonyl group are more acidic than hydrogens of other hydrocarbons (e.g. alkanes, alkenes, aromatic). Acidity is measured as Ka O H α H α H H H A + H 2O K eq = Note: and s are not used in K H 3O + + A [H 3 O + ] [A - ] [H A ] [H 2 O ] [H 3 O + ] [A - ] [H A ] [H 3 O + ] [A - ] [H A ] [H 2 O ] K e q = Freshman Flashback!! Ka = Acidity of α-Hydrogens Acidity Hydrogens alpha to a carbonyl group are more acidic than hydrogens of alkanes, alkenes, and alkynes but less acidic than the hydroxyl hydrogen of alcohols Type of Bond pKa 16 20 25 44 51 pKa = -log Ka CH3 CH2 O-H O H CH3 CC 2 -H CH3 C C-H CH2 =CH-H CH3 CH2 - H α-Hydrogens are more acidic because the enolate anion is stabilized by: 1. delocalization of its negative charge 2. the electron-withdrawing inductive effect of the adjacent electronegative oxygen OCH3 -C=CH2 + H-A O CH3 -C-CH2 - H + :A - O CH3 -C CH2 Re so nanc e -stabi l i z e d e n ol ate ani o n Note: α-hydrogens are not so acidic that they will destroy organometallic reagents Keto-Enol Tautomerism – protonation of the enolate anion on oxygen gives the enol form*; protonation on carbon gives the keto form O CH3 - C-CH2 H- A - OCH3 - C= CH2 H- A Enolate anion O Keto form OH A - + CH3 - C-CH3 CH3 - C= CH2 + A Enol form - *Enol: made from 2 functional groups-alkene and alcohol Keto-Enol Tautomerism – acid-catalyzed equilibration of keto and enol tautomers occurs in two steps Step 1: proton transfer to the carbonyl oxygen O CH3 -C-CH3 + H-A Keto form fas t and reversib le + O H • • CH3 -C-CH3 + A The conju gate acid of the ke to ne Step 2: proton transfer to the base A+ O H - CH3 -C-CH2 -H + :A slow OH CH3 -C=CH2 + H-A En ol f o rm Keto-Enol Tautomerism Keto-enol enol equilibria equilibria for simple aldehydes and ketones lie far toward the keto form Keto form O CH3 CH O CH3 CCH3 O Enol form OH CH2 = CH OH CH3 C= CH2 OH % Enol at Equilibrium 6 x 10-5 6 x 10-7 1 x 10-6 O OH 4 x 10-5 Keto-Enol Tautomerism For certain types of molecules, however, the enol is the major form present at equilibrium – for β-diketones, the enol is stabilized by conjugation of the pi system of the carbon-carbon double bond and the carbonyl group – for acyclic β-diketones, the enol is further stabilized by hydrogen bonding (i.e.1,3 diones) ...
View Full Document

Ask a homework question - tutors are online