310-10 - CH 310 N T Th 2-3:30 LECTURE 10 Textbook...

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Unformatted text preview: CH 310 N T Th 2-3:30 LECTURE 10 Textbook Assignment: Chapter 16 Continue Homework (for credit): POW 5 posted Today’s Topics: Aldehydes & Ketones (cont’d) Notice & Announcements: Papers in Undergrad office WEL 2.212 Organic Organic Lecture Series Aldehydes And And Ketones Ketones 2 Organic Organic Lecture Series 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 + H- OEt H OEt OEt A d iethyl acetal + H2 O 3 Organic Organic Lecture Series 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 4 Organic Organic Lecture Series 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 5 Organic Organic Lecture Series 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 6 Organic Organic Lecture Series Dean-Stark Trap 7 Organic Organic Lecture Series 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 8 Organic Organic Lecture Series 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 9 Organic Organic Lecture Series 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 10 Organic Organic Lecture Series 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) 11 Organic Organic Lecture Series 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 12 H Organic Organic Lecture Series 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 13 Organic Organic Lecture Series Addition of Nitrogen Nucleophiles Addition Nucleophiles • Secondary amines react with the C=O group of aldehydes and ketones to form enamines 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 14 Organic Organic Lecture Series Morphine NaloxoneAntagonist for acute opiate overdose NatrexoneLonger acting Antagonist Used for opiate & alcohol dependence 15 Organic Organic Lecture Series Addition of Nitrogen 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 H + N H + H2 O An imine (a Schiff base) Ammonia 16 Organic Organic Lecture Series 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 O H 17 C N-R H H H + C N-R + H O + H2 O H A n imin e Organic Organic Lecture Series 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 18 Organic Organic Lecture Series 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 19 Organic Organic Lecture Series 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 20 Organic Organic Lecture Series 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 21 Organic Organic Lecture Series 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 22 NNH 2 + 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 Organic Organic Lecture Series 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 23 Organic Organic Lecture Series H A + H 2O + H 3O [H 3 O ] [A ] [H A ] [H 2 O ] [H 3 O ] [A ] [H A ] [H 3 O + ] [A - ] [H A ] + - + +A - K eq = Note: l and s are not used in K [H 2 O ] K e q = Freshman Flashback!! Ka = 24 Organic Organic Lecture Series 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 25 pKa = -log Ka CH3 CH2 O-H O CH3 CC 2 -H H CH3 C C-H CH2 =CH-H CH3 CH2 - H Organic Organic Lecture Series 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 26 Organic Organic Lecture Series 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 OH A - + CH3 - C-CH3 Keto form CH3 - C= CH2 + A Enol form - *Enol: made from 2 functional groups-alkene and alcohol 27 Organic Organic Lecture Series 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 slow OH CH3 -C=CH2 + H-A En ol f o rm CH3 -C-CH2 -H + :A 28 Organic Organic Lecture Series 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 29 Organic Organic Lecture Series 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) 30 ...
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This note was uploaded on 10/31/2009 for the course CH 310n taught by Professor Iverson during the Spring '08 term at University of Texas.

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