Chapter 20: Aldehydes And Ketones

Chapter 20 Aldehydes and Ketones Ketones and Aldehydes • Only carbon and hydrogen atoms bonded to the carbonyl group • Aldehydes and ketones exhibit dipole-dipole interaction. • Aldehydes and ketones give a strong peak at ~1700 cm-1 due to the C=O; The sp2 hybridized C – H bond of an aldehyde shows two peaks at 2720 and 2820 cm-1 • The sp2 hybridized C – H proton of an aldehyde absorbs at 9 -10 ppm in a 1H-NMR; the carbonyl carbon appears in the 190215ppm region in 13C-NMR • Protons on the α carbon to the carbonyl group absorb at 2-2.5ppm Nomenclature 1. 2. 3. 4. Identify and name the parent chain Identify the name of the substituents (side groups) Assign a locant (number) to each substituents Assemble the name alphabetically 1. Identify and name the parent chain – For aldehydes, replace the “-e” ending with an “-al” – the parent chain must include the carbonyl carbon The aldehydic carbon is assigned number 1: Nomenclature 1. Identify and name the parent chain – For ketones, replace the “-e” ending with an “-one” – The parent chain must include the C=O group – the C=O carbon is given the lowest #, and can be expressed before the parent name or before the suffix Reactivity increasing reactivity Reactivity: When ranking the reactivity for all carbonyl compounds Reactivity: most reactive O R Cl acid chlorides least reactive > O R O O O O R acid anhydrides > R H aldehyde > R ketone O O > R OH ~ carboxylic acids R O OMe esters > R NH2 amides Carboxylic acids and their derivatives react with nucleophiles to form substitution products (See Chapter 21). Aldehydes and ketones react with nucleophiles to form addition products – carbon anion and hydride anion are extreme strong bases and therefore very poor leaving group. Nucleophilic Addition Reactions • The carbonyl carbon is electrophilic (with partial positive charge) O R Y O R C Y Nu + Nu H H OH R C Y Nu Y = carbon or hydrogen O or H3O+ a tetrahedral intermediate 1. React with hydride (Reduction reactions) O R R1 + H R, R1 = H,alkyl, aryl O R C R1 H H H O HO or H3O+ R C H R1 H = NaBH4 and LiAlH4 Both NaBH4 and LiAlH4 donate H-; NaBH4 only react with acid chlorides, aldehydes, and ketones; LiAlH4 react with all carbonyl compounds in the previous slide. Nucleophilic Addition Reactions 1. React with hydride (Reduction reactions) H R O C O LiAlH4 R C H Z O Z R O R C H H H H H H O HO or H3O+ R C R = H,alkyl, aryl Z = Cl, OR Also, R O C 1) LiAlH4 HO OH 2) H O+ 3 R C H R H O 1) NaBH4 NH2 1) LiAlH4 H 2) H2O R R = H,alkyl, aryl R = H,alkyl, aryl O O C 1) LiAlH4 OCH3 2) H O+ 3 2) H3O+ O O 1) LiAlH4 2) H3O+ O 1) NaBH4 (xs) 2) H2O HO O O 1) LiAlH4 (xs) NH2 2) H2O C H NH2 H H 2. React with carbon anions RCH2 O R O R C R1 CH2R RCH2MgBr R1 or RCH2Li H H HO O or H3 R O+ C CH2R R1 R, R1 = H,alkyl, aryl RCH2MgBr (Grignard) and RCH2Li (Organolithium reagents) RCH2 R O C RCH2MgBr Z H O O R C Z CH2R or RCH2Li R = H,alkyl, aryl R RCH2 CH2R H O O R C CH2R or H3O+ CH2R Z = Cl, OR O 1) EtMgBr H O O 1) CH3MgBr 2) H2O + 2) H3O O 1) MeLi 2) H2O HO R C CH2R CH2R 2. React with carbon anions • Grignard, Organolithium reagents, and hydrides = basic conditions Mg 2Li • Synthesis: R Br R MgBr R Li + LiBr R Br • Both Grignard and Organolithium are water sensitive, means that they react first with hydrogen of OH group of H2O, alcohols, and carboxylic acids. RCH H 2 O C R RCH2MgBr H O R or RCH2Li O C H O O or H3O+ R O C OH • Grignard can react with CO2 to produce a carboxylic acid. R O C O RMgBr + CO2 O HO 1) MgBr (1 eq.) O R O- H3O+ O R 1) Mg 2) D2O Br 1) Mg 2) CO2 3) H3O+ OH Br 2) O OEt 3) H2O n ---- -H 1 - ↳ 2) D20 a -H Gracie Y: on - EtoD O -o ~ pay mos OH ① ⑦ examples ↓I T -H -- ↑ A Will with - -- A react CH3 - will react with Grignard H -- ↑ Grignard I 0 organolithiumA or /-- first Organolithium D first Or ⑪ : ↑ 0 ⑭n inspi** " : H3 - 0 - I H Sibli 15-de --- S -- ⑦ A e H-0 Grignard with can CO2 -> react forms S 1) Et RMgBr n E - -nett 0 - - - H carboxylic Acid " -Br - 1 COOH . - BrMg/- 3) A30 Answer : I - ot - v ⑧ - - Ill -- - O 11 -- - - 0H * amaterial again 3. Aldehydes&Ketones react with triple bond R O C C N NaCN R1 HCl O R C CN R1 H+ R, R1 = H,alkyl, aryl R C C H O NaNH2 NaCN HCl R C C R O C R1 OH R C CN R1 R R C C C O R1 H3C C C H 1) NaNH2 2) 3) H2O O H NaCN HCl O H2O R R C C C OH R1 4. Aldehydes&Ketones react with 1° and 2° amines H+ O C TsOH + RNH2 R1 R 1° amine R, R1 = H,alkyl, aryl R O C H+ TsOH R + R2NH 2° amine R, R1 = H,alkyl, aryl R1 R O C H O C RNH2 R1 H OH R C N H R1 R H R1 R2NH R TsOH : OH2 R C R1 H OH C N R R1 R R N H R R H3C C R1 SO3H H N R R1 Imine R TsO R1 R N R R1 R N R R TsO N R OH2 R H N R • Both reactions are reversible. • Both imine and enamine are aqueous acid sensitive, means that, in any aqueous acid solutions, imine and enamine are reverse back to aldehyde/ketone. The mechanism of hydrolysis for imines and enamines is simply the reverse of their mechanisms of formation. O TsOH N H H3O+ R1 Enamine • Both reactions need the catalyst, TsOH (HCl gas or trace H+ in some books) CH3NH2 R S sign-of · S want- R -x ei9 ② " I + - / R - C=C H - R - - -] E C=C C =C I H --I - R - ↑* R - c = c -- + :: reaction j - Wa ⑦ SNL NaNHz - - C= C : wa e I need a BASE this string to remove * hydrogen ... NHe Nat -- H , - 3) H2 A : D - Ketones : Aldehydes React Withi 1 amines and 20 amines ⑤ Ex -PE At acid : TsOH It R ]_ ")JustDaSo : ③ R it * -- - + ↑ di i - CH3N2 * reversible - " -- [Ss) R - C ⑰ vi H I i - - G ensur It CH3 -- * since this is reversible, to it Tot motia I use go back Hzot ! imine R - -- Itee To Examples O H + NH2 TsOH H3O+ N O N N H examiHCl(aq) ne TsOH O C O NH2OH O C TsOH O C H2NHN H2NHN NH2 TsOH NO2 O2N TsOH O NH2 TsOH + N H3O amples - ... 10 I1 + TsOH + / I ~ 1I ve CHNA2+1I H - 17 . 8 H / / 1 + NH - l - I ⑧ / - N - H &Ii - Ell / -> - - I - H + -1t - I & ⑦ - - - H e 1 N- --N- ⑰ - H * CH3 - "I F E -> n .. -- -N- - : ↳ I 1 it H - - 9 H D H Il & ⑧ - H SiN &- -> * -I -1 --④ - 1 - g Kell -> - i CH3 : Sn --- - ↑ O H NE reversible ! -- * - - For Gr * on i -> ... / ab I i -- CH3NHz- H - ↑ T + - & -aN-CHzCl3 NI+ 2 0 ↑ + - it Ts : I - /X -> I i - - - / --H III [F+ ! It TSOH - ⑰ / =o 1 - I H -> - - I I-> I ⑰ - -> I& - e - / - &: -- > I 1 - ↓ [ It - Ts ⑦ I - H30 -I -- ~ - 1 Il -- Wolff-Kishner and Clemmensen • Wolff-Kishner reduction is a two-step synthesis, converting a ketone to an alkane: Zn-Hg, HCl O C ∆ R1 NH2NH2, KOH ∆ H2 C R1 H2 C R1 Clemmensen reduction Wolff-Kishner reduction 5. Addition of H2O – hydration • In the presence of an acid or base, an aldehyde/ketone in H2O is in equilibrium with its hydrate: O R H2O R1 H O+ or -OH 3 OH R R1 OH • With less stable carbonyl starting materials, equilibrium favors the hydrate product, whereas the more stable carbonyl starting materials, equilibrium favors the carbonyl staring materials. • Electron-donating groups near the carbonyl carbon stabilize the carbonyl group, decreasing the amount of the hydrate at equilibrium. • Electron-withdrawing groups near the carbonyl carbon destabilize the carbonyl group, increasing the amount of hydrate at O O O O equilibrium. Cl Br Cl A C B D Cl Rank from the most hydrate to least hydrate RX- - 0 Il - ↳enyde with * water acidic/baric reaction in electron group * ⑮ E * H20FH-i 0 Il with .. CH3 & I Rether drawing close to the hydrate - increase c=o ; hydrate + must D > A hydrate -> least * Ketones and Alconol Aldehydes reacting with - I E : - e ranser intermolecular Proton A H iso. o . - o- H a S -Ag-b- need ⑰ gi ] * . N - L CH3 -- - - - - + CHI OH 11 - -> & Lintramol H20 ~- F [is) I C - ② S CH30oltz 30+ It . R CH30 n R H - a- -chs Ho · ↳! [KIT CHOH -H - / 1403 / 1 = 11 -~ ⑰ CH3 - Il - ⑰ - : -- >--H / I - , acctal & CH3 ③ - ⑦ -Jes - - - . It - i OCH3 - - CHs c · [ ⑰ ET-i i cit ! or C40 / -- E I reversible Fetal Alt ] ] · - j · - H C3D d I ⑰CH3 & I , RXX - - - -c O + [ /]-] - Il -- - it / send ~ ] :o a - Vane a 3 0 positive charge= base; good earing group B >C > cetal weaker hydrate to a Or amount e - ketal product B CHO/octs R - ⑰ · H . ·. . - I o H & 0 It /- - - H - I CH3 : - 0 2 + CH30 : 0 - -- 1 + Hor- Ho o · ⑦ A - - i!H - L L 1 ↑ H - I " Ho H -O - G~~⑰ / -> - + H20 : I " ⑰ -8 ⑰ b 2 &It -- > H 5 1 - - : T - -o L - - I / - 6. Aldehydes&Ketones react with alcohols R O C H+ + ROH R1 TsOH R O C H ROH R1 R, R1 = H,alkyl, aryl H OH R C O R1 R TsO OR R C OH R1 hemiacetal H+ RO OR R R1 acetal TsO OR R R C O R1 H R ROH R O C R1 OH2 R C OR R1 Conversion of an aldehyde or ketone to an acetal or ketal is a reversible reaction, so an acetal or ketal can be hydrolyzed to an aldehyde or ketone by treatment with aqueous acid. O H CH3OH TsOH MeO OMe H H3O+ Examples O OH O EtOH O O TsOH O O TsOH HO HO CH3OH H TsOH actual ether reaction etual ! MeO OMe O acid aqueous solution H3CO 0 + N - CH30H alcohol ↓ OH · OH alcohol -accomOH hymine ↓ ⑧ OH CH2OH CH3OH (xs) TsOH 0 ·C3 in -- OH ↓H I HzC0-19 H3O+ ⑧ ether ether H3CO O OCH3 · ④ actor/retal ⑨yether OCH3 - Jaz OCH3 CH2OCH3 /oH - di Mymine ·H H30 H3CO H3CO a O ether Nether CH2OH O icono · astal Fetal A HCl (aq) ----II happens ↳o acidaguerese OCH3 ↓ ↓ H3O+ HO TsOH HzC0 H3O+ ICOCH3 - 10-OH I I its-oclts -> CO 0- o ! · O Fit : ! T ↓ - -> --0O H : 2 ,e - - - ↓ / : O ↓ - H ~ I - !* -g I 8 ↓II I ↳ I 0 -11 /2 ... -H ! It - / ,- - H ⑦ - H - & -O r - H + no Examples / - it ↓ , ② Ho-XR ⑦ I TSOH Y -H &It - = i 3 / 4 - S 2 I - H ~ /H · - H ! Id - -: 0 . - ↳ - H - I o *. - H n, So S - CHz - E s Protecting groups • Acetals and ketals are valuable protecting groups for aldehydes and O ketones. O O ? ? a ↓E OH COOH further -* nicunmainant ita 0 COOCH3 * cannot go - 0 re - I - ↳ * cannot as or - carbon tertiary SN2 AHACK is carbon backside D O O OCH3 Yester d O ? OH ISOH HOTH 1 00 17 d 0 AzOT ↓ - LIAIH4 oct3 - * will the XoH H30 protonate 8 and will change the acetal/ retal back to a double bond carbonyl Wittig Reactions • Ketone/aldehyde is converted to an alkene, with the formation of a R1 new C=C double bond O R Ph3P Ph3P R R R2 C R2 R1 O 2 R1 PPh3 ylide R R • A ylide is synthesized in two steps from the corresponding alkyl halide: S 2 PPh3 + R Br N Ph3P R KOBut Ph3P R H O H + Ph3P COOEt Br CH3I 1) PPh3 2) KOBut O 3) 1) PPh3 2) KOBut O 3) - ⑪ &⑧ It R Ph3 + -- - ylide : I D -- I - I ⑩o Phy C a 0 - ans RI * positive being 0 I - a ↑ ... 12 i grig 2 men CHzCuLi-1 , 4 , 2 ④ addition addition Li 1 , 4 addition * -- : 1 in - it - C < = WherYoth with the OH X + 1 0 act Fit + PhP - - --- Past e 0 the double group bond - * ... -R Wi 0 Ph3P It En L & functional = so CH3I 0V have R-x- ving CHzMgBr-1 ⑦ -> ⑧Phy CH3Br addition ph3P - - - 2is de or ring i the the CH3 * I 12 (ULl organithium nauch with from * H - - - it as Hacks A (CHz) 4 = 0 ⑦ = aringor a or ⑳ four-membered stable Vee NOT is not L form negative ↓minel ⑧ e - only R R- -> me-undtagwowisie ⑦ - adding 0-PPh3 Ie SI ↑ a + -- ⑦ - O phyP - PhyP -> = P enol 1 ! group tab * uns -Phy 'H2 : : - I - 2 Po + 2 S ⑰ ⑦ in I ↑ O 3 = ↳ - PP43 ↓ 0 0 S 3 dHz * 2 + Ph3P=2 , 00E+ -then , Ketone -T-A - coot will replace the or alphal anlithium with nipha : Beta unsaturated Ketores and aldehydes Ketore ⑤ ·double R-X oxygen L & &1/2 COUNT YOUR CARBONS !!! 0 : TWO Targets To have choose - l! 3 CzMg BU - ↓ Us I 0 i : I -> Grignard cr ⑰ Rex ⑦ have a i 0--1 - 2 , unsaturated you'll position position Bor4 a On : - R 1 NEVER beta aldehydes reacting and remove the oxyen on the carbonyl double bond * Grignard Org ↑COOEt Il 0 -- - H k ↓ 443 - - - -- - = - : ⑪ %Ateculi HO I - .. ⑪ I - Ets ⑦ :; - I n 0H + - 11 -- -- R ⑲ Reaction of α, β - unsaturated aldehydes & ketones. O1 R 2 O 4 R 3 • Can have 1,2-addition or 1,4-addition. • Grignard and Organolithium have 1,2-addition. CH3 1 O R 2 4 1) MeMgX or MeLi 1 O R 2 3 4 2) H3O+ 1 HO R 2 3 4 3 • Gilman reagents have 1,4-addition. CH3 1 O R 2 3 1) (CH3)2CuLi 4 1 O R 2 3 2) H3O+ 4 1 O R 2 3 4 Reaction of α, β - unsaturated aldehydes & ketones. O A ? 1) EtLi 1) Et2CuLi 2) H3O+ 2) H3O+ O I HO ? E O O 2 3 B A 4 O F G C D OH OH H O additasa E events e Preparation of Aldehydes and Ketones • aldehyde preparation R OH 1°alcohols R H R1 O R O PCC R Z O R + H O R1 H H DIBAL = H Al H2SO4, H2O R 1) O3, -78°C 2) CH3SCH3 R R O 2) H2O + R O R1 O 1) R2CuLi Cl R2 O HgSO4 H R1 R1 or PCC O 1) LiAl(OBut)3H or O DIBAL R R2 2°alcohols R O O or KMnO4+ H2SO4 H -OH 1) O3, -78°C 2) H2O Z = Cl, OR R1 R 2) H2O2, K2Cr2O7+ H2SO4 OH H 1) BH3 2) CH3SCH3 R ketone preparation R R O + O R AlCl3 Cl R ③ ampec - CH3 M At conditions, aldehyde bread For = 0 K2CV20 RX - Y H 10 I 172202 aldehyde To make aldehyde He : i alkyne ⑤ - OH can carboxylic reactive - HH32) Hz0z -OH , RH ⑧ R + in c , R -- oH # -Rit 1 ↓ ② zo carbon co = as - 0 It - -H !-H H2SO4 PCC 3 nO reactiontertiary with carbon PCC : treat ↑ -> * retire cout kMnOY & excess XXXoH AOOlt e = Aldehyde 2 0 It --- ↓ * kMNOY 10 = R or Carboxylic Acid KzCV20n 3: no Ketone , nothing reaction H / H " aldehyde - H20 - H itzo R- platone R methyl replaced the chloride 10 primary - , Finalis * ① 1 = ⑬ adid , since more - ④ oxidize to further R R kmnot - 2 it It UV a ④ ↑ out 0 k2CV201 2x OH I its z I H2804 *+ -Mister R-* dition T 0 i R Summary of reactions R O C 1) H R1 2) H3 HO O+ R C H R R1 R, R1 = H,alkyl, aryl O C 1) LiAlH4 Z HO 2) H3O+ C R H H R = H,alkyl, aryl R O C 1) LiAlH4 H NH2 2) H O 2 R C H NH2 R = H,alkyl, aryl Z = Cl, OH, OR H = NaBH4 and LiAlH4 R O C 1) RCH2 R1 2) H3O + HO R C CH2R R R1 R, R1 = H,alkyl, aryl O C 1) RCH2 Z HO 2) H3O+ R C CH2R CH2R O 1) CO2 RMgBr 2) H3O+ R = H,alkyl, aryl R OH Z = Cl, OR RCH2 = Grignard and Organolithium reagents R O C R1 NaCN HO HCl R R, R1 = H,alkyl, aryl C CN R1 1) NaNH2, NH3(l), -78 C R H 2) R O C HO R R R1 3) H3O + R1 0 R ocity it ⑧ [R--H] ↑ more - reactive Then ester! Can react 0 -*-ocHs R No R RN-OH Mo - LiAlH(OBut) "3 CHcs R 2) H20 +-BUOK * again ! bulky : is very reaction reaction won't proceed - * it so at stops far * aldehyde its not strong enough Nomenclature Carboxylic Acids : * H .. . I --- remove H = ↓ aldehyde peritance = YH -2 "I * remove e =pentans / 4 -Methyltexanoic = -> e*s pentory id pental acid Acid 3 05 I 4 34 2 H = ↓ Hexene (2)-4-methyl H the Zzz I 17 I 0 It 4 O -- 123 5 = - 3-hexenoic same -Fetore = nepten one -> S-hepten-2-one Acid side H ! -trans -it - (E) Summary of reactions R NH2 TsOH O C H3O+ R N C R O C N H TsOH H3O+ R N C R 1) PPh3 Br 2) KOBut 3) O C R R C R O C 1) (CH3)2CuLi 2) H3O+ R O C O C OH TsOH H3O+ 1) CH3MgBr or CH3Li 2) H3O+ O R HO C R C O