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Transcript
CARBONYL COMPOUNDS ALDEHYDES AND KETONES 1 1 Aldehydes and Ketones H R R C O R Aldehyde 118o H C O H3C 121o 118o C O Ketone H H C C H 121o H Resonance Structures H H C O C O δ+ δ− H3 C H3 C 2 2 Some naturally occurring aldehydes and ketones 3 3 Formalin, 35-40% formadehyde in water Preservative that reacts with proteins causing them to resist decay Coelacanth, “prehistoric fish” H O C H O H Acrolein (2-propenal) - lachrymator and pleasant "odor" from barbacuing meat 4 4 Preparation of Carbonyls 1. Oxidation of Alcohols Primary alcohols can be oxidized with pyridinium chlorochromate (PCC) to aldehydes. Ketones can be obtained from secondary alcohols by oxidation with sodium dichromate/sulfuric acid or KMnO4. 5 5 Preparation of Carbonyls 2. Friedel Crafts Acylation Aromatic ketones (acyl benzenes) can be produced from the reaction of benzenoid compounds with acyl chlorides, which are derived from carboxylic acids. 6 6 Preparation of Carbonyls 3. Ozonolysis of Alkenes The cleavage of an alkene with ozone produces carbonyl compounds. Recall that disubstituted double-bonded carbons become ketones and monosubstituted double-bonded carbons become aldehydes through ozonolysis. 7 7 Preparation of Carbonyls 4. Aldehydes from Acid Chlorides Aldehydes are easily oxidized to carboxylic acids but carboxylic acids are difficult to reduce to aldehydes. This difficulty is circumvented by converting a carboxylic acid into the more reactive acid chloride, which can be readily reduced to an aldehyde. Lithium tri-t-butoxyaluminum hydride is a mild reducing agent that displaces chloride with hydride to produce an aldehyde. 8 8 Preparation of Carbonyls 4. Ketones from Acid Chlorides Alkyl groups can replace the chlorine to produce ketones. 9 9 A Grignard (or organolithium) reagent would react with an acid chloride to produce a ketone, but then the ketone would react immediately with additional Grignard reagent in the solution to form a tertiary alcohol. This problem is circumvented by using the weakest of the organometallic reagents, an organocuprate, which is too weak a nucleophile to add to a ketone. 10 10 11 11 Reactions of Aldehydes and Ketones 12 12 Addition to Carbonyls: Simple Nucleophile Carbonyls readily undergo Nucleophilic Attack δ− O C δ+ O C Nuc O H H+ C Nuc Nuc Alkoxide Alcohol Aldehyde is more reactive than ketone δ− O C δ+ R H δ− O C δ+ R R 13 13 1. Reduction of Carbonyls The most useful reagents for reducing aldehydes and ketones are the metal hydride reagents.The two most common metal hydride reagents are sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). These reagents contain a polar metal-hydrogen bond that serves as a source of the nucleophile hydride, H:-. LiAlH4 is a stronger reducing agent than NaBH4, because the Al-H bond is more polar than the B-H bond. 14 14 MECHANISM LiAlH4 Reduction of RCHO and R2C=O 15 15 2. Reaction of Carbonyls with Cyanide Ion • The reaction is conducted using sodium cyanide at pH 10 to yield cyanohydrin. 16 16 17 17 Addition to Carbonyls: Primary Amines and Alcohols 1. Addition of primary amimes Condensation Reaction – Elimination of water 18 18 Reaction between an amine and a carbonyl compound 19 19 General reaction 20 20 DNP test for aldehydes & ketones gives crystalline hydrazones NO2 O2N H 3C C O + H 3C acetone H O2N - H2O N N H H 2,4-dinitrophenylhydrazine 2,4-diphenylhydrazine H3C NO2 C N N H3C H hydrazone of acetone orange crystals 21 21 Nucleophilic Addition of Hydrazine: The Wolff-Kishner Reduction 22 22 Mechanism: The Wolff-Kishner Reduction 23 23 Addition to Carbonyls: Primary Amines and Alcohols 2. Addition of alcohols Weak nucleophiles “Acid catalyzed” 24 24 Mechanism of hemiacetal formation 25 25 Mechanism of acetal formation 26 26 27 27 Addition to Carbonyls: Carbanions Carbanion : strong Nucleophile - Grignard reagent : an organomagnesium bromide (RMgBr or ArMgBr). - Organolithium compounds (RLi and ArLi) 1. Addition of Grignard reagents 28 28 Professor Victor Grignard (1912 Nobel Prize) Developed this chemistry with Professor P. A. Barbier H δ− δ+ R C X H X = I or Br Mg Ether H δ− δ+ R C MgX H Grignard Reagent RCH2 MgX 29 29 Grignard reagent add to carbonyls to give alcohols MgBr H Ether C O MgBr H H H3O+ H C O H H Benzylalcohol C O H C O 1. MgBr C OH Ether 2. H3O+ Triphenylmethanol 30 30 Nucleophilic Addition Reactions H O H C H Ph Primary alcohols H O C H Formaldehyde + Ph MgI H O R C H Ph Secondary alcohols R O C H Aldehydes + Ph MgI H O R C R Ph tertiary alcohols O C R R Ketone + Ph MgI 31 31 32 32 2. Addition of Organolithium compounds (RLi and ArLi) H δ− δ+ R C X H Li Ether X = I or Br H δ− δ+ R C Li RCH2 H Organolithium Reagent Li ADDITION δ− R C O δ− δ+ Li δ+ R C O H+ H 2O Li Protonation R C O H Alcohol 33 33 Problems 34 34 Problems 35 35 Oxidation of Aldehydes The most common oxidation reaction of carbonyl compounds is the oxidation of aldehydes to carboxylic acids. A variety of oxidizing agents can be used, including CrO3, Na2Cr2O7, K2Cr2O7 and KMnO4. Aldehydes are also oxidized selectively in the presence of other functional groups using silver(I) oxide in aqueous ammonium hydroxide. This is called Tollens reagent. Because ketones have no H on the carbonyl carbon, they do not undergo this oxidation reaction. 36 36 Problems 37 37 Reactivity of Enolate Ions O H C αC Base 38 38 Reactivity of Enolate Ions Reaction on carbon is more common. 39 39 1. Haloform reaction If excess base and halogen are used, a methyl ketone is triply halogenated and then cleaved by base in the haloform reaction. The product are carboxylic and haloform. + -CX3 + CHX3 haloform 40 40 2. Alkylation of Enolate Ions เกิดขึ้นไดกับ ketone ที่มี α-hydrogen โดยทําปฏิกิริยากับเบสจะให enolate ion ซึ่งสามารถทํา ปฏิกิริยาไดอยางรวดเร็วกับ alkyl halide เกิดสารผลิตภัณฑคือ α- alkylketone O C C H ketone 1) LDA, THF 2) R-X O C C R α-alkylketone LDA = lithium diisopropylamide 41 41 3. Aldol Condensation เกิดเมื่อ aldehyde หรือ ketone ที่มี α-hydrogen เปลี่ยนเปน enolate ion และทําหนาที่ เปน nucleophile เพิ่มเขาไปที่ aldehyde หรือ ketone อีกโมเลกุลหนึ่ง เกิดสารผลิตภัณฑคือ β-hydroxy carbonyl หรือที่เรียกกันวา aldol (aldehyde + alcohol) 42 42 Mechanism: Aldol Condensation 43 43 สาร β-hydroxy aldehyde หรือ ketone ที่เกิดขึ้น ถายังมี α-hydrogen เหลืออยูจะสูญเสีย โมเลกุลของน้ําไดงายโดยเกิดเปนสารที่ไมอิ่มตัวโดยมีพันธะที่ตําแหนง α,β เรียกวา α,βunsaturated aldehyde หรือ ketone ซึง่ สารที่เกิดขึ้นนี้เปนสารที่เสถียรมีการเคลื่อนที่ของ electron ไปไดทั่วทั้ง 4 atom + H2O 44 44 Crossed Aldol Condensation เกิดระหวาง aldehyde หรือ ketone ตางชนิดกัน สวนใหญมักเลือกใหสารหนึ่งมี α-hydrogen และอีกสารหนึ่งไมมี α-hydrogen เพือ่ ปองกันการเกิดผลิตภัณฑหลายชนิดผสมกัน 45 45 Problem : จงเลือกสารตั้งตนที่ใชสําหรับสังเคราะหสารในแตละขอตอไปนี้ 46 46 CARBOXYLIC ACIDS 47 47 Carboxylic Acids pKa = 4 - 5 , O C O water = 16 C O H + H2O O + H3O Carboxylic acids are strong organic acids O C O O H + NaOH H2O C Benzoic acid Cl Cl O C C Cl pKa = OH 0.7 Na Sodium Benzoate H Cl O O C C Cl 1.48 OH H Cl O 2.86 O H C C C C H H OH H 4.76 OH 48 48 Carboxylic Acids Highly Polar Low molecular weight acids show Appreciable Solubility in Water High B.p.– Extensive H-bonds to themselves and water Ethanoic acid Red ants rhubarb Vinegar H 4-Bromo-2-ethylpentanoic acid O O OH Methanoic acid H3C O OH Acetic acid O Aspirin OH CH3 O 49 49 Reactions of Carboxylic Acids 50 50 Conversion of RCOOH to RCOCl Carboxylic acids can't be converted to acid chlorides by using Cl- as a nucleophile, because the attacking nucleophile Cl- is a weaker base than the departing leaving group, -OH. But carboxylic acids can be converted to acid chlorides using thionyl chloride, SOCl2. 51 51 Mechanism 52 52 Conversion of RCOOH to (RCO)2O Carboxylic acids cannot be readily converted to anhydrides, but dicarboxylic acid can be converted to cyclic anhydrides by heating to high temperatures. This is a dehydration reaction because a water molecule is lost from the diacid. O O OH OH O O + O H2O 53 53 Conversion of RCOOH to RCOOR Treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst forms an ester. This reaction is called a Fischer esterification. 54 54 Mechanism O R OH 55 55 Esterification of a carboxylic acid occurs in the presence of acid but not in the presence of base. Base removes a proton from the carboxylic acid, forming a carboxylate anion, which does not react with an electron-rich nucleophile. 56 56 Intramolecular esterification of γ- and δ-hydroxy carboxylic acids forms five- and six-lactones. 57 57 Draw the products of each reaction 58 58 Conversion of RCOOH to RCONR’2 The direct conversion of a carboxylic acid to an amide with NH3 or an amine is very difficult. The problem is that carboxylic acids are strong organic acids and NH3 and amines are bases, so they undergo an acid-base reaction to form an ammonium salt before any nucleophilic substitution occurs. The overall conversion of RCOOH to RCONH2 requires two steps: [1] Acid-base reaction of RCOOH with NH3 to form an ammonium salt [2] Dehydration at high temperature (>100 oC) 59 59 A carboxylic acid and an amine readily react to form an amide in the presence of an additional reagent, dicyclohexylcarbodiimide (DCC), which is converted to the by-product dicyclohexylurea in the course of the reaction. 60 60 Mechanism O R OH R'NH2 61 61 Cleaning Action of Soaps 62 62