Reactions of aldehydes and ketones: oxidation reduction nucleophilic addition 1) Aldehydes are easily oxidized, ketones are not. 2) Aldehydes are more reactive in nucleophilic additions.
Download ReportTranscript Reactions of aldehydes and ketones: oxidation reduction nucleophilic addition 1) Aldehydes are easily oxidized, ketones are not. 2) Aldehydes are more reactive in nucleophilic additions.
Reactions of aldehydes and ketones: oxidation reduction nucleophilic addition 1) Aldehydes are easily oxidized, ketones are not. 2) Aldehydes are more reactive in nucleophilic additions than ketones. alkane alcohol reduction reduction aldehyde ketone oxidation carboxylic acid addition product nucleophilic addition nucleophilic addition to carbonyl: O C + YZ OY C Z Mechanism: nucleophilic addition to carbonyl 1) O C 2) O C Z Z O C Z Y OY C Z RDS + + Mechanism: nucleophilic addition to carbonyl, acid catalyzed 1) O C 2) OH C 3) OH C ZH + OH C H OH C ZH RDS + HZ OH C Z + H Aldehydes & ketones, reactions: 1) Oxidation 2) Reduction 3) Addition of cyanide 4) Addition of derivatives of ammonia 5) Addition of alcohols 6) Cannizzaro reaction 7) Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions) 1) Oxidation a) Aldehydes (very easily oxidized!) CH3CH2CH2CH=O + KMnO4, etc. CH3CH2CH2COOH carboxylic acid CH3CH2CH2CH=O + Ag+ CH3CH2CH2COO- + Ag Silver mirror Tollen’s test for easily oxidized compounds like aldehydes. (AgNO3, NH4OH(aq)) Ketones only oxidize under vigorous conditions via the enol. O + KMnO4 NR Cyclohexanone O + KMnO4, heat HOOCCH2CH2CH2CH2COOH adipic acid OH enol b) Methyl ketones: R O C CH3 + OI- R O C O- + CHI3 iodoform Yellow ppt test for methyl ketones O CH3CH2CH2CCH3 2-pentanone + (xs) NaOI CH3CH2CH2CO2- + CHI3 2) Reduction: a) To alcohols O C H2, Ni NaBH4 or LiAlH4 then H+ OH C H H2, Pt H O OH cyclopentanol cyclopentanone O C CH3 acetophenone 1. NaBH4 2. H+ OH CHCH3 1-phenylethanol O H2, Pt C H CH2OH benzaldehyde CH3 CH3CHCH=O isobutyraldehyde benzyl alcohol LiAlH4 H+ CH3 CH3CHCH2OH isobutyl alcohol hydride reduction mechanism: nucleophilic addition; nucleophile = hydride 1) 2) O C O C H RDS H: Al + + Al O C H + Al H C O Al Then + H+ alcohol Reduction b) To hydrocarbons O C NH2NH2, OH- O C Zn(Hg), HCl CH2 Wolff-Kishner Clemmensen CH2 O Cl + O AlCl3 Zn(Hg), HCl n-pentylbenzene cannot be made by Friedel-Crafts alkylation due to rearrangement of carbocation 3) Addition of cyanide O C 1. CN- OH C CN cyanohydrin 2. H+ + O + NaCN; then H OH CN mechanism for addition of cyanide nucleophilic addition 1) 2) O C O C C N RDS + C N + Na+ O C C N ONa C C N then + H+ Cyanohydrins have two functional groups plus one additional carbon. Nitriles can be hydrolyzed to carboxylic acids in acid or base: OH CH2CH C N H2O, OH- OH CH2CH C N H2O, H+ heat heat OH CH2CH COO- C C COOH H H 4) Addition of derivatives of ammonia O + H2N G (H+) + H2O N G O H2N NH2 H2N OH hydrazine hydroxylamine NH2 H2N N H semicarbazide O2N H2N HN H2N HN NO2 phenylhydrazine 2,4-dinitrophenylhydrazine acid catalyzed nucleophilic addition mechanism followed by dehydration 1) 2) 3) O C OH C OH C NH2 G + OH C + H OH C NH2 G + H2N G C N + G RDS H2O + H+ CH2 CHO + H2NOH CH2 CH NOH hydroxylamine an oxime phenylacetaldehyde H+ O O + H2NHNCNH2 O NHNCNH2 semicarbazide cyclohexanone CH3CH2CH2CH2CHO pentanal a semicarbazone + NH2 NH phenylhydrazine CH3CH2CH2CH2CH N NH a phenylhydrazone melting points of derivatives ketones bp 2-nonanone 195 119 56 acetophenone 202 199 240 60 menthone 209 189 146 59 2-methylacetophenone 214 205 159 61 1-phenyl-2-propanone 216 200 156 70 propiophenone 220 174 191 54 3-methylacetophenone 220 198 207 55 isobutyrophenone 222 181 163 94 semi2,4-dinitrooxime carbazone phenylhydrazone 5) Addition of alcohols O C + ROH, H+ OH C OR OR C OR hemiacetal acetal Mechanism = nucleophilic addition, acid catalyzed 1) O C + OH C H RDS 2) 3) OH2 C OH C HOR + ROH OH C OR OH C HOR + H (xs) EtOH, H+ CH2CHO OEt CH2 CH OEt acetal O (xs) CH3OH, dry HCl OCH3 OCH3 ketal H OH HO HO HO H H OH H OH H HO H H CHO OH H OH OH CH2OH H OH HO HO HO H H H OH OH nucleophilic addition of -OH on carbon 5 to the aldehyde functional group H OH H HO H H CHO OH H OH OH CH2OH H HO H HOH2C CH O OH H OH H OH rotate C-5 OH to rear HO HO HO H H H OH OH H OH HO HO HO H H OH H OH 6) Cannizzaro reaction. (self oxidation/reduction) a reaction of aldehydes without α-hydrogens COO- CH2OH CHO conc. NaOH + Br Br conc. NaOH H2C=O CH3OH + HCOO- Br Formaldehyde is the most easily oxidized aldehyde. When mixed with another aldehyde that doesn’t have any alphahydrogens and conc. NaOH, all of the formaldehyde is oxidized and all of the other aldehyde is reduced. Crossed Cannizzaro: CH=O CH2OH + H2C=O conc. NaOH + HCOO- OCH3 OH vanillin OCH3 OH 7) Addition of Grignard reagents. O C + RMgX O MgBr + H2O C R O MgBr C R OH + Mg(OH)Br C R larger alcohol mechanism = nucleophilic addition 1) O C 2) O C R RDS + RMgBr + MgBr O C R + MgBr OMgBr C R #3 synthesis of alcohols. Used to build larger molecules from smaller organic compounds. RMgX + O C H H formaldehyde RMgX + O C R' H other aldehydes RCH2OMgX H+ RCH2OH 1o alcohol + 1 C R'CHOMgX R H+ R'CHOH R 2o alcohol + X C's O R-MgX + C R' R" R' R-COMgX R" ketone O RMgX + H2C CH2 ethylene oxide R' H+ R-COH R" 3o alcohol + X C's H+ RCH2CH2OMgX RCH2CH2OH 1o alcohol + 2 C's Aldehydes & ketones, reactions: 1) Oxidation 2) Reduction 3) Addition of cyanide 4) Addition of derivatives of ammonia 5) Addition of alcohols 6) Cannizzaro reaction 7) Addition of Grignard reagents 8) (Alpha-halogenation of ketones) 9) (Addition of carbanions) Planning a Grignard synthesis of an alcohol: a) The alcohol carbon comes from the carbonyl compound. b) The new carbon-carbon bond is to the alcohol carbon. O C + RMgX H+ New carbon-carbon bond OH C R “The Grignard Song” (sung to the tune of “America the Beautiful”) Harry Wasserman The carbonyl is polarized, the carbon end is plus. A nucleophile will thus attack the carbon nucleus. The Grignard yields an alcohol of types there are but three. It makes a bond that corresponds from “C” to shining “C.” CH3 CH3CH2CH2CH2 C CH3 OH 2-Methyl-2-hexanol H2O O CH3CH2CH2CH2MgBr + CH3CCH3 or CH3 CH3CH2CH2CH2 C CH3 OH 2-Methyl-2-hexanol H2O O CH3CH2CH2CH2CCH3 + CH3MgBr HX ROH Mg RX RMgX H2O R´OH ox. -C=O larger alcohol Stockroom: alcohols of four-carbons or less: (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-2-propanol, 2-methyl-1-propanol.) benzene cyclohexanol any needed inorganic reagents or solvents. Grignard synthesis of 4-methyl-2-pentanol from alcohols of four-carbons or less: Step one: determine the carbonyl compound and Grignard reagent that you would use: CH3 CH3CHCH2MgBr + CH3CH=O H2O CH3 CH3CHCH2CHCH3 OH Step two: show the syntheses of the Grignard reagent and the carbonyl compound from alcohols… CH3 HBr CH3 CH3CHCH2OH CH3CHCH2Br Mg CH3 CH3CHCH2MgBr H+ K2Cr2O7 CH3CH2OH CH3CH=O special cond. CH3 CH3CHCH2CHCH3 OH 4-methyl-2-pentanol 2-phenyl-2-propanol Mg Br2,Fe Br MgBr H2O OH CH3CHCH3 CrO3 O CH3CCH3 OH C CH3 CH3 2-phenyl-2-propanol 1-methylcyclohexanol CH3OH HBr CH3Br Mg CH3MgBr H3C H O OH NaOCl Cyclohexanol Cyclohexanone OH H2O 1-Methylcyclohexanol cyclohexylmethanol H OH H HBr Br H MgBr Mg H2O K2Cr2O7 CH3OH H2C=O special cond. H CH2OH Cyclohexylmethanol ketone aldehyde ROR ROH RCOOH alkene RX Alcohols are central to organic syntheses RH alkyne HX ROH Mg RX RMgX H2O R´OH ox. -C=O larger alcohol Using the Grignard synthesis of alcohols we can make any alcohol that we need from a few simple alcohols. From those alcohols we can synthesize alkanes, alkenes, alkynes, alkyl halides, ethers, aldehydes, ketones, carboxylic acids… eg. Outline all steps in a possible laboratory synthesis of 3-methyl-1-butene from alcohols of four carbons or less. CH3 CH3CHCH=CH2 Retrosynthesis: alkenes, syntheses: 1. Dehydrohalogenation of an alkyl halide 2. Dehydration of an alcohol 3. Dehalogenation of a vicinal dihalide 4. Reduction of an alkyne Methods 3 & 4 start with compounds that are in turn made from alkenes. Dehydration of an alcohol? CH3 CH3CHCHCH3 OH H+ CH3 CH3CHCH2CH2-OH yields a mixture of alkenes H+ yields a mixture of alkenes E1 mechanism via carbocation! Dehydrohalogenation of an alkyl halide? CH3 CH3CHCHCH3 Br KOH(alc) CH3 CH3CHCH2CH2-Br yields a mixture of alkenes KOH(alc) CH3 CH3CHCH=CH2 only product E2 mechanism, no carbocation, no rearrangement CH3 CH3CHCH2CH2-OH HBr CH3 CH3CHCH2CH2-Br 1o alcohol, SN2 mechanism, no rearrangement! CH3 CH3CHCH2CH2-Br KOH(alc) CH3 CH3CHCH=CH2 Use the Grignard synthesis to synthesize the intermediate alcohol from the starting materials. CH3 CH3CHCH2-OH PBr3 CH3 CH3CHCH2Br Mg CH3 CH3CHCH2MgBr K2Cr2O7 CH3OH H2C=O special cond. H2O CH3 CH3CHCH2CH2-OH HBr CH3 CH3CHCH=CH2 KOH(alco) CH3 CH3CHCH2CH2-Br