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Transcript
William H. Brown Thomas Poon www.wiley.com/college/brown Chapter Thirteen Aldehydes and Ketones The Carbonyl Group • In this and several following chapters, we study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O. • aldehydes and ketones (Chapter 13) • carboxylic acids (Chapter 14) • acid halides, acid anhydrides, esters, and amides (Chapter 15) • enolate anions (Chapter 16) 13-2 Structure • The functional group of an aldehyde is a carbonyl group bonded to a H atom. • The functional group of a ketone is a carbonyl group bonded to two carbon atoms. O HCH Methanal (Formaldehyde) O CH3 CH Ethanal (Acetaldehyde) O CH3 CCH3 Propanone (Acetone) 13-3 Nomenclature • IUPAC names: • The parent chain is the longest chain that contains the carbonyl group. • For an aldehyde, change the suffix from -e to -al. • For an unsaturated aldehyde, show the carbon-carbon double bond by changing the infix from -an- to -en-; the location of the suffix determines the numbering pattern. • For a cyclic molecule in which -CHO is bonded to the ring, add the suffix -carbaldehyde. 13-4 Nomenclature O O 3 4 1 3 H 2 2 3-Methylbutan al HO Cyclopen tanecarb aldehyde 5-Methyl-3h exanone H 4 5 7 8 6 3 4 1 H 2 (2E)-3,7-D imeth yl-2,6-octad ienal (Geran ial) 2-Propen al (A crolein ) CHO O O 1 1 CHO trans -4-Hyd roxycyclohexan ecarbald ehyde O 2-Methylcycloh exanone O Acetop hen on e O Benzoph enone 13-5 Nomenclature • Table 13.1 Increasing Order of Precedence of Six Functional Groups. 13-6 Nomenclature • Common names • For an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid. • For a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone. O H H Formaldehyde O O H OH Formic acid H Acetaldehyde O Ethyl is opropyl ketone O OH Acetic acid O O Diethyl ketone Dicyclohexyl ketone 13-7 Number Prefixes for Common Names PREFIX # C FORM ACET PROPIO BUTYR VALER 1 2 3 4 5 PREFIX CAPRO CAPRYL CAPR LAUR #C 6 8 10 12 SO.... BUTYRALDEHYDE IS AN ALDEHYDE OF 4 CARBONS. ….. THE SAME PREFIXES ARE USED FOR ACIDS. 13-8 Physical Properties • Oxygen is more electronegative than carbon (3.5 versus 2.5) and, therefore, a C=O group is polar. • Aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipole interactions. • They have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight. 13-9 Physical Properties • In liquid aldehydes and ketones, there are weak intermolecular attractions are between the partial positive charge on the carbonyl carbon of one molecule and the partial negative charge on the carbonyl oxygen of another molecule. H + C O H O C+ HH H + C O H H O C - +H • No hydrogen bonding is possible between aldehyde or ketone molecules. • Aldehydes and ketones have lower boiling points than alcohols and carboxylic acids, compounds in which there is hydrogen bonding between molecules. 13-10 Physical Properties •Formaldehyde, acetaldehyde, and acetone are infinitely soluble in water. •Aldehydes and ketones become less soluble in water as the hydrocarbon portion of the molecule increases in size. 13-11 Reactions • The most common reaction theme of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound. 13-12 Grignard Reagents • Addition of carbon nucleophiles is one of the most important types of nucleophilic additions to a C=O group. • A new carbon-carbon bond is formed in the process. • We study addition of carbon nucleophiles called Grignard reagents. • Victor Grignard was awarded the Nobel Prize for chemistry in 1912 for their discovery and application to organic synthesis. • Grignard reagents have the general formula RMgX, where R is an alkyl or aryl group and X is a halogen. 13-13 Grignard Reagents • Grignard reagents are prepared by adding an alkyl or aryl halide to a suspension of Mg metal in diethyl ether. Br + Mg eth er 1-Bromobutane Br + Mg Bromoben zene MgBr Butylmagn esium bromide eth er MgBr Phenylmagn esium bromide 13-14 Grignard Reagents • Given the difference in electronegativity between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with C- and Mg+. • in its reactions, a Grignard reagent behaves as a carbanion. • Carbanion: An anion in which carbon has an unshared pair of electrons and bears a negative charge. • A carbanion is a good nucleophile and adds to the carbonyl group of aldehydes and ketones 13-15 Grignard Reagents • Reaction with protic acids • Grignard reagents are very strong bases and react with proton acids to form alkanes. - + CH3 CH2 - MgBr + H-OH p Ka 15.7 Stronger Stron ger bas e acid CH3 CH2 -H + Mg 2+ + OH- + BrpK a 51 Weaker Weaker acid base • Any compound containing an O-H, N-H, or S-H group reacts with a Grignard reagent by proton transfer. HOH Water ROH Alcoh ols ArOH Phenols RCOOH Carboxylic acids RNH2 Amines RSH Thiols 13-16 Grignard Reagents • Reaction with formaldehyde gives a 1° alcohol. O eth er CH3 CH2 -MgBr + H-C-H Formaldeh yd e O [MgBr]+ HCl CH3 CH2 -CH2 H2 O A magnes ium alkoxide OH CH3 CH2 -CH2 + Mg 2+ 1-Propanol (a 1° alcoh ol) • Reaction with any aldehyde other than formaldehyde gives a 2° alcohol. O Ph MgBr + CH3 -C-H eth er Acetaldeh yd e O [MgBr] Ph CHCH3 A magnes ium alk oxid e + HCl H2 O OH Ph CHCH3 + Mg 2+ 1-Ph enyleth anol (a 2° alcohol) 13-17 Grignard Reagents • Reaction with a ketone gives a 3° alcohol. O [ MgBr] + O Ph MgBr + CH3 -C-CH3 Acetone eth er Ph CCH3 CH3 A magnes ium alkoxide HCl H2 O OH Ph CCH3 CH3 + Mg 2+ 2-Phen yl-2-propanol (a 3° alcoh ol) • Problem: Show how to synthesize this 3° alcohol by three different routes. OH C-CH2 CH3 CH3 13-18 Addition of Alcohols • Hemiacetal: A molecule containing an -OH group and an -OR group bonded to the same carbon. H O CH3 CCH3 + OCH2 CH3 OH CH3 C-OCH2 CH3 CH3 A h emiacetal H+ • Hemiacetals are minor components of an equilibrium mixture except where a 5- or 6-membered ring can form. 5 3 4 O 2 1 H OH 4-Hydroxyp entanal redraw to show th e OH close to th e CHO grou p 3 5 4 2 O H 1 3 H O 5 2 4 O 1 OH A cyclic h emiacetal (major form presen t at eq uilibrium) 13-19 Addition of Alcohols • Acetal: A molecule containing two -OR groups bonded to the same carbon. OH CH3 C-OCH2 CH3 + CH3 CH2 OH CH3 A hemiacetal H OCH2 CH3 + CH3 C-OCH2 CH3 + H2 O CH3 A diethyl acetal O H OH 4-Hydroxypentan al O OH CH3 OH + H O OCH3 + H2 O A cy clic acetal 13-20 Acetal Formation 1. Proton transfer from HA to the hemiacetal oxygen. + H O H R-C-OCH3 + A HO R-C-OCH3 + H A H An oxonium ion H 2. Loss of H2O gives a cation. + H O H R-C-OCH3 H + R-C OCH3 + R-C OCH3 + H2 O H H A resonan ce-stabilized cation 13-21 Acetal Formation 3. Reaction of the cation (an electrophile) with an alcohol (a nucleophile). + H + CH3 -O + R-C OCH3 H H O CH3 R-C-OCH3 H A p rotonated acetal 4. Proton transfer to A- gives the acetal and regenerates the acid catalyst. + H O CH3 O CH3 A + R-C-OCH3 H A p rotonated acetal HA + R-C-OCH3 H An acetal 13-22 Acetals • Draw a structural formula for the acetal formed in each reaction. (a) OH O + HO Eth ylen e glycol OH (b) O + H2 SO4 H2 SO4 OH 13-23 Acetals as Carbonyl -Protecting Groups • One way to synthesize the ketoalcohol on the right is by a Grignard reaction. O Ph O H + Benzaldehyde Br H 4-Bromobutanal OH ?? O Ph H 5-Hydroxy-5-phenylpentanal • But first the aldehyde of the bromoaldehyde must be protected; one possibility is as a cyclic acetal. O Br H + OH HO Eth ylene glycol H O + Br + H2 O O A cyclic acetal 13-24 An Acetal as a Carbonyl -Protecting Group • Now the Grignard reagent can be prepared and the new carbon-carbon bond formed. O O Br O A cyclic acetal O Ph BrMg + Mg ether O A Grignard reagent - H + BrMg O MgBr O + O O Ph A magnesiu m alk oxid e O • Hydrolysis gives the hydroxyaldehyde. - + O MgBr Ph OH O O HCl, H2 O Ph O H + HO OH 13-25 Imines • Imine: A compound containing a C=N bond; also called a Schiff base. • Formed by the reaction of an aldehyde or ketone with ammonia or a 1° amine. O + H+ NH3 Cycloh exanone A mmonia O An imine + CH3 CH + H2 N Ethanal NH + H2 O Aniline H CH3 CH=N + H2 O An imine 13-26 Formation of Imines 1. Addition of the amine to the carbonyl carbon followed by proton transfer gives an aminoalcohol. O C + H2 N-R O- H + N-R C H O H N-R H A tetrah edral carb on yl ad dition intermediate C 2. Two proton-transfer reactions and loss of H2O. H + O H + H O C H N-R H H + H O C H C N-R + H2 O + H O H N-R H O H H An imine 13-27 Rhodopsin • Reaction of vitamin A aldehyde (retinal) with an amino group on the protein opsin gives rhodopsin. 11 12 + H2 N-Opsin 11-cis -Retinal H C=O Rhodopsin (Vis ual purple) H C= N-Opsin 13-28 Reductive Amination • Reductive amination: The formation of an imine followed by its reduction to an amine. + O + H2 N Cyclohexanone Cyclohexylamine (a 1° amine) H -H2 O N H2 / Ni An imine (n ot isolated) H N D icyclohexylamin e (a 2° amine) • Reductive amination is a valuable method for the conversion of ammonia to a 1° amine, and a 1° amine to a 2° amine. 13-29 Keto-Enol Tautomerism • Enol: A molecule containing an -OH group bonded to a carbon of a carbon-carbon double bond. O CH3 -C-CH3 Acetone (keto form) OH CH3 -C=CH2 Aceton e (enol form) The keto form predominates for most simple aldehydes and ketones 13-30 Keto-Enol Tautomerism • Problem: Draw two enol forms for each ketone. O O (b) (a) • Problem: Draw the keto form of each enol. O OH CHOH (a) (b) OH (c) OH 13-31 Keto-Enol Tautomerism • Interconversion of keto and enol forms is catalyzed by both acid and base. • Following is a mechanism for acid catalysis 1. Proton transfer to the carbonyl oxygen. 2. Proton transfer from the a-carbon to A:- 13-32 Racemization an at a-Carbon • When an enantiomerically pure aldehyde or ketone with at least one a-hydrogen is treated with a trace of acid or base, it gradually becomes a racemic mixture; it loses all optical activity. Ph O C C H OH Ph + C - or OH H3 C CH3 H (R)-3-Phenyl-2butanone H3 C C CH3 An ach iral en ol H + or OH- Ph O C C H CH3 H3 C (S)-3-Ph enyl-2b utanone 13-33 a-Halogenation • Aldehydes and ketones with an a-hydrogen react with Br2 and Cl2 to give an a-haloaldehyde or an ahaloketone. O O + Br2 A cetophenone CH3 COOH Br + HBr a-Bromoacetophen on e 13-34 a-Halogenation • The key intermediate in a-halogenation is an enol. 1. Formation of the enol. OH O H+ Keto form En ol form 2. Nucleophilic attack of the enol on the halogen. H O O + Br Br Br + H-Br 13-35 a-Halogenation • A value of a-halogenation is that the carbon adjacent to the aldehyde or ketone now bears a good leaving group and is susceptible to nucleophilic attack. O O Br N + H N A n a-bromok eton e Diethylamine + HBr An a-dieth ylaminoketone 13-36 Oxidation • Aldehydes are one of the most easily oxidized of all functional groups. CHO H2 CrO4 Hexan al MeO HO Van illin 2 COOH Hexanoic acid CHO + Ag2 O THF, H2 O NaOH CHO + O2 Benzald ehyde HCl H2 O 2 COOH + Ag MeO HO V anillic acid COOH Benzoic acid 13-37 Oxidation • Ketones are not normally oxidized by H2CrO4; in fact this reagent is used to oxidize 2° alcohols to ketones. • They are oxidized by HNO3 at higher temperatures. • Oxidation is via the enol. O OH O HNO3 HO OH O Cycloh exanone (k eto form) Cyclohexan one (enol form) Hexan edioic acid (Ad ipic acid ) • Adipic acid is one of the starting materials for the synthesis of nylon 66. 13-38 Oxidation • Tollens’ reagent: Prepared by dissolving AgNO3 in water, adding NaOH to precipitate Ag2O and then adding aqueous ammonia to redissolve silver ion as the silverammonia complex ion. Tollens’ reagent is specific for the oxidation of aldehydes. If done properly, silver deposits on the walls of the container as a silver mirror. O R-C-H + 2 Ag( NH3 ) 2 + + 3 OHA ldehyde Tollens' reagen t O R-C-O- + 2 Ag + 4 NH3 + 2 H2 O Carboxylic Silver an ion mirror 13-39 Reduction • Aldehydes are reduced to 1° alcohols. • Ketones are reduced to 2° alcohols. O R-CH A n aldehyde reduction R-CH2 OH A p rimary alcohol O OH reduction R-C-R' R-CH-R' A second ary A k eton e alcohol 13-40 Catalytic Reduction • Catalytic reductions are generally carried out from 25° to 100°C and 1 to 5 atm H2. OH O + H2 Pt 25 o C, 2 atm Cyclohexanone Cyclohexanol • A carbon-carbon double bond may also be reduced under these conditions. O H trans- 2-Butenal (Crotonaldehyde) 2 H2 Ni OH 1-Butanol 13-41 Metal Hydride Reductions • The most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4. • Both reagents are sources of hydride ion, H:-, a very strong nucleophile. H Na + H- B- H H Sodium borohydride H Li + H- A l- H H Lithium aluminum hydride (LAH) H: Hydride ion 13-42 NaBH 4 Reductions • Reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol. • One mole of NaBH4 reduces four moles of aldehyde or ketone. O 4 RCH + NaBH4 methanol - + ( RCH2 O) 4 B Na A tetraalkyl borate H2 O 4 RCH2 OH + borate salts 13-43 NaBH 4 Reductions • The key step in metal hydride reductions is transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound. H O + Na H-B-H + R-C-R' H O BH3 Na + R-C-R' H from the hydride reducing agent H2 O from w ater O-H R-C-R' H 13-44 Metal Hydride Reductions • Metal hydride reducing agents do not normally reduce carbon-carbon double bonds, and selective reduction of C=O or C=C is often possible. O RCH= CHCR' 1 . Na BH 4 2 . H2 O O RCH= CHCR' + H2 Rh OH RCH= CHCH R' O RCH2 CH 2 CR' 13-45 Aldehydes and Ketones End Chapter 13 13-46