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Transcript
ALDEHYDE & KETONES ROHAZITA BAHARI COURSE OUTCOMES INVOLVED CO #3: Ability to DEMONSTRATE the reactions involving alcohol, ether, aldehyde, ketone, carboxylic acid and aromatic compounds 2 OUTLINES Naming of Aldehyde and Ketones Relative Reactivity of Carbonyl Group Oxidation Reaction of Aldehydes and Ketones Nucleophilc Addition Reaction 3 ALDEHYDES AND KETONES Aldehydes (RCHO) and ketones (R2CO) are characterized by the the carbonyl functional group (C=O) The compounds occur widely in nature as intermediates in metabolism and biosynthesis 4 NAMING ALDEHYDES : Aldehydes are named by replacing the terminal -e of the corresponding alkane name with –al The parent chain must contain the CHO group • The CHO carbon is numbered as C1 Ethanal acetaldehyde Propanal Propionaldehyde 2-Ethyl-4-methylpentanal 5 N A M I N G A L D E H Y D E S A N D K E TO N E S (Common) Methanal (IUPAC) (Common) Propanone (IUPAC) 6 NAMING ALDEHYDES If the CHO group is attached to a ring, use the suffix carbaldehyde. Cyclohexanecarbaldehyde 2-Naphthalenecarbaldehyde 7 NAMING ALDEHYDES: Common Names end in aldehyde 8 NAMING KETONES Replace the terminal -e of the alkane name with –one Parent chain is the longest one that contains the ketone grp • Numbering begins at the end nearer the carbonyl carbon 3-Hexanone (New: Hexan-3-one) 4-Hexen-2-one 2,4-Hexanedione (New: Hex-4-en-2-one) (New: Hexane-2,4-dione) 9 KETONES WITH COMMON NAMES IUPAC retains well-used but unsystematic names for a few ketones Acetone Acetophenone Benzophenone 10 K E TO N E S A N D A L D E H Y D E S A S SUBSTITUENTS The R–C=O as a substituent is an acyl group, used with the suffix -yl from the root of the carboxylic acid The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain 11 PHYSICAL PROPERTIES Have higher boiling points than hydrocarbon because they are more polar and the forces between molecules are stronger More soluble than hydrocarbons but less soluble than alcohols in water 12 RELATIVE RECTIVITY OF THE CARBONYL GROUP 13 THE RELATIVE REACTIVITIES OF CARBONYL GROUP The partial positive charge on the carbonyl carbon causes that carbon to be attacked by nucleophiles: An aldehyde has a greater partial positive charge on its carbonyl carbon than does a ketone: 14 15 ALDEHYDES ARE MORE REACTIVE THAN KETONES Steric factors contribute to the reactivity of an aldehyde. • The carbonyl carbon of an aldehyde is more accessible to the nucleophile because the hydrogen attached to the carbonyl carbon of an aldehyde is smaller than the second alkyl group to carbonyl carbon of a ketone. • Ketones have greater steric crowding in their transition states, so they have less stable transition states. 16 ALKYL GROUP STABILIZED THE R E AC TA NT 17 The reactivity of carbonyl compounds is also related to the basicity of Y–: (lone pair of an atom) 18 Carbonyl compound other than aldehyde and ketone have a lone pair (Y-)on an atom which attached to carbonyl compound group that can be shared by resonance e- donation. This makes the carbonyl carbon less electron deficient and less reactive. 19 HOW ALDEHYDES AND KETONES REACT 20 OXIDATION OF ALDEHYDES & KETONES CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids (acidic conditions) Tollens’ reagent Silver oxide, Ag2O, in aqueous ammonia oxidizes aldehydes (basic conditions) 21 HYDRATION OF ALDEHYDES Aldehyde oxidations occur through 1,1-diols (“hydrates”) Reversible addition of water to the carbonyl group Aldehyde hydrate is oxidized to a carboxylic acid by usual reagents for alcohols 22 KETONES OXIDIZE WITH DIFFICULTY Undergo slow cleavage with hot, alkaline KMnO4 C–C bond next to C=O is broken to give carboxylic acids Reaction is practical for cleaving symmetrical ketones 23 REACTIONS OF ALDEHYDES AND KETONES Aldehydes and ketones undergo a variety of reactions that lead to many different product. The most common reactions are NUCLEOPHILIC ADDITION REACTIONS. The main reactions of the carbonyl group are nucleophilic addition to the carbon-oxygen double bond. 24 NUCLEOPHILIC ADDITION REACTION When a nucleophile attacks an aldehyde or ketone carbon, there is no leaving group. The incoming nucleophile simply “pushes” the electrons in the pi bond up to the oxygen. (eg: ) Alternatively, if start with the minor resonance contributor: attack by a nucleophile on a carbocation. (eg: ) After the carbonyl is attacked by the nucleophile, the negatively charged oxygen has the capacity to act as a nucleophile. However, most commonly the oxygen acts instead as a base, abstrating a proton from a nearby acid group in the solvent or enzyme active side. (eg) 25 NUCLEOPHILES 26 RELATIVE REACTIVITY OF ALDEHYDES AND KETONES Aldehyde are usually more reactive toward nucleophilic substitutions than ketones because of both steric and electronic effects. In aldehydes, the relatively small hydrogen atom is attached to one side of the carbonyl group. While a larger R group is affixed to the other side. In ketones, however, R group are attached to both sides of the carbonyl group. Thus, steric hindrance is less in aldehydes than in ketones. 27 Electronically, aldehydes have only one R group to supply electrons towards the partially positive carbonyl carbon, while ketones have two electronsupplying group attached to the carbonyl carbon. The greater amount of electrons being supplied to the carbonyl carbon, the less partial positive charge on this atom and the weaker it will become as a nucleus. Due to differences in electronegativities, the carbonyl group is polarized. The carbon atom has a partial positive charge, and the oxygen atom has a partially negative charge. 28 R E L AT I V E R E A C T I V I T Y O F A L D E H Y D E S A N D K E TO N E S Aldehydes are generally more reactive than ketones in nucleophilic addition reactions • Aldehyde C=O is more polarized than ketone C=O • Ketone has more electron donation alkyl groups, stabilizing the C=O carbon inductively 29 ADDITION OF H 2 O: HYDRATION The addition of water to an aldehyde or a ketones results in the formation of a hydrate. 30 NUCLEOPHILIC ADDITION OF H 2 O: HYDRATION A hydrate is a molecule with two OH groups bonded to the same carbon. Eg: 31 MECHANISM FOR ACID CATALYZED HYDRATE FORMATION 1)Water, acting as a nucleophile, is attracted to the partially positive carbon of the carbonyl group, generating an oxonium ion. (eg) 2) The oxonium ion liberates a hydrogen ion that is picked up by the oxygen anion in an acid-base reaction. (eg) 32 MECHANISM FOR ACID CATALYZED HYDRATE FORMATION Small amount of acids and bases catalyze this reaction. This occurs because the addition of acid causes a protonation of the oxygen of the carboyl group, leading to the formation of a full positive charge on the carbonyl carbon, making the carbon a good nucleus. Adding hydroxyl ions changes the nucleophile from water ( a weak nucleophile) to a hydroxide ion ( a strong nucleophile). Ketones usually do not form stable hydrates. 33 MECHANISM FOR ACID CATALYZED HYDRATE FORMATION 34 A D D I T I O N O F WA T E R TO F O R M HYDRATES (GEM-DIOS) It has been demonstrated that water, in the presence of an acid or a base, ass rapidly to the carbonyl function of aldehydes and ketones establish a reversible equilibrium with a hydrate (menial-diol or gemdiol). The word germinal or gem comes from the Latin word for twin. Eg: 35 NUCLEOPHILIC ADDITION OF H 2 O: HYDRATION Aldehydes and ketones react with water to yield 1,1diols (geminal (gem) diols) Hydration is reversible: a gem diol can eliminate water 36 REVERSIBILITY OF THE REACTION Isolation of gem-diols is difficult because the reaction is reversibly. Removal of the water during a reaction can cause the conversation of a gem-diol back to the corresponding carbonyl. Eg: 37 MECHANISM OF GEM-DIOL FORMATION The mechanism is catalyzed by the addition of an acid or base. Basic conditions speed up the reaction because hydroxide is a better nucleophilic than water. Acidic conditions speed up the reaction because the protonated carbonyl is more electrophilic. 38 MECHANISM OF GEM-DIOL FORMATION Under Basic Condition 1) Nucleophilic attack by the hydroxide 2) Protonation of the alkoxide 39 BASE-CATALYZED ADDITION OF WATER Addition of water is catalyzed by both acid and base The basecatalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water 40 MECHANISM OF GEM-DIOL FORMATION Under Acidic Conditions 1) Protonation of the carbonyl 2) Nucleophilic attack by water 3) Deprotonation 41 ACID-CATALYZED ADDITION OF WATER Protonation of C=O makes it more electrophilic 42 Examples 1) Draw the expected products of the following reactions 43 REACTIONS OF ALDEHYDES AND KETONES Relative Reactivity Nucleophilic Addition Reactions Reduction Of Aldehydes and Ketones - To Hydrocarbons - Using Hydrides to give Alcohols Using Carbon Nucleophiles - Formation of Cyanohydrins - Reactions of Grignard Reagents (Organometallic Reagents) - The Wittig Reaction 44 REACTION OF ALDEHYDES AND KETONES Reduction of Aldehydes and Ketones 1) To Hydrocarbons Reduction of hydrocarbons: Wolff-Kishner Reduction (basic conditions) 2) Using Hydrides to give Alcohols 45 REDUCTION OF ALDEHYDES A N D K E TO N E S 1) To hydrocarbones; Reduction of Hydrocarbons: Wolff-Kishner Reduction (basic conditions) NH2NH2/KOH/ethylene glycol reduces the C=O into –CH2- (convert carbonyl functionalities into methylene groups) 46 WO L F F - K I S H N E R M E C H A N I S M Reaction of aldehydes or ketones with hydrazine produces a hydrazone : Reaction with a base and heat converts a hydrazone to an alkene: Both reactions together produces the Wolff-Kishner Reduction: 47 : MECHANISM OF THE WOLFF KISHNER REDUCTION 1) Deprotonation of Nitrogen 2) Protonation of the Carbon 3) Deprotonation of Nitrogen 4) Protonation of Carbon 48 NUCLEOPHILIC ADDITION OF HYDRAZINE: THE WOLFF–KISHNER REACTION Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature 49 TH E WOLFF –K ISH N ER R EACTION: EXA MPLES 50 REDUCTION OF ALDEHYDES A N D K E TO N E S 2) Hydride Reduction (to alcohols) - Reactions usually in Et2O or THF followed by H3O+ work-ups - Eg: 51 HYDRIDE ADDITION Convert C=O to CH-OH LiAlH4 and NaBH4 react as donors of hydride ion Protonation after addition yields the alcohol 52 Reactions of Carbonyl Compounds with Hydride Ion Hydronium ion Hydride ion Alkoxide ion Ketone or aldehyde is reduced to primary or secondary alcohol 53 Sodium borohydride –NaBH4 54 USING CARBON NUCLEOPHILES (REDUCTIONOF ALDEHYDES & KETONES) 1) Formation of Cyanohydrins 2) Reactions of Grignard reagents / Organometallic Reagents 3) The Wittig Reaction ./ NUCLEOPHILIC ADDITION OF HCN : CYANOHYDRIN FORMATION Using carbon Nucleophiles 1) Formation of Cyanohydrins Cyanide adds to aldehydes and ketones to give a cyanohydrin The reaction is usually carried out using NaCN or KCN with HCl HCN is a fairly weak acid, but very toxic The reaction is useful since the cyano group can be converted into other useful functional groups (-CO2H or –CH2NH2) 56 NUCLEOPHILIC ADDITION OF CYANIDE TO AN ALDEHYDE Step 1: The nucleophilic C in the cyanide adds to the electrophilic C in the polar carbonyl group, electrons from the C=O move to the electronegative O creating an intermediate alkoxide. Step 2: An acid/base reactions. Protonation of the alkoxide oxygen creates the cyanohydrin product. 57 NUCLEOPHILIC ADDITION OF GRIGNARD REAGENTS AND HYDRIDE REAGENTS: A L C O H O L F O R M AT I O N Using carbon Nucleophiles 2) Reactions of Grignard reagents / Organometallic Reagents Grignard reagents react with aldehydes, ketones, and carboxylic acid derivatives 58 R E A C T I O N S O F G R I G NA R D REAGENTS Grindard reagents react with the carbonyl group, C=O, in aldehydes or ketons to give alcohols The substituents on the carbonyl dictate the nature of the product alcohol Addition to methanal (formaldehyde) gives primary alcohols Addition to other aldehydes gives secondary alcohols Addition to ketones gives tertiary secondary alcohols The acidic work-up converts an intermediate metal alkoxide salt into the desired alcohol via a simple acid base reaction. 59 Formation of a New Carbon–Carbon Bond Using Grignard Reagents 60 REACTIONS OF GRIGNARD REAGENTS Reactions of RLi and RMgX with aldehydes and ketones • Reactions usually in Et2O or THF followed by H3O+ workups. • Eg: Treatment of aldehydes or ketones with Grignard reagents yields an alcohol • Nucleophilic addition of the equivalent of a carbon anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +. 61 MECHANISM OF ADDITION OF G R I G NA R D R E A G E N T S NUCLEOPHILIC ADDITION OF RLi OR RMgX TO AN ALDEHYDE Step 1 : The nucleophilic C in the Grignard Reagent adds to the electrophilic C in the polar carbonyl group, electrons from the C=O move to the electronegative O creating an intermediate metal alkoxide complex. Step 2 : This is the work-up step, a simple acid/base reaction. Protonation of the alkoxide oxygen creates the alcohol product from the intermediate complex. 62 MECHANISM OF ADDITION OF GRIGNARD REAGENTS Complexation of C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol Grignard additions are irreversible because a carbanion is not a leaving group 63 Grignard reagents are used to prepare alcohols: 64 Nucleophilic Addition of Phosphorus Ylides: Using carbon Nucleophiles 3) The Wittig Reaction The Wittig reactions is an important method for the formation of alkanes The double bond forms specially at the location of the original aldehyde or ketone Ylides are naturel molecules but have +ve and –ve centers on adjacent atoms that are connected by a s bond The ylids is prepared via a 2 step process: An SN2 reaction between triphenyl phosphine and an alkyl halide followed by treatment with a strong base as an Grignard reagent. 65 NUCLEOPHILIC ADDITION OF PHOSPHORUS YLIDES: THE WITTIG REACTION The sequence converts C=O C=C A phosphorus ylide adds to an aldehyde or ketone to yield a dipolar intermediate called a betaine The intermediate spontaneously decomposes through a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O An ylide 66 MECHANISM OF THE WITTIG REACTION Step 1: The nucleophilic C of the ylid Wittig reagent adds to the electrophilic C in the polar carbonyl group, electrons from the C=O pi bond are used to form a σ bond to the +ve P atom. This creates a cyclic intermeiate called an oxaphosphate. Step 2: Decomposition of the intermediate by breaking the C-P and C-O σ bonds leads to the formation of the C=C π bond of the alkene and triphenyl phosphine oxide. 67 MECHANISM OF THE WITTIG REACTION 68 N U C L E O P H I L I C A D D I T I O N O F A M I N ES: I M I N E A N D E N A M I N E F O R M AT I O N RNH2 adds to C=O to form imines, R2C=NR (after loss of HOH) R2NH yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine) 69 MECHANISM OF F O R M AT I O N O F IMINES Primary amine adds to C=O Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine) Protonation of OH converts into water as the leaving group Result is iminium ion, which loses proton Acid is required for loss of OH – too much acid blocks RNH2 70 ENAMINE FORMATION After addition of R2NH, proton is lost from adjacent carbon 71 IMINE / ENAMINE EXAMPLES 72 NUCLEOPHILIC ADDITION OF ALCOHOLS: ACETAL FORMATION Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal 73 ACETAL FORMATION 74