2302272 Org Chem II Part I Lecture 3 Aldehydes & Ketones I Instructor: Dr. Tanatorn Khotavivattana E-mail: tanatorn.k@chula.ac.th Recommended Textbook: Chapter 18 in Organic Chemistry, 8 th Edition, L. G. Wade, Jr., 2010, Prentice Hall (Pearson Education)
Aldehyde = Latin alcohol dehydrogenatus (dehydrogenated alcohol) 1 Ketone = Aketon (an old German word for acetone) formaldehyde methanal acetone propanone
Compounds containing a carbonyl group 2 Important in chemistry, biochemistry, biology Constituents of fabrics, flavourings, plastics, drugs, etc.
Aldehydes and Ketones 3 Ketones and aldehydes are similar in structure, and they have similar properties In most cases, aldehydes are more reactive than ketones
Structure of the Carbonyl Group 4 sp 2 hybridised carbon Bonded to 3 other atoms through coplanar sigma bonds oriented about 120 apart Unhybridized p orbital overlaps with a p orbital of Oxygen to form a pi bond C=O bond has similar geometry to C=C but C=O bond is shorter, stronger and more polarized than C=C bond
Structure of the Carbonyl Group 5 C=O has a large dipole moment because O is more electronegative than C and the bonding electrons are not shared equally (resonance) more bonds and less charge separation
Nomenclature IUPAC Names of Aldehydes 6 Replace -e of alkane name with al Aldehyde C is at the end of a chain: (almost) always number 1 If aldehyde is attached to a large unit (ring): use suffix carbaldehyde
Nomenclature IUPAC Names of Ketones 7 Replace -e of alkane name with one Number longest chain containing C=O from the end closest to C=O Indicate position of the C=O by a number In cyclic ketones, carbonyl carbon is assigned number 1
Nomenclature Aldehydes and Ketones 8 Also be named as a substituent on a molecule with a higher priority group A ketone or aldehyde carbonyl is named by the prefix oxo- if it is included as part of the longest chain in the root name Priority Ranking When an aldehyde group is a substituent and not part of the longest chain, it is named by the prefix formyl
Nomenclature Common Names of Aldehydes 9 Derived from the common names of carboxylic acids
Nomenclature Common Names of Ketones 10 Naming 2 alkyl groups bonded to the C=O; add ketone at the end Some ketones have historical common names
Problem #1 11
Physical Properties of Aldehydes and Ketones 12 Polarization of the carbonyl group creates dipole dipole attractions between the molecules Higher boiling points than for hydrocarbons and ethers of similar M.W.
Physical Properties of Aldehydes and Ketones 13 Pure aldehydes or ketones cannot form H bonding with each other They can form H bonding with compounds having O-H or N-H bonds Aldehydes and ketones are good solvents for polar hydroxylic compounds (eg. Alcohols)
Physical Properties of Aldehydes and Ketones 14
Industrial of Aldehydes and Ketones 15
Reactions of Aldehydes and Ketones 16 The most common reaction is nucleophilic addition (addition of a nucleophile and a proton across the double bond) The reactivity of the carbonyl group arises from the electronegativity of the oxygen atom and the resulting polarization of the carbon oxygen double bond The electrophilic carbonyl carbon atom is sp 2 hybridized and flat, leaving it relatively unhindered and open to attack from either face of the double bond The carbon atom changes hybridization from sp 2 to sp 3 The electrons of the pi bond are forced out to the oxygen atom to form an alkoxide anion, which protonates to give the product of nucleophilic addition
Reactions of Aldehydes and Ketones 17 Aldehydes vs. Ketones towards Nucleophilic Addition In most cases, aldehydes are more reactive than ketones; they usually react more quickly (Kinetics), and the position of the equilibrium usually lies more toward the products (Thermodynamics) than with ketones Electronic Effect Steric Effect
Nucleophile: Alkyl or Aryl source 18 Grignard Reagents Formula: R Mg X (alkyl magnesium halide) Reacts like R - + MgX May be formed from any halides (alkyl, vinyl or aryl halides) Ethers are used as solvents to stabilise the complex Chapter 10 Wade - Prentice Hall
Nucleophile: Alkyl or Aryl source 19 Organolithium Reagents Formula: R Li (alkyl lithium) Reacts like R - + Li May be formed from any halides (alkyl, vinyl or aryl halides) Ether not necessary, wide variety of solvents can be used Examples Chapter 10 Wade - Prentice Hall
Nucleophile: Hydride source 20 Common Reagents #1: Sodium Borohydride (NaBH 4 ) #2: Lithium Aluminium Hydride (LiAlH 4 ) Aluminium is less electronegative than boron. Therefore, lithium aluminium hydride (LAH) is a much stronger reducing agent, and it is much more difficult to work with. LAH reacts explosively with water and alcohols, liberating hydrogen gas and sometimes starting fires. Sodium borohydride reacts slowly with water and alcohols. Sodium borohydride is a convenient and highly selective reducing agent. Chapter 10 Wade - Prentice Hall
Reactions of Aldehydes and Ketones 21 1) Reaction with Grignard Reagent (and other carbanions, R - ) Attack by R - gives an alkoxide that protonates to form an alcohol 2) Hydride Reductions Attack by hydride gives an alkoxide that protonates to form an alcohol
Problem #2 22
Reactions of Aldehydes and Ketones 23 3) Formation of Cyanohydrins Hydrogen cyanide (HCN) is a toxic, water-soluble liquid that boils at 26 C The conjugate base is the cyanide ion (CN - ), which is a strong nucleophile; It attacks ketones and aldehydes to give addition products called cyanohydrins
Reactions of Aldehydes and Ketones 24 3) Formation of Cyanohydrins The millipede stores mandelonitrile which is a cyanohydrin of benzaldehyde Cyanohydrin formation is reversible; when attacked, it discharges mandelonitrile through a reaction chamber containing enzymes that catalyse the conversion of the cyanohydrin to benzaldehyde and HCN
3) Formation of Cyanohydrins 25 Cyanohydrin formation is reversible; the equilibrium constant may or may not favour the cyanohydrin Aldehydes are more likely than ketones to form stable cyanohydrin (electronic and steric effects); Formaldehyde is even more reactive than other aldehydes. < < Reactivity
Reactions of Aldehydes and Ketones 26 4) Hydration In an aqueous media, a ketone or an aldehyde is in equilibrium with a geminal diol The reaction is very slow because water is a weak nucleophile; Either activation of the electrophile (the carbonyl group) or of the nucleophile (the water) is required A carbonyl group that is protonated (or bonded to some other electrophile) is strongly electrophilic, inviting attack by a weak nucleophile
Reactions of Aldehydes and Ketones 27 4) Hydration Mechanism for acid-catalysed hydration Mechanism for basic-catalysed hydration Hydroxide is a much stronger nucleophile than water
4) Hydration 28 With most ketones, the equilibrium favours the unhydrated keto form Ketone Aldehyde Formaldehyde Reactivity The reactivity follows the same trend as other reactions
Reactions of Aldehydes and Ketones 29 5) Formation of Acetals Aldehydes and Ketones react with Alcohols to form Acetals Acetal formation must be acid-catalysed (not base-catalysed) hemi = half
5) Formation of Acetals 30 Example Mechanism:
5) Formation of Acetals 31 Mechanism (continued):
5) Formation of Acetals Carbohydrate Chemistry Aldehyde 32 Glucose is a six-carbon sugar that is most stable as a hemiacetal Alcohol Lactose is a disaccharide (composed of two sugar units) that has one acetal and one hemiacetal Alcohol 2 x
5) Formation of Acetals 33 Equilibrium of Acetal Formation Acetal formation is reversible For simple aldehydes, equil. const. generally favour the acetals With hindered aldehydes and most ketones, equil. const. favour the carbonyl Most acetals are hydrolysed by shaking with dilute acid in water Large excess of water drives acetals back to C=O
Problem #3 34
5) Formation of Acetals 35 Cyclic Acetals Formation of an acetal using a diol as the alcohol gives a cyclic acetal Cyclic acetals often have more favourable equilibrium constants, since there is a smaller entropy loss (2 molecules condense instead of 3 for normal alcohol) Ethylene glycol is often used to make cyclic acetals
5) Formation of Acetals 36 Acetals as Protecting Groups If the aldehyde is protected as an acetal, it is unreactive toward a Grignard reagent Acetals are stable to strong bases and nucleophiles
Problem #4 37
Reactions of Aldehydes and Ketones 38 6) Formation of Imines Ammonia or a primary amine reacts with ketone or aldehyde to form an imine via condensation reaction Imines are nitrogen analogues of aldehydes and ketones with C=N bond in place of C=O bond Like amines, imines are basic; a substituted imine is also called a Schiff base
6) Formation of Imines 39 Mechanism acid-catalysed
6) Formation of Imines 40 The proper ph is crucial to imine formation The second half of the mechanism is acid-catalysed, so the solution must be somewhat acidic. However, if the solution is too acidic, the amine becomes protonated and non-nucleophilic, inhibiting the first step. Example
6) Formation of Imines 41 Other Types of Amines
6) Formation of Imines 42 Reaction with 2,4-DNP a qualitative test for aldehydes and ketones 2,4-dinitrophenylhydrazine (2,4-DNP) dinitrophenylhydrazone yellow, orange or red precipitate
Reactions of Aldehydes and Ketones 43 7) Oxidation of Aldehydes Easily oxidized to carboxylic acids by common oxidants (unlike ketones) Common oxidants: bleach (sodium hypochlorite), chromic acid, permanganate
Reactions of Aldehydes and Ketones 44 7) Oxidation of Aldehydes Tollens Test Tollens reagent: a solution of silver ammonia complex Silver ion (Ag + ) is a mild oxidising agent; oxidises aldehydes selectively Convenient functional-group test for aldehydes If an aldehyde is present, its oxidation reduces silver ion to metallic silver in the form of a black suspension or a silver mirror deposited on the inside of the container.
Problem #5 45
Reactions of Aldehydes and Ketones 46 8) Reduction of Aldehydes and Ketones Most commonly reduced by sodium borohydride (NaBH 4 ) Lithium aluminum hydride (LiAlH 4 ) also works, but it is more powerful (less selective), and it is much more difficult to work with Sodium triacetoxyborohydride [NaBH(OAc) 3 ] is less reactive than NaBH 4, and it selectively reduces aldehydes even in the presence of ketones.
Reactions of Aldehydes and Ketones 47 8) Reduction of Aldehydes and Ketones Clemmensen Reduction: convert aldehydes and ketones to alkanes The carbonyl compound is heated with an excess of amalgamated zinc and hydrochloric Limitation: some compounds might decompose in hot and acidic conditions
Reactions of Aldehydes and Ketones 48 8) Reduction of Aldehydes and Ketones Wolff Kishner Reduction: convert aldehydes and ketones to alkanes The carbonyl compounds is treated with hydrazine to form hydrazones, which is heated with a strong base such as KOH to facilitate the elimination of N 2 gas
Reactions of Aldehydes and Ketones 49 9) Wittig Reaction Wittig received the Nobel Prize in Chemistry in 1979 for this discovery Converts C=O to a new C=C using phosphorus ylide (phosphorus-stabilized carbanion) Often results in a mixture of cis- and trans- isomers
9) Wittig Reaction 50 Preparation of Phosphorus Ylide Step 1: nucleophilic attack by triphenylphosphine on an unhindered alkyl halide to give alkyltriphenylphosphonium salt Step 2: The phosphonium salt is treated with a strong base (usually butyllithium) to abstract a proton
9) Wittig Reaction Mechanism 51
Problem #6 52
Homework 1 53 Homework 2
Homework 3 54
Homework 4 55