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2302272 – Org Chem II – Part I

Lecture 3

Aldehydes & Ketones I

Instructor: Dr. Tanatorn Khotavivattana

E-mail: [email protected]

Recommended Textbook:

Chapter 18 in Organic Chemistry, 8th 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

Chapter 18 – Wade - Prentice Hall

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

• sp2 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 #111

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


15Industrial of Aldehydes and Ketones

16Reactions of Aldehydes and Ketones


• 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 sp2 hybridized and flat, leaving it

relatively unhindered and open to attack from either face of the double bond

• The carbon atom changes hybridization from sp2 to sp3

• 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


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

Steric Effect


Electronic Effect


18Nucleophile: “Alkyl” or “Aryl” source

• 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

Grignard Reagents


19

• 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

Organolithium Reagents

Examples

Nucleophile: “Alkyl” or “Aryl” source


20

#1: Sodium Borohydride (NaBH4) #2: Lithium Aluminium Hydride (LiAlH4)

Common Reagents

• Aluminium is less electronegative than boron. Therefore, lithium aluminium hydride(LAH) is amuch stronger reducing agent, and it is much more difficult to work with.

• LAH reacts explosively with water and alcohols, liberating hydrogen gas and sometimesstarting fires. Sodium borohydride reacts slowly with water and alcohols.

• Sodium borohydride is a convenient and highly selective reducing agent.

Nucleophile: “Hydride” source



1) Reaction with Grignard Reagent (and other carbanions, R-)

2) Hydride Reductions

• Attack by R- gives an alkoxide that protonates to form an alcohol

• Attack by hydride gives an alkoxide that protonates to form an alcohol

Problem #222


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




• 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

• Aldehydes are more likely than ketones to form stable cyanohydrin (electronic and

steric effects); Formaldehyde is even more reactive than other aldehydes.



• Cyanohydrin formation is reversible; the equilibrium constant may or may not

favour the cyanohydrin

< <Reactivity


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


• Mechanism for acid-catalysed hydration

Reactions of Aldehydes and Ketones

4) Hydration

• Mechanism for basic-catalysed hydration

Hydroxide is a much stronger nucleophile than water

27

4) Hydration28

• With most ketones, the equilibrium favours the unhydrated keto form


• The reactivity follows the same trend as other reactions

Ketone

Aldehyde

Formaldehyde

Reactivity


5) Formation of Acetals

• Aldehydes and Ketones react with Alcohols to form Acetals

• Acetal formation must be acid-catalysed (not base-catalysed)

Chapter 18 – Wade - Prentice Hallhemi = half

Example

30



Mechanism:

31



Mechanism (continued):

32



Carbohydrate Chemistry

• Glucose is a six-carbon

sugar that is most stable

as a hemiacetal

Alcohol

Aldehyde

2 x

Alcohol

• Lactose is a disaccharide (composed of two sugar units) that has one acetal and

one hemiacetal

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 #334

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


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 #437


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



Mechanism – acid-catalysed



• 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



Other Types of Amines



Reaction with 2,4-DNP – a qualitative test for aldehydes and ketones

2,4-dinitrophenylhydrazine

(2,4-DNP)dinitrophenylhydrazone

yellow, orange or red precipitate

43



7) Oxidation of Aldehydes

• Easily oxidized to carboxylic acids by common oxidants (unlike ketones)

• Common oxidants: bleach (sodium hypochlorite), chromic acid, permanganate

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 #545

46



8) Reduction of Aldehydes and Ketones

• Most commonly reduced by sodium borohydride (NaBH4)

• Lithium aluminum hydride (LiAlH4) 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 NaBH4,

and it selectively reduces aldehydes even in the presence of ketones.

47




• 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

48




• 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 N2 gas

49



9) Wittig Reaction

• Converts C=O to a new C=C using phosphorus ylide (phosphorus-stabilized

carbanion)

• Wittig received the Nobel Prize in Chemistry in 1979 for this discovery

• Often results in a mixture of cis- and trans- isomers

50


9) Wittig Reaction

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

519) Wittig Reaction – Mechanism

Problem #652

Homework – 1 53


Homework – 2

54


Homework – 3

55


Homework – 4

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