Aldehydes and ketones DR AKM SHAFIQUL ISLAM SCHOOL OF BIOPROCESS ENGINEERING UNIVERSITY MALAYSIA PERLIS (UniMAP)

Carbonyl group One of the most important functional groups in organic chemistry. It is present in aldehydes and ketones

Carbonyl Compounds

Aldehydes A compound in which the carbonyl group is connected to a hydrogen and an alkyl group or aromatic ring ( or to two hydrogens ).

Ketones A compound in which the carbonyl group is connected to two alkyl groups or aromatic rings ( or one of each ).

IUPAC Nomenclature of Aldehydes Find the longest continuous chain that includes the aldehyde group Follow all the IUPAC naming rules for alkanes. The carbonyl carbon is always at the end of the chain, so it is carbon number 1. Replace the final -e ending of the alkane with -al. Locate and name any other groups attached to the chain. Aldehydes containing two aldehyde groups are called dials.

IUPAC Nomenclature of Aldehydes The aldehyde group is abbreviated by CHO. The IUPAC retains the common names benzaldehyde and cinnamaldehyde, as well formaldehyde and acetaldehyde.

IUPAC Nomenclature of Ketones Because ketones have the general formula, the shortest ketone chain length is 3 carbons. The carbonyl group cannot be at the end of the chain; it must be in the middle.

IUPAC Nomenclature of Ketones Find the longest continuous chain that includes the carbonyl group Follow all the IUPAC naming rules for alkanes. The chain is numbered from the end closest to the carbonyl group. Replace the final -e ending of the alkane with -one. Locate and name any other groups attached to the chain.

Name the following ketones using IUPAC names and common names. 2-propanone dimethyl ketone acetone 2-butanone ethyl methyl ketone methyl ethyl ketone MEK 5-chloro-4,4-dimethyl-2-hexanone 4 5 1 2 3 6 Copyright© 2005, Michael J. Wovkulich. All rights reserved.

Common names - ketones name each alkyl group bonded to the carbonyl carbon as a separate word, followed by the word "ketone”

Natural Products

Physical Properties What kind of intermolecular forces are possible between carbonyl groups? Is H-bonding possible? How do you think the boiling point of aldehydes and ketones compares to alkanes and alcohols? Alkanes – very weak forces Alcohols – H-bonds

Physical Properties A C=O bond is polar, with oxygen bearing a partial negative charge and carbon bearing a partial positive charge therefore, aldehydes and ketones are polar molecules

Dipole/Dipole Interactions The electronegativity number (E.N.) of carbon is 2.5. The E.N. of oxygen is 3.5. As a result of unequal sharing, the carbonyl bond is polar covalent and the oxygen acquires a partial negative charge. Dipole/dipole interactions aren’t as strong as hydrogen bonds, but they do cause aldehydes and ketones to boil at higher temperatures than alkanes. d+ d- d+ d- dipole/dipole interaction d+ d-

Lack of Hydrogen Bonding Because aldehydes and ketones lack a hydrogen on the oxygen, they cannot form hydrogen bonds between other aldehyde or ketone molecules. Thus, their boiling points are lower than those of alcohols with similar molecular weights (which have extensive hydrogen bonding). Aldehyde Ketone

Solubility Even though it cannot H-bond with other carbonyls, the carboxyl group can accept H-bonds from water formaldehyde, acetaldehyde, and acetone are infinitely soluble in water As the hydrocarbon portion of the molecule increases in size, solubility in water decreases Larger ketones and aldehydes are soluble in organic solvents

Water Solubility Aldehydes and ketones form strong hydrogen bonds with water: As a result, low-molecular weight aldehydes and ketones show appreciable solubilities in water. Acetone and ethanal are soluble in water in all proportions.

Oxidation Aldehydes are oxidized to carboxylic acids Change the –H to an –OH Ketones are not oxidized further

Oxidation of Primary Alcohols General equation: oxidize oxidize RCH2OH RCHO RCOOH Primary alcohol Aldehyde (in anhydrous media) Carboxylic acid (when water is present) (O) + H2O (O)

Oxidation of Primary Alcohols Examples: (O) (O) CH3CH2OH ethanol ethanal ethanoic acid (O) (O) CH3(CH2)5CH2OH 1-heptanol heptanal heptanoic acid

Tests for Aldehydes Tollens’ reagent and Benedict’s reagent are two common chemical reagents used to test for the presence of aldehydes. Both are mild oxidizing solutions.

Tollens’ Reagent Tollens’ reagent is a solution of aqueous silver nitrate (AgNO3) with aqueous ammonia (NH3). All aldehydes give a positive Tollens’ test. In general, ketones don’t react with the Tollens’ reagent except a-hydroxy ketones. NH3, H2O + Ag+(aq) + Ag(s) heat +1 oxidation state 0 oxidation state

Tollens’ Reagent (Silver Mirror Test) If the rate of reaction is slow and the test tube or flask is clean, metallic silver deposits on the sides as a mirror.

Benedict’s Reagent Benedict’s reagent is a solution containing blue, Cu2+ ions. The copper is reduced from the +2 oxidation state to the +1 oxidation state. Red Cu2O is precipitated, giving a positive test. + Cu2+ + Cu2O +2 oxidation state +1 oxidation state

with adjacent alcohol group with adjacent alcohol group Benedict’s Reagent Aldehydes and one type of easily oxidized ketone give a positive test result. The structural features necessary are: Aldehyde Aldehyde with adjacent alcohol group Ketone with adjacent alcohol group These features are found in a number of sugars.

Benedict’s Reagent Benedict’s reagent is the key material in a test kit available from drugstores that permits individuals to monitor the glucose levels in their urine.

Nucleophilic Reaction Reagents that attack the electron-rich d- end of the C=O bond are called electrophiles (literally, "lovers of electrons"). Electrophiles include ions (such as H+ and Fe3+) and neutral molecules (such as AlCl3 and BF3) that are Lewis acids, or electron-pair acceptors. Reagents that attack the electron-poor d+ end of this bond are nucleophiles (literally, "lovers of nuclei"). Nucleophiles are Lewis bases (such as NH3 or the OH- ion).

Nucleophilic Addition A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. A weak nucleophile will attack a carbonyl if it has been protonated, thus increasing its reactivity. Aldehydes are more reactive than ketones. =>

Reaction Themes, Nu attack at C One of the most common reaction themes of a carbonyl group is addition of a nucleophile to form a tetrahedral carbonyl addition compound.

Reaction Themes, O attack at H A second common theme is reaction with a proton or other Lewis acid to form a resonance-stabilized cation. protonation increases the electron deficiency of the carbonyl carbon and makes it more reactive toward nucleophiles.

Addition of C Nucleophiles 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 these carbon nucleophiles.

A. 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.

Grignard Reagents, 1o alcohols addition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1° alcohol. these reactions require two steps.

Grignard Reagents, 2o alcohols addition to any other aldehyde, RCHO, gives a 2° alcohol (two steps).

Grignard Reagents, 3o alcohols addition to a ketone gives a 3° alcohol (two steps).

B. Organolithium Compounds Organolithium compounds, RLi, give the same C=O addition reactions as RMgX but generally are more reactive and usually give higher yields. Lithium is monovalent and does not insert between C and X like Mg. Like the Grignard this requires two steps.

C. Salts of Terminal Alkynes Addition of an alkyne anion followed by H3O+ gives an acetylenic alcohol.

Salts of Terminal Alkynes Addition of water or hydroboration/oxidation of the product gives an enol which rearranges.

D. Addition of HCN HCN adds to the C=O group of an aldehyde or ketone to give a cyanohydrin. Cyanohydrin: a molecule containing an -OH group and a -CN group bonded to the same carbon. O O H C H 3 + H C N C H 3 - N H 2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin)

Addition of HCN Mechanism of cyanohydrin formation: Step 1: nucleophilic addition of cyanide to the carbonyl carbon. Step 2: proton transfer from HCN gives the cyanohydrin and regenerates cyanide ion.

Cyanohydrins The value of cyanohydrins: 1. acid-catalyzed dehydration of the alcohol gives an alkene. 2. catalytic reduction of the cyano group gives a 1° amine.

Cyanohydrins The value of cyanohydrins: 3. acid-catalyzed hydrolysis of the nitrile gives a carboxylic acid. O H acid catalyst O H C H 3 N C H 3 - COOH H 2 O 2-Hydroxypropanenitrile (Acetaldehyde cyanohydrin) 2-Hydroxypropanoic acid

Mechanism of Aldol Reactions Aldol reactions, like all carbonyl condensations, occur by nucleophilic addition of the enolate ion of the donor molecule to the carbonyl group of the acceptor molecule The addition intermediate is protonated to give an alcohol product

Conditions for Condensations A small amount of base is used to generate a small amount of enolate in the presence of unreacted carbonyl compound After the condensation, the basic catalyst is regenerated