Lecture 10 - The Carbonyl Group - LS4002 - PDF
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Uploaded by PreferableClavichord4560
Kingston University
2019
Ian Beadham
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Summary
This document presents a lecture on the carbonyl group, discussing reactions of aldehydes and ketones, imines, and redox reactions. It provides a detailed overview of the various types of chemical reactions and includes chemical formulas and diagrams.
Full Transcript
# The Carbonyl Group - O=C - R - R' ## LS4002 - Lecture 10 **Dr Ian Beadham - Room MB 2008 - E-mail: [email protected]** # Reactions of Aldehydes and Ketones 1. Imine **formation** from aldehydes and ketones 2. Imine **hydrolysis** to aldehydes and ketones 3. Alcohol **oxidation** to al...
# The Carbonyl Group - O=C - R - R' ## LS4002 - Lecture 10 **Dr Ian Beadham - Room MB 2008 - E-mail: [email protected]** # Reactions of Aldehydes and Ketones 1. Imine **formation** from aldehydes and ketones 2. Imine **hydrolysis** to aldehydes and ketones 3. Alcohol **oxidation** to aldehydes and ketones 4. Aldehyde or ketone **reduction** to alcohols # Imine formation from aldehydes & amines - Amines react with aldehydes to form imines CH3 - H - C - O - + - H - H - N - -> - CH3 - H - C= - N - + - H - O - H - **aldehyde** **amine** **imine** **water** - Water is lost: this is referred to as a **condensation reaction** # Reverse reaction: Imine hydrolysis - With excess water, imines hydrolyse to aldehydes - CH3 - C= - N - + - H - O - H -> - CH3 - C - O - + - H - N - **imine** **water** **aldehyde** **amine** - Hydrolysis = 'splitting by water' (imine splits to RCHO + R'NH<sub>2</sub>) # Imine formation from ketones & amines - Amines also react with ketones to form imines - CH3 - C - O - CH3 - + - H - N -> - CH3 - C= - N - CH3 - + - H - O - H - **ketone** **amine** **imine** **water** - Water is lost: this is referred to as a **condensation reaction** # Reverse reaction: Imine hydrolysis - With excess water, imines hydrolyse to ketones - CH3 - C= - N - CH3 - + - H - O - H -> - CH3 - C - O - CH3 - + - H - N - **imine** **water** **ketone** **amine** - Hydrolysis = 'splitting by water' (imine splits to R₂C=O + R'NH<sub>2</sub>) # Imine formation is important in biology - Biological example: vitamin B6 (pyridoxal) - P - CO<sub>2</sub>H - H - C=O - + - H - N - OH - CO<sub>2</sub>H -> - P - O - O - O - + - H - - N - CO<sub>2</sub>H - H - C= - N - OH - CO<sub>2</sub>H - + - H - O - H - **aldehyde** **amine** **imine** **water** - Transaminase enzymes use pyridoxal (aldehyde) as **co-factor** # Redox reactions of Aldehydes & Ketones - **Losing electrons [or H] is oxidation (Leo)** - Red - H - C - O-H - H - + - Hydride acceptor <-> - Ox - H - C - O + H - CH3 - + - Hydride donor CH3 - **alcohol** **oxidising agent** **aldehyde** - **Oxidation Is Loss, Reduction Is Gain (Loss /Gain e's or H's)** # Ethanol is oxidised to acetaldehyde -(causes a hangover!) by Alcohol Dehydrogenase - **Losing H [or electrons] is oxidation (Leo)** - H - C - O-H - H - + - H - C - O= - NH<sub>2</sub> - CH3 - N - Adenine dinucleotide - NAD+ -> - CH3 - H - C - O + H - + - H - C - O= - NH<sub>2</sub> - N - Adenine dinucleotide - NADH - **alcohol** **oxidising agent** **aldehyde** - NAD+ = Nicotinamide Adenine Dinucleotide - a hydride acceptor # Alcohol dehydrogenase enzymes oxidise alcohols - using the hydride (H-) acceptor, NAD+ - Enzyme - H - C - O-H - H - CH3 - + - NAD+ -> - H - C - O - CH<sub>3</sub> - Oxidation # Alcohol dehydrogenase enzymes can work in reverse - (reduce carbonyls to alcohols) by using NADPH - CH3 - C - O - CH3 - + Enzyme -> - H - C - O-H - CH3 - + - NADPH - Reduction - NADPH is a reduced cofactor & hydride donor # In bacteria, acetone is reduced to isopropanol -by Secondary Alcohol Dehydrogenase - **Gaining electrons [or H's] is reduction (RIG)** - CH3 - C - O + H - CH3 - + - H - C - O = - NH2 - + - N - Adenine dinucleotide phosphate - ketone - reducing agent NADPH co-factor -> - CH<sub>3</sub> - C - O - H - CH<sub>3</sub> - + - H - C - O = - NH2 - N - Adenine dinucleotide phosphate - alcohol - NADP oxidised cofactor - NADP = Nicotinamide Adenine Dinucleotide Phosphate # Substitution Reactions of Carbonyls 1. What is a substitution reaction 2. Which carbonyls can undergo substitution 3. What is a leaving group 4. What is a nucleophile; what is an electrophile 5. How do biological substitution reactions occur # Substitution reactions occur when 1 of the 2 - groups on the carbonyl is replaced by a new group # Carbonyl substitution reactions: - R - C - O - X - + - :Nu -> - R - C - O - Nu - + - X - R-CO-X - **Nucleophile** - **(New Group)** - **New carbonyl** - **compound** - **Leaving** - **Group** - X = "SR (good) OPO<sub>3</sub>H<sub>2</sub>(good) OR (medium) "OH, NR<sub>2</sub> (poor) - Note: aldehydes and ketones cannot undergo - substitution reactions at the carbonyl group (no X) # Impossible carbonyl substitution reactions: - R - C - O - H - + - :Nu -> - R - C - O - Nu - + - H - R - C - O - CH<sub>3</sub> - + - :Nu -> - R - C - O - Nu - + - CH<sub>3</sub> - H & CH<sub>3</sub> cannot be leaving groups (H & CH<sub>3</sub> are too high in energy) # Leaving groups contain heteroatoms (i.e. not C or H) - such as S, Cl, O or N covalently bonded to C=O # Good leaving groups can stabilise a (-) charge - R - C - O - SR - + - :Nu -> - R - C - O - Nu - + - SR - leaving group - R - C - O - O - P - OH - OH - + - :Nu -> - R - C - O - Nu - + - O - P' - OH - OH - leaving group - SR & OPO<sub>3</sub>H<sub>2</sub> conjugate anions of acids so can stabilise (-) # Leaving groups contain heteroatoms (i.e. not C or H) - such as S, Cl, O or N covalently bonded to C=O # Good leaving groups can stabilise a (-) charge - R - C - O - SR - + - :Nu -> - R - C - O - Nu - + - SR - leaving group - R - C - O - O - P - OH - OH - + - :Nu -> - R - C - O - Nu - + - O - P - OH - OH - leaving group - thioesters and acyl phosphates contain biological leaving groups - SR & OPO<sub>3</sub>H<sub>2</sub> conjugate anions of acids so can stabilise (-) # Neutral nucleophiles (e.g. RNH<sub>2</sub>) lose a proton which - is transferred onto the leaving group in the reaction # Amine (RNH<sub>2</sub>) as the nucleophile: - R - C - O - SR - + - H - NHR -> - R - C - O - NHR - H - + - HSR - Electrophile Nucleophile - Thioester Amine Amide Thiol - Electrophile = 'electron-lover' (reacts with lone pair or minus charge) # Neutral nucleophiles (e.g. ROH) lose a proton which - is transferred onto the leaving group in the reaction # Alcohol (ROH) as the nucleophile: - R - C - O - SR - + - H - OR -> - R - C - O - OR - + - HSR - Electrophile Nucleophile - Thioester Alcohol Ester Thiol - Electrophile = 'electron-lover' (reacts with lone pair or minus charge) # The carbonyl compound is an electrophile - (it reacts with molecules rich in electrons) - Electrophile = loves electrons Alcohol oxygen has lone pairs of electrons - R - C - O - SR - + - HO - R' -> - R - C - O - OR' - + - HS - R - Thioester Alcohol Ester Thiol - ↓ ↓ - Electrophile Nucleophile - Thioesters are electrophiles (electron lovers) they react with molecules that contain available electron pairs (e.g. alcohols or amines) # The carbonyl compound is an electrophile - (it reacts with molecules rich in electrons) - Electrophile = loves electrons Amine nitrogen has a lone pair of electrons - R - C - O - SR - + - H<sub>2</sub>N - R' -> - R - C - O - NR' - H - + - HS - R - Thioester Amine Amide Thiol - ↓ ↓ - Electrophile Good Nucleophile (donates electrons very readily) - Thioesters are electrophiles (electron lovers) they react with molecules that contain available electron pairs (e.g. alcohols or amines) # Electrophiles want electrons because they - contain an atom which is (slightly) positive - Electrophile = loves electrons Amine nitrogen has a lone pair of electrons - R - C - O - SR - + - H<sub>2</sub>N - R' -> - R - C - O - NR' - H - + - HS - R - Oxygen slightly - negative - δ- - | - Carbon slightly - positive - R - C - O - SR - δ+ - Oxygen is more electronegative than carbon, - i.e. in C-O bonds, electrons are more drawn - towards oxygen, making carbon slightly positive # Which of these contain (good / poor / no) leaving groups? - R - C - O - OH - + - R - C - O - OR' - + - R - C - O - NH - H - + - R - C - O - O - R - + - R - C - O - Cl - Carboxylic acid Ester Amide Acid anhydride Acid chloride - poor poor poor good good - R - C - O - H - + - R' - C - O - R' - + - R' - C - O - SR' - + - R - C - O - O - R' - + - H<sub>2</sub>N - C - O - NH<sub>2</sub> - Aldehyde Ketone Thioester Mixed anhydride Urea - no no good good poor - These FGs are called carbonyls as all contain C=O, the carbonyl group # Which of these contain (good / poor / no) leaving groups? - R - C - O - OH - + - R - C - O - OR' - + - R - C - O - NH - H - + - R - C - O - O - R - + - R - C - O - Cl - Carboxylic acid Ester Amide Acid anhydride Acid chloride - poor poor poor good good - R - C - O - H - + - R' - C - O - R' - + - R' - C - O - SR' - + - R - C - O - O - R' - + - H<sub>2</sub>N - C - O - NH<sub>2</sub> - Aldehyde Ketone Thioester Mixed anhydride Urea - no no good good poor - These FGs are called carbonyls as all contain C=O, the carbonyl group - All including this lecture in MCQ test 12th Dec. # Chemistry for the Biosciences (Crowe) - 380-382 (nucleophile & electrophile) - 203-12 (carbonyls) - 418-419 (leaving group) - 407-409 (redox)
