Carbonyl Compounds - Lecture notes MCAT WEek PDF

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Ch 6 | Carbonyl Chemistry Wednesday, May 19, 2021

11:41 AM

Nucleophilic Substitution -

Reaction that replaces the leaving group in an electrophilic substrate with a nucleophile ○ No net change in the number of pi or sigma bonds in the reaction

SN2 Reactions -

Nucleophile: strong nucleophiles, non-bulky, negatively charged ○ Ex. Cl-, I-, Br-, CN-, SH-, RSSubstrate: primary or secondary substrate with a good leaving group ○ Ex. Alkyl halides Solvent: polar aprotic solvents ○ Ex. acetone, DMF, DMSO Notes: ○ Nucleophile does a backside attack - stereochemistry is inverted at the carbon that is attacked only ○ Single step reaction ○ Bimolecular: reaction rate depends on both the concentration of the nucleophile and the substrate

SN1 Reactions -

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Nucleophile: weak, uncharged ○ Ex. H2O, MeOH, EtOH Substrate: tertiary substrates, secondary with a good leaving group Solvent: polar protic solvents ○ Ex. Water, alcohol ○ Stabilizes the carbocation and solvates the leaving group Notes: ○ Carbocation intermediate (+) forms ○ Racemic ○ Carbocation rearrangement may occur

Protection Alcohol Protection - Mesylate / Tosylate -

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Adding a mesyl (CH3-SO3-) or tosyl (CH3C6H4-SO3-) group to an alcohol protects them from reacting in a multistep mechanism ○ Done with mesyl chloride or tosyl-chloride (TsCl) in the presence of a base (TEA or Pyr) Can also be used to protect Amino groups Protection is easily removed under reductive conditions Mesylates and tosylates can also make OH good leaving groups

Acetals and Hemiacetals -

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Made by nucleophilic additions to aldehydes or ketones Formed when carbonyls react with alcohols in the presence of an acid Reagent: 1. Strong acid, ROH (I eq) i. forms hemiacetal 2. Strong acid, ROH (2 eq) i. Forms acetal + H2O Substrate: Aldehyde or ketone Product: Hemiacetal with one equivalent of alcohol, acetal with 2 equivalents Mechanism for formation involves acid protonation of the oxygen to make it more electrophilic, then nucleophilic attack of the alcohol at the carbon ○ Subsequent elimination of water and another addition of the alcohol to form full acetal

Cyanohydrin Formation -

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Nucleophilic attack of a cyanide ion on a carbonyl (similar to hemiacetal formation) Reagent: 1. NaCN 2. Proton source workup Substrate: Aldehyde or Ketone Product: Tertiary alcohol with a nitrile group

Nitrogenous Compounds -

Amines ○ Can be primary, secondary, tertiary, or a quaternary ammonium ion ○ Function as both nucleophiles and bases in various reactions

Imine Formation -

Reaction of a ketone or aldehyde with a primary amine forms an imine under weakly acidic conditions (pH 4-5) Reagent: RNH2 Substrate: Aldehyde or Ketone Product: Imine (O in carbonyl replaces with N-R) and H2O

Enamine Formation -

Reaction of a ketone or aldehyde with a secondary amine forms an enamine under weakly acidic conditions (pH 4-5) Reagent: R2NH, cat. H2SO4 Substrate: Aldehyde or Ketone Product: Enamine (resembles enol) and H2O Enamine is nucleophilic at the alpha carbon, and in the presence of an alkyl halide, will generate an iminium ion that will attack itself and reform the carbonyl under workup conditions

Carboxylic Acids -

Form strong hydrogen bonds because they contain an H-bond donor and acceptor

Carboxylic Reduction (Making a 1° Alcohol) -

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Reagent: 1. LiAlH4 2. H3O+ workup Substrate: Carboxylic acid Product: Primary alcohol Using NaBH4 does NOT work for carboxylic acids

Decarboxylation of B-Keto Acids -

B-keto acids are carboxylic acids that have a carbonyl group beta to it

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Will undergo a decarboxylation reaction, which essentially removes the carboxylic acid CO2 and leaves behind the carbonyl

Esterification of Carboxylic Acids -

Carboxylic acid reacts with an alcohol in the presence of catalytic acid Reagent: ROH and acid Substrate: Carboxylic acid Product: Ester and water

Hydrolysis of Ester (reforms C.A.) - Can be acid or base catalyzed - Reagent: H3O+ (acidic conditions) - Substrate: Ester (COOR) - Product: Carboxylic acid and ROH alcohol Note that the acid/base catalyst is not consumed at all in the reaction, and is regenerated at the end - Reagent: OH- catalyst (basic conditions) - Substrate: Ester (COOR) - Product: Carboxylic acid and ROH alcohol Very important reaction! Why is this done? - Transesterification- ester can by hydrolyzed to a carboxylic acid and then reesterified to install a different R group and create a different ester ○ Using a large amount of the alcohol that would provide the desired ester shifts the equilibrium towards the desired ester...