Organic Chemistry II - Aromatic Reactions and Carbonyls!

This lecture covers type ii carbonyls, aldehydes and ketones, undergoing nucleophilic addition to form a tetrahedral intermediate, with strong nucleophiles driving and weak or moderate ones allowing reversibility.

The lecture explains how a nucleophile attacks a carbonyl of an aldehyde to form a tetrahedral intermediate, and introduces turning carbon into a nucleophile with a metal for Grignard reaction.

Discover how to form Grignard reagents from alkyl halides using magnesium in ether, and harness them to create new carbon–carbon bonds in reactions.

Explore making Grignard reagents from sp2-hybridized carbons, showing magnesium inserts between carbon and bromine and the nucleophilic carbon attacks an alkyl halide to form a new C–C bond.

Grignard reagents are not only strong nucleophiles but also very strong bases; presence of water or acidic groups destroys their nucleophilicity and can derail carbon–carbon bond formation.

Reacting a Grignard reagent with type two carbonyls (aldehydes or ketones) forms a tetrahedral intermediate and, after acid workup, yields alcohols; aldehydes give secondary alcohols, ketones give tertiary alcohols.

Explore Grignard reactions with type i carbonyls, including esters; form tetrahedral intermediates and ketone or alcohol products. Excess Grignard biases the reaction toward alcohol by converting ketones.

Turn alcohols into Grignard reagents via a two-step route: convert to an alkyl bromide, then form the Grignard with magnesium in ether and trap with CO2 to ibuprofen.

learn how hydrides attack type two carbonyls to form tetrahedral intermediates, then are quenched to give alcohols, using sodium borohydride as a safer hydride source.

Sodium borohydride reduces acyl chlorides to aldehydes and further reduces aldehydes and ketones to alcohols. Esters show no reaction, illustrating the difference between type one and type two carbonyls.

Understand why sodium borohydride fails on carbonyls and how lithium aluminum hydride more readily reduces esters and aldehydes to alcohols, often without stopping at aldehyde.

Discover how DIBAL-H reduces esters to aldehydes at −78 °c with a brief acid workup. See backward synthesis from aldehydes to carboxylic acids via Fischer esterification and Grignard pathways.

Explore how carboxylic acids and amides react with lithium aluminum hydride, showing carboxylic acids convert to alcohols and esters sit on roughly equal footing in reactivity, with mechanism notes.

Explore the lithium aluminum hydride mechanism: reduction of carboxylic acids and amines, forming aldehydes and alcohols via tetrahedral intermediates and hydride transfers.

Explore how weak to moderate nucleophiles, especially amines, react with type II carbonyls under catalytic acid to form imines via a reversible addition–dehydration pathway, with water as the leaving group.

Explore how secondary amines react with type II carbonyls to form enamines via dehydration, and identify the key cut point for reverse synthesis.

Learn how secondary amines react with type II carbonyls under acid to form inamines, identifying the single cut point and the carbonyl carbon, then account for water byproducts.

Master reductive amination, a two-step process that forms an imine from a carbonyl and amine, then reduces it to an amine using mild reagents such as sodium borohydride.

Explore reductive amination by converting imines formed from a ketone and primary or secondary amines into amines using reducing agents; apply intramolecular reactions and dehydration to build a six-atom ring.

Examine how alcohols add to type II carbonyls to form hemi-ketals, and, with excess alcohol, ketals, guided by equilibria, acid protonation, and water loss.

Explore how alcohols react with aldehydes to form hemiacetals and acetals, predict products for more complex carbonyls, and distinguish acetyl from acetone while naming the derived groups.

Investigate selective reductions of ketones versus esters using sodium borohydride and lithium aluminum hydride, and discuss why each reagent behaves differently.

Explore how lithium aluminum hydride spares ethers, enabling a protect–react–protect sequence that forms a ketal from a ketone with alcohol, then reverts to the ketone with water and strong acid.

Focus on deprotecting ketals and acetals by locating the carbon bonded to two oxygens and determining cut points to reform the carbonyl using two alcohols.

Show how the alpha carbon next to a carbonyl becomes nucleophilic after deprotonation, forming an enolate with resonance structures, and enabling reaction with electrophiles.

Apply a base to deprotonate the alpha carbon of a ketone, producing water. Use pKa values (alpha carbon ~20, water ~15) to assess the acid-base equilibrium.

This lecture covers the aldol reaction: enolates attack type two carbonyls to form an alkoxide that protonates to an alcohol, with mixed aldol products and addition behavior.

Explore aldol reactions with multiple alpha carbons, where enolates attack carbonyls to form additions under one-to-one ratios. Shift to a one-to-two ratio biases toward double additions, utilizing both alpha carbons.

Explore aldol dehydration, where removal of a beta hydroxy and an alpha hydrogen forms a double bond and water, with heat and high conjugation promoting dehydration.

In the mixed aldol, two type 2 molecules A and B under base form alpha enolates that can act as nucleophiles or electrophiles, producing four distinct products.

Discover the mixed aldol reaction, yielding four distinct products from two aldehydes, and practice dehydration to forge a new alpha–beta double bond.

Leverage bulky bases like lda to fully form the enolate, shifting equilibrium to the nucleophile and avoiding multiple aldol products. This yields a cleaner one-to-one reaction with easier purification.

Investigate reactions on benzene, where hydrogenation with hydrogen and palladium on carbon fails under normal conditions, highlighting aromaticity as benzene's unexpected stability.

Learn the four aromatic criteria—cyclic pi-electron cloud, uninterrupted circuit, planar geometry, and an odd number of resonating electron pairs—and see how resonance and pi systems illustrate them.

Assess aromatic criteria by confirming planarity and sp2 hybridized carbons, then count lone pairs that participate in resonance to yield an odd total of electron pairs.

Determine aromaticity by evaluating a cyclic pi electron cloud, possible resonance, uninterrupted circulation, planarity, and odd electron-pair count; neither molecule is aromatic due to octet and odd-pair failures.

Explore aromaticity criteria through practice problems, counting pi bonds and lone pairs, delocalizing electrons via resonance, and recognizing thymine as aromatic; note orbital orientation governs lone-pair participation.

Assess aromaticity by confirming a cyclic, uninterrupted ring of pi electrons, planarity, and an odd number of electron pairs, including delocalization through lone pairs and bonds.

Reclassify molecules as aromatic, anti aromatic, or non aromatic by counting even electron pairs, assess stability on energy diagrams, and analyze which undergoes the substitution reaction fastest via carbocation intermediates.

Explore how benzene and other aromatics react by using a pi bond as a nucleophile to attack an electropositive atom, illustrating addition mechanisms and loss of aromatic stabilization.

Explore how benzene reacts via aromatic substitution rather than addition, emphasizing why the blue product is the major outcome and how energy diagrams explain the preference.

Examine halogenation and nitration of benzene using Br2 with FeBr3 for single bromination, and HNO3/H2SO4 to form a nitro group, emphasizing aromaticity and acid-base roles.

Explore the nitration mechanism: protonated nitric acid forms the nitronium ion after water leaves, then benzene attacks to yield nitrobenzene via a two-step electrophilic aromatic substitution.

Explore the Friedel–Crafts isolation between benzene and a type one carbonyl via aluminum trichloride, highlighting benzene as nucleophile and chlorine as leaving group in electrophilic aromatic substitution.

Explore Friedel-Crafts alkylation of benzene with alkyl halides under AlCl3 catalysis, including carbocation formation, hydride shifts, and key rearrangements that affect product structure.

this lecture demonstrates a Friedel-Crafts alkylation of benzene with an alkyl halide under AlCl3, highlighting possible carbocation rearrangements like methyl shifts that can alter the product.

Explore how electron donating groups accelerate and electron withdrawing groups slow electrophilic aromatic substitution by affecting the benzene pi bond acting as a nucleophile, via inductive effects and hyperconjugation.

Explore how resonance dominates the rate of EAS, weighing inductive versus resonance effects with examples like methoxy donating electrons and nitro withdrawing electrons.

Examine how substituents direct electrophilic aromatic substitution to the ortho and para positions on methoxybenzene. Predict two major nitro products from nitration, based on resonance and electron density.

Explore how electrophilic aromatic substitution directs nitro group placement on benzene, predicting major products using resonance contributors and electron density, with a 66:33 ortho:para distribution.

Learn how electron-donating groups accelerate electrophilic aromatic substitution and direct ortho/para activation, while electron-withdrawing groups slow and direct meta, with examples like amines, ethers, and nitro groups.

Explore how weak electron-withdrawing groups like halogens still direct electrophilic aromatic substitution to ortho and para positions, not meta, due to inductive withdrawal overpowering resonance.

esters on benzene can act as activators or deactivators; attachment through oxygen directs meta, while attachment through the carbonyl directs ortho-para, with resonance controlling electron withdrawal or donation.

Classify activators and deactivators for aromatic rings as strong, moderate, or weak, highlighting amines, alcohols, ethers as activators and nitro or ammonium as deactivators, with resonance and induction driving effects.

Predict substitution in disubstituted benzenes undergoing electrophilic substitution by weighing activating and deactivating groups. Evaluate ortho, para, and meta directing effects and steric hindrance to determine major and minor products.

Explore how steric blockade from bulky groups redirects electrophilic aromatic substitution from ortho toward para, reducing ortho selectivity from about 66% to ~50/50.

Examine the limitations of friedel crafts on deactivated benzene and nitro groups, where sluggish reactions yield little product, and aluminum chloride–nitrogen complexation can turn activators into deactivators, with workarounds discussed.

Explore Friedel–Crafts limitations on deactivated benzene rings, using nitration to direct meta, then isolation and Wolf Kissner reduction. Avoid overreach to carboxylic acids or esters.

Explore arene diazonium salts formed from primary amines at 0 °C, and use them in nitrile formation via copper cyanide and in azo dye synthesis through electrophilic substitution.

Explore the SNAr mechanism on arenes, where external nucleophiles displace leaving groups on benzene, aided by nitro groups and electron-withdrawing effects to stabilize intermediates.

Discover benzyne reactions on benzene using sodium amide in liquid ammonia, forming unstable benzyne intermediates and yielding two distinct products with different orientations.