Organic Chemistry I Review Cheat Sheet, Cheat Sheet of Organic Chemistry

Download Organic Chemistry I Review Cheat Sheet and more Cheat Sheet Organic Chemistry in PDF only on Docsity! Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 1 Some Arrow-Pushing Guidelines (Section 1.14) 1. Arrows follow electron movement. 2. Some rules for the appearance of arrows • The arrow must begin from the electron source. There are two sources: a. An atom (which must have a lone pair to give) b. A bond pair (an old bond that breaks) • An arrow must always point directly to an atom, because when electrons move, they always go to some new atom. 3. Ignore any Spectator Atoms. Any metal atom is always a “spectator” • When you have a metal spectator atom, realize that the non-metal next to it must have negative charge 4. Draw all H’s on any Atom Whose Bonding Changes 5. Draw all lone-pairs on any Atom whose bonding changes 6. KEY ON BOND CHANGES. Any two-electron bond that changes (either made or broken) must have an arrow to illustrate: • where it came from (new bond made) or • an arrow showing where it goes to (old bond broken) 7. Watch for Formal Charges and Changes in Formal Charge • If an atom’s charge gets more positive Þ it’s donating/losing an electron pair Þ arrow must emanate from that atom or one of it’s associated bonds. There are two “more positive” transactions: • When an anion becomes neutral. In this case, an arrow will emanate from the atom. The atom has donated a lone pair which becomes a bond pair. • When a neutral atom becomes cationic. In this case, the atom will be losing a bond pair, so the arrow should emanate from the bond rather than from the atom. • If an atom’s charge gets more negative Þ it’s accepting an electron pair Þ an arrow must point to that atom. Ordinarily the arrow will have started from a bond and will point to the atom. 8. When bonds change, but Formal Charge Doesn’t Change, A “Substitution” is Involved • Often an atom gives up an old bond and replaces it with a new bond. This is “substitution”. • In this case, there will be an incoming arrow pointing directly at the atom (to illustrate formation of the new bond), and an outgoing arrow emanating from the old bond that breaks Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 2 4.16 Reactive Intermediates: Stability Patterns • Shortlived, unstable, highly reactive intermediates • Normally lack normal bonding These are tremendously important: 1. They will be the least stable intermediate in any multistep mechanism 2. When formed, they are products of the rate-determining step 3. Factors that stabilize them will speed up reaction rates Thus it is very important to know their stability patterns! Class Structure Stability Pattern Carbocations Allylic > 3º > 2º > 1º > methyl > alkenyl (vinyl, aryl) Electron Poor Electrophilic/ Acidic Carbon Radicals Allylic > 3º > 2º > 1º > methyl > alkenyl (vinyl, aryl) Electron Poor Electrophilic/ Acidic Carbanions Allylic > alkenyl (vinyl, aryl) > methyl > 1º > 2º > 3º Electron Rich Nucleophilic/ Basic Notes 1. Both carbocations and radicals have the same pattern. So you don’t need to memorize them twice! 2. Carbanions are almost exactly the reverse, except that being allylic is ideal for both. 3. All benefit from resonance (allylic). 4. Cations and radicals both fall short of octet rule. As a result, they are both electron deficient. Carbanions, by contrast, are electron rich. 5. Alkyl substituents are electron donors. As a result, they are good for electron deficient cations and radicals (3º > 2º > 1º > methyl) but bad for carbanions. 6. Alkenyl (vinyl or aryl) carbons are inherently a bit electron poor. This is excellent for carbanions, but terrible for cations or radicals. C C C Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 5 3. Transition-State Stability/Reactivity: The more stable the transition state, the faster the reaction will be. (The concept here is that the lower the transition state, the more easily it will be crossed.) • SN2 Reactivity Why: The pattern reflects the relative stability of the transition states. In the case of 3˚ versus 2˚ versus 1˚, the issue is steric congestion in the transition state. The transition states for the more highly substituted halides are destabilized. In the case of allylic halides, the transition state is stabilized for orbital reasons, not steric reasons. < BrBr Br < Br < 3° 2° 1° 1° plus allylic Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 6 Chem 350 Jasperse Ch. 6 Summary of Reaction Types, Ch. 4-6, Test 2 1. Radical Halogenation (Ch. 4) Recognition: X2, hv Predicting product: Identify which carbon could give the most stable radical, and substitute a Br for an H on that carbon. Stereochemistry: Leads to racemic, due to achiral radical intermediate. Mech: Radical. Be able to draw propagation steps. 2. SN2 Substitution Any of a large variety of nuclophiles or electrophiles can work. Recognition: A. Anionic Nucleophile, and B. 1° or 2º alkyl halide (3º alkyl halides fail, will give E2 upon treatment with Anionic Nucleophile/Base. For 2º alkyl halides, SN2 is often accompanied by variable amounts of E2.) Predicting product: Replace the halide with the anion nucleophile Stereochemistry: Leads to Inversion of Configuration Mech: Be able to draw completely. Only one concerted step! 3. E2 Reactions. Recognition: A. Anionic Nucleophile/Base, and B. 3º or 2º alkyl halide (1º alkyl halides undergo SN2 instead. For 2º alkyl halides, E2 is often accompanied by variable amounts of SN2.) Orientation: The most substituted alkene forms (unless a bulky base is used, ch. 7) Predicting product: Remove halide and a hydrogen from the neighboring carbon that can give the most highly substituted alkene. The hydrogen on the neighboring carbon must be trans, however. Stereochemistry: Anti elimination. The hydrogen on the neighbor carbon must be trans/anti. Mech: Concerted. Uses anion. Be able to draw completely. Only one concerted step! Br resonance stabilized>3º>2º>1º>alkenylBr2, hv H Br Br • • Br•+ Br Br + H-Br slow step ready to repeat first step OCH3Br SN2: 1º>2º>3º> alkenylNaOCH3 OCH3Br SN2: 1º>2º>3º> alkenyl OCH3 + Br Br OCH3HH H OCH3 Br NaOCH3 H OCH3 + E2: 3º>2º>1º> alkenyl Mech: + + Br Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 7 4. SN1 Reactions. Recognition: A. Neutral, weak nucleophile. No anionic nucleophile/base, and B. 3º or 2º alkyl halide. (Controlled by cation stability). (1º alkyl halides undergo SN2 instead. For 2º alkyl halides, SN1 is often accompanied by variable amounts of E1.) Predicting product: Remove halide and replace it with the nucleophile (minus an H atom!) Stereochemistry: Racemization. The achiral cation intermediate forgets any stereochem. Mech: Stepwise, 3 steps, via carbocation. Be able to draw completely. 5. E1 Reactions. 3º > 2º > 1º (Controlled by cation stability) Recognition: A. Neutral, weak nucleophile. No anionic nucleophile/base, and B. 3º or 2º alkyl halide. (Controlled by cation stability). (For 2º alkyl halides, E1 is often accompanied by variable amounts of SN1.) Orientation: The most substituted alkene forms Predicting the major product: Remove halide and a hydrogen from the neighboring carbon that can give the most highly substituted alkene. The hydrogen on the neighboring carbon can be cis or trans. Stereochemistry: Not an issue. The eliminating hydrogen can be cis or trans. . Mech: Stepwise, 2 steps, via carbocation. Be able to draw completely. Sorting among SN2, SN1, E2, E1: How do I predict? Step 1: Check nucleophile/base. • If neutral, then SN1/E1  mixture of both • If anionic, then SN2/E2. Step 2: If anionic, and in the SN2/E2, then Check the substrate. o 1º  SN2 o 2º  SN2/E2 mixture. Often more SN2, but not reliable… o 3º  E2 OCH3Br SN1: resonance >3º>2º>1º> alkenyl+ H Br HOCH3 OCH3 + H Br HOCH3 Br Br + Br slow step OCH3 H Br E1: 3º>2º>1º HOCH3 H+ BrH H + H Br Br + Br slow step Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 10 Reaction Mechanisms (see p. 310) A. Recognizing/Classifying as Radical, Cationic, or Anionic 1. Radical  initiation requires both energy (either hv or Δ) and a weak, breakable heteroatom-heteroatom bond o Cl-Cl, Br-Br, O-O (peroxide), N-Br, etc.. 2 Guides for That are Usually Reliable: hv  radical mechanism peroxides  radical mechanism 2. Anionic  a strong anion/base appears in the recipe  no strong acids should appear in the recipe  mechanisms should involve anionic intermediates and reactants, not strongly cationic ones • (except for do-nothing spectators like metal cations)  The first step in the mechanism will involve the strong anion/base that appears in the recipe 3. Cationic  a strong acid/electrophile appears in the recipe  no strong anion/base should appear in the recipe  mechanisms should involve cationic intermediates and reactants, not strongly anionic ones • (except for do-nothing spectators like halide or hydrogen sulfate anions)  The first step in the mechanism will involve the acid that appears in the recipe. The last step will often involve a deprotonation step. Often the main step occurs in between the proton- on and proton-off steps B. Miscellaneous Mechanism Tips 1. Keep track of hydrogens on reacting carbons 2. Each step in a mechanism must balance 3. The types of intermediates involved (cation, anion, or radical) should be consistent with the reaction classification above a. If the reaction is cationic, don’t show anionic intermediates b. If the reaction is anionic, don’t show cationic intermediates 4. Usually conditions are ionic. 5. Use a reactive species, whether strong anion or an acid, to start the first step a. If acidic, first step will involve protonation of the organic b. If anionic, the first step will involve the anion attacking the organic. 6. While it isn’t always easy to figure out what is a good mechanism, you should often be able to eliminate an unreasonable mechanism. Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 11 Chapter 7 Reactions and Mechanisms, Review E2 On R-X, Normal Base Notes 1. Trans hydrogen required for E2 2. Zaytsev elimination with normal bases 3. For 3º R-X, E2 only. But with 2º R-X, SN2 competes (and usually prevails) 4. Lots of “normal base” anions. E2, On R-X, Bulky Base Notes: 1. Hoffman elimination with Bulky Bases 2. E2 dominates over SN2 for not only 3º R-X but also 2º R-X 3. Memorize NEt3 and KOC(CH3)3 as bulky bases. Acid- Catalyzed E1- Elimination Of Alcohols Notes: 1. Zaytsev elimination 2. Cationic intermediate means 3º > 2º > 1º 3. 3-Step mechanism CH3 Br OCH3HH H OCH3 Br NaOCH3 H OCH3 + Mech: + + Br (Normal base) Br NEt3 or KOC(CH3)3 (Bulky bases) H2 C BrMech: H NEt3 + Et3NH Br OH H2SO4 H OH+ H2SO4 + HSO4 + OH2 -H2O HSO4 + H2SO4 Protonation Elimination Deprotonation OH OH2 H H H Mech Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 12 Summary of Alkene Reactions, Ch. 8. Memorize Reaction, Orientation where Appropriate, Stereochemistry where Appropriate, and Mechanism where Appropriate. -all are drawn using 1-methylcyclohexene as a prototype alkene, because both orientation and stereochemistry effects are readily apparent. Orientation Stereo Mechanism 1 Markovnikov None Be able to draw completely 2 Anti-Markovnikov Nonselective. Both cis and trans Be able to draw propagation steps. 3 Markovnikov None Be able to draw completely 4 Markovnikov None Not responsible 5 Anti-Markovnikov Cis Not responsible 6 Markovnikov None Not responsible 7 None Cis Not responsible BrHBr (no peroxides) H CH3 Br both cis and trans HBr peroxides OH CH3H2O, H+ OH CH31. Hg(OAc)2, H2O 2. NaBH4 H CH3 OH 1. BH3•THF 2. H2O2, NaOH OR CH31. Hg(OAc)2, ROH 2. NaBH4 H CH3 HD D H2, Pt Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 15 8 9 4 Notes 1. Cation intermediate is cyclic bromonium (or chloronium) ion 2. The nucleophile captures the bromonium ion via backside attack (ala SN2) -this leads to the trans stereochemistry 3. The nucleophile attacks the bromonium ion at the *more* substituted carbon -this explains the orientation (Markovnikov) a. There is more + charge at the more substituted carbon b. The Br-C bond to the more substituted carbon is a lot weaker 4. Alcohols can function in the same way that water does, resulting in an ether OR rather than alcohol OH. Br CH3 H Br Br2 (or Cl2) H HH Cation Capture Br Br BrBr Br Br 3 Notes1. Cation intermediate is cyclic bromonium (or chloronium) ion 2. The nucleophile captures the bromonium ion via backside attack -this leads to the trans stereochemistry 3. The nucleophile attacks the bromonium ion at the *more* substituted carbon OH CH3 H Br Br2, H2O (or Cl2) H HH Cation Capture Br Br Br Br OOH2 H H H Br OH-H HCH3 H Br Br O H H H Br OH-HMore Substituted End H Br O H H H Br OH-H Less Substituted End Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 16 Ch. 15 Conjugated Systems The General Stabilization Effect of Conjugation (Section 15.1, 2, 3, 8, 9) Conjugated (more stable) Isolated (less stable) Notes: 1 Cations 2 Radicals 3 Anions 4 Dienes 5 Ethers An N or O next to a double bond becomes sp2. An isolated N or O is sp3 6 Amines 7 Esters 8 Amides Very special, chapter 23, all of biochemistry, proteins, enzymes, etc. 9 Oxyanions (Carboxylates) Very special, chapter 21 10 Carbanions (Enolates) Very special, chapter 22 11 Aromatics Very special, chapters 16 + 17 Conjugation: Anything that is or can be sp2 hybridized is stabilized when next to π bonds. • oxygens, nitrogens, cations, radicals, and anions Notes: 1. Any atom that can be sp2 will be sp2 when next to a double bond 2. “Conjugation” is when sp2 centers are joined in an uninterrupted series of 3 or more, such that an uninterrupted series of p-orbitals is possible 3. Any sp2 center has one p orbital O sp2, not sp3!! O sp3 N H sp2 HN sp3 O sp2 O O O sp3 N H sp2O H N sp3 O sp2 O O O O sp 3 sp2 O sp3 O Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 17 Impact of Conjugation 4. Stability: Conjugation is stabilizing because of p-orbital overlap (Sections 15.2, 4, 7) • Note: In the allyl family, resonance = conjugation One p Two p’s Three p’s Four p’s Six p’s in circuit Unstabilized π-bond Allyl type Butadiene type Aromatic Isolated C=C C=O C=N 5. Reactivity: Conjugation-induced stability impacts reactivity (Sections 15.4-7) • If the product of a rate-determining step is stabilized, the reaction rate will go faster (product stability-reactivity principle) o Common when allylic cations, radicals, or carbanions are involved • If the reactant in the rate-determining step is stabilized, the reaction rate will go slower (reactant stability-reactivity principle) o Why aromatics are so much less reactive o Why ester, amide, and acid carbonyls are less electrophilic than aldehydes or ketones 6. Molecular shape (Sections 15.3, 8, 9) • The p-orbitals must be aligned in parallel for max overlap and max stability • The sp2 centers must be coplanar 7. Bond Length: Bonds that look like singles but are actually between conjugated sp2 centers are shorter than ordinary single bonds • In amides, esters, and acids, the bond between the carbonyl and the heteroatom is shortened • 8. Bond Strength: Bonds that look like singles but are actually between conjugated sp2 centers are stronger than ordinary single bonds O O O O NH2 O OH O OR O All four sp2 carbons must be flat for the p's to align O NH2 1.33 A normal double 1.54 A normal single 1.48 A = Shortened and Strengthened conjugated single Shortened and Strengthened O OHO OR Shortened and Strengthened Shortened and Strengthened Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 20 Section 15.10 SN2 on Allylic, Benzylic Systems Are Really Fast Ex. Why? Because the backside-attack transition-state is stabilized by conjugation! (Transition state-stability-reactivity principle). 1. Neither the product nor the reactant has conjugation, so it’s hard to see why conjugation should apply 2. However, in the 5-coordinate T-state the reactive carbon is sp2 hybridized  the nucleophile and the electrophile are essentially on opposite ends of a temporary p-orbital. 3. That transient sp2 hybridization in the transition-state is stabilized by π-overlap with the adjacent p-bond. 4. This stabilization of the transition-state lowers the activation barrier and greatly accelerates reaction Br H NaOCH3 H OCH3 Br H NaOCH3 H OCH3 Slow, and contaminated by competing E2 Fast and Clean 15 min 10 hours 100% yield 80% yield Br H HH3CO Br H OCH3 Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 21 Section 15.11 The Diels-Alder Reaction. The Reaction of Conjugated Dienes (Dienes) with Electron-Poor Alkenes (Dienophiles) to make Cyclohexenes. Quick Overview Summary 1. 2. s-cis diene conformational requirement: The diene must be locked or be able to single-bond rotate it’s way into the “s-cis” conformation in order to react 3. Rate Factors 1. Dienophile  activated by electron withdrawing groups (“W” or “EWG”) for electronic reasons 2. Diene:  Deactivated by substituents that make it harder or less stable to exist in the s-cis conformation. This is true when a diene alkene has a Z-substituent.  Steric factors equal, activated somewhat by electron donating groups (“D” or “EDG”) 4. Concerted Mechanism 5. Orbital Picture 6. Product Prediction Highlights  Try to match up the 4 diene and 2 dienophile carbons with the product o The product double bond will be between C2 and C3 of the diene  Substituents are spectators  1,4/1,2 Rule: when asymmetric dienes react with asymmetric dienophiles o Match δ- end of nucleophilic diene with δ+ end of electrophilic dienophile  For disubstituted dienophiles: o cis-substituents end up cis, and trans-substituents end up trans 1 2 3 5 6 1 2 3 4 5 6 4 diene dienophile heat 1 2 3 4 1 2 3 4 "cisoid" or "s-cis" -meaning that it's "cis" relative to the single bond -even though the single bond is capable of rotation "transoid" or "s-trans" -relative to the single bond can react can't react 1 2 3 5 6 1 2 3 4 5 6 4 heat All bond making and breaking happens at once: *3 !-bonds break *2 "-bonds and 1!-bond form The diene is really the "nucleophile" (HOMO) The dienophile is really the "electrophile" (LUMO) Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 22 A. The General Diels-Alder Reaction 1. Electronics: The diene HOMO reacts with the dienophile LUMO  Effectively the diene is the nucleophile and the dienophile functions as the electrophile 2. The dienophile usually needs an electron-withdrawing attachment (“W”) (at least one)  This makes the dienophile more electrophilic  Electron Withdrawing Groups to Memorize:  Keys:  The atom that is connected to the alkene has δ+ charge  Anything with a double-bond to a heteroatom tends to have this o C=O, C≡N, N=O, S=O B. Predicting Products When the Diene or the Dienophile (or both) is Symmetric 1. Always make a cyclohexene 6-ring product 2. Number the diene from 1-4, and identify those four carbons in the product ring. 3. A double bond in the product will always exist between carbons 2 and 3. 4. Any substituents on the diene or dienophile are spectators: they will be attached to the same carbons at the end. • Beware of cyclic dienes • Beware of dienes that are drawn in their zigzag s-trans form, but could react following rotation into an s-cis form C. Stereochemistry: For Cis- or Trans- Disubstituted Dienophiles • Both carbons of a disubstituted dienophile usually turn into stereocenters. 1. Cis in  cis out: If two substituents on the dienophile are cis to begin with, they will still have a cis relationship on the product cyclohexene 2. Trans in  trans out: If two substituents on the dienophile are cis to begin with, they will still have a cis relationship on the product cyclohexene • Note: this is for the dienophile only. The diene alkenes may also have substitution such that one or both diene double bonds are cis or trans, but the “cis-in-cis-out” guideline does not apply to the diene. 1 2 3 5 6 1 2 3 4 5 6 4 diene dienophile heatW W C O H C O R C O OR C O NH2!+ !- !+ !- !+ !- !+ !- C N CN !+ !- Carbonyls Others NO2 N O O SO3H S O O OH!+ !- !- CF3 C F F F !+ !- !- !- Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 25 16.5,6, 7 Aromatic, Antiaromatic, Nonaromatic. Huckel’s Rule: For a planar, continuous ring of p-orbitals, (sp2 all around): • If the number of π-electrons = 2,6,10 etc. (4N + 2)  AROMATIC, STABILIZED • If the number of π-electrons = 4,8,12 etc. (4N )  Anti-aromatic, destabilized • Why: the 4N+2 rule always goes with favorable Frost diagrams: bonding and only bonding MO’s are always filled. • Generality: Huckel’s Rule applies for cycles, bicycles, ionic compounds, and heterocycles. a. Cycles (one-ring) b. Polycycles (2 or more) c. Ionic rings d. Heterocycles Keys to Recognizing Aromatic or Not: 1. Do you have an uninterrupted sp2 ring? 2. Apply Huckel’s Rule: Do you have 2,6,10 etc. π electrons? 3. Applying Huckel’s Rule requires that you can accurately count your π-electrons. Be able to count: • Anions: contribute 2 π-electrons • Cations: contribute 0 π-electrons • Heteroatoms (O or N): can provide 2 π-electrons if it helps result in aromatic stability. 16.8 Aromatic Ions 3 common, important Aromatic Ions 15.2 Heterocyclic Aromatics. Memorize 3. Pyridine Pyrrole Furan Nitrogens: Atom hybridization, Lone-Pair hybridization, and Basicity • Amine nitrogens are normally basic, but not when the N-lone pair is p-hybridized • Rule: If a nitrogen lone pair is p (used in conjugation)  nonbasic • Nitrogen lone-pair basicity: sp3 > sp2 >>> p Situations N-Atom N-Lone Pair N-Basicity 1. Isolated sp3 sp3 Normal 2. Double Bonded sp2 sp2 Normal (a little below, but not much) 3. Conjugated (not itself double bonded, but next to a double bond) sp2 p Nonbasic p-lone pairs are less basic because conjugation stability in the reactant is lost upon protonation. N N H O N N H O Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 26 16.13 AROMATIC NOMENCLATURE 1. Memorize Special Names. • Six Special Monosubstituted Names You Must Memorize Toluene Phenol Aniline Benzoic Acid Nitrobenzene Anisole 2. Mono-substituted benzenes, if not one of the special memory names: use “benzene” as core name 3. Di- or polysubstituted aromatics a. If one of the “special” memory names can be used, use that as the core name and number with the special substituent on carbon 1. b. Special Terms: • "ortho" or o- 1,2 relationship • "meta" or m- 1,3 relationship • "para" or p- 1,4 relationship CH3 OH NH2 CO2H NO2 OCH3 Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 27 Activating/ Deactivating Ortho/Para Or Meta Directing Book 1 Deactivating Ortho/Para 17.2 Deactivating Ortho/Para 17.2 The halides are unique in being deactivating but ortho/para directing. All other o/p- directors are activating, and all other deactivating groups are m-directors. Mech 2 Deactivating Meta 17.3 The product can be reduced to Ar-NH2 by Fe/HCl or Sn/HCl. Nitration/Reduction provides an effective way to introduce an NH2 group. Reduction converts m-directing NO2 group into an o/p-directing NH2 group. Mech required. 3 Activating Ortho/para 17.10 a. Restricted to 3º, 2º, or ethyl halides. 1º halides suffer carbocation rearrangements. b. Since product is more active than starting material, polyalkylation is often a serious problem. c. Fails with strongly deactivated benzenes. Mech required. 4 Deactivating Meta 17.11 a. The product can be reduced to -CH2R by Zn(Hg)/HCl. b. The acylation-reduction sequence provides an effective way to introduce a 1º alkyl group. c. Reduction converts meta-directing acyl group into an ortho/para-directing alkyl group. Mech required. 5 Deactivating Meta 17.4 The sulfonyl group is a useful para-blocking group, since it can later be removed upon treatment with H2O/H+. No mech required. 5 Major Electrophilic Aromatic Substitution Reactions (+ HBr) FeBr3 (cat.) (or Fe cat) + Br2 H Br + Cl2 AlCl3 (cat.) (+ HCl) ClH + HNO3 (+ H2O) NO2H H2SO4 (+ HCl)+ AlCl3 (cat.) RH R-X + (+ HCl) AlCl3 (cat.)H Cl R O O R + H SO3HH2SO4SO3 Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 30 Formation of the Active Electrophiles 1. In each case, the cationic form of the thing that adds must be generated 2. The arrow pushing in the E+ generation always involves an arrow going from the cation precursor to the Lewis or Bronsted acid 3. For class, we will focus on sulfuric acid as Bronsted acid, and AlCl3 or FeBr3 as Lewis acids  But in an actual synthesis lab, other Bronsted or Lewis acids are available and may sometimes provide superior performance. Cation Needed 1 2 3 4 5 (+ HBr) FeBr3 (cat.) (or Fe cat) + Br2 H Br Br Br Br Br FeBr3 FeBr3Br + Cl2 AlCl3 (cat.) (+ HCl) ClH Cl Cl Cl Cl AlCl3 AlCl3Cl + HNO3 (+ H2O) NO2H H2SO4 NO2 NO2O2N OH H2SO4 + H2O + HSO4 + AlCl3 (cat.) RH R-X R R R X AlCl3 AlCl3X + AlCl3 (cat.)H Cl R O O R O R O R AlCl3 AlCl3ClClR O + H SO3HH2SO4SO3 SO3H SO3H H2SO4 + HSO4SO3 Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 31 The Situation with an Electron Donor/Cation Stabilizer (Ortho-Para Director) (Section 17-6) Summary: Electronic Factor: An electron donor (cation stabilizer) is especially beneficial electronically when the electrophile adds ortho or para relative to the donor.  Thus donors are ortho/para directors. Steric Factor: Ortho addition relative to the donor is always destabilized somewhat by steric interactions. Thus, when addition para relative to the donor does not involve any steric interactions, (usually but not always the case), para addition is faster than ortho addition. The Situation with an Electron Withdrawer/Cation Stabilizer (Ortho-Para Director) (12.13) Summary: An electron withdrawer (cation destabilizer) is especially harmful electronically when the electrophile adds ortho or para relative to the withdrawer. Thus withdrawers are meta directors. Not because meta is that good; it’s just not as bad as ortho or para. Note: Meta is still deactivated somewhat, it’s just not as slow as ortho or para addition. Boxed form is especially good electronically. Ortho addition often has some steric destabilization. H E H E H E D DD Ortho Addition Relative to a Donor H E H E H E D D D Meta Addition with a Donor None of the three resonance forms benefits from the electron donor. H E H E H E D D DPara Addition Relative to a Donor Boxed resonance form is especially benefitted electronically. Boxed form is especially bad electronically. H E H E H E W WW Ortho Addition Relative to a Withdrawer None of the three resonance forms suffers badly from the electron donor. H E H E H E W W W Meta Addition Relative to a Withdrawer Boxed form is especially bad electronically. H E H E H E W W WPara Addition Relative to a Withdrawer Organic Chemistry I Review: Highlights of Key Reactions, Mechanisms, and Principles 32 Seeing the Mechanism and Resonance Structures from Different Perspectives NOTES: 1. These focus on drawing the resonance structures and seeing how the positive charge is delocalized in the cation. 2. Notice that regardless of which position the electrophile adds to, the positive charge still ends up delocalized onto the positions ortho and para relative to the site of addition 3. Notice that the site of addition does not have positive charge 4. Notice that the hydrogen that is lost is from the same carbon where the electrophile adds, not from an ortho carbon H1 E H1 E H1 E H1 H2 H3 H4 H5 H6 E E H2 H3 H4 H5 H6 Addition to Site 1 Resonance Pictures -H1 H2 E H2 E H2 E H1 H2 H3 H4 H5 H6 E H1 E H3 H4 H5 H6 Addition to Site 2 Resonance Pictures -H2 H3 E H3 E H3 E H1 H2 H3 H4 H5 H6 E H1 H2 E H4 H5 H6 Addition to Site 3 Resonance Pictures -H3 H4 E H4 E H4 E H1 H2 H3 H4 H5 H6 E H1 H2 H3 E H5 H6 Addition to Site 4 Resonance Pictures -H4 H5 E H5 E H5 E H1 H2 H3 H4 H5 H6 E H1 H2 H3 H4 E H6 Addition to Site 5 Resonance Pictures -H5 H6 E H6 E H6 E H1 H2 H3 H4 H5 H6 E H1 H2 H3 H4 H5 E Addition to Site 6 Resonance Pictures -H6