Topic+5+Notes+_acids+and+bases_ - L TOPIC 5. ORGANIC...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: L TOPIC 5. ORGANIC REACTIONS: ACIDS AND BASES (Chapter 3) OBJECTIVES 1. Classify types of reaction:   -Addition, Substitution, Elimination, Rearrangement 2. Define the concept of “Mechanism” 3. Discuss the thermodynamics (equilibrium) and kinetics (rate) of organic reactions 4. Describe acid-base reactions 5. Develop relationships between structure and acidity/basicity 6. Take a first look at acid-promoted reactions  Practical Aspects of Running a Reaction BEGINNING Starting material (“substrate”) END Product Byproducts Unreacted reactants Catalyst Solvent SEPARATION PURIFICATION IDENTIFICATION Reagents Catalysis (lowers activation energy) Solvent (allows for mixing) Time Temperature (heating/cooling) Environment Stirring (avoid O2, H2O?) Mode of addition % yield = moles of product moles of limiting reactant x 100  Representations of reactions  ...more commonly written as…. S:3.1 CLASSIFYING REACTIONS Reactions are conveniently classified as substitutions, additions, eliminations and rearrangements. These terms describe the overall process, simply comparing the structure of starting materials and products. They do not indicate anything about the pathway (“mechanism”) by which the reaction proceeds. Substitutions Additions Eliminations Rearrangements (often in combination with another type of reaction) Substitution Addition Elimination Rearrangement A Preview of Reactivity In Class Problem: Designate each of the following reac1ons as (a) a subs1tu1on, (b) an elimina1on, (c) an addi1on, (d) a rearrangement, or (e) some combina1on of the former. WHAT IS A MECHANISM? A mechanism is a proposal for a step-by-step pathway by which a reaction proceeds. Each step involves bond making and/or breaking. The mechanism takes into account all currently available evidence (kinetics, formation of byproducts, effect of structure on reactivity). Any new data collected must be consistent with the proposed mechanism, or the mechanism itself must be modified to account for the new finding. An understanding of common mechanistic steps can be applied to new combinations of reagents to predict the outcome of a new reaction. As such, development of an understanding of mechanisms will save you from memorizing a huge amount of material. While you must develop a familiarity with reactions, do not try to pass this course by just memorizing the outcome of reactions! Electrophiles and Nucleophiles Nucleophile Electron-rich, “nucleus-loving” species seek a proton or some other positively charged center Representation: Nu or Nuc (if neutral) or Nu or Nuc (if anionic) Electrophile Electron-deficient, “electron-loving” species seek electrons to obtain a stable valence shell of electrons Representation: E or El The Use of Curved Arrows in Illustra6ng Reac6ons S:3.4 Prob 3.20,25, 31,36,37,40 Curved arrows show the flow of electrons in a reac1on and not the movement of atoms. An arrow starts at a site of higher electron density (a covalent bond or unshared electron pair) and points to a site of electron deficiency. Example: Mechanism of reac1on of HCl and water. S:3.3 Cleavage of Covalent Bonds Homolysis Heterolysis Homolysis of Bonds to Carbons: Radicals Homolytic bond cleavage leads to the formation of radicals (also called free radicals). Radicals are highly reactive, short-lived species. Single-barbed arrows are used to show the movement of single electrons. Production of Radicals: Homolysis of relatively weak bonds such as O-O or X-X bonds can occur with addition of energy in the form of heat or light. Reactions of Radicals: Radicals tend to react in ways that lead to pairing of their unpaired electron. Hydrogen abstraction is one way a halogen radical can react to pair its unshared. Heterolysis of Bonds to Carbons: Carbanions and Carboca6ons Reac1on can occur to give a carboca1on or carbanion depending on the nature of Z. CarbocaBons (Lewis acids) have only 6 valence electrons and a posi1ve charge. Carbanions (Lewis bases) have 8 valence electrons and a nega1ve charge. Heteroly1c reac1ons almost always occur at polar bonds. The reac1on is oIen assisted by forma1on of a new bond to another molecule. The following two examples illustrate two types of heteroly1c cleavage reac1ons: (1) An example of a unimolecular reac1on process: (2) An example of a bimolecular reac1on process: Problem 3.20(c). Provide curved arrows to account for the changes in bonding in the following reaction step. Problem 3.31(d). Show the curved arrows to account for the following reaction step. Problem: Show the curved arrows to account for the following reaction step. Problem: What is wrong with each of the following mechanistic steps, suggested by students in previous classes? [consider what the curved arrow is meant to depict, or draw the products of the suggested flow of electrons and comment on why that product is not stable] Problem: What is wrong with each of the following mechanistic steps suggested by students in previous classes? Introduc6on to Acid ­Base Chemistry Brønsted ­Lowry Defini6on of Acids and Bases Acid: a substance that can donate a proton. Base: a substance that can accept a proton. Example: Hydrogen chloride is a very strong acid. When dissolved in water essen1ally all hydrogen chloride molecules transfer their proton to water. S:3.2; 3.6 3.15 Prob 3.15,17,19, 22 ­24 Example: Aqueous hydrogen chloride and aqueous sodium hydroxide are mixed. The actual reac1on is between hydronium and hydroxide ions. Lewis Defini6on of Acids and Bases Lewis Acid: electron pair acceptor Lewis Base: electron pair donor (Curved arrows show movement of electrons to form and break bonds.) Opposite Charges AGract and React BF3 and NH3 react based on their rela1ve electron densi1es. BF3 has substan1al posi1ve charge on the boron. NH3 has substan1al nega1ve charge localized at the lone pair on nitrogen. In Class Problem: Write an equa1on that shows the Lewis acid and Lewis base in the reac1on of (a)  molecular chlorine (Cl2) with aluminum chloride (AlCl3). (b)  boron trifluoride (BF3) with tert ­butyl alcohol ((CH3)3COH).  Ka and Acid Strength   A–H acid + H 2O base Keq A conjugate base + H2O–H conjugate acid     Dilute acids have a constant concentration of water (about 55.5 M) and so the concentration of water can be factored out to obtain the acidity constant (Ka). Any weak acid (HA) dissolved in water fits the general Ka expression.   The stronger the acid, the larger the Ka. Ka ↑ , acid strength ↑   Acidity is usually expressed in terms of pKa. pKa is the nega1ve log of Ka. The pKa for ace1c acid is 4.75. The larger the value of Ka the stronger the acid. The larger the pKa, the weaker the acid. Bo]om line: pKa ↑ , acid strength ↓ Aspirin Acetyl Salicylic Acid Neutral and Zwi]erionic Amino Acids The Rela6onship Between Structure and Acidity Acidity increases going down a row of the periodic table. The reason is a combina1on of bond strength, electron affinity, and solva1on. Acidity increases from leI to right in a row of the periodic table. Increasingly electronega1ve atoms (1) polarize the bond to hydrogen and (2) stabilize the conjugate base. pKa values H He H-H 55 Li Be B C acid strength ↑ N O F Ne H-CH3 H-NH2 35 38 Na Mg Al Si P H-OH 15.7 S H-F 3.2 Cl Ar acid strength ↑ H-SH 7.04 K Ca Ga Ge As Se H-Cl -7 Br Kr H-SeH 3.9 Te H-Br -9 I H-TeH 2.6 H-I -10 S:3.5 Rela6ve Strenghts of Selected Acids and Their Conjugate Bases Prob 3.16,18,21 27 ­29 Predic6ng the Outcome of Acid ­Base Reac6ons Acid ­base reac1on always favor the forma1on of the weaker acid/weaker base pair. The weaker acid/weaker base are always on the same side of the equa1on. Keq – A–H B: + B–H A:−  log Keq = pKa (conjugate acid) – pKa (acid) + Examples: HCl pKa =  ­7 + NaOH Keq NaCl + H2O pKa = 15.7 CH3OH + H2SO4 pKa =  ­9 Keq CH3OH2 + pKa =  ­2.5 HSO4 Species that can act as either an acid or as a base e.g., methylamine and water Water as the acid CH3NH2 + H 2O pKa = 15.7 CH3NH3+ pKa = 10.6 versus + HO¯ Methylamine as the acid CH3NH2 + H 2O pKa = 38 CH3NH¯ pKa = -1.74 + H3O+ Access which species is the strongest acid Amine + Acid CH3COOH pKa = 5.5 + CH3NH2 pKa = 38 CH3COO¯ + CH3NH3+ pKa = 10.6 Amino acids Amino acids in aqueous solution STRUCTURE-ACIDITY RELATIONSHIPS S:3.7; 3.8A;3.12 In order to assess the relative strengths of acids, consider the ability of the acid to donate a proton (ability to break the H-A bond) and for the conjugate base to accommodate negative charge. Stronger acids have weaker conjugate bases... A–H + B:– A:– + H–B We have ways to assess the ability of ions (anions and cations) to accommodate negative charge based on:  – Inductive effects (substituents donate or withdraw electron density via sigma bonds)  – Resonance effects (electron donation or withdrawal by pibonds)  – Hybridization Induc6ve Effects Electronic effects of subs1tuent groups are transmi]ed to a reac1on center by at least two mechanisms: (1) through space (electrosta1c field effect) and (2) through the bonds of a molecule (induc1ve effect). In ethyl fluoride the electronega1ve fluorine is drawing electron density (polarizing) away from the carbons. Fluorine is termed “an electron withdrawing group (EWG).” The effect of the fluorine gets weaker with increasing distance from the reac1on center. The Effect of Resonance Carboxylic acids are much more acidic than alcohols. Deprotona1on is unfavorable in both cases (posi1ve ΔGo) but much less favorable for ethanol. Explana6on based on resonance (delocaliza6on) effects Both ace1c acid and acetate are stabilized by resonance. Acetate is more stabilized by resonance than ace1c acid. This decreases ΔGo for the deprotona1on. Neither ethanol nor its anion is stabilized by resonance. There is no decrease in ΔGo for the deprotona1on. Calculated Electrosta6c Poten6al Maps Explana6on Based On Induc6ve Effect In ace1c acid the highly polarized carbonyl group draws electron density away from the acidic hydrogen. Also the conjugate base of ace1c acid is more stabilized by the carbonyl group. Induc6ve Effects of Other Groups The electron withdrawing chloro subs1tutent makes chloroace1c acid more acidic than ace1c acid. In this case we are comparing the effect of a C ­Cl bond to a C ­H bond. Cl is more electronega1ve than H; it is more electron ­withdrawing thereby (1) increasing the “electronega1vity” of the hydroxyl oxygen and (2) stabilizing the nega1ve charge associated with the conjugate base. The Effect of Hybridiza6on on Acidity Hydrogens connected to orbitals with more s character will be more acidic. s orbitals “feel” the presence of the posi1vely charged nucleus more than p orbitals. As a consequence, nega1ve charges (anions) residing in hybrid orbitals with more s character will have greater stability. Acidity Conjugate bases > > Lone pair in lower energy hybrid orbital stabilizes conjugate base and increases acidity The Effect of Solvent on Acidity Acidity values in gas phase are generally very low. It is difficult to separate the product ions without solvent molecules to stabilize them. Ace1c acid has pKa of 130 in the gas phase: _ A pro1c solvent is one in which hydrogen is a]ached to a highly electronega1ve atom such as oxygen or nitrogen e.g. water. Solva1on of both ace1c acid and acetate ion occurs in water although the acetate is more stabilized by this solva1on. This solva1on allows ace1c acid to be much more acidic in water than in the gas phase. In Class Problem: Place the following carboxylic acids in the order of decreasing acidity: Organic Compounds as Bases Any organic compound containing an atom with a lone pair (O,N) can act as a base. Proton transfer reac1ons like these are oIen the first step in many reac1ons of alcohols, ethers, aldehydes, ketones, esters, amids and carboxylic acids. π Electrons can also act as bases. π Electrons are loosely held and available for reac1on with strong acids. Predic6ng the Strengths of Bases The stronger the acid, the weaker its conjugate base. An acid with a low pKa will have a weak conjugate base. Chloride ion is a very weak base because its conjugate acid HCl is a very strong acid. Methylamine is a stronger base than ammonia. The conjugate acid of methylamine is weaker than the conjugate acid of ammonia.   The Effect of S tructure on Basicity Charge – anions more basic than neutral form ElectronegaBvity – electronegaBve atoms beVer accommodate negaBve charge HybridizaBon  ­ electrons in lower energy orbitals are more Bghtly held Resonance – stabilizes conjugate base Effect of alkyl subsBtuents (gas phase basicity) Acids and Bases in Nonaqueous Solu6ons Water has a leveling effect on strong acids and bases. Any base stronger than hydroxide will be converted to hydroxide in water. S:3.11; 3.14 Prob 3.38,39 Sodium amide can be used as a strong base in solvents such as liquid NH3. Alkyl lithium reagents in hexane are very strong bases. The alkyl lithium is made from the alkyl bromide and lithium metal.  In any solvent, the strongest acid [base] which can be present is the conjugate acid [base] of the solvent. The choice of solvent for acid-base reactions is important…   conjugate conjugate   solvent acid base  e.g., CH3OH2+ is the strongest acid possible in methanol (i.e., H2SO4, a stronger acid, is completely dissociated in methanol). CH3O- is the strongest base present in methanol (i.e., NH2-, a stronger base, is completely protonated by methanol). Synthesis of Deuterium ­ and Tri6um ­Labeled Compounds Deuterium (2H) and tri1um (3H) are isotopes of hydrogen. They are used for labeling organic compounds to be able to track where these compounds go (e.g. in biological systems). An alkyne can be labeled by deprotona1ng with a suitable base and then 1tra1ng with T2O. In Class Problem: Complete each of the following reac1ons: PRACTICAL APPLICATIONS OF ACID-BASE CHEMISTRY L Separation of Neutral, Acidic and Basic Compounds Challenge: Separate a mixture of hexanoic acid and nonane. 1. Separate the layers, distill off the ether to isolate nonane 2. Acidify the separated aqueous solution, extract neutral hexanoic acid into another portion of ether. Separate these two layers, remove ether. Neutral organic component in Et2O sodium carboxylate in aqueous base Problem: Design a procedure to separate hexylamine (C6H13NH2) from nonane. Water Solubility as a Result of Salt Forma6on Organic compounds which are water insoluble can some1mes be made soluble by turning them into salts i.e. reac1on with sodium hydroxide. Water insoluble amines can become soluble in aqueous hydrogen chloride. Provide Greater Water-solubility to Drugs Naproxen sodium” (Aleve) Go directly to jail….. Catalysis of Reactions Proton transfer is usually fast. Protonation (or deprotonation) of an organic starting material with an acid (or base) often catalyzes reactions which do not take place in the absence of catalyst. Bases deprotonate molecules and make them better (i.e., more reactive) nucleophiles Acids protonate molecules and make them better electrophiles Energy Changes in Chemical Reac6ons Energy: the capacity to do work. KineBc energy is the energy an object has because of its mo1on; K.E.=1/2mv2. PotenBal energy is stored energy. The rela1ve stability of s system is inversely related to its rela1ve poten1al energy. The more poten1al energy an object has, the less stable it is. Poten1al energy can be converted to kine1c energy (e.g. energy of mo1on). Poten6al Energy and Covalent Bonds Poten1al energy in molecules is stored in the form of chemical bond energy. A convenient way to represent the rela1ve poten1al energies of molecules is in terms of their rela1ve enthalpies, or heat contents (ΔHo). The change in enthalpy of a chemical reac1on, ΔΗo , is a measure of the change in bond energies. Exothermic reacBons: ΔHo is nega1ve and heat is evolved. The poten1al energy in the bonds of reactants is more than that of products. Endothermic reacBons: ΔHo is posi1ve and heat is absorbed. The poten1al energy in the bonds of reactants is less than that of products. Example: Forma1on of H2 from H atoms. Forma1on of bonds from atoms is always exothermic . The hydrogen molecule is more stable than hydrogen atoms. S:3.8-3.9 THERMODYNAMICS Equilibria Reactants (R) Keq Products (P) Keq = [products] [reactants] Prob 3.35 Enthalpy, H  ΔH° = H°products – H°reactants  based on changes in bonding Relationship Between ΔH°, ΔG° , and Keq Equilibrium constant depends on changes in enthalpy and entropy (change in disorder) Change in Gibbs free energy for a reaction: ΔG° = ΔH° – T ΔS°  ΔG° = G°products – G°reactants  ΔG° = –RT lnKeq = –2.303 RT logKeq   R = 8.314 J/K.mol = 1.987 cal/K.mol T = temperature (in K) P G ΔG° > 0 R (positive) endothermic  When ΔG° = 0; Keqm  When ΔG° >0; Keqm  When ΔG° < 0; Keqm R eqm eqm G ΔG° < 0 (negative) exothermic P For the equilibrium: ΔG o = –RT lnKeq = –2.303 RT logKeq A   B Keq at equilibrium  ΔG o(kcal/mol)   +5 +4 +3 +2 +1 0 -1 -2 -3 -4 -5 %A 99.98 99.88 99.38 84.42 16 3.3 0.63 0.12 0.02 0.0002 0.001 0.006 0.03 96.71 0.2 1 50 5 29 159 862 4670 %A ΔG (kcal/mol) » A small change in the ΔH of a reaction has a large influence on K If ΔG° more negative than -4 kcal mol-1, K >100 eq Thermodynamics tells us the extent to which a reaction CAN occur, but nothing about how FAST it will be O2 KINETICS Transition State Theory: Energy-Reaction Coordinate Diagram for a One-Step Reaction Energy P Reaction Coordinate Energy Energy R Reaction Coordinate Reaction Coordinate Transition state (‡): species with partial bonds at top of energy barrier Rate constant: k = Ae-Ea/RT Catalysis - k = Ae-Ea/RT Effect of Ea on Rate (at 25 °C) Ea logk 5 14.7 10 11.0 15 7.3 20 3.7 25 0 (i.e., krel=1) logkrel Ea (kcal/mol) krel kcal/mol Effect of Temperature on Rate For reaction: A → B (for Ea = 25 kcal/mol) T/°C 0 0.05 10 0.17 20 0.56 25 1 30 1.75 40 5.05 50 13.7 60 34.9 70 84.2 80 193 90 424 100 893 krel T/°C » A small change in the E of a reaction has a very large influence on k » A small increase in temperature can have a large influence on k a Energy-Reaction Coordinate Diagram for Two-Step Reaction Reactants Intermediate Product Energy Reaction Coordinate S:3.13 A Mechanism for an Organic Reac6on ReacBon Mechanism: a descrip1on of the events that take place on a molecular level as reactants become products. The SubsBtuBon ReacBon of tert ­Butyl Alcohol: All steps are acid ­base reac1ons: Step 1 is a Brønsted acid ­base reac1on. Step 2 is a Lewis acid ­base reac1on in reverse with heteroly1c cleavage of a bond. Step 3 is a Lewis acid ­base reac1on with chloride ac1ng as a Lewis base and the carboca1on ac1ng as Lewis acid. TOPIC 5 FOR EXAM 3  Types of Questions - Classify organic reactions - Compare acid (or base) strength - Show movement of electrons The problems in the book are good examples of the types of problems on the exam!  Preparing for Exam 3: - Get up to date now! - Work as many problems as possible - Work in groups - Do the “Learning Group Problem” at the end of the chapter Problem 3.20(c). Provide curved arrows to account for the changes in bonding in the following reac1on step. Problem 3.31(d). Show the curved arrows to account for the following reac1on step. Problem: Show the curved arrows to account for the following reac1on step. Problem: What is wrong with each of the following mechanis1c steps, suggested by students in previous classes? [consider what the curved arrow is meant to depict, or draw the products of the suggested flow of electrons and comment on why that product is not stable] Problem: What is wrong with each of the following mechanis1c steps suggested by students in previous classes? ...
View Full Document

Ask a homework question - tutors are online