Organic Reactions How and Why Reactions "Go" 1 Different Kinds of Reactions We NEED some language and notation to distinguish among various kinds of organic reactions 1. Addition Reactions (introduced in Alkenes) Br H adds H3C H H–Br + C C H3C C C H H3C H H3C H addition to the alkene • H and Br are added to the C=C double bond of the alkene 2. Substitution Reactions (introduced in Alkyl Halides) substitutes HO + H3C–Br HO–CH3 + Br substitution of the methyl bromide • Br is substituted for OH in the alkyl halide 3. Elimination Reactions (introduced in Alkyl Halides) H Br H C H H C C CH 3 HO + 3 HO–H + C C + Br H CH3 H3C H H and Br eliminated/removed from the alkyl bromide • H and Br are eliminated from the alkyl bromide • the HO– is required to "make" this particular elimination reaction "go" 4. Rearrangement Reactions (introduced later in Alkynes, Alcohols etc.) O OH + new bonds (H3O ) BUT C C CH H3C CH2 H3C 3 no atoms added or removed + • the reactant and product are structural isomers, the bonds are rearranged• the H3O is required to "help" this particular rearrangement reaction "go", it is a catalyst 5. Protonation/Deprotonation Reactions base O acid H O C + H Cl + Cl THIS Me Me C Me Me gets PROTONATED THIS PROTONATES protonated ketone • A proton is transferred from the acid (H-Cl) to the ketone • the ketone becomes protonated • the H-Cl protonates, it becomes deprotonated Reactions : page 1 2 Brønsted Acidity • Acid/Base reactions play a DOMINANT ROLE in organic chemistry, we need to understand this VERY WELL • A Brønsted acid DONATES a proton • A Brønsted base ACCEPTS a proton Example: from general chemistry H+ –Cl + Na+ – OH O + Na+ –Cl H H acid base new bond • WHY does an acid react with a base to give a salt plus water? A. Because in doing so it MAKES A NEW BOND, and lowers the energies of a pair of electrons Example: from organic example CH3 O H3C CH3 O N H N CH + H3C C + 3 H3C C CH O O H 3 CH3 organic acid organic base new bond • hydrogen moves from the acid to the base, but leaves its electron "behind" (is given to the oxygen). A hydrogen with no electron is a proton, therefore a proton is transferred from the acid to the base. • This reaction makes a strong new bond and replaces a localiZed non-bonding pair with a resonance stabiliZed pair, even though an anion is formed, the electrons are stabilized by resonance, which is usually the most important factor for non-bonding electrons 2.1 Brønsted Acid Strength Measured in terms of pKa (usually in water) H Ka H O H–A + H2O A + makes a bond H breaks a bond – + [ A ] [H3O ] pKa = - log (Ka) Ka = [ HA] [H O] 2 smaller pKa = stronger acid • Bronsted acidity involves heterolytic cleavage of a bond to hydrogen, with liberation of a proton • Stronger Bronsted acids have smaller pKa values. • This description ignores the role of solvation, but it is sufficient for now and helps us to understand Bronsted acidity and basicity within the context of bonding that we are using to describe most of the chemistry in this course. 2.2 Range of Acidities in Organic Chemistry • We will encounter acids with a VERY WIDE RANGE of acidities • We will consider the acidity of some protons that are so weakly acidic that they would not normally be considered as acids • We will also encounter some organic species that are a lot stronger acids than sulfuric acid (although they will not normally be very long lived, especially in water!) • Remember, the pKa scale is logarithmic! So, an acid with a pKa of 10 is not ten times stronger than an acid with a pKa of 20, it is 10 orders of magnitude stronger! Reactions : page 2 Some Example Acids We will Meet Acid Structure Conjugate Base pKa (in water) extremely methane H3C H H3C ~ 50 weak acid ammonia H2N H H2N ~ 35 acetylene HC C H HC C ~ 25 methanol H3CO H H3CO ~ 15 increasing water HO H HO ~ 15 acidity O O H3C C H3C C ~ 4 acetic acid O H O ~ –7 hydrochloric acid Cl H Cl extremely protonated O H O H C C H C C ~ –8 strong acid carbonyl 3 3 H H 2.3 Factors Controlling Brønsted Acidity • Absolute acidity (pKa) is difficult to predict, relative acidity is much easier!! • Just as when we considered BDE as a simple chemical reaction, we need to consider BOTH the electrons that are involved in the reactant and the product i.e. before and after bond heterolysis When Considering the Energetics of any chemical Reaction: We need to consider both the energy of the electrons in the reactant (where we "start") and also the product (where we "end") • A stronger acid "wants" to go from left to right more than a weaker acid, either because the energy of the electrons in the bond in the REACTANT acid are high, or because the electrons in the PRODUCT conjugate base anion are low electrons "before" A H A + H electrons "after" in a bond generic acid conjugate base on an atom • Note, this is heterolytic bond cleavage (this is NOT given the bond dissociation energy). • A stronger acid has a less reactive conjugate base anion, thus weaker base. • In general, an acid will be stronger if the electrons in the bond are high in energy, i.e. if the bond is weak • Most of the time, an acid will be stronger if the energy of the non-bonding electrons on the conjugate base (usually on an anion) are lower in energy, e.g. if B is more electronegative than A in the example above, the conjugate base B is easier to form, B-H is the stronger acid. • Problem: these two effects sometimes oppose, how to know which one "wins"? 2.4 Factors That Determine Bronsted Acidity ENERGIES OF ELECTRONS IN THE REACTANTS • In contrast to the BDE trends we looked at above, most of the trends on Bronsted acidity can be understood in terms of the energy of the electrons in the reactants, not the product, however, there is one very strong effect on Bronsted acidity that is determined by the energy of the electrons in the reactant. • Acidity increases with increasing atomic siZe going down a group in the periodic table. Reactions : page 3 Example stronger bond H O 2 + weaker acid H Cl Cl + H3O stronger base even though more H O electronegative 2 + stronger acid H I I + H3O weaker base weaker bond, by a lot • H-I is a stronger acid than H-Cl • Chlorine is smaller than iodine, the H-Cl bond is much stronger than the H-I bond because of poor orbital overlap between the very small hydrogen and very large iodine • Note: that we are using the same arguments we used for homolytic BDE here, these same effects influence the heterolytic cleavage associated with Bronsted acidity • The iodide conjugate base anion is the weaker base because it makes weaker bonds when it reacts as a base • The stronger acid has the weaker conjugate base. • The stronger acid is the one with the weaker bond. • Note: we could have tried to argue that the chloride anion should have been the weaker base, because chlorine is more electronegative than iodine and the energy of the electrons in the conjugate base anion should be lower, however, we need to consider BOTH the reactant and product, and it turns out that the bond strength effect "wins" • There are often competing arguments when considering Bronsted acidity, the energy of the electrons in the acid reactant wins here. Atomic siZe effects are often a dominant effect in organic chemistry. 2.5 Factors That Determine Bronsted Acidity ENERGIES OF ELECTRONS IN THE PRODUCTS • MOST of the trends on Bronsted acidity can be understood in terms of the energy of the electrons in conjugate bases anion products. 1. Influence of Resonance on the stability of the conjugate base anion products • Acidity increases with increasing resonance stabiliZation of the non-bonding electrons in the conjugate base anion. Resonance decreases the energy of the electrons in the conjugate anion base, making the anion easier to form, the acid is stronger. Resonance stability effects in the conjugate base anion usually dominate over all other possible factors. Example: H stronger base H H weaker H C CH O H O H C CH O + 3 2 H 3 2 O acid or H O O H H3C stronger H3C C H H C O + O acid H O O H H electrons electrons O weaker "before" "after" H3C C base reaction reaction O • The energy of the electrons is lower in the second conjugate base anion due to resonance stabilization • The second reaction "wants" to go from left to right more than the first, the second structure is the stronger acid • Resonance stabiliZation in the anion and bond strength contribute to making the second structure more acidic • The second conjugate base is the weaker base, it is the more stable anion • The stronger acid has the weaker conjugate base. • The stronger acid has the conjugate base with the lower energy electrons • There are no competing factors, this is straightforward, the lower energy electrons in the base argument works well Reactions : page 4 2. Influence of Electronegativity on the stability of the conjugate base anion products • Acidity increases going from left to right across the periodic table.