ORGANIC CHEMISTRY 307 Fall 2012

Lecture Notes IV
Chapter 4 R. Boikess

One of our major focuses this year will be the study of how and why organic reactions take place. We will learn to write reaction mechanisms, which are the how. We will also seek to predict chemical behavior, the why. Both of these goals require an understanding of chemical principles. Our approach will require us to apply some of the basic chemical knowledge from General Chemistry. Of course, it all starts with the electronic structure of organic species, which you should have firmly under control by now. Remember chemical reactions result from breaking and making of bonds. Lets start by looking at one of the most general and straightforward reactions in chemistry, the reaction of an acid and a base.

I.

Acids and Bases

Remember the problems you had understanding this topic. It is one of the more difficult ones in Gen Chem. Acid/Base chemistry is very important in Orgo. But it should be much easier for you now than it was in Gen Chem. We only consider a few of the aspects of acid/base chemistry presented in Gen Chem and we even make some simplifications in our approach to those. Accordingly you are probably better off starting all over again with this topic, rather than trying to go back and review it in your Gen Chem book. This topic is redeveloped the way we will need it in Chapter 3 of CP, as well as in Chapter 4 of BF. Use this material to relearn acid/base chemistry. Lets consider some of the differences in the approach to acid/base chemistry between Orgo and Gen Chem. 1. In Gen Chem we did KA and KB (and pKA and pKB).. Here we do only KA (and pKA) for all situations: neutral acids and the charged conjugate acids of neutral bases. For

example we will use KA of NH4+ and RNH3+ and not KB for ammonia or the amines. 2. In Gen Chem almost all acid base chemistry took place in water. In Orgo we will encounter a range of solvents. So we want to think of acids and bases in the most general way. 3. Brnsted acids and bases. Just remember, A Brnsted acid is a proton donor. So it will generally be a species in which a hydrogen is bonded to an electronegative atom. The resulting polar bond can readily dissociate (because it is polar) to give two ions H+ and Y-. But since free protons (H+) can never exist in condensed phases, there must be something to accept the proton. A proton acceptor is a Brnsted base. So the emphasis in the Brnsted theory is on pairs of substances. There is the acid, which is the proton donor, and the base, which is the proton acceptor. a. Conjugate Pairs When an acid transfers a proton to a base, what is left behind is a species that is a base. Why? Because if it formed by proton donation, it could always accept the proton back. This base is called the conjugate base of the acid. We think of a conjugate acid-base pair, as two substances related to each other by the presence (acid) or absence (base) of a proton. In the same way, when a base accepts a proton, it forms an acid, which could give back the proton. This acid is called the conjugate acid of the base. Again we have a conjugate acid-base pair. How do you know which is the acid and which is the conjugate base or which is the base and which is the conjugate acid. The use of the word conjugate is completely arbitrary. It refers to the species on the right of the equation. So when an acid donates a proton we form its conjugate base. When a base accepts a proton we form its conjugate acid. So there are actually two pairs of substances involved in a Brnsted acid-base reaction; they are two different 2

conjugate acid/base pairs. The reaction is one in which a proton is transferred from the acid of one pair to the base of the other pair. We can summarize these relationships with the following very general equilibrium reaction: HA + B A- + BH+ Notice that the actual charges might be different. For example if we start with an acid with a positive charge such as methyl ammonium ion, CH3NH3+, then its conjugate base, methyl amine, CH3NH2, is neutral. Or if we start with a base that has a negative charge, such as formate, HCO2then its conjugate acid formic acid, HCO2H is neutral. But very often we will start with a neutral acid and a neutral base. b. Strength and pKA The idea of acid strength (and indirectly base strength) will be a very important one for us. A strong acid is one that is very good at donating a proton; a weak acid is not as good. A strong base is very good at accepting a proton; a weak base is not as good. It is very useful to be able to express strength in a quantitative way. The method we will use employs K, an equilibrium constant, and in particular the equilibrium constant of the above reaction, for this purpose. Suppose we want to compare the acid strengths of two acids HA1 and HA2. We allow each to react with a given base, B, in the above reaction, and measure the K for each. The one with the larger K is the stronger acid. If the K for HA1 is 102 greater than for HA2, then we say that HA1 is 100 times stronger the HA2. Now think about the equilibrium proceeding in the other direction. This time lets think about A1- and A2- reacting with the same acid, BH+. You can predict that A1- will have a K 102 smaller than A2- . In other words the strengths of the two species of a conjugate acid base are connected. The stronger the acid, the weaker its conjugate base. The stronger the base, the

weaker its conjugate acid. It is because of this relationship that KA is all we need. The range of KA values is enormous, but the ones that are less than 1 are the most meaningful. To make handling the KA values a little simpler, we express them as the negative log10 , symbolized as pKA. Review negative logs. Note: the negative log of X is logX not log(-X) Remember, the trend with pKA is the opposite of KA. The acid with the smaller pKA is the stronger acid and its conjugate base is the weaker base. Why are KAs most meaningful when they are less than 1? Once they get larger than 1, they are very difficult to measure accurately. So we will talk about strong acids as those whose KA is too large to measure (>1). We are able to differentiate among the strengths of a group of strong acids by using indirect methods and we are able to assign them pKAs using indirect methods. c. Acid Base Reactions All acid base reactions are equilibrium reactions. It will be very useful if we can predict the extent of reaction between a given acid and a given base, both qualitatively and quantitatively. Qualitative ideas about the relative strength of acids allow qualitative predictions. Data about acid strength in the form of measured pKA values allow quantitative predictions. Suppose we mix a given acid with a given base (equimolar concentrations), what happens. We know they react, but to what extent. It depends on the strength of each of them. The stronger the acid the further the reaction goes from left to right. Same for the base, the stronger, the further. Lets again designate the reaction as HA + B A- + BH+ We can make qualitative predictions of relative strengths of acids based on their structure and our general chemical knowledge. We can do the same for the relative strengths of bases. But, in a system with one acid (HA) and one base (B), we cannot compare their strengths directly. We can, 4

however, compare the relative strength of the acid (HA) with the relative strength of the conjugate acid of the base (BH+). If HA is stronger than BH+ the reaction of HA with B will proceed mostly to the right. (See if you can justify this statement). If HA is not stronger than BH+, then the reaction will not proceed to a significant extent and it will not be very useful. We can use the same reasoning to make quantitative predictions, if we have data on the relative strengths of HA and BH+. Those data are the pKA values of HA and BH+. We can use these values to calculate the pK for the above reaction. If you combine the equilibrium constants for the reactions defined by the two pKAs to get the equilibrium constant for the acid base reaction you will find that the pK of the reaction is defined by pK = pKA (of HA) pKA (of BH+) As you will see, pKA data are usually presented in tables in which the acids are listed in order of increasing or decreasing strength. You can make these kinds of predictions about acid base reactions just by looking at the relative positions of HA and BH+ in the table. For example Table 3.2 in CP) Tables of data are not always available, so you should be able to make qualitative predictions about relative strengths of acids. There are a number of competing factors to consider that are discussed at some length in CP 3.4 and BF 4.6. Here are some simplifications. a. Comparison of acids in which the H is bonded to different atoms. (For example HCl, HBr, and HI). There are two trends to know. If the different atoms are in the same column of the periodic table, the bigger the atom the stronger the acid. So HI>HBr>HCl. If the atoms are in the same row of the periodic table then the further to the right the atom the stronger is its acid. So 5

HF>H2O>NH3, (which is a very weak acid) b. Comparison of acids in which the H is bonded to the same atom (For example HClO, HClO2, and HClO3 in all of which the H is bonded to an O). There is almost always one overriding effect. Electron withdrawal from the bond to H makes acids stronger.[And therefore electron donation toward the basic atom makes bases stronger]. Remember these very important principles; we will use them often. Many of the organic reaction mechanisms we will study have at least one step that is a Brnsted acid-base reaction, which is a proton transfer from an acid to a base. You can always tell which is which. The acid gives, the base receives.

4.

Lewis Acids and Bases An electron pair donor is a Lewis base. An electron pair acceptor is a Lewis acid. More general than Brnsted. Includes most (but not all) Brnsted acids and bases. And in addition nonprotonic acids such as BF3 (because of an incomplete octet). Anions such as X- are usually Lewis bases and some cations (subject to restrictions on octet expansion) can be Lewis acids. So ammonium is not a Lewis acid, although it is a Brnsted acid. (contrary to BF) It cant accept electrons, but it can donate a proton. But cations such as CH3+ or Cl+ are Lewis acids. They can accept electrons because they have incomplete octets.

A firm grasp of thermodynamics and kinetics is also essential to any discussion of chemical reactions.

II Kinetics and Thermodynamics.

Once again, the coverage of these topics in Gen Chem dealt with a broader range of topics than we need for Orgo. But there are some aspects of Thermo and Kinetics that are very important for us and need special amplification or explanation. These topics are presented in BF Section 4.5 and in CP Chapters 4 and 5. We will discuss some of these aspects of Thermo and Kinetics now and some others later in the semester when you need them. But overall, this material is primarily review and you should be sure you master it on your own. In general, Thermo tells us whether or not something can happen. Kinetics tells us how long it will take to happen if it can. Remember that time is not a thermodynamic variable.
In particular, we will focus on and use

A.

Enthalpy (H) is defined as the heat flow that accompanies a process that takes place at constant pressure. Most processes in organic chemistry take place at constant pressure. Most of the energy change associated with most organic reactions is due to the change in enthalpy between products and reactants. We say most organic reactions (unless they are taking place at relatively high temperatures) are enthalpy controlled. Exothermic reactions (H negative) are usually favorable and endothermic reactions (H positive) are usually not. Organic chemists tend to use more general sounding terms, such as heat or energy, when they really mean enthalpy. We will refer to various measures of chemical behavior as heat of reaction, heat of combustion, heat of hydrogenation, bond energy, resonance energy, and strain energy. These are measures that are all enthalpies. B. Entropy (S and S) can be loosely understood as a measure of disorganization. The greater the entropy, the more disorganized a given state. Because the natural tendency of change is to increase disorganization, a positive S is favorable. But for most organic reactions, H is controlling. At relatively high temperatures S plays a more important role.

C.

Free Energy (G) is the actual measure of whether a chemical system will undergo change. A process with a negative G is spontaneous and will occur if we wait long enough. A process with a positive G will not occur unless we provide energy in some form to the system. The G is directly related to the equilibrium constant of a reaction by the equation G = -RTlnK It is also related to enthalpy and entropy by the equation G = H -TS Be sure you know and understand these two equations. They are among the 10 most important equations in chemistry.

D.

Interpretation of Thermochemical Relationships

We will use energy diagrams to help us to understand and analyze relative stabilities as well as the relationship between structure and stability. We will also use this approach to help us understand resonance energy and strain energy. So you should learn how to construct and interpret these kinds of diagrams. a. They are not really graphs, only the y-axis has meaning. It shows increasing energy (or enthalpy). Remember that high energy or enthalpy is bad and low is good. So lower on the page is more stable and higher on the page is less stable b. Ideally, we want to compare processes that either start or finish with the same substances. Look at the following very simple energy diagrams

Case 1

Case 2

c. When looking at endothermic reactions, (going up the page) the larger the energy change, the less stable the product when the starting material is the same (Case 1). Or the larger the energy change, the more stable the starting material when the product is the same.(Case 2) d. When looking at exothermic processes, (going down the page) the larger the energy change (absolute value), the less stable the starting material as in (Case 1) when the product is the same. Or the larger the energy change, the more stable the product when the starting material is the same (Case 2). e. As we will see, we can also use these kinds of diagrams to assess the energy contribution of such things as strain, which is destabilizing; or resonance, which is stabilizing. The approach is to compare a measured value of some property of a substance, such as heat of combustion, with a calculated value of the property, using just bond energies. Remember (from Gen Chem) that bond energies are given as positive numbers so H of reaction = bond energies broken bond energies made.

The value calculated from bond energies alone is different from the measured value if there is some kind of additional stabilization or destabilization. f. In the case of a strained substance, the measured value of the enthalpy of an exothermic process (for example combustion) will be more negative than the calculated value. The measured or real value includes the strain, which is destabilizing. The difference between the two values is called the strain energy. The value calculated from bond energies alone is more stable than the actual substance because the calculated one does not include the destabilization resulting from strain. In the case of resonance the measured value of the enthalpy of an exothermic process will be less negative than the calculated value. The measured or real value includes the resonance energy, which is stabilizing. The difference between the two values is called the resonance energy. If the words are confusing, look at the picture. There are many worked out examples in CP Section 4.3.

D.

Kinetics
There are a number of topics from Kinetics that are important for organic chemistry. Review them from Gen Chem

1. Rate Law, which comes from the measured relationship between rate and concentration for a given reaction. It is important because it can give a great deal of information about how a reaction takes place, the reaction mechanism. 2. Activation Energy, which comes from the measured relationship between rate and temperature. It can also give us a great deal of information about reaction mechanisms, because it gives us information about the transition state. 3. Transition State, which is the highest energy of a reacting system between reactants and products.

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E.

Reaction Coordinate Diagrams

Lets look at the details of such a diagram a. y-axis, energy (E) choice of what to plot, we can do free energy (usually, but not always approximated by enthalpy) or potential energy. Remember there are no numbers on either axis, so this diagram is giving us information about relative magnitudes. b. x-axis reaction coordinate, an imprecise term, which means more or less the progress of the reaction. iii. The diagram conveys a great deal of information: the overall energy change for the reaction, the relative height of the transition state (the higher it is the slower the reaction), the number of steps (each step corresponds to a maximum, which is its transition state), the relative energy of any intermediates, etc. iv Review the different reaction coordinate diagrams in CP Sections 4.3-4.4. Being able to draw and interpret these kinds of diagrams is another important skill. F.

Transition state theory.

Although we can never observe a transition state directly, we can use indirect methods, as well as theory, to learn about it. The more we understand about the transition state of a reaction, the more we understand about its mechanism. We can analyze the free energy of activation (G ), which is the difference in free energy between the reactants and the transition state, in terms of a measured H and a measured S . The (called a dagger) designates the transition state and thermodynamic functions associated with the difference between it and the reactants.The H gives us information about partial bond making and breaking in the transition state. The S gives us information about the relative disorganization of the transition state and reactants. Remember one of our main goals this year will be to understand how and why organic reactions take place. One reason this knowledge is so important is because it makes it possible for us also to understand the chemistry of life, virtually all of which is organic chemistry. Another reason is that it enables us to use these reactions for a variety of purposes. One very important use of organic chemistry has been to synthesize millions of new substances that have transformed our lives and our world. None of these things are possible without a solid foundation and understanding of the underlying principles.

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