Freshman Organic Chemistry
Since 1972 a course of organic chemistry has been taught to a class made up exclusively of Yale freshmen who have a strong background in chemistry and physics. At first the course enrolled fewer than 30 students, and its content was the same as that of a traditional elementary organic course, except that a little more time was spent reviewing concepts from general chemistry during the first semester.
Over time the enrollment in Chemistry 125 has more than doubled, and its emphasis, especially in the first semester, has shifted in an attempt to create a more effective bridge between science as it is commonly taught in many schools (and in many courses in colleges) and science in a university setting, where the focus is on creating new knowledge, rather than simply mastering what is already known. Students come to the course knowing a good deal about chemistry. If the course succeeds, they will leave with a sound knowledge of organic chemistry and a better appreciation of the logic of creative science.
The time devoted to meeting this goal has forced some traditional "first semester" topics into the second semester and required the teacher to be more selective in choosing second semester topics. There is less time for biochemical topics than in a traditional organic course, but Chemistry 125 alumni are a year ahead of their classmates and typically take a subsequent course in biochemistry, in which they have excelled. The goals of Chemistry 125 are to master the core of organic chemistry and its logical basis and to spend enough time on selected topics to show how this discipline exemplifies much of what is most admirable in science. Creative science depends on close observation, and one does not learn to be a good observer by reckless speeding.
One of the goals of the course is to encourage students to ask questions. Asking should never embarrass the student who asks, even when the question might embarrass the teacher. If you don't understand something, it is likely that others don't understand either but haven't realized it yet or are too shy to ask. The teacher may not have explained clearly, or perhaps hasn't thought about the subject carefully enough. Once after the teacher explained that Pekeris had calculated the energy of the helium atom to 9 or 10 significant figures, a freshman asked how this was possible when the mass of the particles was known to only 7 significant figures. Good question.
The prime question, and the theme of the course, is "How do you know?"
Too much science teaching consists of drill on facts, or supposed facts, and on half-thought-through theories that generations of students have swallowed in the struggle to get on to more advanced topics. Preparing to make new contributions to science requires developing the habit of thinking carefully. The only authority should be experimental observation and logical argument - never simple assertions of the teacher or the textbook. As often as is practical the examples used in lecture not only are real, but also are those actually used when key concepts were initially formulated. The aim is to be as honest as possible about the fact that chemistry is an empirical science, based in concrete experiments.
The fall semester of Chem 125 emphasizes physical-organic, as opposed to synthetic organic chemistry, which will follow in the spring semester. Half of the first semester is taken up with questions of structure (what atoms and molecules look like and what bonds are) and of what makes molecules reactive. Having mastered the physical basis of these topics a student can understand and predict much of organic chemistry, rather than just memorizing it. It is easier to learn the facts when one has a reliable perspective from which to view them. When students come into a traditional course of organic chemistry as sophomores they are supposed, rightly or wrongly, to know enough about these fundamental topics, so less time is spent on them. Freshmen are not supposed to know, so we can spend enough time to learn about them properly.
We start our study of bonding with Lewis structures and resonance theory and see that, useful as they can be, there is not a whole lot of there there. We'll spend enough time to see how great scientists make mistakes en route to finding the truth, and how great scientists differ from snake-oil salesmen.
We then examine reality - the most direct experimental evidence on the structure of atoms, molecules, and bonds. It is derived from "feeling" them by SPM (scanning probe microscopy) and "seeing" them by X-ray diffraction. We want to understand not only what these techniques show, but how they show it.
In modern chemical practice quantum mechanics is as central to understanding bonds as x-ray diffraction is to seeing them. So we learn enough quantum mechanics to appreciate how it works and to understand bonding and reactivity. We spend time on quantum mechanics because, to the best of our knowledge, it is the only theory that describes how molecules actually behave. Molecular quantum mechanics is very unfamiliar, but it is not really difficult, if you can be content with understanding why Schrödinger's Equation works the way it does, and leave the numerical solution to computers. The qualitative ideas of energy match and overlap, HOMOs LUMOs and SOMOs will illuminate all our subsequent discussions of reactivity.
In the third quarter of the semester we turn from these physical topics to more traditional organic chemistry by asking how it is possible that chemists were not surprised when the methods of experimental and theoretical physics finally could show what molecules look like. Chemists weren't surprised because they already knew! The development of the organic molecular model over the century following the "Chemical Revolution" of the late 1700s is at the same time a great romance, a great puzzle, a great way of organizing structural organic chemistry and learning its nomenclature, and an outstanding example of how good science works. As we learn how organic chemistry developed we also begin to learn some of its key reaction types and how to understand them in terms of our qualitative quantum mechanical theory. This is preparation for the second semester which presents individual reaction types more systematically.
The remainder of the first semester associates energy with molecular structure, shows how enthalpy and entropy control equilibrium and dynamics, and describes some of the tools that are used to study reaction pathways. These topics are illustrated by systematic study of organic free-radical reactions. These reactions are addressed on the basis of a solid understanding of what molecules are, and what makes them reactive. At the end of the semester we show how solvent effects make polar reactions more complex than those that involve free radicals.
Most of the material above is covered in more detail than is available in elementary textbooks. The Chemistry 125 web site, and particularly the wiki that class members prepare, play a key role in this part of the course.
The second semester presents additional synthetic transformations, spectroscopic methods, and the properties of more complex molecules, including biologically important ones like proteins and nucleic acids.
Most courses of organic chemistry spend less time on physical and logical principles, and more time on specific reactions. The Chemistry 125 approach is certainly no less rigorous, and it has seemed to work for many well-prepared Yale freshmen. Alumni report feeling well prepared for the dreaded MCAT exam, and one alumnus thinks he was accepted to a leading medical school because of an interview in which he discussed negative kinetic energy, from Chem 125 quantum mechanics, as the most interesting thing he had learned in college.
The goal of the course is not just to master the tools of organic chemistry, but also to gain some insight into the workings of the material world and how humans can discover them. The benefit of understanding things has been recognized for a long time. About 30 B.C. the Roman poet Virgil wrote in Book II of Georgics or Art of Husbandry:
(Happy the one who has been able to learn the
cause of things
and trample on all fear, and inexorable fate,
and the roar of greedy Acheron.)
The Acheron, like the Styx, is a river of the underworld in Greek mythology. It stands for Death.