Why We Learn Organic Chemistry

Most drugs are small organic molecules. The pharmaceutical industry needs lots of scientists that know how to make them. Organic chemists also make plastics and advanced polymers for electronic devices.

Why Organic Chemistry is a Premed Class

Organic chemistry requires lots of memorization as well as the understanding of hard concepts. The kind of thinking and studying that is required to get an A in organic chemistry is very similar to what you will do in medical school. If a student does well in organic chemistry, they have proven that they will be able to do well in pharmacology classes and anatomy classes in medical school.

What you should do before taking organic chemistry

Do this at the beginning of the year or before you take organic chemistry.

Ask your friends for old exams and answer keys from organic chemistry classes or find them on the Internet. Give yourself a preview of what organic chemistry exams are like. Try to get exams and answer keys that were written by your instructor. Try to get a copy of the syllabus too.

Memorize the names and structures of different functional groups, common organic chemicals, and solvents. Make flash cards if necessary. You can print out the pictures in this guide and cut them into mini flash cards.

Read a prep book like Schaum's Easy Outline of Organic chemistry or some good tutorial websites that explain individual concepts from your textbook. Using online tutorials to study is much more effective than just reading the textbook. If you want to know reaction mechanisms really well, there are some excellent websites that you can visit or you can get a copy of The Art of Drawing Reasonable Reaction Mechanisms.

Students are welcome to print out the pictures in this guide and use them as flash cards.

Summary of What You Should Do Before Taking Organic Chemistry

1. Memorize common functional groups.

2. Memorize the names of common organic chemicals.

3. Learn to name organic chemicals with the IUPAC system.

4. Memorize the common reagents and what they do.

5. Memorize the named reactions and their mechanisms.

6. Develop a conceptual understanding of how reaction mechanisms work.

This may require getting a tutor or reading a really good book.

Classic Questions

There are classic organic chemistry questions that show up on tests no matter what school you go to or what instructor you get. At some point, almost everyone is asked to look at a picture of a molecule and write the name, look at two molecules with the same chemical formula and say what kind of isomers they are, predict the product of a chemical reaction, rank molecules from most acidic to least acidic.

Predicting Chemical Reactions

There are several strategies for predicting the product of a chemical reaction. You can memorize what the reagents do and what products they make and you can develop an intuition for what will happen by understanding the mechanisms of reactions. It is important to use a combination of these techniques. Students that only memorize the reactions in their notes will not do as well as the students that also have a good grasp on how to feel their way through reactions by looking at the acidity of the molecules, their dipole moments, and other features that govern where electrons will move.

There are some reagents that absolutely everyone should memorize. These are so common that it is almost certain that they will pop up on an exam at one time or another. The same is true for chemical reactions of these include Sn1, Sn2, E1 and E2 reactions.

Named Reactions That You Must Know

Some reactions are named after the person that discovered them. There are a handful of named reactions that you can expect to see in almost any organic chemistry class. You should absolutely learn the mechanisms of these reactions because they often show up on exams. There are telltale signs for named reactions. If you see a diene and an alkene, the reaction is most probably a Diels Alder Cycloaddition.

Absolute Classics

• Fisher Esterification
• Michael Addition
• Diels Alder Cycloaddition
• Friedl Crafts Alkylation
• Friedl Crafts Acylation
• Suzuki Coupling
• Aldol Condensation
• Claisen Condensation

Less Common

• Jones Oxidation
• Nicholas Reaction
• Bayer Villager
• Swern Oxidation

Reaction Mechanisms

Drawing reaction mechanisms may be the hardest part of organic chemistry. Even really smart people think that they look like gibberish at first. All they are is a diagram of where the electrons move during a chemical reaction. Arrows represent the movement of electrons. There are lots of rules that govern where electrons can move. Several good books have been written to make understanding those rules easier.

If you understand reaction mechanisms well, it makes predicting the products of chemical reactions way easier. It is a building block for understanding how enzymes work when you take biochemistry, and it is arguably the most important part of organic chemistry.

Research Experience

Getting some experience working in a real laboratory will allow you to decide if you want a research career. There are hundreds of programs that will pay you to do a research project during the summer after your second or third year of college. You must apply to most of them by February 15^th of the winter before you would participate.

Reagents to Know

Reagent	Abbreviation
Gringard Reagent	RMgX, RMgBr, RMgI
Pyridinium Chlorochromate	PCC
Lithium Aluminum Hydride	LiAlH4
Sodium Borohydride	NaBH4
Aluminum Trichloride	AlCl3
Boron Tribromide	BBr3
Palladium on Carbon	Pd/C
Rhodium on Carbon	Rh/C
Metal Acetylides	R≡:Na, R≡:Li
Halogens	Cl2, Br2, I2, F2

This is a list of chemicals that you should absolutely be familiar with. You must know what they do and their limitations. This will help you predict the products of chemical reactions.

Common Solvents

You should not only know the name and structure of solvents, but also their dielectric constants and boiling points. Some reactions only happen in high dielectric constant solvents, others only happen in low dielectric constant solvents.

Benzene

Toluene

Phenol

Ethyl Ether

Chloroform CHCl₃

Dichloromethane CH₂Cl₂

Ethyl Acetate

Acetic Acid

Methanol MeOH

Ethanol EtOH

Dimethyl Sulfoxide DMSO

Dimethyl Formamide DMF

Pyridine

Tetrahydrofuran THF

Acetonitrile CH₃CN

Petroleum Ether

Cyclohexane

Pentanes

Hexanes

Acidity

Acidic molecules form stable conjugate bases. Molecules that are stabilized by inductance are not as stable as those that are stabilized by resonance. The reason that acetic acid is more acidic than ethanol is that the anion formed when the proton dissociates off of the carboxyl group can delocalize onto the carbonyl oxygen. The reason that trifluoroacetic acid is stronger than acetic acid is because it has three additional electron withdrawing groups to delocalize the anion formed when the proton breaks off.

Boiling Points and Solubility

Chemicals are soluble in other chemicals that can form the same intermolecular forces. Water is not soluble in ethyl ether because water is very polar and can hydrogen bond and ether is almost nonpolar and cannot hydrogen bond.

Chemicals that can hydrogen bond will have higher boiling points than those that are polar but cannot hydrogen bond. Nonpolar compounds that cannot hydrogen bond have the lowest melting and boiling points.

Interpreting Nuclear Magnetic Resonance Spectroscopy

There are two key things to look at when interpreting an NMR spectrum. The shift of each signal and it’s multiplicity. The further downfield a signal is, the more deshielded the electrons are. That means that the nucleus that creates a signal that is pretty far downfield has something quite electron withdrawing near it. Carboxyl groups withdraw electrons by resonance. This is stronger than inductance so nuclei that are near them show up further downfield than those that stand next to halides or other things that loose electron density by inductance.

Multiplicity tells you how many neighbors a nucleus has. It follows the n + 1 rule. A nucleus will have one more signal than it has neighbors. A proton with two neighbors will be a triplet. A proton with three neighbors will be a quartet.

NMR can only measure asymmetric nuclei like ¹H and ¹³C. In other words, it only measures nuclei with an odd number of particles. Since ¹³C is not as abundant as ¹²C, it takes a longer time to run a carbon NMR experiment.

Oxidation and Reduction

Oxidation can be thought of as the loss of hydrogen or the gain of oxygen. Reduction can be thought of as the gain of hydrogen or loss of oxygen. When an alcohol is oxidized, it becomes a ketone or aldehyde. When a ketone or aldehyde is oxidized, it becomes a carboxylic acid. When an alkyne is reduced, it becomes an alkene, when an alkene is reduced, it becomes an alkane.

Separating Mixtures of Organic Compounds

When chemicals are mixed, several reactions often take place at the same time. Often, only one product is desired. As a matter of routine, chemists must often purify the product of a reaction to get rid of excess starting materials, side products, and degradation products. There are several ways to do this with varying degrees of difficulty.

Distillation

Since chemicals boil at a variety of temperatures, they can be separated by their boiling point.

Recrystallization

Growing crystals and washing them can yield a pure product.

Aqueous Workup

If the product is soluble in a solvent that the contaminants are not

soluble in, it can be extracted into that solvent. This is often performed in a separatory funnel.

Preparative Thin Layer Chromatography

A big plate with silica gel on it is spotted with a line of the mixture. When the edge of the plate is dipped into solvent, each compound in the mixture will run up the plate at a different speed.

Column Chromatography

If a mixture is put into a silica, alumina, or florisil column, polar compounds will move down the column more slowly than nonpolar compounds. Each compound will elute from the column at a different time. Unless the compound is colored, aliquots of liquid must be collected in test tubes every several minutes and checked to see if the sample is in them.

Flash Chromatography

Adding a pressurized inert gas to the column to speed up the separation.

Preparative High Performance Liquid Chromatography

A variation on flash chromatography that uses a mechanical pump instead of compressed inert gas.

Automated Flash Chromatography

Machines like a Biotage Flash Master can do your work for you.

Rotary Evaporation

If you mix two powders together, they will not react with each other very quickly. This is why almost all organic chemistry is done in solution. Once the reaction is complete, the solvent must be removed. This is most often done with a machine called a rotary evaporator. It contains a vacuum pump that lowers the boiling point of the solvent. The solvent evaporates and is caught in a condenser before it can reach the pump. Some solvents require a liquid nitrogen cold trap because they have such a low boiling point and high vapor pressure that without extreme measures, they would get past the condenser into the vacuum pump and contaminate the pump oil.

Thin Layer Chromatography

Thin layer chromatography is a very quick and easy way to check the purity of a chemical, see if a reaction is over, estimate how polar a chemical is, or verify the identity of a chemical. A drop of the chemical is dissolved in a solvent and spotted onto an aluminum or plastic sheet with a thin layer of silica gel on it. When the edge of the sheet is dipped into a solvent, the drop will run up the paper. If the compound is impure or a reaction is not over, one spot will divide into many. The most polar compounds will be at the bottom of the paper and the least polar will travel the furthest. The R_f value of a spot is how far the spot traveled, divided by how far the solvent front traveled.

Dry Solvent

Some chemical reactions require extremely dry solvents. This is because water can interfere with chemical reactions in many different ways. If the product of a reaction is water, any excess water can prevent the reaction from occurring because of the Le Chatlier principle. In other words, if the equilibrium constant for the reaction favors the reactants, and water is a product, the other product will not be formed. Water is very reactive and often unwanted reactions will happen if water is present. This is particularly a problem in organometallic chemistry. To obtain extremely dry solvents, solvent delivery systems or stills are often used. Organic solvents are often distilled over sodium, because it reacts violently with water and removes even trace amounts from the liquid.

Microwave Synthesis

Previous generations of chemists would often heat chemicals with electrical heating mantles. Microwave synthesizers are a much more modern way to carry out high temperature chemical reactions. They can even be automated to run many reactions overnight. Running a chemical reaction at the boiling point of the solvent is called reflux. Microwave synthesizers allow a chemist to easily run a reaction at a temperature well above the boiling point of the solvent. Since reactions tend to be twice as fast with each ten degrees centigrade that the temperature is increased, reactions that would take days can sometimes be finished in an hour.

Journals

Scientists share their findings by writing papers in peer reviewed journals like Organic Letters and Organometallics. The peer review system means that several anonymous scientists read their paper and decide if it is worthy of publication. This prevents suspicious data from being published.

Publishing papers is a source of prestige. The skill of a scientist is partially measured by how many publications they have, the quality of the journals that they publish in, and how many times their papers were cited by other researchers.

Perhaps one of the most important skills that a scientist can have is an effective ability to search through the scientific literature and find answers to their questions. When someone wants to make a new chemical, often they can find a procedure that will give them the chemical they desire in a journal paper that may be quite old.