Reaction of the Week: Aldol Condensation/Addition

written by Faith of @premedprobs01

Aldol condensation is a useful reaction mechanism that you will encounter towards the end of your organic chemistry career. It’s a useful mechanism because the steps are very similar to several other reactions that you’ll run into-like crossed aldol condensation, Claisen-Schmidt condensation, Claisen condensations, crossed Claisen condensations, and Dieckmann condensations. Pay attention to the electron arrows! I apologize in advance if they are unclear, my chemsketch program is not the best.

Mechanism Breakdown
We’re going to demonstrate aldol condensation with a molecule of acetaldehyde, which for those of you who hate nomenclature looks like this:

An aldol condensation happens in three steps with one intermediate resonance structure. The first step is the formation of the enolate anion (for which I will show the resonane structures). The second step is the addition of that enolate to another molecule of acetaldehyde. The third step is the protonation of the addition product to result in the aldol product. Ready? Take a deep breath. Here we go!

The first step in aldol condensation is forming the enolate anion. This particular example is base-catalyzed aldol condensation. We’ll go over acid-catalyzed in another posting. In base-catalyzed aldol condensation, OH- ions in solution will remove a proton from the methyl group next to the carbonyl carbon. (The carbonyl carbon is the one with the oxygen attached). This proton can be removed from the methyl group because of its proximity to the oxygen atom! Being near an oxygen atom tends to make protons more acidic, or more readily available to be removed. This combined with a strong base allows the methyl group to be deprotonated and an anion to be formed with water as a byproduct. Let’s look at the resonance stabilization of this anion!

This resonance stabilization is important because it confirms that the enolate anion is stable enough to carry on to the next step of the reaction. The fact that the electrons are delocalized between the CH2 and the oxygen lends it a bit of extra stability so that it won’t immediately be re-protonated. Now it’s time to look at the addition reaction of the enolate to another molecule of acetaldehyde.

In this step of the reaction the negatively charged enolate attacks the most electrophilic part of the second acetaldehyde molecule. This would be the carbonyl carbon, or the carbon directly attached to the oxygen! The enolate ion attacks the carbonyl carbon, which breaks the double bond to the oxygen and gives the oxygen an extra pair of electrons, leaving it negatively charged. We are so close to the product now, and the last step is stupid easy. Here it is!

In this last step, the negatively charged oxygen picks up a proton from water you have in solution, and the electrons from that proton are kicked back off onto the oxygen, thereby regenerating your base! Since the base is regenerated, this reaction is referred to as base-catalyzed. The final product’s structure gives us a clue as to why this is called an aldol reaction. It’s because the final product contains an aldehyde functional group and an alcohol functional group. Practice this reaction, and tune in next time (probably not next week as I will be on vacation) when we look at crossed aldol condensations!

This post was made by Faith, @premedprobs01, a premed student in Colorado aspiring to become an MD working either in oncology or rural primary care internationally. Check out her original blog at www.goodandfaithfulservice.wordpress.com

How to succeed in Organic Chemistry by a Premed with a job.

The following are a series of steps I consider necessary for doing well in Organic chemistry 1. I am currently preparing for Orgo 2 and would have loved someone to give me more of the heads up when the first one hit. I had a little prep but not nearly as much as I needed. I did not do as well as I wanted to in the class therefore I am learning from my mistakes and helping YOU not to make the same.

Here are what I consider the necessary steps for succeeding in Orgo:

1.Prep: start studying MONTHS prior to taking the class. I did a month and it was not enough. Try reading a book other than your textbook. There are several Orgo prep books such as "Organic Chemistry as a Second language" and "Organic Chemistry for Dummies"* which will give you the basics broken down so you can easily grasp the SKILLS which will prepare you for the DENSITY of the material. Once you begin the semester, you wont be a blank page. The teachers words will be familiar. DO NOT GO IN blank.

2. Attend: I personally did not attend my Gen Chem lecture and did fine, but for this one you NEED to attend. You will learn the expectations of the professor as opposed to just learning every chapter fully on your own and wasting time on subjects they teacher does not want you to know. Some teachers suck, I know, but they are the ones MAKING the test and you need to know what is on the test. Go to class.

3. Study: and by this mean teach yourself. Some people work better studying a little every day. I work better studying a lot once a week. However with this class I studied a lot two to three times a week, by a lot I mean around 4hrs at a stretch. Find what works for you and DO IT with discipline. PRACTICE. Don't read over and over. Do exercises. If your teachers dont provide you with materials to practice look them up online or do the back the book but PRACTICE. Draw mechanisms, invent reactions. TIME YOURSELF every exercise should take your around 10mins with accurate answers. PRACTICE until you can beat this speed.

4. Dont cram: needs no explanation. Every chapter has at least six reactions to master. Every reaction has start materials mechanism and products. If you cram even just two chapters you'll be lost. Do the math.

5. Dont share: this class will consume your time. I know people got to work* (I work) but you will only succeed if this is your priority. So don't take with other big classes nor sciences, take it with history or sports. Work as little hours as your budget allows, take a break from all those clubs you've been joining. Invest yourself.

6. Take breaks: this may sound like an oxymoron but make sure you sleep some. Take a day or two a week in which you do not look at Orgo stuff at all. You do not check grades or your email or even see your study buddy. Dont drink, the hangover will make you waste an extra day.

7. Seek help: the SECOND you feel lost go talk to someone about it. Even if it is your mom or your BFF, they may provide the support you need to keep going. Try your school learning center, go to review sessions, join a study group, find a tutor*, go to the instructor and tell them you are struggling they like to see your effort. Dont wait till you are about to drop it. Seek help as soon as you feel you need it.

8. Keep going: If you are determined to go into medicine nothing should stop you. You may feel like this is too much for you, like you cannot do it, like Med school will just be worse and you don't have the brains for it. I promise you do. Do not let the "weed out" class weed you out. Beat the statistics. And whenever all the brainiacs around you are pretending the class isn't hard, IGNORE them. They probably don't have as many responsibilities to juggle as you do.

*I have to make a note for independent students, post bach and every on on the non traditional track. This class needs to be your priority and that may bring problems financially or at work. Talk to your supervisor and tell them you may need to leave early or come late on occasion. Take a day off before the exam. Minimize your expenses so you can survive on less hours at work. This class took a big financial hit on me which took down anxiety attacks so I know what I am talking about. For things like tutoring and books which some of us cannot POSSIBLY afford there are ways to do it. You can a group tutor which are generally cheaper or trade services with someone (You tutor me I clean your house kinda thing). For books I mostly download pdfs.

FEEL FREE TO ADD YOUR OWN TIPS!!!!