RBF Teaches: Column chromatography

All right! Listen up kiddies,

Column chromatography is much the same as TLC. Except this time the solvent front is forced down instead of being drawn up. All of the principles remain the same. So let's get straight into how to set up a nice column that should provide you with great separation of your compounds and be a great aid to you in your (awesome) organic life. The guide here is for a simple Flash column (forced with compressed air) but is translatable to a gravity forced column (which isn't really used much anymore by the stressed PhD student with a slave-driving supervisor). Aso guys, bear in mind that as you do more and more columns you get a feel for them and they do become like second nature.

IMPORTANT NOTE: Silica dust is toxic to inhalation (similar to asbestos) and all measuring of silica should be done in a fume hood and FOR GOD'S SAKES DON'T BREATHE IT IN!

Step 1: Choosing the column

There is a rule-o'-thumb in the lab that goes something along the lines of if you have a good separation (on TLC) of your desired spot from the undesired components you can use a ratio of ~20:1 (silica:mixture) or if its much more close running then you increase the ratio to ~100:1 (this should separate even the closest spots). The easiest way to measure out your silica is calculate what you need first then weigh out approximately what you need (in a clean conical flask/beaker), weigh it and so forth. If you have a bit too much or too little you can probably get away with it in the end anyway. But bear in mind the supervisors don't like forking out money and silica is exy $$$ (unless you buy cheap Chinese stuff like us :P). [MSG edit: With practice and experience, choosing a column becomes second nature.]

This leads us to the important bit: the actual column. So APOC - a book I regard as a mini lab bible for undergrads as well as honours students (Read Chapter 11.6.2)- recommends choosing a column that will fit the silica you want to use up to a length of 18cm. This is a good guide but for me I basically like to do the following:

1. Take a long pasteur pipette and attach a rubber dropper to it.
2. Insert it into a column (that looks about the right length and width to fit the silica) and put it in until your fingers (holding the rubber dropper) are at the lip of the column. Mark the tube with a marker pen.
   
3. This is the minimum height that your silica must reach. The maximum height is about 3cm from the bulb (solvent reservoir) of the column (if it has one) or the same distance as in step 2 if it doesn't.
4. Pour in the silica dry and tap the column gently to settle the silica. Check the height of the silica if it is above the line in step 2 you are good to go if not just pour in a bit more silica until you reach it. If it is way off grab a different column. (Sometimes you have to make do with what the lab has to offer). I suppose I should mention here that if you have a column that has a glass frit then YAY and if not then you have to stuff some cotton wool in from the top of the column into the bottleneck of the column just above the tap.

[MSG edit: everyone has their own way of packing the column. I don't do any weighing or anything but again, with experience, you will get a feel for the amount of silica required to achieve a given separation using a given solvent system.]

Step 2: Preparing the column

This is a bit tricky but I am sure you will be able to do it if you take a bit of time to read through the instructions and don't rush into anything, BUT, don't be afraid to try it. It isn't terrifyingly difficult.

1. Once you have the right amount of silica to fit the column to the minimum height pour the dry silica into your conical flask.
2. Using the solvent system you figured out from your TLC pour enough solvent onto the dry silica and swirl the flask/stir with a clean glass rod until you have a free moving slurry. By this I mean you want the silica to move completely without lumps. In this case more solvent is better than too little as you are going to pour it so think of it like pouring soup (you would find it hard to pour a thick soup right? and yes that is rhetorical)
3. MAKE SURE YOUR COLUMN IS (vertically) STRAIGHT (in both dimensions) and the tap is closed. Pour a small amount of the solvent into the column (3-5cm is plenty) and then add a small amount of sand (about 1cm thick) and tap the column to get it to settle nice and flat. Wash any sand that sticks down with a bit more solvent (use a pipette). [MSG edit: Alternatively you could put the sand in first then add solvent so that you don't have to wash down the grains of sand. Give the sand layer a few taps with your hand afterwards to liberate any gas bubbles.]
   
4. ONCE AGAIN, MAKE SURE YOUR COLUMN IS STRAIGHT then pour the slurry (for heaven's sake use a funnel) into the column. [MSG edit: make sure your solvent level in the column is high enough so that the sand layer isn't disturbed when you pour in your silica slurry.]
   
5. Open the tap and pour all your slurry in but don't overfill the column. REMEMBER the tap is open so you will have some solvent dripping through. In this case I usually have my solvent mixture bottle underneath the column but if you haven't poured all the silica into the column you can put this flask under the column collect a bit more solvent then pour it into the top of the column again.
   
6. Once it is all in, gently start tapping the column. I use a piece of metal rod wrapped in rubber hose but you can just use your hand or some rubber tubing. Whatever makes you feel good.
7. As I said earlier this is Flash chromatography so you can whip out your gooseneck and attach it to a compressed air line and gently OH SO GENTLY push compressed air into your column forcing the solvent through the silica much faster. I personally keke-clip my gooseneck to the top of the column have a long compressed air line with a three way tubing adapter halfway along that allows me to regulate the flow of air with a thumb gently covering the open port of the three way but MSG likes to regulate the air flow with his hand holding the gooseneck. I like my way for sitting down and I haven't had a problem when I use this correctly but neither has MSG. Too much compressed air into the column is not a good thing! [MSG edit: Running flash columns are one of the safer operations done in an organic lab, but you still have to be careful. One of the obvious dangers is exploding columns (because after all, you are forcing air into a semi-sealed glass tube). So whatever method you choose, make sure you're comfortable with it. Safety first! Personally I regulate airflow with my hand. Apart from the fact that you probably get more tired using this method, it is superior in almost every other way. So even if you find this method more difficult, I would recommend running the column in this way. As a student you're here to learn, and so don't worry about making mistakes or stuffing things up: it's all part of the process!]
   
8. As the solvent is pushed through the silica is also packing into a highly ordered form and if you have done the previous steps correctly the silica should form a flat surface at approximately the mark you made earlier. HOWEVER, you DO NOT want to push all the solvent through, you want to have a good amount of solvent covering the silica at this point. If you see the solvent is running out then use a pipette to add some more, it is ok to shut the tap of the column as well. You may also have some silica stuck to the sides of the column and while it doesn't really matter you can wash this down with a bit of solvent (using a pipette).
9. Finally, with about 3cm of solvent remaining above the silica level you can add about 0.5cm of sand to the top of the column (THIS IS OPTIONAL BUT ADVISED). This just prevents the disturbance of the nice flat silica (you want your compounds to all start at the same point as in TLC) when you pour in more solvent. [MSG edit: I usually do this step AFTER loading the column (see below)]
   

Step 3: Loading the column

This is quite easy to do but don't go to sleep yet.

1. After adding the MINIMUM amount of solvent necessary to dissolve your sample (generally you use the same solvent as the column but sometimes DCM is necessary) take a tiny amount for TLC comparison. [MSG edit: if you do use DCM, don't be surprised if you don't get as good a separation as you intended. When dissolving your sample, use at least the same amount of solvent as your sample. That is, if you have 1g of sample, use at least 1mL. This is more relevant when you have a liquid as your product. On a volume ratio, if the amount of solvent is less than your sample then technically your solvent is dissolved in your sample rather than the other way round]
   
2. Allow the solvent level in the column to reach the same level as the top of the silica.
   
3. Using a long pasteur pipette very carefully transfer the compound across. (Now do you see why we made the minimum height mark?) It is wise to load the sample on by running it down the side of the column but do this as close to the top of the silica (or the 0.5cm layer of sand if you have it).
4. Once you have added all of your sample run the column down to level with the top of the silica once more and rinse your product flask with the solvent.
5. Add this to the column again and repeat step 4.
6. Very carefully add ~1cm solvent to the top of the column using a clean pipette and repeat step 4 once more.
7. Carefully add solvent to the top of your column with a pipette to ~5-10cm then you can try gently running the solvent down the edge of the pipette to prevent the disturbance of the silica.
8. Once you have ~25cm of solvent in there you can carefully pour the solvent mixture into the column using a funnel until the column is full.

[MSG edit: After ensuring the silica level is completely even, I load my sample solution straight onto the top of the silica, without the sand layer. The most important part of getting a good separation is a loading of a thin even layer of sample. I add my sand layer after I am finished with adding solvent to my column. This saves having sand stuck to the side of the column, but actually it doesn't really matter anyway.
]

Step 4: Running the column

Now for the easy part. While it is probably unecessary at this point it is still prudent to place the first collection vial underneath your column. Sometimes compounds can just fly off the column and it is easy to lose them in your waste solvent beaker if you are not careful.

1. Open the tap
2. Using compressed air you can force the solvent through or simply wait for gravity to do its job. It is important in both these cases that the flow rate remains roughly regular. If you are using compressed air for Flash chromatography a fast flow rate is important for good separation. You want the solvent to be pouring in a continuous flow from the tip of the column not dripping.
3. Change your collection vials at about 2/3 full (a rule-o'-thumb is each fraction is half the weight of the silica e.g. 20g silica column = 10mL fractions) and rinse the tip of the column with a small amount of the solvent mixture before exchange (or you can dip the tip of the column in the solvent in the collection vial if it reaches).
4. I personally relieve the flow rate when I am exchanging collection vials but like I said the quicker the better.
   
5. Run TLC's on the fractions (for larger columns TLC every 2nd or 3rd fraction to save a bit of time). I generally take 10 fractions then TLC and while the TLC is running I collect another 10. I am spotting the TLC plates while forcing the solvent through the column. (This comes with experience; some people are even more insanely awesome LabChimp)
   
6. Analyse your fractions fully (when you find a spot in your "every 2nd fraction TLC" it is often necessary to test some in between fractions (e.g. spot appears in 8 ends in 12 but need to check 9 and 13) against the reference sample you took) and group similar fractions together.

Step 5: Workup

I know, I know the whole process of columning is the workup but I couldn't call it "rotavapping".

After you have fully analysed your fractions you can now put them in a PRE-WEIGHED RBF. Chuck that bad-boy on the rotavap and remove the solvent as best you can - sometimes the volatility of the product can cause problems here. Dry your compound, either under high vac. or in the case of the undergrads here under a stream of N2. Then weigh your product, run NMR do the science thing and go home satisfied you did a column yay!

Once again I am making a video of this WOOPEE! and some nice pics might happen to add in here one day if I get a chance. Hopefully, MSG and I can comment on this one too once it is done.

One reaction, three bonds

I was just catching up on some of the overnight publications and this one from Song and Dong in ACIE stuck out: Pd-catalysed intramolecular carboesterification of olefins.

A scheme will probably clear things up:


As the authors describe, what this Pd mediated transformation achieves is a formal [3+2] cycloaddition. It is certainly only a cycloaddition in a formal sense if one takes a look at the mechanism proposed by the authors (which I have no problems with). It's all pretty well established stuff (chloropalladation, reductive elimination etc) as well as based on mechanistic studies (that's the oxypalladation step). I've certainly seen Pd catalysed reaction mechanisms which... let's just say a great deal of Jedi mind tricks will be required for me to accept them.


A bit about the conditions: The catalyst loading is low (1%, no conversion without the presence of catalyst), in a polar solvent (acetic acid or MeCN). The highest yield observed on the model system (in the first scheme) was 83% using MeCN and 3eq of LiCl. Apparently the reaction is not air or moisture sensitive either which is great; using inert gas reaction atmosphere isn't that annoying, but drying and degassing solvents do take up time.

But there are two things I really like about this publication:

1. In one step you form three bonds. Fair enough, only one of them is a C-C bond (Diels-Alder is still king) but you do form two rings. And the C-Cl bond is awesome because...

2. ... the vinyl halide functionality of the product is primed for another Pd catalysed C-C forming reaction. I'm thinking Stille, Heck etc. Now I wonder if you can tweak it so that you can add a stannane in there and do a Stille in the same pot...

I want a nano-dragster for xmas

So I came across this today in my ASAP feed. It's a sweet nano-dragster with super awesome upgraded front wheels for directional steering. You can like take it off sweet jumps and drive it around and stuff. Oh and if you buy the super awesome scanning electron microscope you may actually see it. AWESOME!
But W did happen to ask me one very simple question, WHY!? Well I will tell you why, because its a nano-dragster that's why! As if you wouldn't want it. It has methyl-scythed-p-carborane front wheels that give it some directionality and HUGE C-60 rear wheels for good traction on GOLD surfaces. ROCK ON!

 With the nano-dragster you can even make it do sweet tricks like wobbling the front axle. SUPER COOL! Forget about those old boring normal sized cars or even those sweet mini RC cars. This is the future! I want one for XMAS and so should you!

Comments Are Back Online

Ok everyone you can now post comments again. I was starting to wonder why we didn't have any and now I see why.

New Moon Buffoon

So I took my lovely fiancee out to the advanced midnight screening of the Twilight Saga's New Moon last night. What a mission. While the movie was quite good and the little woman really did love it. I think next time the option will be to wait for a normal hour to go watch it. Unless of course someone finally makes a Wheel of Time movie. Then I will be there.

But after getting home at 3am and then crawling out of bed at 9am this morning I am seriously regretting being such a "sweety". Seriously, I am rooted and I have a full day in the lab today. DUMB!

Oh well, I did earn some bonus points with the little lady and she has bragging rights with her mates now so that's good. I guess.... Anyway, I have to say that the movie really was very good. Unfortunately, the "wolf-man" Jacob was a little too ripped and now it looks like I will have to be pushing myself to go to the gym quite a bit until the hype with this dude wears off. But all that aside, the action scenese were very good, and the "Volturi" were pretty cool and Christoper Heyerdahl was hilarious, reminiscent of the good old drac.

And the best part of all was that Edward was made to look like a pasty little weiner, which he is. Anyway, go and see it is my advice, cuz if you don't people will make your ear hurt until you do go see it.

BACK TO THE LAB!

Uncle OO's story time: How TLC works

Gather round younglings it's time for Uncle OO's story corner,

Today I will tell you a great story, of mystery and magic....ok so it's not so much that as chemistry and common sense. Basically, I'm going to give you my patented "How chromatography works" story. Hopefully somewhere along the line some cool cartoons can also be added but for now your imagination will have to suffice.

Ok so I detailed to you the way in which to run a TLC. But now for a nice little explanation of how they work.

Imagine a large forest of trees. This large forest of trees represents the silica on a plate or in a column. Now imagine that this forest (all of these trees are identical and evenly spaced) is very tightly packed all crammed in together. Now imagine you are a really skinny person and your friend is rather large (but for fairness let's say they are muscular). You, being skinny represent a non-polar molecule and your friend represents a polar molecule. You are both at the edge of the forest and want to race through.

Suddenly riot police jump out of nowhere (these riot police are of varying sizes some are as large as your friend and some skinnier than even you). Now these riot police represent a solvent system (once again large is polar and skinny is non-polar).

Still with me? Ok here is where it gets interesting. The riot police want to force through the trees to the other side but in doing so they scare the crap out of you and your friend. So you start to push through the forest. You, being skinny are able to move through the trees easier, you don't get stuck and the trees can't grab onto you as easily, unfortunately your mate is not so lucky, he is struggling through the forest but can't get very far as the trees can't move aside for him very much and they grab him along the way.


Now the riot police, are still pushing through the forest too and just like your mate the bigger guys are moving more slowly but their sheer numbers are pushing your mate through and the skinnier riot police are overtaking you to the other side of the forest. You keep running through and eventually make out to the other side.

Now the speed with which you and eventually your mate made it depends on the number and size of the riot police. More large riot police moving through the forest will clear the trees down and allow you to move through the forest more easily as a result but you and your mate will like both just rush out so fast you both can't tell who won.

If there are more skinny riot police they are liable to overtake you both and make you both feel like losers. So you will have to wait for all the riot police to pass. But you, being skinny, will be able to move through the forest more easily so you will win but not in good time.

If the riot police were all roughly the same size somewhere in between you and your friend (indicating a good polarity for the solvent system) you should make it out before your mate but only enough that he doesn't lose sight of you in the trees and hate you for the rest of your life. If this is the case you might end up with your friend stuck in the forest and have to call for a gang of riot police to flush him out. (sometimes compounds get stuck on the column and need to be flushed out with a polar solvent).

The same is basically true for chromatography, the more polar the solvent system the slower it will run through the column (it is the mobile phase). But the more it will take up your compounds and force them through the column. If the solvent system is not polar enough the solvent will run through the column but not interact with the compounds on the column and the compounds will remain on the column for longer. If your compound is polar it will stick to the column more and therefore elute (i.e. come off the column) later. Inversely, if your compound is non-polar then it will not stick at all to the column and move very quickly through as the mobile phase passes.

RBF Teaches: Thin Layer Chromatography (TLC)

Welcome Kiddies,

To the first ever RBF teaches blog post. In these posts we will be uploading a number of videos that go through the various techniques used in an organic chemistry lab and perhaps outside of one [MSG EDIT: Please don't try experiments at home kiddies] also.

Today we will be learning all about Thin Layer Chromatography (TLC). This is perhaps one of the most useful widely used techniques in the organic chemistry lab as it provides a fast, reliable and reproducible qualitative analysis of most reactions in the lab. YAY!

So, what does that mean? Well, for instance, let us assume we are performing a reaction in the lab. WOOOO! Now, how do we know when the reaction is complete? If your compounds are all colourless and no colour change occurs upon completion (as is usually the case) how can you know whether to stop the reaction? The answer my young friends is TLC! And Here is How we do it!

By taking a tiny sample of the reaction mixture (and I mean tiny, usually a drop is plenty) and comparing that to your starting material(s) you can determine whether the reaction is complete or not.

So, you may now be thinking "OK cool its magic or something, but I must know the secret Oh Great One!" Well its just chemistry these secrets will be revealed.

Here's how it works and how to run a TLC all of your very own and on the cheap from the very beginning:

1. TLC plates can usually be purchased as large square (20x20cm) sheets or as a large roll of silica (SiO4) (or aluminium oxide AlO4) adsorbed onto an aluminium backing sheet. You can also get TLC sheets with plastic or glass backing.
2. From these large square sheets you can cut them using a sharp knife (mark the whole plate or a guillotine (cut the plates silver side up). I usually aim for my TLC plates to be 5cm long and 2cm wide, this gives me 40 plates per sheet. To cut the plates it is possible to mark with a pencil on the silica side (i.e. the white side) HOWEVER you must press very gently so that the silica is not etched with your pencil you only want to lightly glide the pencil over the silica.
3. Once you have cut your plate it can be used for a TLC analysis. To begin with a straight baseline must be drawn across the bottom of the plate usually 0.5-1cm from the bottom and parallel to the base. This is your baseline and all of your spots will begin from this point so that there is no error. It should look something like this:
   
   
   
4. Once you have this base line you can begin to plan your TLC. Usually, you spot at least 3 spots depending on the reaction. If for example, you have one starting material and a reagent which does not run on TLC the TLC would be spotted as follows 1. Starting material (SM) 2. Reaction mixture (R) 3. Co-spot (C, a spot on which both starting material and reaction mixture is spotted. This reduces the chance of a false positive due to a poor solvent front etc.). [MSG EDIT: The use of a co-spot lane is also helpful when your product and starting material spots have very similar Rfs. You will read about Rfs later] If you have more than one material or a reagent that runs then this spot should also be added as well as being spotted to the co-spot. Also, if you have a pure sample of the desired product then it is also a good idea to spot this too to ensure that your reaction mixture has the correct product being formed (this is also the case in which a known by-product that can be produced from the reaction). This should also be spotted on the co-spot.
   
5. Having the plan in place you can now gently mark the TLC plate with a pencil. Remember, lightly so as not to scratch the silica. Mark the plate so that you can understand it and not be confused as well as marking it so that all the spots are evenly spaced from each other and not too close to the edge of the plate. A good example can be seen below:
   
   
   
6. Once you have a sample that is reasonably well diluted (5mg/mL usually suffices) you can begin to spot the plate. [MSG EDIT: In general, aim for higher dilution, that is, lower concentration. Using high concentration spotting solutions leads to larger spots, which means poor resolution. If the concentration is too low, then you can simply spot more] Using a TLC spotter (these can be purchased or made simply by blunting the end of a small 21-23G needle) gently spot a small spot on the plate. This may take some practice. It is easiest to use a quick motion to avoid leeching of the solvent from the TLC spotter onto the plate this avoids overflow of the spot onto other spots. Do not over spot the plate. After you have run the TLC, if there is a large streak this means your spot was too concentrated. Your spots should appear as below:
   
   
   
7. Time to run the TLC. This is reasonably straightforward. Place your solvent system in a small glass jar or beaker. It is a good idea to only have 0.5-1cm of solvent in the bottom of your jar so that the level sits just below the baseline of your TLC plate.
   If you like [MSG EDIT: you should!] you can line the beaker with some absorbent paper (this will saturate the atmosphere of your beaker with solvent fumes allowing the plate to run quickly and smoothly. It is a good idea not to lean the TLC plate against the paper as it may leech solvent onto the plate). Place a watchglass or lid over the jar. Take your TLC plate by the top with a pair of tweezers and, after removing the lid of your jar, gently place the plate into the beaker try to make sure the plate is inserted levelly so that the solvent runs up the plate evenly.
   
8. Once the solvent level reaches 0.5cm from the top of the plate you can remove the plate from the jar. Gently mark the plate at the solvent front (i.e. the level the solvent reached on the plate) with a pencil.
   
9. Now you can develop your plate. This can be done with either UV light (most plates are fluorescent at 254nm) or using a dip. [MSG EDIT: UV light is especially useful as a visualisation tool if you know your product/starting material is aromatic or contains conjugated bonds]. To dip, simply take the chosen dip (selection of a dip depends on your compound) dip your plate quickly into the dip up to the solvent front and remove. Ensure that all the dip drips back into the dip jar to save on making up more dip and gently heat the plate with either a heat gun or on a heat plate. [MSG EDIT: Make sure your plate is free of solvent before dipping. I usually use a heat gun to blow dry the plate before dipping, and when I use a higher boiling solvent (such as ethyl acetate or methanol), I blow dry my plate for longer before dipping. A common mistake made by students is not heating the plate sufficiently. The colour of the spots depends on the dip you're using. When using a PMA (or Goofy's) dip, the spots should come up as dark blue spots on a green/blue background. Heat the plate until you see this. When the plate starts to turn dark blue (or just black), that's too much heating: stop. When using a permanganate dip, the spots should come up bright yellow against a pink/purple background. If the background goes yellow, then that's more than sufficient heating.]
   
10. Now you can see your spots on the TLC plate. HOORAY! The next step is simply perfecting the method for your particular reaction.
    
11. Find a solvent system that works for your particular reaction - This can often take some time. Basically, you want a system that is polar enough to move your spots up off the baseline but not take any spots off the plate. A good system to start with is 15% Ethyl Acetate (EtOAc) in Petroleum Spirits (PetSp) or Hexane. In this case the EtOAc is the polar solvent. If the spots are seen to move too far up the plate then lowering the amount of this polar solvent should lower the distance the spots travel. (See the OrganicOverdose explanation of this in the following post). Ultimately, you should have a TLC plate that looks something like this:
    
    
    
    Here you can see that some SM remains and that the reaction mixture contains a new product. The co-spot shows both spots which indicates that the final R spot is not a false positive. It is usually a good idea to try to get the topmost spot to fall below halfway up the plate. (Reasons for this will come up later). [MSG EDIT: As a rule of thumb, the spot you're trying to isolate should be just less than 1/3 up the plate, ie Rf ~0.3)
    
    To measure the Retention Factor (Rf) of the spot is as follows:
    Rf = distance of spot/distance of solvent front
    the solvent front is the distance you let the solvent move up the plate. This means that no matter how far up you let the solvent front move the Rf of a particular spot should remain the same (to a degree). This means that it is very important to mark the solvent front when you have finished running the TLC and before you begin to develop the TLC.
    
12. Once you have all these points down pat you can run a TLC every reaction to make sure that the reaction is complete.

Important points to remember:

• Mark your plates gently with a pencil (don't use pen: it will be very embarrassing)
  
• Spread your spots out evenly and leave a good distance from the side of the plate.
• Don't overspot the plate. If you have a large streak on the plate it is a good indication of overconcentration. [MSG EDIT: Remember, TLC is a visualisation tool for your reaction. As long as you can see the spots, it's fine, so there's no need to make spots extra intense. Less intense and smaller spots means better resolution, which is always good, especially if you have spots which are very close running]
  
• Don't overfill your TLC jar above the baseline of the TLC plate.
• Don't lean your TLC plate against the absorbent paper in the TLC jar.
• Make sure your solvent system is good you want decent separation between spots (this will be covered at a later date)
• Be sure to mark your solvent front before developing your TLC.
  
• Don't leave your plate in the dip. It is a quick dip and then removal.
• When developing your plate under UV use a pencil to mark in the spots that appear under UV light.

To sum all of these points up we have created the following video:

Please Note that the video has no sound at present but we will add a commentary to the video soon.

[MSG EDIT: If you're an undergrad who wants to ask questions about anything on this post or laboratory techniques in general, feel free to post them on the comments section. OO and I (and I'm sure grad students around the world who visit here) are more than happy to answer your questions and give you a helping hand]

Breaking Bad

So while MSG and I get organised and ready to start work on our tutorials I thought I would just take a moment to post on something that has had me rapt since I first came across it a couple of years ago. The TV series "Breaking Bad".

This show is awesome. It has everything you could possibly want in a show.

1. It has a great plot and storyline - A career chemist turned high school teacher gets lung cancer and decides to manufacture crystal meth on the side.
2. Great comedy
3. Great action
4. Great characters
5. CHEMISTRY YAY!

So while it doesn't specifically spell out how to make crystal meth it does come close and a lot of side plots involve even more nifty MacGyver-esque (which is also a totally awesome show) chemistry.

If you haven't seen this show yet I suggest you get watching as it is awesome! I have posted a small clip that I think sums up how awesome this show is whilst showing the cool chemistry side of it too.



Note the use of HF in the bathtub LAWLZ (You'll have to watch the show to find out just why they had to dispose of a body named Emilio (P.S. See A Night At The Roxbury EMILIOOO!)) Season 3 starts March 2010 I think.

Further Education for Chemistry Undergrads

While it has probably been done several times before, MSG and I have decided to knuckle down and share a little of our knowledge and experience in an effort to teach and enlighten undergraduate chemistry students.

While it isn't much it will most definitely save a lot of time as well as a lot of headaches on our end. So MSG and I decided to put together a series of experiments that will illustrate the basic techniques that students should learn starting from first year in a chemistry lab. And yes, that includes the lazy slack-arse Engineering students who are all but hopeless (most likely due to excessive alcohol consumption performed in their ample spare time).

We hope to begin with the very basics, e.g. seperatory funnels, pipettes (both mechanical, glass and pasteur) through to the more technical, e.g. recrystalisation, column chromatography and probably a lot more.

Hopefully, if we can figure it out we will be putting youtube links of some experiements that the second year undergrads do in the second semester. We will probably source some of the other reactions from first and third year as well to show basic and advanced techniques.

All things willing everyone should benefit from these posts regardless of whether they have been done before or not. So keep an eye on this space kiddies.

Superfreakonomics

Got my copy of Superfreakonomics today, and I can't wait to get stuck right into it. [EDIT: for those who are unfamiliar with Freakonomics, here is the official site and blog, and probably more importantly, the wiki entry]. I thoroughly enjoyed the first one, and the authors reckon that this sequel is much better than the first. Well of course they would, but nonetheless I am looking forward to spending some time away from non-chemistry. I'm still working my way through Nicalaou and Snyder's Classics II but I think my PhD would really benefit from my brain taking some time away from curly arrows, pentagons and hexagons, and RBFs.

The success of the Freakonomics series made me think: are there any chemistry books written for the general public that has received such high acclaim? If so, I'd certainly like to know what they are. The Freakonomics series are hugely popular. On the day I bought Freakonomics (the original) four years ago, it was in the top 10, if not top 5 (memory fails me) bestsellers. Today, according to the NY times, Freakonomics is number 1 paperback non fiction, and Superfreakonomics is number 2 hardcover non fiction. When did a popular science (and in particular, chemistry) book make such a big splash?

Pros and Cons of Two Organic Chemists Dating - Add your experiences

Pros

You can roll over in the middle of the night and ask "What do i distill TMSCl over?"

You will always be able to understand each others frustrations: "I lost 3 months work today because it fell in the oil bath" or
"I just racemised my product after 20 steps!"

You won't have to explain jargon such as NMR, enantiomers, flash chromatography, GC-MS etc.

They can proof read your experimental / publications etc.

Cons

You can't have a break from chemistry at home.

You may compete for the same job / grant proposals

After finishing your PhD(s), you are usually expected to do a postdoc overseas. Trying to find a postdoc for both in the same place is difficult.

You may be, or end up working together in the same building / lab and see each other all day.

Trapped in a chemistry circle. Possible limited associations with normal people.

Iron Catalysis

Recently, I have been having trouble with performing a Wittig reaction on a particularly unstable aldehyde that had been giving me all sorts of problems. While a literature procedure exists to synthesise and isolate the said compound the amount of material that remains after workup is volatile and decomposes readily whether under argon or even stored in the freezer.

But, just the other day MSG gave me an interesting paper. It shows the use of an Iron catalyst (FeCl3) to form C(sp3)-C(sp3) bonds via an alcohol and an alkene. This would be extremely handy for me if it works as I am able to make the alcohol realatively easily and it is stable. However, while it won't give me my product in one step it will provide an alternative method of formation.

Anyway, seeing as this is a chemistry blog I thought I would try my hand at going through this paper while I read through it.

Basically, the authors intended to couple an alcohol to an alkene in the following manner.

The resultant C-C bond is particularly handy as the alcohol functional group remains and provides an excellent handle for further reactions to the center as well as having the potential to be removed at a later step in further synthesis.

From previous investigations the authors had found that Lewis acids in conjunction with a metal catalyst would achieve the desired coupling. However, the Lewis acid was used in excess amounts and more to the point you are using expensive metals, which the Boss has already told us is best avoided especially on a tight Aussie chemist budget (unless you are my old boss who is a legend in academia and gets some nice grant money).

Fortunately for the authors they found an alternative reagent that provided not only a nice metal catalyst but, lo and behold, it's also a Lewis acid! ZOMFG its FeCl3!

Initially, the authors investigated a test system with several different solvents in order to gauge any solvent effects. Their initial substrates remained constant. 3-Phenylpropanol (their alchol) and 1,1-diphenylethylene (the alkene). Their results showed that dichloroethane (DCE) gave the best results although I find it strange that they didn't try DCM which is a much more common solvent in labs. :S Nevertheless it was deemed "essential" to the reaction and was shown to promote the reaction when used as an additive in other solvent systems.

A few other iron salts were tried as well as a varied amounts of catalyst along with some promoting ligands (e.g. TMEDA, NEt3 and DACH) but to no avail and it was seen that FeCl3 in these proportions was goldilocks.

A number of reations were performed on various alcohols and alkenes and all showed that the reaction did work quite well. They explained the proposed mechanism to work in the following manner.

This is a handy reaction to have if you cant form a stable aldehyde allow you to perform a Wittig reaction. Also, FeCl3 seems like a fairly inexpensive reagent especially when you can use it in catalytic amounts. I will have to give this a shot some time soon.

Aside from the second word in the article being a spelling mistake (ze Germans are slipping), the paper illustrates quite well this new application of iron to develop C-C bonds without the use of expensive metals etc. There is also another similar paper on the use of metals in a similar manner that can be found here.

Zhang, S.-Y. et al, Angew. Chem. Int. Ed. 2009, 48, ASAP

JOC Fail

When you publish in any decent journal article these days you are expected to submit a nice picture to go in the table of contents. These pictures can be colour and often a lot of time and effort goes into simply designing the picture of your article.

So it's good to see when someone goes above and beyond to supply the journal with a nice picture. In this case, a JOC article.

I was scanning through my newly set up RSS feed for JOC ASAP articles and saw this little gem that I had to share here. I have no idea what the article is about other than building aromaticity in a ladder-like structure.

Pyrazinacenes: Aza Analogues of Acenes

Gary J. Richards, Jonathan P. Hill, Navaneetha K. Subbaiyan, Francis D’Souza, Paul A. Karr, Mark R. J. Elsegood, Simon J. Teat, Toshiyuki Mori and Katsuhiko Ariga

J. Org. Chem., Article ASAP

Publication Date (Web): November 2, 2009

Now while it is a great picture and I am sure the guy now feels good about the height he has gained via synthesis of these molecules I am not above pointing out the funny points in this picture.

1. Why would you include a picture of yourself in a chemical synthesis?
   
   
2. Why would you send the picture in to a reputable publication like JOC?
   
   
3. Why didn't you make sure the picture was accurate before sending it in to JOC?(N.B. Final structure is almost definitely missing some nitrogens from the second from top ring system).
   
   
4. You shouldn't advertise the fact that you don't know how to safely operate a step ladder.

But regardless, I must thank the author, you brightened up an otherwise dreary day. HILARIOUS!!!

Breaking News

Modern Talking are still alive and back. Have a look at this wonderful medley. Appearently they did not get younger, but still are rocking the house!