Photo session

Today I got to take some photos of my friends' little son. He is 5 months old and we only had a very short amount of time to take the photos, but I was very happy with the results. Here are two of them:

The little guy showed a lot of patience, and it is the first time I have a photo session with a baby. It is hard as hell to make them look at the camera or to get them to pose as you would like... but hell it is worth the time :). I used my reflective screen (silver) and my flash (SB900, Nikon) together with a 50 mm f1.8. The aperture was set to f2.2 most of the time. I do not know what is the best aperture to use, but had a hard time to focus correctly using f1.8 (he moved to much).

Well, I just send all of the picts to my friends... lets hope they like :))

Eschenmoser's Salt

On monday, just gonna start easy on the lab. Going to make some kind of alkylation using Eschenmoser's salt (N,N-Dimethylmethyleneiminium iodide), which is a hygroscopic crystalline substance having a melting point of 240 °C (although I have seen everything from 117 °C and 147 °C as melting points, but this is the one you find at Sigma and other serious producers).

Safety Information

Symbol	GHS07
Signal word	Warning
Hazard statements	H315-H319-H335
Precautionary statements	P261-P305 + P351 + P338
Personal Protective Equipment	dust mask type N95 (US), Eyeshields, Gloves
Hazard Codes	Xi
Risk Statements (Europe)	36/37/38
Safety Statements (Europe)	26-36

It is used to prepare compounds of the type RCH2N(CH3)2, and is very compatible with enolates, enolsilyl ethers and ketones. The mechanism of reaction is quite simple, and I have seen many different solvents and bases being used (like Et3N and Dichloromethane, or Et3N in acetonitrile).

Lägg till bildtext

Now, the salt we have at the lab is quite old and dirty, so I have some different alternatives:

• Buy a new bottle
• Recrystallize the dirty compound
• Synthesize new salt
• Use it as it is

Of coure, I'll go for re-crystallization of the outdated compound. But, to synthesize some more should be quite easy:

Well, so I guess I will have to recrystallize then....

Uppdate,

So, I said I was planning to recrystallize the salt. I did not manage to find a proper solvent for recrystallization so I opted to test the salt as it was, since I supposed I would get some product and then I could purify it. I was quite wrong. I did run the reaction (in dry Acetonitrile, reflux) and got a by-product in HUGE amounts. This by-product had a molecular mass of 12 a.u. higher than the expected compound. So, of course, a carbon was added to my molecule somehow.  

I got curious to know what this was and started to purify the stuff and run NMR (H, C, COSY, HSQC, HMBC) to see what the hell was happening. It turned out that there was a big amount of decomposed Eschenmoser's salt (i.e., it had decomposed to formaldehyde). So what was happening was that the formed product was subjected to a second enolization, which resulting in the attack of formaldehyde present in the mixture. Apparently, there is a publication about this reaction and would I have come around this problem 15 years ago, I would have invented a new methodology 8-)).

Reaction of arylketone with Eschemoser's salt

So, I really had to purify the salt, and the best way was actually to run a bulb-to-bulb. I crushed the salt (with a mortar) and put the temperature at 80 °C and the pressure at 8 mbar. It did the trick. All paraformaldehyde sublimated. Raising the temperature to 95 °C resulted in slow sublimation of the Eschenmoser salt. I did this quite quickly and I do not think those temperatures are optimal, but the product was pure enough for my purposes. Now the reaction is running and I hope I can get some pure product by tomorrow :))

BJJ training 20120926, techniques from half-guard

So, today Wednesday Nils was the instructor. He is quite good attacking from the half-guard and just being annoying with his sweeps from any guard. So, he shares with us three different techniques he uses. I know two of them will be very useful for me anyway. The language on the video is Swedish and it is just a bit shaky, but hell... what you gonna do.

So, in this technique is quite important to know. Is like a basic form the half-guard (I am not very good from half-guard though ://). Very important is to really lock his leg with your "free leg" and grab the back of your opponent really tightly. If your opponent manage to avoid the first sweep (which most people with some BJJ experience do), then the second sweep is very useful and works very well (see the clip at 2:10 approx to see the second technique).

Here is the third technique.

A little bit more unusual and I have actually never had to use it. But might be good to know, you could bait your opponent to go to that position. 

Design of Experiments (DoE)

Well, there is a lot of discussion whether to use DoE on method development when working in organic chemistry or not. According to me, you should use it as fast as you can. I mean, the industry has adapted to this quite well and it is now a standard procedure so I do not understand the reluctance from academics to adapt to this powerful tool. There is an excellent article by Torbjörn Lundstedt et al. about DoE (here).

One major reason I like DoE is, I guess, doe to my engineering background. As an engineer, you like graphs, you like correlations and you like computers. DoE offers all of this and assist you in your work. In the paper to which I linked (see above), they address some of the common objections from people reluctant to use DoE. Here is a summary of the normal arguments people use to avoid using DoE (that I have heard my self, there are many more for sure)

“Why Bother When the Results Are Blindingly Obvious?”

Personally I think there is a lot of ego in this kind of statements. Of course you have to have an idea of what will work and what wont work, but given the fact that chemistry is affected by so many parameters (temperature, time, pressure, reagents, rate of addition, catalyst, solvent, concentration, pH, etc), it is worthwhile to try a small screening design at the beginning of any project. At the end, all information might be used and the effect of a given variable can be calculated .

Many people expect DoE to provide miracle results. But, visualize that one-factor-at the time is the counterpart of running with boots, DoE is the counterpart of running with proper running shoes. Having to run is a pain in the *ss no matter the shoes you choose, but you cannot deny that is h*ll more easy to run with Asics Gel-Scout than using a pair of gothic boots.

What If We Miss a Factor? Will My DOE Work Not Be Wasted?

If you miss a factor using DoE, you will probably miss it using the usual approach (one factor at a time). With DoE you can actually use Lack of Fit tests and residual analysis  which may help you find that missing variable (with a little bit of thinking and analysis).

Other stuff you may hear are that the resources are limited. But, using this argument just proves that you have missed the whole point of DoE, it is designed to minimize costs and the amount of experiment that have to be performed in order to find optimal responses. The thing is that you see in beforehand the amount of material that will be "wasted". Changing one-factor-at-the time, you waste while you progress and at the end, you do not realize that the amount of material used just surpassed the amount of material that would be needed to make a screening design and an optimization.

So, I do not have so much more time to use here. I may be wrong in some points, but my advice for them who are new at DoE in method development are (besides reading the papers above)

• Search the literature. Remember, four weeks in the lab will save you four hours in front of the computer (or library).
• Start with a screening design. What parameters are important? (usually, temperature and solvent have to be included...)
• Do not forget to try to minimize the number of variables used. Sometimes using A, B and C (three variables) is just as meaningful as using ratios of these factors (i.e. A/B and C/B, which give you two variables instead of three)
• When you are done with the screening design and have found the most important variables, is time to optimize. Response surface design is usually the way to go.

Well, the reason I posted this is because of a little bit of frustration I feel due to the almost non-existent use of DoE at academic organic chemistry labs, while this is a method that is a must out in industry. I have been striving to work with it as much as I possibly can, and one day, I hope it will be a tool as frequently used as an analytical HPLC. 

First Post and Presentation

Well, I guess it is time to try to keep track of myself and what I am doing. This is by no means meant to instruct anyone in anything, but the idea is for me to keep myself busy and improving. If I can share some ideas with someone else it is just a bonus for me.

I will post stuff about chemistry (mostly problems I encounter and hopefully the solutions I find), photography, Brazilian Jiu-Jitsu and I guess some philosophical and political stuff.



So, who am I? Well, if you are asking that in a professional way, here is my CV. The rest of this text will be very informal.

I am a Colombian/Swedish citizen, living in Sweden since I was 14 years old. I was born in Pereira, a medium-sized city in Colombia which is known as the capital of the coffee triangle (the other two cities are Manizales and Armenia).

Since 1996 I have been living in Sweden. I started in a small city called Flen, and in 1997 I moved to Stockholm (the city who chose to call it self "the capital of Scandinavia" and pissed off the people of  Oslo (I guess Copenhagen is to confident of its real position to argue about niceties).

Anyway, in 2001 I decided to become a Chemical Engineer and moved to Uppsala, where I met my wife Julia. In 2006 we got our lovely daughter Miranda and another little baby is on its way at the moment (planned to november 2012) .

Well, lets go back in time a bit. Before finishing my studies, I decided  to become a medicinal chemist, and my grand plan was to end up working in scale-up or process development. Therefore, at the end of 2006 I chose to start my Ph.D. studies at the Department of Medicinal Chemistry, also in Uppsala, supervised by Prof. Mats Larhed. I had the opportunity to work in the area of Palladium catalyzed coupling reactions (publications here, here, here, here and here) and HIV-protease and integrase inhibitors (publications here and here respectively).



I get a lot of questions about how it is being a Ph.D. student in organic chemistry. First of all: I did never consider myself to be a student. Of my five years of education, I only had to go three courses, the rest of it was plain work. What I  most enjoyed was the possibility of driving your own projects. It is like having your own mini-coorporation. You learn a lot about planning, finding information and applying it to real case scenarios. Moreover, you get the opportunity to really understand a subject to its core and to test own theories. If sometimes I wanted to test a new purification technique, no problem, go ahead. If it did not work, well, I always tried it at least three time before giving up. Most of the times I got it right after a few modifications that suited my style of work better. Being a Ph.D. is like being a child again; a curious child. You are allowed to test and try whatever you like (almost), as long as you manage to keep delivering results from your main projects.

One of the things I loved the most as a Ph.D. student, and that I will miss now that I have defended, is the teaching. Some people detest this, but I just loved it. It is quite satisfying having a big crow of students in front of you smiling because you managed to explain reaction mechanisms, trends and patterns in a way they understand. One of the most important things about teaching is, in order to make a good job, you actually have to understand the subject pretty well. Planning the lectures/seminars/labs gave you the opportunity to discover your weaknesses and go fix them. Moreover, most students are very fun and outgoing.


Well, I guess I will finish here for now. I will continue posting less about me and more about chemistry, photography and BJJ in no especial order.

Peace

// Alejandro