Mechanism 3

Thus, now that I have a small bit of time, I might want to quickly head over Mechanism 3.

As recommended, this is a Fries Rearrangement. Without anyone else present, this is a genuinely exhausting response with numerous sources itemizing potential components (here and here). What I discovered fascinating was that Bagno et al. distributed an exceptionally pleasant NMR and DFT study taking a gander at the itemized component of the Fries Rearrangement of 3-methoxyphenyl formate (JOC, 25, 2006, pg.

I truly like system papers, there is something in a general sense exploratory about them. In this time of exceptionally various synthetic themes discovering their route into the diaries, it is invigorating to see that great obsolete robotic examinations are as of now being carried out. This paper specifically was luring to peruse on the grounds that the creators join exploratory results (NMR: 1h, 13c and 11b) with computational (DFT) ones to examine the framework.

The fundamental instrument they propose for this framework is appeared:

Step #1: The Lewis corrosive directions to the carbonyl oxygen. All things considered, "duh!" you may say, however consider why you say this. It is safe to say that it is "self-evident" that the Lewis corrosive arranges here? Assuming this is the case, where is the proof to help it? All things considered, for this situation the creators make a decent showing of giving some persuading NMR proof.

Step #2: Through one of two cyclic move expresses, the adduct reworks and takes out formyl chloride. Once more, NMR proof is given to help this.

Confirmation is given to backing the regioselectivity (ortho v. para) of the response.

I am not going to go into the bare essential of the paper, there is simply an excess of and I would inexorably forget something. I recently needed to draw it out into the open. This is great science, you ought to simply go read it. The creators additionally benefit a vocation of qualifying their results and conclusions, strengthening the thought that diverse substrates and conditions may adjust the response way and consequently distinctive models may apply to distinctive frameworks. This is a thought that is lost in some individuals, the way that instruments are not composed in stone, distinctive substrates, solvents, temperatures and so forth can change the response way.

Doubtlessly, the NMR proof, the clarifications and the DFT computations speak to a decent bit of work that the creators ought to be glad for and JOC ought to be pleased to distribute.

Chemistry

Chemistry, a branch of physical science, is the study of the composition, properties and behavior of matter. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds. Chemistry is also concerned with the interactions between atoms and various forms of energy. Chemistry is sometimes called "the central science" because it bridges other natural sciences like physics, geology and biology with each other. Chemistry is a branch of physical science but distinct from physics. The etymology of the word chemistry has been much disputed. The genesis of chemistry can be traced to certain practices, known as alchemy, which had been practiced for several millennia in various parts of the world, particularly the Middle East.

Chemistry

Chemistry, a branch of physical science, is the study of the composition, properties and behavior of matter. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds. Chemistry is also concerned with the interactions between atoms and various forms of energy. Chemistry is sometimes called "the central science" because it bridges other natural sciences like physics, geology and biology with each other. Chemistry is a branch of physical science but distinct from physics. The etymology of the word chemistry has been much disputed. The genesis of chemistry can be traced to certain practices, known as alchemy, which had been practiced for several millennia in various parts of the world, particularly the Middle East.

Marcgraviaceae

Marcgraviaceae is a neotropical angiosperm family in the order Ericales.

The members of the family are shrubs, woody epiphytes and lianas with alternate, pinnately-nerved leaves. The flowers are arranged in racemes. The flowers are accompanied by modified, fleshy saccate bracts which produce nectar. Flowers are pentamerous. The fruit is a capsule.

Reproducibility

(Note: I modified this a wee bit on 12.17.06, nothing big, just minor rephrasing.)

In the December 4th, 2006 issue of Chemical & Engineering News is a good article on the issues a researcher may face when their work, or the work of a fellow scientist, cannot be reproduced. The notion of reproducibility is a fundamental pillar on which scientific discovery rests. How can we as scientists ever hope to move forward if the work we rely on for direction and precedence cannot be reproduced?

It should be clear to all my readers that most cases (at the ones I know about) of irreproducible work come the academic world. Industry has multiple checkpoints for a product or a process, so errors or mistakes are caught pretty quickly. Things are different in the Ivory Tower. Let me illustrate this with a story…

I had a postdoc in a large lab (~50 people) that contained researchers from a multitude of fields; from toxicology to organic chemistry. Given that the lab was so large, the PI felt it was reasonable to just give a general research direction to individual researchers. For instance: “Milo, try to develop a better assay for this enzyme.” We would then plan the project, execute experiments and write journal articles on our results, all on our own. More often than not, when we handed a draft manuscript to the PI, it was the first time he was seeing how we approached the project and the data we generated. He was not real good at keeping tabs on his researchers and on their techniques and he seemed lax at challenging our conclusions. I guess he was too busy getting grants.

Now, this system tended to work moderately well (which is quite surprising), most of the researchers were contentious enough to repeat experiments, to ask to opinions from their peers, to use statistics and to generally do all they could to ensure the results were real. However, there was one guy who published two synthetic papers that I needed to follow. I was asked to scale up one of his molecules for a collaborator (the researcher in question had left California at this point), so I pulled up the papers and set to work.

For the life of me, I could not make the molecules. I even had a colleague try the prep, and he failed as well. The boss kept saying: “Milo, it is in the paper, so I don’t see why you cannot follow his prep. It is published!” Now, I am not talking about getting 50% yield instead of the published 79% yield. I am talking about not getting anything. Nada. Zip. Zilch.

So I called the now departed postdoc and explained my problem and asked for advice. Instead of being helpful, he accused me of being a hack and trying to discredit him, this was not the response I was anticipating.

WTF? I just wanted to reproduce his work, but I could not.

Alas, 6 weeks later I had my own route to the molecules. These molecules, as luck would have it, behaved better in the biological model than his “identical” ones.

Was this a case of fraud? I don’t think so. I think that this is a case of poor research ability and poor oversight. Since the PI is the one who will ultimately take credit for positive results, the PI should also move heaven and earth to ensure that their postdocs and student are generating reproducible results. Had the PI in question paid more attention to this particular researcher, he would have known that he was sloppy, did not keep a note book, and was simply a poor chemist.

I don't think a PI needs to check every NMR, every TLC and read the notebooks every night. I also do not expect a PI to give his postdocs and grad student all the answers. I do expect a PI to teach the postdocs and grad students how to do good, solid research, how to think and how to critically analyze data. He also needs to teach them the value of reproducibility. To be blunt, if a PI in unwilling or incapable of doing these things then maybe they need to think of another career path.