Art of Synthesis

It is a great as well as a trembling moment when something that has been established for over a century is proven wrong. One such instance occurred in 1919, when Eddington's team verified General Theory of Relativity against Newton's Gravitation, literally disproving him over Einstein. This time, it may not be as legendary as overthrowing Gravity, but we are shocked to discover what we have been doing as a valid reaction mechanism is completely wrong. Jakob Meisenheimer published his famous paper " About Aromatic Nitro body Reactions " in 1902. And since then, over the past century, research has culminated in what is now known as Aromatic Nucleophilic Substitution , where nucleophilic substitution takes place at electron-poor aromatic rings. This is already of great interest because nucleophilic substitutions do not occur at vinylic and phenylic positions as the corresponding transition states or the carbocation intermediates are very high in energy. Th...

Introduction:  - still, it is not often that we find Art in Science. Although, as humans, we can argue that every piece of work is an art, be it setting up a reaction or writing a screenplay. But, let's cut the crap okay, there is no aesthetics in doing pages of calculations on the solution of Schrodinger equation or finding out the local minima of potential surfaces in a multidimensional space. The very definition of Art  is rooted in the fact that it demands an appreciation of its creative beauty. It is what you feel after reading a Rumi poem, or when you marvel at a da Vinci masterpiece. And that feeling is not always easily found in science, except a few cases. And those cases are the topic of this introduction. Before I go further, just for the sake of clarity, let's make a layman's list of 'what constitutes an art'. Identifying traits of an Art: You appreciate it naturally, especially more when you understand it Often hard to understand, especia...

Mitsunobu reaction is 50 years old and still is of high importance to synthetic organic chemistry   Although we have discussed it from the point of view of Remove-that-OH agenda, it was originally developed as just another ester formation reaction that results in inversion of stereochemistry. The success of the reaction was immediately followed in its use of natural product synthesis ( Yaay !). Let's then go into the reaction itself. Reaction overview: Substrate : primary/secondary alcohol ( 1 ) Nucleophile : carboxylic acids, hydrazoic acid ( 2 ) Reagents : Triphenylphosphine ( 3 ), Diethyl Azodicarboxylate (DEAD) ( 4 ) Product : Ester/azide ( 13 ) Stereochemistry : Inversion of configuration. Mechanism: I am going to break the reaction mechanism into steps, in a way that makes the connection with the previous post, where I presented how you can design the whole reaction from scratch. If you don't remember the sequential deduction it would be a good t...

Those of you love to do some organic conversions now and then (Like 'Conversions and espresso' sounds like 'Netflix and pizza'), must have felt the frustration when you had to face the challenge of removing an OH leaving group. 'Cause that group is stubborn as hell. You can almost never remove an OH group by a direct nucleophilic substitution at the carbon center. So, what do you do? There must be ways to avoid this, and there are, which you must be knowing if you have faced this problem several times. There are, roughly speaking, 3 possible strategies … or Tricks to remove an OH. If S N 2 doesn’t work, well, try something else : Most nucleophiles have, to some extent, a basic nature. So, the conditions in which    S N 2 reactions commonly works are basic, neutral at most. But if that’s not going to work then we can change the conditions from basic to acidic. In an acidic medium, the OH group will take up a proton, becoming O...