The Most Annoying Exceptions in Org 1 (Part 1)

by James

in Alcohols, Alkenes, Alkyl Halides, Organic Chemistry 1

One of the common complaints you hear a lot from people learning English is that there are just so many exceptions. The plural of “goose” is “geese”, but the plural of “moose” is “moose”.  Why is that? Who knows. You just have to memorize it. (Edit: well, when learning English, you do have to memorize it. But that’s not going to be the point of this post. Maybe this wasn’t the best example to choose).

Organic chemistry is also rife with many exceptions (real and apparent) to the beginning student. It isn’t long after you learn about Markovnikoff’s rule, for instance, that you learn when this “rule” is broken. And that’s just the first of several exceptions that come up in the course.

So one common approach is to simply memorize these exceptions, the way you might memorize “i before e, except after c”.  While a memorization approach could be effective for exams that test the ability to regurgitate book knowledge, however, any instructor looking to test problem-solving ability could easily design a test that will render such pure memorization efforts ineffective.

Behind every exception there is a deep reason why things occur the way they do, and these reasons illustrate deeper principles of organic chemistry.  The purpose of today’s post is to illustrate the key concepts behind some of the most common “exceptions” in Org 1.

Annoying exception #1 : Hydroboration. Not long after you learn about Markovnkoff’s rule, you learn that when you add a borane to an alkene, it adds the “opposite way”. What’s going on here? Interestingly, it isn’t as much of an exception as it seems. Things make a lot more sense if you examine the relative electronegativities of the atoms being added. In all cases – whether adding HBr, HCl, H3O(+), or BH3, the most electronegative atom always adds to the most substituted carbon, because that’s the carbon that best stabilizes positive charge. In BH3, it just so happens that the most electronegative atom is hydrogen. It’s not really that weird after all.

1-hydroboration

Annoying exception #2 – “Peroxides”. HBr by itself does Markovnikoff addition to alkenes but if peroxides are present, it adds the opposite way. Again, one approach here is to just memorize that if you see “peroxides”, it goes the other way. However, it isn’t much more effort to understand that what is going on in both cases is exactly the same: just as in the above example, an electron-deficient intermediate (carbocation or radical) ends up on the most substituted carbon.

2-peroxides

Annoying exception #3 – the nucleophilicity of halides in polar protic vs. polar aprotic solvents. Iodine is a better nucleophile than F(-) in polar protic solvents, but fluoride is a better nucleophile than I(-) in polar aprotic solvents.

What’s the key lesson here? There are really three key trends here. 1)  nucleophilicity is decreased by hydrogen bonding – and a nucleophile in a protic solvent will be surrounded by solvent molecules it is hydrogen-bonded to 2) hydrogen bonding ability decreases as one goes down a column in the periodic table 3) in the absence of hydrogen bonding, nucleophilicity increases with basicity.

In fairness, thiis example is tough, because the key trends oppose each other and the relative nucleophilicities are not something that could have easily been predicted from first principles, but result from actual measurement of reaction rates. Furthermore, basicity and nucleophilicity are measured by different yardsticks – one (basicity) is measured according to equilibrium, and the other (nucleophilicity) is measured according to reaction rate. There’s no getting around having to memorize these trends, but understanding why they operate is key.

3-polar protic
Annoying exception #4 – Primary carbocations and radicals are unstable, unless they are stabilized by resonance. This example illustrates the importance of resonance, which is one of the key stabilizing factors in organic chemistry. In general, any factors which allow a charge (or unpaired electron, in the case of the radical) to be distributed over a larger area tends to be stabilizing, which makes up for the otherwise unstable situation of having a carbocation on a primary carbon.

4-allylic

That takes care of some of the common “electronic” effects. Next post, we’ll look at some of the “steric” effects that lead to weird exceptions in Org 1.

 

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{ 9 comments… read them below or add one }

zohra

I’m somewhat confuse… just memorize? I can do that.

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james

Thanks for pointing that out… the example in the first paragraph was probably not the best.

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Moyukh

Very helpful, I must say! Awesome! Just one point. The point #3.. In the diagram, the last two images both show fluoride being surrounded by DMSO. I think one of them should be Iodide.

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jye

I’m a Korean student studying Organic Chemistry for entering medical school. I’ve studied Organic Chemistry for a while but always thought that I’m missing something very important. But since I found your website coincidentally, I can understand the things that I just memorized before. I’m very appreciate that. Everyday I come here and I see myself not just memorizing reactions but just feeling them..

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james

Excellent. If you learn just one thing, I hope it’s that there are key patterns and rules in organic chemistry, and it’s not just arbitrary.

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asdf

Hi, this is a great website!

I just noticed, though, that the McMurry 8th ed. textbook gives a different explanation for the Anti-Markovnikov hydration reaction with borane. On page 224, it says that the hydroboration reaction does not occur with a carbocation intermediate, but instead proceeds as a concerted reaction in which Markovnikov regiochemistry of the boron atom is disfavored by steric hindrance. This mechanism is supported by the fact that hydroboration results in the syn addition of water.

Actually, on looking at your mechanism again, the concerted step appears to be present. However, I think that the syn stereochemistry is best explained by sterics. Otherwise, it leaves the question of racemization hanging.

Thanks for maintaining this website!

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Aaron

Hi!

Just wanted to point out that in this case, sterics explains the anti-Markonikov addition in hydroboration, NOT the syn stereochemistry. (Of course, the explanation provided in point #2 of the post is also a sensible explanation for anti-Markonikov addition!)

The concerted addition is what explains the syn stereochemistry.

Racemization does occur actually, since the concerted addition can occur either above or below the plane of C=C.

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Tom

This is helpful! Thanks for taking the initiative and wanting to teach, regardless!

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Eric

Thanks! Now I understand why Nuc decreases in polar protic solvents. But one question, and it seemed to stump some fellow classmates: suppose you have a strong Nuc/weak base in a polar protic solvent. If the C is secondary, will it prefer to undergo Sn1 or Sn2? What if the beta carbon has a double bond, would that increase the likeliness of an Sn1?

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