Anslyn pp. 537 – 626

I’m beginning to see what Tom Lowry meant when he told me physical organic chemistry was dead in the USA a few years ago. I can see why.  It seems to have done itself in.  This chapter on mechanism of 20 some reaction types is so complete and clever, that there seems to be little else to do with the classic organic reactions we studied and worked with 50 years ago.

Whether or not organometallic chemistry is equally well understood, is unclear to me at this point.  I’ll have to wait until Chapter 12 (pp. 705 –> ) to find out.  There was very little going on in the 50’s and 60’s aside from the Grignard reagent, chromium oxidations and ferrocene.   However on p. 560 we find out that they still don’t really know the structure of the Grignard reagent.  I wrote my junior paper on it in ’58.  Interestingly, there is some evidence for a radical mechanism some of the time. 

p. 538 — Good to see Edwin Gould getting a mention (by his last name only).  His book “Mechanism and Structure In Organic Chemisty” was the Bible for Physical Organic Chemistry in ’60.  He was a good amateur violinist and I had the pleasure of playing with him at a chamber music festival for amateurs at Interlaken, Michigan years ago.  Sad to note that he passed away at age 85 14 October ’11.  It’s even more interesting that he was not an organic chemist when he wrote his book, but rather a hard core physical chemist.  He was still pumping out papers in 2010 some  60 years after getting his PhD in 1950.  RIP Edwin.

pp. 1061 – 1074 — Appendix A.5  — This was suggested reading before plunging further.  It’s incredibly basic arrow pushing, detailed and specific.  Sort of ‘No organic chemist left behind”.

p. 543 — “The acid catalyzed hydration of most carbonyl structures involves alternative C of the reaction cordinates in Figure 9.13”   Why not give the page number for backward references.  The indexing software should accomodate this.  If not get some new indexing software. 

P. 548 — The cleverness involved in teasing out mechanistic details for what used to be a fairly simple reaction (HX addition to an alkene) is impressive.  Termolecular collisions — who’d a thunk it? 

p. 548 — The squalene –> lanosterol conversion, and the enzyme holding the reactant in place so the correct stereochemistry is obtained, while NOT reacting with the carbenium ion intermediates — are all reasons why it seems improbable (to me at least) that this exquisite chemistry arose by chance (or natural selection operating on chance events if you prefer).  The steroid nucleus is very fundamental to membrane fluidity, and individual steroids are intimately involved in metabolism, so the reaction is fairly fundamental for the existence of multicellular organisms. 

p. 552 — Great to see the inverse isotope effect put to some use.  Caution — although .53 isn’t higher than .8, it does represent a more pronounced inverse isotope effect. 

p. 553 — Although I’ve been snarky about kinetics — I never would have suspected that the kinetics of iodination of an alkene could have been third order.  I’d love to see the data points which separated a cubic rate dependence on iodine from a quadratic rate dependence.

p. 555 — Since steric effects are apparently in hydroboration (antiMarkownikoff etc. etc.)  It would be nice to know how big BH3 actually is.  I couldn’t find this anywhere.

p. 560 — They still don’t really know the structure of the Grignard reagent.  I wrote my junior paper on it in ’58.  Interesting, that there is some evidence for a radical mechanism in some cases. 

p. 561 — Why isn’t the Burgi Dunitz angle exactly that of sp3 hybridization (109 45′)? 

p. 573 — Good to see that high level theory explains carbenes — can’t wait to see how this stuff is actually calculated, but it’s several hundred pages away. 

p. 574 — “Diazomethane explodes on contact with ground glass joints”.  I don’t think this was known ’60 – ’62 when I was trying to work with the stuff.  We knew it was explosive, but weren’t sure just why.  Tom Lowry also had to work with it and, as I found out later, was just as frightened of it as I was.

p. 574 — Basic treatment of N-nitroso ureas generates carbenes.  Interesting as nitroso ureas (such as N-ethyl-N-nitrosourea) are used to produce mutations in experimental animals.   [ Cell vol. 89 pp. 487 – 490, 641 – 653, 655 – 667  ’97 ]  

Not many comments over all these pages.  The chemistry is great as is the understanding of mechanism.  But it’s so good, that it makes me wonder if there’s anything significant left to discover.  Is this why physical organic chemistry is said to be dead?

p. 595 — Aconitase — Interesting chemistry.  But the control mechanisms in the cell are tricky.  Because of the iron sulfur cluster, it exists in a different conformation when iron is deficient (e.g. it no longer has the cluster).  In this form it migrates to the nucleus to turn on transcription of genes which increase the cell’s ability to get iron (by stabilizing the messenger RNA for proteins like ferritin which bind iron).  Organic chemists should love subtlety like this. 

p. 597 — Why does attaching an oxygen or a nitrogen to an imine make it more stable (to hydrolysis)?

p. 606 — “If we have a 95% coupling yield, but we have to perform the reation 40 times to make a peptide with 41 amino acids our overall yield will be .95^40  = < .13.”  This is exactly the problem physicians face when ordering chemistry profiles (panels) — a measurement of a number of unrelated blood constituents — say glucose, sodium ion, calcium ion etc. etc.  When the number of constituents is even 20 the chance of them all being normal (e.g. in the range into which 95% of people fall) is only 35%.  It has to be this way if all the 20 constituents are statistically independent of each other — and usually they are and if they have essentially a Gaussian distribution (bell curve) which they largely do.  This is where the 95% comes from — it includes almost exactly two standard deviations on each side of the mean of a bell curve.  Statistical independence explains the choice of particular constituents to study.  Try explaining why you aren’t going to follow up a minor abnormality to a nervous patient using statistics.  

p. 609 — “Sigma complexes can be observed spectroscopically”  — How do you know what you are seeing spectroscopically is actually a sigma complex?  How was the spectroscopic signature of a sigma complex determined?

p. 616 — How do you make a phenyl radical?
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Comments

  • Monado, FCD  On November 3, 2011 at 1:17 am

    The squalene –> lanosterol conversion, and the enzyme holding the reactant in place so the correct stereochemistry is obtained, while NOT reacting with the carbenium ion intermediates — are all reasons why it seems improbable (to me at least) that this exquisite chemistry arose by chance (or natural selection operating on chance events if you prefer).

    Uncounted quadrillions of molecules, innumerable molecular collisions, and eons of time–anything could happen.

  • Curious Wavefunction  On November 4, 2011 at 2:58 pm

    -while NOT reacting with the carbenium ion intermediates

    The likely explanation here is an intramolecular (easy) vs intermolecular (harder) reaction.

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