The New Clayden pp. 222 – 268

p. 228 A picture of a Dean Stark head would be useful. 

p. 230 — Second paragraph from the bottom, 4th line ‘hemiacetal’ should be ‘hemiaminal’

p. 231 — Hard (for me) to see why stereoisomers of imines should interconvert and those of oximes should not.  Perhaps the oxygen is also hybridized sp2?  On p. 232 this appears to be the case, in explaining the stability of oximes, hydrazones and semicarbazones. 

p. 238 — The 4 membered ring of the Wittig intermediate isn’t as strained as it might look because the P – O bond is 1.76 Angstroms, and the P-C bond is 1.87 giving the ring a bit more room, but the spiro bond shown can’t change much due to the cyclohexane ring.  If anyone has actually seen the intermediate and measured its shape it would be interesting to know exactly what it looks like. 

p. 246 — A way to think of enthalpy change, is to remember the first law of thermodynamics — energy is neither created or destroyed. Crudely, enthalpy is just a measure of internal energy.   Also rather crudely, if the products of a reaction are of lower energy than the starting material, some form of energy must be given off (usually heat), and the products have lower enthalpy (a measure of internal energy).  Why ‘crudely’?  Because the discussion ignores entropy. 

p. 247 — Amusing, how chemists possess a very intuitive understand of entropy and enthalpy giving them essentially all the thermodynamics they need.  Think of the hard intellectual work involved in the Clausius’ definition of entropy  — the reversible heat supplied divided by the temperature at which it is supplied.  Chemical thinking is far closer to Boltzmann —  S = k log W. 

p. 248 — It’s worth thinking why the enthalpy of a molecule doesn’t change much with temperature.  It’s basically the energy of the bonds it contains, which is pretty much the same until the bonds are broken (and the molecule changes). 

It’s also worthwhile pausing and thinking what we mean by a ‘strong bond’ — it’s one that requires a large input of energy to break.  So even though we describe a strong bond as high energy, it’s really much lower in enthalpy than separating the atoms that make it up. 

p. 248 — Le Chatelier’s principle may be the basis of a treatment to dissolve the senile plaques of Alzheimer’s disease (and help the condition if they are what’s causing the problem — something rather contentious as of 5/12).  For details see —

p. 251 — The concept of a transition state is valid (because we use it all the time and it appears to work).  But, by definition, a transition state can’t be isolated (unlike reaction intermediates), so is it as scientifically valid as the number of Angels which can fit on the head of pain or is it ‘real’ in a truly scientific sense?  

The transition state concept assumes that the states of a molecule are ‘complete’ in the following mathematical sense.  By complete, I mean the following.  Consider the rational numbers (ratios of whole numbers).  We can get as close as we wish to the square root of 2, but the fact that sort(2)  cannot be a rational number is said to have driven the Pythagoreans to murder one of their own who threatened to divulge this to the laity.  So while we today regard sqrt(2) as a number, it exists essentially by the assumption of any number of equivalent postulates. 

Personally, I find equivalence classes of Cauchy sequences the most intuitive definition of real number (of which rational numbers are a part).  The completeness property of the real numbers allows us to prove that any continuous function on a closed interval of real numbers reaches a maximum (the transition state) and a minimum.

Since energy levels are quantized, why not reaction states?  Then there would be no such thing as a continuous transition between reactant and product, and no transition state.

p. 258 — Proton transfers are fast.  Well how fast?
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  • MJ  On June 1, 2012 at 10:44 pm

    It’s late, so I apologize if any of this is unclear or kind of handwavy.

    Re: p. 251 – Transition state theory (from the early to mid 1900s) had this element of reducing the fudge factor and give a more detailed form for said empirically determined factors (the Arrhenius prefactor, for example), as well as being able to take experimentally determined rate constants and extract out thermodynamic quantities related to the reaction. So it would seem that, if nothing else, it was a useful fiction at this point.

    Transition states are fleeting, to be sure, in the fraction of a picosecond range (which relates to converting a vibration into a translation, or something along those lines). But that’s why we have time-resolved laser spectroscopy – look up Ahmed Zewail’s 1999 Nobel Prize as a starting point. I suppose if one wants to really carefully parse what a transition state is – much like how an orbital is, strictly speaking, a one-electron wavefunction – then I suppose this may not be all that convincing. Or if you really prefer the idea of being able to work it up and isolate it into a stable form, and aren’t happy with just pointing to a spectrum and say, “I assigned that!” I’m a biophysical chemist, so I tend to like spectra of all sorts. Heh.

    Going back to the idea of useful fictions – transition state analogues have been synthesized for enzymes, where a model is constructed of the transition state and someone has followed up by actually making it. I know it’s been demonstrated in academic circles (Vern Schramm at Albert Einstein is the name I typically associate with this, as I’ve heard him speak), but you’ll need to ask someone with a lot more pharma/drug discovery knowledge to see if it’s gotten any application elsewhere.

    Re: p. 258 – I think the Grotthuss mechanism as involved with the autoionization of water is somewhere in the picosecond/sub-picosecond timescale. Which may be more useful as a limiting case, I suppose, depending on the context in the book.

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