Clayden pp. 176 – 350

No, I haven’t gone through 175 more pages of Clayden since the 4th of March denovo.  At that rate I’d be done with it in under 2 months.  Most of the comments were produced a few years ago when I read up to around p. 400.  I’ve reread about up to there presently.  Page progress should be much slower in the future.  The book continues to impress.

Please answer any questions of mine you can, add points in the book that are confusing to you and put in suggestions to improve the next edition.  Here we go. 

p. 176 — “closed shell structure” — not in the index, first time the concept (for molecules) has appeared (I think) — why should a closed shell structure be more stable ?  I can see why an unclosed shell might be more reactive — but why should a closed shell  be more stable.  Is this just an analogy from atoms, where the concept has been worked out (well, we all use it, but has there been any theoretical justification?).
p. 180 — Problem #5 — has the cyclobutadiene derivative actually been 
made? 
p. 181 — Chapter 8 — introduction — you assume all sorts of chemical knowledge on the part of your initial reader (electronegativity, lone pair, radical etc. etc.) — yet despite the warning given here,  the math in this chapter is pretty trivial.  At least in the USA, undergraduates have had calculus before they hit organic chemistry (usually in their junior year of college) and the logarithm should be no stranger to them.  
p. 182-3 — It seems clear that (aq) is stands for aqueous, and (g) for gas.  But what does (l) stand for — top equation on p. 183?   The mystery is explained on p. 190 where you say (l) stands for liquid.  But say it here.
p. 183 — It seems to be a matter of definition on which side of the acid base reaction  what you call an acid and a conjugate acid and a base and a conjugate base.  You could regard NH4+ as the acid and NH3 as the conjugate base, rather than what you have (acid being acetic acid and the conjugate base the acetate ion). 
p. 191 — Why is the H-I bond weaker than the H-F bond (less of the larger p orbital of I involved in bonding to the H 1s orbital than that of F??).
        Does the greater acidity of HI than HF reflect in any way the entropy of solvation of the ions (and if so which way — more water required to solvate I-, but greater charge density on F- means more ordered water).  Could it also reflect the fact that being smaller the fluoride anion binds the water dipole with greater enthalpy? 

p. 204 — “What the developers of cimetidine at SmithKline wamted was a drug that would bind to these receptors without activating them and thereby prevent histmaine from binding but not stimulate acid secretion itself.”  What you are describing is what pharmacologists call a competitive antagonist    If you decide to include the beautiful structure of curare, the South American arrow poison,  in your next edition —  it works the same way on the receptor for the neurotransmitter acetyl choline at the junction of nerve and muscle, paralyzing the target. 
p. 208 — Answer Book Problem #1  Ch8 p. 46 — don’t you mean pKaH of 5.5 for pyridine rather than pKa ??
Answer Book Problem #2 Ch. 8 p. 46 — if you need a pH of 5 shouldn’t the concentration of hydroxide ion be 10^-9 rather than 10^-5 as you state?
Answer Book Problem #8 p. 50 — Does the use of deuterium sharpen the 13-C spectrum because of the lack of spin-spin coupling, since 2-H doesn’t have a magnetic moment? 
p. 210 — The electronegativity of Li is given as 1.0.  So is that of Calcium.  So why don’t we have Grignard reagents containing calcium?  This was also a problem (for me) with transition metal organic chemistry my first time through it 50 years ago  — why is a particular transition metal used rather than all of them (not that calcium is a transition metal but the principle is the same).  (Along these lines p. 217 — Why Cerium for transmetallation — can you use the other 13 metals in the same f orbital? 
p. 211 — You speak of the “larger coefficient on carbon” of the C-Li bond.  In the introduction to LCAO on p. 95 the combination of the orbitals is symmetric (each coefficient is 1).  I don’t think you ever explictly state that LCAO can involve different amounts of the atomic orbitals (the coefficients), unlike your (excellent) discussion of atomic orbital hybridization. 
p. 224 — In the picture of the six-centered transition state a methyl group is missing (attached to the carbon of the ketone).  You may have left it out for clarity.
p. 225  — problem 9  -You say ‘bromides are more reactive than chlorides towards Grignard formation” — clearly true by this example but why? 

p. 230 — “In acrolein, the HOMO is in fact not the highest filled pi orbital you see here, but the lone pairs on oxygen”  — How are a lone pair of electrons confined to one atom a MOLECULAR orbital? 
p. 238 — “hard nucleophiles prefer to react with hard electrophiles, and soft nucleophiles with soft electrophiles.”  Yes, but why?   Also your discussion of nucleophiles appears to be rather spread out — in the next edition you might put a pointer on pp. 115 –> (where they are first discussed) to further discussion such as appears here.
Chapter #10 — problem 3  (answer) — “Michael acceptor”  — undefined as of this point — also the index points to p. 29 where there is nothing about it.   If the term is defined in chapter 10 — I missed it.

 

p. 244 — “There is inevitably less change possible in the distribution of two electrons found around a hydrogen nucleus than in that of the 8 valence electrons around a carbon nucleus”  — don’t the two 1s electrons of carbon have any diagmagnetic effect?  I’d have thought they’d be even more important as they are closer to the nucleus (then the valence electrons of carbon — and possibly even closer than the 1s electrons of hydrogen — don’t know this). 
p. 247 — “Rotation about C – C single bonds . .. is fast”   Well just how fast is it?  Some physical parameters would be nice — perhaps you give them later in the book.   
p. 248 — you are quoting the electronegativities of carbon and hydrogen (given on p. 121) as parts per million — I think this is a mistake.
p. 249 — why such a large difference (2.49 vs. 1.04 ppm) difference between the two bridge hydrogens on myrtenal?  Is it the ‘ring current’ on the conjugated aldehyde which makes the hydrogen over them so low?  One could argue that there is some sort of current set up in conjugated ketone which acts to shield the hydrogen as you show in the cyclophane p. 252
p. 249 — “It also has a CH group between the amino and carboxylic acid groups”   — you might mention that this true for all amino acids found in proteins, except glycine.

p.252 — bottom example — if theNMe2 group is injecting electrons into the ring this should result in a GREATER ring current and more deshielding  of the 2 protons adjacent to the group?   I’m clearly missing something.
p. 253 — If the nitro group withdraws electrons from the benzene ring, it should make the ring current less and result in a lower magnetic field at the ortho proton — shouldn’t this result in less of a chemical shift? 
p. 254 — Why are protons on a double bond so deshielded ?  There must be some sort of current induced by the pi bonds, but this isn’t discussed.
p. 259 — last paragraph “the pyrimidine spectrum” — a biochemist or a molecular biologist would say that both cytosine and 2,6 diamino pyrimidine are pyrimidines (as opposed to purines — like the other two components of DNA — adenine and guanosine) 
p. 262 — Why is the coupling constant invariant with respect to the applied external field ?   Also thein the diagram at the top of the page, the stronger magnetic field appears to push the doublets together (making them harder to measure) — doesn’t the ppm scale expand as you get to higher and higher magnetic fields? 
p. 266 — the CH2 far away from the O in oxetane is nearly at 3 ppm (not 1.3) — why such a high ppm? — is it the ring strain — 
p. 267 — Along these lines, why does parallel alignment of the orbitals produce a greater degree of coupling?   It is less than crystal clear why trans orbitals are better than cis (which appear closer together) –not to argue with the data (because you can’t) — but the explanation could use some elaboration. 
p. 268 — In the two spectra given here the distance between 1.2 ppm and 1.6 ppm doesn’t change, but the peaks are much sharper.  There are (presumably) 90 data points/ppm in the first spectrum and 500 data points/ppm in the second.  
p. 269 — It would be nice to have the actual bond lengths for C-C, C=C (which the organic chemist should know by heart anyway) and benzene (which I had trouble finding in the book — and never did accepting the Wikipedia value of 1.39 Angstroms) in the discussion of HH coupling. 
p. 270 — W coupling seems closer to the cis situation in which J coupling is less than to trans.  This is starting to resemble my experience in medical school in which an endless and arbitrary (but correct) collection facts must be memorized without understanding — e.g. the heart is on the left, the appendix is on the right, etc. etc.  Is there an explanation for W coupling? 
p. 272  At the bottom you have p.000 (which will need to be filled in the new edition).

p. 282 — In more details at the top of the page you say 1. Pyridine is consumed during both of these reactions since it ends up protonated.  The diagram doesn’t show a protonated pyridine at the end of the reaction (on the right).  It took a while for me to figure out that HCl is formed in the reaction which protonates the pyridine.  Perhaps you should be more explicit in the next edition.
p. 287 — Are the lone pairs of oxygen of lower energy than the lone pair of nitrogen because oxygen is more electronegative or is this just saying the same thing in fancier language?  Also a pointer back to p. 102 where how close two orbitals are to each other in energy determines where the combinations of the two end up would be good at this point. 
p. 289 — (Acid catalysts) “lower the pKaH of the leaving group” — not exactly true — the pKaH of each chemical moiety is a fixed number, that of H30+ is -2 that of OH- is 15 etc. etc. 
p. 291 —   “read a specialist textbook” — Since your book is so good, and since people in organic chemistry writing in the blogosphere love it (which is how I got to it in the first place) you really should recommend a specific physical organic chemistry textbook (or multiple ones that you like) in the next edition.
p. 295 — how about putting in the electronic structure and stereochemistry of PCl5?    The mechanism given here is quite unsatisfying.  Clearly the structure of PCl5 is unlike anything you’ve shown to this point.

p. 301 — how come the ortholitiated compound in the top row doesn’t react with another molecule of itself?  — You answered this on p. 331 (the reaction is carried out at low temperatures).
p. 302 — problem #8 — Cordura is a fabric, Doxazosin is Cardura
p. 305 — reflux — you’ve defined just about everything you need in the book, except reflux.  This isn’t the earliest the term appears, but I realized that I wasn’t sure what you mean by it and couldn’t find it in the index.  Clearly it doesn’t mean distill.   Wikipedia has the following:
Reflux is a technique involving the condensation of gases and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations. It is also used in chemistry to apply energy to reactions over a long period of time.
I guess this is what you mean.
p. 305      ‘this compound is more stable than that compound.’ What we really mean is that one compound has more or less energy than another. ” Actually what you mean is that one compound has less or more energy than another.  So I think this is a mistake.
pp. 305 – 306 — You might mention that our cells contain enzymes called peptidyl isomerases to make amide isomers containing proliine interconvert (and at body temperature to boot).
p. 314 — I’m occasionally dipping into Anslyn and Dougherty as I read your book, having read (lightly) Chs 1 and 14 at this point .  At some point they note that the poisitve charge in NMe4+ is spread all over the ion and not concentrated on N (as is usually drawn).  Presumably this is from molecular orbital calculations — has anything similar been done for CCl3COOH  etc. ?
By the argument given, there should be less entropy involved in solvating K+ than Na+.  
A bit lower, I think the intercept should be deltaS/R not delta S.
The discussion in the last paragraph is hopelessly confused and should be rewritten, along with an actual plot of lnK vs. 1/T (you seem to be talking about a plot of ln K vs. T. 
p. 316 — A appears to be a fudge factor which presumably varies with each reaction.  Is there any way to calculate it from first principles?  A does seems to be measurable by an appropriate plot.
p. 317 — From the table it’s clear that  reactions with an activation energy of 70 kiloJoules/mole go well at  298 K  ( = 75F room temperature) because there is enough energy in enough molecules at this temperature to surmount this barrier.  While with an activation energy 108 kiloJoules/mole the reaction goes slower by a factor of (5 * 60 * 60 * 24 * 11 = 4,752,000).   The question is, the distribution of energies of room temperature molecules.  
What is the median energy? What is the lowest energy of the top 1%?, the top .1%  etc.  

p. 336 — Problem #1  You have p. 000 to refer back to the Lumeiere Barbier method — this should be fixed in the next edition.  It is p. 188 in this edition.  Also I think pKa for phenyl-NH3+ should really be pKaH. 
p. 342 — “that acid or base catalysts increase the rate of equilibration of hemiacetals with their aldehyde and alcohol components — the catalysts do not change the position of that equilibrium !”  
 Probably better to say 
“that acid or base catalysts increase the rate of equilibration of hemiacetals with their aldehyde and alcohol components — catalysts NEVER change the position of equilibrium !”   The unitiated might think that this is peculiar to acid and/or base catalysis.
p. 344 — “consult a specialized book on organic reaction mechanisms” — you should point the reader to books you like.
p. 350 — are the geometrical isomers of oximes stable when imines are not because of partial double bond character of N-O due to resonance? 
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Comments

  • Adolfo  On March 17, 2010 at 4:24 pm

    “p. 262 — Why is the coupling constant invariant with respect to the applied external field ? Also thein the diagram at the top of the page, the stronger magnetic field appears to push the doublets together (making them harder to measure) — doesn’t the ppm scale expand as you get to higher and higher magnetic fields? ”

    The ppm scale does not expand. He explained that in pages 60 and 261
    The doublet couplings are only harder to measure on paper, not with a computer
    The coupling constant does not change with magnetic field because it tells us about the interactions between nuclei, not about population distributions, which is the information given by the chemical shift. I guess this might be confusing the way it’s explained.

    “p. 268 — In the two spectra given here the distance between 1.2 ppm and 1.6 ppm doesn’t change, but the peaks are much sharper. There are (presumably) 90 data points/ppm in the first spectrum and 500 data points/ppm in the second. ”

    I’m not sure I understand your comment. I see an unfair comparison, as the 90 MHz spectrum is taken from a CW machine and the 500 MHz from a FT one.
    The number of points is unrelated to the power of the machine. The CW spectrum wouldn’t have datapoints by standard means, and I would expect at least 16k in the 500.

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