Clayden pp. 749 – 850

p. 750 — a pointer to p. 236 where kinetic vs. thermodynamic control is discussed would be good in the top sidebar.

p. 750 — you use the term ‘frontier orbital’, but the only  reference to the term in the index involving an earlier page is to p. 230 where the term is nowhere to be found.  Amazing that you’ve gone through nearly half the book with only one or two undefined terms (Michael acceptor comes to mind).   Googling the term, it just seems to mean HOMO and LUMO, so you should say so back there. 

p. 754 — “heating reactants together sometimes neat”   What does neat mean chemically?   I should know, but it isn’t in the index.  Some explanation should be given (assuming this is the first time you’ve used the term). 

p. 756 — MeSiCl, TiCl4 — by now old friends.  Just like medical school where if you repeat anything enough it eventually sinks in. 

p. 759 — The chemistry keeps getting better and better as old reactions are combined in new ways.  The musical analogy wouldn’t be a symphony, but rather a passacaglia in which the base line is constant, but the improvisations on top get progressively more complicated. Bach wrote a great one for the organ. 

p. 771 — In Greek geometry all reasoning backwards from the final result of a theorem was never shown (and probably considered bad form).  All their mathematics starts with a statement of the result to be obtained followed by whatever postulates and/or previous proved theorems they and a series of logical deductions based on them.  Descartes didn’t like this, and thought the Greeks knew far more than they were saying. 

Gauss did the same thing, removing all the scaffolding that allowed him to achieve his incredible results, leaving lesser mathematicians (which was everyone else) to scratch their heads.  This chapter is just the opposite, showing us not just the syntheses but the thinking that led to them.
I wrote a post about the issues raised by this chapter:  Here’s the link  https://luysii.wordpress.com/2010/06/20/retrosynthetic-analysis-and-moliere/

p. 771 — Sidebar — “read a specialist text” — at this point your readers trust you, so why not point to a text or two, or have a bibliography at the back of the chapter (or the book) along with articles for further reading.  Clearly all the reactions you describe with yields represent original papers.  Pointing to them would be far too much, but pointing to introductory books would not.  Ditto for the consult a specialized book on p. 799.

p. 771 — I did recall seeing a whole book on the subject by Warren (out in 2009), so you should point to it in the coming edition. 

p. 773 — Second sidebar  “try to do the retrosynthetic analyses in this chaper as you read it, before looking at the suggested solutions.”  True enough, but,  as you read the text after this page with which does have an undecomposed structures of Daminozide in the sidebar, this is impossible to do before p. 780 (terodilin), because the structure to be analyzed and the analysis are one and the sameYou should either change the way the text is organized or warn the reader. (This was the only example you could do this with in the next 10 pages, all other examples that I saw up to p. 791 also had the sites of disconnection given in the initial structure encountered.   This is true for the next 10 pages as well.  The disconnections are already in all the examples ! ! !  

p. 775 — “You shouldn’t have expected to predict that sodium ethoxide would be the base used”  — true, but if you just put in a table of pKaHs of conjugate bases somewhere in the book (perhaps in the acid base chapter) the reader would have some idea of the base to use (or at least bases not to try).

p. 779 — “Ocfentanil is an opioid painkiller that lacks the addictive properties of morphine”.   I doubt that this is still true.  In clinical medicine from ’64 – ’00 — this sort of claim was made for a number of new narcotic derivatives (Talwin comes to mind — plenty of people became addicted to it in the early days despite the early hype) none of which turned out to be true.   Check this statement VERY carefully before including it in your next edition.  

p. 783 — with the example of an Sn2 reaction occuring at a tertiary center, you might put in a note to modify the table on p. 426

p. 787 (top line) — Diethyl malonate is NOT the synthon for RO-CO-CH2- (because R stands for any alkyl group, not just ethyl)

p. 791 — You might make donor and acceptor synthons clearer to the reader by saying that they combine by donating and accepting ELECTRONS. 

p. 799 — The 24 June ’10 Nature has an article on an umpolung route to the amide bond (vol. 465 pp. 1020, 1027 -1032).

p.801 — On finishing the chapter I feel like Monsieur Jourdain in “Le Bourgeois Gentilhomme”, astounded to realize that he had been speaking prose all his life without knowing it.  I’ve made a separate post on this.  Here’s the link  https://luysii.wordpress.com/2010/06/20/retrosynthetic-analysis-and-moliere/

p.801 — A reference to further reading on retrosynthetic analysis would be good.  

p.803 — A discussion of why the physical properties of fumaric and maleic acids are so different would be good (my guess — crystal packing).

p. 804 — The sidebar about where to look for the Z and E rules (p. 487) and their real origin (p. 387) should be on this page rather than 806 for the memory challenged.

p. 805 — The top sidebar referring to the exact pages of discussions appearing over 300 pages earlier is good. There should be a lot more of them in the next edition.  The first edition is not overcrowded with sidebars.

p.806 — What does Li(O) mean in the third line of structures?

p. 809 — A discussion of why trans-alkenes absorb better than cis alkenes would be good. Also why they absorb light of higher wavelength (lower energy), although I can guess (the cis alkenes pi bonding is destabilized by the steric effects which probably twist  the bond slightly).  

p. 810 — I wonder if this Julia is related to the mathematician for whom Julia sets are named. 
  
p. 814 — “The phosphorus-oxygen double bond is extremely strong”  — well, just how strong is it?  

p. 814 —  Would trimethylamine oxide be considered a ylid?   Where do the double bond electrons go on the phosphorus (in the phosphorane structure), in a d orbital, and if so which d orbital?

p. 819 — “sphingosine a constituent of cell lipids”, well it is in the same way that ethanol is a constituent of ethyl acetate.  Sphingosine is present in cell lipids the same way — as a constituent of sphingolipids.  Sphingosine 1 phosphate is a potent compound as it is an intracellular messenger molecule, so the cell is quite careful about free spingosine.  

p. 822 — answer to #8 — I had it that the carbocation was sufficiently longlived that the tBu group could rotate to a less hindered possibility (as the carbanion mechanism shown in the Julia reaction).  I suppose using more and less bulky groups would settle the issue. 

p. 822 — Great chapter.  Absorb a few simple principles and facts and you can figure most things out.  Great problems at the end (although there are a lot of misprints and errors in their statements and answers.  I imagine that people who are good a Sudoku are good at NMR interpretation.  
The whole chapter is new stuff (to me).  Granted that you’ve shown all sorts of carbonyl chemistry not known 50 years ago, but a carbonyl group back then is still a carbonyl group today.

p. 822 — “An undergrad and an NMR spectrometer can solve in a few minutes strucural problems that challenged teams of chemists for years half a century ago”  True, but solving them taught us a lot of chemistry back than and stretched our analytic skills to the utmost. 

In grad school, a chemist (David Ginsburg from Israel) gave us a series of lectures on the opium alkaloids (I think in the fall of ’60).  I’m not sure just how many but my retranscribed notes on them go for 46 pages of which the first 32 were on the determination of the structure of morphine, and the last 14 concerned its synthesis.  As I recall, Woodward attended all of them.

p. 825 — “axial/equatorial couplings are usually slightly larger than equatorial/equatorial ones” — why if the both angles are 60 degrees?  Then two paragraphs down you say “this is not surprising since the dihedral angles are both 60 degrees”

p. 827 — Why does the hydrogen in the acetal have a chemical shift of 4.40 when it is axial, and 5.29 when equatorial.  It must be interacting with the free electron pairs on the ring oxygen?  True?  That’s a fairly large difference which could use some explanation in the text of the second edition.  

p. 834 — “This exchange is rapid on the NMR time-scale”  — well, what IS the NMR timescale? 

p. 837 — last bullet “If they are diasAterioisomers . . “

p. 838 — second paragraph — what are you referring to (the cyclohexanone ?)  If you are, its structure should appear.

p. 840 — the sidebar explaining where to look up A, B, X to describe proteins should appear on p. 838 where AB systems were first discussed.

p. 841 — “may be simplified by irradiating the brown hydrogen to remove any coupling to it”  — how in the world is this done?   I don’t think the technique has been mentioned earlier. Can you irradiate two hydrogens at distinct chemical shifts simultaneously? 

p. 846 — Problem #1 — The mass spectrum gives C9 H16 O not C9 H15 0 as stated.  Fortunately the numbers in the hydrogen chemical shifts do correctly add up to 16.  Very nice to see real world problems

p. 846  — Problem #6 — The protons on the tBu group were left out in the problem (9 H at a chemical shift of 1.47) —  they are there in the answer.

p. 846 — Problem #7 — Bromine has an electronegativity of 3.44, oxygen of 2.96 — so why is the chemical shift of H-C-Br (4.3) higher than that of H-C-0 (3.9) ??

p. 847 — Problem #8 — there aren’t enough carbons (3) not attached to the P in the Wittig reagent to account for the product (which has an n-butyl group hanging of the ketone.

p. 848 — Problem #9 — The answer says that the MeO signal is 2.07 (but the problem says that it is a ring hydrogen).  It should show which hydrogens are on the same side of the ring.  
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Comments

  • Wavefunction  On July 7, 2010 at 11:38 pm

    -Ocfentanil is an opioid painkiller that lacks the addictive properties of morphine”. I doubt that this is still true

    I doubt if it was ever true. As a fentanyl analog, ocfentanil would bind to the mu-opioid receptor which mediates both the good and bad effects of morphine. To do away with the bad ones you would really have to selectively bind to the kappa receptor, a goal that’s still elusive to my knowledge.

    -What does neat mean chemically?
    It simply means doing a reaction by mixing together ‘pure’ reactants, without dissolving them in a solvent. Ever had a glass of ‘neat’ scotch?

  • CFan  On October 6, 2010 at 7:16 am

    p. 756 — MeSiCl, TiCl4 — by now old friends. Just like medical school where if you repeat anything enough it eventually sinks in

    Did you mean Me3SiCl, TiCl4 combo used with silyl enol ethers?

    Yes

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