Clayden pp. 928 – 1000

Well, I’ve reread the first 1000 pages of Clayden and am ready to finish the rest (hopefully before the end of the year so I can more on to Anslyn and Dougherty  etc. etc.   This may seem foolhardy, but the last 150 pages or so seem to involve biochemistry which should go pretty quickly.  

The content gets more and more interesting, particularly the last chapter on rearrangements which contains some great syntheses.

Not really part of Clayden, but too good to resist.  An enzyme has been computationally designed which catalyzes the Diels Alder reaction — [ Science vol. 329 pp. 285 – 287, 309 – 313 ’10 (16 July ’10 ) ].  However there are actually two enzymes performing (intramolecular) DIels Alder reactions found in nature.   However a closer look at the paper shows that both the dienophile and the diene contain amide groups attached to the double bonds, making it (to me at least) slightly less impressive, since it seems likely that the amides of the enzyme and the amides of the reactants interact with each other.  Still, impressive overall. 

p. 933 — How do you make a hydroxyamine?  Can nitrones be trans or cys, or do the two forms equilibrate?  Can you make them from ketones as well as aldehydes? 

p. 933 — How weak is the N – O bond ?  You give the answer on p. 938  (180 kiloJoules/mole == 43 kiloCalories/mole).  Why not give the actual bond strength every time you say a bond is strong or weak?  Presumably all of them are known.

p. 940 — C-C sigma bonds are stronger than C – C pi bonds.  It seems that at the outset that you could say exactly how much energy is gained by replacing a C=C with 2 C-Cs.

p. 940 — Answer to Problem #1  — In the next edition it would be a good idea to show the transition state of the 2 + 2 reaction.  I had no idea that the ketene and the enol ether would approach each other orthogonally.  In fact they don’t in the first reaction. Why the difference ? 

p. 944 — “the new sigma bond is formed from two p orbitals that point directly at each other”  — this is probably why the chair form is required in the transition state.  Correct? 

p. 945 — How high is the boiling point of propanoic acid?  Why not give it? 

p. 946 — In #2 of the orbital description of [3,3] sigmatropic rearrangements, it should read “All the starting bonds taking part .. ” rather than “All the bonds taking part . . ” which would make things less ambiguous.  Also, it might be a good idea to repeat the definition of component found on p. 922

p. 947 — A pointer to p. 525 where the bond strengths of keto and enol components were shown would be better than ‘think back to our discussion of enols’

p. 948 — The transition state shown in second set of reations looks far more chairlike than boatlike.  Apparently not a problem, but the point could use some discussion. 

p. 949 — How in the world do you make the fused 5 and 3 membered ring — carabenes?

p. 949 — For some, organic chemistry is an esthetic pursuit.  Thanks for putting in the marvellous synthesis of citral. 

p. 950 — “Indoles are of some importance in biology and medicine”  — well, how about serotonin, melatonin and tryptophan, indoles all ! 

p. 950 — Just how weak is an N – N sigma bond? 

p. 952 — “The element is sulfur, which can form stable compounds at three oxidation states S(II), S(IV) and S(VI).”  Why?  Why just those states?

p. 956 — All medical students study vitamin D, but the biochemistry as taught back then never made any sense.  It’s great to see how the [1,7] sigmatropic shift and electrocyclic reaction explain things.  Did the biochemistry lead the organic chemists to electrocyclic reactions or was it the other way around? 

p. 957 — ” Electrocyclic reactions, cycloadditions and sigmatropic rearrangements are the three main classes of pericyclic reactions.”   Are there other classes?

p. 959 — I’ve not read the history of how Woodward and Hoffmann came to their rules (developed after I left in ’62), but I had the pleasure of watching Woodward in action from ’60 – ’62.  I’d be willing to bet that it was something like the stereochemistry of the cyclization and uncyclization of the 1, 2 dimethyl cyclobutadienes that led him to the rules .  Like Willie Sutton robbing banks because that’s where the money is, unexplained results (or results contradicting known theory) are where future careers are built. 

p. 959 — A good use for the green arrows introduced at the bottom of the page would have been in the description of the stereochemistry of the Diels Alder reaction (particularly showing why the inner hydrogens of the diene rotate up). 

p. 961 — The conjugated polyene precursor (in vitro) of endiandric acid A zips itself up without any help.  An amazing sequence of reactions.
     l. Is the polyene made in nature?
     2.  Have people messed around with other polyenes to see what happens?

p. 964 — The right most structure on the top line has its right side cut off.  It should look like the left most structure in the next row down. 

p. 966 — Question #1 — what is P2O5 doing in one of the steps?  Extracting a hydrogen from MsOH? 

p. 967 — Problem #13 — one of the few times you’ve used something without explaining it first — namely DMAP which isn’t explained until p. 1153.

p. 970 — Both the HOMO and LUMO shown are really atomic orbitals, essentially confined to one atom.  Can atomic orbitals be considered HOMOs and LUMOs?  If so you should make this clear when they are first discussed.  Looking back to chapter 6, I don’t think the discussion made this clear.  Also what is an ‘n orbital’ shown in the box at lower right?

P. 971 — I think S-2 bromopropanoic acid is mislabeled as is R lactic acid

p.973 — Top sidebar — I am unable to find ANY discussion about the rates of formation and stability of different ring sizes in chapter 13. 

p. 973 — The structure of the intermediate — prolonged and acrimonious debate — I wasn’t around that long, but I can attest to the acrimony.  My senior thesis advisor (Paul Schleyer) was involved as was Sol Winstein (Solvolysis Sol as he was called back then < behind his back > ).    Surely, low temperature crystallography and NMR have settled this by now.  

p. 988 — The pointer back to pp. 597 – 598 is a good idea.  There should be a lot more of them in the next edition. 

pp. 990, 991 — American chemists appears twice — why not give their names, and omit the American.  

p. 992 — The structure of pathidine (Demerol) as given, is incorrect — it is the ethyl ester of what you have shown.  Pethidine is far more than a painkiller — it is an opiate and addiction to it has been quite a problem. 

p. 992 — Why not say the 0 – 0 bond has a strength of 33 kCal/mole (138 kJoules/mole).  Even better why not have a table of bond strengths somewhere in the next edition. 

p. 993 — The table in the middle is incorrectly labeled.  The first yield for R in bold should be yield for phenyl

Also neat to see how chemists make L-DOPA which I used for years to treat patients with Parkinsons disease using Friedel Crafts  and hydrogen peroxide in separate steps.  The body uses just one enzyme (tyrosine hydroxylase) to get there. 

p. 995  — The second paragraph doesn’t make sense (to me), because an empty sigma* orbital is used in both Sn2 and the Baeyer Villiger reaction. 






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  • Wavefunction  On November 10, 2010 at 8:59 pm

    -Indoles are of some importance in biology and medicine

    Classic British understatement?!

    -I’ve not read the history of how Woodward and Hoffmann came to their rules

    Apparently Woodward got the idea from a key step in the Vitamin B12 synthesis where an electrocyclic reaction was taking place. He then recruited Hoffmann who was working with Bill Lipscomb.

    -Surely, low temperature crystallography and NMR have settled this by now.

    Absolutely. The two zingers were George Olah’s isolation of carbocations in superacid (eg. George A. Olah, Gao Liang, J. Am. Chem. Soc., 1975, 97 (23), pp 6803–6806) and Martin Saunders’s elegant NMR experiments involving C13 labeling (eg. Paul v. R. Schleyer, Keith. Laidig, Kenneth B. Wiberg, Martin. Saunders, Michael. Schindler, J. Am. Chem. Soc., 1988, 110 (1), pp 300–301).

    As you probably know, the main debate was between Winstein and H C Brown. It is very nicely fought out in a book by Schleyer and Brown (The nonclassical ion problem, New York : Plenum Press, 1977)

    Also, here’s a nice group meeting PDF on nonclassical carbocations with lots of references:

  • James  On November 24, 2010 at 9:56 am

    Couple of things –

    -Oximes (assume you meant this and not nitrones) can isomerize quite readily with base – they tautomerize to the nitroso species (N=O) and then reform the oxime.

    -You make hydroxylamines through partial reduction of nitro compounds, usually with zinc and acetic acid.

    959 – yet another reason to buy “RBW – artist and architect in the world of molecules” is the discussion (his Nobel Lecture) of how the woodward hoffman rules were developed.

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