Clayden pp. 1100 – 1199


p. 1100 — In the bottom series of reactions, I assume that when rho is being studied for one phenyl group, the other phenyls have hydrogens, otherwise some n^3 combinations would have to be tested. In the earlier work n = 12. Probably some wretched grad student has probably done something like this to see if effects were additive or subtractive.

p. 1101 — A pointer back to pp. 314, 319 where you give a hint of how to determine deltaS (but for equilibria not for activation energy) would be good. Even better would be a short explanation of how the entropy of activation is experimentally determined –right here.

p. 1103 — The dienone-phenol rearrangement — interesting that the methyl group is held to migrate faster than the hydrogen. I’d expect the opposite. Any explanation ?

p. 1103 — O – H has a greater frequency of vibration than D – H. The reduced mass (inversely proportional to frequency) is under 1 for OH, while for D – H the reduced mass is nearly 2. To really be sure we need to know the bond strength of the two bonds (which is directly proportional to frequency). Why should an increased frequency of vibration make a stronger hydrogen bond?

p. 1103 — Why not say what the pKaH of D3O+ in D2O actually is rather than saying that D30+ in D2O is a stronger acid than H3O+ in H2O?

p. 1103 — bottom you have r = -6.0 instead of the (Greek) rho = 6.0

p. 1104 — Why should the rate of ester hydrolysis be zero at around neutral pH? Here the concentration is of OH- and H+ is low (.1 microMolar) but not zero. I can see why it might be a minimum at neutral pH, but not zero.

p. 1106 — Why is proton transfer to and from carbon slow, and proton transfer between heteroatoms “always fast” It certainly isn’t bond strength:
C – H 96 – 105 (100 — Clayden p. 1004)
Primary -CH2-H 101 (Clayden p. 1026)
Secondary CH – H 98 (Clayden1026)
Tertiary C – H 95 (Clayden1026)
N – H 107
O – H 119

pp. 1118 – 1119 — Very nice to see that some of the problems are not at all contrived, but examples of stuff that people actually worked on and published.

Solution to prolem #7 — MeCN is stated to be a polar aprotic solvent. Then why not give its actual dipole moment.

Chapter 42 — The chapter gives lots of specific page references when referring to previous material. All the chapters in the new edition should be like this.

p. 1124 “The exposed nature of the nitrogen atom in cyclic amines” means that “nitrogen heterocycles are very frequently encountered in drug molecules, particularly those operating on the central nervous system”
Both statements are true but I don’t see that the second follows from the first.

p. 1126 — “Aziridine is, in fact much less basic than pyrrolidine and piperidine” — the pKaH of pyrrolidine is nowhere given. Piperidine’s is 11.2 (p. 1123). Why not give them both here? Digging around for them interrupts the flow of the discussion.

p. 1127 — TMEDA is nowhere described (that I can find). It isn’t in the index.

p. 1128 — The complex of the oxygen heterocycle with BF3 in the diagram at the top of the page is missing a ( )n at the top of the ring.

p. 1128 — “Since the sulfur atoms have lone pairs, they to occupy axial and equatorial positions” — Whatever happened to molecular orbitals?

p. 1130 — “we would expect a molecule to be stabilized if an adjacent heteroatom could donate electrons into this orbital in the same way”. Perhaps a statement to the effect that anything the delocalizes electrons lowers energy, although (to me) weakening a bond seems like a wierd way of lowering energy. In general the stronger the bond the lower the energy (relative to dissociated atoms).

p. 1136 — Again, somewhere in the book should be an explanation of how one can determine the entropy of activation for a reaction.

p. 1140 — “Victorian desire” — I didn’t think they had any. Also isn’t compulsive classification teutonic rather than English? (Spoken like the Yank I am).

p. 1143 — “Baldwin’s rules work because they are based on whether or not orbital overlap can be readily achieved”. Isn’t it better to think of reactions this way rather than memorizing a bunch of what appears to be arbitrary rules about phonetically ugly names for reactions? In medicine, any time a mechanism for disease is discovered, it’s far better to think about the mechanism rather than memorize arbitrary facts (which, malheureusement, you must do for a lot of medicine).

p. 1146 — Problem #6 — the product has one more carbon in the starting material, both in the problem and in the solution manual.

p. 1145 — Problem #8 — unfortunately what should have been a great problem was destroyed by repeating 1.33 (3H d J6 Hz) between 3.99 (1H dq, J10, 6Hz) and 4.24 (1H ddd jJ3,3, 3.5). The answer doesn’t help.

p. 1149 — “Pyridine is a weak base with a pKa of 5.5” — shouldn’t this be a pKaH of 5.5 ???

p. 1150 — “The lower energy of the orbitals of pyridine’s pi system means that electrophilic attack on the ring is difficult” — lower energy than what?

p. 1151 — “Finally, one amino group is acylated in the presence of 3 others” — why this particular one?

p. 1153 — How about a mechanism for the formation of pyridine N-oxide with m-CPBA?? My guess is that it’s similar to that shown for the formation of epoxides from m-CPBA and alkenes (p. 506).

p. 1156 — Why does Bipy show a ‘preference’ for Fe? Is it the match of Fe ionic radius and the distance between the two nitrogens or are other things involved. Also, where does the hydrogen go?

p. 1157 — “The pKa of pyrrole acting as a base is -4” shouldn’t this be the pKaH?

p. 1159 — “You may be surprised that thiophene is the least reactive of the three (the other two are pyrrole and furan), but this is becase the p orbital of the long pair of electrons on sulfur that conjugates with the ring is a 3p orbital rather than the 2p orbital of N or O, so overlap with the 2p orbitals on carbon is less good.” I’d think that this would make thiophene less aromatic and hence MORE reactive.

p. 1160 — Butenedial is said to be very unstable. What happens to it if left alone?

p. 1164 — “The PkA of pyrroidine is 35 while that of pyrrole is 16.5 making it some 10^23 times more acidic” not 10^18 or 10^19. How do you get 10^23??

p. 1171 — Third reaction sequence from the top with structures. Are you saying that the leaving group is negatively charged Me2N:: ?? or does HCN protonate it before leaving?

p. 1176 — “the weak O – N or S – N bonds” How weak are they? A table of bond strengths should be in the next edition.

pp. 1182 – 1183 — I like the literature pointers in the answers to the questions.

p. 1182 — Problem #6 — What is Nitromethane doing in this reaction? The answer and the mechanism gives no clue.

p. 1183 — Problem #14 — Compound A has the incorrect atomic composition, showing only 2 nitrogens, when in fact there are 3. This caused me to abandon the problem (probably true for anyone else attempting it).

p. 1193 — Calcium channel blockers don’t block all calcium channels (or we’d be dead). Neurons use another type of calcium channel when they talk to each other). This stuff is probably too detailed for an organic chemistry book to get into. For the record, Amlodipine just blocks the L class of calcium channels. N, T, P, Q and R classes of calcium channels exist as well.

p. 1194 — What does FGA stand for? It’s not in the index.

p. 1196 — Viagra — what a dog’s breakfast of a molecule. It looks like it was put together from the leftovers of a chemical modeling set (assuming people still make such things).

p. 1199 — The label in the bottom row of reactions reads “unstable primary enami”
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