Homotopic hydrogen atoms

An exception is the halogenation of an alkane (or cycloalkane) whose hydrogen atoms are all equivalent (i.e., homotopic). [Homotopic hydrogen atoms are defined as those that on replacement by some other group (e.g., chlorine) yield the same compound (Section 9.8).]... 

For example, analyzing 4-bromonitrobenzene (6) by the substitution test leads to the conclusion that there are two sets of homotopic hydrogen atoms, and HjjHj,. The two protons in each set have ecjuivalent chemical shifts. However, the coupling constants between all members of the spin set are not equivalent. Namely,... 

The term equivalent is overly general and therefore bland and of equivocal meaning. Thus the methylene hydrogen atoms in propionic acid (Fig. 1) are equivalent when detached (i.e. they are homomorphic), but, as already explained, they are not equivalent in the CH3CH2C02H molecules because of their placement — i.e. they are heterotopic. Ligands that are equivalent by the criteria to be described in the sequel are called homotopic from Greek homos = same and topos = place 6>, those that are not are called heterotopic . 

The symmetry planes (a) in molecules 30, 32, 34, 36, 38, Fig. 13 should be readily evident. It is possible to have both homotopic and enantiotopic ligands in the same set, as exemplified by the case of cyclobutanone (34) HA and HD are homotopic as are HB and Hc, HA is enantiotopic with HB and Hc HD is similarly enantiotopic with Hc and HB. The sets HAjB and HC>D may be called equivalent (or homotopic) sets of enantiotopic hydrogen atoms. The unlabeled hydrogens at position 3, constitutionally distinct — see Section 3.4 — from those at C(2, 4), are homotopic with respect to each other. Enantiotopic ligands need not be attached to the same atom — viz. the case of mew-tartaric acid (32) and also the just-mentioned pair Ha, Hc [or Hb, Hd] in cyclobutanone. 

The correct description for this pair of hydrogen atoms is homotopic. They are the same (homo) topologically and cannot be distinguished by chemical reagents, enzymes, NMR machines, or human beings. The molecule is achiral—it has no asymmetry at all. 

And yet a rational explanation can be found that is also consistent with and complementary to the stereochemical and mechanistic data on other AdoCbl-dependent rearrangements already discussed in this chapter. Once again a loss of stereospecificity in the enzymic reaction points to the transient existence of a trigonal intermediate the faces of which are quasi-homotopic because rotation about the C—C bond is faster than the subsequent hydrogen-atom transfer step (Fig. 31). 

Unlike the above, the two hydrogen atoms labeled Ha and Hb in propane 184 are homotopic because a C2 operation converts one into the other, so that they are considered to be equivalent in all possible ways. Even if one of these hydrogen atoms is replaced by a substituent other than methyl and hydrogen, resultant molecule is not chiral. Homotopic groups remain indistinguishable under chiral influence, i.e., in the presence of chiral ligands. 

STRATEGY AND ANSWER The hydrogen atoms of the alkane must all be equivalent (homotopic), so that replacing any one of them leads to the same product. The only five-carbon alkane for which this is true is neopentane. 

Label the sets of connectively equivalent sets of protons in the molecules (a)-(j) according to whether they are homotopic, enantiotopic, or diastereotopic. Using Tables 8.3 and 8.4, predict the approximate chemical shifts, in 8, and the splitting patterns expected for each chemically distinct type of hydrogen atom that you identify. Assume in this analysis that the coupling constants of all nearest neighbors are identical. 

It is useful to compare two chirotopic A/Gs within the same molecule that have the same bonding connectivity. We will find that they are either enantiotopic (have enantiomeric environments), diastereotopic (have environments that are more different than mirror image), or homotopic (have identical environments). Consider again the two hydrogens in bromochloromethane. These hydrogen atoms reside in mirror-image environments and are thus enantiotopic to each other. There are no enantiotopic A/Gs in molecules that are chiral, but they exist in meso compounds and molecules as simple as butane. 

This molecule, the most symmetrical of the three, is achiral. The central carbon atom is completely nonstereogenic. Both planes are planes of symmetry and the hydrogens are homotopic. They are chemically and magnetically equivalent. 

If replacing the hydrogens by a different atom gives the same compound, the hydrogens are said to be homotopic. 

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