ANALYTICAL CHEMISTRY
98 and to verify this it immediately became necessary to establish beyond a reasonable doubt that the natural and the synthetic products were identical. KOone method was available by which this could be done, nor was any single instrument capable of furnishing as proof of identity experimental data which could not be questioned to Some degree. As a result of the fact that almost complete agreement was found between the analvtical values obtained from the two materials through the combined use of an impressive list of chemical, biological, and physical methods, it is possible to state that this one type of penicillin had bern isolated in a relatively high state of purity and that the yynthetic and the natural products were identical with a high degree of probabilitx-.
I n the above example, and in dozens of other cases which might be cited, the usefulness of the various instrumental methods cannot be overemphasized. S o r can too much stress be placed upon the need which still exists for the development of analytical methods possessing a n even greater power of discrimination, methods which will increase still further the probability that our results are correct. LITERATURE CITED (1) Strong, F. C., a h a ~CHEM., . 19, 968 (1947). R E C E I V EJanuary D 17, 1948
Philosophy of the Purity and Identity of Organic Compounds HENRY EYRING Cniversity of C‘tah, Salt Lake City, C‘tah
If a molecular system cannot be fractionated, it should be regarded as a pure system; this is the definition of a component in the thermodynamic sense of the phase rule. In cases of metastability, the length of waiting for equilibrium is determined by the experiment to be performed, and it is concluded that a system is pure for a particular purpose, if further fractionation would not yield products whose use would change the result of the experiment.
0
XE might adopt an abstract definition of purity such as
*
a pure compound is one in which all molecules are identical.’’ A meaning still must be given to “identical molecules.” From the third law of thermodynamics, the entropy of a pure crystalline solid at’ the absolute zero can be taken as zero. This is equivalent to saying that under these conditions, all the molecules are in identically the same state-Le., the molecules arc all identically alike. However, a t all realizable temperatures the molecules exist in different energy states; so that under ordinary conditions one must give up any idea of such complete identity. Thus \re turn to a definition of purity in terms of operations t o be performed. 9 system of molecules is a pure compound if an exhaustive series of fractionations fails t o produce fractions with different properties. K h a t one calls a pure compound thus changes as neJT mclhods ‘becaome available for separating material into fractions, or for more accurately measuring the properties of the fractions. The usual “pure” hydrocarbons still have about evt thousandth hydrogen atom twice as heavy as the rest and havti a small amount of carbon 13. Khether it is proper to regard such a system as “pure” depends entirely on the use to be made of it. If further purification would have changed the measured properties, it xvas not pure, and conversely. Thus, we arrive at a standard of purity which varies with the use to be made of the material. This lack of an absolute standard of purity may seem unsatisfactory, but it is unavoidable if purity is to mean anything but an unattainable abstraction. It is an unusual organic molecule which does not have more than one conformation. The boat and chair form of six-membered rings is an example. If the activation energy for a molecule to change from one configyration to another is 25 kg.-cal., then one can separate the isomers, and they will be stable for a matter of days at room temperature. When the activation energy is half as large, the same stability will be obtained only below 150” K.Le., a t half room temperature on the absolute scale. I t is thus a matter of considerable interest to consider types (*
of isomers which coexist in systems frequently considered to bc pure compounds. NUCLEAR SPIN ISO,\IERS
Ortho- and para-hydrogen are well knowi and change into each other only in the presence of paramagnetic molecules such as osygen, paramagnetic ions such as S i - - or in reactions in which the atoms of a hydrogen molecule gain nexv partners. I n para-hydrogen, the molecules’ nuclear spins are antiparallel, and thc molecule can exist only in even rotational states; whereas the ortho-hydrogen has the nuclear spins parallel and can exist only in odd states. *kt very low temperatures only para-hydrogen in the zeroth rotational state is stable, so that in the presence of a catalyst such as charcoal, ortho-hydrogen changes over into para-hydrogen. If it is removed from the catalyst while still cold, it then can be kept a t ordinary temperatures indefinitely. 1Iore generally, any symmetrical molecule which has a number of indistinguishable orientations, U, in space Jvhich go over into each other by rotations is said to have a symmetry number u. Thus, hydrogen has two indistinguishable configurations, and the rotational states break up into tn-o classes-the odd and the even state. The odd rotational states of ortho-hydrogen correspond to triplet states, and the even rotational states of parahydrogen correspond to singlet states for nuclear spin. In methane, there are twelve Tvays of orienting the molecule which are indistinguishable, so that the symmetry number u is twelve and the rotational states break up into t5velve sets. However, only three of the tlyelve possible sets of states are allowed for methane. I n one of the allowed sets, the hydrogen nuclear spins add up to make a quintet state ( 4 ) . I n a second of the allowed sets, the hydrogen nuclear spins add up to make a triplet state in three different ways; and finally, in the third allowed set of rotational states, the spins add up to make a singlet in two way: Thus, the first set of rotational states with quintet spin is fivefold degenerate due t o spin; the second set is 3 X 3 = ninefold degenerate due to spin; and the third set is twofold degenerate.
V O L U M E 20, NO. 2, F E B R U A R Y 1 9 4 8 Actually then, a sample of methane consists of a mixture of three nuclear spin isomers which in the absence of paraniagnet,ic molecules may not change over into each other during the lifetime of the molecule. According to 11acDougall’s calculations (Zi, the three isomers have different specific heats below 80” K.; and if a suitable catalyst could be discovered in this low temperature range, mixtures other than the met,astable 5:9:2 mixture should be realized. Similar considerations apply to the possibilities of measurable separation for other molecules with sufficiently low moments of inertia, such as water and ammonia. Honever, all symmetrical molecules (unless the identical atoms interchanged by rotation have no nuclear spin) consist of such mixtures of stable nuclear spin isomers, whether or not you can devise experiments to isolate the isomers. I t is the fashion to forget about such complications, with respect to purity, on the theory that “what the e)-e doesn’t see, the heart doesn’t grieve.” This is of course the only practical procedure. To say that no procedurc exists for separating isomers into fractions is to say that no error is made by treating the mixture as a pure compound, and ~ v cmay anticipate a continuance of the general policy of ignoring nuclcar spin isomers in organic chemistry. ISOTOPIC MIXTURES
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