Determination of Chiral Molecule Configuration in Fischer Projections Gary A. Epling University of Connecticut, Storrs, CT 06268
A recent article1 provided a rule for mathematical comparison of the priority numbers of a chiral compound in a Fischer projection to make it possible to determine whether the arrangement of groups represents an R or S configuration without the need of any three-dimensional manipulation. The objective is worthwhile for two reasons: (1)In general, students have difficulty in ~erformingthe required three-dimensional manipulations of the two-d&ensiond representations so that the molecule is transformed into the required molecular orientation for application of the sequence rules, and (2) more often than not the chiral molecule is encountered as aFischer projection, so a simple procedure is extremely useful. In recent years I have taught a simple, non-mathematical "very good" procedure which students master quickly and remember easily. This procedure is described below. There are 24 possible ways to orient the four priority numbers about a Fischer projection. In half of these arraneements the correct confieurational assimment is ohtained determining wheiher the seque& of numbers 1 to by 2 to 2 is clockwise ( R j or counterclockwise (S).7'he correct ansuer is a l w a ~ obrained s when rhegruup being "ignored" ( 4 ) is un a vc~ticalaxis. (The mnemonic'very good" procedure is a shortening of rhe phrnse "vertical = good assignment.") On the other hand, if the group being "ignured" is on a horizontal axis, merely examining the sequence 1 ti>2 to 3 will give the wrong assignment, and the apparent answer must be switched. Some exumoles will illustrate the urocedure:
2 (iv)
3+4
1
Once again the number 4 group is on the horizontal axis. We note that 1 to 2 to 3 is counterclockwise, an apparent S if a "good" procedure was being used. But 4 horizontal not being a good procedure we must reverse this answer to get the correct assignment of R.
I n summary, (1) After assigning priority labels to a Fischer projection, determine
whether the lowest orioritv. erouu .. . is on the vertical. contain the numher I ~roup,simply make the asvignmmt of cunf~gurationusing thexrandard rulrs is rclockwiir sequence g,f 1 to 2 to 3 in H.wunrerrl~ckw~se $I -,. (3) If the horizontal line contains the number 4 group, proceed as in (2) above, hut after getting the initial answer, switch it to get the correct assignment. (21 If the vertical line &a
The advantages of the ahove system are threefold: ( I J it is short and simple, (2) it requires no additional memorization other than the mnemonic "very good" once a student has mastered the standard definitions of the R and S nomenclature, and (3) it is easy to show why the system works, vide infra. T h e origin of the procedure can he seen upon examination of what happens to a tetrahedron oriented in the Fischer projection as the lowest priority group (4) is moved, in the standard fashion, farthest away from the observer.
The number 4 group is on the vertical line. Since vertical = good ("very good") the correct answer is obtained by ignoring it and looking at the sequence 1 to 2 to 3,which is counterclockwise here: the corred assignment is S. Again, thr number I group is un t h p wrtirsl mi*. and rhr corrert assignment here is fuund 1," noting that rhe sequenw 1 t u 2 to R ir clwkwise, henre H. In this example the number 4 group is on the horizontal; thus, to ignore it would not give a "good" assignment directly. The apparent assignment of R based uuon theseouence 1 to 2 to 3 is wrong. and must he reversed to give the correct assignment of S.
650
Journal of Chemical Education
Thus, only when 4 is on the horizontal is there an apparent "crossing" of the numbers, whichis the origin of the need for "switching" the simple-minded initial assignment in which the lowest priority group is "ignored."
' Dietzel, R. A., J. CHEM.EDUC..56,451 (1979).
