In the Classroom
Bird-in-the-Hand Method for Determination of Absolute Configuration on Fischer Projections Edward Siloac University of Virginia, Charlottesville, VA 22906
For beginners with little experience in stereochemistry, determining the absolute configuration of chiral molecules can be difficult. Fischer projections may be particularly confusing to the new student. To dispel confusion, many methods have been developed to help students determine the absolute configuration of chiral molecules and Fischer projections (1–13). Some focus on geometric or rotating techniques (6–12); others use the hands as three-dimensional molecular models to help visualize Fischer projections (1–5). It is up to the student to choose the technique that fits his or her own strengths the best. However, one obstacle that students may face when applying these techniques is memorizing the method’s protocol, be it reading from a table (7), drawing a triangle (6 ), or remembering which hand to apply to a particular stereogenic center (1). For example, Beauchamp (1) uses the hand to form the tetrahedron of a chiral molecule. The lowest-ranked substituent by the Cahn–Ingold–Prelog system is placed on the wrist, then is rotated away. His model is then applied to Fischer projections with more than one stereogenic center by considering each center as one molecule, then determining its absolute configuration. Beauchamp’s technique and others like it (2–5) are very useful, especially for sawhorse models and ball-andstick models of chiral molecules. For Fischer projections, however, there is an easier method. The Bird-in-the-Hand Technique The bird-in-the-hand technique for Fischer projections creates a model with the hand that mimics the 3-dimensional conventions of the Fischer projection. All one needs to understand to use this method is: 1. That vertical lines of the Fischer projection go away from the viewer and horizontal lines project towards the viewer (14) 2. The Cahn–Ingold–Prelog R–S notational system (13, 14) 3. Clockwise from counterclockwise
Consider a Fischer projection with one stereogenic center (Figs. 1, 2). With palm up, the index finger is pointed away from the viewer, and the thumb and middle finger are pointed up (Fig. 3). This represents the Fischer projection; the index finger is the substituent at the top of the vertical line, the thumb and index finger are the substituents on the horizontal lines, and the arm represents the bottom substituent (usually down the carbon chain). Next, using the Cahn– Ingold–Prelog system, the substituents are numbered on the Fischer projection in decreasing priority and are assigned to the representative fingers or the arm (Fig. 3). The hand or arm is rotated so that the lowest-ranked substituent (in example 1 this would be hydrogen) points away from the viewer (if the observer uses her right hand, the hydrogen group is on the thumb and the thumb should be turned to point away (Figs. 4, 5). The viewer should end up looking at the back of the hand with the index finger and the middle finger pointing up. If the lowest-rank substituent is on the arm, the viewer 798
H3 C 3
Figure 1. A simple Fischer projection, in order of priority (highest is 1, lowest is 4) from the stereogenic central carbon is 1, chlorine; 2, the trichloromethyl group; 3, the methyl group; and 4, the hydrogen.
H Cl Cl Cl
Cl
H
1
4 Cl3C 2
Figure 2. A molecular model of the Fischer projection. Note that the trichloromethyl group and the methyl group project back away from the viewer and the chlorine and hydrogen atoms project up towards the viewer.
Cl
Figure 3. With palm up, index finger pointing away, and thumb and middle finger pointing up, the fingers are numbered according to the Fischer projection. Note that the hand orientation matches the standard orientation of Fischer projections (see molecular model).
Figure 4. Rotate the thumb so that it faces down (note that if the hydrogen is on the middle finger stop here and point the middle finger away from the viewer, then assess the direction from 1 to 2 to 3). Since the hydrogen is on the thumb in example 1, rotate the thumb so that it points away.
Figure 5. After the hand has been rotated so that the thumb points away from the viewer, then the direction from 1 to 2 to 3 is determined. In this case, the direction is clockwise, so the absolute configuration of the stereogenic center is R.
Journal of Chemical Education • Vol. 76 No. 6 June 1999 • JChemEd.chem.wisc.edu
In the Classroom
should be looking at the three fingers pointing towards her; if the lowest-rank substituent is on the middle finger, the viewer should be looking at an “L” on the back of the hand made by the index finger and thumb. Finally, the order of substituents from 1 to 2 to 3 is determined (clockwise direction vs counterclockwise direction). As is customary, clockwise is R and counterclockwise is S. For Fischer projections with more than one stereogenic center, the viewer starts at one center, then systematically proceeds to the next applying the same method. Unlike other methods of absolute configuration determination using hands (1–5), it does not matter which hand one uses to apply the bird-in-the-hand method. Also, the bird-in-the-hand model takes the Fischer projection into three dimensions; there is no need to shift any perspective until after the substituents have been numbered. This is particularly important to new students who have trouble enough remembering the standard convention of Fischer projections. Garret (3) noted that using the hands to observe chiral molecules provides a molecular molecule set that the student can apply anywhere. The bird-in-the-hand method helps make Fischer projections easily visualized and absolute configuration of stereogenic centers on those projections quickly identified. After all, a bird in the hand is worth two in the classroom: visualization and absolute determination of stereochemistry on Fischer projections.
Acknowledgments The bird-in-the-hand method was developed during my undergraduate study of organic chemistry under Francis A. Carey at the University of Virginia. I would like to thank the following for their help on the bird-in-the-hand technique: my father for giving me all of the resources, Francis A. Carey for his expertise, Stephanie Thompson for her drawings, Kian Tan for his encouragement, Joyce Wong for her support, and Barry Matrana for his review. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
Beauchamp, P. S. J. Chem. Educ. 1984, 61, 666–667. Mattern D. L. J. Chem. Educ. 1985, 62, 191. Garret, J. M. J. Chem. Educ. 1978, 55, 493. Charles J.; Thoman S. J. Chem. Educ. 1976, 53, 502–503. Barta, N. S.; Stille, J. R. J. Chem. Educ. 1994, 71, 20–23. Yongsheng, H.; Cailan, W. J. Chem. Educ. 1992, 69, 273. Reddy, K. R. N. J. Chem. Educ. 1989, 66, 480. Bhushan, R.; Bhattacharjee, G. J. Chem. Educ. 1983, 60, 181. Epling, G. A. J. Chem. Educ. 1979, 59, 650. Idoux, J. P. J. Chem. Educ. 1982, 59, 553. Brun, Y.; Leblanc, P. J. J. Chem. Educ. 1983, 60, 403–404. Ayorinde, F. O. J. Chem. Educ. 1983, 60, 928–929. Cahn, R. S. J. Chem. Educ. 1964, 41, 116–125. Carey, F. A. Organic Chemistry, 3rd ed.; McGraw-Hill: New York, 1996; pp 274–279.
JChemEd.chem.wisc.edu • Vol. 76 No. 6 June 1999 • Journal of Chemical Education
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