Stanley G. Smith
schoolof
Chemical Sciences University of Illinois Urbana, Ulinois 61801
1(
~~~~~~~~Aided Teaching of OrgcldC Synthesis
Development of the facility to outline suitable schemes for the synthesis of compounds is an important component of introductory courses in organic chemistry. Even relatively simple molecules can provide a stimulating intellectual challenge to beginning students. However, to encourage imaginative a p proaches, it is important to allow each individual wide freedom in the choice of starting materials andreactants. I n addition, rapid evaluation of the correctness of a proposed synthetic scheme promotes interest and confidence. These goals can now be largely achieved through computer-based teaching methods (1-3) which make possible essentially instantaneous evaluations of students' work on an individual basis. The utilization of computer-based teaching methods is often optimized by programs which permit the computer to calculate the correctness of a given response rather than to compare a student's answer to some preconceived and preprogrammed solution. Although multistep organic synthesis cannot be readily defined by a solvable mathematical equation, algorithms have been devised which permit a computer to judge the correctness of a proposed synthesis, step by step, based on general principles rather than on preconceived particular reactions or synthetic schemes. This approach permits a student to verify the correctness of his work even though it may be quite different from that outlined in the textbook or lectures and, in fact, not even considered during the design of the instructions to the computer. The approach to computeraided teaching of organic synthesis illustrated here wes written (4) on the PLAT0 computer-based educational system developed a t the University of Illinois (6). At present twenty students can work independently using a typewriter keyset to communicate in normal chemical notation with the computer. Both the student's work and the computer-generated formulas and comments appear on individual television screens. Response times are less than 1 see. To minimize the requirement for typing s k i and provide for rapid progress through a problem, the computer has been assigned the task of drawing the appropriate structural formulas. The start of a typical problem, a t the first semester organic chemistry level, is illustrated in Figure 1. The student is first asked to indicate the starting material of his choice. Either formulas, common names, or IUPAC names may be used. The requirement of three carbons or less in the starting material was imposed because of the desire, for pedagogical reasons, to restrict these particular problems to compounds with relatively few carbon atoms in order to focus attention on the chemical reactions involved. At present, 53 diierent starting materials are recognized, each by several names (6).
Figure I. wonmg pomr ror o lypmeol synmaslr promem. m rnw oxamplo. the studea must reled o rtorting moteriol with three carbons or lers for the preparation of 3-pentanone.
lm tk name or formula o f the startIra m ~ l e r l d (3 carbons or less).
Figure 2. Propionaldehyde hor boon roloded b y student as the starting moteriol. The name appears on the screen as it is typed. Either namesor formulor may be used.
T o s t a r t awln press DATA. Figure 3. In response to the suggested starting moterid, the computer has drawn tho structural formulo of the starting material and the produd on the r e The .*dent must now indicate the reomnh for the first stelr in his reaction sequence.
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m synthesis Is completed. lo wrk THIS problem eseln 10 lo on press NEXT
c%~"z="z% TO
start e s d n
ptess
ORT~.
Figure 4. Here, a student has selected ethylmognerivm bromide as t h e second reoctont, and t h e computer has determined the natureof t h e product ond d r o w n it on the screen. T h e reagents for t h e next step can now b e indicated,
I
WT~.
Figure 6. The selection of the reagent CrOi by the student has completed the synthesis. The choice of working this problem a different w a y or o f selecting o new problem is offered b y the computer.
lk hc.mthes1s I S Carplsted.
TO s t a r t aseln Press OnTn
-
lo w k THIS problm asaln 10 go on press NEXT :
, -.
-
m~n.
-. ..
Figure 5. The computer has i d t h a t 3-pentanol is the p r o d u d which results from treatment of t h e mognerivm salt, Figure 4, with aqueous w i d .
Figure 7.
The computer responds to a suggested starting material by drawing the structural formula and requesting that the student type the name or formula of the reagents to be used in the first step of the synthesis. In Figure 2, propionaldehyde has been selected as the starting material, and in Figure 3 the reagent for the first step is to be indicated. Any of 134 reagents, which can be either organic or inorganic, may be used in each step. Again, to promote ease of use, each reagent is recognized by several names. Additional synonyms or chemically similar reagents may be incorporated into the lesson in about 1 miu (6), even while a class is using the program. Additional reagents and reactions are currently being added to expand the capability of the program. After a reagent has been indicated by the student, the computer draws the structure of the organic product of the reaction (Fig. 4). To determine the structure of the product, the computer first classifies the starting material by type, location, and number of functional groups. Then checks are made to see if the reaction between the indicated reactant and the general class of compound represented by the starting material is in the program. If the conversion is not recognized, the student is advised that PLAT0 does not know that reaction. If the combination corresponds to a type of reaction recognized by the computer, then additional checks on the chemistry are made where appropriate. For example, the questions of substitution versus elimi-
nation and orientation of elimination or orientation of addit,ion to multiple bonds are resolved by calculations based on linear free energy (7) type considerations. This approach provides the flexibility required to determine the course of the reaction between reactants not specifically considered in the computer program. The alternative approach of cataloging the reaction of each reagent with every possible molecule a student might construct rapidly becomes quite cumbersome as the student is given increased flexibility in the choice of react,ion sequences and was therefore not used. The product of the react,ion automatically becomes the starting material for the next step, Figures 4 and 5, until the synthesis is completed, Figure 6. Should a given scheme not lead to the product, it is possible to start over at any stage by pressing a single key. Since there are many acceptable solutions to each problem, upon completion of a synthesis the student is asked whether he wants to work the problem again or try a different problem. An alternative approach to this particular problem is summarized in Figure 7. Of course, many ot,her routes are acceptable. Because all of the chemistry programmed into the computer is available to the student at any h e , the only change in the computer program required for each new problem is the information on the structure of the final product needed to recognize the completion of the synthesis. Thus, the present set of twenty problems is readily modified or expanded.
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Students may obtain help in working any given problem by simply pressing a key labeled HELP. For these problems, the help sequence consists of a discussion of an approach to the synthesis. It should be noted that, in actual use, this lesson is preceded by a more classical computer-based tutorial development of both the specific chemistry required and general approaches to multistep synthesis. In addition to providing an efficient way to study some aspects or organic synthesis, the program described here provides a format by which a chemist may communicate with a computer in the mutually understandable language of chemical names and structural formulas to address the predictive power of complex equations which summarize a large body of chemical information (8). That is, with the introduction of additional predictive routines, such a program becomes not only a flexible and highly personalized learning aid but an efficient summary of some aspects of the chemical literature. This work was made possible by the cooperation and
assistance of Professor D. L. Bitzer, Director of the Computer-Based Educational Research Laboratory, his staff, Mr. Paul Tenczar, who developed many aspects of the programming procedures used, and Professor D. Y. Curtin. The Computer-Based Educational Research Laboratory is supported by ONR NONR 3985 (08), Advanced Research Projects Agency; National Science Foundation, Metropolitan Museum of Art, Mercy Hospital Nursing Training, U. 8. Health Education and Welfare; and the U. S. Navy. Literature Cited (1) SMITH, 8. G., J. C ~ MEouo., . 47,608 (1970). (2) T h ~ s u r rF. , D., Chem. ondEno. NCWD. 44 (Jan. 19, 1970). S., *ND L*GOIVBKI,J. 1.. J. CHEU. EDUC..47, 01 (3) (a) CABTLEBERRY. (1970): (b) ROnExr*Lo, L. B., CUPL,G. H., A N D L*eow8n, J. J., Cneu. Enuc., 47, 134 (1070). (4) Am==. R. A.. A N D TENCZAR, P., "The TUTOR Manual." Report X-4. Computer-Based Eduoational Laboratory, University of Illinois. Urban*. Ill.. 1969. ( 5 ) AL?enT, D., AND B m e ~ n D. , L., Science, 167, 1582 (1970). R ,unpublished work. (6) T E N C ~P., (7) HAUMETT.L. P.. " P h y d d Organic Chemistry," 2nd ed., MoGrswHill Book Company, New York. 1970. (8) COB&=, E. J. AND WIPBE, W. T . , Sciance, 166, 178 (1969).
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