Directive effects in electrophilic aromatic substitution. An organic

Robert R. Beishline. J. Chem. Educ. , 1972, 49 (2), p 128. DOI: 10.1021/ed049p128. Publication Date: February 1972. Cite this:J. Chem. Educ. 49, 2, XX...
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Directive I ffects in Electrophilic Robelt R. Beirhlina

Weber State College Ogden, Utah 84403

Aromatic Substitution A n organic chemistry experiment

This experiment applies the classical ideas of structure proof to establish the position of substitution in an electrophilic aromatic substitution reaction. Though the experimental work is synthesis, a problem-solving approach is used in an attempt to avoid the routine, cook-book attitude that is often generated by synthetic type experiments. Before he can complete this experiment, a student must consider some concepts that are new to him, and obtain certain information from the literature. The general concepts and goals of the experiment must therefore be discussed in some detail with the student prior to the time the work is to be performed. The student is given the procedure for the monobromination of acetanilide in glacial acetic acid,' but is not told where on the ring the bromine will substitute. After the synthesis has been completed, he is required to prove the structure of the product (estahlish the position of bromination) by either an unambiguous, independent synthesis or by the preparation of a known derivative. By searching the literature (mostly secondary sources such as textbooks and laboratory manuals) the student will discover that the bromine substitutes almost entirely in the para p o ~ i t i o n . ~This knowledge does not defeat the problem-solving approach, however, since the student must still prove that the bromine has substituted in the position indicated by the literature. The student then chooses which method of structure proof he will use, and must determine for himself what chemical reactions will be needed to accomplish it. He is given extra credit if he finds his own experimental procedure to carry out the desired reactions. (A variety of laboratory manuals are made available for the students' perusal.) Alternatively, for no extra credit, the instructor will give him the needed procedure. I n either case, he must have the instructor's approval before he begins the structure proof. After completing the experimental work, the student is asked to write a mechanism for the bromiuai tion of acetauilide that is consistent with the determined position of bromination. In actual practice, the most commonly used independent synthesis is the preparation of p-hromoacetanilide from, p-hromoaniline. This specific synthesis is not given in the usually available laboratory manuals; however, general procedures for the acetylation of arylamines are readily adapted to the acetylation of p-bromoaniline. For example, the LumiereBarbier method for acetylation of arylamines with 128 / lournd of Chernicol Education

acetic anhydride in aqueous medium3 works well for the acetylation of p-bromoaniline. The most commonly used derivative preparation is the hydrolysis of the p-bromoacetanilide to p-bromoaniline. This specific procedure is included in many of the current organic laboratory manuals. Experience has shown that the more satisfactory methods are those which use steam distillation to separate t,he pbromoaniline from unreacted p-bromoacetanilide.' When steam distillation is not used, separation of unreacted starting material from the desired product is a problem. Reaction schemes other than the two mentioned above are approved if they are not precluded by excessive time requirements or the unavailability of chemicals. Either mixed melting points or infrared spectroscopy can he used to show the identity of the brominated acetanilide with the independently synthesized product, or the identity of the derivative with an authentic sample. The students need an explanation of the principles involved in a structure roof bv inde~endentsynthesis or derivative preparation. The explanation is facilitated by an example such as the following



Prove that nitration in reaction (1) actually occurs at the position meta to the carboxyl group. Proof by an unambiguous, independent synthesis

'For example: ADAMS,R.,

J o n ~ s o ~J., R.,



C. F. JR., "Laboratory Experiments in Organic Chemistry," 6thed., The Maemillan Co., New York, 1970, p. 307. a R ~ ~ ~ 1%. R T M.,~ GILBERT, , J. C., RODEWALD, L. B., -4ND WINGROV~, A. S., "An Introduction to Modern Experimental Organic Chemistry,'' Holt Rinehilrt, and Winston, Ine., New York, 1969, p. 293. a Footnote 1, p. 300. R. Q., VANDERWERF, C. A., A N D 'For example: BREWSTER, McEwrN, W. E., "Unitized Experiments in Organic Chemistry," 3rd ed., Van Nostrand Reinhold Co., New York, 1970, p. 161.

The essential features of this structure proof are

The essential features of this structure proof are


The structure of I1 must be known. b. During the course of reaction (2), neither the methyl-ring bond nor the nitrogen-ring bond is broken. e. Structure 111 must be shown to be identical to structure I.

d . During the course of reaction (3), neither the earboxyl-ring bond nor the nitrogen-ring bond is hroken. e. Structure IV must be shown to be identical to a n authentic sample of m-aminohenaoic acid.

Reasoning: Since the substituents in I1 are known to be meta to one another (a, above), and since b (above) is valid, tthen the carboxyl and nitro substituents in I11 must also be meta to each other. If I and 111 are identical (c, above) then the nitro group must be meta to the carboxyl group in (I), just as it is in (111). Proof by preparation of a known derivative

Reasoning: If IV is identical to an authentic sample of m-amino beneoic acid (e, above), then the carboxyl and amino groups in IV are obviously meta to each other. Since d (above) is valid, then the nitro group must be meta to the carboxyl group in I. In actual practice, the above described experiment is done in conjunction with a study of relative rates of electrophilic aromatic ~ubstitution.~The total experiment takes two laboratory periods, the first being devoted to the relative rate work and the bromination of acetanilide, and the second to the structure proof. The int,ervening week allows the students time to complete their literature research and finalize their procedures for the structure proof. CASANOVA, J., J. CREM.EDUC.,41,341 (1964).

Volume 49, Number 2, February 1972