In the Laboratory
Preparation and Identification of Benzoic Acids and Benzamides: An Organic “Unknown” Lab Douglass F. Taber,* Jade D. Nelson, and John P. Northrop Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716; *
[email protected] Wet chemistry for the determination of the structure of an “unknown” has long been part of the organic laboratory curriculum. Traditionally, a several-week segment of the laboratory course has been devoted to tests for functional groups and to the preparation of crystalline derivatives. One of the primary purposes of this segment was to teach students to have confidence in their own scientific results. We describe here an experiment that retains many of the intellectual aspects of the more extensive exercise, yet can be easily accomplished in two laboratory periods. In this experiment, the unknown is drawn from the set of monosubstituted and disubstituted benzene derivatives whose the substituent(s) can be methyl, methoxy, bromo, or chloro. With four possible substituents and the possibility of 1,2-, 1,3- or 1,4-substitution when two substituents are present, the list of potential unknowns is quite extensive. To deduce the structure of the unknown, illustrated by toluene 1 (see Scheme I), it is reacted with oxalyl chloride and AlCl3, to give the acid chloride 2 (1). Hydrolysis of 2 gives the crystalline acid 3; reaction of 2 with aqueous ammonia gives the benzamide 4. O
O
Cl Cl
Cl
O
AlCl3
1
2
aq. NH3
H2O
O
O
OH
NH2
3 4 Scheme I
By titration with 0.1 N aqueous NaOH (standardized by titration against benzoic acid) (2), the student can derive the molecular weight of the acid and so determine which substituents are attached. For monosubstituted unknowns, the melting points of the acid and the benzamide confirm the substituent deduced from the equivalent weight. For disubstituted unknowns, these melting points also allow the assignment of the pattern of the substituents on the benzene ring. We have found two limitations to this procedure. The first is that the initial unknown cannot be dimethoxy (an electron transfer reaction intervenes [1 ]) or dihalogen (unreactive). The other limitation is that the acid 2 must be water free 828
before the titration. This requirement is easily accomplished by letting the acid oven dry between laboratory periods. Although one might expect the initial electrophilic aromatic substitution to give mixtures of regioisomers, it in fact appears to be highly selective, converting monosubstituted aromatics to the 1,4products. Disubstituted benzene derivatives give single products also. Structures of unknowns and their product acids and melting points of the product acids are shown in Table 1. Experimental Section
Acid Chloride To 1.0 g of the unknown aromatic compound in a 50-mL Erlenmeyer flask add 10 mL of CH2Cl2 containing 10 wt % of oxalyl chloride (in hood! CAUTION: Corrosive!). Stir the mixture while it cools in an ice-water bath. Add 1.0 g of anhydrous AlCl3 (CAUTION: Corrosive! Do not breathe dust!) in portions with swirling. Allow the reaction to subside after each addition. If the AlCl3 does not visibly react (dissolution, gas evolution), add the rest of it and then warm the mixture to room temperature until a reaction is observed. Most of the AlCl3 should dissolve to provide a clear orange-yellow solution. When the reaction has stopped bubbling, pour the mixture over 50 mL of crushed ice in a beaker and rinse the reaction flask with a little additional CH2Cl2. Swirl the mixture until the orange color fades to a pale yellow. Separate the layers, extract the aqueous layer with 10 mL of CH2Cl2, and concentrate the combined CH2Cl2 extracts in vacuo or by distillation. Acid Preparation To the concentrated residue, add 20 mL of 1 M aqueous KOH and stir for 15 min at room temperature. Extract the KOH solution with 2 × 10 mL of MTBE (methyl t-butyl ether; diethyl ether would be acceptable also) and set the extract aside to recover the unreacted unknown, if necessary. Acidify the aqueous phase with concentrated aqueous HCl to pH = 1, and filter the precipitated acid. Wash the solid acid with cold distilled water and let it thoroughly air dry (drying it in an oven is even better) overnight before titration. A portion of the acid should be recrystallized from ethanol–water to constant melting point. If the acid does not precipitate directly on acidification, extract the aqueous layer with 3 × 10 mL of CHCl3, dry the combined CHCl3 extracts with sodium sulfate, filter, and concentrate in vacuo or by distillation. Acid Titration Following the published procedure (2), precisely standardize 0.1 M aqueous NaOH by titration of benzoic acid
Journal of Chemical Education • Vol. 76 No. 6 June 1999 • JChemEd.chem.wisc.edu
In the Laboratory Table 1. Melting Points of Some Product Acids Unknown
Product Acid Structure
mp/ºC 182
CO2H
OCH3
OCH3
184
CO2H Br
Br
254.5
CO2H
Cl
Cl
243
CO2H
in ethanol, using a phenolphthalein (or bromthymol blue) endpoint. Dissolve the unknown acid in ethanol and titrate it using the standardized aqueous NaOH. From the titration, calculate the exact molecular weight of the unknown acid.
Amide Preparation To the initial crude acid chloride, add 20 mL of concentrated aqueous ammonia (in the hood!) and stir for 15 min. The solid amide will usually precipitate and can be filtered and washed with cold distilled water before air drying. If the amide does not precipitate directly, extract the aqueous layer with 3 × 10 mL of CHCl3, dry the combined CHCl3 extracts with sodium sulfate, filter, and concentrate in vacuo or by distillation. Dissolve a small portion of the amide for a TLC sample. If a mixture is observed, work out the TLC separation, then separate the components by silica gel chromatography. A TLC solvent of 10–30% by volume acetone–CH2Cl2 works well for these amides. Recrystallize the amide(s) from ethanol– water to a constant melting point. IR Spectroscopy If an IR instrument is available to the students, an instructor might consider making available IR spectra of each of the product benzoic acids (and amides, if that part of the lab is used) that the students are expected to make, with the correct structure on each. The students could then use IR comparison to confirm the structural assignments. Acknowledgments
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We thank D. A. Nicolson and B. B. Street for their unfailing support.
CO2H
Literature Cited 127
CO2H
1. Osman, M. A. Helv. Chim. Acta 1982, 65, 2448. 2. Bell, C. E. Jr.; Clark, A. K.; Taber, D. F.; Rodig, O. R. Organic Chemistry Laboratory: Standard and Microscale Experiments, 2nd ed.; Saunders: Philadelphia, 1997; p 397.
JChemEd.chem.wisc.edu • Vol. 76 No. 6 June 1999 • Journal of Chemical Education
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