In the Laboratory
A General Chemistry Experiment Incorporating Synthesis and Structural Determination1 Hal Van Ryswyk Department of Chemistry, Harvey Mudd College, Claremont, CA 91711-5990 The typical general chemistry laboratory curriculum offers few synthetic opportunities. Synthetic experiments provide insight into central topics such as structure and bonding, which are difficult to illustrate in lecture. More importantly, synthetic experiments provide a laboratory experience unique to chemistry. Modern chemical instruments facilitate meaningful synthetic experiences and serve as a point of departure for the introduction of many topics considered in general chemistry (1). We describe the use of gas chromatography–mass spectrometry (GC-MS) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) coupled with a series of previously published microscale reactions of vanillin (2) to illustrate the concepts of synthesis, structure, bonding, and spectroscopy at the level of general chemistry.
H
O
H
C
O C
Br2
OCH3
CH3OH, H2O
Br
OCH3
OH
OH
(1)
(2) O
O O
NaBH4 NaOH NaOH
H
O C
CH2OH OCH3
Experimental Procedure The synthetic procedures of Fowler (2) were used with the following modifications to streamline reagent handling. In the esterification reaction, a 2-mL syringe is used to remove acetic anhydride from a septum-capped reagent bottle and add this reagent to the reaction mixture. Alternatively, an automatic pipetter or a solution dispenser can be used to expedite this step. The reduction reaction utilizes pre-cut NaBH4 pellets. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was performed with a Specac diffuse reflectance accessory mounted in a Nicolet Impact 400 spectrometer. Spectra were typically recorded as 32 scans at 8 cm{1 resolution and were referenced to a KBr background collected at the beginning of the laboratory period. Nicolet Omnic, Macro Basic, and Macro Panel software were used to provide macros for collecting, labeling, and printing the spectra. GC-MS was performed on an HP 5890 Series II gas chromatograph equipped with an HP-5MS column (30 m × 0.25 mm i.d., 5% phenyl-substituted methylpolysiloxane) and an HP 5971A mass selective detector. The GC temperature program started at 110 °C for 2 min, then ramped at 25 °C min{1 to a final temperature of 200 °C, which was maintained for 3 min. The flow rate was 0.8 mL min {1 using splitless injection. HP Chemstation macros were used to automate collection of the total ion chromatogram, integration, and printing of this information along with mass spectra for each peak. Results and Discussion Vanillin, with its characteristic pleasant aroma, is a natural product familiar to students. Figure 1 shows an ensemble of microscale vanillin reactions reported by Fowler (2). The synthetic procedures are fast, the slowest one requiring 45 min. The short reaction times allow students to run a reaction more than once in a normal laboratory period, should they encounter difficulties. Each reaction produces an easily isolated solid product. Yields are good, ranging from 30% for bromination to 70–95% for esterification
842
OCH3 OH (4)
O
O CH3 (3)
Figure 1. Microscale reactions of vanillin.
and reduction. The purity of the products, as determined by gas chromatography, is high, ranging from 80 to 95%. In fact, the purity is so high that recrystallization can be omitted without detriment to the subsequent spectroscopy. These microscale reactions utilize simple glassware and equipment. Reagents can be supplied in easy-to-use form; for example, NaBH4 pellets are used for the reduction. The products of these reactions are analyzed by DRIFTS and GC-MS. The use of macros on both instruments allows semiautomated analysis and greatly facilitates the turnaround time required to service a laboratory section in real time. A diffuse reflectance accessory allows students to acquire an infrared spectrum of their solid products in a total time of two minutes, without the need to make KBr windows or mix a Nujol mull. Software macros label peaks in the carbonyl region. In a similar fashion, macros on the HP GC-MS allow students to obtain a total ion chromatogram, mass spectra of all peaks, and an integration report within 9 min of sample injection. Examples of DRIFTS spectra are shown in Figure 2. These spectra provide information on the retention or transformation of functional groups in the products. Vanillin shows a broad O–H stretch at 3300 cm{1 and a C=O stretch at 1670 cm { 1 , features retained in the spectrum of bromovanillin. Vanillyl alcohol shows the characteristic O– H stretch, but has lost the carbonyl stretch present in vanillin. Vanillyl acetate shows a new, second carbonyl stretch at 1750 cm{1 , coupled with loss of the O–H stretch present in vanillin. Figure 3 shows the total ion chromatogram for a composite sample containing vanillin and its various microscale products; mass spectra for each of the products are also shown. Each product has an easily identified M+ peak, with the exception of the bromovanillin, which shows an M+2 peak characteristic of bromine incorporation.
Journal of Chemical Education • Vol. 74 No. 7 July 1997
In the Laboratory
Figure 2. DRIFTS spectra of (a) bromovanillin, with O–H stretch at 3300 cm {1 and aldehyde carbonyl stretch at 1672 cm{1; (b) vanillyl acetate, lacking an O–H stretch, with aldehyde and ester carbonyl stretches at 1692 cm {1 and 1753 cm {1 , respectively; (c) vanillyl alcohol, with O–H stretch at 3200 cm {1 but no carbonyl stretching band.
Figure 3. Total ion chromatogram for a composite sample containing vanillin and its various microscale reaction products. Mass spectra, indexed by retention time, are shown for vanillin (5.40 min), vanillyl alcohol (5.69 min), vanillyl acetate (6.14 min), and bromovanillin (7.40 min).
As an example of the chain of reasoning involved in this experiment, consider the reduction of vanillin by sodium borohydride to produce a white powder. DRIFTS of the product shows spectrum 2c, with a characteristic O–H stretch but no C=O peak. GC-MS shows the spectrum indexed at 5.69 min in Figure 3, corresponding to a product with a molecular weight of 154 g mol {1 . The total ion chro-
matogram provides an estimate of the purity of the product, typically 90–95% for this reaction. From the DRIFTS, we infer that the C=O in the vanillin aldehyde group is no longer present, whereas the product retains an O–H group. The mass spectrum shows an increment of 2 in the molecular weight relative to vanillin. Augmented with the knowledge that we have executed a reduction, we attempt to find a Lewis structure for the product consistent with this information and the spectral evidence. The structure of vanillyl alcohol is consistent with this information; comparison of the oxidation number for the methylene carbon in vanillyl alcohol with the carbonyl carbon in vanillin convinces us that a reduction has occurred. This experiment integrates a number of general chemistry concepts. We typically introduce mass spectroscopy early in the companion lecture course to illustrate the existence of isotopes. This experiment extends this first encounter with mass spectroscopy to the determination of molecular weights. The chemistry required to understand the esterification reaction can be approached from a discussion of acid anhydrides of the various second-row elements. If students understand the reaction of acetic anhydride with water to produce acetic acid, then the reaction of acetic anhydride with an alcohol to produce the corresponding ester is a logical extension. The reduction of an aldehyde to the corresponding alcohol can follow from a discussion of redox half-reactions; oxidation numbers can be assigned to individual carbons in organic molecules. Characteristic stretching frequencies of various functional groups in organic molecules can be understood at a basic level with reference to a simple ball-and-spring model, where, to first approximation, the spring force constant of all bonds is constant. The frequency of the resulting vibration will vary inversely with the reduced mass of the atoms bonded, and directly with the bond order, which can be modeled as the number of springs present. We do not require spectral interpretation beyond that presented here, but acquisition of real spectra tied to a molecule they have created often leads students to pose openended questions, such as, “What do these other peaks in the mass spectrum mean?” Such questions provide rich opportunities for one-on-one discussions on a wide range of topics, ranging from ionization potentials to bond energies to normal modes of vibration. We require students to produce a Lewis structure for their product that is consistent with the spectral evidence. In the case of the bromination, there are three products that cannot be distinguished at this level of analysis. For the bromination and esterification, we ask students to write a reaction that yields their product. For the reduction, we ask for a half-reaction involving vanillin. We require students to keep a laboratory notebook, showing procedure, observations, reactions, and reactant/product tables. Finally, we require a summary or abstract of what they have accomplished. We typically have up to 24 students in a laboratory section, supported by one FT-IR and one GC-MS. A four-hour laboratory period is more than sufficient time for students, working in pairs, to run one of the vanillin reactions (perhaps more than once), obtain DRIFTS and GC-MS spectra, and begin to interpret spectra. Students’ reactions to this experiment have been largely strong and positive. They enjoy making new molecules and appreciate hands-on access to modern instrumentation. The puzzlelike quality of drawing a structure of their product consistent with the spectral information appeals to many. On the other hand, some students find the lack of a printed, linear algorithm for structural determi-
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In the Laboratory nation to be disorienting. Being held accountable for a large amount of material from lecture is sometimes daunting. Despite these concerns, we find synthetic experiments valuable for the insight they generate and the experience they provide in an area of chemistry poorly represented in the general chemistry curriculum. Conclusions Microscale reactions of vanillin provide a fast and easy sequence of synthetic reactions for the general chemistry laboratory. The infrared and mass spectra of these products can be analyzed to provide an integrated exercise in general chemistry, covering synthesis, bonding, and spectral interpretation. Modern instrumental methods, such as DRIFTS and GC-MS, can be incorporated into the general chemistry laboratory in support of such integrated experiences, given sufficient attention to sampling accessories and software.
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Acknowledgments The GC-MS and FT-IR used in this experiment were acquired with support from the NSF Instrumentation for Laboratory Improvement program, DUE-9350633. W. G. Sly provided many helpful comments in the development of this experiment. Note 1. This paper was presented at the symposium “NSF-Catalyzed Innovations in the Undergraduate Laboratory” during the Fall 1995 ACS Meeting in Chicago.
Literature Cited
Journal of Chemical Education • Vol. 74 No. 7 July 1997
1. See “Highlights: Projects Supported by the NSF Division of Undergraduate Education” in recent issues of J. Chem. Educ. for a general discussion of innovative uses of instrumentation in undergraduate laboratories. 2. Fowler, R. G. J. Chem Educ. 1992, 69, A43.
