Using GC-MS to Determine Relative Reactivity Ratios R. Daniel Bishop, Jr. Colorado State University, Fort Collins, CO 80523 We have developed a simple experiment that demonstrates the use of GC-mass spectrometry in the separation and analysis of mixtures while a t the same time teaching some of the basic concepts involved in the analysis of mass s ~ e c t r adata. l Furthermore. this experiment uses the GCmass spectrometer a s a tool for solving a fundamental physical organic problem, finding the relative reactivity ratios of primary, secondary, and tertiary hydrogens toward free-radical substitution hv chlorine atoms. The experiment fits nicely into one three-hour laboratory period, uses microscale techniques, . . and consistently. eives - -good results. Organic students are taught early in the first semester that free-radical halogenations occur preferentially a t tertiary sites, and many organic texts list "relative reactivity ratios" to indicate how much more reactive tertiarv "hvdro. gens are than secondary or primary hydrogens toward abstraction by halogen atoms. For example, a table in Fessenden and Fessenden ( I ) lists a primary to secondary to t e r t i a n relative reactivitv ratio of 1.0 to 4.3 to 6.0 for chlorinkion reactions invoiving molecular chlorine. Before GC-mass spectrometry, any experiment that might allow students to determine these values for themselves would be a daunting task for an undergraduate laboratory. The main difficulties to be overcome in a n experiment of this type are adequate separation, identific'ation, and auantification of seometric isomers in the nroduct mixture. Modern gas chromatography, with temperature programming and high resolution capillary columns provides the tool for solving the separation and quantification problems. The attached mass spectrometer provides the iuformation necessary to identify the specific geometric isomers as they elute from the column. The microscale svnthesis reaction we chose for this experiment uses me~hylcyclohexanea s the substrate, a hydrocarbon with three orimarv hvdro~ens.one tertiarv hvdrogen, and 10 second& hydro~ens.%ulfurylchloride and benzoyl peroxide are used to generate chlorine atoms (2). These reagents are mixed together and the mixture is refluxed for 30 min in a s e t that ~ ~ e m ~ l o v sa eas trap to entrain HCI and SOz gases i h a t are ieneratei. Aftepthe reflux oeriod. the reaction mixture is distilled and the distillate is subjected to analysis on the GC-mass spectrometer. There are eight monochloro methylcyclohexane isomers (not counting enantiomers) produced in this reaction. Only one of these isomers has the chlorine a t a nrimarv site. and only one is a tertiary isomer. The remaining six compounds are secondaw monochloro isomers. with the chlorine attached to one of the five remaining ring carbons, and ori. the ented either cis- or trans- to the methvl e r o u ~ With column and temperature program des&ed Gelow, six or seven of the eight isomers are clearlv distinmishable in the gas chroma~ogram.Furthermore, the primary and tertiary isomer peaks are separated from the cluster of secondariisomer peaks, making analysis by comparing peak areas quite feasible. The retention times for the monochloro methylcyclohexanes all fall within the six to 10-min range. Part A of the figure shows this portion of the GC trace of a student's distillate from a typical run.
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Identification of the peaks in the gas chromatogram is based on analysis of the mass spectrum associated with each peak. First. the student must identifv those GC oeaks t h a t 'are the monochloro isomers of m~hylcyclohe'xane. This is done hv identifvina those GC oeaks that have a cor" responding mass spectrum with a molecular ion showing UD a t rnlz 132. the molecular weieht for C?H,aCI (with Cl2 ( m l z 134) that 3 b . One might also look for the ~ + peak corres~ondsto C7Hj1C1(with C1-37). There should be a roughiy 3:l intensit$ ratio of these two peaks-the signature for monochloro compounds. Unfortunately, not all of the monochloro isomers yield stable enough molecular ions to show consistentlv the M+2 Deak. A coude do, however. and students can see that thisrelationship doesoccur. Once the monochloro methylcyclohexane peaks in the gas chromatogram have been identified, the mass spectrum for each of these isomers is analyzed to identify which of the peaks corresponds to the primary isomer and which to the tertiary isomer. The primary isomer is the only one capable of fragmenting with loss of a CHZCIgroup (mass = 49 with Cl-351, and only one of the mass spectra shows a very strong fragment peak a t mlz 83 (M-49) (Part D of the figure). Unlike some of the other mass spectra, this spectrum also shows no fragment peak a t rnlz 117 (M151, because, of course, there is no methyl group that could he lost from this isomer! The tertiary isomer also has a distinctly identifiable mass spectrum. All eight isomers should he expected to be able to lose a chlorine atom.. eiviup rise to a n M-35 fraement peak a t rnlz 97. However, because the relative intensities of the peaks in a mass s ~ e c t r u mreflect the relative carbocation &abilities, with the most stable cation fragments giving rise to the strongest peaks, the intensities of the m l z 97 peaks in the different spectra should be very different, with only the tertiary isomer having a significant, intense peak a t rnlz 97 because loss of its chlorine atom gives rise to the stable tertiary cation. Indeed, only one of the mass spectra shows this intense peak a t rnlz 97 (Part B of the figure). The remaining four monochloro isomers' peaks that show up in the gas chromatogram clustered around eight minutes all have mass spectra that look similar to that shown in Part C of the figure. These isomers are clearly secondary monochloro isomers. For sake of the analvsis. the Deak areas for all of the secondary monochloro isomers ;an be added together. Because of this, it isn't necessary to achieve a clean seDaration of these peaks with the gas chromatograph. T;pical peak areas printed out for this analysis are 85 for the primary isomer, 1073 for the sum of the secondary isomer peak areas, and 320 for the tertiary isomer. Dividing the first value by three and the second value by 10 to obtain a ratio on a "per hydrogen" basis gives values of 18,107, and 320. Normalizing the ratio by dividing each number by the smallest value, 18, gives a relative reactivity ratio of 1 to 5.9 to 18 for primary, secondary, and tertiary hydrogens. Ratios ranging down to 1:6:10 have been obsewed a s well. Students might then be asked to discuss whv this e x ~ e r i mentally determined ratio is different from &e ratio huhlished in their text. This discussion should include differences in reactions involving molecular chlorine versus
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Figure 1. A. Segment of the distillate gas chromatogram showing six peaks for the monochloro product isomers. (The remaining two isomer peaks are presumed to be buried beneath the four peaks clustered around the eight-minute mark). B. Mass spectrum for the peak at 7.087 min retention time. C. Mass spectrum for the peak at 7.963 min retention time. D. Mass spectrum for the peak at 9.059 min retention time.
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Journal of Chemical Education
sulfuryl chloride, differences between using t-butyl versus methyl cyclohexyl tertiary hydrogens, and propyl versus cyclohexyl secondary hydrogens. Experimental conditions (e.g., reaction temperature) might also have an effect. Is it valid to assume that the combined peak areas for the overlamine secondarv isomers orovides the same area value that one would odtain if thebeaks were clearly separated? And what of the one or two secondarv isomers whose oeaks do not show up on the GC trace? he assumption that all 10 secondarv hvdroeens are eauallv susce~tibleto attack " and abstraction may not be correct! Final&, if your teaching goals include a more detailed analysis of mass spectral d a t a and mechanistic interpretations-for the formzkion of other important fragment peaks, this experiment provides a good ~ ~ ~ o r t u n i t ; t odo 'this a s well. %or example, the f r a m e n t peaks a t miz 39,41, and 55 might correspond to a n iromaiic cyclopropenyl carbocation, the ally1 carbocation, and perhaps a nonclassical C4H7+tetracyclic carbocation structure. One final note worth emphasizing. Too often we simplify organic reactions when teaching the basic principles of organic chemistry. Give a student a n exam question that asks him or her to show the major product one might obtain in the free-radical chlorination of 2-methylpropane. The "correct" answer will show substitution a t the tertiarv site. This experiment demonstrates clearly that things are much more complicated! Though the tertiary site might be more reactive, if there are enough other sites available, the major . -product(s) might indeed be those with substitution a t secondary or evenprimary sites. For example, if the tertiary hydrogen on 2-methylpropane is six times as reactive a s the primary hydrogens toward chlorination by Clz, a s indicated in Fessenden and Fessenden ( I ) , the major prodsince uct of chlorination will be l-chloro-2-methylpropane, there are nine possible primary hydrogens that could be attacked. The tertiary isomer, 2-chloro-2-methylpropane will constitute only 40% of the monochlorinated product mixture. A
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Experimental Agas trap is prepared by placing 2 to 5 mL of 10% NaOH into a beaker large enough to accommodate a n inverted funnel. Afunnel that is attached to a length of latex tubing is inverted and suspended just above the surface of the NaOH solution. A syringe needle is attached to the other end of the latex tubing. In this reaction, a f&e-fold excess of methylcyclohexane is used to reduce the amount of dichloro oroducts that also are pnduc(4 in this reaction. I n tht: hood, to a 5-mL roundbottomed flask cmtainine il b d i n e rhiu IS added 0.40 mL t5 mmoles of sullul:vl rihorlde, soi),~ii),, and 3.2 m1. ,25 mmolrs of methylcyrlohexane. .Caution: SulFur~Ichloride i~ n highly roxie a n d eomoiivr liqtlid E w n its w p o v s n r r rorrosiw to humnn skin nnd mucous
mrmhmnrs
Approximately 0.03 g of benzoyl peroxide is added to the reaction mixture.
Caution: Benzoyl peroxide is a strong oxidizing agent, and the pure reagent will explode, if heated.
The flask is then equipped with a reflux condenser. The top of the condenser is capped with a rubber septum through which the syringe needle is inserted. The round-bottomed flask is then placed in a n aluminum heating block or sand bath and the mixture is heated to reflux (methyl cyclohexane boils a t 101 "C). Agentle reflux is maintained for 30 min. After 30 min, the flask is cooled to room temperature and the apparntus is set up for s~mple distillation. l'he nt~ckof the: flask and thc. distilliltion head are wrapped with aluminum foil for insulation, and all but the last 112 mL of reaction mixture is distilled over into the receiver. The distillate should be colorless. About 1 uL of the samole is iniected into the GC-mass spectrometer for analysis. Our GC-Mass spectrometer is a Hewlett-Packard Model 5890 Series gas chromatograph with a Hewlett-Packard Model 5970 quadrupole mass spectrometer attached a s the detector. The column used for the analysis is a 30 m x 0.25 mm capillary column packed with DB1701 with a 0.25 micron film thickness. The temperature program has a 2.5-min solvent delay period (during which the mass spectrometer detector is turned off) to accommodate the large amount of unreacted methylcyclohexane that comes through a t the beeinning of the run. The initial temperature i i 6 0 'C, which is heid for 5 min, then the oven temperature is ramped upward a t a rate of 10 deglmin to 100 "C, then ramped upward a t 25 deglmin to 25 "C and held a t 250 "C for 5 min before cooling to 60' for the start of another run. Because of the size of our class, only two or three student samples are actually run during the last half of each lab period. These runs are used a s live demonstrations for six to eight students a t a time. The maioritv . . of students then do tgeir actual analysis on data presented to them in a handout. This handout consists of the chromatomam peak list (including retention times and relative peak areas), a cops of the full chromatopram, and three mass spectra, one each for the primary and tertiary isomers, a n d a representative mass spectrum from one of the secondary isomer peaks, as in the figure. Acknowledgment 'lh(~ author would like to acknowledge the support of the National Science Foundation IGrant CHE-8952157, whirh provided the funds for the purchase of our GC-mass spectrometer. Thanks also to Don Dick, our technician specialist, who keeps our instruments maintained and in good working order and to Marie Risheill, our indefatigable laboratory coordinator, who keeps our undergraduate organic labs humming along. Literature Cited 1. Fessenden, R. J.: Fessenden, J S. Organic Chemislq 4th ed.; Brooka4ole: Pacific Grave. CA. 1990: p 236. 2. Landgrebe. J.A. T h o r y ."dPmctiCe in the OrgonicLabornfary. 2nd. ed.: D. C. Heath, Lexington, MA, 1977;pp 232-326.
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