Bromination of Disubstituted Arenes: Kinetics and Mechanism

GCIMS Experiments for the Instrumental Analysis and Organic Chemistry Labs

D. Allen Annis, Davld M. collard,' and Lawrence A. Bottomley School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332

The canillarv eas chromatomanh interfaced with the .. . mass apec~rom&& is the centerpicce of most academic and industrial snalvtical luboraturies. Yet, few undermaduutc analytical labhratory courses include experiments i n GCIMS. A limited number of experiments can be found in common textbooks and laboratory manuals. Experiments dealing with the combined techniques of gas chromatogra- phy and mass spectrometry that have been published in this Journal include the determination of amino acid com- position of small peptides, identification of reaction prod- ucts, identification of components in mixtures of "un- knowns," and t he mass spectra of multi-halogen compounds (16). Only recently have experiments de- signed to introduce students to this indispensable tool of research been described (6).

We have developed a new experiment for GC/MS in which the students do more than just analyze a static mixture. Students perform the bromination of l,2-dichlorobenzene and follow the progress of the reaction over time with GC/MS. From the total ion chromatograms and the mass spectra of each peak in the chromatogram, they determine the identities and relative concentrations of the starting material, three intermediates and the final product of this reaction. This experiment presents students with a prob- lem-solving task that relies on laboratory technique, logical argument, and on the recall of specific fads from their or- ganic chemistry lecture courses. The pedagogical approach is designed to illustrate the power of GC/MS analysis in the solution of complex chemical problems rather than to carry out a sophisticated analysis just for the sake of doing it. The experiment is simple to set up and is performed on a small scale. It involves reagents that can be dispensed expedi- ently and safely, limiting exposure to hazards and minimiz- ing chemical waste. The approach is open-ended, allowing students to propose their own short research projects by studying analogous reactions on different substrates.' We have chosen to incorporate this experiment into the labora- tory portion of our instrumental analysis course. However, i t is also appropriate for inclusion into an advanced labora- tory course in organic chemistry.

Experimental Section

Procedure

. Caution: Due to the evolution of small amounts of HBr over the course of this reaction and the toxicity of halogenated arenes, all procedures should be conducted in an efficient

'Author to whom correspondence should be addressed. 21f a mass selective detector is not available, the laboratory re-

mains a useful demonstration of the principles and utility of gas chro- matography.

3These solutions remain stable in tightly sealed bottles stored in the dark. By dispensing dilute solutions the need to measure milli- gram quantities of liquids is avoided

Figure 1. Gas chromatograms (a-d) of aliquots taken at times shown from the reaction of 1.4-dichlorobenzene with excess bromine (see Experimental section for details). Mass spectra (e-h) of the molecu- lar ion (Mt) are shown for each gas chromatographic peak: (e) Mi of peak at 2.21 min, CsH4CIz; (f) M+ (2.46 min) CsH3BrCln; (g) M+ (3.06 and 3.24 min) C6HzBr2C12: (h) Mi (4.25 min) CeHBr3CIz.

fume hood, and students should wear protective lab coats, goggles, and gloves.

Analyses were performed on a Hewlett Packard 5890 Se- ries I1 gas chromatograph equipped with a Model 5971 mass selective detector. Each m u p of students (preferably two per group) is introduced to the i&trumentation by the l&ora&y instructor. A 1-uL auantitv of a mixture of chlorobenzene. di- chlorobenzene,'bmkobe&ene and dibromobenzene (each'l % vh) in dichloromethane is injected into the inlet of the gas chromatograph and the mass spectrum of each peak eluting from the column is acquired. Isothermal elution (170 "C) on a 15 m DB-5 ,250 Fm diameter, capillary column (J & W Scien- tific) affords rapid separation of the mixture. By evaluation of the molecular ion region of each spectrum, the students may identify the order of elution.

Students are then supplied with a vial containing a preweighed 120-mg sample of anhydrous aluminum chlo- ride. The aluminum chloride and 4 mL of -0.22 M bromine solution in dichloromethane are combined in a dry 30-mL test tube. The solution is stirred with the aid of a flea mag- netic stir bar. Next, 4 mL of - 22 mM 1,Z-dichlorobenzene in dichloromethane is added.3 The reaction begins imme- diately with the evolution of HBr, and the color of dissolved bromine gradually fades. Aliquots (100 FL) are taken at regular intervals, carefully added to 0.25 mL of 2 M aque-

460 Journal of Chemical Education

ous NaOH in a small test tube, and gently shaken until the color of bromine disappears. Over the course of two hours, one student continues to acquire and quench aliquots from the reaction mixture. Meanwhile a second student ana- lyzes each aliquot by injecting a l-pL portion of the bottom laver into the inlet of the GCIMS. In this fashion, this pro- cedure can be completed in less than three hours.

We reauire tha t each student group investieate the - . - brwnination of dichlorobeneene and either xylene or tolu- ene. The brorninations ofxslene and toluene follow similar procedures, but the reaction is complete in approximately five minutes. The entire procedure can be completed in less than four hours.

Variations

This procedure can be used by students to investigate analogous reactions with other substituted benzenes such as fluoro-, chloro- and bromo- toluenes; bromoethylbenzenes; xylenes; 1.4-diethylbenzene; and fluorobenzene (all available from Aldrich Chemical Co., Milwaukee, WI). Arenes bearing secondary and tertiary akyl substituents lead to produds re- sulting from Lewis acid catalyzed deakylation.

Results

Students monitoring the bromination of 1,2-dichlorobeu- zene find that within two minutes of adding excess bro- mine, all of the substrate has reacted to afford a mixture of mono and dibrominated products. Only one peak corre- sponding to monobrominated product is observed, and al- though there is a rapid increase in its intensity, i t is sub- sequently depleted by fur ther reaction leading to dibrominated products. Figure 1 contains GC tracings of reaction products a t the indicated times as well as the mo- lecular ion regions of the mass spectra acquired on the products of the bromination reaction.

Two peaks arising from dibrominated products are ob- served. These two signals (in an 8:l ratio) account for aD- proximately 90% of k e total peak intensity at t = 10 mk . Over the next two hours the minor disubstituted product is converted to trilmrninn~ed product; whereas, the &nction of the malor dibrominated product is necli~+le. '1%~. wrnpleta mass spectrum of the tnbrominated product is depicted in Figure 2. A typical reaction profile is depicted in Figure 3.

There are two possible monobrominated, four possible dibrominated, two tribrominated, and one tetrabromi- nated products in the Reaction. However, we have only ob- served one ~ e a k in the eas chromatoeraoh corresoondine - - . - to monobrominated intermediate, two peaks correspond- ing to dibrominated compounds, and one peak for one tri- brominated product. Under the present conditions, we do not observe formation of tetrabromo-1.2-dichlorobenzene. The GCMS data does not afford information regarding the regiochemistry of the sequential substitution reactions. Al- though we have not shown definitively that components do not coelute from the gas chromatograph, students should be able to predict the structure of each of the isomers, based on steric and electronic effects, and propose a reac- tion pathway to account for the experimental observations.

Students monitorine the bromination of xvlene with an ex- cess of bromine find &at the reaction proceeds rapidly and leads to the tetrabrominated product within five minutes. Students monitoring the bromination of toluene find that the reaction proceeds ra~ id lv to a tribrominated product in a . "

similar time interval. In either case, when the reaction is re- peated with bromine as the limiting reagent, mono- and di- brominated products can be detected. The distributions of starting materials, intermediates, and products can be treated in terms of orientation effects of the methyl suhsti- tuent, and relative rates of electrophilic substitution.

Figure 2. Mass spectrum of tribromo-1.2-dichlorobenzene (GC peak

0 2 0 40 6 0 8 0 100 120

time 1 rnin

Figure 3. Plot of reaction product and intermediate concentration versus time for the bromination of 1,2-dichlorobenzene.

Discussion

The Lewis acid catalyzed bromination of arenes is a general reaction that can be performed on numerous substrates un- der a wide variety of conditions. Methyl substituents activate the ring to electrophilic substitution by donation of electrons, with particular activation of the ortho and para positions. Halogen substituents withdraw electrons through inductive effects with a resultine deactivation of the rim. Substitution - in the ortho and para posiuons still dornin:ltrs by virtue of stabilizatiun of the inkrmed~ste cvclohexad~envl cation by resonance donation of e1ectrons.p-Xylene can be brominated on a large scale and, after aqueous work-up, the tetrabm- moxylene is isolated in high yield (7). Treatment of toluene with an excess of bromine-aluminum chloride leads rapidly to 2,4,6-tribromotoluene. The tribromo derivative is SUFI- ciently deactivated that subsequent bromination is slow un- der these conditions. Xylene has two electron-donating methyl gmups, and bromination continues until the arene is completely substituted.

1.2-Dichlorobenzene is sufficientlv electron-noor that the broknation is slow. The total ion c&omatogr&ns and mass spectra obtained demonstrate the dvnamic nature of the re- akion and allow identification of th;intermediates and prod- uct as the mono-, di-, and tri-brominated compounds. All pos- sible bromination sequences are shown in Figure 4. Students should be able to comment on the likelihood of each of these paths based on their experimental observations that:

1. monobrominated intermediate is rapidly converted to di- brominated intermediate, and

2. of the two peaks in the gas chromatogram corresponding to dibrominated products, the minor one is diminished rapidly, and the major one is long-lived.

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