Chromatography
GC/MS Experiments for the Organic Laboratory II. Friedel-Crafts Alkylation of pXylene Michael ~ o v a k and ' Julie Heinrich Miami University, Oxford, OH 45056
In this, as in the previous paper, we present experiments for the B.S. sophomore organic laboratory that make use of capillary GC/MS, teach the use of MS fragmentation patterns in structure determination, and also illustrate the effects of reaction conditions on product distributions in well-known organic reactions. The Friedel-Crafts alkylation of p-xylene 1with n-propyl halides in the presence of aluminum halide catalysts is known to produce significant yields of both rearranged and unrearranged products (1).The relative yields of the three major monoalkylation products (24of eq 1)depends on X and also on temperature (1).In these alkylations other minor monoalkylated and dialkylated products are o h n found ( I , 2). (1)
Experimental The reagenbgradep-xylene used in this experiment was shown to contain no detectable amounts of the ortho and meta isomers by GC/MS before the start of the experiment. The alkylation of p-xylene was canied out under three different sets of conditions: n-propyl chloride reagent; NC13 catalyst;room temperature n-pmpyl bmrmde rewent;AIBrJcatalyst; room temperature an-propyl chloride reagent; NClj catalyst; 50 'C
Each student used one of these conditions. The dryp-xylene (0.37 mL, 3 mmol) was added to a dry 3-mL conical vial fitted with a stir vane, a Claisen adapter, and a drying tube containing CaC12. The other opening of the Claisen adapter was sealed by a septum cap. The A& (0.15 mmol) was weighed out quickly to avoid reaction with atmospheric moisture. (The watersensitive aluminum halides were purchased in 5-g bottles (Aldrich) to minimize waste by decomposition.) It was immediately added to the reaction vial, which was then sealed. The contents of the vial were stirred at room temperature or 50 'C (water bath). Then 1.5 mmol of the n - ~ r o ~halide vl was added via syringe to the reakidri mixture in a I dropwise fashion. The reaction mixture was stirred at room temperature or 50 'C for 2 h. Then 400 pL of H20was added to the stirred solution until the A& was consumed. The aqueous solution was then removed with a disposable pipet and discarded. The organic solution was washed with 300 pL of 5% aqueous NaHC03 and then with another 300 p L of HzO. After removal of the last aqueous wash, the organic solution was diluted with 1 mL of CHzClz and dried over
h An Adaptatlon of a Popular Synthesis A Friedel-Crafts alkylation experiment similar to the one presented here appears in Roberts, Gilbert, Rodewald, and Wingrove (3). We have adapted that experiment to a microscale laboratory Identifying the Products
The GC/MS analysis used in this experiment makes it alkvlation ~otisibleto distinrmish n-oroovl from iso~roovl *broducts becauselthe MS-fra&nentation patterns a& sensitive to chain branchine (4). Fraementation Datterns and the known boiling poi& (5-8)'bf the various isomeric monoalkylation products allow the student to be actively involved in identifying the materials. This was not possible in the previously published experiment in which simple GC analysis was used (3). This experiment required two laboratory periods for completion. In the second period the students carried out the GC/MS analysis and began work on another experiment. The experiment has been run for two consecutive years near the end of the first semester of the laboratory course. It provides the students with their first experience with GCMS.
-
'Author to whom correspondence should be addressed, A150
Journal of Chemical Education
Erratum for Part I Several typsographic errors were not corrected in Part I of this paper, which appeared on pages A103-A110 of the April 1993issue. Specilically,the paragraph starting at the bonom of the left column had several cases of mL, pL, and L mnfused. The correct wording of that paragraph is The capillary inlet was used in the splitless mode at 140 'C with a total He flow of 25 mL'min. An inlet purge flow of 20 mWmin was started 45 s afkr injection. Column flow
rate was approximately 0.5 mWbin. Under these conditions 0.5 j& of solution was injected into the GCIMS. The column was kept at 35 'C for 3 min after injection and then ramped at 10 'Clmin. Ionization of the GC eluent was carried out by the electmn ionization (EI)technique at 70 eV.
The Modern Student lclboratorv Na2S04.This solution was then decanted or pipetted from the drying agent into a clean, dry vial for storage until GC/MS analysis. GC/MS Conditions The solution for GC/MS analysis was obtained by diluting 3.5 fi of the reaction solution with 5.0 mL of CH2C12. The GCMS conditions used were identical to those mentioned in the previous paper. The injection volume was 0.5 pL. Results and Discussion Under all sets of mnditions, between three and eight different monoalkylation products were observed by the students.
Figure 1. Chromatogram obtained from the total ion current of the mass-selective detector for the alkyiation of pxylene with n-propyl chloride at 50 'C. Identities of isomers are indicated. Tentative identities are given in parentheses. (See text fordetails.)
Figure 2. Mass spectra for the two major isomeric monoalkyiation products. (A) Isomer with retention time 9.37 min: 2-isopropyi-1,4-dimethylbenzene 3. (B)Isomer with retention time 9.85 min: 1,4dimethyl-2-propyibenlene2.
A152
Journal of Chemical Education
ChromatographicRuns Figure 1 shows a typical chromatogram for the reaction I W n with n - ~ m ~chloride/AlCl~ vl at 60 'C. (Odv that Dortion of theckkomatogram isdisplayedin which-the monoalkvlation ~roductsare found.) A fair amount of unreacted jkylen; is always present because it is added in 2-fold excess in the alkvlation emeriments. Most students also observed a low $ld of a n&ber of diakylated products at longer - retention times. These were not examined in detail. Mass Spectra The mass spectra (Fig. 2) of the momalkylated products were characterized by molecular ion peaks at mle 148 and a base peak at mle 119 or mle 133.These base peaks can be used to distinguish n-propyl and isopropyldimethylbenzenes. Figure 2 shows typical mass spectra for the two major isomers with retention times of 9.37 and 9.85 min. The base peaks are created by cleavage of a C-C bond P to the aromatic ring in a process that yields a stabilized tropylium ion (4). This process is illustrated for the molecular ions of 2 and 3 in eqs 2 and 3.The isomers with a base peak of mle 133 have lost CH8. to generate the tropylium ion:
These materials must have isopropyl substituents. (See eq 3 on next page.) The isomers with a base peak of mle 119 have undergone p cleavage with loss of Et. to generate a tropylium ion 14 amu lighter than that obtained from the isopropyl com-
Chromatography pounds (eq 3). These materials must have n-propyl substituents.
Table 1. Dimethylpropylbenzenes Arranged by Boiling Points Isomer l-isopropyl-3,5-dimethyl(4)
2-isopropyl-1A-dimethyl (3) 1-isopropyl-2,4-dimethyl(6)
2-isopropyl-1,Sdimethyl 4-isopropyl-1.2-dirnethyl(7)
I -isopropyl-2,3-dirnethyl 1,3-dimethyl-5-propyl(5)
The Boiling Points All twelve isomers are known, and their boiling points have been determined to a high degree of accuracy (5-8). These are collected in Table 1. Not surprisingly, the isopropyldimethylbenzenes have lower boiling points than the corresponding n-propyldimethylhenzeues, and the 1,3,5-isomers have the lowest boiling point in each series.
1.4-dimethyl-2-propyl(2) 2,4-dimethyl-l-propyl(8) 1,3-dimethyl-2-propyl 1,2-dimethyl-Cpropyl(9) 1.2-dimethyl-3-propyl 'The firstvalue for each isomer is from Ref 5. %sf 6 %ef 7 %ef 8
bpm ('C)a 194.5. 194.6' 196.2. 196.2~ 199.1. 199.0~ 199 201.8 202.6 202.2, 202.3' 204.3, 204.6~ 206.6 207.6 208.9 21 0.7
Percentage Yields The student results for the percentage yields of the monoalkylation products for both the 1990-1991 and 1991-1992 classes were averaged and appear in Table 2. These were obtained by integration of the total ion current from the mass-selective detector. There was remarkably good agreement among the data sets. ~articularlvfor the L o exierirncntn that were carried O U ~at room iemperature. The meater variation among the individual student results fo;the experiment carries out at 50 'C is apparently due to poor temperature control. The identity of the propyl substituent of each isomer can be ascertained from the MS data. This is also indicated in Table 2.
Identification of the Isomers Several of the isomers observed in these experiments were unambiguously identified. Alkylation of p-xylene with n-propyl halides near room temperature leads predominately to 2 and 3 (1). This indicates the following.
The isopropyl isomer of retention time 9.37 min is 3 The n-pmpyl isomer of retention time 9.85 minis 2. The following isomers are the only ones more volatile than the respective 1,Cdimethyl compounds (see Table 1). I-isopropyl-3.5-dimethylbenzene 4; retention time: 9.13 min 13-dimethyl-5-propylbenzene 5; retention time: 9.60 min
Isomer 4 has previously been identified as a product of the alkylation ofp-xylene with n-propyl chlo~idelA1Cl~ a t temperatures above 30 'C (I). The other four isomers can be tentatively identified. kiedel-Crafts alkylation of all three xylene isomers with a variety of catalysts, as well as A1C13catalyzed isomerization of n-propyldimethylbenzenes, indicate that isomers with 1,2,3-substitution patterns are not formed (1,2,6,9). This eliminates four of the remaining eight isomers listed in Table 1.
Volume 70 Number 6 June 1993
A153
The Modern Student laboratory Chromatography here has better resolution and sensitivity than the packed-column GC techniques used in the earlier work.
Table 2. Student Results for the Frledel-Crafts Alkylatlon of pXylene
Percentage yields of monoalkylation products
Conditions
The Class Assignment and Challenges G U M S Runs and Identifications
by retention time (min)
9.13
9.37
9.43
~propylCl AICb. R P
2fl
41f3
n-propylCl AICb, 50 'cb
1 8 f 5 2 2 f 3 1.0* 0.5
n-propylBr
2f 1
27 3
Type of pro I substituentp
i
i
i
ldentifj'
4
3
(6)
9.55
't 1.9f 0.7
9.85
9.91
10.04
57f3t
7f2
43f7 5 f 1
t
71 f3 t
i
n
n
n
n
(7)
5
2
(8)
(9)
*
AlRh
9.60
1.7f 0.8
Literature Searches
'RBYIID are averaged for 14 students in 1990-1991and 1991-1992 laboratory wurses. b ~ e w l t s a r e ~ e r a g IoreigM ed students in 1S9C-1991 and 1991-1992 laboratory courses. Three data sets were exduded because the resub were quivalent, within experimental error. lo IIm mom-temperatureexprimem. C R e w bare averaged for 12 Merits in 1990-1991and 1991-1992 laboratory courses. 'less than 0.5%.but present. a. I = isopwyl; n = Rpmpyl 'Those isomers Indicatedin parenthesesare tentatively identified.
Careful measurements of retention times of dimethylalkylbenzenes, including those described in this paper, on nonpolar capillary GC columns show the following order of elution (10f
This order, with one exception, follows the order of boiling points shown in Table 1.These considerations indicate the following isopropyl isomers and retention times
Similarly, the n-propyl isomers are tentatively identified as
The results shown in Table 2 are in very good agreement with those previously published by Roberta and Shiengthong at similar concentration and temperature (1).We have been able to find some minor products that they did not identify because the capillary GCiMS method used
A154
In this experiment the students were asked to turn in their raw GC/MS integration data and mass spectra. After tabulation, the data were returned to them. They were asked to identify their alkylation products on the basis of the MS fragmentation patterns and GC retention times.
Journal of Chemical Education
To assist them, they were told the identity of the two major room-temperature alkylation products, although they were not told the retention times of any specific products. They were also urged to look up the boiling points of the various isomers. (They had recently had an introduction to the chemical literature, including the use of Beilstein.) Writing the Mechanisms
ARer considering the mechanism of the reaction and the factors affecting the stability of the various isomers, the students were asked to provide a mechanistic ex&nation for the results shown ih Table 2. They were also asked to give reasonable mechanisms for the formation of all the isomers they identified. Acknowledgment The GC/MS was purchased with funds from an NSF ILI Grant (CHE-8951897). We also acknowledge the contribution of the 1990-1991 and 1991-1992 CHM 2541255 laboratory students in the development of this experiment. Literature Cited 1. kberta,R. M.; Shiengthong, D. J . A m C k m Soe 1964,86,2ffil-2851. 2. NighWtiasal, D. t ShsclreIford J. M. J. Am Ckm. Sm. 1 W 78,lZE-lZZT. Rob erts. R.M.; W , A hA; Dough, J. E. J. Og. C k m 188429.1611-1514. a. b ~ ~ , ~ . ~ . ; c i ~ ~ . c . ; ~ a d ~ s Drgonic Chrmistry, 4+h ad.; Saundm:Phibdelphi., I-, pp 417428 H.; Djeralsi C.;Willisma, D. H. Mos. SpmwuI'yofOIgMC Corn4. Budiki-r, pun& Holde~Day:Sari- S6861:pp 73-86. 5. bsaini F. R.; HUe., K 8; Amnf R L.; Brawn, R. M.; Pimental. 0. C. Se*Eted Vhluoa 0fPhyriml Md T l u r n u x l ~ ~ MRop& e #Hydmmrbommrbo Md Ilrlotnl Crmpwnda; Came* Emburgh, 1963; pp 15-14. 6. R i r b d , E.V.; Fvnderhrrk, 0. P.;Wadaamth F. T. J. Olg. Chrm. 1NS.23.16311695. 7. Fe.rin,J.P.,~T.B.;Koslin,N.~Orreolee.KW.;DsrleqJ.M.;bmd,C.E.J. hg.c l u m 1 m . 19.9aM27. 8. la Cbng, T.C.; k, C.hL Chim Aet. lSS0,21.474-490. 9. Fu,X:He,M.; Lei Q.; Luo, B.Synth. Commvn 1#01,21,121M219. Kumar,V. 0.; Sh0ba.T. S.;Rao.KV.C,rrtmhpdmnirll.1USd,B5.328137.M. 10. Matiava.E.;Kov~ovdmva, E.;Ra,P.T.; Kolek,E.;Emdd.W. J. Chmmnfogmphy 1#09,476, 115-129. hmw,N.; Matinova, E. J Chmmnfogmphy 1901,549, 3 2 6 533.
l
d
