Friedel-Crafts Acylation and Alkylation with Acid Chlorides Ronald M. Janet1, Nora Keil, Susan Allen, Lisa Cannon, Julie Coughlan, Leonarda Cusumano, and Brian Nolan College of the Holy Cross, Worcester, MA 01610 The Friedel-Crafts acvlation reaction is a standard oreanic laboratory exercise in electrophilic aromatic substitution. We have recently converted a Friedel-Crafts experiment (1) to run smoothly on semimicroscale and find that less time is required to complete the exercise. The extra available laboratory time allows for the demonstration andlor execution of additional ex~erimentsthat are designed to illustrate finer points of the Friedel-Crafts reaction such as electrophile rearrangement (2)and decarbonylation of acyl cations (3). Results and Discussion The acetylation of biphenyl (eq 1) is a reliable example of the Friedel-Crafts reaction. Multi~leadditions are not a concern, the electrophile does n o t rearrange (unlike norborn-5-en-2-vl chloride. Fie. 1) and does not decarbonvlate (unlike trim~thylacetyl'chl;oride,Fig. 2) in the presence of a Lewis acid. The synthesis also proceeds cleanly on semimicroscale to generate 4-acetylbiphenyl as the only product. Recrystallization removes starting material and significantly improves the observed melting point of the product. The exercise also makes use of some interesting innovations: A moistened foam collar transforms a test tube into a reaction flask-reflux condenser unit, and an inverted funnel attached to an aspirator serves as a mini-hood for the laboratory bench.
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The t-butyl carbocation is the electrophile that adds to the aromatic ring, just as if t-hntyl chloride had been used in place of trimethylacetyl chloride. 4-t-Butylbiphenyl has a relatively low melting point of 52-53 "C (7)and is isolated as an oil (when the reaction mixture is worked up as described for 4-acetylhiphenyl). This oil gives an expected negative test with 2,4-dinitrophenylhydrazine,and no carhonyl stretch is detected in the IR spectrum (Fig. 2). The aliphatic and aromatic C-H vibrations (3035. 2960. and 1480 cm-') are the most intense bands in the IR spectrum of 4-I-butylbiphenvl. The simple N M R spectrum (Fia. 2) has two sian&: the aromatic brotons a t 5.6-7.1 p p m - ( 9 ~ ,m) and the aliphaticprotonsat 1.35 ppm (9H, s). The broadsignal in the aromatic region does not display the AX splitting pattern observed when an electron withdrawing group (-0) is para to an aryl group, as in lacetylbiphenyl. Similar results are obtained when either naphthalene, anthracene, or t hntylbenzene is substituted for biphenyl.
The reaction is also appealing because it lends itself to product analysis by chemical tests andlor spectroscopic ohservations. For example, the reaction product gives a strongly positive test with 2,4-dinitrophenylhydrazine.The simple NMR and IR spectra obtained (Fig. 2) match those of the literature (4.5) and are readily interpreted. The conjugated carhonyl stretch (at 1689 cm-') is the most intense band in the IR spectrum. The NMR spectrum displays two signals: the aromatic protons a t 8.0-7.2 ppm (9H, m) and the aliphatic protons a t 2.5 ppm (3H, s). The acylation also proceeds smoothly when either propionyl or isobntyryl chloride is used in place of acetyl chloride. These variations are encouraged so that a series of diphenyl derivatives is produced that can be readily identified with NMR analysis (by their classic splitting patterns). When trimethylacetyl chloride is substituted for acetyl chloride, the reaction takes a different course: 4-t-butylbiphenyl is the onlv observed nroduct and is eenerated bv FriedelCraftsa&lation. he production of zkyl cation ieq 2) from acvl cation (3.6) causes violent huhhline as carbon monoxide
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' Author to whom correspondence should be addressed.
1056
Journal of Chemical Education
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Figure 1. NMR spectra (60 MHz. CDC13: bottom, nwbom-5-en-Byl chloride: top, same sample after addition of SnCI+
Experimental 4Acetylbiphenyl A funnel is attached to an aspirator and inverted over the work surface. Place 0.2 g of aluminum chloride in a dry test tube. Cover with 1 mL of methylene chloride. Slowly add 10 drops (0.14 g) of acetyl chloride. Gently swirl until there is s clear yellow solution; if necessary, add a few extra drops of acetyl chloride. Dissolve 200 mg of biphenyl in 2 mL of methylene chloride, and slowly add this solution dropwise to the solution containing aeetyl chloride. Comolete the transfer with a 112 mL rinse of methvlene , ~ chloride. Reflux the reartron mixture for I0 min; a moistened foam collar on the upper part of the teat tuhe makes the twt tuba an ercellmt reaction flasklcondmrer unit. Slowly transfer the cooled reaction mixture to atest tube containing 2 g crushed ice and 1mL eonc HCI. Mix well, then separate the Layen using a Pasteur pipet. Wash the organic layer with water, 1M aqueous NaOH, and saline. Add calcium chloride pellets to the test tuhe, then transfer the organic layer to a 10-mLround-bottom flask using a 112-mLrinse of methylene chloride to complete the transfer. Remove the methylene chloride by semimicro distillation. Students typically collect 0.1 g (40%yield) of crude material with a melting point of 110-115 "C. Recrystallization from 95% ethanol removes unreacted biphenyl. A melting point of 115-117 OC is recorded for the dry recrystallized product. ~~~~
Flwe 2. NMR I60 Mblz. CDCld end IR spscna (CCI, solut~an):bonorn, + acewlblphenyl (otpheoyland acwl chlarldel: top, bt-burylbbhenyl(biphsny an0 lrlrnethylaceryl chlalde).
I n addition t o these experiments that examine the nature of Friedel-Crafts acylation, rearrangements under FriedelCrafts alkylation conditions can be readily demonstrated in the time it takes to record two NMR snectra. The NMR spectra of norborn-5-en-2-yl derivatives (Fig. 2), as well as 3buten-l-vl and endo-norbom-2-vl comoounds. recorded beacid are drastically fore andimmediately after addkion different. With the homoallvl svstems. the alkene sienals disappear as cyclization occu&; in norbomyl derivatives, the exo proton signal diminishes in intensitv and the well-resolved endo proton signal intensifies as cation mediated equilibration takes place.
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Conclusion The svnthesis of 4-acetvlhiohenvl is a fine examole of ~riedel-kraftsacylation, ;hi& c k b e conducted smoothly on semimicroscale. A sinele solid oroduct is obtained. which can be readily purified b;recrystallization. Other aromatic compounds are readily prepared by substituting propionyl chloride or isobutyryl chloride for acetyl chloride andlor substituting biphenyl with naphthalene, anthracene or t butylbenzene. Product analysis may be readily conducted with spectroscopic observations andlor chemical tests. The extra time made available from running the reaction on semimicroscale, allows for the demonstration/execution of related reactions such as acid catalyzed isomerization of electrophiles andlor decarbonylation of acylium ion where Friedel-Crafts mono-alkylation is successfully conducted with an acid chloride.
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4-t-Butylbiphenyl Besides substituting trimethylaeetyl chloride for acetyl chloride, there is a slight modification in the manner of reagent addition (as outlined above for 4-acetylbiphenyl). Trimethylacetyl chloride is added to the mixture of biphenyl, aluminum chloride, and methylsince ene chloride. This addition should he conducted in a hood. ~~~~,~ carbon monoxide is liberated. The reaction workup remains the same (as described above) hut the product is isolated as an oil. If the manner of reagent addition is not modified as described, side products (including2,2,5-trimethyl-4-hexen-3-one) result (8). ~
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Rearrangement of Electrophile A drop of norbornd-en-2-yl chloride (2) is placed in an NMR tuhe, an appropriate volume of perdeuterated solvent (chloroform, methylene chloride, nitromethane, or nitrotoluene) is added, and the NMR spectrum is recorded. A small amount (drop or spatula tin) of Lewis acid (aluminum chloride or tin tetrachloride) is added. and the soectrum is recorded. The outlined orocedure nlw works ~~~~~~well for hut.3-en-1-yland endo-norborn-2-ylhalides. Similar renrrangemenu result if the corresponding acrrstev (0.2 g j are refluxed in acetic acid (2 mL) and sulfuricacid (0.1 mL) for 10 min ~~~
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Acknowledgment We would like to thank Helene Arcand, Joseph Bradley, Emily Costa, Cynthia Gallagher, Elizabeth O'Brien, and Kazimierz Wrzeszczynski for their assistance in conducting and developing this laboratory exercise. Financial support, of the research which established this work, from a Bristol-Meyers Company Grant of Research Corporation (C-2239) and from the Donors of the Petroleum Research Fund, administered bv the American Chemical Societv (19391-GB41 is ereatlv, appreciated. We are also grateful for partial support from NSF-REL1 (CHE-8712543)and thecontlnuinesuooort .. from the College of the Holy cross.
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Literature Clted 1. Adama, R.: Johnson, J. R.; WIlcox. C. F., Chemislru: Macmillen: New Ynrk. 1979.
Jr. Laboratory
Experiments in Orgonie
h e , 1974. 5. Pouchert. C . J. Tka Aldrick Library o/lnliamd Spoelm: Aldrieh: Milwaukee, 1970. 6. Olah.C.A.;Toleyesi.W.:Kuhn,S.;Moffat.M.;Bastien,I.;Bsker,E. J.Am.Chem.Soe.
1963.85.1328-1334.
7 . Rondertvedt.C. S. Jr.;Blenchsrd,H.S.J. Am. Chrm.Soc. 1955.77. 176%1774. 8. Olah, G. A . Ed. FILedei--Cm/t~ and Relofed Reactions; Intemcience: New York, 1964.
Volume 66
Number 12
December 1989
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