Friedel-Crafts Alkylatio Reaction Catalysts an 0 lexes HERBERT C. BROWN, HOWARD W. PEARSALL', LOWELL P. EDDY2, WILLIAM J. WALLACE3, MARTIN GRAYSON4, AND K. LeROl NELSON5 Purdoe Universify, lafayette, ind.
The investigations reported in this paper were undertaken to obtain an understanding of the mechanism of the alkylation of aromatics catalyzed b y Friedel-Crafts catalysts. Complexes of aromatic hydrocarbons with metal halides and with metal halide-hydrogen halides have been prepared and their composition studied. Complexes of alkyl halides and Friedel-Crafts catalysts have been isolated. A new interpretation of the role of these complexes in
Friedel-Crafts alkylation reactions is proposed. A kinetic study of alkylation of aromatics indicates the probable existence of two different mechanisms corresponding to the SN1 and S N displacement ~ reactions of alkyl halides. A new explanation i s proposed for the unusual orientations encountered in aromatic alkylation. The theory permits an understanding of the effect of reaction conditions on the course of the Friedel-Crafts reaction.
T
tion of the factors controlling meta substitution in ortho-para directing systems has been made. This study has revealed a simple relationship between the degree of meta substitution and the activity of the substituting reagent and has led to a new simple explanation for the observed directive effects in Friedel-Crafts alkylations. The carbonium ion scheme shown above is no longer tenable as a general mechanism for the alkylation of aromatic hydrocarbons by alkyl halides. Instead it appears necessary to postulate the existence of two distinct mechanisms-one a carbonium ion mechanism which operates primarily in the case of tertiary alkyl halides and other easily ionized halides, and the other a displacement mechanism involving nucleophilic attack of the aromatic component upon the alkyl halide-metal halide addition compound. With these two mechanisms and associated postulates it now becomes possible to offer a simple consistent interpretation of the known established facts about Friedel-Crafts alkylation reactions. The proposed mechanism is the result of some 8 years of active investigation in the field. It is highly probable that this interpretation will require modification and elaboration in the light of new information turned up as a result of further investigation. This summary of results and conclusions is offered a t this time in the hope that it may prove helpful to other n-orkers interested in the Friedel-Crafts reaction and will encourage experimental testing of the proposed mechanism. In presenting this survey in this paper, the authors are faced with a difficult problem. There exist several thousand papers m hich deal -with the Friedel-Crafts reaction. These papers contain innumerable observations, as well as suggestions as to the niechanism of the reaction. Many of these are conflicting. I t was obviously impossible to attempt to assign full credit for each original observation and suggestion in a paper of this kind. Therefore, references are primarily to those papers which have reported experimental observations t h a t have withstood the test of time and those suggestions which were based upon careful experimental work. Only in this manner could the references be reduced to a number t h a t could be managed.
HE reaction of alkyl halides with aromatic hydrocarbons, catalyzed by metal halides (Friedel-Crafts catalysts), is generally believed to proceed through the following mechanism (28>6d).
RX R+ H-
+ h.IXs e R+ + SIXd+ ,4rH R,4r + H i + iIfX4- HX + MX,
-
+
Although this mechanism offers a reasonable answer as to the function of the catalyst in Friedel-Crafts alkylation reactions, it leaves unanswered many other questions-the precise nature and role of Friedel-Crafts complexes, the nature of the producte formed from isomeric halides and alcohols, and the unusual orientations observed in Friedel-Crafts alkylations (d6,49,62,70). At the present time there is available an immense literature which deals with the Friedel-Crafts alkylation reaction ( 7 0 ) . It is therefore surprising that there is not now available a detailed mechanism for the Friedel-Crafts alkylation reaction, one capable of organizing the available facts into a single consistent picture of the reaction. Unfortunately, much of the work available in the literature was carried out before it was recognized that traces of air and water have an immense effect on Friedel-Craits catalysts and upon the reactions catalyzed by these substances (65). bIoreover, there is even a t the present time little general agreement as to the basic facts about the reaction. With the facts themselves in dispute, the development of a satisfactory theory has been retarded. I n an attempt to obtain data from which a consistent theory of the Friedel-Crafts reaction might be developed, the authors have undertaken a detailed study of aromatic alkylations. This study has included examination of the complexes of Friedel-Crafts catalysts with aromatic hydrocarbons in the presence and absence of hydrogen halides, and complexes of Friedel-Crafts catalysts with alkyl halides. Rates of reaction of selected alkyl halides witharomaticshave been evamined and the dependence of thereaction rate upon the concentration of the metal halide, alkyl halide, and aromatic has been established. Finally, a detailed examinaPresent Present s Present 4 Present 5 Present 1 2
1462
address, address, address, address, address,
General Motors Corp., Detroit, Mioh. Reed College, Portland, Ore. Merck 8: Co , Rahway, N. J. Allied Chemical and Dye Corp., Hopewell, \'a. University of California, Los Angeles, Calif.
Studies of the Catalyst Couple, MX8-HX It has frequently been assumed that the catalytic activity of aluminum chloride plus hydrogen chloride and aluminum bromide
INDUSTRIAL AND ENGINEERING CHEMISTRY
Vol. 45, No. 7
(i
v
plus hydrogen bromide is due t o the formation of stable substances, HAICla and HAIBr4, which presumably function as exceedingly strong acids (39, 55, 60, 70). A careful examination of the hydrogen chloride-aluminum chloride system under a variety of conditions, including temperaturesas low as - 120" C., yielded no evidence indicating any combination of the two components (6). A similar study of the hydrogen chloride-gallium chloride system gave the same result (18). I n the case of hydrogen bromide-aluminum bromide the solubility of the salt in liquid hydrogen bromide at -80" C. was determined to be 1.77 grams per mole of solvent. From the vapor pressure lowering the aluminum bromide is present as AlzBrewhich again points to the absence of complex formation (74). The same conclusion was previously reached by Fontana and Herold as a result of their study of the solubility of hydrogen bromide in aliphatic hydrocarbons containing dissolved aluminum bromide (25). Likewise McCaulay, Shoemaker, and Lien found no evidence of compound formation in solutions of boron trifluoride in liquid hydrogen fluoride (42). I t follows t h a t the postulated substances, HMX4, must be considered as hypothetical acids whose salts are stable but which do not themselves exist in detectable concentrations.
Complexes of Aromatic Hydrocarbons
*
I n the absence of hydrogen chloride, aluminum chloride does not dissolve or otherwise interact with aromatic hydrocarbons ( 7 ) . However, aluminum bromide dissolves readily in aromatic hydrocarbons and there is available considerable evidence t o support the conclusion that complexes of some kind exist. However, the information available in the literature is confused and does not permit an unequivocable formulation of the complex. Thus, Ulich and Nespital ( 7 2 )and Plotnikov (58)found aluminum bromide to have a high dipole moment in benzene. However, Plotnikov disagrees with the former workers in reporting that the dipole moment dropped t o zero at higher concentrations of aluminum bromide. This he attributed to the existence of aluminum bromide as AlBr3 in dilute solutions (complexed with aromatic) and its dimerization t o A12Bre in the more concentrated solutions. The parachor measurements of Poppick and Lehrman (59) and the freezing point determinations of Van Dyke (73) showed that aluminum bromide is indeed dimeric in benzene solution. Poppick and Lehrman worked in solutions sufficiently dilute to establish that the postulated dimerization could not account for the change in dipole moment with increasing concentration reported by Plotnikov. Moreover, these high dipole moments are not compatible with the observation of Korshak, Lebedeev, and Fedoseev (38) t h a t the molar refractivities of solutions of aluminum bromide in benzene and toluene exhibit strict additivity. Menshutkin (45) studied the systems of aluminum bromide with benzene, toluene, and p-xylene and came t o the conclusion that complex formation did not occur in these systems. I n a similar investigation, Plotnikov (56, 57) found that aluminum bromide did form incongruent melting complexes with benzene, m-xylene, and p-xylene. The arrests in the phase diagram all occurred on the hydrocarbon-rich side of equimolar proportions of aluminum bromide and hydrocarbon so t h a t the complexes were assigned the empirical formula AIBrrArH. (This may explain Menshutkin's failure to observe these compounds in his phase studies. If his solutions were richer in aluminum bromide than 44 mole %, the solid phase separating would have been aluminum bromide and there would have been no arrests or maxima on the diagram.) Recently Eley and King (19) confirmed Plotnikov's conclusion. In the benzenealuminum bromide system they observed the formation of a complex which they formulate as C6H6.AlBr3,with an incongruent melting point of 37" C. Moreover, Van Dyke (73) studied the variation in vapor pressure of a solution of aluminum bromide in benzene with the composition of the solution. July 1953
He concluded that the solid compound which separated from these solutions should be formulated as Al~Br,dC6&. In an effort to clarify theseconflicting reports the authors undertook a study of systems of aluminurn bromide with benzene, toluene, m-xylene, and mesitylene (74). It was observed that aluminum bromide dissolved readily in these hydrocarbons to form colored solutions. The color varied from a slight, faint yellow for benzene t o a lemon yellow for toluene, t o yellow-orange for m-xylene, to orange for mesitylene. The molecular weight of aluminum bromide in benzene corresponds t o the dimeric formula, AlzBrs. As excess benzene is removed, solid is precipitated. The composition of the solid corresponds to AlzBr6.C6H6. Similar results are obtained with toluene. In the case of m-xylene and mesitylene the solid phase which separates appears to be crystalline aluminum bromide. The dissociation pressures of CsHa.AlnBrsand CHsCaHs.Al~Bre lead to a heat of vaporization of benzene from the complex of 10.1 kcal. and for toluene of 12.2 kcal. From these values the heats of formation of the two solid complexes from solid aluminum bromide and benzene or toluene can be calculated as 2.0 and 3.1 kcal., respectively. It was surprising that m-xylene and mesitylene, which are by most criteria much more basic than toluene, did not show the formation of solid complexes. However, the color of the solutions pointed to the formation of complexes in solution. This question was therefore investigated by dissolving aluminum bromide and mesitylene in cyclopentane and observing the lowering of the vapor pressure of the solvent. The lowering was less than would be expected for each component independently. An equilibrium constant, K N , of 3.91 at 0" C. and 2.74 a t 20.5" C. was calculated for the reaction: AlzBr6(soln.)
+ mesitylene ( s o h ) + AlZBr6.ArH(soln.)
These results demonstrate conclusively that benzene and tjoluene form unstable solid compounds with aluminum bromide and that mesitylene forms a oomplex in solution. I t is probable that all four hydrocarbons form similar complexes in solution, but that the solid complexes are unstable in the case of m-xylene and mesitylene, perhaps because of packing difficulties in the crystals. Plotnikov (56, 67) has reported a solid complex between mxylene and aluminum bromide. However, his compound melted incongruently a t 4 C. and the authors' measurements were made above this temperature. A more serious difficulty stems from the difference in the empirical formulas which have been assigned t o the compounds. Plotnikov (56, 57) and Eley and King (19) inferred from the position of the incongruent melting points (around a 44 mole % ' A1Br3) t h a t the solids had a composition corresponding t o AIBr3.ArH. This is not necessarily the case. The authors believe t h a t their results definitely establish t h a t aluminum bromide exists in aromatic hydrocarbons predominantly in the dimeric form and there is weak interaction between the r-electrons of the aromatic systems and the AlzBrBmolecule. The complex can be formulated as a r-complex with the probable structure O
Br
fik-
\
AI-Br-AI-Br
4 & , /BrJ /
\
Br
There appears to be no evidence that aluminum bromide dimer dissociates significantly in aromatic solvents t o form complexes of monomeric aluminum bromide, as has been frequently postulated. There is no evidence at present available t o suggest that these r-complexes play any significant role in Friedel-Crafts reaction.
INDUSTRIAL AND ENGINEERING CHEMISTRY
1463
Complexes of Aromatic Hydrocarbons with Catalyst Couples, MXa-HX At low temperatures (-80" C.) aluminum chloride neither dissolves in nor reacts with aromatic hydrocarbons such ae toluene ( 7 ) . I n the presence of excess hydrogen chloride, the aluminum chloride dissolves in the toluene to give a clear solution, brilliant green in color. From the decrease in pressure of the hydrogen chloride, it appears that one mole of the gas is taken up per mole of aluminum chlqride (illCl3) which goes into solution. The reaction is reversible: that is, removal of the hydrogen chloride precipitates the aluminum chloride and the toluene is recovered unchanged. The reaction is believed t o involve the formation of a carbonium ion salt of the hypothetical acid, HAICId:
Studies of the interaction of aluminum bromide-h\ drogcn bromide with aromatic hydrocarbons h a w been carried through by techniques which permit folloning the change in pressure of hydrogen bromide in the system with changes in composition. I n the case of benzene, toluene, m-xylene, and mesitylene, it was observed that one mole of hydrogen bromide i q absorbed per mole of aluminum bromide dimer. ArH -t- AlLBls+ HBr
+
.IrHI-hlABri-
In the rase of the more basic hydrocarbons, toluene, ~n-\ylene, and mesitylene, it was also possible t o prepare stable complexes nhich contained one mole of hydrogen bromide per mole of aluminum bromide monomer. 2ArH
+ &Br6 + 2HBr
--f
2ArH2+A1Br4-
dlthough stable compounds 'irere prepared containing the aromatic hydrocarbons in the mole ratios indicated, it was noted that in the presence of exceSs aromatic, products were obtained containing additional niolecules of hydrocarbon. The following formulations were indicated.
forms _I
L 3 forms
At -45.4' C. one mole of hydrogen chloride is taken up for each two moles of AICla:
CHs I
CH3 I
H-C
'1 It
H+
The complexes which form in the course of Friedel-Crafts reactions are believed t o be carbonium ion salts of this kind. It is proposed t h a t the high solubility of aluminum halides in these Friedel-Crafts complexes is due to the formation of a series of higher complexes of this kind, with the general formula ArHz+ [AIX4.nAIX3]-. In other words, it is proposed that aluminum halides dissolve in these liquid carbonium ion salts, just as sulfur trioxide dissolves in sulfuric acid to form a series of higher acids: HzS04,HzSz07, H2S3OI0,HzSrO1a,etc.
-, ArHz-AlX,-, ArHz+-41zX7-,ArH2+AlaXm-, ArHz+, A I ~ X I ~etc. It is further proposed that these complexes play a n important role in those Friedel-Crafts reactions involving carbonium ions by furnishing a highly polar medium in which the ionic intermediates may form and react ( 7 ) . Systems of aromatic hydrocarbons with aluminum bromidehydrogen bromide were previously investigated by h'orris and Ingraham (50). They reported a number of complexes with the formulas
HBr.A12Br6.(C6H6)8 HBr.AIZBre.(C7Hs), 2 H B ~ 9 1 ~ B r ~ .m-xylene 3.4 2HBr.Al2Br6.3.4mesitylene
It should be emphasized that the evperimental technique and equipment were particularly suited t o establish precisely the aluminum bromide and hydrogen bromide ratio and were not, as TTell adapted t o study of the hydrocarbon ratios. The value for benzene is particularly subject t o some uncertainty. These results definitely point t o the existence of aromatic carbonium ion salts, ArHZ+AIBr4- and ArHz+ AI2Br7-. It is probable that with higher ratio' of A12Rrs to HBr higher products will be formed: ArHs" -41?Brlo-, etc. These carbonium ion salts or u-complexes (6) are believed to be important in FriedelCrafts reactions in carrying active aluminum halide catalysts and in furnishing a highly polar medium for the formation and reaction of ionic intermediates. The interaction of aromatic hydrocai bons with hydrogen fluoride-boron trifluoride has been the subject of a careful study by McCaulay and Lien (40). They have demonstrated t h a t in this system the more basic aromatic hydrocarbons are converted to similar u-complexes. ArH
+ HF + BFP
ArHz+BFb-
Moreover, they have demonstrated that the reaction can be utilized to extract aromatic hydrocarbons from other hydrocarbons, and even to separate more basic aromatics from less basic. Highly important from the theoretical viewpoint is their determination of the relative stability constants for the u-complexes. These data reveal a simple linear relationship between the stability of u-complexes and the rate of aromatic substitution (5, I d ) . A similar linear relationship does not exist between the stability of r-complexes and the rate of aromatic substitution ( 5 ) . It follows that Dewar's proposal that the rate of aromatic substitution will be determined by the rate of formation of the r-complex ( 1 6 ) is no longer acceptable.
Complexes of Alkyl Halides
Recently, Baddeley and his coworkers ( a ) reported a study of similar complexes i lvolving m- and p-xylene. They report the isolation of crystalline complexes with the formulation (nz-Xylene)a.(HBr.AIBr& (p-Xylene)3.( HBr.AlBra)z 1464
I n the commonly accepted mechanism for the Friedel-Crafts reaction, it has been generally assumed that the alkyl halide is ionized by a direct attack of the catalyst (28, 62).
RX
+ 31x3
R+i\lXc-
In order to test this assumption the interactions of gallium chloride with methyl and ethyl halides (8, 18) and aluminum chloride, bromide, and iodide with these halides ( 7 4 ) were examined.
INDUSTRIAL AND ENGINEERING CHEMISTRY
Yol. 45, No. 7
i Gallium chloride and alkyl halides (methyl chloride, methyl bromide, methyl iodide) form stable 1:1 addition compounds a t -46Oto -80" C.
RX
I
+ 1/2Ga2Cle = RX:GaCls
Thus, a t -78.5' C. gallium chloride dissolves in excess methyl chloride to form a clear solution. As the excess methyl chloride is removed, two pressure plateaus are observed: 26.0 mm. between 5.4: 1 and l : l mole ratios of methyl chloride to gallium trichloride and 3.2 mm. between 0.9: 1 to 0.1: 1 mole ratios. The first plateau corresponds to a saturated solution of addition compound in methyl chloride; the second t o a dissociation of solid addition compound. Similar data were obtained for the other halides. Molecular weight determinations support the existence of CHaCl :GaCI3 in solution. The vapor pressure a t - 78.5 C. of a solution containing 0.447 millimole of gallium chloride in 3.067 millimoles of methyl chloride was 28.94 mm. as compared t o 34.00 for the pure solvent. On the assumption that the solution contains free gallium trichloride the molecular weight calculated from these data is 147. On the alternative assumption that 0.447 millimole of solvent is effectively removed to form a stable 1: 1 complex CHBCl: GaCla in solution, the molecular weight is calculated as 172. The latter value is in excellent agreement with the actual molecular weight of 176 for monomeric gallium trichloride. Dissolved gallium chloride exchanges very slowly with methyl bromide a t -80" C., only 25% in 10 days. The exchange may occur either through an ionization mechanism, O
*I
MeBr :GaC13 Ft. Me +GaCI3BrMe+GaCIaBr- & MeCl: GaClsBr
or possibly through a mechanism not involving ionization,
..
..
: c1: :q:** Me: Br :GL :CI : -+ :Br :Ga :C1:
'L: ki: ..
..
.. : c1: .. .. Me
*
R
It follows that the addition compound involves a largely covalent carbon-halogen bond and t h a t ionization must be a relatively slow process under these conditions, if i t occurs at all. Aluminum chloride is only slightly soluble in methyl chloride a t -31.3 C. and no evidence for complex formation was observed ( 7 4 ) . The patent literature is replete with references to the use of "solutions" of aluminum chloride in methyl and ethyl chlorides for polymerization of olefins, addition of hydrogen chloride t o olefins, etc. ( 7 0 ) . The apparent solubility of aluminum chloride in these instances must be due either to the presence of impurities or to secondary reactions involving partial breakdown of the alkyl chlorides. In contrast to the behavior of the chloride, aluminum bromide and iodide were readily soluble in alkyl bromides and iodides, respectively, and molecular weight determinations demonstrated that the salts were present as the monomers in these solutions (74). Analysis of the data by methods similar to those previously described for the gallium chloride system demonstrated conclusively that aluminum bromide exists in methyl bromide solution as a 1:1 complex, CH3Br: AIBr3. Aluminum bromide dissolves in methyl bromide to give a clear, colorless solution. As portions of the methyl bromide are removed a t -78" C., the pressure drops sharply when the mixture contains a solid composed of equimolar quantities of methyl bromide and aluminum, CH3Br:AIBra. At -64.4' C. there is observed an additional break correfiponding to two moles of aluminum bromide per mole of methyl bromide. At -45.8" July 1953
and -31.3' C. only the second of these two discontinuities was observed. At 0 O C. no stable solid complex phase was observed, although the vapor pressure data demonstrate the existence of a stable MeBr :AlBrs complex in solution. Ethyl bromide also forms a 1: 1 complex with aluminum bromide, EtBr:AIBrs. Study of this system was complicated by a slow evolution of hydrogen bromide from the reaction mixture. Both n-propyl and isopropyl bromides undergo secondary reactions with aluminum bromide too rapidly to carry through satisfactory studies of this kind. Fairbrother, who has carried through several careful studies of the interaction of Friedel-Crafts catalyst with alkyl halides (2% as), has estimated that a solution of aluminum bromide in ethyl bromide is 3 t o 4% ionized (23). Unfortunately, as mentioned above, the authors have observed t h a t such solutions are unstable and liberate hydrogen bromide. This decomposition severely complicates physical measurements on the system. The study of aluminum halides with methyl halides, systems relatively free of this complication, was therefore emphasized. Mixtures of the three aluminum halides with the three methyl halides were prepared: CHaCl-AIBra, CH3CI-AI13,CHaBr-AICls, CHaBr-Al13, CH31-AIC13, CH31-AIBr3. The reaction mixtures were maintained at 0 O C. for 24 hours and then examined. The following reactions proceeded essentially to completion: AlBra f 3CHgCI = AICla f 3CHaBr AlIa 3CHaCI =z AlCls 3CHJ A& 3CH3Br = AIBr3 3CHaI
++
+ +
The remaining three reaction mixtures, which would require the reverse reactions as written above, did not exhibit a n y appreciable exchanges. Attempts were made to determine the rates of certain of these exchange reactions at -80" t o 0" C. However, the rates were erratic from experiment to experiment and further work will be required t o develop satisfactory techniques and t o overcome the 0 difficulties. These results with gallium chloride and the aluminum halides point to the ready formation of relatively stable 1:1 addition compounds of alkyl halides with Friedel-Crafts catalysts. These addition compounds apparently exist primarily in unionized form and undergo ionization only slowly, if at all. It follows that t h e initial stage in Friedel-Crafts reactions with alkyl halides probably involves the formation of these addition compounds, with the ionization represented as a possible, but not essential, second stage. RX
+ MXa
RX:MXa
RX:MX3 F? R+MXdThe relative difficulty involved in the ionization of alkyl halides is pointed up by Fairbrother's results on the interaction of stannic bromide with triphenylmethyl bromide in benzene solution (23). From the absorption spectra he concluded t h a t the ionization must be very small, not greater than 0.1%. Since triphenylmethyl halides are particularly renowned for the ease with which they undergo ionization t o the particularly stable triphenylmethyl carbonium ion, it appears that ionization of alkyl halides by Friedel-Crafts catalysts is not the simple, rapid reaction that has been commonly assumed.
Kinetic Data for Alkylation of Aromatics by Substituted Benzyl Halides I n spite of the enormous quantity of work which has been carried out on aromatic alkylation, there does not exist in the literature today a single complete kinetic study of this reaction. Olivier and Berger (63)observed that the reaction of the addition
INDUSTRIAL A N D ENGINEERING CHEMISTRY
1465
compound of p-nitrobenzyl chloride and aluminum chloride in aromatic solution n-as first order in the addition compound. Cnfortunately, they did not establish the order with respect to the aromatic component, nor with respect to the individual components of the addition compound. Ulich and Heyne ( 7 1 ) reported a kinetic study of the reaction between n-propyl chloride and benzene, catalyzed by gallium chloride. Unfortunately, there are serious difficulties in the experimental techniques they used for following the rate and they did not take into consideration complications resulting from the possible isomerization and dehydrohalogenation of n-propyl chloride under their experimental conditions. For these reasons it is necessary to accept with caution their conclusion that the reaction rate does not follow the termolecular law rate = k [GaCI,] [n-PrC1I [CcHel but instead follows the expression rate = k [c&][n-PrC1.GaCls] with estimated values of k for the reaction rate and of K for the equilibrium constant for the formation of the assumed n-PrCI.GaC12 complex. In order to reach an understanding of the mechanism of the Friedel-Crafts reaction it appears desirable to have detailed kinetic data on typical alkylation reactions free of the complication encountered by Ulich and Heyne. As a first step in this direction kinetic studies have been made of the reactions of 3,4dichloro- and p-nitrobenxyl chloride with several aromatic compounds in nitrobenzene solution, using aluminum chloride as catalyst. Both benzyl chloride and p-chlorobenzyl chloride reacted very rapidly, too rapidly for convenient measurement of the rate, whereas p-nitrobenzyl chloride was somewhat too slow. For this reason, 3,4-dichlorobenzyl halide, which reacts a t a convenient rate, was primarily utilized in this exploratory study (27).
It was observed that the reaction n-as of the third order-&., first order in aluminum chloride, first order in the benzyl chloride, and first order in benzene. rate = li~[AIC13][RCl] [c&] Moreover, the rate depends not only on the concentration of the aromatic, but increases with increasing basic properties of the aromatic component (the number in parenthesis gives the relative rate constant a t 25" (3.). C1C& (0.47) CsH.5 (1.00) CHzCeHs (1.64) m-(CIh)sCsH* (2.08) The reactions are accompanied by slower, competitive dialkylation reactions at low aromatic concentrations. The kinetic analysis of the consecutive reactions was confirmed by the preparation of 3,4-dichlorodiphenylmethaneand measurement of its rate of reaction with 3,4-dichlorobenzyl chloride. The reaction is not very sensitive t o the dielectric constant of the medium. Use of mixed methylcyclohexane-nitrobenzene solvents containing 60% by volume of the less polar component resulted in only a twofold decrease in rate. Similar results have been obtained with p-nitrobenzyl chloride. These results definitely rule out any mechanism based upon a rate-determining ionization of the benzyl halide followed by rapid attack of the carbonium ion upon the aromatic. Moreover, rapid ionization of the halide followed by a rate-determining electrophilic displacement on aromatic carbon is improbable, since the p-nitrobenzyl carbonium ion should be more reactive than the unsubstituted ion and its reaction should proceed a t a faster rate. The data are consistent with a mechanism involving a ratedetermining nucleophilic attack by the aromatic component on a benzyl halidealuminum chloride complex. 1466
RCl -4rH
+ AIC1, Ft RCI:AlCls
- RC1: MC1, s ArH
C1: A I C l a a * R (activated complex)
r
HI+
0
(stable intermedizitcb)
I t should be pointed out that Swain's concerted mechanism ( 6 9 ) furnishes an alternative interpretation of the facts. Further studies are being carried out in an attempt to reach a decision between these two' possible interpretations. Dependence of Mechanism upon Structure of the Alkyl Halide
From the results of the above kinetic study it appears safe to conclude that the generally accepted carbonium ion mechanism (%?,sa)is no longer applicable to all Friedel-Crafts alkylations. It appears fairly definite that the reactions of primary halides in this reaction involve a transition state containing both the aromatic component undergoing alkylation and the Friedel-Crafts catalyst. On the other hand, tertiary halides are converted to carbonium ions much more readily than primary halides. Moreover, Condon has demonstrated that the reaction of alkyl carbonium ions with aromatic nuclei is a very fast reaction (13). It is therefore probable that the Friedel-Crafts reaction of tertiary chlorides with aromatic hydrocarbons involves prior formation of the carbonium ion. This conclusion may be tested soon by a kinetic study. If this interpretation is substantiated, i t will follow that the reaction of alkyl halides with aromatics is quite similar to other substitution reactions of alkyl halides. The classical work of Hughes and Ingold (3.2)has established that the substitution reactions of primary halides proceed predominantly by a displacement reaction, the rate of Tvhich is proportional to the concentration of the displacing agent, whereas the corresponding reactions of tertiary halides usually involve a prior ionization of the halide and the rate expression does not depend upon the concentration of the substituting agent. Secondary halides may then be made to react predominantly by either mechanism by proper control of the experimental conditions. The small quantity of optically active sec-butylbenzene which is formed in the alkylation of benzene with active see-butyl alcohol (9, 63, 6 4 ) might represent that portion of the reaction which arises from a typical nucleophilic displacement by the aromatic component. The experimental establishment of a displacement mechanism for the reactions of primary halides permits a simple explanation of certain anomalous results. Ipatieff, Pines, and Schmerling (34) have reported that the alkylation of benzene with n-propyl chloride results in the formation of 40% n-propylbenzene a t 35" C. and 60% a t -6" C. (The remainder of the monoalkyl product is the isopropylbenzene.) PvIoreover, the use of n-propyl alcohol in this reaction results in the sole formation of n-propylbenzene (34). hccording to the inteipretation here advanced, the npropylbenzene arises from the displacement mechanism:
INDUSTRIAL AND ENGINEERING CHEMISTRY
Vol. 45, No. 7
On the other hand, the isopropylbenzene either arises from an isomerization of the halide without prior ionization, or it may arise from the isomerization of the primary carbonium ion. CH3CHaCHpX: MX3
+
CHsCHCHa
I
X MXa
+
(CH3)zCH +pvIXdor
CH3CHpCHzX: MXI
+ (CH3)zCH+
+
CH&HzCHz+MX4-
There is little concrete evidence at this time upon which to base a decision between these alternative mechanisms. Doering's failure t o observe deuterium exchange in the course of isomerizing n- to isopropyl chloride in the presence of deuterium chloride and aluminum chloride suggests that the isomerization does not proceed through a carbonium ion (46). Moreover, the difficulty encountered in demonstrating the formation of primary carbonium ions from primary halides leads to the proposal that the first of these alternative mechanisms is the more probable. Studies currently under way on the kinetics of alkylation of aromatics, as well as of isomerization of n-propyl halides, may permit a clearcut differentiation between the two possible reaction paths. Orientation in Aromatic Alkylation
Much of the early literature on orientation in aromatic alkylation is confusing and misleading (26,49,66,70). Recent developments in techniques of separation and analysis have demonstrated that the frequently reported high selectivity of certain catalysts is erroneous (66,67). There is now little doubt that alkylation of monoalkyl aromatics even under relatively mild conditions is accompanied by the formation of relatively large amounts of the meta substitution products (11,44).This has been considered to be an anomaly in view of the almost exclusive ortho-para orientation observed in other substitution reactions of these aromatics
Table 1.
Relative Rates of Substitution Toluene/ ReferBenzene ence
Reaction Bromination Brz in HOAc (72) a t 467 26" c. Chlorination C1z in HOAc a t 353 24' C. Chloromethylation CHzO plus HC1 in 112 HOAc a t 60" C. Merouration 25 Hg(0Ac)z in HOAc plus HCIO4 Nitration AcONOa in AcrO 23 HNOa with HzSOk at 30" C. Acetylation AcCl with AlCla at Oo 1 3 . 3 At 50' C. 8.4 Sulfonation 100% HaS04 at 350
(f6) Very large, no meta
reported
(16)
...
c.
HzSOd i n nitrobennene at 40° C. Isopropylation CIHO with AlCla in nitromethane or BFs: OEtz as catalysts a t 40" C. At 65' C.
Para/Meta
Verylarge, no meta reaorted
Reference
(4)
. ..
49 10.6 5.3 8.5 Large, no meta observed
10
5.1
...
2.1
... 1.3
The beautiful work of McCaulay and Lien (40)has established that the carbonium ion salts or u-complexes of m-xylene and mesitylene are far more stable than those of the isomeric di- and trimethylbenzenes, respectively. The above equilibrium will be effectively shifted completely to the right in the presence of molar amounts of HX-MX3 by the formation of the highly stable Ucomplexes.
($4). The problem consists of two parts. First, there is the observation of Norris and his coworkers that alkylation of aromatics can be made to proceed with practically exclusive meta orientation in the presence of molar quantities of Friedel-Crafts catalysts (51). Second, there is the now well-established fact t h a t even in the presence of relatively small quantities of catalysts and mild conditions the alkylation of toluene and similar monoalkyl benzenes yields large quantities (=t30%)of the meta isomers (11, 44, 67). Norris and Rubinstein proposed that the high yields of 1,3,5triethylbenzene (85 t o 90%) and of mesitylene (87%) in the presence of molar ratios of catalyst was the result of the formation of a stable 1: 1 compound of the aluminum halides with 1,3,5-trialkyl aromatics (61). However, it has been demonstrated that the addition compound of mesitylene with aluminum bromide is not very stable-if anything it is less stable than the corresponding derivatives of aluminum bromide and benzene or toluene (74). McCaulay and Lien have recently advanced a satisfactory explanation (40,41). Baddeley, Holt, and Voss (8)demonstrated t h a t p-xylene is readily isomerized into m-xylene by aluminum bromide and hydrogen bromide at a rate which is dependent upon the concentration of hydrogen bromide. They proposed the following mechanism:
July 1953
L
H Very stable, nine resonance structures
J
McCaulay and Lien have recently reported a kinetic study of the isomerization of the methylbenzenes under the influence of hydrogen fluoride-boron trifluoride (41). The results offer strong support for their proposed interpretation of isomerization of alkyl groups to predominant meta orientation. The problem of accounting for the large quantities of meta substitution obtained under conditions where isomerization does not occur is a more difficult one. Dealkylation and transfer of alkyl groups occur only under conditions more vigorous than are required for isomerization (8, 41,51). Obviously, the frequent suggestion that the meta orientation arises from the prior formation of a l,2,4-trialkyl derivative, followed b y dealkylation of the group in the 1-position, is not tenable. We must therefore account for the phenomenon in terms of a n unusually rapid, direct substitution of the meta position. Although there have been a number of discussions of the factors controlling ortho-para ratios in aromatic substitution (14,17), there does not appear t o have been a careful examination of the factors controlling the meta-para ratios. Ortho substitution is affected b y steric effects (48), whereas substitution in the meta and para positions is free of this complication. A careful analysis of the data, together with experimental results of this study, has demonstrated t h a t in aromatic substitution there is no sharp division between reactions giving a high proportion of meta
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,
substitution in ortho-para directing systems and those giving little or no meta substitution. On the contrary, there appears to be a general gradation in the amount of meta substitution which depends both on the nature of the substituent and the nature of the substituting reagent. For example, bromination is a mild, highly selective substituting reaction. The ratio of rates of halogenation of toluene to benzene is 467. Similarly, the reagent is highly selective between the meta and para positions of toluene-no significant quantities of the meta isomer have been reported in the halogenation of toluene. Nitration involves a more vigorous substituting agent which is much less selective both between toluene and benzene and between the para and meta positions in toluene. The relative rates of substitution of toluene and benzene is 23. The ratio of para to meta substitution is 8.5. Isopropylation apparently involves a highly reactive substituting agent of quite low selectivity. The ratio between toluene and benzene is only 2: 1; the para-meta ratio is 1.3. These and other data are summarized in Table I. A linear relationship is observed for a plot of the log ( k t o l u e n e l kbenzene) versus log (kDsra/kmets). There is some scattering. However, the data are of greatly variable quality. It is probably significant that those data which appear most reliable fit the linear relationship most closely. It follows that the orientation rules in Friedel-Crafts reactions are not anomalous. It is also important that this interpretation suggests that a consideration of the relative electron density a t individual positions of an aromatic ring cannot form the basis of a fully satisfactory theoretical approach to orientation problems (61, 65). Consideration of the relative stability of an idealized transition state or carbonium ion intermediate without reference to the composition of the attacking agent also cannot be satisfactory ( 7 5 ) . The orientation depends upon the nature of the substituting agent-a satisfactory theoretical approach must include this factor and account for its influence on the para-meta ratio. It has been recently reported that the isopropylation of tertbutylbenzene results in much larger amounts of the meta isomer than does the tert-butylation of isopropylbenzene (29). The authors propose that this results from a novel steric effect. Actually the results are in complete accord with the theory presented in this paper. From their relative ease of formation by the action of FriedelCrafts catalysts on the halides, the stability of the carbonium ions apparently increases in the order CzHs"
,
RX
Summary The proposed mechanism of the Friedel-Crafts reaction of alkyl halides with aromatic nuclei may be summarized as follows:
+ MXs e RX:MXa
In the case of primary, difficultly ionizable, alkyl halides, the aromatic constituent reacts by a nucleophilic displacement reaction.
H ArH
+ RX:MX3
+
A&-R---XMX3 + ArR (transition state)
+ H X + 1\1&
The formation of n-propylbenzene from the reaction of benzene with n-propyl chloride and n-propyl alcohol is attributed t o a reaction of this kind. The formation of isopropylbenzene in this reaction is attributed to isomerization of the n-propyl to the isopropyl halide, followed by ionization and reaction.
I n the case of tertiary, easily ionizable alkyl halides, the reaction proceeds through the formation and reaction of carbonium ions.
RX:MX, Ft R'
+ MX4-
Secondary halides probably aleo react by this mechanism. However, by control of the reaction medium (low dielectric constant) and use of a highly nucleophilic aromatic constituent (m-xylene or naphthalene) i t may be possible to demonstrate a displacement mechanism in the case of secondary halides. Hydrogen halides and soluble metal halides (Friedel-Crafts catalysts) independently form relatively unstable r-complexes with aromatic hydrocarbons. CHI
CHI
+ HC1 e
3
/'
CH,
CH3 CH,
< (CH3)zCH' < (CHa)sC+ < CH&O+
This is also the order of stabilitv predicted on theoretical grounds. According to the interpretation of this study, the less reactive acetyl carbonium ion should be far more selective than the more reactive isopropyl carbonium ion. This is actually the case (Table I). It follows that the more reactive ethyl carbonium ion should be even less selective than the isopropyl carbonium ion and should give an even greater proportion of meta substitution. Contrariwise, the tert-butyl carbonium ion should be more selective between benzene and toluene and should give a smaller quantity of meta substitution. Thus, as found experimentally by Hennion ( W ) ,the theory predicts that terl-butylation of a monoalkyl benzene should result in a smaller yield of the meta derivative than does isopropylation. In order to test the quantitative aspects of the theory for aromatic alkylation, it will be necessary to determine the toluenebenzene and para-meta ratios under identical, carefully controlled conditions. A study of this kind has been undertaken.
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An unionized complex is formed between the Friedel-Crafts catalyst and the alkyl halide.
I
HCI
\
CH3
CH3 I
These do not appear to have any significant role in the FriedelCrafts reaction. Hydrogen halides and metal halides (Friedel-Crafts catalysts) together form the relatively stable a-complexes. CHI I
These products constitute a highly polar medium for the solution of additional metal halide and for the formation of ionic intermediates. They therefore play a n important part in the Friedel-Crafts reaction. The high yield of meta derivative in the alkylation of toluene and other monoalkyl benzenes under nonisomerization conditions
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Vol. 45, No. 7
is attributed t o the high activity of the attacking species. A highly reactive intermediate, such as the isopropyl carbonium ion will not differentiate greatly between the meta and para pos)itions of toluene or other monoalkyl benzenes. It follows that the para-meta ratio should increase from ethylation to isopropylation, to tert-butylation, and finally t o acylation. The practically exclusive formation of meta dialkyl benzenes and 1,3,5-trialkyl benzenes in the presence of molar amounts of HX-MX3 is attributed, in accordance with the suggestion of McCaulay and Lien (41), to isomerization of the u-complex to the most stable species-i.e., that containing the most basic aromatic constituent.
Fontana, C. M., and Herold, R. J., J . Am. Chem. SOC.,70, 2881 (1948).
Francis, A. W., Chem. Revs., 43, 257 (1948). Grayson, M., Ph.D. thesis, Purdue University, 1952. Hammett, L. P., “Physical Organic Chemistry,” New York, McGraw-Hill Book Co., 1940. Hennion, G. F., Driesch, A. J., and Dee, P. L., J . Org. Chem., 17, 1102 (1952).
Holleman, A. F., and Caland, P., Ber., 44, 2504 (1911). Holleman, A. F., Vermeulen, J., and DeMoody, W. J., Rec. trav. chim., 33, 1 (1914).
Hughes, E. D., Quarterly Revs. (London), 5, 245 (1951). Ingold, C. K., Lapworth, A., Rothstein, E., and Ward, D., J . Chem. SOC.,1931, 1959.
CHs
I
. 5, 253 Ipatieff, V., Pines, H., and Schmerling, L., J . O T ~Chem., (1940).
Jacobsen, 0. G., Ber., 18, 342 (1885). Jones, W. W., and Russell, M., J . Chem. SOC.,1947, 921. Klapproth, W. J., and Westheimer, F. H., J . Am. Chem. SOC., 72, 4461 (1950).
H‘ H ~9 resonance
Korshak, V. V., Lebedeev, N. N., and Fedoseev, S. D., J . Gen.
~
6 resonance forma
Chem. (U.S.S.R.), 17, 575 (1947).
Leighton, P. A., and Heldman, J. D., J. Am. Chem. Soc., 65,
forms
2276 (1943).
McCaulay, D. A., and Lien, A. P., Ibid., 73, 2013 (1951). Ibid., 74, 6246 (1952).
In presenting this interpretation of the Friedel-Crafts alkylation reaction the authors have merely attempted a synthesis of their own work and views with the experimental observations and theoretical deductions of a multitude of prior workers in the field. The authors have attempted to credit each worker who is responsible for a major advance based upon sound experimental work with his own contributions to the picture. Unfortunately, with such a voluminous literature it is impossible in a survey paper of this kind to credit properly every person who has made a valuable contribution to the understanding of the Friedel-Crafts alkylation reaction. In applying this policy, the authors have doubtless overlooked important contributions. If so, they wish t o apologize for any oversights or errors in judgment which were made.
McCaulay, D. A., Shoemaker, B. H., and Lien, A. P., IND. ENO.CHEM.,42, 2103 (1950). XcDuffie, H. F.,and Dougherty, G., J . Am. Chem. Soc., 64, 297 (1942).
Melpolder, F. W., Woodbridge, J. E., and Headington, C. E., Ibid., 70, 935 (1948).
Menshutkin, B. N., J . Rz~ss.Phys. Chem. SOC., 41, 1089 (1908). Nash, L. M., Taylor, T. I., and Doering, W. von E., J . Am. Chem. Soc., 71, 1516 (1949).
Nelson, K. L., Ph.D. thesis, Purdue University, 1952. Nelson, K. L., and Brown, H. C., J . Am. Chem. Soc., 73, 5605 (1951).
Nightingale, D. V., Chem. Revs., 25, 329 (1939). Norris, J. F., and Ingraham, J. N., J . Am. Chem. SOC., 62, 1298 (1940).
Norris, J. F., and Rubinstein, D., Ibid., 61, 1163 (1939). Ogata, Y., and Oda, R., Bull. Inst. Phys. Chem. Research
Acknowledgment
(Tokyo),21, 728 (1942).
Olivier, S. C. J., and Berger, G., Rev. trav. chim., 45, 710 (1926). Pajeau, R., Bull. soc. chim., 1946, 545. Pines, H., and Wackher, R. C., J . Am. Chem. SOC.,68, 595, 599
This investigation was greatly assisted by graduate fellowships supported by the Standard Oil Co. (Indiana) and by the Atomic Energy Commission. The authors wish to acknowledge their indebtedness to these organizations for this support.
(1946).
Plotnikov, V. A., and Gratsianskii, N. N., BUZZ. mad. sci. U.S.S.R., Classe sei. chim., 1947, 101.
Plotnikov, V. A., and Gratsianskii, N. N., Mem. Inst. Chem., Akad. Sci. Ukr. S.S.R., 5, 213 (1938). Plotnikov, V. A., Sheka, I. A., and Yankelurirch, 2. A,, Ibid.,
References
*
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July 1953
4, 382 (1939).
Poppick, L., and Lehrman, A,, J . Am. Chem. SOC.,61, 3237 (1939).
Powell, T. M., and Reid, E., Ibid., 67, 1020 (1945). Price, C. C., Chem. Revs., 29, 37 (1941). Price, C. C., “Organic Reactions,” Vol. 111, Chap. 1, New York, John Wiley & Sons, 1946. Price, C. C., and Ciskowski, J. M., J . Am. Chem. SOC.,60, 2499 (1938).
Price, C. C., and Lund, M., Ibid., 62, 3105 (1940). Ri, T., and Eyring, H., J . Chem. Phys., 8 , 4 3 3 (1940). Serijan, K. T., Hipscher, H. F., and Gibbons, L. C., J . Am. Chem. Soc., 71, 873 (1949).
Simons. J. H.. and Hart. H.. Ibid.. 69, 979 (1947). (68) Stubbs,‘ F. J.’, Williams, C. D., and Hinshelwood, C. N., J. Chem. SOC.,1948, 1065. (69) Swain. C. G.. and Lancrsdorf. , W. P.. . Jr... J . Am. Chem. SOC..73. 2813 (1951’). (70) Thomas, C. A., Moshier, M. B.. Morris, H. E., and Moshier, R. W., “Anhydrous Aluminum Chloride in Organic Chemistry,” A.C.S. Monograph No. 87, New York, Reinhold Publishing Corp., 1941. (71) Ulich, H., and Heyne, C.,2.Elektrochem., 41, 509 (1935). (72) Ulich, H., and Nespital, W., Ibid., 3 7 , 5 5 9 (1933). (73) Van Dyke, R. E., J . Am. Chem. SOC.,72, 3619 (1950). (74) Wallace, W. J., Ph.D. thesis, Purdue University, 1952. (75) Wheland, G. W., J . Am. Chem. SOC..64, 900 (1942). .
I
RECEIVED for review December 22, 1952.
INDUSTRIAL AND ENGINEERING CHEMISTRY
ACCEPTED April 8, 1953.
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