Chemoselective catalytic side-chain alkylation of aromatics by ethylene leading to sterically demanding alkylbenzenes [11]

Full text of DOI:10.1021/ja994432p

J. Am. Chem. Soc. 2000, 122, 2391-2392
2391
known to act both as a solubilizing agent of organoalkali metals
in hydrocarbons8 as well as a modifier of their reactivity.9 It is
probable that both of these properties are responsible for its
beneficial effect in the present case.
Chemoselective Catalytic Side-Chain Alkylation of
Aromatics by Ethylene Leading to Sterically
Demanding Alkylbenzenes
The substrates studied were a series of methylated benzenes
from toluene up to hexamethylbenzene as well as n-butylbenzene.
The results indicate that a methyl group which is flanked by two
neighboring methyl groups can only add one molecule of ethylene,
whereas if there is a vacant ortho site, it can add a second
molecule at the benzylic position. Addition of a third molecule
of ethylene to give a tertiary alkyl-substituted benzene was
observed to only a very minor extent. Thus, toluene, the xylenes,
mesitylene, and durene are ultimately converted to the corre-
sponding 3-pentyl derivatives, while n-butylbenzene adds one
molecule of ethylene to give 3-hexylbenzene (eq 1). Hexameth-
ylbenzene, on the other hand, undergoes a clean conversion to
hexapropylbenzene, while pentamethylbenzene gives 1,5-bis(3-
pentyl)-2,3,4-tripropylbenzene [eq 2].10
Barry R. Steele and Constantinos G. Screttas*
Institute of Organic and Pharmaceutical Chemistry
National Hellenic Research Foundation
48 Vas. Constantinou AVe., 116 35 Athens, Greece
ReceiVed December 20, 1999
The preparation of sterically demanding aromatic molecules
has always provided a challenge for the synthetic chemist.1 These
derivatives are important target compounds, however, since they
play an important role in the organometallic chemistry of main
group and transition metals,2 as well as in the synthesis, isolation,
and study of once elusive organoelement species.3 Here we report
a convenient process in which ethylene, via anionic catalysis using
a higher-order LICKOR system,4 ethylates the side chains of
alkylaromatics to produce bulky arenes, many of which, despite
their relatively simple structures, have not been previously
reported. Although the addition of ethylene to benzylic carbanions
has been known for some time, particularly from the work of
Pines and co-workers,5 it usually gives rise to mixtures of
monoethylated, polyethylated, and telomeric products, and in some
cases indane derivatives, and it is probably for this reason that
the reaction has not found favor as a synthetic procedure. We
have now found that a catalytic system comprising the very
powerful metalating mixture of n-BuLi and LiK(OCH2CH2-
NMe2)2,4 in combination with Mg(OCH2CH2OEt)2, promotes the
multiple and clean addition of ethylene to a series of alkylaro-
matics. The above metalating agent has been previously shown
to combine the activating effect of a tertiary amine6 with that of
a potassium alkoxide,7 while magnesium 2-ethoxyethoxide is
The results are summarized in Table 1. The catalytic activity
of the system decreases over a period of several hours under the
conditions employed,11 probably due to gradual quenching of the
organometallic compounds by reaction with the alkoxide groups,
and the amount of initial base required for the reaction to go to
completion is of the order of 2.5% per ethylene added with respect
to the substrate. It is of particular interest and importance to note
the remarkable effect of adding magnesium 2-ethoxyethoxide. The
reaction with m-xylene was carried out under the usual conditions
both with and without addition of Mg(OCH2CH2OEt)2. It was
found that in its presence the reaction proceeded to completion
(addition of 4 molecules of ethylene) and that no partially
(1) (a) Prinz, P.; Lansky, A.; Haumann, T.; Boese, R.; Noltemeyer, M.;
Knierem, B.; de Meijere, A. Angew. Chem. 1997, 109, 1343-1346; Angew.
Chem., Int. Ed. Engl. 1997, 36, 1289-1292. (b) Yokota, T.; Sakurai, Y.;
Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1997, 38, 3923-3926.
(2) (a) McGlinchey, M. J. AdV. Organomet. Chem. 1992, 34, 285-325.
(b) Johnson, E. S.; Balaich, G. J.; Fanwick, P. E.; Rothwell, I. P. J. Am. Chem.
Soc. 1997, 119, 11086-11087. (c) Dilworth, J. R.; Hu, J. AdV. Inorg. Chem.
1994, 40, 411-59.
(3) For recent examples and reviews, see: (a) Loss, S.; Widauer, C.;
Gru¨tzmacher, H. Angew. Chem., 1999, 111, 3546-3548; Angew. Chem., Int.
Ed. 1999, 38, 3329-3331. (b) Suzuki, H.; Tokitoh, N.; Okazaki, R.; Nagase,
S.; Goto, M. J. Am. Chem. Soc. 1998, 120, 11096-11105. (c) Stu¨rmann, M.;
Weidenbruch, M.; Klinkhammer, K. W.; Lissner, F.; Marsmann, H. Orga-
nometallics 1998, 17, 4425-4428. (d) Su, J.; Li, X.-W.; Robinson, G. H.
Chem. Commun. 1998, 2015-2016. (e) Rabe, G. W.; Heise, H.; Yap, G. P.
A.; Liable-Sands, L. M.; Guzei, I. A.; Rheingold, A. L. Inorg. Chem. 1998,
37, 4235-4245. (f) Cardin, C. J.; Cardin, D. J.; Constantine, S. P.; Drew, M.
G. B.; Rashid, H.; Convery, M. A.; Fenske, D. J. Chem. Soc., Dalton Trans.
1998, 2749-2756. (g) Beck, A. K.; Dobler, M.; Plattner, D. A. HelV. Chim.
Acta 1997, 80, 2073-2083. (h) Trommer, M.; Miracle, G. E.; Eichler, B. E.;
Powell, D. R.; West, R. Organometallics 1997, 16, 5737-5747. (i) Saito, S.;
Yamamoto, H. Chem. Commun. 1997, 1585-1592. (j) Reddy, S. S.;
Shashidhar, G.; Eur. Polym. J. 1997, 33, 583-585. (k) Tokitoh, N.;
Matsumoto, T.; Okazaki, R. J. Am. Chem. Soc. 1997, 119, 2337-2338. (l)
Rappoport, Z.; Frey, J.; Sigalov, M.; Rochlin, E. Pure Appl. Chem. 1997, 69,
1933-1940. (m) Takeda, N.; Suzuki, H.; Tokitoh, N.; Okazaki, R.; Nagase,
S. J. Am. Chem. Soc. 1997, 119, 1456-1457. (n) Weidenbruch, M.; Wilms,
S.; Saak, W.; Henkel, G. Angew. Chem. 1997, 109, 2612; Angew. Chem., Int.
Ed. Engl. 1997, 36, 2503-2504.
(8) Screttas, C. G.; Micha-Screttas, M. J. Organomet. Chem. 1985, 290,
1-13.
(9) (a) Screttas, C. G.; Steele, B. R. J. Org. Chem. 1989, 54, 1013-1017.
(b) Kostas, I. D.; Screttas, C. G. ibid. 1997, 62, 5575-5577. (c) Kostas, I.
D.; Screttas, C. G. Main Group Met. Chem. 1997, 20, 787-790.
(10) The products from mesitylene, durene, and pentamethylbenzene have
not been previously reported. Hexapropylbenzene has been obtained previously
by Friedel-Crafts reaction of benzene with chloropropane or by trimerization
of oct-4-yne; Hopff, H.; Gati, A. HelV. Chim. Acta 1965, 48, 509-517.
(11) Full experimental details for all the products listed in Table 1 are
provided in the Supporting Information. In a typical procedure, a stirred
pressure reactor was charged with durene (13.4 g; 100 mmol), LiK(OCH2-
CH2NMe2)2 (30 mL of a 0.67 M solution in methylcyclohexane [MCH]; 20
mmol), Mg(OCH2CH2OEt)2 (2.8 mL of a 1.8 M solution in MCH.; 5 mmol),
n-BuLi (14 mL of a 1.6 M solution in MCH.; 20 mmol), and 10 mL MCH.
After stirring for 30 min, the reactor was filled with ethylene to 20 atm and
stirred with heating at 80 °C. The pressure was maintained at 20 ( 2 atm.
The reaction was stopped when no further gas consumption was evident (
∼24-36 h). The mixture was hydrolyzed and acidified, and the product was
extracted with hexane. Removal of solvents, fractional distillation under
reduced pressure, and recrystallisation from ethanol gave 1,2,4,5-tetrakis(1-
ethylpropyl)benzene as a white crystalline solid, yield: 21.5 g (60%), mp
79-80 °C. Analogous stoichiometric ratios of the reactants were employed
for entries 6, 8, and 9 (Table 1), while for entries 1-5 the ratio for substrate/
n-BuLi/LiK(OCH2CH2NMe2)2/Mg(OCH2CH2OEt)2 was 100/10/10/2.5.
(4) Screttas, C. G.; Steele, B. R. J. Organomet. Chem. 1993, 453, 163-
170.
(5) (a) Pines, H.; Vesely, J. A.; Ipatieff, V. N. J. Am. Chem. Soc. 1955,
77, 554-559. (b) Pines, H.; Mark, V. ibid. 1956, 78, 4316-4322. (c) Schaap,
L.; Pines, H. ibid. 1957, 79, 4967-4970. (d) Pines, H. Acc. Chem. Res. 1974,
7, 155-162. (e) Pines, H.; Stalick, W. M. Base-Catalyzed Reactions of
Hydrocarbons and Related Compounds; Academic Press: New York, 1977;
pp 240-308.
(6) Screttas, C. G.; Eastham, J. F. J. Am. Chem. Soc. 1965, 87, 3276-
3277.
(7) (a) Schlosser, M. J. Organomet. Chem. 1967, 8, 9-16. (b) Lochmann,
L.; Pospisil, J.; Lim, D. Tetrahedron Lett. 1966, 257-262.
10.1021/ja994432p CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/29/2000

2392 J. Am. Chem. Soc., Vol. 122, No. 10, 2000
Communications to the Editor
Table 1. Products and Yields of Catalyzed Addition of Ethylene to
Methylbenzenes
preferentially, and that the reaction is driven by the effectively
irreversible protonation of the addition product.14 Metalation of
1 would produce a tertiary 3-arylpentyl carbanion which would
be expected to be even more reactive than the secondary
1-arylpropyl carbanion, but we found no evidence for the
production of triethylated compounds, except in trace amounts
from the reaction with toluene. We infer from this that the benzylic
site of a 3-arylpentane is either not susceptible to metalation under
the conditions used or that steric factors prevent addition of
ethylene. That there do indeed appear to be appreciable steric
constraints to the addition of ethylene is indicated by the lack of
diethylation of methyl groups flanked by neighboring methyl
groups.
yield
entry
substrate
toluene
n-butylbenzene
o-xylene
m-xylene
p-xylene
mesitylene
durene
product
(%)a
1
2
3
4
5
6
7
8
9
3-pentylbenzene
3-hexylbenzene
68
66
61
79
75
72
60
1,2-bis(3-pentyl)benzene
1,3-bis(3-pentyl)benzene
1,4-bis(3-pentyl)benzene
1,3,5-tris(3-pentyl)benzene
1,2,4,5-tetrakis(3-pentyl)benzene
pentamethylbenzene 1,5 bis(3-pentyl)-2,3,4-tripropylbenzene 75
hexamethylbenzene hexapropylbenzene 68
a Iisolated yields.
The preparation of these new sterically demanding arenes can
be now readily carried out in substantial quantities using
inexpensive starting materials.15 Alternative procedures might be
envisaged but suffer from various drawbacks. The Friedel-Crafts
reaction is rarely a satisfactory method for the introduction of
alkyl groups into specific positions and without isomerization,
while other more selective procedures such as the transition metal
catalyzed trimerization of alkynes or the alkylation of transition
metal complexed arenes require more expensive starting materials
and are not readily applicable to large-scale preparations.1,16,17
One of the subsequent objectives will be to explore their
applications to organometallic synthesis and catalysis while an
investigation into the extension of the process described here to
the preparation of heteroatom analogues is now underway.
ethylated products were observable by GC. The only side products
observed were higher molecular weight products, presumably
telomers, which could be separated by distillation. In the absence
of Mg(OCH2CH2OEt)2 the reaction did not proceed to completion,
and a mixture of partially ethylated products were obtained,
mainly 1-methyl, 3-(3-pentyl)benzene (44%), and 1-methyl,3-
propylbenzene (20%), as well as unreacted m-xylene (25%). The
tetra-ethylated product constituted only 4.6% of the mixture.
The reaction is believed to take the following course. After
the initial metalation of substrate to give a benzylic carbanion,
addition of a molecule of ethylene gives rise to a very reactive
3-arylpropylcarbanion. This will provide a metalating agent as
strong as that originally applied and will metalate available
benzylic sites. Normally a methyl group will be metalated more
easily than a secondary benzylic site, but it was observed that
there is a strong preference for ethylation at the latter. To illustrate
this point, the course of the reaction with m-xylene as substrate
was investigated, and it was found that the formation of
1-methyl,3-(3-pentyl)benzene,1, was greatly favored over that of
1,3-dipropylbenzene, 2, (ratios of 1/2 of 4:1 to 20:1 were found
depending on the time of reaction; shorter reaction times gave
the higher ratios). Previous detailed studies have been made by
Maercker et al. on systems of this type in ethereal solvents and
support an intermolecular process.12 The observed results indicate,
therefore, that, although the metalation of the benzylic position
of the propyl side chain is less favorable than that of the methyl
group, the resulting secondary carbanion is sufficiently more
reactive toward ethylene,13 that products such as 1 are formed
Supporting Information Available: Full experimental procedures
1
for all alkylations, analytical data, H and 13C NMR spectral data, and
mass spectral data for the products for entries 3-9 of Table 1 (PDF).
This material is available free of charge via the Internet at http://pubs.acs.org.
JA994432P
(13) Assadourian, L.; Gau, G. New J. Chem. 1990, 14, 57-62.
(14) Maercker, A.; Passlack, M. Chem. Ber. 1982, 115, 540-577.
(15) Using a 250 mL pressure reactor it is quite straightforward to use up
to 250 mmol of substrate and to isolate 35-40 g of pure product. No problems
are envisaged in scaling up the process for the production of larger quantities.
(16) (a) Maitlis, P. M. J. Organomet. Chem. 1980, 200, 161-176. (b)
Vollhardt, K. P. C. Acc. Chem. Res. 1977, 10, 1-8. (c) Yur’eva, L. P. Russ.
Chem. ReV. 1974, 43, 48-68.
(17) (a) Moulines, F.; Gloaquen, B.; Astruc, D. Angew. Chem. 1992, 104,
452-454; Angew. Chem., Int. Ed. Engl. 1992, 31, 458-460. (b) Astruc, D.;
Hamon, J. R.; Mandon, D.; Moulines, F. Pure Appl. Chem. 1990, 62, 1165-
1168.
(12) Maercker, A.; Sto¨tzel, R. J. Organomet. Chem. 1983, 254, 1-12.