Detailed Characterization of p-Toluenesulfonic Acid Monohydrate as a Convenient, Recoverable, Safe, and Selective Catalyst for Alkylation of the Aromatic Nucleus

Article abstract of DOI:10.1021/jo971832r

Alkylation of the aromatic nucleus, an important reaction in industry and synthetic organic chemistry, has traditionally been carried out by the well-known Friedel-Crafts reaction employing Lewis acid catalysts such as AlCl₃ and BF₃ or by using highly reactive organometallic reagents. Although protic acids such as anhydrous HF and concentrated H₂SO₄ have also been used in the alkylation of the aromatic nucleus, the notoriously corrosive, highly toxic, and hazardous nature of these agents has precluded their common use under ordinary laboratory conditions. Various organic sulfonic acids have, on occasion, been used as catalysts in Friedel-Crafts alkylations, but to our knowledge the chemistry and the scope of these reactions for common laboratory use have never been exploited in detail. In the present study we have characterized commercially available p-toluenesulfonic acid monohydrate (TsOH) as an efficient catalyst for the intermolecular coupling of the aromatic nucleus with activated alkyl halides, alkenes, or tosylates under mild conditions in an open atmosphere. In comparison to conventional Friedel-Crafts catalysts such as AlCl₃, BF₃, HF, and concentrated H₂SO₄, the extent of the formation of undesired products from side reactions such as transalkylation, polymerization, etc. was minimal with the TsOH-catalyzed reaction. The ability to recover and reuse the catalyst from the reaction mixtures, minimal generation of environmentally unfriendly waste, high specificity of the reaction, and the low cost of the catalyst are important advantages of the TsOH catalyst over the other conventional Friedel-Crafts catalysts.

Full text of DOI:10.1021/jo971832r

2858
J . Org. Chem. 1998, 63, 2858-2866
Deta iled Ch a r a cter iza tion of p-Tolu en esu lfon ic Acid Mon oh yd r a te
a s a Con ven ien t, Recover a ble, Sa fe, a n d Selective Ca ta lyst for
Alk yla tion of th e Ar om a tic Nu cleu s
Mathew P. D. Mahindaratne and Kandatege Wimalasena*,†
Department of Chemistry, Wichita State University, Wichita, Kansas 67260
Received October 3, 1997
Alkylation of the aromatic nucleus, an important reaction in industry and synthetic organic
chemistry, has traditionally been carried out by the well-known Friedel-Crafts reaction employing
Lewis acid catalysts such as AlCl3 and BF3 or by using highly reactive organometallic reagents.
Although protic acids such as anhydrous HF and concentrated H2SO4 have also been used in the
alkylation of the aromatic nucleus, the notoriously corrosive, highly toxic, and hazardous nature
of these agents has precluded their common use under ordinary laboratory conditions. Various
organic sulfonic acids have, on occasion, been used as catalysts in Friedel-Crafts alkylations, but
to our knowledge the chemistry and the scope of these reactions for common laboratory use have
never been exploited in detail. In the present study we have characterized commercially available
p-toluenesulfonic acid monohydrate (TsOH) as an efficient catalyst for the intermolecular coupling
of the aromatic nucleus with activated alkyl halides, alkenes, or tosylates under mild conditions in
an open atmosphere. In comparison to conventional Friedel-Crafts catalysts such as AlCl3, BF3,
HF, and concentrated H2SO4, the extent of the formation of undesired products from side reactions
such as transalkylation, polymerization, etc. was minimal with the TsOH-catalyzed reaction. The
ability to recover and reuse the catalyst from the reaction mixtures, minimal generation of
environmentally unfriendly waste, high specificity of the reaction, and the low cost of the catalyst
are important advantages of the TsOH catalyst over the other conventional Friedel-Crafts catalysts.
In tr od u ction
despite some unfavorable properties such as limited
solubility in organic solvents and sublimation at higher
temperatures, in solution chemistry. In addition, in some
cases AlCl3 is known to result in extensive undesirable
side reactions such as degradation, polymerization, and
isomerization, causing the reduction of expected product
yields significantly. Boron trifluoride has also become a
widely used catalyst since the 1920s following initial
studies by Meerwein, Nieuwland, and others.4,5 Since
BF3 is a low-boiling gas (bp -101 °C), some of its more
convenient complexes such as ether complexes are fre-
quently used despite their low reactivity. Although a
significant number of other Lewis acid halides and
pseudohalides are also used in Friedel-Crafts reactions,
none of them have achieved the wide applicability in
solution chemistry that AlCl3 and BF3 have.4
Although various other methods for alkyl substitution
in the aromatic nucleus have also been exploited, still
no common convenient method which is suitable for a
majority of alkyl substituents is available. For example,
until recently, no simple and mild method has been
described for the intermolecular arylation of cyclic and
bicyclic substrates.6 In recent years, a number of studies
on aromatic substitution using olefins by the action of
organometallic reagents, especially palladium and copper
Alkylbenzenes and alkylphenols are important raw
materials in industry and in scientific research. For
example, alkylbenzenes with 10-14 side chain carbon
atoms are starting materials for the manufacture of
sulfonates which are important raw materials for the
industrial production of anion-active detergents and
polymers.1 Annual production of alkylbenzenes for this
purpose is estimated to be over one million tons in
Western Europe, USA, and J apan. On the other hand,
alkylphenols are widely employed as antioxidant and
antibacterial agents.2
Alkylation of the aromatic nucleus has been tradition-
ally carried out with the well-known Friedel-Crafts
reaction using Lewis acids or organometallic reagents
using the corresponding alkyl halides.3 In the course of
more than 100 years of Friedel-Crafts chemistry, only
two catalysts, AlCl3 and BF3, have gained wide recogni-
tion.4 Especially, anhydrous AlCl3 maintained its wide
use ever since it was introduced by Friedel and Crafts,3
† Tel. (316) 978-3120. Fax. (316) 978-3431. E-mail: wimalase@
wsuhub.uc.twsu.edu.
(1) Weissermel, K.; Arpe, H.-J . Industrial Organic Chemistry, 2nd
ed.; VCH Verlagsgesellschaft mbA: Weinheim, Germany and VCH
Publishers: New York, 1993.
(2) Reichle, W. T.; Konrad, F. M.; Brooks, J . R. In Benzene and Its
Industrial Derivatives, Chapter 8; Hancock, E. G., Ed.; J ohn Wiley &
Sons: New York, 1975; pp 344-445.
(5) Bowlus, H.; Nieuwland, J . J . Am. Chem. Soc. 1931, 53, 3835.
Meerwein, H.; Pannwitz, W. J . Prakt. Chem. 1934, 141, 123. Booth,
H. S.; Martin, D. R. Boron Trifluoride and Its Derivatives; Wiley: New
York, 1949. Topchiev, A. V.; Zavgorodnii, S. V.; Paushkin, Y. M. Boron
Trifluoride and Its Compounds as Catalysts in Organic Chemistry (Eng.
Ed.); Pergamon Press: New York, 1959.
(6) Larock, R. C.; J ohnson, P. L. J . Chem. Soc., Chem. Commun.
1989, 1368. Holland, H. L.; Kindermann, M.; Kumaresan, S.; Stefanac,
T. Tetrahedron: Asymmetry 1993, 4, 1353. Olah, G. A.; Lee, C. S.;
Prakash, G. K. S. J . Org. Chem. 1994, 59, 2590.
(3) Friedel, C.; Crafts, J . M. Compt. Rend. 1877, 84, 1392, 1450.
Friedel, C.; Crafts, J . M. Compt. Rend. 1877, 85, 74.
(4) For review see: (a) Friedel-Crafts and Related Reactions; Olah,
G. A., Ed.; Wiley: New York, 1963-64; Vol. I-IV. (b) Olah, G. A.
Friedel-Crafts Chemistry; Wiley-Interscience: New York, 1973. (c)
Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
New York, 1991; Vol. 3, pp 293-339.
S0022-3263(97)01832-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/14/1998

p-Toluenesulfonic Acid Monohydrate
J . Org. Chem., Vol. 63, No. 9, 1998 2859
containing,7 have been reported. However, the useful-
ness of these sensitive organometallic reagents under
ordinary laboratory conditions is limited by the rigorous
inert conditions required and the relatively high cost of
the metal catalysts used in these reactions. On the other
hand, although protic acids such as anhydrous HF and
concentrated H2SO4 have also been successfully used in
the alkylation of the aromatic nucleus using simple
olefins,8 the notoriously corrosive, highly toxic, and
hazardous nature of these agents has precluded their
common use under ordinary laboratory conditions.
Various organic sulfonic acids4,9 including perfluoro-
sulfonic acids9a,b (superacids), methanesulfonic acid,9c and
benzenesulfonic acid9d have, on occasion, been used as
catalysts in Friedel-Crafts alkylations. In addition,
p-toluenesulfonic acid (TsOH) has also been occasionally
used as a Friedel-Crafts alkylation catalyst9f-n (mainly
for the alkylation of phenols9i-l and other highly activated
aromatic nuclei9g,h). However, to our knowledge the
chemistry and the scope of these reactions for common
use have never been exploited in detail. For example,
TsOH has not been described as a useful catalyst for the
alkylation of the aromatic nucleus with haloalkanes,
haloalkenes, alkyl sulfonates, or cycloalkenes. The lack
of the popularity of TsOH as a Friedel-Crafts alkylation
catalyst is also quite apparent from the fact that the most
recent review by Olah et al.4c on the subject has not even
cited TsOH as a catalyst for the reaction.
In the present study we have carried out a systematic
characterization of the alkyl substitution of the aromatic
nucleus using commercially available p-toluenesulfonic
acid monohydrate (TsOH) as a catalyst. Our results
demonstrate that TsOH is a very effective environmen-
tally friendly catalyst for the alkylation of the aromatic
ring with activated aliphatic halides, alkenes, and sul-
fonic esters. While this reaction could be carried out in
an open atmosphere to produce high yields of the desired
products, most of the catalyst could be recovered by
simple filtration and reused. The scope and mechanism
of the reaction is discussed in detail.
standard reactions were carried out in an open pot under
refluxing conditions using the desired alkyl substrate,
toluene (also the solvent), and the catalyst, TsOH. To
explore the scope and the selectivity of the reaction, three
different types of alkylating reagents (Scheme 1), allylic
and activated halides (type A), tosylates (types B, E, and
F), and cyclic (type C) and acyclic (types D and G)
alkenes, have been used as substrates. In addition to
these, we have also used secondary, tertiary, and benzyl
halides as alkyl substrates to further examine the
selectivity and the scope of the reaction and to compare
and contrast with the corresponding conventional Friedel-
Crafts alkylations (Scheme 1 and Table 1).
Initial experiments indicated that TsOH is an effective
recoverable catalyst for the alkylation of toluene with the
above listed alkyl substrates. Studies of the effects of
catalyst concentration (0.3-2.2 equiv) on the distribution
and yield of the products showed that, while substoichio-
metric amounts of the catalyst are effective in promoting
the reaction, the use of higher concentrations reduced the
reaction time considerably. An optimum ratio of catalyst
to alkyl substrate was estimated to be about 1:1.2.
However, the use of increased amounts of the catalyst
neither decreased the yield nor promoted the side reac-
tions such as polymerization, which is a common problem
with most other conventional Friedel-Crafts catalysts.
For example, in the case of alkene arylation, most protic
acid catalysts form byproducts, believed to be the alkyl
esters of the catalyst, which promote polymerization upon
heating and lead to a significant reduction in the yield
of the reaction.10 Although TsOH also produces tosylate
byproducts11 from alkenes under the reaction conditions
used, these tosylates were also found to be excellent
substrates for the alkylation reaction, giving the same
products as the original olefin (see below) rather than
the polymerized products.
Most conventional Friedel-Crafts catalysts generally
give complex reaction mixtures which could be worked
up and separated with difficulty12 and with the loss of
generally expensive catalysts, producing environmentally
unfriendly, toxic waste. In contrast, TsOH is completely
soluble in most aromatic solvents such as toluene under
refluxing conditions to give homogeneous solutions, and
when the reaction mixture is cooled to room temperature,
most of the TsOH separates as a crystalline solid. More
than 75% of the solid catalyst could be conveniently
recovered at the end of the reaction by simple filtration,
and the catalyst could be reused without any loss of
catalytic activity. Simple solvent extraction of the reac-
tion mixture with hexane and a solution of 0.1 M sodium
bicarbonate removes the small contamination of the
catalyst, and evaporation of the hexane extract yields a
relatively clean crude mixture of products.
Resu lts a n d Discu ssion
Alkylation of the toluene nucleus by various alkylating
agents was chosen as a model reaction for our study. The
(7) Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J . A. Tetrahedron
1984, 40, 5005. Corey, E. J .; Posner, G. H. J . Am. Chem. Soc. 1967,
89, 3911. Brunner, H.; Kramler, K. Synthesis 1991, 1121. Fujiwara,
Y.; Moritani, I.; Danno, S. J . Am. Chem. Soc. 1969, 91, 7166. Danno,
S.; Moritani, I.; Fujiwara, Y. Tetrahedron 1969, 25, 4809. Heck, R. F.
J . Am. Chem. Soc. 1968, 90, 5518. Heck, R. F. J . Am. Chem. Soc. 1969,
91, 6707. Garves, K. J . Org. Chem. 1970, 35, 3273. Horino, H.; Inoue,
N. Bull. Chem. Soc. J pn. 1971, 44, 3210. Horino, H.; Arai, M.; Inoue,
N. Tetrahedron Lett. 1974, 647. Catellani, M.; Chiusoli, G. P. J .
Organomet. Chem. 1988, 346, C27.
(8) Olah, G. A., in ref 4a, 1963; Vol. I, Chapter 4, pp 201-366.
(9) (a) Fu, X.; He, M.; Lei, Q.; Luo, B. Synth. Commun. 1991, 21,
1273. (b) Olah, G. A. Can. Patent 1,152,111, 1983; Chem. Abstr. 1984,
100, 34291. (c) Proell, W. A.; Adams, C. E. Ind. Eng. Chem. 1949, 41,
2217. (d) Nenitzescu, C. D.; Ioan, V.; Teodorecu, L. Chem. Ber. 1957,
90, 585. (e) Isham, R. M. U. S. Patent 2,014,766, 1935; Chem. Abstr.
1935, 29, 7346. (f) Zaitsev, B. A.; Kiseleva, R. F.; Denisov, V. M.;
Kol'tsov, A. I. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.)
1990, 39, 2323. (g) Gosser, L. W. U.S. Patent 4,255,343, 1981; Chem.
Abstr. 1981, 95, 42763. (h) Wodsworth, F. T.; Lee, R. J . U.S. Patent
2,462,792, 1949; Chem. Abstr. 1949, 43, 4458. (i) Chandra, K. G.;
Sharma, M. M. Catal. Lett. 1993, 19, 309. (j) Chaudhuri, B.; Sharma,
M. M. Ind. Eng. Chem. Res. 1991, 30, 227. (k) Chaudhuri, B.;
Patwardhan, A. A.; Sharma, M. M. Ind. Eng. Chem. Res. 1990, 29,
1025. (l) Dean, R. E.; Midgley, A.; White, E. N.; McNeil, D. J . Chem.
Soc. 1961, 2773. (m) Pratt, E. F.; Preston, R. K.; Draper, J . D. J . Am.
Chem. Soc. 1950, 72, 1367. (n) Pratt, E. F.; Segrave, H. J . E. J . Am.
Chem. Soc. 1959, 81, 5369.
Alk yla tion of Tolu en e by Ha loa lk en es. Unsatur-
ated alkyl halides such as allylic halides possess two
reactive centers susceptible to Friedel-Crafts alkylation.
It is known that these haloalkenes react either at the
double bond or at the allylic center depending on the type
of catalyst and the reaction conditions used.13 While
(10) Olah, G. A. In ref 4a, 1963; Vol. I, Chapter 2, pp 25-168.
(11) Proell, W. A.; Adams, C. E.; Shoemaker, B. H. Ind. Eng. Chem.
1948, 40, 1129.
(12) Roberts, R. M.; Khalaf, A. A. Friedel-Crafts Alkylation Chem-
istry; Marcel Dekker: New York, 1984.
(13) Koncos, R.; Friedman, B. S. In ref 4a, 1964; Vol. II, Chapter
15, pp 289-412.

2860 J . Org. Chem., Vol. 63, No. 9, 1998
Mahindaratne and Wimalasena
Sch em e 1
protic catalysts such as H2SO4 generally favor the reac-
tion at the double bond, less reactive metal halide
catalysts such as ZnCl2 and FeCl3 favor the reaction at
the allylic position initially and then the electrophilic
addition of the aromatic nucleus to the double bond. To
examine the selectivity of the TsOH-catalyzed alkylation
reaction, we have initially examined trans-cinnamyl
chloride (1) as an alkyl substrate under the standard
reaction conditions (type A, Scheme 1). These studies
revealed that 1 is an excellent substrate for the reaction
and produces trans-1-phenyl-3-tolyl-1-propenes (2; entry
1, Table 1) as the exclusive product, in excellent yield
(98%) under the conditions used. We believe the high
selectivity of the reaction toward the allylic position must
be a consequence of the extra stability of the double bond
of 1 due to the direct conjugation with the phenyl ring
and the mild nature of the reaction conditions used. In
addition, we note that, to our knowledge, this is the first
example of the direct arylation of any cinnamyl halide
and the first one-step preparation of unsymmetrical 1,3-
diarylpropenes from commercially available starting
materials. The simplicity of the procedure makes this
method even more attractive over the other methods
reported in the literature.14
As expected, trans-crotyl chloride (3) also behaves in
a similar manner to that of 1, but with less reactivity
and selectivity (entries 2-5, Table 1), giving relatively
low yields of trans-1-tolyl-2-butenes (4) as the initial
products (entries 2 and 3, Table 1) at shorter reaction
times. Prolongation of the reaction time (entries 4 and
5, Table 1) results in the formation of 1,1-ditolylbutane
(20; type D, Scheme 1) which was rather unexpected
since most reported disubstituted products from allylic
halides are 1,2-diarylalkanes.13 However, under mild
reaction conditions formation of the 1,1-aryl product is
expected since the benzylic carbenium ion 4c from the
initial product (4) is more stable than the other possible
(14) Raunio, E. K.; Bonner, W. A. J . Org. Chem. 1966, 31, 396.
Rondestvedt, C. S., J r. J . Am. Chem. Soc. 1951, 73, 4509 and references
therein.
(15) Patinkin, S. H.; Friedman, B. S. In ref 4a, 1964; Vol. II, Chapter
14, pp 1-288.

p-Toluenesulfonic Acid Monohydrate
J . Org. Chem., Vol. 63, No. 9, 1998 2861
an 87% total yield.18 The ratio of the two products, 18
to 22-p , is not significantly dependent on the reaction
time (18 h). In addition, prolonged refluxing of 22-p in
the presence of TsOH in either toluene or xylenes did
not cause further ring contraction or expansion of the
compound and the starting material, 22-p , was isolated
almost quantitatively. In contrast to the behavior of 17,
cyclohexene (16) exclusively gave tolylcyclohexane (11;
entry 15, Table 1), with no evidence of the ring-contracted
products.19 These results further confirm the early
observation that while AlCl3-catalyzed alkylation of cy-
cloheptene predominantly produces 1,3- and 1,4-substi-
tuted cyclohexanes20 as ring-contracted products, protic
Ta ble 1. Alk yla tion of Tolu en e in th e P r esen ce of
p-Tolu en esu lfon ic Acid a
%
% isomer
ratio
sub- time
%
total
entry strate
(h)
products
convnb yieldc
(o, m, p)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1
3
3
3
3
5
7
10
10
12
21
21
23
14
16
17
19
30
33
33
3
1
3
9
2
4
4
100
33
67
>98 35, -, 65
∼90
∼91 37, 4, 59
-
4, 20 (66%)
20
6
85
∼95
-
18
100
100
100
42
100
100
54
100
100
100
100
100
100
100
tr
100 46(op), -, 54(pp)
100 19, 3, 78
∼99 16, 0, 84
100 27, 17, 56
100 28, 18, 54
100 34, 18, 48
6
12
3
18
18
8
11
11
13
1.5 22
100
-
21
acids such as H2SO4 and TsOH give 1,1-substituted
cyclohexanes and/or cyclopentanes.
3
18
4
6
6
5
48
3
22
100 -, tr, >99
100 -, 4, 96
24 (86%),e 25
15
11
85 33, 23, 44
98 29, 18, 53
87 30, 21, 49
100 34, 18, 48
97 ∼16, tr, 84
Alk yla tion of Tolu en e by Alk yl Tosyla tes. Al-
though alkyl arenesulfonates, particularly alkyl tosylates,
are very active alkylating agents compared to the corre-
sponding alkyl halides, their use in conventional Friedel-
Crafts alkylation is not widespread. Since TsOH-
mediated alkylation appears to proceed through a
carbenium ion intermediate, we have examined several
secondary tosylates (types B, E, and F, Scheme 1) as
possible alkyl substrates, since these may also easily
produce the corresponding carbenium ions under these
reaction conditions. As expected, both cyclohexyl (10;
entry 9, Table 1) and exo-2-norbornyl (12; entry 10, Table
1) tosylates gave the expected products (11 and 13,
respectively) in quantitative yields. However, when
trans-2-methyl-1-(tosyloxy)cyclohexane (21; entry 12,
Table 1) or trans-1-(benzenesulfonyloxy)-2-methylcyclo-
hexane was used as the alkyl substrate (type E, Scheme
1), the coupling took place smoothly within a short period
of time to give the unexpected 1,1 isomer 22-p as the sole
product in 100% yield rather than the 1,2 isomer. The
acyclic counterpart, 4-methyl-2-(tosyloxy)pentane (23;
entry 13, Table 1) or 2-(benzenesulfonyloxy)-4-methyl-
pentane, while requiring a longer reaction time (18 h)
for the quantitative conversion, yielded two structural
isomers (type F, Scheme 1), 2-methyl-2-tolylpentane (24;
86%) and 3-methyl-3-p-tolylpentane (25-p ; 14%). The
notable feature of the latter reaction is the very high
proportion of 24 over 25 despite the fact that both must
have been derived from the electrophilic arylation of
tertiary alkyl carbenium ions.
18 (65%),e 22
13
31
11
11
9
-
80
-
-
84
50
-
32
t-BuCl 30
34 60
40f 0, 5, 95
35
100 35, 25, 40
a
Reactions were carried out with ∼1 M solutions of the
substrate and 1.2 molar equiv of p-toluenesulfonic acid in toluene.
Calculated from the 1H NMR of the crude products. c Isolated
b
d
yield with respect to the % conversion. Calculated from the
intensity of the corresponding 1H NMR signals of un-isoltated
product mixtures. e o, m, p isomer ratios indicated are for these
major products. f Significant amount of the substrate may have
been lost during the reaction due to the low boiling point.
isomeric carbenium ions15 (Scheme 2). Isolation of trace
amounts of trans-1-(2-methylphenyl)-1-butene (32-o) from
the reaction mixture confirms that 20 must be arising
from the acid-assisted double bond migration13,15 of the
initially generated carbenium ion 4a to produce 4c
followed by a simple acid-assisted second arylation
(Scheme 2; also see alkene arylation; entries 14-18,
Table 1). In addition, the absence of diortho product of
20, 1,1-bis(2-methylphenyl)butane, suggests that the
arylation of 4 is strongly dependent on steric factors. To
our knowledge, 1,1-diarylalkanes, except 1,1-diarylethane
from vinyl chloride16 and styrene,17 are not commonly
obtained from a one-step reaction of conventional Friedel-
Crafts alkylation conditions using allylic halides or any
other common substrates in good yield.
Alk yla tion of Tolu en e by Active Alk yl Ha lid es.
Unactivated alkyl halides were found to be not as reactive
as tosylates toward the TsOH-catalyzed arylation reac-
tion (entries 19-22, Table 1). For example, bromocyclo-
hexane (33; entry 20, Table 1) needed 84 h for 50%
conversion to 11 with 80% yield, while only 32% of benzyl
chloride (34; entry 22, Table 1) was converted to phenyl-
tolylmethane (35) in 60 h. However, the activated halide
bromodiphenylmethane (5; type A, Scheme 1) undergoes
arylation much more efficiently and quantitatively to
yield the corresponding diphenyltolylmethane (6; entry
6, Table 1) within 6 h. Similarly, 9-bromofluorene (7;
type A, Scheme 1) is also converted to the corresponding
Alk yla tion of Tolu en e by Alk en es. Since cyclic
olefins usually behave in a manner similar to that of their
acyclic counterparts as alkyl substrates in Friedel-Crafts
reactions (except the possible ring contraction or expan-
sion side reactions), and since cyclic alkenes could be
more reactive toward electrophiles due to the extra
torsional energy of the ring double bond, we predicted
that cyclic alkenes could also be good alkyl substrates
for TsOH-catalyzed alkylation of the aromatic nucleus.
As expected, TsOH-catalyzed catalyzed alkylation of
toluene by monocyclic and bicyclic alkenes (type C,
Scheme 1) proceeds remarkably well, giving high yields
of the desired products (entries 14-18, Table 1). In
addition, cycloheptene (17) undergoes alkylation quite
readily (entry 16, Table 1) to give a mixture of products,
tolylcycloheptane (18; 65%) and the ring-contracted
product 1-methyl-1-p-tolylcyclohexane (22-p ; 35%), with
(18) Careful 1H and 13C NMR analysis unequivocally confirmed the
structure of 22-p which is identical to the product obtained from the
tosylate 21 (entry 12, Table 1).
(19) Saunders: M.; Rosenfeld, J . J . Am. Chem. Soc. 1969, 91, 7756.
(20) Pines, H.; Edeleanu, A.; Ipatieff, V. N. J . Am. Chem. Soc. 1945,
67, 2193. Friess, S. L.; Pinson, R., J r. J . Am. Chem. Soc. 1951, 73,
3512.
(16) Davidson, J . M.; Lowy, A. J . Am. Chem. Soc. 1929, 51, 2978.
(17) Kraemer, G.; Spilker, A.; Eberhardt, P. Ber. 1890, 23, 3269.
Spilker, A.; Schade, W. Ber. 1932, 65B, 1686.
(21) Pokrovskaya, E. S.; Stepantseva, T. G. J . Gen. Chem. U.S.S.R.
1939, 9, 1953.

2862 J . Org. Chem., Vol. 63, No. 9, 1998
Mahindaratne and Wimalasena
Sch em e 2
Sch em e 3
9-tolylfluorene (8) under the standard reaction conditions
in excellent yield (99%; entry 7, Table 1) after 12 h of
refluxing. Although both 5 and 7 have very similar
electronic and steric properties, the above results indicate
that the arylation of 7 is somewhat slower than that of
5. We believe this significant difference in reactivity may
primarily be due to the steric effect. In addition, no meta
isomer was detected in the reaction of 7 in contrast to
the reaction of 5 where about 3% of the meta isomer was
produced. These results, especially the difference in
relative reactivities of 5 and 7, may provide important
information about the detailed mechanism of the TsOH-
catalyzed aromatic alkylation reaction. In addition, we
emphasize that 9-arylfluorene has not been previously
obtained by the Friedel-Crafts alkylation reaction using
conventional Lewis acid or protic acid catalysts. The
major product from 7, 9-(4-methylphenyl)fluorene (8-p ;
84%), was easily purified by simple column chromatog-
raphy. The other 16% of the product was exclusively the
ortho isomer, 8-o, which was identified by characteristic
deshielding of 9-H (5.33 ppm of 8-o vs 5.00 ppm of 8-p )
and benzylic-CH3 (2.71 vs 2.30 ppm) proton signals in
1H NMR and shielded 9-C (50.00 vs 54.09 ppm) and
benzylic-CH3 (20.41 vs 21.05 ppm) signals in 13C NMR.22
reaction conditions.25 Furthermore, careful inspection of
the reactivities of various substrates, especially the
reactions which could generate identical (e.g., entries 9,
15, and 20 or 10 and 17, Table 1) or energetically similar
(e.g., entries 6 and 7 or 9 and 12, Table 1) initial
carbenium ion intermediates indicate that the relative
reactivities of the carbenium ions do not correlate with
the observed rates of the reactions, suggesting that the
initial carbenium ion generation step may be the rate-
determining step.26a Formation of carbon skeleton rear-
ranged, thermodynamically more stable products also
provides further support for a SN127 type two-step
mechanism for the reaction.
The carbon skeleton rearrangement in the Friedel-
Crafts reaction is well-documented. The most important
driving force for the formation of only two rearranged
products, 24 and 25, from alkyl substrate 23, which
would presumably generate carbenium ion 23a initially
(Scheme 3), must be the thermodynamic stability of the
tertiary carbenium ions 23c and 23e over the secondary
carbenium ions 23a , 23b, and 23d .27 The product, 24,
must arise from the tertiary carbenium ion 23c, which
could be generated from 23a by two successive 1,2
hydride shifts (Scheme 3). On the other hand, 25 could
Review of th e Mech a n ism . Although stereochemical
and mechanistic studies of the Friedel-Crafts reaction
have been limited, the generation of a complex species
with carbenium ion character from the alkyl substrate
is commonly accepted.23 The formation of most of the
products from TsOH-catalyzed reactions (types B-G,
Scheme 1) could also be best explained by assuming the
formation of an initial carbenium ion intermediate,24 even
though a free radical mechanism could also be possible
under the thermal and nonpolar reaction conditions used.
We believe TsOH is capable of generating a carbenium
ion intermediate from most of the alkyl substrates tested
at higher temperatures which could readily undergo
electrophilic substitution (before or after skeletal rear-
rangement) with the readily available aromatic solvent.
The initial carbenium ion intermediate could possibly be
generated by acid-catalyzed elimination of the tosyloxy
group (types B, E, and F, Schemes 1 and 3) or electro-
philic addition of a proton to the double bond (types C,
D, and G, Schemes 1, 2, and 4) under appropriate
(25) However, generation of a carbenium ion intermediate from type
A alkyl substrates could not be easily envisioned.
(26) (a) Brown, H. C.; Grayson, M. J . Am. Chem. Soc. 1953, 75, 6285.
(b) Brown, H. C.; J ungk, H. J . Am. Chem. Soc. 1955, 77, 5584. (c)
Brown, H. C.; J ungk, H. J . Am. Chem. Soc. 1956, 78, 2182. (d) J ungk,
H.; Smoot, C. R.; Brown, H. C. J . Am. Chem. Soc. 1956, 78, 2185.
(27) Nenitzescu, C. D. In Carbonium Ions; Olah, G. A., Schleyer, P.
v. R., Eds.; J ohn Wiley-Interscience: New York, 1968; Chapter 1, Vol.
I, pp 1-75.
(22) Nakamura, M.; Nakamura, N.; Oki, M. Bull. Chem. Soc. J pn.
1977, 50, 1097.
(23) Hart, H. In ref 4a, 1963; Vol. I, Chapter 13, pp 999-1015.
(24) Gates, B. C. Catalytic Chemistry; J ohn Wiley & Sons: New
York, 1992.

p-Toluenesulfonic Acid Monohydrate
J . Org. Chem., Vol. 63, No. 9, 1998 2863
Sch em e 4
Sch em e 5
arise from the symmetrical tertiary carbenium ion 23e
presumably generated by successive 1,2 hydride and
methide shifts followed by a second 1,2 hydride shift
(Scheme 3). The predominant formation of 24 over 25
must be at least partly due to the relatively slow rate of
formation of 23e in comparison to 23c as a consequence
of a slow 1,2-methide shift relative to the competing 1,2-
hydride shift. In addition, other steric and electronic
factors such as hyperconjugation may also play an
important role in the overall product distribution of the
reaction. The high sensitivity of the reaction toward
steric and electronic factors27,28 is also clearly reflected
in the observed product distribution of 4-octene29 (26; type
G, Scheme 1). The observed high percentage of 2-phen-
yloctane (27; 65%) in comparison to 3- and 4-phenyloc-
tanes [28 (21%) and 29 (15%), respectively] could be due
to the steric preference of the arylation step. The absence
of ortho products derived from the tertiary carbenium
intermediates further suggests that the isomer ratio of
the final product is mainly determined by the steric
factors (entries 12-13 and and 21, Table 1).
Formation of 20 as the only product from the alkyl
substrate 2 in high yield at longer reaction times (entry
5, Table 1) is intriguing and has not been observed with
conventional Friedel-Crafts alkylation reactions.13,15
Examination of the product distribution with time (en-
tries 2-5, Table 1) further indicates that arylation
initially occurs at the allylic position of the substrate,
although initial alkylation of H2SO4-catalyzed reactions
is known to predominantly occur at the double bond.13
In addition, although the nonclassical bridged carbenium
ion 4b (Scheme 2) which is proposed to be characteristic
under acid-catalyzed Friedel-Crafts reaction condi-
tions4c,27,30 should lead to the formation of only the 1,2-
diaryl products, 3 gives 1,1-diarylbutane (20) as the sole
product. These results appear to suggest that carbenium
ion 4b may not be present under our reaction conditions30
(Scheme 2). As shown in Scheme 2, we believe that the
observed 1,1-diarylated products could simply be gener-
ated from the resonance-stabilized benzylic carbenium
ion 4c which may be generated by a 1,2-hydride shift of
the initially produced, relatively less stable carbenium
ion 4a .
In the literature there is no detailed discussion on the
rearrangement of initially produced cycloheptylium ion
(17a , Scheme 4) during the Friedel-Crafts alkylation
from 17. Reported rearranged products of 17 in the
Friedel-Crafts reaction are, however, 1-aryl-3-methyl-
and 1-aryl-4-methylcyclohexanes with AlCl3 as the cata-
lyst (none reported with protic acid catalysts such as H2-
SO4 and HF), and to our knowledge, there is no strong
evidence for the formation of 1-aryl-1-methylcyclohex-
ane.15 The production of 22-p in addition to 18 in the
reaction of 17, even under the relatively milder conditions
used, is therefore highly intriguing. The formation of
22-p as a rearranged product from 17 could be rational-
ized by proposing that the initially formed 17a may be
first isomerized to the carbenium ion 17c by a Wagner-
Meerwein type rearrangement through ring opening of
the protonated cyclopropyl intermediate 17b and then a
1,2-hydride shift31,32 to produce the more stable tertiary
carbenium ion 17d followed by electrophilic attack on
toluene (Scheme 4). Lack of further ring-contracted,
cyclopentane products32 suggests that both the 1,2-
hydride shift and arylation steps must be faster than the
possible further ring contraction reactions of 17c and
17d .33 The ratio of products 18 to 22-p (65% to 35%)
may, therefore, indicate the relative thermodynamic
stabilities and the reaction rates of ions 17a and 17b.
At present we do not have a reasonable mechanism
for type A reactions, since acid-catalyzed formation of an
isolated carbenium ion could not be easily justified for
this type of reaction. The absence of free carbenium ion
in these reactions is strongly supported by the observa-
tion that only 2 and 4 (Scheme 5) are formed from 1 and
3, respectively, without other possible carbenium ion
rearranged products such as 3-phenyl-3-tolyl-1-propene
(31) Weitkamp, J .; Ernst, S. In Catalysis by Acids and Bases; Imelik,
B., Naccache, C., Coudurier, G., Taarit, Y. B., Vedrine, J . C., Eds.;
Elsevier Science Publishers B.V.: Amsterdam, The Netherlands, 1985;
pp 419-426.
(32) Guisnet, M. In ref 31, 1985, pp 283-297.
(33) This proposal is also consistent with the observation that 22-p
is the only product from 21.
(28) McCaulay, D. A. J . Am. Chem. Soc. 1959, 81, 6437.
(29) In this reaction, benzene was used instead of toluene to avoid
further complication of the product distribution due to the formation
of ortho, meta, and para isomers of the products.
(30) Ransley, D. L. J . Org. Chem. 1966, 31, 3595.

2864 J . Org. Chem., Vol. 63, No. 9, 1998
Mahindaratne and Wimalasena
from 1 and 3-tolyl-1-butene from 313 (Scheme 5). There-
fore, the formation of only 2 from 1 and 4 from 3 could
only be explained by considering the Friedel-Crafts
reaction as a displacement type reaction as proposed by
Brown and co-workers26 (Scheme 5). For example, ini-
tially formed alkyl halide-TsOH adduct 36 does not
ionize until nucleophilic attack of arene takes place to
form the complex 37, avoiding the possibility of a rear-
rangement of the carbon skeleton.26a Although this
interpretation is reasonable and in good agreement with
the product isolated, it is clear that further study is
necessary to propose a detailed mechanism for these
types of reactions. In addition, the formation of 2 and 4
from 1 and 3, respectively, at shorter reaction times
demonstrates that the allylic halide functionality is more
reactive than the double bond under these reaction
conditions.
Selectivity. The results presented in Table 1 clearly
demonstrate that unactivated primary and secondary
alkyl halides are much less reactive than the correspond-
ing arenesulfonate esters under identical reaction condi-
tions (see entries 8 and 19; Table 1). On the other hand,
alkenes are generally much more reactive than either
alkyl halides or arenesulfonate esters under similar
experimental conditions (entries 9, 15, and 20; Table 1).
In addition, alcohols were found to be completely inactive
toward the TsOH-catalyzed alkylation under the above
conditions, unexpectedly.9m,n Therefore, TsOH could be
used to arylate either alkene- or arenesulfonates selec-
tively, conveniently and efficiently, in the presence of
unactivated primary and/or secondary halide and/or
alcohol groups. Furthermore, entries 2-5 in Table 1
clearly show that further selectivity of the desired
products can be obtained by carefully controlling the
reaction conditions. We also note that although cyclo-
hexenes are excellent substrates for the reaction, 2-cy-
clohexenone is completely inactive under the same
reaction conditions, probably due to the slight deactiva-
tion of the double bond toward protonation. Similarly,
both ethyl 2-(tosyloxy)propanoate and ethyl 2-bromopro-
panoate failed to alkylate toluene or xylene and instead
both underwent de-esterification during extended reac-
tion times (3 days), further suggesting that even slightly
deactivated tosylates or halides are not good alkyl
substrates for TsOH-catalyzed aromatic alkylation reac-
tions. These observations strongly suggest that TsOH-
catalyzed aromatic alkylation could also be carried out
selectively in the presence of such slightly deactivated
tosyl and halide groups.
tional Friedel-Crafts catalysts. Studies of the scope and
the synthetic utility of this reaction with more function-
alized analogues of aromatic substrates are in progress.
Exp er im en ta l Section
1
Gen er a l. All H (300 MHz) and 13C NMR (75 MHz) were
recorded in CDCl3 with TMS as an internal standard. All
chemical shifts were reported on the δ (ppm) scale relative to
TMS (0.00 ppm) for 1H and CDCl3 (77.00 ppm) for 13C NMR.
All the coupling constants (J ) were in hertz. Unless otherwise
noted, commercially available chemicals with at least 98%
purity were used throughout this study. All solvents were
reagent grade and freshly distilled. The notations -o, -p , -m
following the compound numbers indicate the ortho, para, and
meta isomers of the products with respect to the methyl
substituent in the aromatic ring.
Gen er a l P r oced u r es. Tosyla tion of Alk yl Alcoh ols. A
mixture of alcohol (0.05 mol) and p-toluenesulfonyl chloride
(11.4 g, 0.06 mol) in 25 mL of carbon tetrachloride was stirred
for 15 min. Dried triethylamine (7.6 g, 0.075 mol) was then
added dropwise, and the mixture was stirred for 4 h. The solid
amine hydrochloride was separated by filtration, and the
filtrate was washed several times with distilled water and
dried over anhydrous Na2SO4. The evaporation of the solvent
in vacuo yielded a crude solid which was purified by column
chromatography.
Alk yla t ion of Tolu en e. A mixture of the desired alkyl
substrate (0.05 mol) and p-toluenesulfonic acid monohydrate
(11.4 g, 0.06 mol) in 53 mL of toluene (0.5 mol) was refluxed
for the appropriate times indicated in Table 1, with magnetic
stirring. The reaction mixture was cooled to room tempera-
ture, allowing the crystalline catalyst to separate. The solid
catalyst was then filtered and washed with hexane (2 × 25
mL). The resultant organic filtrate was washed first with 0.1
M NaHCO3 solution and then with distilled water and dried
over anhydrous Na2SO4. The evaporation of the organic
solvent in vacuo yielded crude product mixtures which were
subjected to further purification whenever it was appropriate.
Alk yla tion of Tolu en e w ith tr a n s-Cin n a m yl Ch lor id e
(1). 3-(4-Met h ylp h en yl)-1-p h en ylp r op en e (2-p ). 1H
NMR: δ 2.32 (3H, s), 3.50 (2H, d, J ) 6.84), 6.34 (1H, dt, J )
15.74, 6.40), 6.42 (1H, d, J ) 15.87), 7.03-7.21 (5H, m), 7.23-
7.36 (4H, m). 13C NMR: δ 21.00 (q), 38.92 (t), 126.11 (d),
127.02 (d), 128.46 (d), 128.54 (d), 129.18 (d), 129.53 (d), 130.87
(d), 135.65 (s), 137.07 (s), 137.58 (s).
3-(2-Meth ylp h en yl)-1-p h en ylp r op en e (2-o). 1H NMR: δ
2.32 (3H, s), 3.52 (2H, d, J ) 5.32), 6.33 (1H, dt, J ) 15.84,
5.26), 6.36 (1H, d, J ) 15.87), 7.03-7.21 (5H, m), 7.23-7.36
(4H, m). 13C NMR: δ 19.42 (q), 36.86 (t), 126.06 (d), 126.06
(d), 126.40 (d), 127.02 (d), 128.46 (d), 128.50 (d), 129.22 (d),
130.22 (d), 130.92 (d), 136.38 (s), 137.58 (s), 138.24 (s).
Alk yla tion of Tolu en e w ith tr a n s-Cr otyl Ch lor id e (3).
1-(4-Meth ylp h en yl)-2-bu ten e (4-p ). 1H NMR: δ 1.66 (3H,
dq, J ) 6.16, 1.30), 2.30 (3H, s), 3.26 (2H, br d, J ) 5.55), 5.35-
5.63 (2H, m), 7.04-7.11 (4H, m). 13C NMR: δ 17.83 (q), 20.95
(q), 38.63 (t), 126.00 (d), 128.34 (d), 129.01 (d), 130.36 (d),
135.25 (s), 137.98 (s).
Taken together, the present studies have clearly shown
that TsOH could be used as an efficient catalyst in the
intermolecular coupling of the aromatic nucleus with
activated alkyl halides, alkenes, or tosylates under
relatively mild conditions in an open atmosphere. All the
model reactions which were carried out using toluene as
the aryl substrate resulted in excellent yields of coupled
products. In contrast to conventional catalysts such as
AlCl3, BF3, HF, and concentrated H2SO4 catalyzed
Friedel-Crafts reactions, the extent of the formation of
undesired products from side reactions such as tran-
salkylation, polymerization, etc. was minimal with the
TsOH-catalyzed reaction. The ability to recover and
reuse the catalyst from the reaction mixtures, minimal
generation of environmentally unfriendly waste, high
specificity of the reaction, and the low cost are important
advantages of the TsOH catalyst over the other conven-
1-(2-Meth ylp h en yl)-2-bu ten e (4-o). 1H NMR: δ 1.66 (3H,
dq, J ) 6.19, 1.38), 2.28 (3H, s), 3.29 (2H, dt, J ) 6.24, 1.30),
5.42 (1H, dtq, J ) 15.16, 1.38, 6.24), 5.56 (1H, dtq, J ) 15.16,
6.27, 1.41), 7.08-7.15 (4H, m). 13C NMR: δ 17.83 (q), 19.28
(q), 36.51 (t), 125.94 (d), 126.06 (d), 126.11 (d), 128.95 (d),
129.17 (d), 130.05 (d), 136.15 (s), 139.07 (s).
1-(2-Meth ylp h en yl)-1-(4-m eth ylp h en yl)bu ta n e (20-op ).
1H NMR: δ 0.91 (3H, t, J ) 7.33), 1.20-1.38 (2H, m), 1.96
(2H, dt, J ) 5.29, 7.67), 2.25 (3H, s), 2.27 (2H, s), 4.06 (1H, t,
J ) 7.69), 7.01-7.20 (8H, m). 13C NMR: δ 14.14 (q), 19.88
(q), 20.94 (q), 21.20 (t), 38.55 (t), 46.28 (d), 125.80 (d), 125.94
(d), 126.62 (d), 128.06 (d), 128.92 (d), 130.41 (d), 135.19 (s),
136.20 (s), 141.91 (s), 143.24 (s).
1,1-Bis(4-m eth ylp h en yl)bu ta n e (20-p p ). 1H NMR:
0.90 (3H, t, J ) 7.30), 1.20-1.38 (2H, m), 2.00 (2H, dt, J )
5.51, 7.75), 2.27 (6H, s), 3.83 (1H, t, J ) 7.81), 7.05 (4H, d, J
δ

p-Toluenesulfonic Acid Monohydrate
J . Org. Chem., Vol. 63, No. 9, 1998 2865
) 8.20), 7.10 (4H, d, J ) 8.30). 13C NMR: δ 14.07 (q), 20.94
(q), 21.20 (t), 38.05 (t), 50.27 (d), 127.68 (d), 129.02 (d), 135.27
(s), 142.63 (s).
1-(2-Meth ylp h en yl)-1-bu ten e (32-o). 1H NMR: δ 1.10
(3H, t, J ) 7.47), 2.22-2.25 (2H, m), 2.33 (3H, s), 6.13 (1H, dt,
J ) 15.68, 6.51), 6.56 (1H, dt, J ) 15.62, 1.52), 7.08-7.15 (4H,
m). 13C NMR: δ 13.81 (q), 19.77 (q), 26.37 (t), 125.45 (d),
125.97 (d), 126.69 (d), 126.69 (d), 130.11 (d), 133.98 (d), 134.86
(s), 137.06 (s).
Alk yla tion of Tolu en e w ith ((4-Meth ylben zen esu lfon -
yl)oxy)cycloh exan e (10). ((4-Meth ylben zen esu lfon yl)oxy)-
cycloh exa n e (10). 1H NMR: 1.16-1.36 (3H, m), 1.40-1.59
(3H, m), 1.60-1.82 (4H, m), 2.44 (3H, s), 4.50 (1H, tt, J ) 3.72,
5.12), 7.33 (2H, d, J ) 8.02), 7.79 (2H, d, J ) 8.30). 13C NMR:
δ 21.50 (q), 23.29 (t), 24.79 (t), 32.26 (t), 81.55 (d), 127.47 (d),
129.63 (d), 134.84 (s), 144.22 (s).
Alk yla tion of Tolu en e w ith Cycloh exen e (16). (4-
Meth ylp h en yl)cycloh exa n e (11-p ). 1H NMR: δ 1.15-1.45
(5H, m), 1.65-1.90 (5H, m), 2.31 (3H, s), 2.37-2.51 (1H, m),
6.90-7.20 (4H, m). 13C NMR: δ 20.94 (q), 26.23 (t), 26.98 (t),
34.60 (t), 44.19 (d), 126.66 (d), 128.94 (d), 135.12 (s), 145.12
(s).
(2-Meth ylp h en yl)cycloh exa n e (11-o). 1H NMR: δ 1.15-
1.45 (5H, m), 1.65-1.90 (5H, m), 2.32 (3H, s), 2.62-2.74 (1H,
m), 6.90-7.20 (4H, m). 13C NMR: δ 19.29 (q), 26.38 (t), 27.21
(t), 33.70 (t), 40.16 (d), 125.34 (d), 125.43 (d), 126.07 (d), 130.17
(d), 135.05 (s), 145.86 (s).
(3-Meth ylph en yl)cycloh exan e (11-m ). 1H NMR: δ 1.15-
1.45 (5H, m), 1.65-1.90 (5H, m), 2.31 (3H, s), 2.37-2.51 (1H,
m), 6.90-7.20 (4H, m). 13C NMR: δ 21.47 (q), 26.23 (t), 26.98
(t), 34.52 (t), 44.60 (d), 123.80 (d), 126.50 (d), 127.64 (d), 128.15
(d), 137.69 (s), 148.05 (s).
Alk yla tion of Tolu en e w ith Cyclop en ten e (14). (4-
Meth ylp h en yl)cyclop en ta n e (15-p ). 1H NMR: δ 1.50-1.85
(6H, m), 1.95-2.07 (2H, m), 2.30 (3H, s), 3.18 (1H, tt, J ) 7.60,
9.25), 6.95-7.23 (4H, m). 13C NMR: δ 19.79 (q), 25.61 (t),
34.66 (t), 45.58 (d), 126.95 (d), 128.90 (d), 135.03 (s), 143.43
(s).
Alk yla tion of Tolu en e w ith tr a n s-1,2-Dip h en yleth en e
(30; tr a n s-St ilb en e). 1-(4-Met h ylp h en yl)-1,2-d ip h en yl-
eth a n e (31-p ). 1H NMR: δ 2.55 (3H, s), 3.32 (2H, d, J ) 7.81),
4.18 (1H, t, J ) 7.76), 6.92-7.26 (14H, m). 13C NMR: δ 20.96
(q), 42.15 (t), 52.66 (d), 125.80 (d), 126.05 (d), 127.86 (d), 127.99
(d), 128.26 (d), 129.02 (d), 135.57 (s), 140.37 (s), 141.47 (s),
144.72 (s).
Alk yla tion of Tolu en e w ith 9-Br om oflu or en e (7). 9-(4-
Meth ylp h en yl)flu or en e (8-p ). 1H NMR: δ 2.30 (3H, s), 5.00
(1H, s), 6.97 (2H, d, J ) 7.30), 7.07 (2H, d, J ) 7.78), 7.20-
7.40 (6H, m), 7.78 (2H, d, J ) 7.60). 13C NMR: δ 21.05 (q),
54.09 (d), 119.80 (d), 125.27 (d), 127.20 (d), 127.25 (d), 128.17
(d), 129.37 (d), 136.34 (s), 138.50 (s), 140.96 (s), 148.08 (s).
Alk yla tion of Tolu en e w ith (Ben zen esu lfon yloxy)-2-
m et h ylcycloh exa n e a n d 2-Met h yl-((4-m et h ylb en zen e-
su lfon yl)oxy)cycloh exa n e (21). (Ben zen esu lfon yloxy)-
2-m eth ylcycloh exa n e. 1H NMR: δ 0.79 (3H, d, J ) 6.53 Hz),
0.92-1.07 (1H, m), 1.09-1.32 (2H, m), 1.37-1.52 (1H, m),
1.52-1.65 (2H, m), 1.67-1.79 (2H, m), 1.96-2.04 (1H, m), 4.15
(1H, dt, J ) 4.37, 10.23), 7.54 (2H, ddt, J ) 8.38, 7.40, 1.44),
7.63 (1H, tt, J ) 7.40, 1.38), 7.93 (2H, dt, 8.37, 1.44). 13C
NMR: δ 18.33 (q), 24.63 (t), 24.73 (t), 32.73 (t), 33.40 (t), 37.53
(d), 88.22 (d), 127.59 (d), 128.99 (d), 133.31 (d), 137.85 (s).
2-M e t h y l-((4-m e t h y lb e n z e n e s u lfo n y l)o x y )c y c lo -
h exa n e (21). 1H NMR: δ 0.80 (3H, d, J ) 6.51), 0.92-1.07
(1H, m), 1.08-1.31 (2H, m), 1.35-1.49 (1H, m), 1.49-1.61 (2H,
m), 1.63-1.78 (2H, m), 1.94-2.03 (1H, m), 2.44 (3H, s), 4.11
(1H, dt, J ) 4.39, 10.25), 7.32 (2H, d, J ) 7.95), 7.79 (2H, d, J
) 8.33). 13C NMR: δ 18.34 (q), 21.52 (q), 24.60 (t), 24.72 (t),
32.66 (t), 33.38 (t), 37.52 (d), 87.86 (d), 127.59 (d), 129.57 (d),
134.85 (s), 144.23 (s).
1-Met h yl-1-(4-m et h ylp h en yl)cycloh exa n e (22-p ). 1H
NMR: δ 1.16 (3H, s), 1.34-1.59 (8H, m), 1.98 (2H, dd, J )
7.49, 13.00), 3.31 (3H, s), 7.12 (2H, d, J ) 8.03), 7.23 (2H, d,
7.30). 13C NMR: δ 20.80 (q), 22.70 (t), 26.43 (t), 30.55 (q), 37.54
(s), 37.98 (t), 125.73 (d), 128.89 (d), 134.53 (s), 147.00 (s).
Alk yla tion of Tolu en e w ith 2-Bicyclo[2.2.1]h ep ten e
[19; exo-2-Nor b or n en e] or 2-((4-Met h ylb en zen esu lfon -
yl)oxy)b icyclo[2.2.1]h ep t a n e [12; 2-Tosyln or b or n a n e].
exo-2-((4-Me t h ylb e n ze n e su lfon yl)oxy)b icyclo[2.2.1]-
h ep ta n e [2-(Tosyloxy)n or bor n a n e, 12]. 1H NMR: 0.92-
1.04 (2H, m), 1.10-1.17 (1H, m), 1.30-1.62 (5H, m), 2.21-
2.27 (1H, m), 2.31-2.37 (1H, m), 2.43 (3H, s), 4.43 (1H, m),
7.33 (2H, d, J ) 8.74), 7.77 (2H, d, J ) 8.35). 13C NMR: δ
21.34 (q), 23.67 (t), 27.64 (t), 34.75 (t), 35.09 (d), 39.40 (t), 41.85
(d), 85.13 (d), 127.36 (d), 129.56 (d), 134.44 (s), 144.20 (s).
2-(4-Met h ylp h en yl)b icyclo[2.2.1]h ep t a n e (13-p ). 1H
NMR: 1.12-1.41 (3H, m), 1.48-1.84 (5H, m), 2.24-2.41 (2H,
m), 2.30 (3H, s), 2.70 (1H, dd, J ) 5.93, 8.42), 7.05 (2H, d, J )
8.06), 7.23 (2H, d, J ) 7.57). 13C NMR: δ 20.87 (q), 28.93 (t),
30.57 (t), 36.00 (t), 36.80 (d), 39.09 (t), 43.06 (d), 46.93 (d),
126.93 (d), 128.84 (d), 134.71 (s), 144.58 (s).
(2-Meth ylph en yl)cyclopen tan e (15-o). 1H NMR: δ 1.50-
1.85 (6H, m), 1.95-2.07 (2H, m), 2.34 (3H, s), 2.94 (1H, tt, J
) 7.45, 9.60), 6.95-7.23 (4H, m). 13C NMR: δ 20.93 (q), 25.52
(t), 33.61 (t), 41.67 (d), 125.20 (d), 125.43 (d), 126.04 (d), 130.07
(d), 135.85 (s), 144.52 (s).
(3-Meth ylp h en yl)cyclop en ta n e (15-m ). 1H NMR:
δ
1.50-1.85 (6H, m), 1.95-2.07 (2H, m), 2.32 (3H, s), 2.94 (1H,
tt, J ) 7.45, 9.60), 6.95-7.23 (4H, m). 13C NMR: δ 21.46 (q),
25.58 (t), 34.61 (t), 45.92 (d), 124.07 (d), 126.41 (d), 127.91 (d),
128.12 (d), 137.65 (s), 146.47 (s).
Alk yla tion of Tolu en e w ith Cycloh ep ten e (17). (4-
Meth ylp h en yl)cycloh ep ta n e (18-p ). 1H NMR: δ 1.35-2.03
(12H, m), 2.30 (3H, s), 2.56-2.65 (1H, m), 6.90-7.20 (4H, m).
13C NMR: δ 20.93 (q), 27.23 (t), 28.02 (t), 36.95 (t), 46.64 (d),
126.53 (d), 128.91 (d), 134.32 (s), 147.02 (s).
2-(2-Met h ylp h en yl)b icyclo[2.2.1]h ep t a n e (13-o). 1H
NMR: δ 1.12-1.41 (3H, m), 1.48-1.84 (5H, m), 2.24-2.41 (2H,
m), 2.33 (3H, s), 2.80 (1H, dd, J ) 5.71, 8.45), 6.93-7.25 (4H,
m). 13C NMR: δ 20.05 (q), 29.13 (t), 30.54 (t), 36.34 (t), 36.91
(d), 38.70 (t), 41.47 (d), 43.87 (d), 124.70 (d), 125.20 (d), 125.62
(d), 130.20 (d), 136.13 (s), 145.46 (s).
(2-Meth ylph en yl)cycloh eptan e (18-o). 1H NMR: δ 1.35-
2.03 (12H, m), 2.32 (3H, s), 2.81-2.91 (1H, m), 6.90-7.20 (4H,
m). 13C NMR: δ 19.45 (q), 27.72 (t), 27.91 (t), 36.05 (t), 41.82
(d), 125.19 (d), 125.58 (d), 126.13 (d), 130.07 (d), 134.82 (s),
148.02 (s).
2-(3-Met h ylp h en yl)b icyclo[2.2.1]h ep t a n e (13-m ). 1H
NMR: δ 1.12-1.41 (3H, m), 1.48-1.84 (5H, m), 2.24-2.41 (2H,
m), 2.30 (3H, s), 2.70 (1H, dd, J ) 5.93, 8.42), 6.93-7.25 (4H,
m). 13C NMR: δ 21.52 (q), 28.93 (t), 30.62 (t), 36.09 (t), 36.80
(d), 39.09 (t), 42.93 (d), 47.26 (d), 124.00 (d), 126.07 (d), 127.94
(d), 128.06 (d), 137.60 (s), 147.55 (s).
(3-Meth ylp h en yl)cycloh ep ta n e (18-m ). 1H NMR:
δ
1.35-2.03 (12H, m), 2.31 (3H, s), 2.56-2.65 (1H, m), 6.90-
7.20 (4H, m). 13C NMR: δ 21.47 (q), 27.30 (t), 28.02 (t), 36.86
(t), 47.04 (d), 123.65 (d), 126.23 (d), 127.51 (d), 128.18 (d),
137.69 (s), 149.97 (s).
Alk yla tion of Tolu en e w ith Br om od ip h en ylm eth a n e
(5). (4-Meth ylp h en yl)d ip h en ylm eth a n e (6-p ). 1H NMR:
δ 2.31 (3H, s), 5.50 (1H, s), 7.00 (2H, d, J ) 8.06), 7.02-7.30
(12H, m). 13C NMR: δ 20.97 (q), 56.50 (d), 126.17 (d), 128.22
(d), 128.98 (d), 129.30 (d), 129.39 (d), 135.70 (s), 140.94 (s),
144.10 (s).
(2-Meth ylp h en yl)d ip h en ylm eth a n e (6-o). 1H NMR: δ
2.21 (3H, s), 5.67 (1H, s), 7.02-7.30 (14H, m). 13C NMR: δ
19.87 (q), 53.55 (d), 125.74 (d), 126.17 (d), 126.35 (d), 128.22
(d), 129.41 (d), 129.58 (d), 130.37 (d), 136.53 (s), 142.31 (s),
143.38 (s).
Alk yla tion of Tolu en e w ith 2-(Ben zen esu lfon yloxy)-
4-m et h ylp en t a n e a n d 4-Met h yl-2-((4-m et h ylb en zen e-
su lfon yl)oxy)p en ta n e (23). 2-(Ben zen esu lfon yloxy)-4-
m eth ylp en ta n e. 1H NMR: δ 0.91 (3H, d, J ) 6.55), 0.92 (3H,
d, J ) 6.59), 1.19 (3H, d, J ) 6.16), 1.26 (1H, dd, J ) 5.00,
13.21), 1.41 (1H, ddd, J ) 5.95, 8.16, 13.78), 1.74 (1H, dhep, J
) 5.62, 6.57), 3.88 (1H, ddq, J ) 5.00, 8.16, 6.13), 7.63 (2H,
ddm, J ) 7.33, 8.03), 7.76 (1H, tt, J ) 7.45, 1.25), 8.05 (2H,
dt, 8.60, 1.30). 13C NMR: δ 22.29 (q), 23.12 (q), 23.97 (q), 24.79
(d), 48.62 (t), 66.12 (d), 126.91 (d), 129.65 (d), 135.19 (d), 144.41
(s).

2866 J . Org. Chem., Vol. 63, No. 9, 1998
Mahindaratne and Wimalasena
4-Meth yl-2-((4-m eth ylben zen esu lfon yl)oxy)pen tan e (23).
1H NMR: δ 0.76 (3H, d, J ) 6.54), 0.82 (3H, d, J ) 6.37), 1.26
(3H, d, J ) 6.24), 1.16-1.34 (1H, m), 1.45-1.64 (2H, m), 2.44
(3H, s), 4.68 (1H, ddq, J ) 5.15, 7.84, 6.24), 7.33 (2H, d, J )
7.98), 7.79 (2H, d, J ) 8.31). 13C NMR: δ 21.20 (q), 21.48 (q),
21.89 (q), 22.62 (q), 24.22 (d), 45.78 (t), 79.01 (d), 127.61 (d),
129.61 (d), 134.72 (d), 144.29 (s).
Rea ction of Tolu en e w ith Eth yl 2-((4-Meth ylben zen e-
su lfon yl}oxy)p r op a n oa te. Eth yl 2-Hyd r oxyp r op a n oa te
(Eth yl La cta te). 1H NMR: δ 1.30 (3H, t, J ) 7.13), 1.42 (3H,
d, J ) 6.94), 2.98 (1H, br s), 4.24 (2H, q, J ) 7.14), 4.27 (1H,
q, J ) 6.92). 13C NMR: δ 14.00 (q), 20.21 (q), 61.41 (t), 66.67
(d), 175.56 (s).
Eth yl 2-((4-Meth ylben zen esu lfon yl)oxy)p r op a n oa te.
1H NMR: δ 1.21 (3H, t, J ) 7.14), 1.51 (3H, d, J ) 6.94), 2.45
(3H, s), 4.12 (2H, q, J ) 7.16), 4.93 (1H, q, J ) 6.95), 7.34 (2H,
d, J ) 8.00), 7.82 (2H, d, J ) 8.36). 13C NMR: δ 13.83 (q),
18.29 (q), 21.53 (q), 61.68 (t), 74.10 (d), 127.91 (d), 129.68 (d),
133.44 (s), 144.94 (s), 168.91 (s).
2-((4-Meth ylben zen esu lfon yl)oxy)p r op a n oic Acid . 1H
NMR: δ 1.54 (3H, d, J ) 7.00), 2.45 (3H, s), 4.97 (1H, q, J )
7.00), 7.35 (2H, d, J ) 7.97), 7.82 (2H, d, J ) 8.31), 9.45-9.70
(1H, br s). 13C NMR: δ 18.19 (q), 21.58 (q), 73.21 (d), 127.92
(d), 129.84 (d), 133.11 (s), 145.28 (s), 174.01 (s).
2-Meth yl-2-(4-m eth ylp h en yl)p en ta n e (24-p ). 1H NMR:
δ 0.81 (3H, t, J ) 7.2), 1.00-1.15 (2H, m), 1.27 (6H, s), 1.50-
1.59 (2H, m), 2.30 (3H, s), 7.09 (2H, d, J ) 7.97), 7.21 (2H, d,
J ) 8.33). 13C NMR: δ 14.77 (q), 18.01 (t), 20.81 (q), 29.01
(q), 37.38 (s), 41.15 (t), 125.68 (d), 128.66 (d), 134.56 (s), 146.79
(s).
2-Met h yl-2-(3-m et h ylp h en yl)p en t a n e (24-m ).
1H
NMR: δ 0.81 (3H, t, J ) 7.23), 1.00-1.15 (2H, m), 1.27 (6H,
s), 1.50-1.59 (2H, m), 2.30 (3H, s), 7.05-7.25 (4H, m). 13C
NMR: δ 14.77 (q), 18.01 (t), 21.21 (q), 29.07 (q), 37.39 (s), 41.15
(t), 122.85 (d), 126.00 (d), 126.57 (d), 127.82 (d), 137.26 (s),
149.86 (s).
3-Meth yl-3-(4-m eth ylp h en yl)p en ta n e (25-p ). 1H NMR:
δ 0.66 (6H, t, J ) 7.45), 1.16-1.25 (4H, m), 1.27 (3H, s), 2.34
(3H, s), 7.09 (2H, d, J ) 7.97), 7.16 (2H, d, J ) 8.11). 13C
NMR: δ 8.67 (q), 20.81 (q), 23.00 (q), 35.09 (t), 40.71 (s), 126.47
(d), 128.59 (d), 134.37 (s), 144.53 (s).
Ack n ow led gm en t. This work was partially sup-
ported by a research grant (R29 GM 45026) from the
National Institutes of Health. Critical reading of the
manuscript by Dr. D. S. Wimalasena is greatly appreci-
ated.
Alk yla tion of Tolu en e w ith 2-Ch lor o-2-m eth ylp r op a n e
(ter t-Bu tyl Ch lor id e). 2-Meth yl-2-(4-m eth ylp h en yl)p r o-
p a n e (9-p ). 1H NMR: δ 1.30 (9H, s), 2.30 (3H, s), 7.10 (2H,d
m, J ) 7.95), 7.27 (2H, d, J ) 8.30). 13C NMR: δ 20.83 (q),
31.45 (q), 34.31 (s), 125.13 (d), 128.76 (d), 134.76 (s), 148.16
(s).
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of many compounds (49 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
2-Meth yl-2-(3-m eth ylp h en yl)p r op a n e (9-m ). 1H NMR:
δ 1.31 (9H, s), 2.34 (3H, s), 7.05-7.30 (4H, m). 13C NMR: δ
20.85 (q), 31.41 (q), 34.35 (s), 122.29 (d), 126.05 (d), 126.17
(d), 127.98 (d), 137.47 (s), 151.17 (s).
J O971832R