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Friedel-crafts cyclohexylation of arenes with 1,3-dicyclohexylcarbodiimide (DCC)
TetnzhedronL.etters, Vol. 35. NO. 6. pp. 903-904. 1994 Elsevier Science Ltd Printed in Great Britain 0040-4039,94 S6.ODi4MO
Friedeldraffs cyclohexylation of Arenes with 1,3-Dicyclohcxylcarbodiimi& (Dee) Jae Nyotmg Kim, Kurt Hoe Chung, aud Eung K. Ryu* Korea Research Institute of Chemical Technology, P. 0. Box 9. Daedeog-Kanji. Daejeon 305406. Korea
A&J&
: 7he naction ofanmes with 1.3dic~iohexyhrimdiimide
in thep~~~ef’~~0fconce.n tJ73tedstdhtn.c
acid or anhydnw ahninum chloride gave the correspondingcyclohexyiatcd
Ftiedel-Crafts
alkylation reactions are important in organic synthesis. These and related reactions have Various electmphile sources could be used in
been well studled and reviewed in many teports and monographs.’ the Friedel-Crafts
~JWX in good yields
alkylation reactions including alkyl halides, alkenes. alkynes, alcohols, esters, ethers, alkanes,
tnexcaptans, and thiocyanates. In our continuing
efforts to examine the electrophilic aromatic substitution
reactions in the pmsence of
Lewis or Bronstead acid,’ we found that the reaction of 1,3dicyclohexylcrbodiimide presence
ofconcentrated sulfuric
acid affonled cyclohexylbenxene
the most widely used reagent in chemistry,’ especially in the peptide-coupling and oxidation
reactions.
With best of our knowledge,
electmphile in the aromatic elecuophilic various aromatic
compounds
substitution
@CC) with benzene in the DCC is a pivotal and probably
in good yield
reactions, dehydration reactions, that DCC could be used as
there have no reports
reaction !
Thus we examined the reaction of DCC with
in the presence of anhydrous aluminum chloride or concentrated sulfuric acid and
the results are summan ‘xed in Scheme 1 and Table 1.
~N-c-N~
Ii SOE::.5.
p
or2Al& I rt I 3.5 h
0-Q””
As shown in Table 1, the reaction of benzene and DCC in the presence of 5 equiv of H2S04 gave cyclohexylbenxene
in 98% isolated yield after refluxing the reaction mixture for 3.5 h (entry 1). The use of H$O,
less than 5 equiv Wd
the yields of cyclohexylbenxene
and the use of I-&SO, more than 5 quiv
did not
imptove the yields. When we used AlCl, instead of H,SO, in the same teaction, cyclohexylbenxene
was obtained
in good yield at room temperature
manner,
corresponding
cyclohexylated
toluene, pxylene,
mesitylene,
cyclohexylchlombenxene
for 3.5 h by using 2 cqulv of AlCb.
(entries 5-10 and 12). In the case of chlorobenxene,
was obtained in low yield (entry 11). The naction
compound as solvent, thus monocyclohexylated easily from the small amounts
an analogous
the
were obtained in moderate to good yields in the cases of
aromatic compounds and naphthalene
In
however,
was performed in an ammatic
product could be obtained as a major product and separated
ofpoly-cyclohexylated
compounds
903
by distillation.
In the reaction of benzene and
904
DCC in carbon disulftie
as solvent, mono-, di-, n-i-, and even tetra-cyclohexylatcd
benzenes were detected on the
mass spectrum of the crude extracts of the reaction mixtures (entry 3). The reaction of benzene and DCC (3.0 equiv) in carbon disulfi&
as solvent in the presence of 6.0 equiv of AlCl, gave 1,3,5-tricyclohexylbenenzene in
32% isolated yield (entry 4). The reaction mechanism is uncettain at the present time. The general nature of these observations and the reaction mechanisms are currently under investigation. Table 1. The Reaction of DCC with Atenes in the Presence of I-I$O, or AlCl,.’ Entry
Substrate
Solvent
Catalyst (equiv) HiSo, (5-O) AlCl, (2.0)
ProducP
Yield(%)’
cyclohexylbenzene
98
cyclohexylbenzene
104 (120)
1
benzene
benzene
2
benzene
benzene CS,
AlCl, (2.0)
mixture(mono-.
AlCl, (6.0)
tricyclohexylbenzene”
32
HZSG, (5.0) AlCl, (2.0)
cyclohexyltoluene’
97
cyclohexyltoluener cyclohexyl-pxylene
(104) 103 (116)
3
benzened
4
benzenedf
5
toluene
CS, toluene
6
toluene
toluene
di-, tri-, tetra-)
7
pxylene
pxylene
H,SO, (5.0)
8
pxylene
pxylene
AlCl, (2.0)
cyclohexyl-pxylene
9
mesitylene
mesitylene
10
msitylene
mesitylene
HZSG, (5.0) AlCl, (2.0)
cyclohexylmesitylene
11
chlorobenzene
chlorobenzene
H,SO, (5.0)
cyclohexylchlorobenzeene’
cyclohexylmesitylene
(107)
104 (103)
98
(94) (107)
23
(89) (31)
12 8-cyclohexylnaphthaleneh naphtbalened AlCl, (2.0) (70) CS, a. Reaction condmons: DCC (10 mmol) / &SO4 (3u mmol) or AlCl, (20 tnmol) / solvent (25 ml of arenes or CSJ /ma&on time (3.5 h). b). Products were identified by ‘H NMR and mass spectra. c). Isolated yields were determined based on mols of DCC, and the values in parentheses were obtained by GC using 1,3dichlorobenzene as an external standard GC analysis was performed with a HelwettPackard 589OA with a 25 m x 0.2 mm x 0.33 urn fused silica HP-l capillary column. d). 10 mrnol of substrate was used. e). Reference 5. f.l. Benzene/DCC/AlC1,= 1 : 3: 6. g). A mixture of ortho- and para- isomers. h). Reference 6. RCfCEtlCCSlUldNOtCS 1. (a) C. C. Price, in “Organic Reactions,” ed. by R. Adams. John Wiley & Sons, New York, 1956, vol 3, p_ l- 82. (b). G. A. Olah. “Friedel-Crafts Chemistry,” Wiley, New York, 1973. (c) G. A. Olah, R. Krishnamurti and G. K. S. Prakash, in “Comprehensive Organic Synthesis,” ed. by B. M. Trost, Pergamon Press, Oxford, 1991, vol. 3, p. 293-339. 2. J. N. Kim and E. K. Ryu. Tetrahedron Lett, 1993,34,3567-3570. 3. For a review of advances in the chemistry of carbodiimides, see: (a) A. Williams and I. T. Ibra him, C&em. Rev., 198 1,81,589-636. (b) M. Mikolajczyk and P. Rielbasinski, Tetrahedron, 1981,37,233-284. 4. The reaction of DCC and benzene in the presence of sulfuric acid has been studied and was not described 1969, any formationof cyclohexylbenzene, see: C. P. Ho&erg and R. D. Mumtna, J. Am. Chem. Sue., 91,4273-4278. 5. B. B. Carson and V. N. Ipatieff, .T.Am. Chem. Sot., 1937,59,645-647. 6. C. C. Price and J. M. Ciskowski, J. Am. Chem. Sot., 1938,60,2499-2502.
(Received in Japan 12 October 1993)
Friedeldraffs cyclohexylation of Arenes with 1,3-Dicyclohcxylcarbodiimi& (Dee) Jae Nyotmg Kim, Kurt Hoe Chung, aud Eung K. Ryu* Korea Research Institute of Chemical Technology, P. 0. Box 9. Daedeog-Kanji. Daejeon 305406. Korea
A&J&
: 7he naction ofanmes with 1.3dic~iohexyhrimdiimide
in thep~~~ef’~~0fconce.n tJ73tedstdhtn.c
acid or anhydnw ahninum chloride gave the correspondingcyclohexyiatcd
Ftiedel-Crafts
alkylation reactions are important in organic synthesis. These and related reactions have Various electmphile sources could be used in
been well studled and reviewed in many teports and monographs.’ the Friedel-Crafts
~JWX in good yields
alkylation reactions including alkyl halides, alkenes. alkynes, alcohols, esters, ethers, alkanes,
tnexcaptans, and thiocyanates. In our continuing
efforts to examine the electrophilic aromatic substitution
reactions in the pmsence of
Lewis or Bronstead acid,’ we found that the reaction of 1,3dicyclohexylcrbodiimide presence
ofconcentrated sulfuric
acid affonled cyclohexylbenxene
the most widely used reagent in chemistry,’ especially in the peptide-coupling and oxidation
reactions.
With best of our knowledge,
electmphile in the aromatic elecuophilic various aromatic
compounds
substitution
@CC) with benzene in the DCC is a pivotal and probably
in good yield
reactions, dehydration reactions, that DCC could be used as
there have no reports
reaction !
Thus we examined the reaction of DCC with
in the presence of anhydrous aluminum chloride or concentrated sulfuric acid and
the results are summan ‘xed in Scheme 1 and Table 1.
~N-c-N~
Ii SOE::.5.
p
or2Al& I rt I 3.5 h
0-Q””
As shown in Table 1, the reaction of benzene and DCC in the presence of 5 equiv of H2S04 gave cyclohexylbenxene
in 98% isolated yield after refluxing the reaction mixture for 3.5 h (entry 1). The use of H$O,
less than 5 equiv Wd
the yields of cyclohexylbenxene
and the use of I-&SO, more than 5 quiv
did not
imptove the yields. When we used AlCl, instead of H,SO, in the same teaction, cyclohexylbenxene
was obtained
in good yield at room temperature
manner,
corresponding
cyclohexylated
toluene, pxylene,
mesitylene,
cyclohexylchlombenxene
for 3.5 h by using 2 cqulv of AlCb.
(entries 5-10 and 12). In the case of chlorobenxene,
was obtained in low yield (entry 11). The naction
compound as solvent, thus monocyclohexylated easily from the small amounts
an analogous
the
were obtained in moderate to good yields in the cases of
aromatic compounds and naphthalene
In
however,
was performed in an ammatic
product could be obtained as a major product and separated
ofpoly-cyclohexylated
compounds
903
by distillation.
In the reaction of benzene and
904
DCC in carbon disulftie
as solvent, mono-, di-, n-i-, and even tetra-cyclohexylatcd
benzenes were detected on the
mass spectrum of the crude extracts of the reaction mixtures (entry 3). The reaction of benzene and DCC (3.0 equiv) in carbon disulfi&
as solvent in the presence of 6.0 equiv of AlCl, gave 1,3,5-tricyclohexylbenenzene in
32% isolated yield (entry 4). The reaction mechanism is uncettain at the present time. The general nature of these observations and the reaction mechanisms are currently under investigation. Table 1. The Reaction of DCC with Atenes in the Presence of I-I$O, or AlCl,.’ Entry
Substrate
Solvent
Catalyst (equiv) HiSo, (5-O) AlCl, (2.0)
ProducP
Yield(%)’
cyclohexylbenzene
98
cyclohexylbenzene
104 (120)
1
benzene
benzene
2
benzene
benzene CS,
AlCl, (2.0)
mixture(mono-.
AlCl, (6.0)
tricyclohexylbenzene”
32
HZSG, (5.0) AlCl, (2.0)
cyclohexyltoluene’
97
cyclohexyltoluener cyclohexyl-pxylene
(104) 103 (116)
3
benzened
4
benzenedf
5
toluene
CS, toluene
6
toluene
toluene
di-, tri-, tetra-)
7
pxylene
pxylene
H,SO, (5.0)
8
pxylene
pxylene
AlCl, (2.0)
cyclohexyl-pxylene
9
mesitylene
mesitylene
10
msitylene
mesitylene
HZSG, (5.0) AlCl, (2.0)
cyclohexylmesitylene
11
chlorobenzene
chlorobenzene
H,SO, (5.0)
cyclohexylchlorobenzeene’
cyclohexylmesitylene
(107)
104 (103)
98
(94) (107)
23
(89) (31)
12 8-cyclohexylnaphthaleneh naphtbalened AlCl, (2.0) (70) CS, a. Reaction condmons: DCC (10 mmol) / &SO4 (3u mmol) or AlCl, (20 tnmol) / solvent (25 ml of arenes or CSJ /ma&on time (3.5 h). b). Products were identified by ‘H NMR and mass spectra. c). Isolated yields were determined based on mols of DCC, and the values in parentheses were obtained by GC using 1,3dichlorobenzene as an external standard GC analysis was performed with a HelwettPackard 589OA with a 25 m x 0.2 mm x 0.33 urn fused silica HP-l capillary column. d). 10 mrnol of substrate was used. e). Reference 5. f.l. Benzene/DCC/AlC1,= 1 : 3: 6. g). A mixture of ortho- and para- isomers. h). Reference 6. RCfCEtlCCSlUldNOtCS 1. (a) C. C. Price, in “Organic Reactions,” ed. by R. Adams. John Wiley & Sons, New York, 1956, vol 3, p_ l- 82. (b). G. A. Olah. “Friedel-Crafts Chemistry,” Wiley, New York, 1973. (c) G. A. Olah, R. Krishnamurti and G. K. S. Prakash, in “Comprehensive Organic Synthesis,” ed. by B. M. Trost, Pergamon Press, Oxford, 1991, vol. 3, p. 293-339. 2. J. N. Kim and E. K. Ryu. Tetrahedron Lett, 1993,34,3567-3570. 3. For a review of advances in the chemistry of carbodiimides, see: (a) A. Williams and I. T. Ibra him, C&em. Rev., 198 1,81,589-636. (b) M. Mikolajczyk and P. Rielbasinski, Tetrahedron, 1981,37,233-284. 4. The reaction of DCC and benzene in the presence of sulfuric acid has been studied and was not described 1969, any formationof cyclohexylbenzene, see: C. P. Ho&erg and R. D. Mumtna, J. Am. Chem. Sue., 91,4273-4278. 5. B. B. Carson and V. N. Ipatieff, .T.Am. Chem. Sot., 1937,59,645-647. 6. C. C. Price and J. M. Ciskowski, J. Am. Chem. Sot., 1938,60,2499-2502.
(Received in Japan 12 October 1993)