8814 J . Org. Chem., Vol. 64, No. 24, 1999
Liguori et al.
1H NMR spectra were recorded at 250 and 400 MHz in
CDCl3 using TMS as internal reference. Mass spectra were
performed on a GLC-MS instrument equipped with an SBP-1
fused silica column (30 m × 0.2 mm i.d., 0.2 µm film thickness)
and with He as carrier gas. GC analyses were performed on a
capillary gas-chromatograph equipped with an SB-5 fused
silica column (25 m × 0.25 mm i.d., 1 µm film thickness) at a
hydrogen flow rate of 8 cm3 min-1, PTV injector, and flame
ionization detector. Most of the reaction products were com-
mercially available and were analyzed by comparison of GC-
MS spectra with authentic samples.10 In numerous experi-
ments no violent decomposition or explosion took place. In any
case, it is opportune to use safety precautions when working
with hydroperoxides.
sults. By using an excess of p-cresol, 2-tert-butyl-4-
methylphenol was the only substantial reaction product;
by using an excess of 2 in an attempt to prepare BHT,
the latter was not formed in significant amount, while
an almost quantitative yield of 2,2′-dihydroxy-3,3′-di-tert-
butyl-5,5′-dimethyldiphenyl, 5, was obtained. The forma-
tion of 5 certainly involves the coupling of the phenoxyl
radical (eq 7).
Decom p osition of 1. (A) A 5 mmol sample of 1 was
unchanged after refluxing for 2 h in 10 mL of CCl4.
(B) A 5 mmol sample of 1 in 10 mL of CCl4 and 5 mmol of
TiCl4 were refluxed for 2 h. The solution was washed with 10%
HCl aqueous solution and analyzed by GC-MS. 2,4-Diphenyl-
4-methyl-2(Z)-pentene was the only substantial reaction prod-
uct, as it results by comparison with an authentic sample (87%
yield). MS (m/z) peaks at 236 (M+), 221, 143.
(C) A 5 mmol sample of 1 in 10 mL of CCl4 and 2.5 mmol of
FeCl3 were refluxed for 2 h. GC-MS analysis revealed that 3
was the main reaction product (56%), but 4 (18%) and
acetophenone (7%) were also obtained as byproducts.
(D) A 5 mmol sample of 1 in 10 mL of AcOH was refluxed
for 2 h. HPLC analysis revealed that 83% of 1 had reacted,
giving 75% yield of phenol.
Equations 8-10 account for the phenoxyl radical
formation.
(E) A 5 mmol sample of 1 in 10 mL of AcOH and 5 mmol of
TiCl4 were refluxed for 2 h. Conversion of 1 was complete
(HPLC analysis); GC-MS analysis revealed the formation of
phenol (35%), 3 (7%), and 4 (12%).
(F) A 5 mmol sample of 1 in 10 mL of AcOH and 2.5 mmol
of FeCl3 were refluxed for 2 h. Conversion of 1 was complete
(HPLC analysis); GC-MS revealed the formation of phenol
(15%), 3 (18%), 4 (31%), and acetophenone (8%).
Gen er a l P r oced u r e for th e Alk yla tion of Ar om a tic
Su bstr a tes by Cu m yl Hyd r op er oxid e, 1. The aromatic
substrate and 1 in the amounts reported in the tables were
added to a solution of TiCl4 in 5 mL of CCl4. The solution was
stirred for 4 h at 20 °C (in a few cases at 80 °C, Table 2). The
solution was washed with 10% aqueous HCl and analyzed by
GC-MS by using authentic samples as references. When these
were not available, the reaction products were isolated by
flash-chromatography (hexane/ethyl acetate, 9:1) and analyzed
by NMR and MS. The results are reported in Tables 1 and 2.
4-Cu m ylp h en ol (4). Anal. Calcd for C15H16O: C, 84.91; H,
7.55. Found: C, 84.83; H, 7.51.10a
Since the reactivity of p-cresol and 2-tert-butyl-4-
methylphenol toward electrophilic alkylation should not
be very different, we suggest that the introduction of a
tert-butyl group onto the p-cresol ring decreases the redox
potential of the phenol derivative, thus making its
electron-transfer oxidation by Fe(III) salt9 (eq 8) easier.
The high yield and the simple and cheap procedure for
the synthesis of 5 suggest its potential application as
phenolic antioxidant.
The most interesting conclusions of Tables 1-3 concern
(i) the possibility to utilize tertiary hydroperoxides for
electrophilic aromatic alkylation, even if the range of
useful applications is, at present, more restricted com-
pared to other alkylating reagents (alkenes, alkyl halides,
alcohols);3-5 (ii) the nature of the used acid affects the
course of acid-catalyzed decomposition of hydroperoxides;
(iii) 1 and 2 require different catalysts; (iv) the regio-
selectivity (ortho:para ratio) in the alkylation of phenol
or anisole by 2 is affected by the amount of catalyst; and
(v) FeCl3 can act as an electrophilic or free-radical
catalyst with different phenolic derivatives, allowing the
synthesis in high yields of 5, an antioxidant of potential
industrial interest.
2-Cu m yl-4-m eth ylp h en ol. Anal. Calcd for C16H18O: C,
84.96; H, 7.96. Found: C, 84.87; H, 7.99.10b
2-Meth yl-4-cu m ylp h en ol. Anal. Calcd for C16H18O: C,
84.87; H, 7.96. Found: C, 85.11; H, 7.91.10b
4-Cu m ylr esor cin ol. Anal. Calcd for C15H16O2: C, 78.95;
H, 7.02. Found: C, 78.79; H, 6.98.10c
4-Cu m yl-r-n a p h th ol. MS: m/z 262 (M+); 247; 169. Anal.
Calcd for C19H18O: C, 87.02; H, 6.87. Found: C, 86.88; H, 6.86.
1H NMR (CDCl3): δ 1.65 (s, 6H), 6.72 (d, 1H), 7.14 (d, 1H),
7.24 (m, 5H), 7.53 (m, 2H), 7.96 (m, 1H), 8.20 (m, 1H).
3-Cu m ylp yr r ole. MS: m/z 185 (M+); 170; 108. Anal. Calcd
1
for C13H15N: C, 84.32; H, 8.11. Found: C, 84.19; H, 8.04. H
NMR (CDCl3): δ 1.63 (s, 6H), 6.05 (m, 1H), 6.48 (m, 1H), 6.61
(m, 1H), 7.22 (m, 5H).
2-Meth oxy-4-cu m ylp h en ol. MS: m/z 242 (M+); 227; 212;
165; 133. Anal. Calcd for C16H18O2: C, 79.34; H, 7.44. Found:
C, 79.48; H, 7.51.
Exp er im en ta l Section
Ma ter ia ls a n d Gen er a l Meth od s. All the chemicals were
reagent grade and obtained from Aldrich Chemical Co. and
were used without further purification.
(10) For 4, MS: Iida, Y.; Daishima, S.; Shibata, A. Org. Mass
Spectrom. 1993, 28, 433. 1H NMR: Koshchii, V. A.; Kozlikovskii, Ya.
B.; Matyusha, A. A. J . Org. Chem. USSR (Engl. Transl.) 1988, 1358-
1361. (b) For 2-methyl-4-cumylphenol and for 4-methyl-2-cumylphenol,
1H NMR: Rosevear, J .; Wilshire, J . F. K. Aust. J . Chem. 1985, 38,
1163-1176. (c) For 4-cumylresorcinol, 13C NMR: Yamamura, T.;
Nishiwaki, K.; Tanigaki, Y.; Terauchi, S.; Tomiyama, S.; Nishiyama,
T. Bull. Chem. Soc. J pn. 1995, 68, 2955.
(8) Perkins, M. J . Radical Chemistry; Ellis Horwood: New York,
1994; p 122.
(9) ref 8, p 91.