Synthesis of 2-isobutylphenol
were calculated as follows: BDE values are based on B3LYP/6-
31G**//AM1 energies22–24 and were obtained using Jaguar 3.025
(default numerical grids) and Spartan 5.0.26 Effective core
potentials were used for bromine- and iodine-substituted mol-
ecules (LACVP**).27 BDE values for diphenols refer to the
lower-energy phenoxyl radical. The L–H gap was calculated
according to previously delineated procedures.10
2-Isobutylphenol was synthesized by the rearrangement of
methylallylphenyl ether to the corresponding (methylallyl)-
phenol, followed by catalytic reduction as shown in the liter-
ature.18 The starting material, methylallyl phenyl ether, was
prepared by the reaction of phenol with methylallyl chloride.
Methylallyl phenyl ether: (65%) bp 65–66 ЊC (10 mm) [lit.,18
70 ЊC (8 mm)]; δH (400 MHz; CDCl3): 1.92 (s, 3H, CH3), 4.5 (s,
Acknowledgements
This research was supported by NIEHS grant R01ES 07595-02
(CH/CS) and in part by NSF-CHE 9724418.
2H, –CH –), 5.03 (s, 1H, ᎐CH ), 5.18 (s, 1H, ᎐CH ), 7.02 (m,
᎐
᎐
2
2
2
3H, Ph), 7.38 (m, 2H, Ph); m/z 148(Mϩ, 26%) 133(42), 94(30),
55(100). 2-(Methylallyl)phenol: (70%) bp 92 ЊC (10 mm) [lit.,18
95 ЊC (9 mm)]; δH (400 MHz, CDCl3): 1.72 (s, 3H, CH3), 3.55
(s, 2H, –CH –), 4.80 (s, 1H, ᎐CH ), 4.88 (s, 1H, ᎐CH ), 5.5 (s,
᎐
᎐
2
2
2
1H, –OH), 6.82 (m, 2H, Ph), 7.1 (m, 2H, Ph); νmax/cmϪ1 3638
(OH), m/z 149(Mϩ ϩ 1, 9%), 148 (Mϩ, 85), 133(100), 105(70),
91(22), 77(52). 2-Isobutylphenol: (30%) bp 57 ЊC (10 mm) [lit.,18
86 ЊC (6 mm)]; δH (400 MHz; CDCl3): 0.93 (d, J 7.5, 6H,
2 × CH3), 1.94 (m,1H, –CH ), 2.48 (d, J 6.5, 2H, –CH2–), 5.12
(s, 1H, –OH), 6.74 (d, J 8, 1H, Ph), 6.85 (t, J 7, 1H, Ph), 7.06 (t,
J 7, 2H, Ph); δC (400 MHz, CDCl3): 23.067 (s, 2 × CH3), 29.272
(s, –CH ), 39.702 (s, –CH2), 115.715 (s, C6), 120.981 (s, C4),
127.514 (s, C5), 128.042 (s, C3), 131.712 (s, C2), 154.046 (s, C1);
νmax/cmϪ1 3637.6 (OH), m/z 150(Mϩ, 22%), 107(100), 77(14).
References
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Synthesis of 2-methylmercaptophenol
2-Methylmercapto derivative of the phenol was synthesized
from 2-methylmercaptoaniline by a diazo reaction.19 (61.5%) bp
96–97 ЊC (10 mm) [lit.,20 105 ЊC (22 mm)]; δH (400 MHz;
CDCl3): 2.35 (s, 3H, –SCH3), 6.73 (s, 1H, –OH), 6.91 (t, J 7.5,
1H, Ph), 7.02 (d, J 8.25, 1H, Ph), 7.27 (t, J 7.5, 1H, Ph), 7.53 (d,
J 8.25, 1H, Ph); δC (400 MHz, CDCl3): 20.197 (s, –SCH3),
115.192 (s, C6), 121.415 (s, C4), 131.072 (s, C2), 134.792 (s,
C5), 135.480 (s, C3), 156.643 (s, C1); νmax/cmϪ1 3638.3 (OH),
1300(SCH3), m/z 142(Mϩ ϩ 2, 5%), 141(Mϩ ϩ 1, 9), 140(Mϩ,
100), 125(47), 97(55).
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Cytotoxicity studies
The IC50 values in the L1210 cell line were determined accord-
ing to previously published protocols.9 The IC50 is defined as the
concentration of X-phenol that inhibits growth by 50%.
QSAR Analysis
The C-QSAR suite of programs was used in the derivation of
the various models.21 P represents the octanol–water partition
coefficient of the phenol. Most of the log P values were experi-
mentally determined while in a few cases, they were calculated
using the CLOGP program. The agreement between measured
(M log P) and calculated partition coefficients (C log P) is
excellent: M log P = 0.96 C log P ϩ 0.02 (n = 40, r2 = 0.973,
s = 0.183). Sigma-plus (σϩ) is the Brown variation of the
Hammett electronic substituent constant. σϩ represents σϩ for
ortho substituents while σp represents σϩ in the para position.
ϩ
The excellent correspondence between σo and σpϩ, led to the
ϩ
ϩ
usage of σp for all the phenols in this study. In all equations,
27 W. R. Wadt and P. J. Hay, J. Chem. Phys., 1985, 82, 284.
n represents the number of data points, r is the correlation
coefficient, and s is the standard deviation of the regression
equation while q2 comprises the cross validated r2. BDE values
Paper 9/05764A
J. Chem. Soc., Perkin Trans. 2, 1999, 2729–2733
2733