3916 J . Org. Chem., Vol. 63, No. 12, 1998
Vasil’ev and Engman
the procedure for the preparation of compound 12 (allyl
bromide instead of MeI). 1H NMR δ 3.90 (s, 6H), 4.50 (dt, J )
5.8, 1.4 Hz, 2H), 5.32 (dq, J ) 10.4, 1.7 Hz, 1H), 5.53 (dq, J )
17.1, 1.6 Hz, 1H), 6.21 (m, 1H), 6.25 (s, 1H). 13C NMR δ 56.8,
73.1, 73.6, 91.8, 118.6, 133.0, 160.4, 160.4. Anal. Calcd for
C11H12I2O3: C, 29.62; H, 2.71. Found: C, 29.69; H, 2.56.
Typ ica l P r oced u r e. Deiod in a tion of Meth yl 3,5-Di-
iod o-4-h yd r oxyben zoa te (2a ) w ith Na HTe. A stirred
mixture of freshly finely powdered tellurium (0.16 g, 1.25
mmol) and NaBH4 (0.113 g, 3.0 mmol) in EtOH (12 mL) was
heated at reflux under nitrogen for ca. 20 min to give a pale
purple solution of Na2Te (see ref 29). To the cooled solution
was added HOAc (0.5 mL), followed by methyl 3,5-diiodo-4-
hydroxybenzoate (0.102 g, 0.25 mmol), while a brisk stream
of nitrogen was passed through the open system. The reaction
mixture was heated at reflux for 4 h, cooled, and stirred in
the open air for about 10 min to complete precipitation of
elemental tellurium. After filtration the solvents were evapo-
rated in vacuo, the residue was treated with NaHCO3 (5%
aqueous), and the organic products were extracted into CH2Cl2.
The combined extracts were dried over Na2SO4, and the solvent
was evaporated to afford 0.069 g (99%) of methyl 4-hydroxy-
3-iodobenzoate (3a ), mp 158 °C (lit.30 mp 155-156 °C), from
hexane/benzene ) 4/1.
3,3′,5-triiodothyronine as described above. An inseparable 9/1
mixture (38% yield) of the title compound and an unknown
iodothyronine derivative were isolated by column chromatog-
raphy.
4-Br om op h en ol (4d ). 4-Bromo-2,6-diiodophenol was re-
fluxed with Na2Te for 6 h according to the typical procedure.
After filtration and evaporation, the residue was taken up into
KOH (5 mL of 5% aqueous), and the aqueous phase washed
with ether. Acidification, ether extraction, drying, and evapo-
ration afforded the pure title compound, identical to an
authentic sample, in 76% yield.
N-Bu tyr ylth yr on in e Eth yl Ester (4g) was isolated as an
oil by column chromatography (1-2% MeOH in CH2Cl2). 1H
NMR δ 0.91 (t, J ) 7.0 Hz, 3H), 1.28 (t, J ) 7.3 Hz, 3H), 1.63
(m, 2H), 2.18 (t, J ) 7.2 Hz, 2H), 3.07 (m, 2H), 4.18 (q, J ) 7.2
Hz, 2H), 4.85 (m, 1H), 5.90 (br s, 1H), 6.03 (br d, J ) 8.8 Hz,
1H), 6.70-6.95 (several peaks, 6H), 7.01 (dm, J ) 8.7 Hz, 2H).
13C NMR δ 13.7, 14.1, 19.0, 37.2, 38.4, 53.1, 61.7, 116.3, 117.3,
121.0, 129.5, 130.4, 149.3, 152.7, 157.8, 171.8, 173.1. MS m/z
371 (M+).
During the purification of this material a product with a
higher Rf value was isolated, supposedly a N-butyrylmonoiodo-
thyronine ethyl ester of unknown structure. 1H NMR δ 0.92
(t, J ) 7.0 Hz, 3H), 1.26 (t, J ) 7.3 Hz, 3H), 1.63 (m, 2H), 2.17
(t, J ) 7.2 Hz, 2H), 3.08 (m, 2H), 4.18 (q, J ) 7.2 Hz, 2H),
4.86 (m, 1H), 5.37 (br s, 1H), 5.91 (br d, J ) 8.0 Hz, 1H), 6.85
(dm, J ) 8.8 Hz, 2H), 6.95 (m, 2H), 7.05 (dm, J ) 8.8 Hz, 2H),
7.33 (dd, J ) 2.2, 0.9 Hz, 1H); irradiation at 7.33 ppm resulted
in the collapse of the multiplet at 6.95 ppm.
Except for the omission of the HOAc addition, Na2Te was
prepared as described in the typical procedure. By replacing
tellurium for selenium or sulfur, NaHSe, Na2Se, and Na2S
were similarly prepared. Selenium and sulfur were reduced
by NaBH4 already at ambient temperature. Product composi-
tions in NaHTe- and Na2Te-induced deiodinations of di-
iodophenols 2 are shown in Table 1.
Methyl 4-hydroxybenzoate (4a ), 4-hydroxybenzonitrile (4b),
4-methylphenol (4c), and 4-phenoxyphenol (4e) obtained dur-
ing deiodination experiments were identical to authentic
samples.
4-Hyd r oxy-3-iod oben zon itr ile (3b). To the black reac-
tion mixture obtained in the reduction of 3,5-diiodo-4-hydroxy-
bensonitrile (typical procedure) was added silica gel (3 mL),
and the solvent evaporated in vacuo. The solid material thus
obtained was loaded on top of an SiO2 column and eluted first
with CH2Cl2/pentane ) 1/1 and then with CH2Cl2 to afford the
pure title compound, mp 142 °C (lit.31 mp 144 °C), in 62% yield.
2-Iod o-4-m eth ylp h en ol (3c). By using NaHTe as a reduc-
ing agent, the pure title compound, mp 34.5 °C (lit.32 mp 35
°C), was isolated in 37% yield by column chromatography (5%
EtOAc in pentane).
Deiod in a tion of Meth yl 3,5-Diiod o-4-h yd r oxyben zoa te
(2a ) w ith P h TeH. A degassed suspension of Ph2Te2 (0.307
g, 0.75 mmol) in EtOH (25 mL) was treated under nitrogen
with NaBH4 (0.076 g, 2.0 mmol). To the colorless solution was
injected HOAc (1 mL) followed by methyl 3,5-diiodo-4-hydroxy-
benzoate (0.202 g, 0.50 mmol) while nitrogen was flushed
through the open system. The mixture was stirred overnight
and evaporated to dryness, NaHCO3 (5% aqueous) was added
to the residue, and the organic components were extracted into
CH2Cl2. The combined extracts were dried and evaporated and
some residual EtOH coevaporated with added toluene. Col-
umn chromatography (pentane then CH2Cl2) afforded the
following products:
Meth yl 4-Hyd r oxy-3-iod oben zoa te (3a ). Yield 0.057 g
(41%). This material was identical to an authentic sample.30
Meth yl 4-Hyd r oxy-3-(p h en yltellu r o)ben zoa te (5). Yield
0.013 g (7.0%), mp 156 °C. 1H NMR δ 3.88 (s, 3H), 6.64 (br s,
1H), 7.10 (d, J ) 8.6 Hz, 1H), 7.20 (m, 3H), 7.51 (dm, J ) 8.1
Hz, 2H), 8.03 (dd, J ) 8.6, 2.2 Hz, 1H), 8.56 (d, J ) 2.2 Hz,
1H). 13C NMR δ 52.0, 103.7, 113.3, 113.6, 123.7, 128.1, 129.8,
136.1, 134.3, 143.9, 161.4, 166.0. Anal. Calcd for C14H12O3-
Te: C, 47.25; H, 3.40. Found: C, 47.08; H, 3.30. Meth yl
4-Hydr oxy-5-iodo-3-(ph en yltellu r o)ben zoate (6). Less than
1 mg of the title compound, contaminated with compound 2a ,
and presumably [1H NMR δ 3.77 (s, 3H), 7.10 (br s, 1H), 8.13
(s, 2H)] methyl 3,5-bis(phenyltelluro)-4-hydroxybenzoate was
obtained. 1H NMR δ 3.84 (s, 3H), 6.65 (br s, 1H), 7.30 (m,
3H), 7.70 (dm, J ) 8.1 Hz, 2H), 8.16 (d, J ) 1.8 Hz, 1H), 8.35
(d, J ) 1.9 Hz, 1H). 13C NMR δ 52.2, 81.2, 103.2, 112.6, 125.5,
128.8, 130.0, 138.4, 140.7, 141.4, 158.5, 164.7. MS m/z 484
(M+).
4-Br om o-2-iod op h en ol (3d ), mp 70 °C (lit.33 mp 71 °C),
was isolated in 80% yield from the crude reaction product by
column chromatography (50% CH2Cl2 in pentane).
2-Iod o-4-p h en oxyp h en ol (3e) could not be isolated in pure
form from the crude mixture of deiodination products (Table
1). An authentic sample of the material, mp 41 °C, was
isolated in 37% yield by treatment of 4-phenoxyphenol (4e)
with 1 equiv of I2 (see ref 23), column chromatography (0.2%
EtOH in CH2Cl2), and crystallization from hexane. 1H NMR
δ 5.14 (br s, 1H), 6.95 (m, 4H), 7.07 (t, J ) 9.0 Hz, 1H), 7.31
(m, 3H). 13C NMR δ 85.0, 115.2, 117.9, 121.5, 123.0, 128.8,
129.8, 150.5, 151.3, 157.8. Anal. Calcd for C12H9IO2: C, 46.18;
H, 2.91. Found: C, 46.08; H, 2.84.
N-Bu tyr yl-3-iod otyr osin e Meth yl Ester (3f), mp 140 °C,
was isolated in 61% yield from the crude product by column
chromatography (25-40% EtOAc in pentane). 1H NMR δ 0.93
(t, J ) 7.3 Hz, 3H), 1.64 (m, 2H), 2.19 (t, J ) 7.7 Hz, 2H), 2.96
(dd, J ) 14.0, 5.9 Hz, 1H), 3.07 (dd, J ) 14.0, 5.7 Hz, 1H),
3.76 (s, 3H), 4.86 (m, 1H), 5.58 (br s, 1H), 6.04 (br d, J ) 7.9
Hz, 1H), 6.85 (d, J ) 8.5 Hz, 1H), 6.96 (dd, J ) 8.3, 2.2 Hz,
1H), 7.40 (d, J ) 2.1 Hz, 1H). 13C NMR δ 13.7, 19.1, 36.6,
38.4, 52.5, 53.0, 85.0, 115.1, 129.4, 130.5, 139.17, 154.6, 172.1,
3,5-Dim eth oxyp h en ol (8) was obtained as the only prod-
uct in essentially quantitative yield by deiodination of 2,6-
diiodo-3,5-dimethoxyphenol (7) by any of the reagents NaHTe,
Na2Te, NaHSe, Na2Se, or Na2S following the typical procedure.
The product was identical to an authentic sample.
3,5-Dim eth oxy-2-iod op h en ol (9). To a stirred degassed
suspension of Ph2Te2 (0.307 g, 0.75 mmol) in EtOH (20 mL)
was added NaBH4 (0.070 g, 1.85 mmol) under nitrogen until
the red color of ditelluride had disappeared (20 min). The
solution was then acidified by injection of HOAc (0.4 mL) and
2,6-diiodo-3,5-dimethoxyphenol (7) (0.203 g, 0.50 mmol) was
173.1. Anal. Calcd for
Found: C, 43.14; H, 4.65.
C14H18INO4: C, 42.98; H, 4.64.
N-Bu tyr yl-3,3′,5-tr iiod oth yr on in e Meth yl Ester (3g)
obtained by deiodination of the corresponding thyroxine
derivative was identical to authentic material prepared from
(29) Akiba, M.; Cava, M. P. Synth. Commun. 1984, 14, 1119.
(30) Auwers, K. Ber. Dtsch. Chem. Ges. 1897, 30, 1473.
(31) Berg, S. S.; Newbery, G. J . Chem. Soc. 1949, 642.
(32) Dimroth, O. Ber. Dtsch. Chem. Ges. 1902, 35, 2853.
(33) Brenans, P.; Yeu, K. C. r. 1931, 192, 1037.