Silica-supported sodium hydrogen sulfate catalyzed facile transformation of p-hydroxybenzyl alcohols to p-hydroxybenzyl ethers and thioethers

Article abstract of DOI:10.1081/SCC-200028584

The heterogeneous catalyst, silica-supported sodium hydrogen sulfate (NaHSO₄·SiO₂) has been found to be highly efficient in carrying out the transformation of p-hydroxybenzyl alcohols at room temperature to p-hydroxybenzyl ethers and thioethers in very high yields.

Full text of DOI:10.1081/SCC-200028584

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Silica‐Supported Sodium
Hydrogen Sulfate Catalyzed
Facile Transformation of
p‐Hydroxybenzyl Alcohols to
p‐Hydroxybenzyl Ethers and
Thioethers
R. Ramu a , N. Ravindra Nath a , M. R. Reddy a &
Biswanath Das a
a Organic Chemistry Division‐I , Indian Institute of
Chemical Technology , Hyderabad, 500 007, India
Published online: 12 Jan 2011.
To cite this article: R. Ramu , N. Ravindra Nath , M. R. Reddy & Biswanath Das
(2004) Silica‐Supported Sodium Hydrogen Sulfate Catalyzed Facile Transformation
of p‐Hydroxybenzyl Alcohols to p‐Hydroxybenzyl Ethers and Thioethers, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:17, 3135-3145, DOI: 10.1081/SCC-200028584
To link to this article: http://dx.doi.org/10.1081/SCC-200028584
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 17, pp. 3135–3145, 2004
Silica-Supported Sodium Hydrogen Sulfate
Catalyzed Facile Transformation of
p-Hydroxybenzyl Alcohols to
p-Hydroxybenzyl Ethers and Thioethers#
R. Ramu, N. Ravindra Nath, M. R. Reddy,
*
and Biswanath Das
Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad, India
ABSTRACT
The heterogeneous catalyst, silica-supported sodium hydrogen sulfate
.
(NaHSO4 SiO2) has been found to be highly efficient in carrying out
the transformation of p-hydroxybenzyl alcohols at room temperature to
p-hydroxybenzyl ethers and thioethers in very high yields.
Key Words: p-Hydroxybenzyl alcohols; p-Hydroxybenzyl ethers and
.
thioethers; NaHSO4 SiO2; Heterogeneous catalyst.
#Part 31 in the series, “Studies on Novel Synthetic Methodologies,” For part 30 see
Ref.[1]
.
Correspondence: Biswanath Das, Organic Chemistry Division-I, Indian Institute of
*
Chemical Technology, Hyderabad 500 007, India; Fax: þ91 (40) 27160512; E-mail:
biswanathdas@yahoo.com.
3135
DOI: 10.1081/SCC-200028584
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

3136
Ramu et al.
The conversion of p-hydroxybenzyl alcohols into p-hydroxybenzyl ethers
and thioethers is a useful transformation in synthetic organic chemistry. The
p-hydroxybenzyl ether moiety has been observed in some bioactive natural
products.[2] Recently two methods[3,4] have been developed for the prep-
aration of p-hydroxybenzyl ethers and thioethers. The first method utilized
CAN (ceric ammonium nitrate) and the second method applied rare earth
metal triflate as catalysts. All of these catalysts work under homogeneous con-
ditions. Note that CAN is also an oxidizing agent and may affect the phenolic
hydroxyl group. On the other hand, rare earth triflates catalyze at higher temp-
erature (808C) and the total experimental operation takes a longer time.
In recent years heterogeneous catalysts has been preferred for carrying
out various chemical transformations due to environmental considerations.
.
We have observed that silica-supported sodium hydrogen sulfate (NaHSO4
SiO2) efficiently catalyzes the conversion of p-hydroxybenzyl alcohols into
p-hydroxybenzyl ethers and thioethers.
p-Hydroxybenzyl alcohols were reacted with various alcohols and thiols
.
in the presence of NaHSO4 SiO2 at room temperature to produce
p-hydroxybenzyl ethers and thioethers, respectively (Tables 1 and 2). The
conversion was completed within 1.5–2 hr and the yields of the products
were very high. Different p-hydroxybenzyl alcohols (primary, secondary,
and tertiary) were utilized for the conversion. The yields of the ethers and
thioethers were observed to be low when the reactions were carried out
with only NaHSO4 without using silica support. The reactions were also
tried with neutral alumina-supported NaHSO4, but the yields were not
improved. Methylene chloride was found to be a suitable solvent, as the
other solvents used somewhat decreased the yields of the products (Table 3).
It has been observed that the presence of hydroxy group at the para-position
of the starting primary and secondary benzyl alcohols is vital. The etherification
.
of benzyl alcohol using NaHSO4 SiO2 was not successful. p-Methoxybenzyl
alcohol also afforded low yields of the products under similar reaction conditions.
The hydroxy group at the para-position of the aromatic ring stabilizes the benzyl
cation formed during etherification and thioetherification of p-hydroxybenzyl
alcohols. However, for a tertiary benzyl alcohol, a hydroxy group at the para-
position is not essential to form a stable benzyl cation.
Scheme 1.

.
NaHSO4 SiO2 Catalyzed Facile Transformation
3137

3138
Ramu et al.

.
NaHSO4 SiO2 Catalyzed Facile Transformation
3139

3140
Ramu et al.

.
NaHSO4 SiO2 Catalyzed Facile Transformation
3141
Table 3. Conversion of p-hydroxybenzyl alcohol into p-hydroxy-
benzyl isopropyl ether in different solvents.a
Isolated yield of
ether (%)
Entry
Solvent
a
b
c
d
e
CH2Cl2
DMF
THF
92
0
55
88
86
CH3CN
Toluene
aThe time of conversion was 1.5 hr. bis-(4-Hydroxybenzyl) ether
was obtained in very minor quantity (4%–5%) in each case
(except entry b).
[5]
.
The catalyst, NaHSO4 SiO2, can easily be prepared from the readily
available NaHSO4 and silica gel (100–200 mesh). Because it works under
heterogeneous conditions, it can easily be handled and removed from the reac-
tion mixture by simple filtration. The ingredients are cheap. The conversion of
p-hydroxybenzyl alcohols carried out with silica gel alone afforded the ethers
and thioethers in very low yields (12%–15%).
In conclusion, we have developed a simple and novel method for efficient
conversion of p-hydroxybenzyl alcohols into p-hydroxybenzyl ethers and
.
thioethers using NaHSO4 SiO2 as a heterogeneous catalyst at room tempera-
ture. The simple experimental procedure, readily available and inexpensive
catalysts, the mild reaction conditions, and high yields of the products (both
ethers and thioethers) are great advantages of the present protocol.
EXPERIMENTAL
1
The spectra were recorded with the following instruments: H nuclear
magnetic resonance (NMR): Varian Gemini 200 MHz and electron-impact
mass spectra (EI-MS): VG Micromass 7070 H (70 eV). The elemental analysis
was performed with Elementar Vario EL equipment. The alcohols and thiols
were obtained commercially (Aldrich, USA).
Etherification and Thioetherification of p-Hydroxybenzyl
Alcohols: General Procedure
p-Hydroxybenzyl alcohol (1 mmol) and reacting alcohol (or thiol)
.
(3 mmol) was taken in CH2Cl2 (5 mL). NaHSO4 SiO2 (100 mg) was added.

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Ramu et al.
The catalyst was prepared from the readily available ingredients, NaHSO4 and
silica gel (finer than 200 mesh), by following the reported method.[5] The reac-
tion mixture was stirred at room temperature and the reaction was monitored
by thin layer chromatography (TLC). After completion, the mixture was fil-
tered, the filtrate was concentrated, and the residue was subjected to column
chromatography over silica gel to obtain pure ether (or thioether). bis-(4-
Hydroxybenzyl)-ether (4%–5%) was also obtained while preparing an ether.
The spectral data of unknown products are given below:
4-Hydroxybenzyl n-Butyl Ether (2B)
1H NMR (200 MHz, CDCl3): d 7.14 (2H, d, J ¼ 8.0 Hz), 6.64 (2H, d,
J ¼ 8.0 Hz), 5.82 (1H, br s, OH), 4.38 (2H, s), 3.43 (2H, t, J ¼ 7.0 Hz),
1.62–1.48 (2H, m), 1.42–1.22 (2H, m), 0.86 (3H, t, J ¼ 7.0 Hz). EI-MS:
m/z ¼ 180 (Mþ). Anal. Calcd. for C11H16O2: C, 73.33; H, 8.88. Found: C,
73.23; H, 8.78.
4-Hydroxybenzyl iso-Butyl Ether (3B)
1H NMR (200 MHz, CDCl3): d 7.12 (3H, d, J ¼ 8.0 Hz), 6.68 (2H, d,
J ¼ 8.0 Hz), 5.63 (1H, br s, OH), 3.98 (2H, s), 3.34 (2H, d, J ¼ 7.0 Hz).
1.80 (1H, m), 0.84 (6H, d, J ¼ 7.0 Hz). EI-MS: m/z ¼ 180 (Mþ). Anal.
Calcd. for C11H16O2: C, 73.33; H, 8.88. Found: C, 73.13; H, 8.75.
4-Hydroxybenzyl 10-Methyl Propyl Ether (4B)
1H NMR (200MHz, CDCl3): d 7.18 (2H, d, J ¼ 8.0 Hz), 6.68 (2H, d,
J ¼ 8.0 Hz), 5.10 (1H, s), 4.40 (2H, q, J ¼ 12.0Hz), 3.39 (1H, m), 1.62–1.40
(2H, m), 1.18 (3H, d, J ¼ 7.0 Hz), 0.90 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 180
(Mþ). Anal. Calcd. for C11H16O2: C, 73.33; H, 8.88. Found: C, 73.23; H, 8.58.
4-Hydroxybenzyl n-Octyl Ether (5B)
1H NMR (200 MHz, CDCl3): d 7.12 (2H, d, J ¼ 8.0 Hz), 6.70 (2H, d,
J ¼ 8.0Hz), 5.72 (1H, br s, OH), 4.35 (2H, s), 3.28 (2H, t, J ¼ 7.0 Hz), 1.64–
1.42 (2H, m), 1.32–1.10 (10H, m), 0.78 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 236
(Mþ). Anal. Calcd. for C15H24O2: C, 76.27; H, 10.16. Found: C, 76.07; H, 10.04.
4-Hydroxybenzyl (2)-Menthyl Ether (6B)
1H NMR (200 MHz, CDCl3): d 7.18 (2H, d, J ¼ 8.0 Hz), 6.77 (2H, d,
J ¼ 8.0 Hz), 4.88 (1H, s), 4.56 (1H, d, J ¼ 12.0 Hz), 4.30 (1H, d,

.
NaHSO4 SiO2 Catalyzed Facile Transformation
3143
J ¼ 12.0 Hz), 3.38 (1H, m), 1.78–1.60 (3H, m), 0.98–0.84 (6H, m), 0.90 (3H,
d, J ¼ 7.0 Hz), 0.86 (3H, d, J ¼ 7.0 Hz), 0.68 (3H, d, J ¼ 7.0 Hz). EI-MS: m/
z ¼ 262 (Mþ). Anal. Calcd. for C17H26O2: C, 77.86; H, 9.92. Found: C, 77.46;
H, 9.52.
4-Hydroxy-3-methoxybenzyl 10-Methyl Propyl Ether (7B)
1H NMR (200 MHz, CDCl3): d 6.92–6.73 (3H, m), 5.60 (1H, s), 4.40 (2H,
q, J ¼ 12.0 Hz), 3.86 (3H, s), 3.39 (1H, m), 1.70–1.38 (2H, m), 1.16 (3H, d,
J ¼ 7.0 Hz), 0.86 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 210 (Mþ). Anal. Calcd.
for C12H18O3: C, 68.57; H, 8.57. Found: C, 68.37; H, 8.37.
1-(40-Hydroxyphenyl)-ethyl n-Octyl Ether (10B)
1H NMR (200 MHz, CDCl3): d 7.12 (2H, d, J ¼ 8.0 Hz), 6.76 (2H, d,
J ¼ 8.0 Hz), 5.28 (1H, br s, OH), 4.28 (1H, q, J ¼ 7.0 Hz), 3.20 (2H, t,
J ¼ 7.0 Hz), 1.62–1.44 (2H, m), 1.30 (3H, d, J ¼ 7.0 Hz), 1.28–1.18 (10H,
m), 0.82 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 250 (Mþ). Anal. Calcd. for
C16H26O2: C, 76.80; H, 10.40. Found: C, 76.57; H, 10.04.
4-Hydroxybenzyl n-Decyl Thioether (16B)
1H NMR (200 MHz, CDCl3): d 7.12 (2H, d, J ¼ 8.0 Hz), 6.68 (2H, d,
J ¼ 8.0 Hz), 4.55 (1H, s), 3.59 (2H, s), 2.31 (2H, t, J ¼ 7.0 Hz), 1.58–1.42
(2H, m), 1.40–1.18 (14H, m), 0.83 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 280
(Mþ). Anal. Calcd. for C17H28OS: C, 72.85; H, 10.00; O, 5.71; S, 11.42.
Found: C, 72.45; H, 9.54; O, 5.68; S, 11.32.
4-Hydroxybenzyl n-Dodecyl Thioether (17B)
1H NMR (200MHz, CDCl3): d 7.14 (2H, d, J ¼ 8.0 Hz), 6.70 (2H, d,
J ¼ 8.0 Hz), 4.62 (1H, s), 3.58 (2H, s), 2.32 (2H, t, J ¼ 7.0 Hz), 1.62–1.44
(2H, m), 1.40– 1.12 (18H, m), 0.84 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 308
(Mþ). Anal. Calcd. for C19H32OS: C, 74.02; H, 10.38. Found: C, 74.00; H, 10.14.
4-Hydroxybenzyl n-Hexadecyl Thioether (18B)
1H NMR (200 MHz, CDCl3): d 7.12 (H, d, J ¼ 8.0 Hz), 6.68 (2H, d,
J ¼ 8.0 Hz), 4.46 (1H, s), 3.58 (2H, s), 2.32 (2H, t, J ¼ 7.0 Hz), 1.58–1.40
(2H, m), 1.38–1.10 (26H, m), 0.82 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 364
(Mþ). Anal. Calcd. for C23H40OS: C, 75.82; H, 10.38. Found: C, 75.62;
H, 10.04.

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Ramu et al.
1-(40-Hydroxyphenyl)-ethyl n-Decyl Thioether (19B)
1H NMR (200 MHz, CDCl3): d 7.14 (2H, d, J ¼ 8.0 Hz), 6.70 (2H, d,
J ¼ 8.0 Hz), 4.88 (1H, s), 3.84 (1H, q, J ¼ 7.0 Hz), 2.39–2.10 (2H, m),
1.58–1.37 (2H, m), 1.42 (3H, d, J ¼ 7.0 Hz), 1.34–1.16 (14H, m), 0.82
(3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 294 (Mþ). Anal. Calcd. for C17H30OS:
C, 69.38; H, 10.20. Found: C, 69.18; H, 10.04.
1-(40-Hydroxyphenyl)-ethyl n-Hexadecyl Thioether (21B)
1H NMR (200 MHz, CDCl3): d 7.12 (2H, d, J ¼ 8.0 Hz), 6.70 (2H, d,
J ¼ 8.0 Hz), 6.11 (1H, s), 3.72 (2H, q, J ¼ 7.0 Hz), 2.35–2.18 (2H, m),
1.52–1.40 (2H, m), 1.50 (3H, d, J ¼ 7.0 Hz), 1.32–1.12 (26H, m), 0.84
(3H, d, J ¼ 7.0 Hz). EI-MS: m/z ¼ 378 (Mþ). Anal. Calcd. for C23H42OS:
C, 73.01; H, 11.11. Found: C, 72.62; H, 11.04.
4-Hydroxy-3-methoxybenzyl n-Decyl Thioether (22B)
1H NMR (200 MHz, CDCl3): d 6.84–6.64 (3H, m), 5.48 (1H, s), 3.88 (3H,
s), 3.58 (2H, s), 2.36 (2H, t, J ¼ 7.0 Hz), 1.62–1.44 (2H, m), 1.39–1.15 (14H,
m), 0.88 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 310 (Mþ). Anal. Calcd. for
C18H30OS: C, 69.67; H, 9.67. Found: C, 69.57; H, 9.27.
4-Hydroxy-3-methoxy Benzyl n-Hexadecyl Thioether (24B)
1H NMR (200 MHz, CDCl3): d 6.84–6.64 (3H, m), 5.41 (1H, s), 3.90 (3H,
s), 3.62 (2H, s), 2.38 (2H, t, J ¼ 7.0 Hz), 1.62–1.40 (2H, m), 1.37–1.14 (26H,
m), 0.84 (3H, t, J ¼ 7.0 Hz). EI-MS: m/z ¼ 394 (Mþ). Anal. Calcd. for
C24H42OS: C, 73.09; H, 10.65. Found: C, 72.08; H, 10.04.
ACKNOWLEDGMENT
The authors thank UGC, New Delhi, for financial assistance.
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NaHSO4 SiO2 Catalyzed Facile Transformation
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Received in India May 31, 2004