Efficient synthesis of tert-butyl ethers under solvent-free conditions

Article abstract of DOI:10.1080/00397910701470578

A simple and efficient synthesis of tert-butyl ethers from various alcohols and substituted phenols using tert-butyl bromide in the presence of basic lead carbonate as a catalyst. The catalyst is easily recovered via filtration and can be reused up to three times without appreciable loss of activity. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701470578

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Efficient Synthesis of tert‐Butyl Ethers under
Solvent‐Free Conditions
Neithnadka Premsai Rai a & Pirama Nayagam Arunachalam a
a Syngene International Pvt. Ltd., Bangalore, India
Available online: 30 Aug 2007
To cite this article: Neithnadka Premsai Rai & Pirama Nayagam Arunachalam (2007): Efficient Synthesis of
tert‐Butyl Ethers under Solvent‐Free Conditions, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 37:17, 2891-2896
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Synthetic Communicationsw, 37: 2891–2896, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701470578
Efficient Synthesis of tert-Butyl Ethers
under Solvent-Free Conditions
Neithnadka Premsai Rai and Pirama Nayagam Arunachalam
Syngene International Pvt. Ltd., Bangalore, India
Abstract: A simple and efficient synthesis of tert-butyl ethers from various alcohols
and substituted phenols using tert-butyl bromide in the presence of basic lead
carbonate as a catalyst. The catalyst is easily recovered via filtration and can be
reused up to three times without appreciable loss of activity.
Keywords: tert-butyl bromide, tert-butyl ethers, lead carbonate, reusable catalyst,
solvent free
INTRODUCTION
The protection of alcohols as tert-butyl ethers has become a widely utilized
procedure in organic synthesis.[1] The tert-butyl ether is one of the most
underused alcohol protecting groups, although it is stable under strongly
basic condition and can be cleaved with a relative ease under acidic con-
ditions.[2] The chemical syntheses of tert-butyl ethers are well documented
in the literature.[1,2] Some of the common practices involve the exposure of
the alcoholic or phenolic species to excess of isobutylene in the presence of
acid catalysts such as borontrifluride–phosphoric acid complex or sulfuric
acid at 0–258C[3] or trifluromethane sulfonic acid in dichloromethane at
2508C.[4] In some examples, nonacidic conditions such as reaction of
tert-butanol and alkanol using anhydrous magnesium sulfate are reported to
synthesize t-butyl alkyl ethers. This method is useful for the synthesis of
tert-butyl esters as well.[5] Other methods include Pd/P(t-Bu)3-catalyzed
Received in India January 12, 2007
Address correspondence to Pirama Nayagam Arunachalam, Syngene International
Pvt. Ltd., Biocon Park, Plot Nos. 2 and 3, Bommasandra IV Phase, Jigani Link Road,
Bangalore 560 100, India. E-mail: pn.arunachalam@syngeneintl.com
2891

2892
N. P. Rai and P. N. Arunachalam
Scheme 1.
reactions of aryl halides with sodium tert-butoxide for the synthesis of aryl
tert-butyl ethers[6] and magnesium perchlorate–catalyzed reaction of alcohol
with tert-butyldicarbonate (Boc2O) to get alkyl and aryl tert-butyl ethers.[7]
Most of these protocols require either longer reaction time or critical
reaction conditions such as reaction of low boiling isobutylene under
autoclave conditions. Also in these protocols, they normally require chromato-
graphic separations for obtaining pure products. Herein, we report a method
that works within a couple of hours under mild reaction conditions as shown
in Scheme 1. The products are normally obtained in the pure form by
solvent trituration and filtration Table 1.
RESULT AND DISCUSSION
In this articles, we report a simple and efficient etherification of allyl, alkynyl
alcohols, and substituted phenols, which easily reacted with tert-butyl
Table 1. Reaction of phenol with tert-butyl bromide under various conditionsa in the
presence of 2PbCO3Pb(OH)2
Amount of
Entry t-BuBr (mmol)
2PbCO3Pb(OH)2
(mmol)
Time (h) Temp. (8C) Yieldb (%)
1
2
3
4
5
6
7
20
10
20
10
15
20
40
1
1.5
2
40
50
40
40
50
40
50
.90
55 (45)c
90
1
2
1.5
1.5
1.5
1.5
4
2
,50
65
90 (85)d
,25
2
1(3)d
—
aReaction condition: phenol (10 mmol), t-BuBr, 2PbCO3Pb(OH)2, temperature and
time as shown.
bIsolated product.
cRecovered phenol.
dRun with recycled lead carbonate obtained by washing with ethyl acetate and
drying.

tert-Butyl Ethers
2893
bromide in the presence of lead carbonate at 35–458C under solvent-free
conditions with good to excellent yields of respective tert-butyl ethers
within 1–2.25 h. The results are summarized in Table 2. The same process
was successfully extended to get other tert-butyl ether derivatives; for
example (entry 10, Table 2), 3-hyroxy-benzyl alcohol (10 mmol) reacted
with tert-butyl bromide (40 mmol) in the presence of lead carbonate
(2 mmol) at 408C over 2.25 h to give the corresponding product of 1-tert-
butyl-3-(tert-butoxy methyl) benzene in 88% yield. Similarly allyl, alkynyl,
1-pentanol, and 1-octanol (entries 1–4, Table 2) reacted smoothly with tert-
butyl bromide in the presence of lead carbonate to afford 85, 86, 80, and
82% of 3-tert-butoxy prop-1-ene, tert-butyl prop-2-ynyl ether, tert-butyl
pentyl ether, and tert-butyl octyl ether, respectively.
Recovery of the catalyst was accomplished by simple filtration or by
centrifugation followed by washing with ethyl acetate. Notably, the
reactions gave excellent results with various substituted phenols (entries
5–8); a- and b- naphthol (entries 11 and 12) can be converted into the corre-
sponding tert-butyl ethers in high yields, without any detectable side products
arising from an electrophilic addition to the aromatic ring. The reaction is
highly chemoselective. In fact, other functionalities present in the phenols
such as methoxy, chloro, and fluro groups survived under the adopted
reaction conditions.
EXPERIMENTAL
NMR spectrum was recorded on 300-MHz and 400-MHz Brucker spec-
trometers. All chemicals were commercially available and used without
further purification except 3-hydroxy benzylalcohol, which was synthesized
in house from 3-hydroxy benzaldehyde according to the procedure
mentioned in the literature.[8]
General Procedure for tert-Butyl Ethers
To a mixture of phenol (10 mmol) and lead carbonate (1 mmol) taken in a two-
necked, 50-mL, round-bottomed flask cooled to 08C, tert-butyl bromide
(20 mmol) was added dropwise. The mixture was stirred and heated in an
oil bath at 408C for the given period of time (Table 2). After completion of
the reaction, EtOAc (2 Â10 mL) was added to the reaction mixture, stirred
for a while, and filtered. The filtrate was washed with 10% NaOH followed
by saturated brine solution, dried over anhydrous Na2SO4, and concentrated
on a rotavap to afford pure tert-butoxybenzene (entry 4, Table 2, 2e) in
90% yield. All products were characterized by NMR spectral analysis.
In conclusion, we have developed a new general and convenient method
for the synthesis of tert-butyl ethers under mild conditions.

2894
N. P. Rai and P. N. Arunachalam
Table 2. Synthesis of tert-butyl ether under mild conditions
Time
Temp. Yield
(%)b
Entry
Substrate
(h)
1.25
1.25
1
Producta
(8C)
1
2
3
35
85
35
86
40
80
4
5
1
40
40
82
90
1.5
6
7
1.5
1.5
40
40
92
88
8
9
1.25
1.8
40
40
82
96
10
11
2.25
40
45
88
75
2
12
13
1.5
2
45
45
86
82
14
2
40
84
aAll products are known except 2a, 2b, 2c, and 2j, which are novel and characterized
by NMR spectral analysis.
bIsolated yields.

tert-Butyl Ethers
2895
Data
1
3-Tert-butyl prop-1-ene 2a: H NMR: d (ppm) ¼ 1.2 (s, 9H), 3.90–3.92
(d, 2H), 5.10–5.11 (d, 1H), 5.13–5.14 (d, 1H), 5.8–5.9 (m, 1H); 13C NMR:
d (ppm) ¼ 27.5 (CH3), 63.05 (OCH2), 73.6 (C), 115.6 (C), 136.2 (C).
t-Butyl prop-2-ynyl ether 2b: 1H NMR: d (ppm) ¼ 1.25 (s, 9H), 2.4 (S, 1H),
4.1 (S, 2H); 13C NMR: d (ppm) ¼ 27.3 (CH3), 31.0 (CH), 36.3 (C), 53.24 (C),
72.82 (C).
t-Butyl pentyl ether 2c: 1H NMR: d (ppm) ¼ 0.76 (t, 3H), 1.2 (s, 9H), 1.25
(m, 2H), 1.36 (m, 2H), 1.57 (m, 2H), 3.56 (m, 2H); 13C NMR: d
(ppm) ¼ 14.0 (CH3), 22.7 (CH3), 28.3 (CH2), 29.2 (CH2), 32.0 (CH2), 62.0
(OCH2), 71.9 (C).
1-t-Butoxyoctane 2d:[7] 1H NMR: d (ppm) ¼ 0.88 (t, J ¼ 6.8, 3H), 1.19
(s, 9H), 1.20–1.40 (m, 10H), 1.45–1.55 (m, 2H), 3.32 (t, J ¼ 6.6, 2H); 13C
NMR: d (ppm) ¼ 14.0 (CH3), 22.6 (CH2), 26.2 (CH2), 27.5 (CH3), 29.3
(CH2), 29.5 (CH2), 30.7 (CH2), 31.8 (CH2), 61.6 (CH2), 72.3 (C).
1-t-Butoxybenzene 2e:[7] 1H NMR: d (ppm) ¼ 1.35 (s, 9H), 6.95–7.00
(m, 2H), 7.05–7.10 (m, 1H), 7.25–7.30 (m, 2H); 13C NMR: d (ppm) ¼ 29.4
(CH3), 78.3 (C), 123.3 (CH), 124.2 (CH), 128.8 (CH), 131.9 (C).
1-t-Butoxy-4-methoxybenzene 2f:[7] 1H NMR: d (ppm) ¼ 1.33 (s, 9H), 3.72
(s, 3H), 6.76 (m, 4H); 13C NMR: d (ppm) ¼ 28.0 (CH3), 56 (C), 71.7, 78.0 (C),
113.8 (CH), 123.5 (C), 154.3 (C).
1-t-Butoxy-3-chlorobenzene 2 g:[7] 1H NMR: d (ppm) ¼ 1.35 (s, 9H), 6.88
(dd, 1H), 7.00 (t, 1H), 7.05 (dd, 1H), 7.18 (t, 1H); 13C NMR: d
(ppm) ¼ 28.8 (CH3), 79.2 (C), 122.2 (CH), 123.4 (CH), 124.3 (CH), 129.6
(CH), 134.0 (C), 156.4 (C).
1-t-Butoxy-4-fluorobenzene 2 h:[7] 1H NMR: d (ppm) ¼ 1.31 (s, 9H), 6.93
(s, 2H), 6.94 (s, 2H); 13C NMR: d (ppm) ¼ 28.7 (CH3), 78.5 (C), 115.2
(d, CH), 125.5 (d, CH), 151.1 (C), 159.1 (d, C).
1-(t-Butoxymethyl)benzene 2i:[7] 1H NMR: d (ppm) ¼ 1.31 (s, 9H), 4.47
(s, 2H), 7.25–7.40 (m, 5H); 13C NMR: d (ppm) ¼ 27.7 (CH3), 64.1 (CH2),
73.4 (C), 127.1 (CH), 127.4 (CH), 128.3 (CH), 139.9 (C).
1-t-Butoxy-3-(tert-butoxymethyl)benzene 2j: 1H NMR: d (ppm) ¼ 1.29
(s, 9H), 1.35 (S, 9H), 4.42 (S, 2H), 6.8 (d, 1H), 6.9 (s, 1H), 7.0 (d, 1H),
7.3 (m, 1H); 13C NMR: d (ppm) ¼ 27.6 (CH3), 28.8 (CH), 63.8 (OCH2), 73.3
(C), 77.9 (C), 113.7 (C), 116.7 (C), 119.8 (C), 128.5 (CH), 141.0 (CH),
158.8 (CH).

2896
N. P. Rai and P. N. Arunachalam
1-t-Butoxynaphthalene 2 k:[7] 1H NMR: d (ppm) ¼ 1.46 (s, 9H), 7.10 (dd,
1H), 7.33 (t, 1H), 7.40–7.45 (m, 2H), 7.50 (d, 1H), 7.75–7.80 (m, 1H),
8.20–8.25 (m,1H). 13C NMR: d (ppm) ¼ 29.1 (CH3), 79.7 (C), 116.3 (CH),
122.3 (CH), 123.4 (CH), 125.1 (CH), 125.4 (CH), 125.9 (CH), 127.5 (CH),
130.0 (C), 134.8 (C), 152.1 (C).
2-t-Butoxynaphthalene 2l:[7] 1H NMR: d (ppm) ¼ 1.41 (s, 9H), 7.18 (dd,
1H), 7.35–7.45 (m, 3H), 7.65–7.80 (m, 3H). 13C NMR: d (ppm) ¼ 28.9
(CH3), 78.9 (C), 119.7 (CH), 124.4 (CH), 125.0 (CH), 125.9 (CH), 127.2
(CH), 127.9 (CH), 128.5 (CH), 130.3 (C), 134.1 (C), 152.1 (C).
2-t-Butoxy-1,2-diphenylethanone 2 m:[7] 1H NMR: d (ppm) ¼ 1.25 (s, 9H),
5.62 (s, 1H), 7.20–7.55 (m, 8H), 8.05–8.10 (m, 2H). 13C NMR: d
(ppm) ¼ 28.0 (CH3), 76.0 (C), 79.7 (CH), 126.1 (CH), 127.6 (CH), 128.1
(CH), 128.5 (CH), 130.0 (CH), 132.7 (CH), 135.2 (C), 138.6 (C), 200.1 (C).
t-Butoxycyclopentae 2n:[7] 1H NMR: d (ppm) ¼ 1.18 (s, 9H), 1.40–1.50
(m, 4H), 1.60-1.85 (m, 4H), 3.95–4.05 (m, 1H). 13C NMR: d (ppm) ¼ 23.7
(CH2), 28.6 (CH3), 34.9 (CH2), 72.8 (CH), 73.5 (C).
ACKNOWLEDGMENTS
The authors acknowledge Goutam Das, CEO, Syngene International Pvt. Ltd.
for granting permission to P. S. N. for research work.
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