A mild and selective cleavage of trityl ethers by CBr4-MeOH

Article abstract of DOI:10.1016/S0008-6215(00)00241-X

Trityl ethers are selectively deprotected to the corresponding alcohols in high yields by CBr₄ in refluxing methanol under neutral reaction conditions. Other hydroxyl protecting groups like isopropylidene, allyl, benzyl, acetyl, benzoyl, methyl

Full text of DOI:10.1016/S0008-6215(00)00241-X

www.elsevier.nl/locate/carres
Carbohydrate Research 329 (2000) 885–888
Note
A mild and selective cleavage of trityl ethers by
CBr4–MeOHꢀ
Jhillu S. Yadav *, Basi V. Subba Reddy
Organic Chemistry Di6ision-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 17 April 2000; accepted 8 August 2000
Abstract
Trityl ethers are selectively deprotected to the corresponding alcohols in high yields by CBr4 in refluxing methanol
under neutral reaction conditions. Other hydroxyl protecting groups like isopropylidene, allyl, benzyl, acetyl,
benzoyl, methyl, tosyl, prenyl, propargyl, tert-butyldiphenylsilyl and p-methoxybenzyl ethers are unaffected. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: Trityl ethers; Carbon tetrabromide; Alcohols
Trityl ethers are widely used protecting
groups for primary alcohols, especially in car-
bohydrate chemistry [1], but procedures for
their selective cleavage are scarce. Among var-
ious hydroxyl protecting groups, the trityl
ether is one of the most commonly used due
to its ease of formation/removal and stability
towards a variety of reaction conditions. A
few methods are reported for its cleavage
which include formic acid [2], 80% acetic acid
[3], mineral acids [4], zinc bromide [5], trifl-
uoroacetic acid [6], iodine–MeOH [7], ceric
ammonium nitrate [8], ferric chloride [9] and
BCl3 [10]. In order to avoid the cleavage of the
glycosidic bond and the hydrolysis of acetate,
some of the methods [11,12] are reported un-
der mild conditions. Most of these methods
suffer from the use of strongly acidic condi-
tions, formation of byproducts, cleavage of
the glycosidic bond, hydrolysis of acetates,
unsatisfactory yields and incompatibility with
other functional groups present in the sub-
strate. These limitations prompted us to dis-
close a new and efficient procedure for
selective cleavage of trityl ethers over a wide
range of functional groups.
In this communication, we wish to report a
facile cleavage of trityl ethers using CBr4 in
methanol at reflux temperature. The cleavage
proceeds smoothly in high yields by the reac-
tion of trityl ethers with a catalytic amount of
CBr4 in refluxing methanol. Trityl and
dimethoxytrityl ethers are selectively cleaved
without causing any damage to the glycosidic
bond and the O-isopropylidene group. The
more acid-sensitive dimethoxytrityl group is
removed more rapidly and at a lower tempera-
ture than the trityl group. There are several
advantages for the use of CBr4 in methanol,
which selectively cleaves trityl ethers leaving
other hydroxyl protecting groups intact. Such
ꢀ Indian Institute of Chemical Technology Communication
No. 4432.
* Corresponding author. Fax: +91-40-7170512.
E-mail address: yadav@iict.ap.nic.in (J.S. Yadav).
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00241-X

886
J.S. Yada6, B.V. Subba Reddy / Carbohydrate Research 329 (2000) 885–888
a selectivity is a highly desirable feature in the
cleavage of trityl ethers, which offers various
beneficial prospects to synthetic organic chem-
istry. The reaction conditions are compatible
with other hydroxyl protecting groups like Bn,
Bz, Me, Ac, Ts, allyl, prenyl, propargyl, PMB
and TBDPS present in the substrate. Other
acid-sensitive protecting groups such as BOC
and CBz are also unaffected under these reac-
tion conditions. The trityl group is removed
rapidly in high yields with the migration of
acetate and the O-isopropylidene group left
Table 1
Selective cleavage of trityl ethers by CBr4–MeOH
Entry
a.
Trityl ether 1
Alcohol a
2
Reaction time (h)
2.5
Yield b (%)
88
b.
c.
d.
e.
f.
3.0
3.5
1.5
2.0
3.5
3.0
3.5
1.5
2.5
4.5
4.0
93 d
90 d
94
87 c,d
90
g.
h.
i.
92 e
90
88
j.
91
k.
l.
90 f
85
m.
n.
5.0
1.5
92
88 f
a All products were characterized by 1H NMR and IR spectra and also by comparison with authentic samples. The
spectroscopic data was identical with the data reported in the literature.
b Isolated yields after purification.
c Acetate migration was observed.
d For spectroscopic data see [15].
e For spectroscopic data see [14].
f For spectroscopic data see [13].

J.S. Yada6, B.V. Subba Reddy / Carbohydrate Research 329 (2000) 885–888
887
and chemical shifts are reported as l values.
IR spectra were recorded on a Nicolet 740
FTIR spectrophotometer. Optical rotations
were recorded on Jasco DIP 360 digital polar-
imeter. Thin-layer chromatography (TLC) was
checked on 0.25 mm E. Merck precoated Silica
Gel 60 F254 plates with detection by charring
with 30% (v/v) H2SO4 in MeOH. The solvents
MeOH and MeCN were distilled over magne-
sium cake and P2O5, respectively.
intact (Table 1, entry c). Among various sol-
vents studied, methanol was found to be more
effective for this cleavage. The occurrence of
this cleavage may be attributed to the forma-
tion of HBr in situ itself by the reaction of
CBr4 with MeOH. To confirm the effect of
solvent, the reactions were also carried out in
refluxing acetonitrile in the presence of 10%
CBr4, which resulted in moderate yields (45–
65%) of cleavage products after a long reaction
time (8–12 h). Even though the deprotection is
slow by CBr4 in refluxing acetonitrile, various
functional groups like acetates, THP ethers
and epoxides are unaffected. Most of the start-
ing materials and the products were known in
literature, and their characterization was easily
Detritylation procedure.—A mixture of
trityl ether (5 mmol) and CBr4 (0.5 mmol) in
freshly distilled MeOH (15 mL) was refluxed
for an appropriate time as required to com-
plete the reaction. On completion, as indicated
by TLC, the reaction mass was cooled to rt,
diluted with water, and extracted twice with
EtOAc (2×15 mL). The combined organic
layers were washed with brine, dried over
anhyd Na2SO4 and concentrated in vacuo.
The resulting product was purified by column
chromatography on silica gel (E. Merck, 100–
200 mesh, 2:8 EtOAc–hexane) to afford the
pure alcohol.
1
achieved from H NMR spectra. The starting
materials showed triphenyl proton signals,
while the products showed an upfield shift of
H-5 and H-5% and the disappearance of trityl
signals. The spectroscopic data of the products
was identical with the data reported in the
literature. No racemization was observed un-
der the present reaction conditions, which was
confirmed by the comparison of optical rota-
tion of compound 2b {[h]D −58.5° (c 7.5,
CHCl3)} with an authentic sample [9] {[h]D
−58.7° (c 7.5, CHCl3)}. The results summa-
rized in Table 1 reveal the scope and selectivity
of the reaction with respect to various func-
tionalized ethers.
In summary, this communication describes a
mild and efficient procedure for chemoselec-
tive removal of the trityl group by CBr4 in
refluxing methanol. The method offers several
advantages like mild reaction conditions, sim-
ple experimental/workup procedures, high
yields of detritylated products, inexpensive
reagents and compatibility with other acid-sen-
sitive functional groups. This method will ex-
tend the scope of applicability of the trityl
group by obviating the difficulty often encoun-
tered in its cleavage.
1
The H NMR data of some compounds are
as follows.
1
1a: H NMR (CDCl3): l 7.70 (m, 2 H),
7.45–7.25 (m, 23 H), 5.85 (d, 1 H, J 4.0 Hz),
4.30 (d, 1 H, J 3.7 Hz), 4.20 (d, 1 H, J 4.0 Hz),
4.15 (m, 1 H), 3.60 (dd, 1 H, J 3.8 and 7.8
Hz), 3.15 (dd, 1 H, J 3.8 and 7.8 Hz), 1.45 (s,
3 H), 1.20 (s, 3 H), 0.9 (s, 9 H). 2a: l 7.65 (m,
4 H), 7.40 (m, 6 H), 5.90 (d, 1 H, J 4.1 Hz),
4.30 (d, 1 H, J 3.8 Hz), 4.25 (d, 1 H, J 4.1 Hz),
4.15 (m, 1 H), 3.85 (dd, 1 H, J 4.0 and 8.0
Hz), 3.65 (dd, 1 H, J 4.0 and 8.0 Hz), 1.75
(brs, 1 H, OH), 1.40 (s, 3 H) 1.20 (s, 3 H), 1.05
(s, 9H). 1b: l 7.50–7.30 (m, 20 H), 5.90 (d, 1
H, J 4.2 Hz), 4.58 (d, 1 H, J 4.2 Hz), 4.60,
4.45 (2 d, 2 H, J 12.8 Hz), 4.35 (m, 1 H), 4.05
(d, 1 H, J 3.7 Hz), 3.50 (dd, 1 H, J 4.2 and 8.7
Hz), 3.35 (dd, 1 H, J 4.2 and 8.7 Hz), 1.50, (s,
3 H), 1.30 (s, 3 H). 2b: l 7.45–7.35 (m, 5 H),
5.90 (d, 1 H, J 4.2 Hz), 4.58 (d, 1 H, J 4.2 Hz),
4.65–4.45 (2 d, 2 H, J 12.8 Hz), 4.25 (m, 1 H),
4.05 (d, 1 H, J 3.7 Hz), 3.95–3.85 (m, 2 H),
2.15 (brs, 1 H, OH), 1.55 (s, 3 H), 1.35 (s, 3
H). 1c: l 8.25 (m, 6 H), 7.75 (m, 3 H), 7.55
(m, 7 H), 7.35 (m, 2 H), 7.15 (m, 2 H), 5.90 (d,
1 H, J 4.0 Hz), 5.55 (dd, 1 H, J 3.7 Hz), 5.30
(d, 1 H, J 4.0 Hz), 4.60 (m, 1 H), 3.55 (dd, 1
H, J 4.0 and 8.2 Hz), 3.35 (dd, 1 H, J 4.0 and
1. Experimental
General methods.—1H and 13C NMR spec-
tra were recorded on a Varian Gemini-200
spectrometer. The samples were dissolved in
CDCl3 using Me4Si as the internal standard,

888
J.S. Yada6, B.V. Subba Reddy / Carbohydrate Research 329 (2000) 885–888
8.2 Hz), 1.45 (s, 3 H), 1.25 (s, 3 H). 2c: l 8.15
(m, 2 H), 7.60 (m, 1 H), 7.45 (m, 2 H), 6.0 (d,
1 H, J 4.1 Hz), 5.45 (d, 1 H, J 3.8 Hz), 4.65 (d,
1 H, J 4.1 Hz), 4.50 (m, 1 H), 3.85 (dd, 1 H J
4.0 and 8.2 Hz), 3.70 (dd, 1 H, J 4.0 and 8.2
Hz), 1.45 (s, 3 H), 1.25 (s, 3 H). 1d: l 7.50 (m,
4 H), 7.30 (m, 9H), 5.85 (d, 1 H, J 4.0 Hz), 4.55
(d, 1 H, J 4.0 Hz), 4.35 (m, 1 H), 3.90 (s, 6 H),
3.78 (d, 1 H, J 3.7 Hz), 3.45 (dd, 1 H, J 3.0 and
7.5 Hz), 3.35 (s, 3 H), 3.25 (dd, 1 H, J 3.0 and
7.5 Hz), 1.55 (s, 3 H), 1.35 (s, 3 H). 2d: l 5.87
(d, 1 H, J 4.0 Hz), 4.55 (d, 1 H, J 4.0 Hz), 4.25
(m, 1 H), 3.80 (m, 2 H), 3.75 (d, 1 H, J 3.7 Hz),
3.40 (s, 3 H), 2.30 (brs, 1 H, OH), 1.50 (s, 3 H),
1.30 (s, 3 H). 1f: l 7.75–7.55 (m, 19 H), 5.85
(d, 1 H, J 4.0 Hz), 4.80 (d, 1 H, J 3.8 Hz), 4.45
(d, 1 H, J 4.0 Hz), 4.25 (m, 1 H), 3.55 (dd, 1
H, J 3.7 and 8.7 Hz), 3.15 (dd, 1 H, J 3.7 and
8.7 Hz), 2.45 (s, 3 H), 1.45 (s, 3 H), 1.25 (s, 3
H). 2f: l 7.85 (d, 2 H, J 8.7 Hz), 7.45 (d, 2 H,
J 8.7 Hz), 5.90 (d, 1 H, J 4.0 Hz), 4.85 (d, 1 H,
J 3.7 Hz), 4.50 (d, 1 H, J 4.0 Hz), 4.25 (m, 1
H), 3.75 (dd, 1 H, J 3.7 and 8.7 Hz), 3.60 (dd,
1 H, J 3.7 and 8.7 Hz), 2.40 (s, 3 H), 1.45 (s,
3 H), 1.25 (s, 3 H). 1h: l 7.45 (m, 6 H), 7.25
(m, 9H), 5.85 (d, 1 H, J 4.1 Hz), 4.75 (m, 1 H),
5.18 (m, 2 H), 4.48 (d, 1 H, J 4.1 Hz), 4.30 (m,
1 H), 4.05 (m, 1 H), 3.90 (d, 1 H, J 3.8 Hz), 3.85
(m, 1 H), 3.45 (dd, 1 H, J 2.7 and 8.0 Hz), 3.24
(dd, 1 H, J 2.7 and 8.0 Hz), 1.48 (s, 3 H), 1.30,
(s, 3 H). 2h: l 5.92 (d, 1 H, J 4.0 Hz), 5.85 (m,
1 H), 5.25 (m, 2 H), 4.55 (d, 1 H, J 4.0 Hz), 4.25
(m, 1 H), 4.15 (m, 1 H), 4.05 (m, 1 H), 3.95 (d,
1 H, J 3.7 Hz), 3.85 (m, 2 H), 1.45 (s, 6 H), 1.25
(s, 3 H). 1i: l 7.45 (m, 6 H), 7.20 (m, 9 H), 5.80
(d, 1 H, J 4.0 Hz), 5.25 (m, 1 H), 4.45 (d, 1 H,
J 4.0 Hz), 4.25 (m, 1 H), 4.10 (m, 1 H), 4.05 (m,
1 H), 3.90 (d, 1 H, J 3.7 Hz), 3.40 (dd, 1 H, J
3.7 and 7.8 Hz), 3.20 (dd, 1 H, J 3.7 and 7.8
Hz), 1.75 (s, 3 H), 1.65 (s, 3 H), 1.45 (s, 3 H),
1.25 (s, 3 H). 2i: l 5.90 (d, 1 H, J 4.0 Hz), 5.30
(m, 1 H), 4.50 (d, 1 H, J 4.0 Hz), 4.25 (m, 1 H),
4.15 (m, 1 H), 4.05 (m, 1 H), 3.87 (d, 1 H, J 3.8
Hz), 3.80 (m, 2 H), 2.50 (brs, 1 H, OH), 1.75
(s, 3 H), 1.70 (s, 3 H), 1.45 (s, 3 H), 1.30 (s, 3
H). 1j: l 7.40 (m, 6 H), 7.20 (m, 9H), 5.85 (d,
1 H, J 4.2 Hz), 4.45 (d, 1 H, J 4.2 Hz), 4.25 (m,
1 H), 4.05 (m, 1 H), 3.95 (d, 1 H, J 3.8 Hz), 3.88
(m, 1 H), 3.40 (dd, 1 H, J 3.8 and 8.0 Hz), 3.20
(dd, 1 H J 3.8 and 8.0 Hz), 1.8 (m, 1 H), 1.45
(s, 3 H), 1.25 (s, 3 H). 2j: l 5.90 (d, 1 H, J 4.1
Hz), 4.50 (d, 1 H, J 4.1 Hz), 4.30 (m, 1 H), 4.15
(m, 1 H), 4.05 (m, 1 H), 3.95 (d, 1 H, J 3.8 Hz),
3.85 (m, 2 H), 1.80 (m, 1 H), 1.40 (s, 3 H), 1.25
(s, 3 H). 1l: l 7.45 (m, 5 H), 7.35–7.15 (m, 15
H), 5.75 (brs, 1 H, NH), 5.15 (s, 2 H), 4.45 (m,
1 H), 3.85 (s, 3 H), 3.45 (m, 2 H). 2l: 7.45 (m,
5 H), 5.85 (brs, 1 H, NH), 5.20 (s, 2 H), 4.50
(m, 1 H), 3.95 (m, 2 H), 2.20 (brs, 1 H, OH).
1m: l 7.35–7.25 (m, 20 H), 5.75 (m, 2 H), 4.45
(s, 2 H), 3.65 (d, 2 H J 6.8 Hz), 3.90 (d, 2 H,
J 6.8 Hz). 2m: l 7.30 (m, 5 H), 5.80 (m, 2 H),
4.50 (s, 2 H), 4.10 (d, 2 H, J 6.8 Hz), 4.05 (d,
2 H, J 6.8 Hz), 2.50 (brs, 1 H, OH).
Acknowledgements
BVS thanks CSIR, New Delhi, for the award
of a fellowship.
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