BiCl3: A versatile catalyst for the tetrahydropyranylation and depyranylation of 1°,2°,3°, allylic, benzylic alcohols, and symmetric diols

Article abstract of DOI:10.13005/ojc/330260

Bismuth trichloride as mild reagent, has been found to be a worthful catalyst for tetrahydropyranylation of 1°,2°,3°, allylic, benzylic alcohols, and symmetric di-ols. At room temperature the reagent THP(3,4-dihydro-2H-pyran) was successfully employed as pyranylating agent in presence of BiCl₃catalyst without the use of a solvent and the yields of the products were found to be 90-96%. Further, the depyranylation of alcohols was achieved in quantitative yield by simple addition of MeOH using the same catalyst. The developed method was showed good chemo-selectivity in symmetrical diols for mono THP protection.

Full text of DOI:10.13005/ojc/330260

ISSN: 0970-020 X
CODEN: OJCHEG
2017, Vol. 33, No. (2):
Pg. 1030-1034
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
BiCl3: A Versatile Catalyst for the Tetrahydropyranylation
and Depyranylation of 1°,2°,3°, Allylic, Benzylic alcohols, and
Symmetric Diols
T. VIJAYA DURgA1, K. BALAMURALI KRISHNA1, M. BABY RAMANA1,
M. SANTHA KUMARI2 , K. VIJAY3 and B. HARI BABU1*
1Department of Chemistry, Acharya Nagarjuna University, NNagar-522 510, Andhra Pradesh, India.
2Department of Chemistry, CRR Degree & PG College, Eluru, W.G. Dist, Andhra Pradesh-India.
3College of Pharmaceutical sciences, Acharya Nagarjuna University,
NNagar-522 510, Andhra Pradesh, India.
*Corresponding author E-mail: dr.b.haribabu@gmail.com
http://dx.doi.org/10.13005/ojc/330260
(Received: October 21, 2016; Accepted: February 04, 2017)
ABSTRACT
Bismuth trichloride as mild reagent, has been found to be a worthful catalyst for
tetrahydropyranylation of 1°,2 °,3°, allylic, benzylic alcohols, and symmetric di-ols.At room temperature
the reagentTHP(3,4–dihydro-2H-pyran) was successfully employed as pyranylating agent in presence
of BiCl3 catalyst without the use of a solvent and the yields of the products were found to be 90-96%.
Further, the depyranylation of alcohols was achieved in quantitative yield by simple addition of MeOH
using the same catalyst.The developed method was showed good chemo-selectivity in symmetrical
diols for mono THP protection.
Keywords: Bismuth trichloride, Tetrahydropyranylation, Depyranylation,
alcohols, Symmetrical diols.
INTRODUCTION
remove);and remaining such asTBS, TPS,THP, are
acid labile (easier to remove). Among the reagents
the protection of alcohols and phenols by THP
reagent is one of the important and frequently used
approach1as the preparation of the reagent is easy
and stable in various reaction conditions such as with
alkylating reagents,hydrides, Grignard reagents and
organo metallic agents2.
While doing multi stage organic synthesis,
the protection and deprotection of alcohols by
various reagents is a most common event. The
most common protected forms of alcohols are
ethers and esters, where as in case of alkyl and
benzyl ethers the protection is permanent (difficult to

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DURGA et al., Orient. J. Chem., Vol. 33(2), 1030-1034 (2017)
A large number of reagents such as on API-ES Mass Spectrometer using positive mode
BF3.Et2O,3 PPTS,4Amberlyst,5 PTSA,6 Nafion-H,7 ionization method.
montmorillonite K-10,8 ZnCl2,9 AlPO4 on alumina 10
lithium perchlorate-diethyl ether,11 zeolites,12 sulfuric general procedure for tetrahydropyranylation
acid on silica-gel,13 Bronsted acids14 ZrCl4,15 iodine,16 To a mixture of 1°, 2°, 3°, benzylic, allylic
,
LiBr,17 tetrabutylammonium bromide,18 Lewis acids,19 alcohol or symmetric diol (1 mmol) and THP
In(OTf)3,20 and NbCl521 are useful for the tetrahydro- (1 mmol), bismuth trichloride (5 mol %) was added.
pyranylation of alcohols. Recently an organic Then the reaction mixture was stirred for appropriate
reagent 3,5-dinitrobenzoic acid, was also employed time as given in Table 1 at room temperature. The
for tetrahydropyranylation and depyranylation for reaction as monitored by TLC. After completion of
alcohols and phenols22. However, many of the the reaction it was poured into water and the product
above reported procedures suffers from use of was extracted with ethyl acetate (3x25 mL). Later
toxic and expensive reagents, need of large amount the organic layer was washed with brine, dried with
of catalyst, presence of acid-sensitive functional anhydrous sodium sulphate and concentrated in
groups, low chemo-selectivity, and unsatisfactory vacuum to obtain the crude mass.Which was further
yields. Moreover, the reaction conditions such purified by silica gel column chromatography(1:9
as higher temperatures, longer reaction times, EtOAc, hexane)to afford the corresponding THP
strong oxidizing and acidic conditions, also futile ether.Finally the products were characterized using
the methods. Hence there is a strong requirement 1H NMR and Mass spectra.
for novel catalytic approach to the protection and
deprotection of hydroxyl functional groups in the general procedure for depyranylation
absence of solvent. Bismuth trichloride (BiCl3) has
To the above THP ether solution(1 mmol)
emerged as a catalyst in organic synthesis23 and in methanol (10 mL),5 mol % bismuth trichloride
attracted attention of many researchers because of was added. The reaction mixture was stirred for
its diverse applicability. Moreover, bismuth(III) salts appropriate time as provided in Table 1 at room
are stable in air, relatively inexpensive and nontoxic temperature. The reaction was monitored by TLC.
compared to transition metal complexes. So, in the After completion of the reaction water was added to
present study BiCl3 is employed as a catalyst for the reaction mixture and the product was extracted
pyranylation and depyranylation of alcohols and with ethyl acetate (3x25 mL). Later the combined
symmetric diols (Scheme 1).
organic layer was washed with brine, dried over
anhydrous sodium sulphate and concentrated in
vacuum to give a crude mass, which was purified
over silica gel column to afford parent alcohol in
MATERIALS and METHODS
All the chemicals were obtained from quantitative yield.
Merck Specialties Private Limited, Mumbai, India.
Reactions were monitored by TLC using silica gel-G Analytical Data
(Merck grade) as the adsorbent. Silica gel (100-200 Compound 1
mesh, Merck grade) has been used for column
chromatography.
1H NMR, d = 1.43-1.90 (m, 6H), 2.90
(bs, 1H, OH), 3.52 (m, 1H), 3.85 (m, 1H), 4.02-4.24
(m, 4H), 4.68 (t, 1H), 5.58-5.84 (m, 2H); EIMS: m/z
1
The H NMR spectra of the compounds 172 (M+).
dissolved in duterated chloroform (CDCl3)
were recorded on Bruker AMX 300 MHz NMR Compound 2
spectrophotometer using TMS as an internal
1H NMR, d = 1.50-1.90 (m, 6H), 3.47 (m,
standard and the values are expressed in d ppm. 1H), 3.82 (m, 1H), 3.89-3.97 (m, 1H), 4.15-4.23 (m,
The Mass spectra of the compounds were recorded
3
OH
OTHP
MeOH, BiCl3, rt, 5 min
Scheme 1

DURGA et al., Orient. J. Chem., Vol. 33(2), 1030-1034 (2017)
1032
1H), 4.60 (t, 1H), 5.12-5.16 (m, 1H), 5.23-5.30 (m,
1H); EIMS: m/z 142 (M+).
3.90 (m, 2H), 4.62 (t, 1H); EIMS: m/z 144 (M+).
Compound 6
1H NMR, d = 1.18-1.94 (m, 16H), 3.50
(m, 2H), 3.82 (m, 1H), 4.64 (t, 1H); EIMS: m/z 184
(M+).
Compound 3
1H NMR, d = 1.50-1.90 (m, 6H), 3.45-3.53
(m, 1H), 3.60-3.70 (m, 3H), 3.80-3.90 (m, 2H), 4.65
(t, 1H); EIMS: m/z 154 (M+).
Compound 7
1H NMR, d = 1.48-1.88 (m, 6H), 3.50 (m,
1H), 3.85 (m, 1H), 4.10 (m, 1H), 4.35 (m, 1H), 4.67
(t, 1H), 6.25 (m, 1H), 6.60 (d, 1H, J = 15.8 Hz), 7.45
(m, 5H); EIMS: m/z 216 (M+).
Compound 4
1H NMR, d = 0.90 (t, 3H), 1.40 (m, 2H),
1.50-1.90 (m, 6H), 2.00 (m, 2H), 3.50 (m, 1H), 3.70
(m, 2H), 4.10 (m, 1H), 4.62 (t, 1H), 5.02-5.21 (m,
2H); EIMS: m/z 184 (M+).
Compound 8
1H NMR, d = 1.40-1.90 (m, 6H), 2.85 (t,
2H), 3.40 (m, 1H), 3.62 (m, 2H), 3.80 (m, 1H), 4.52
(t, 1H), 7.20 (m, 5H); EIMS: m/z 206 (M+).
Compound 5
1H NMR, d = 1.13 (d, 3H, J = 6.7 Hz), 1.20
(d, 3H, J = 6.0 Hz), 1.40-190 (m, 6H), 3.45 (m, 1H),
Table 1:Tetrahydropyranylation and depyranylation of alcohols
S.
NO.
Alcohol/
deprotected
alcohol
THP ether
(product)
Protection
Time
Deprotection
Time
(min)
min
%
%
OH
OTHP
1
2
3
12
12
13
90
94
98
04
05
03
93
96
98
HO
HO
OTHP
OH
OH
OTHP
Cl
Cl
HO
THPO
4
5
12
08
95
98
02
03
94
98
OH
OTHP
6
7
10
15
92
96
03
04
98
98
OH
OTHP
OTHP
Ph
Ph
Ph
8
OH
14
96
03
96
Ph
OH
OTHP
9
13
12
94
92
04
03
95
92
OTHP
OH
10
Ph
Ph
OH
11
15
95
03
96
OTHP

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DURGA et al., Orient. J. Chem., Vol. 33(2), 1030-1034 (2017)
compounds were also illustrated inTable 1.The yields
Compound 9
1H NMR, d = 1.47-1.58 (m, 4H), 1.60 (s, of depyranylation products are also good(92-98%).
3H), 1.68 (s, 6H), 1.82 (m, 2H), 2.10 (m, 4H), 3.50 We claim that the developed protocol is quite general
(m, 1H), 3.82 (m, 1H), 4.00 (m, 1H), 4.20 (m, 1H), as it is applicable to a large number of structurally
4.60 (t, 1H), 5.06 (t, 1H), 5.30 (t, 1H); EIMS: m/z 238 different alcohols viz. primary, secondary, tertiary,
(M+).
allylic and benzylic alcohols. The method was also
found to be highly selective for mono tetrahydro-
pyranylation of symmetrical diols. The compound
Compound 10
1H NMR, d = 1.40-1.90 (m, 6H), 2.45 (m, 11(Table 1) an acid sensitive alcohol was underwent
2H), 3.41 (m, 1H), 3.85 (m, 1H), 4.35 (t, 1H), 4.64 (t, THP protection as tetrahydropyranyl ether with 95%
1H), 5.00 (m, 2H), 5.75 (m, 1H), 7.20 (m, 5H); EIMS: yield and no dehydration product was observed.
m/z 232 (M+).
so from these results (Table 1) it is evident that
bismuth trichloride is an excellent catalyst for
tetrahydropyranylation and depyranylation of
Compound 11
1H NMR, d = 1.5 (s, 9H), d = 1.7 (m, 2H), alcohols under solvent-free conditions.
d = 3.3(m, 2H), d = 3.8 (m, 2H), d = 4.5 (m, 2H), d =
4.9 (t, 1H); EIMS: m/z 158.13 (M+).
CONCLUSIONS
RESULTS and DISCUSSIONS
The present protocol developed in this
work demonstrates that bismuth trichloride is an
The present investigation describes a mild efficient catalyst for the tetrahydropyranylation and
and efficient method for the tetrahydropyranylation depyranylation of alcohols. The major advantages
of 1°, 2 °, 3°, benzylic,allylic alcohol and symmetric of this protocol is use of mild catalyst, clean and
diols with THP in the presence of bismuth trichloride environmentally benign reaction conditions.The less
(5 mol %) as catalyst without the use of a solvent at reaction times and good yields of the products are
room temperature.In intial trailsTHP(3,4-dihydro-2H- additional advantages. Simple experimental work-
pyran)was reacted with cinnamyl alcohol (scheme 1) up procedure and mono tetrahydropyranylation
as parent alcohol using 5 mol% of bismuth trichloride selectively of symmetric diols offer significant
at room temperature to produce its corresponding improvements, low cost of the reagent.
THP ether of cinnamyl alcohol. A very good yield
(96%) of the product was found and the same trend
was continued in the remaining tested alcohols
(Table 1).
ACKNOwLEDgEMENTS
We thank Acharya Nagarjuna
University for encouragement and UGC, New Delhi
The depyranylation of the above obtained [F.No. 25-1/2014-15(BSR)/11-67/2008(BSR) dated
THP ether was easily obtained by maintaining the 25-08-2015] for providing Fellowship to the first
same quantities of the reagent in methanol at room author. We also thankful to CSIR, New Delhi for
temperature. All the deprotections were found to financial support to some chemicals (EMR-II/02(198)
be completed with in 5 min. The results of all the dt. 17.11.2014).
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