Efficient and selective oxidative deprotection of tetrahydropyranyl ethers, ethylene acetals and ketals with silver and sodium bromates in the presence of aluminum chloride

Article abstract of DOI:10.1055/s-1999-3410

Primary and secondary tetrahydropyranyl (THP) ethers are efficiently transformed to their carbonyl compounds with AgBrO₃ and NaBrO₃/AlCl_3. Ethylene acetals and ketals are transformed to their carboxylic acids and ketones respectively with AgBrO₃/AlCl₃ in refluxing acetonitrile. AgBrO₃/AlCl₃ is also able to transform ethylene acetals to aldehydes in refluxing carbon tetrachloride in high yields. In refluxing acetonitrile, ethylene acetals and ketals are transformed to aldehydes and ketones with NaBrO₃/AICI_3. We have also found that tetrahydropyranyl ethers are oxidized selectively in the presence of ethylene acetals and ketals with these reagents.

Full text of DOI:10.1055/s-1999-3410

PAPER
487
Efficient and Selective Oxidative Deprotection of Tetrahydropyranyl Ethers,
Ethylene Acetals and Ketals with Silver and Sodium Bromates in the Presence
of Aluminum Chloride
Iraj Mohammadpoor-Baltork,* Ali Reza Nourozi
Chemistry Department, Esfahan University, Esfahan, 81744, Iran
Fax +98(31)687396
Received 19 June 1998; revised 18 September 1998
Abstract: Primary and secondary tetrahydropyranyl (THP) ethers
are efficiently transformed to their carbonyl compounds with
AgBrO3 and NaBrO3/AlCl3. Ethylene acetals and ketals are trans-
formed to their carboxylic acids and ketones respectively with
AgBrO3 /AlCl3 in refluxing acetonitrile. AgBrO3 /AlCl3 is also able
to transform ethylene acetals to aldehydes in refluxing carbon tetra-
chloride in high yields. In refluxing acetonitrile, ethylene acetals
and ketals are transformed to aldehydes and ketones with NaBrO3/
AlCl3. We have also found that tetrahydropyranyl ethers are oxi-
dized selectively in the presence of ethylene acetals and ketals with
these reagents.
Key words: tetrahydropyranyl ethers, acetals, ketals, oxidative
deprotection, bromates
A wide variety of methods are available in the literature
for the conversion of alcohols to their tetrahydropyranyl
ethers and deprotection of these derivatives to the parent
alcohols.1Ð11 But little attention has been paid to the oxida-
tive cleavage of tetrahydropyranyl ethers and only a few
reports are available dealing with the oxidation of these
derivatives to their corresponding carbonyl com-
pounds.12Ð15
Deprotection of ethylene acetals and ketals to their carbo-
nyl compounds under nonaqueous and aprotic conditions
is of practical importance.16Ð20
Recently we have introduced new reagents for the oxida-
tive deprotection of tetrahydropyranyl ethers to their cor-
responding carbonyl compounds.14,15 We now report that
silver and sodium bromates in the presence of 0.3 molar
ratio of aluminum chloride21,22 are also able to oxidize pri-
mary and secondary tetrahydropyranyl ethers 1aÐo with-
out overoxidation to their corresponding aldehydes and
ketones 2aÐo in high yields in refluxing acetonitrile
(Scheme 1, Table 1).
Scheme 1
2aÐj in high yields in the presence of 0.3 molar ratio of
aluminum chloride (Scheme 2, Table 2).
As we have mentioned in our previous publications,21,22
both reagents are effective under nonaqueous conditions
when catalyzed with AlCl3. This trend has been also ob-
served for the oxidative deprotection of tetrahydropyranyl
ethers, ethylene acetals and ketals. Unfortunately the
mechanism of the reaction is not clear to us.
Oxidative deprotection of ethylene acetals and ketals were
also investigated with these reagents. In refluxing acetoni-
trile ethylene acetals 3aÐe and ketals 3fÐj are transformed
to their corresponding carboxylic acids 4aÐe and ketones
2fÐj respectively with silver bromate in the presence of
0.3 molar ratio of aluminum chloride. Under the same re-
action conditions in refluxing carbon tetrachloride, ethyl-
ene acetals are transformed to their aldehydes in high
yields (Scheme 2, Table 2). Sodium bromate in refluxing
acetonitrile is also able to transform ethylene acetals and
ketals 3aÐj to their corresponding carbonyl compounds
We have also investigated the competitive oxidation of
tetrahydropyranyl ethers and ethylene acetals or ketals
with these reagents. We have found that tetrahydropyra-
nyl ethers are oxidized selectively in the presence of eth-
ylene acetals or ketals (Scheme 3). Table 3 shows some
experimental results and illustrates the efficiency, appli-
cability, and scope of this method.
Synthesis 1999, No. 3, 487–490 ISSN 0039-7881 © Thieme Stuttgart á New York

488
I. Mohammadpoor-Baltork, A. R. Nourozi
PAPER
Table 1 Oxidative Deprotection of Tetrahydropyranyl (THP) Ethers with AgBrO3 and NaBrO3/AlCl3
Substrate
Product
Yield % (Time, h)
mp (¡C) or bp (¡C)/Torr
found
reported23
AgBrO3/AlCl3
(Method A)
NaBrO3/AlCl3
(Method B)
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
95 (0.65)a
90 (2.5)
80 (3)
95 (0.65)a
95 (2.5)
85 (3)
176Ð178/760
237Ð238/760
152Ð153/23
57Ð58
151Ð153/760
200Ð202/760
231Ð233/760
117Ð118
153Ð155/760
113Ð115/6
142Ð143/50
106Ð108
178Ð179/760
238/760
153/23
90 (2)
90 (2)
57Ð59
92 (1.5)a
90 (0.6)a
90 (0.6)
75 (2.5)
88 (1.5)a
85 (1.5)
82 (2.5)
78 (2.5)
80 (2)
90 (1.5)a
95 (0.6)a
93 (0.6)
70 (2.5)
86 (1.5)a
95 (1.5)
85 (3)
153/760
202/760
232/760
116Ð118
155/760
113Ð116/6
143/50
105Ð108
97Ð98/12
207Ð210/760
125Ð127
75 (2.5)
75 (2)
78 (2.5)
75 (3)
96Ð97/12
208Ð210/760
124Ð126
80 (2.5)
80 (3)
a Yield based on the isolation of 2,4-dinitrophenylhydrazine derivative.
bromates in the presence of aluminum chloride under non-
aqueous and aprotic conditions.
Tetrahydropyranyl ethers, ethylene acetals and ketals were prepared
according to described procedures.2,9,16 All of the oxidation prod-
ucts were characterized by comparison of their spectral and physi-
cal data with those of authentic samples. Yields refer to isolated
products or their 2,4- dinitrophenylhydrazones. Melting points were
determined using a Mettler FP5 apparatus and are uncorrected. IR
spectra were run on a Philips PU9716 spectrophotometer. 1H NMR
spectra were recorded in CDCl3 solvent on a Bruker AM 80 MHz
spectrometer using TMS as an internal standard. GC analysis was
performed with a Shimadzu 16A gas chromatograph with a flame
ionization detector using a column of 15% Carbowax 20M Chro-
mosorb-W 60Ð80 mesh. Silver bromate was prepared as described
previously.21
Oxidative Deprotection of Tetrahydropyranyl Ethers 1aÐo with
AgBrO3/AlCl3 (Method A); General Procedure
In a round-bottomed flask (50 mL) equipped with a magnetic stirrer
and a condenser containing a solution of tetrahydropyranyl ether 1
(1 mmol) in CH3CN (15 mL) silver bromate (0.236 g, 1 mmol) and
AlCl3 chloride (0.04 g, 0.3 mmol) were added and refluxed for 0.6Ð
3 h. The progress of the reaction was monitored by GC or TLC (elu-
ent: hexane/EtOAc, 10:1). The mixture was filtered and the solid
material was washed with CH3CN (15 mL). The filtrate was evapo-
rated on a rotary evaporator (volatile products were transformed
first to their corresponding 2,4-dinitrophenylhydrazones followed
by solvent evaporation) and the resulting crude material was puri-
fied on a silica gel plate or silica gel column with appropriate eluent.
Pure carbonyl compounds 2aÐo were obtained in 75Ð95% yields
(Table 1).
Scheme 2
Oxidative Deprotection of Tetrahydropyranyl Ethers 1aÐo with
NaBrO3/AlCl3 (Method B); General Procedure
Scheme 3
To a solution of tetrahydropyranyl ether 1 (1 mmol) in CH3CN
(15 mL) in a 50 mL round-bottomed flask equipped with a condens-
er and a magnetic stirrer, sodium bromate (0.151 g, 1 mmol) and
AlCl3 (0.04 g, 0.3 mmol) were added and refluxed for 0.6Ð3 h. The
progress of the reaction was monitored by GC or TLC (eluent: hex-
In conclusion, in this study we have introduced efficient
and selective oxidative deprotection of tetrahydropyranyl
ethers, ethylene acetals and ketals using silver and sodium
Synthesis 1999, No. 3, 487–490 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Oxidative Deprotection of Tetrahydropyranyl Ethers, Ethylene Acetals and Ketals
489
Table 2 Oxidative Deprotection of Ethylene Acetals and Ketals with AgBrO3 and NaBrO3/AlCl3
Substrate
Product
Yield % (Time, h)
mp (¡C) or bp (¡C)/Torr
found
AgBrO3/AlCl3
(Method C)
NaBrO3/AlCl3
(Method D)
reported23
3a
3b
3c
3d
3e
2a
4a
90 (0.75)a,b
95 (0.65)
70 (1.15)a
88 (1)
75 (2)a
87 (1.5)
83 (1)a,c
96 (0.75)
80 (1.5)a,b
94 (1)
95 (1)b
Ð
176Ð178/760
121Ð123
178Ð179/760
122Ð123
2b
4b
82 (1.5)
Ð
237Ð238/760
99Ð101
238/760
98Ð100
2c
4c
80 (2.5)
Ð
152Ð153/23
147Ð148
153/23
146Ð148
2d
4d
85 (1.15)
Ð
86 (1.5)b
Ð
57Ð58
139Ð141
57Ð59
140Ð142
2e
4e
151Ð153/760
222Ð223
153/760
223
3f
3g
3h
3i
2f
2g
2h
2i
90 (0.65)b
92 (0.5)
68 (3)
89 (0.75)b
93 (0.75)
66 (3.5)
200Ð202/760
231Ð233/760
117Ð118
153Ð155/760
113Ð115/6
202/760
232/760
116Ð118
155/760
113Ð116/6
95 (2)b
93 (2.15)b
97 (0.7)
3j
2j
95 (0.5)
a Reaction was carried out in refluxing CCl4.
b Yield based on the isolation of 2,4-dinitrophenylhydrazine derivative.
c In refluxing CH2Cl2 and Et2O, 59 and 38% of 3-nitrobenzaldehyde was obtained respectively after 1.5 h.
and AlCl3 (0.04 g, 0.3 mmol) were added to the solution and stirred
magnetically under reflux conditions for 0.5Ð3 h. The progress of
the reaction was monitored by GC or TLC (eluent: hexane/EtOAc,
10:1). Workup as mentioned in method A afforded pure carboxylic
acids 4aÐe and ketones 2fÐj in 68Ð96% yields. In refluxing CCl4 un-
der the same reaction conditions ethylene acetals were transformed
to the corresponding aldehydes 2aÐe in 70Ð90% yields (Table 2).
Table 3 Competitive Oxidative Deprotection of Tetrahydropyra-
nyl Ethers and Ethylene Acetals (Ketals) with AgBrO3 and
NaBrO3/AlCl3
Substrate Product (Yield %)
AgBrO3 NaBrO3
Time (h)
AgBrO3 NaBrO3
Oxidative Deprotection of Ethylene Acetals and Ketals 3aÐj
with NaBrO3/AlCl3 (Method D); General Procedure:
In a round-bottomed flask (50 mL), a solution of ethylene acetal or
ketal 3 (1 mmol) in CH3CN (10 mL) was treated with sodium bro-
mate (0.151 g, 1 mmol) and AlCl3 chloride (0.04g, 0.3 mmol) and
refluxed for 0.7Ð3.5 h. The progress of the reaction was monitored
by GC or TLC (eluent: hexane/EtOAc, 10:1). Workup as mentioned
in method B afforded pure carbonyl compounds 2aÐj in 66Ð97%
yields (Table 2).
1a+3b
1b+3a
1b+3d
1d+3b
1f+3b
1f+3g
1g+3f
1e+3i
1i+3e
2a (79)+4b (16) 2a (75)+2b (24) 0.6
2b (72)+4a (20) 2b (74)+2a (23) 1.5
2b (70)+4d (26) 2b (67)+2d (28) 1.5
2d (83)+4b (7) 2d (82)+2b (17) 0.75
2f (81)+4b (18) 2f (73)+2b (26) 0.5
2f (87)+2g (9) 2f (70)+2g (24) 0.5
2g (89)+2f (5) 2g (85)+2f (12) 0.5
0.6
2
1.75
0.83
0.65
0.6
0.75
1.5
2e (89)+2i (10) 2e (88)+2i (8)
2i (71)+4e (25) 2i (75)+2e (23)
1.5
1
1.25
Acknowledgement
ane/EtOAc, 10:1). The mixture was filtered and the solid material
was washed with CH3CN (15 mL). The filtrate was evaporated on a
rotary evaporator and the residue was redissolved in Et2O (15 mL).
The resulting yellow solution was treated with 20% aq sodium
sulfite (20 mL) in order to remove excess bromine. The organic lay-
er was separated and the aqueous layer was extracted with Et2O (3
× 15 mL).The combined extracts were dried (MgSO4) and the sol-
vent was evaporated and the resulting crude material was purified
on a silica gel plate or silica gel column with appropriate eluent.
Pure carbonyl compounds 2aÐo were obtained in 70Ð95% yields
(Table 1).
We thank the Esfahan University Research Council for partial sup-
port of this work.
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Synthesis 1999, No. 3, 487–490 ISSN 0039-7881 © Thieme Stuttgart · New York