Deprotection of trimethylsilyl and tetrahydropyranyl ethers and of ethylene acetals with tetramethylammonium chlorochromate

Article abstract of DOI:10.1081/SCC-120016344

This paper describes the preparation of tetramethylammonium chlorochromate (TMACC) as a new and efficient reagent for the oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers or ethylene acetals and ketals to the corresponding carbonyl compounds in refluxing acetonitrile in the presence of catalytic amounts of aluminum chloride.

Full text of DOI:10.1081/SCC-120016344

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Deprotection of Trimethylsilyl and Tetrahydropyranyl
Ethers and of Ethylene Acetals with
Tetramethylammonium Chlorochromate
Abdol R. Hajipour a b & Arnold E. Ruoho a
a Department of Pharmacology , University of Wisconsin Medical School , Madison,
Wisconsin, USA
b Pharmaceutical Research Laboratory , College of Chemistry , Isfahan University of
Technology , Isfahan, IR, Iran
Published online: 17 Aug 2006.
To cite this article: Abdol R. Hajipour & Arnold E. Ruoho (2003) Deprotection of Trimethylsilyl and Tetrahydropyranyl Ethers
and of Ethylene Acetals with Tetramethylammonium Chlorochromate, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 33:6, 871-878, DOI: 10.1081/SCC-120016344
To link to this article: http://dx.doi.org/10.1081/SCC-120016344
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 6, pp. 871–878, 2003
Deprotection of Trimethylsilyl and
Tetrahydropyranyl Ethers and of Ethylene
Acetals with Tetramethylammonium
Chlorochromate
1
Abdol R. Hajipour1,2, and Arnold E. Ruoho
*
1Department of Pharmacology, University of Wisconsin
Medical School, Madison, Wisconsin, USA
2Pharmaceutical Research Laboratory,
College of Chemistry, Isfahan University of Technology,
Isfahan IR, Iran
ABSTRACT
This paper describes the preparation of tetramethylammonium
chlorochromate (TMACC) as a new and efficientreagentfor hte
oxidative deprotection of trimethylsilyl and tetrahydropyranyl
ethers or ethylene acetals and ketals to the corresponding carbonyl
*Correspondence: Abdol R. Hajipour, Department of Pharmacology, University
of Wisconsin Medical School, 1300 University Avenue, Madison, WI, 53706 1532
USA, and Pharmaceutical Research Laboratory, College of Chemistry, Isfahan
University of Technology, Isfahan 84156, IR, Iran; E-mail: arhajipour@facstaff.
wisc.edu or haji@cc.iut.ac.in.
871
DOI: 10.1081/SCC-120016344
Copyright & 2003 by Marcel Dekker, Inc.
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872
Hajipour and Ruoho
compounds in refluxing acetonitrile in the presence of catalytic
amounts of aluminum chloride.
The protection and deprotection of the hydroxy and carbonyl groups
play an essential role in synthetic strategy.[1–7] Chromium (VI) oxide is an
inexpensive, water-soluble and stable oxidizing reagent, that is commer-
cially available, buthtis reagentis insoluble in organic solvenst. Very
recently, we have introduced new reagents to oxidize different sub-
strates.[8] We now report TMACC 1 as a new and efficientreagentfor
the oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers
or ethylene acetals and ketals to the corresponding carbonyl compounds
in refluxing acetonitrile in the presence of catalytic amounts of aluminum
chloride.
This reagentis an orange powder, which is prepared by the dropwise
addition of CrO3 in 6 N HCl solution to an aqueous solution of tetra-
methylammonium chloride at room temperature. Filtration and drying of
the precipitates produced an orange powder, which could be stored for
months without losing its oxidation ability. This reagent is quite soluble
in methylene chloride, chloroform, acetone, and acetonitrile and insolu-
ble in non-polar solvents such as carbon tetrachloride, n-hexane, and
diethyl ether (Sch. 1).
Since deprotection of benzyltrimethylsilyl ether in refluxing acetoni-
trile with this reagent failed in the absence of catalyst, the effect of several
Lewis acids such as ZnCl2, FeCl3, FeBr3, SnCl2, SnCl4, CuCl2, BiCl3,
AlBr3, and AlCl3 were also examined. Surprisingly, only AlCl3 was
shown to be effective catalyst for this purpose (Table 1). The reaction
in the presence of ZnCl2, FeCl3, FeBr3, SnCl2, SnCl4, CuCl2, BiCl3, and
AlBr3 (0.5 mmol) proceeds with lower efficiency even with a higher molar
ratio of the oxidant (1.5 mmol) in comparison with the amount of oxidant
used in the presence of AlCl3 (0.3 mmol). This could be the effect of
hardness of AlCl3 in comparison with the other Lewis acids, which
have been used in these experiments.
Under these conditions primary and secondary trimethylsilyl ethers
were converted to the corresponding carbonyl compounds in high
yields and short reaction times (Table 2). The reaction of primary and
H2O/10 min
Me4N+Cl– + CrO3 (HCl 6 N)
Me4N.CrO3HCl
96 %
1
Scheme 1.

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Tetramethylammonium Chlorochromate
873
Table 1. Deprotection of benzyltrimethylsilyl ether with reagent 1 with different
Lewis acids in acetonitrile under reflux conditions.a,b
Entry
Lewis acid
Time (min.)
Yield (%)
1
2
3
4
5
6
7
8
9
ZnClc2
CuCl2
FeClc3
BiClc3
FeBrc3
SnClc2
SnClc4
AlBr3
AlCl3
80
80
120
70
90
90
90
80
25
30
30
65
40
30
40
70
96
60
aMonitored by TLC analysis.
bOxidant/Alcohol/Lewis acid (1:1:0.3).
cOxidant/Alcohol/Lewis acid (1.5:1:0.5).
1
R
1
R
AlCl (0.3 molar ratio)
3
O
O- G + TMACC (1)
MeCN reflux conditions
2
R
2
R
G = TMS or THP and R1, R2 = H, Alkyl, Aryl
Scheme 2.
secondary tetrahydropyranyl ethers with TMACC was carried out
in acetonitrile under reflux to the corresponding carbonyl compounds
in good to excellent yields (Table 2, Sch. 2).
This reagent was also used to convert ethylene acetals to aldehydes
and ketones in acetonitrile under reflux conditions in good to excellent
yields (Table 3, Sch. 3). Itwas also found htatC ¼C bonds, methoxy
groups, and hydroxy groups remained intact during deprotection
(Table 2 and 3).
The tetramethylammonium cation could be recovered in quantitative
yield. When the reaction was completed, the reaction mixture was cooled
to room temperature and passed through a short pad of silica gel, and
then washed with acetonitrile. The silica gel layer was washed with
HCl 10% and then this aqueous layer was treated with a fresh bath of
a solution of chromium (VI) oxide in HCL 6 N to produce the reagent 1
in quantitave yield.

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874
Hajipour and Ruoho
Table 2. Oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers
with TMACC/AlCl3 in refluxing MeCN.a
Time Yield
(min.) (%)b
Entry
Substrate
PhCH2OTMS
2-MeOC6H4CH2OTMS
3-MeOC6H4CH2OTMS
3-O2NC6H4CH2OTMS
Product
1
2
3
4
5
6
7
8
9
PCHO
65
90
65
100
65
45
80
40
55
80
45
60
55
55
60
60
45
80
60
70
60
60
35
60
35
60
55
50
50
50
50
55
96
86
98
92
95
98
92
98
96
90
88
88
90
98
85
95
98
85
85
80
80
88
98
85
90
94
92
90
90
88
88
92
2-MeOC6H4CHO
2-MeOC6H4CHO
3-O2NC6H4CHO
2,5-(MeO)2C6H3CH2OTMS 2,5-(MeO)2C6H3CHO
PhCH(Me)OTMS
4-ClC6H4CH(Me)OTMS
Ph2CHOTMS
4-PhC6H4CH(Me)OTMS
CH3(CH2)5OTMS
C6H5CH¼CHCH2OTMS
MentolTMS
4-COOH– C6H4CH2OTMS 4-COOH– C6H4CHO
TetralolTMS
2-Methylcyclohexyl-TMS
Benzoin-TMS
PhCH2OTHP
2-MeOC6H4CH2OTHP
3-MeOC6H4CH2OTHP
4-MeOC6H4CH2OTHP
3,4-(MeO)2C6H3CH2OTHP 3,4-(MeO)2C6H3CHO
2,5-(MeO)2C6H3CH2OTHP 2,5-(MeO)2C6H3CHO
PhCH(Me)OTHP
4-ClC6H4CH(Me)OTHP
Ph2CHOTHP
CH3(CH2)5OTHP
C6H5CH¼CHCH2OTHP
MentolTHP
PhCOMe
4-ClC6H4COMe
Ph2CO
4-PhC6H4COMe
CH3(CH2)4CHO
C6H5CH¼CHCHO
Menthone
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Tetralone
2-Methylcyclohexanone
Benzil
PhCHO
2-MeOC6H4CHO
3-MeOC6H4CHO
4-MeOC6H4CHO
PhCOMe
4-ClC6H4COMe
Ph2CO
CH3(CH2)4CHO
C6H5CH¼CHCHO
Menthone
4-COOH– C6H4CH2OTHP 4-COOH– C6H4CHO
TetralolTHP
2-Methylcyclohexyl-TMS
Benzoin-THP
Tetralone
2-Methylcyclohexanone
Benzil
aSubstrate/Oxidant/AlCl3 (1:1:0.3).
bYields based on the products after column chromatography.

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Tetramethylammonium Chlorochromate
875
Table 3. Deprotection of ethylene acetals with TMACC/AlCl3 in refluxing
MeCN.a
Time Yield
(min.) (%)b
Entry
Substrate
Product
1
2
Acetophenone ethylene acetal Acetophenone
2-Methoxybenzaldehyde
ethylene acetal
30
40
94
92
2-Methoxybenzaldehyde
3
4
3-Nitrobenzaldehyde
ethylene acetal
4-Chloroactophenone
ethylene acetal
3-Nitrobenzaldehyde
4-Chloroactophenone
60
50
90
92
5
6
Tetralone ethylene acetal
4-Phenylacetophenone
ethylene acetal
Tetralone
4-Phenylacetophenone
45
50
98
94
7
8
9
Menthone ethylene acetal
Cyclohexanone ethylene acetal Cyclohexanone
Menthone
45
60
60
91
88
90
2-Methylcyclohexanone
ethylene acetal
2-Methylcyclohexanone
10
11
12
4-t-butylcyclohexanone
ethylene acetal
Cinnamaldehyde
ethylene acetal
6-Hydroxyhexanal
ethylene acetal
4-t-butylcyclohexanone
Cinnamaldehyde
70
30
60
88
92
85
6-Hydroxyhexanal
aSubstrate/Oxidant/AlCl3 (1:1:0.3).
bYields based on the products after purification with column chromatography.
R1
R1
O
AlCl (0.3 molar ratio)
3
O
+ TMACC (1)
MeCN reflux conditions
R2
R2
O
R1, R2 = H, Alkyl, Aryl
Scheme 3.
In order to evaluate the synergy between TMACC and aluminum
chloride, several experiments were performed. The reaction of
2-MeOC6H4CH2OTMS (1 mmol) with TMACC (1 mmol) without
aluminum chloride failed after 2 h refluxing in acetonitrile. When equi-
molar amountof aluminum chloride and 2-MeOC 6H4CH2OTMS

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Hajipour and Ruoho
was refluxed in acetonitrile without TMACC for 2 h, the corresponding
alcohol was obtained in only 20% yield. Only when TMACC was used in
the presence of a catalytic amount of aluminum chloride (0.3 mmol) the
corresponding aldehyde obtained in excellent yield (Table 1).
EXPERIMENTAL
Trimethylsilyl ethers, tetrahydropyranyl ethers, ethylene acetals were
prepared according to described procedures.[4–7] All yields refer to
isolated products. The products were characterized by comparison with
authentic samples (IR, 1H-NMR spectra, melting and boiling points and
1
TLC). All H-NMR spectra were recorded at 300 MHz in CDCl3 and
CCl4 relative to TMS (0.00 ppm).
Preparation of Tetramethylammonium
Chlorochromate 1 (TMACC)
A solution of tetramethylammonium chloride (10.95 g, 100 mmol)
in 100 ml of water was prepared, and then CrO3 (10.0 g, 100 mmol) in HCl
6 N (50 ml) was added dropwise to the above solution and stirred for
10 min. at room temperature. The resulting orange precipitate was filtered
and washed with cooled distilled water (2 ꢀ 50 ml), and dried in
a desiccator under vacuum over calcium chloride to afford an orange
powder (20.2 g, 96% yield), which decomposed at210–212 ꢁC t o a
dark-brown material. 1H-NMR:
d 3.58 (s). Anal. Calcd. for
C4H13ClCrNO3: C, 22.80; H, 6.18%. Found: C, 22.96; H, 6.28%.
General Procedures. Oxidative Deprotection of Trimethylsilyl
and Tetrahydropyranyl Ethers with TMACC/AlCl3
In a round-bottomed flask (25 mL) equipped with a reflux condenser
a magnetic stirrer, a solution of trimethylsilyl ether or
and
tetrahydropyranyl ether (1 mmol) and AlCl3 (0.04 g, 0.3 mmol) in aceto-
nitrile (10 mL) was prepared. TMACC (0.21 g, 1 mmol) was added
to the solution and refluxed for time specified in Table 2. The reaction
progress was followed by TLC (eluent: cyclohexane/EtOAc: 8:2).
To remove the tetramethylammonium cation, the reaction mixture
was cooled to room temperature and the mixture was passed through a

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Tetramethylammonium Chlorochromate
877
short pad of silica gel and washed with acetonitrile (15 mL). The filtrate
was evaporated and the resulting crude material was purified
by column chromatography on silica gel using a mixture of ethyl acetate
and hexane as eluent(10:90).
Conversion of Ethylene Acetals and Ketals to the
Corresponding Carbonyl Compounds with TMACC/AlCl3
In a round-bottomed flask (25 mL) equipped with a reflux condenser
and a magnetic stirrer, a solution of ethylene acetal or ketal (1 mmol) and
AlCl3 (0.04 g, 0.3 mmol) in acetonitrile (10 mL) was prepared.
Tetramethylammonium chlorochromate (0.21 g, 1 mmol) was added to
the solution and refluxed for the time being specified in Table 3. The
reaction progress was followed by TLC (eluent: cyclohexane/EtOAc:
8:2). The reaction mixture was then cooled to room temperature and
passed through a short pad of silica gel and washed with acetonitrile
(15 mL). The filtrate was evaporated and the resulting crude material
was purified by column chromatography on silica gel using a mixture
of ethyl acetate and hexane as eluent (10:90).
ACKNOWLEDGMENTS
We gratefully acknowledge the funding support received for this
project from the Isfahan University of Technology (IUT), IR, Iran
(A. R. H.) and Grant GM 33138 (A. E. R.) from the National
Institutes of Health, USA.
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Received in the USA February 21, 2002