Oxidative deprotection of tetrahydropyranyl and trimethylsilyl ethers in water using 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride under neutral conditions

Article abstract of DOI:10.3184/030823407X218101

A facile oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers in water using 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride as a new efficient reagent under neutral conditions is described. This methodology is ecofriendly and environmentally benign since it uses water as a solvent. In all reactions DABCO was regenerated, rechlorinated and reused several times.

Full text of DOI:10.3184/030823407X218101

JOURNAL OF CHEMICAL RESEARCH 2007
JULY, 377–380
RESEARCH PAPER 377
Oxidative deprotection of tetrahydropyranyl and trimethylsilyl ethers
in water using 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride
under neutral conditions
Mahmood Tajbakhsh* and Setareh Habibzadeh
Department of Chemistry, Mazandaran University, Babolsar, Iran
A facile oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers in water using 1,4-dichloro-1,4-diazonia-
bicyclo[2,2,2]octane bis-chloride as a new efficient reagent under neutral conditions is described. This methodology
is ecofriendly and environmentally benign since it uses water as a solvent. In all reactions DABCO was regenerated,
rechlorinated and reused several times.
Keywords: tetrahydropyranyl ethers, trimethylsilyl ethers, 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride, oxidation,
deprotection
Silyl and THP (tetrahydropyranyl) ethers are widely used
as protecting groups for alcohols in synthetic chemistry
because of their low cost, efficiency of preparation, stability
under the intended reaction conditions and ease of removal.1
A variety of methods for the selective removal of these
groups have been developed,2 but the direct synthesis of
carbonyl compounds from tetrahydropyranyl or silyl ethers in
water is not widespread in the literature.3 Nevertheless, such
methods have severe limitations such as tedious work-up,
long reaction times, low yields, high temperatures and they
also require the use of organic solvents, Lewis acid catalysts,
or expensive reagents. Thus, the introduction of new methods
with inexpensive reagents and environmentally-friendly
reaction conditions, especially using water as solvent4 for
such functional group transformations is still in demand.
In continuation of our investigations on oxidation reactions,5
we explored the oxidation ofTHPand silyl ethers in water using
1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride.
The analogous DABCO-bromine complex was previously
prepared and employed as an oxidant for organic substrates,
without regeneration of DABCO.6,7
O
C
Reagent 1
N
RCHR'OR''
+
N
Water, 50°C
R
R'
R'' =
SiMe3
,
O
R or R' = alkyl or aryl
Scheme 1
for the oxidative deprotection of THP and silyl ethers to their
carbonyl compounds involves a 1:0.6 molar ratio of substrate
to reagent at 50°C in water (Scheme 1).
The results are shown in Table 1. Aliphatic THP ethers
(Table 1, entries 1 and 5), aromatic THP ethers (Table 1,
entries 2–4 and 6–9) and a,b-unsaturated THP ether (Table 1,
entry 10) were efficiently cleaved to the corresponding
carbonyl compounds in good yields. The yields were
diminished when a NO2 group was present on the aromatic
ring (Table 1, entry 9) and longer reaction times had no
impact on the yield. THP ethers containing a double bond
(Table 1, entry 10) were also oxidised with no chlorination
of the double bond. Similarly, aliphatic and aromatic silyl
ethers (Table 1, entries 11–19) were also cleaved to the
corresponding carbonyl compounds. No overoxidation
products were detected in the case of aldehydes. Note that both
THP and silyl ethers were not oxidised in the reaction media
and only carbonyl compounds were obtained. An interesting
feature of this method was the recovery of 1,4-diazabicyclo
[2,2,2]octane in nearly quantitative amounts which could
easily be chlorinated and reused several times. In order to
investigate the applicability of this procedure, we have also
carried out the oxidation THP and silyl ether of benzyl alcohol
under our optimum reaction conditions on a larger scale
(60 mmol) and obtained the same yields as in small-scale
reaction.
Results and discussion
1,4-Dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride is
easily and quantitatively prepared when a solution of
DABCO in CHCl3 was treated with a stream of chlorine gas
at room temperature.8 Similar behaviour was observed for
1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane
bis-tetrafluoroborate (Selectfluor),9 and therefore we have
proposed structure 1 for this reagent.
Cl
_
+
N
Cl
+
N
_
Cl
Cl
1
In conclusion, we report here an efficient and simple
method for oxidation of THP and silyl ethers under aqueous
and neutral conditions. The positive features of the present
method are: its ease of operation; facile recycling of the
DABCO; excellent yields; and environmental compatability
since no organic solvent was used in the reaction and only a
small amount was needed in the workup.
The high solubility of this reagent in water (pH = 7) makes it
an efficient oxidant for organic substrates. It is inexpensive
and DABCO is recovered, rechlorinated and reused several
times in the oxidation reactions. Similar reactions with
DABCO–bromine complex under heterogeneous conditions
were carried out at 80°C without regeneration of DABCO.
To gain some preliminary information on this synthetically
useful reaction, THP and silyl ethers of benzyl alcohol were
chosen as model substrates. The optimum reaction conditions
Experimental
All the starting materials were purchased from the Fluka and
Merck companies. All trimethylsilyl and tetrahydropyranyl ethers
are known compounds and were prepared according to described
procedures.12 All oxidation products were known compounds, and
they were identified by comparison of their physical data, IR and
* Correspondent. E-mail: tajbaksh@umz.ac.ir
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378 JOURNAL OF CHEMICAL RESEARCH 2007
Table 1 Oxidative deprotection of tetrahydropyranyl and silyl ethers with 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-
chloride in water
Entry
Substratea
Productb
Time/min
Yield/%c
M.p./°C or B.p./°C/Torr
Found
Reported11
10a
10a
OTHP
1
2
20
25
90
92
99–101/760
100–103/760
CHO
CHO
OTHP
175–176/760
178–179/760
CHO
OTHP
3
4
25
30
90
93
44
45–47
Cl
Cl
10b
CHO
OTHP
121–122/12
118–121/12
MeO
MeO
10c
10d
5
30
89
85–87/12
85–88/12
OTHP
OTHP
O
O
6
7
8
35
35
35
87
88
84
199–201/760
54
202/760
55–57
10e
CHO
OTHP
Br
Br
O
OTHP
49–51
49–50
10f
CHO
OTHP
9
40
30
15
74
91
88
103–105
246
104–106
248
NO2
NO2
10d
CHO
OTHP
10
11
CHO
OTHP
230–231/760
232–235/760
(CH3)CH
(CH3)CH
10g
OSiMe3
12
13
CHO
20
30
95
95
99–100/760
100–103/760
178–179/760
10h
CHO
OSiMe3
174–176/760
CHO
OSiMe3
14
15
25
35
89
86
101–103/13
85–86/12
104–105/13
85–88/12
10g
OSiMe3
O
10g
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JOURNAL OF CHEMICAL RESEARCH 2007 379
Table 1 Continued
Entry
Substratea
Productb
Time/min
Yield/%c
M.p./°C or B.p./°C/Torr
Found
Reported11
OSiMe3
O
16
17
35
40
90
87
200–202
56
201–202
55–57
10h
10h
OSiMe3
CHO
OSiMe3
O
18
19
40
55
85
77
49–51
49–50
CHO
OSiMe3
103–105
104–106
NO2
NO2
aThe tetrahydropyranyl and trimethylsilyl ethers prepared are known compounds and were characterised by comparison of their
physical and spectral data with those reported in the literature.
bAll products showing physical and spectral data in accordance with expected structures.
cThe yields refer to isolated products.
NMR spectra with those of authentic samples. Yields refer to isolated
products or their 2,4-dinitrophenylhydrazones. Melting points were
determined using a Mettler FP 5 apparatus and are uncorrected.
1H NMR spectra were measured at 300 MHz on a JEOL spectrometer
with tetramethylsilane (Me4Si) as an internal reference and CDCl3
as the solvent for aldehydes and ketones. IR spectra were recorded
on Pye-Unicam SP 1100 spectrophotometer. Elemental analysis was
performed on a LECO 250 instrument.
δ = 9.7 (s, 1 H, CHO), 7.3–7.6 (m, 4H, ArH) ppm; 13C NMR (300 MHz,
CDCl3): δ = 129.4 (2 C), 129.9 (2 C), 135.89, 140.1, 192.0 ppm.
THP ether of benzhydrol (entry 8): White solid; m.p. 50–51°C;
1H NMR (300 MHz, CDCl3): δ = 1.52–1.97 (m, 6 H, CH2), 3.47–3.52 (m,
1 H, OCH2), 3.85–3.91 (m, 1 H, OCH2), 4.66 (t, J = 3.2 Hz,1 H, OCHO),
5.79 [s, 1 H, (Ar) 2CH], 7.17–7.36 (m, 10 H, ArH) ppm; 13C NMR
(300 MHz, CDCl3): δ = 19.3, 25.65, 30.7, 62.0, 78.1, 95.4, 126.7 (2 C),
126.9 (2 C), 127.4 (2 C), 127.5 (2 C), 128.0 (2 C), 128.3 (2 C) ppm;
IR (KBr): ν = 2942, 2903, 2877, 1490, 1199, 1121, 1025, 977, 916 cm–1.
Benzophenone (entry 8): 1H NMR (300 MHz, CDCl3): δ = 7.2–7.7
(m, 10 H, ArH) ppm; 13C NMR (300 MHz, CDCl3): δ = 129.1 (4 C),
130.5 (4 C), 131.5 (2 C), 138.1(2 C), 196.81 ppm.
TMS ether of 3-phenylpropanol (entry 14): Colourless liquid,
1H NMR (CDCl3): δ = 7.22–7.18 (5H, m), 3.60 (2H, t, J = 6.5 Hz),
2.68 (2H, t, J = 8.0 Hz), 1.85 (2H, m), 0.11 (9H, s) ppm; 13C NMR
(300 MHz, CDCl3): δ = 33.1, 34.2, 62.5, 127.6, 129.1 (2 C), 129.2
(2 C), 142.5 ppm; IR (KBr): ν = 1251, 1100, 841 cm-1.
Preparation of 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-
chloride
Chlorine gas was bubbled for 10 minutes through a solution of 1,4-
diazabicyclo[2,2,2]octane (DABCO) (6.72 g, 60 mmol) in chloroform
(100 cm3). The solvent was evaporated under reduced pressured to
afford pure product (14.94 g, 98%), m.p. decomp. 125–130°C. Anal.
Calcd for C6H12N2Cl4: C, 28.3; H, 4.7; N, 11.0; Cl, 55.9. Found: C,
27.9; H, 4.6; N, 11.2; Cl, 55.6. 1H NMR (D2O) δ 3.2 (s, 12H, 6CH2).
13C NMR (D2O) δ 91.3. IR 2800, 1500, 1380, 1000 and 750 cm-1.
3-phenylpropanal (entry 14): 1H NMR (300 MHz, CDCl3): δ = 9.61
(d, J = 1.8, 1 H, CHO), 7.3 (m, 5 H, ArH), 2.9 (t, J = 7.1 Hz, 2 H,
CH2), 2.5 (m, J = 7.1, 1.8 Hz, 2 H, CH2) ppm; 13C NMR (300 MHz,
CDCl3): δ = 45.6, 127.1, 129.1 (2 C), 129.3 (2 C), 141.0, 201.4 ppm.
TMS ether of 4-nitrobenzylalcohol (entry 19): Colourless liquid,
1H NMR (CDCl3): d 7.31–7.19 (4H, m), 4.72 (2H, s), 0.10 (9H, s)
ppm; 13C NMR (300 MHz, CDCl3): δ = 66.1, 120.4 (2 C), 128.1
(2 C), 144.2, 171.2 ppm; IR (KBr): ν = m 1253, 1095,844 cm-1.
4-Nitrobenzaldehyde (entry 19): 1H NMR (300 MHz, CDCl3): δ =
10.1 (s, 1 H, CHO), 7.2–7.9 (m, 4 H, ArH) ppm; 13C NMR (300 MHz,
CDCl3): δ = 131.4 (2 C), 133.2 (2 C), 139.7, 146.8, 192.5 ppm.
General procedure for oxidative cleavage of THP and silyl ethers
The appropriate substrate (THP ether or silyl ether, 5 mmol) and
1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bis-chloride (0.76 g,
3 mmol) was added to H2O (15 cm3) in a flask. The reaction mixture
(pH = 7) was warmed to 50°C and stirred. After completion of the
reaction (TLC), Et2O (10 cm3) was added to the reaction mixture.
The extract was washed with solution of 1% aq. HCl (1 ¥ 10 cm3). The
aqueous layer 1 was separated and the organic layer was washed with
3% aq. NaHCO3 (1 ¥ 10 cm3) and water (1 ¥ 10 cm3) respectively.
The organic layer was dried over MgSO4, filtered and evaporated
to dryness under reduced pressure to afford the pure corresponding
carbonyl compound.
Received 7 February 2007; accepted 6 June 2007
Paper 07/4467 doi: 10.3184/030823407X218101
Regeneration of 1,4-diazabicyclo[2,2,2]octane
References
The aqueous layer 1 from above procedure was further treated with
10% sodium bicarbonate solution (2 ¥ 10 cm3) and 1,4-diazabicyc
lo[2,2,2]octane (DABCO) was extracted with ether (3 ¥ 10 cm3).
The ether layer was dried over MgSO4, and evaporated to give
pure 1,4-diazabicyclo[2,2,2]octane (0.31 g, 95%), which can be
chlorinated and reused several times.
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4.44 (d, J = 12.0 Hz, 1 H, ArCH), 4.67 (br s, 1 H, OCHO), 4.72
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