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:10.3184/030823407X209723

The 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. The DABCO was regenerated, rechlorinated and reused several times.

Full text of DOI:10.3184/030823407X209723

JOURNAL OF CHEMICAL RESEARCH 2007
MAY, 259–262
RESEARCH PAPER 259
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
The 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. The 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 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 often described in the literature.3 Such methods have
limitations such as tedious work-up, long reaction times, low
yields, high temperatures and also require the use of organic
solvents, Lewis acid catalysts and expensive reagents. Thus,
the introduction of new methods using inexpensive reagents
and environmentally-friendly reaction conditions with water
as solvent4 for such functional group transformations is still
required. In continuation of our investigations on oxidation
reactions,5 we explored the oxidation of THP and 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
substrate, without regeneration of DABCO.6,7
Cl
Cl
_
+
N
+
N
_
Cl
Cl
1
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
for 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 the 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 yield was reduced
when a NO2 group was present on the aromatic ring (Table 1,
entry 9). Longer reaction times had no effect on the yield.
A THP ether containing a double bond (Table 1, entry 10)
was 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 just hydrolysed by the reaction but 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 amount which can 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.
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 in 80°C without regeneration of DABCO.
O
Reagent 1
RCHR'OR''
N
C
+
N
R
R'
Water, 50°C
R'' =
SiMe
3
,
O
R or R' = alkyl or aryl
Scheme 1
* Correspondent. E-mail: tajbaksh@umz.ac.ir
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260 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 bp/°C/Torr
Found
Reported11
10a
1
2
20
25
90
92
99–101/760
100–103/760
OTHP
CHO
CHO
10a
OTHP
175–176/760
178–179/760
45–47
CHO
OTHP
3
4
25
30
90
93
44
Cl
Cl
10b
CHO
OTHP
10c
121–122/12
118–121/12
85–88/12
MeO
MeO
5
30
89
85–87/12
OTHP
O
10d
OTHP
O
6
7
35
35
87
88
199–201/760
54
202/760
55–57
10e
OTHP
CHO
Br
Br
O
OTHP
8
9
35
40
84
74
49–51
49–50
10f
OTHP
CHO
103–105
104–106
NO2
NO2
10d
OTHP
CHO
10
11
30
15
91
88
246
248
CHO
OTHP
230–231/760
232–235/760
(CH3)CH
(CH3)CH
10g
OSiMe3
CHO
CHO
12
13
20
30
95
95
99–100/760
100–103/760
178–179/760
10h
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
OSiMe3
O
16
35
90
200–202
201–202
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JOURNAL OF CHEMICAL RESEARCH 2007 261
Table 1 Continued
Entry
Substratea
Productb
Time/min
Yield/%c
M.p./°C or bp/°C/Torr
Reported11
Found
56
10h
OSiMe3
CHO
17
40
87
55–57
OSiMe3
10h
O
18
19
40
55
85
77
49–51
49–50
CHO
OSiMe3
103–105
104–106
NO2
NO2
aThe tetrahydropyranyl and trimethyl silyl 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.
THP ether of 4-chlorobenzyl alcohol (entry 3): Colourless viscous
liquid; H NMR (300 MHz, CDCl3): δ = 1.54–1.89 (m, 6 H, CH2),
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: (1) ease of operation; (2) facile recycling of the DABCO;
(3) excellent yields; (4) environmental consciousness: no
organic solvent is used in the reaction and only a small amount
is needed for the workup.
1
3.52 (d, J = 11.2 Hz, 1 H, OCH2), 3.87 (t, J = 8.4 Hz, 1 H, OCH2),
4.44 (d, J = 12.0 Hz, 1 H, ArCH), 4.67 (br s, 1 H, OCHO), 4.72 (d,
J = 12.4 Hz, 1 H, ArCH), 7.29 (br s, 4 H, ArH) ppm; 13C NMR (300
MHz, CDCl3): δ = 19.4, 25.5, 30.6, 62.1, 68.0, 97.7, 128.3 (2 C),
128.9 (2 C), 133.0, 136.65 ppm; IR (neat): ν = 2943, 2867, 1592,
1464, 1358, 1132, 1075, 1038 cm–1.
4-Chlorobenzaldehyde (entry 3): 1H NMR (300 MHz, CDCl3):
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.
Experimental
All the starting materials were purchased from Fluka and Merck.
All trimethylsilyl and tetrahydropyranyl ethers were known
compounds and were prepared according to described procedures.12
The oxidation products were known compounds and they were
identified by comparison of their physical data, IR and NMR spectra
with those of authentic samples. Yields refer to isolated products
or to their 2,4-dinitrophenyl hydrazones. Melting points were
determined using a Mettler FP 5 apparatus and were 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.
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 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
3-phenylpropanal (entry 14): 1H NMR (300 MHz, CDCl3): δ = 9.61
(d, J = 1.79, 1 H, CHO), 7.3 (m, 5 H, ArH), 2.9 (t, J = 7.08 Hz,
2 H, CH2), 2.5 (m, J = 7.08, 1.79 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.
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 the 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.
TMS ether of 4-nitrobenzyl alcohol (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 = 1253, 1095,844 cm-1.
4-nitrobenzaldehyde (entry 19): 1H NMR (300 MHz, CDCl3):
δ=10.1(s,1H,CHO),7.2–7.9(m,4H,ArH)ppm;13CNMR(300MHz,
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 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 reaction mixture and 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 corresponding carbonyl compound.
Received 16 April 2007; accepted 23 April 2007
Paper 07/4596 doi: 10.3184/030823407X209723
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