Cleavage of C=N derivatives and oxidation of thiols in water under neutral conditions with 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bischloride

Article abstract of DOI:10.3184/030823407X240890

1,4-Diazabicyclo[2,2,2]octane (DABCO) is easily chlorinated and gives a complex which efficiently converts aliphatic and aromatic oximes, phenylhydrazones and semicarbazones to their corresponding carbonyl compounds in water at 50°C in high yield. This reagent can also be used for conversion of thiols to their compounding disulfide under the same reaction conditions. DABCO is quantitatively recovered which can be rechlorinated and reused several times.

Full text of DOI:10.3184/030823407X240890

486 RESEARCHꢀPAPERꢀ
AUGUST, 486–489
JOURNAL OF CHEMICAL RESEARCH 2007
Cleavage of C=N derivatives and oxidation of thiols in water under neutral
conditions with 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bischloride
Mahmood Tajbakhsh* and Setareh Habibzadeh
Department of Chemistry, Mazandaran University, Babolsar, Iran
1,4-Diazabicyclo[2,2,2]octane (DABCO) is easily chlorinated and gives a complex which efficiently converts aliphatic
and aromatic oximes, phenylhydrazones and semicarbazones to their corresponding carbonyl compounds in water
at 50°C in high yield. This reagent can also be used for conversion of thiols to their compounding disulfide under the
same reaction conditions. DABCO is quantitatively recovered which can be rechlorinated and reused several times.
Keywords: 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bischloride, oximes, phenylhydrazones, semicarbazones, deprotection,
thiols, oxidation
Oximes, phenylhydrazones and semicarbazones are
utilised for the purification and characterisation of
carbonyl compounds and as protecting groups for carbonyl
compounds.1 Their synthesis from noncarbonyl compounds
provides an alternative pathway to aldehydes and ketones.
Therefore, the regeneration of carbonyl compounds from
their C=N analogues has received much attention.2-4 Although
some of the known methods are very efficient,5-10 most of
them require drastic conditions. Disulfides play important
roles in the biological and chemical processes.11 Oxidation of
thiols is the common method for disulfide synthesis mainly
because a large number of thiols are commercially available
and are easily synthesised.12,13 Organic reactions in water,
are of current interest, because water is an easily available,
economical, safe, and environmentally benign solvent.14
1,4-diazoniabicyclo[2,2,2]octane bischloride17 as a new
efficient and reusable reagent for the cleavage of oximes,
phenylhydrazones, and semicarbazones in water and the
oxidation of thiols (Scheme 1).
Very recently we have used this reagent for oxidation of
alcohols under microwave irradiations and the oxidative
deprotection of tetrahydropyranyl and trimethylsilyl ethers in
water.17
We have studied different substrate/reagent ratio and found
that 1:0.5 is suitable for these transformations. Several
oximes were deoximated to their corresponding aldehydes and
ketones in a good to excellent yield in water. Overoxidation
of the aldehydes to their carboxylic acids was not observed.
The results are shown in Table 1.
As indicated, aromatic oximes bearing both electron
withdrawing and electron releasing groups on the ring were
deoximated with this reagent within 15–45 minute in water
(Table 1, entries 1–7). Aliphatic oximes (Table 1, entries 8–10)
were also deoximated in high yield. The a,b-unsaturated
acroleinoxime was converted to acrolein without affecting
Results and discussion
In our ongoing program to find new oxidising reagents,15-16
we now report the preparation of complex 1,4-dichloro-
Cl
Cl
_
+
N
+
N
N
Oximes, hydrazones, semicarbazones
Water, 50°C
N
Carbonyl compounds
+
Cl
Cl
Cl2
Scheme 1
Table 1 Regeneration of carbonyl compounds from their corresponding oximes, semicarbazones and phenylhydrazones in water
Entry
Substrate
Producta
Time/min
Yield/%
M.p./°C or b.p./°C Torr
Found
174–177
Reported18
NOH
NOH
CH
CH
CHO
1
2
20
20
95
176–179/760
CHO
90
88
35–38
46–48
35–37
45–47
OMe
CH
OMe
CH
NOH
O
3
4
15
25
Cl
Br
Cl
Br
Me
C
COMe
NOH
85
48
49–51
* Correspondent. E-mail: tajbaksh@umz.ac.ir
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JOURNAL OF CHEMICAL RESEARCH 2007 487
Table 1 Continued
Entry Substrate
Producta
Time/min
Yield/%
M.p./°C or b.p./°C Torr
Found
Reported18
Me
C
COMe
NOH
5
15
90
116–117
117–119
Ph
Ph
Ph
C
COPh
NOH
6
7
45
20
89
85
50
49–50
44–48
MeO
CHO
MeO
CH
NOH
45–47
MeO
MeO
O
NOH
8
9
40
15
83
90
176
175–177
CH3CH2CH2CH2CH
CH3CH2CH2CH2CHO
O
NOH
101–104/760
100–103/760
NOH
10
11
12
15
15
20
92
89
91
126–131/760
124–128/11
178/760
127–131/760
125–128/11
178–179/760
Ph
CH
CH CH NOH
NNH
PhCH
CHCHO
CHO
CH
CHO
MeO
N NH
NO2
MeO
CH
13
14
18
20
90
87
118–122/12
118–121/12
CH
O
NO2
NO2
CH
NNH
177–179/760
178–179/760
NO2
CHO
O
CH
N
NH
15
25
86
211–214/760
213–215/760
Cl
Cl
NO2
NO2
N
NH
16
17
25
15
92
86
155/760
101
154–156/760
100–103
NO2
O
CH
NO2
CH
NNH
OH
OH
NO2
CH
O
MeO
MeO
NO2
C
H
NNH
18
19
15
10
95
85
116–120/12
118–121/12
202/760
CH3
COCH3
C
NNHCONH2
NNHCONH2
202–203/760
CH
O
CH
20
21
22
10
15
15
90
89
87
35
35–37
45–47
OMe
OMe
O
CH
NNHCONH2
CH
44–46
Cl
Cl
Me
O
147–150/760
149–152/760
NNHCONH2
NNHCONH2
C
Me
C
COMe
23
20
93
117
117–119
Ph
Ph
aAll products were characterised spectroscopically (1H NMR, IR) and showed physical and spectral data in accordance with their
expected structure and by comparison with authentic sample.
bThe yields refer to isolated products.
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488 JOURNAL OF CHEMICAL RESEARCH 2007
the carbon–carbon double bond (Table 1, entry 11). Even the
sterically-hindered benzophenone oxime and camphor oxime
were converted to their corresponding carbonyl compounds
with a longer reaction time. Similarly aromatic and aliphatic
phenylhydrazones and semicarbazones were deprotected
in high yield in water within 10–25 minute (Table 1, entries
12–23).
Several thiols were also oxidised to their corresponding
disulfides in a good to excellent yield in water (Scheme 2).
As shown in the Table 2 aliphatic and aromatic thiols were
oxidised in water in excellent yield (Table 2, entries 1–9).
Aliphatic thiols (Table 2, entries 1–3), aromatic thiols (Table 2,
entries 4–8) and benzylthiol (Table 2, entry 9) underwent
oxidation with 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane
bischloride in water to afford the corresponding disulfides
in high yields within very short reaction times. These mild
conditions without any catalysts and any co-solvent allow the
oxidation of thiols to disulfide. Under these reaction conditions
sulfides are not oxidised. Thus phenyl methyl sulfide did
not give any oxidised product even after 4 hours (Table 2,
entry 10).
Cl
Cl
_
+
N
N
Water, 50°C
+
N
+
+
SR
RS
RSH
N
Cl
Cl
Cl2
R= Aliphatic or aromatic
Scheme 2
Table 2 Oxidation of thiols to disulfides with the 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bischloride
Entry
Substrate
Producta
Time/min
Yield/%
M.p./°C or b.p./°C Torr
Found
Reported18
S
SH
SH
1
2
25
25
98
113/19
114–115/1919a
92/76019b
S
S
96
90
91–92/760
S
S
3
55
143–144
44–45
144–14519b
SH
S
S
CH3
CH3
4
45
96
4519b
S
SH
H3C
MeO
MeO
Cl
S
5
6
7
18
35
45
90
92
93
44
73
43–4419c
72–7519d
S
SH
OMe
Cl
S
S
SH
Cl
O2N
O2N
S
177–17819e
S
176–177
SH
NO2
SH
S
142–14519f
71–7219c
S
8
30
93
143
SCH2
CH2SH
9
40
91
70–71
N.R.
CH2S
S
CH3
10
N.R.
240
aAll products were characterised spectroscopically (1H NMR, IR) and showed physical and spectral data in accordance with their
expected structure and by comparison with authentic sample.
bThe yields refer to isolated products.
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JOURNAL OF CHEMICAL RESEARCH 2007 489
Regeneration of 1,4-diazabicyclo [2,2,2] octane(DABCO)
The aqueous layer (1) from above procedure was further treated with
10% sodium bicarbonate solution (2 ¥ 10 ml) and 1,4-diazabicyclo
[2,2,2] octane (DABCO) was extracted with ether (2 ¥ 10 ml).
The ether layer was dried over MgSO4, and evaporated to give
pure 1,4-diazabicyclo [2,2,2] octane (0.21 g, 95%), which can be
chlorinated and reused several times.
The 1,4-diazabicyclo[2,2,2]octane which is formed in
this reactions, is recovered almost quantitatively and can be
rechlorinated and reused several times. Moreover, since there
is the possibility of recovering and reusing the DABCO and
water as a solvent, this method might be useful in large-scale
synthesis. We have carried out the oxidation of an oxime,
phenylhydrazone, semicarbazone and thiol under our optimum
reaction conditions on a larger scale and obtained almost the
same yields as in the small-scale reaction.
Received 11 August 2007; accepted 21 August 2007
Paper 07/4791 doi: 10.3184/030823407X240890
References
In conclusion, this paper describes the use of 1,4-dichloro-
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Preparation of 1,4-dichloro-1,4-diazoniabicyclo[2,2,2]octane bischloride
Chlorine gas was bubbled for 10 min at room temperature through
a solution of 1,4-diazabicyclo[2,2,2]octane (DABCO) (6.72 g,
60 mmol) in chloroform (100 ml). The solvent was evaporated under
reduced pressure to afford almost pure product (14.94 g, 98%),
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General procedure for the cleavage of C=N bonds and the oxidation
of thiols
An appropriate substrate (4 mmol) and 1,4-dichloro-1,4-diazoniabi-
cyclo[2,2,2]octane bischloride (0.51 g, 2.0 mmol) was added to H2O
(12 ml) in a flask. The reaction mixture (pH = 7) was warmed to
50°C. After completion of the reaction (TLC), ether was added to the
reaction mixture and the extract was washed with a solution of 1%
HCl (1 ¥ 10 ml). The aqueous layer (1) was separated and the organic
layer was washed with 3% sodium bicarbonate (2 ¥ 10 ml) and water
(1 ¥ 10 ml) respectively. The organic solution was dried over MgSO4,
filtered and evaporated to dryness under reduced pressure to afford
the corresponding carbonyl compound or disulfide.
PAPER: 07/4791