Hexamethylenetetramine-Bromine: A Novel Reagent for Selective Regeneration of Carbonyl Compounds from Oximes and Tosylhydrazones

Article abstract of DOI:10.1039/a706884k

Hexamethylenetetramine-bromine (HMTAB) has been found to be an efficient and selective reagent for the mild oxidative cleavage of the C=N of oximes and tosylhydrazones to yield their corresponding carbonyl compounds in good to excellent yields under mild

Full text of DOI:10.1039/a706884k

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1
54 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
Hexamethylenetetramine±Bromine: A Novel Reagent
for Selective Regeneration of Carbonyl Compounds
from Oximes and Tosylhydrazones$%
1998, 154±155$
a
b
b
Babasaheb P. Bandgar,* Shivaji B. Admane and Sandip S. Jare
a
Organic Chemistry Research Laboratory, School of Chemical Sciences,
Swami Ramanand Teerth Marathwada University, Dnyanteerth, Vishnupuri, Nanded-431 602,
PO Box 87, Maharashtra, India
b
Department of Chemistry R.B.N.B. College, Shrirampur-413709, Dist. Ahmadnagar, India
Hexamethylenetetramine±bromine (HMTAB) has been found to be an efficient and selective reagent for the mild
oxidative cleavage of the C1N of oximes and tosylhydrazones to yield their corresponding carbonyl compounds in good
to excellent yields under mild conditions.
There has been considerable growth in interest in the
development of mild methods for the regeneration of car-
bonyl compounds from stable and readily prepared oximes
1
and tosylhydrazones. This is because such derivatives of
carbonyl compounds serve as e€ective protecting groups for
Scheme 1
2
aldehydes and ketones in organic synthesis. Oximes are
also extensively used for the puri®cation and character-
ization of carbonyl compounds. Since oximes can be pre-
solution of hexamethylenetetramine and it has been used
successfully for the oxidation of primary and secondary
3
pared from non-carbonyl compounds, the regeneration
12
of carbonyl compounds from oximes provides an alter-
native method for the preparation of aldehydes and ketones.
Most of the known methods of regenerating carbonyl
compounds from their nitrogen derivatives have several
alcohols to aldehydes and ketones, respectively.
This
yellow±orange, non-hygroscopic, homogenous solid is very
stable at room temperature and is not a€ected by ordinary
exposure to light, air or water and has no o€ensive odour
of bromine or amine. Ease of work-up and the stability of
the reagent make it a safe and convenient source of active
4
±11
limitations.
It is most important to note that most of
the reported methods are suitable for the regeneration
of ketones but not for aldehydes from their oximes and
tosylhydrazones, and that yields are low owing to the over
oxidation of regenerated aldehydes to acids. Therefore it is
desirable that a method which leads to high recoveries of a
wide range aldehydes and ketones should be available.
We now report an ecient and general method for the
e€ective and selective cleavage of the C1N of oximes
and tosylhydrazones with HMTAB under neutral and mild
conditions (Scheme 1).
1
3
bromine.
into easily removable products and presents a convenient
The reagent is transformed during reaction
14±17
alternative to other N-halogenoamines.
Table 1 summarizes the results of various oximes which
underwent oxidative cleavage with HMTAB to form corre-
sponding carbonyl compounds in good yields under mild
conditions. The rate of oxidative cleavage of benzophenone
oximes (entries 12±14) was fast. Even the sterically hindered
ketone oximes (entries 15, 16) successfully underwent
oxidative deoximation with HMTAB to give ketones in
good yields.
Hexamethylenetetramine±bromine complex could be
readily prepared by adding bromine to
a chloroform
Table 1 Oxidative cleavage of oximes with HMTAB in CCl
Reaction conditions
Temp. (T/ 8C) Time (t/h)
60
4
a
b
Yield (%)
Entry
Substrate
Product
1
2
3
4
5
6
7
8
9
4-Chlorobenzaldoxime
4-N,N-Dimethylaminobenzaldoxime
2-Nitrobenzaldoxime
7
4-Chlorobenzandehyde
4-N,N-Dimethylaminobenzaldehyde
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
Salicylaldehyde
Cyclopentanone
Cyclohexanone
Acetophenone
4-Chloracetophenone
4-Methylacetophenone
Benzophenone
4-Bromobenzophenone
4-Chlorobenzophenone
Camphor
76
77
98
87
69
40
86
85
88
84
77
78
90
76
80
87
25
60
60
60
25
25
25
25
60
25
25
25
25
25
25
3
5.3
7
6
4
4
4
3
4
2.5
1.5
2
2
2
3-Nitrobenzaldoximes
4-Nitrobenzaldoximes
Salicylaldehyde oxime
Cyclopentanone oxime
Cyclohexanone oxime
Acetophenone oxime
4-Chloracetophenone oxime
4-Methylacetophenone oxime
Benzophenone oxime
1
1
1
1
1
1
1
0
1
2
3
4
5
6
4-Bromobenzophenone oxime
4-Chlorobenzophenone oxime
Camphor oxime
Menthone oxime
2
Menthone
a
1
Characterized by IR, H NMR and comparison with authentic samples. Isolated yields.
b
*
To receive any correspondence.
The most remarkable advantage of this methodology
is that it is a general method for oxidative cleavage of a
variety of aldoximes and ketone oximes with HMTAB to
give the corresponding carbonyl compounds in good
yields under neutral, and mild conditions, and no trace of
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
%Dedicated to Professor M. S. Wadia on the occasion of his 60th
birthday.

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J. CHEM. RESEARCH (S), 1998 155
4
Table 2 Oxidative cleavage of tosylhydrazones with HMTAB in CCl at 25 8C
a
b
Yield (%)
Entry
Substrate
Reaction time (t/h)
Product
1
2
3
4
5
6
7
8
9
Butanone tosylhydrazone
0.5
2
1.5
2
1.5
5
6
2
2
2.5
0.5
0.5
a-Bromobutanone
4-Chlorobenzandehyde
2,4-Dichlorobenzaldehyde
Furfuraldehyde
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
Salicyladehyde
Cyclopentanone
Cyclohexanone
4-Chloroacetophenone
Benzophenone
74
69
87
60
88
89
98
40
50
81
69
90
4-Chlorobenzaldehyde tosylhydrazone
2,4-Dichlorobenzaldehyde tosylhydrazone
Furfuraldehyde tosylhydrazone
2-Nitrobenzaldehyde tosylhydrazone
3-Nitrobenzaldehyde tosylhydrazone
4-Nitrobenzaldehyde tosylhydrazone
Salicylaldehyde tosylhydrazone
Cyclopentanone tosylhydrazone
Cyclohexanone tosylhydrazone
1
1
1
0
1
2
4-Chloroacetophenone tosylhydrazone
Benzophenone tosylhydrazone
a
1
Characterized by IR, H NMR and comparision with authentic samples. Isolated product.
b
acid was formed owing to over oxidation of regenerated
aldehyde. This procedure is also useful for chemoselective
oxidative deoximation of ketone oximes in preference to
aldoximes.
Oximes or tosylhydrazones in CCl , when stirred at room tem-
perature (25 8C) or boiled under re¯ux with HMTAB, gave the
corresponding carbonyl compounds in good yields.
4
A Typical Procedure.ÐA mixture of 4-bromobenzophenone
oxime (3 mmol) and HMTAB (3.1 mmol) in CCl (10 ml) and 1 ml
4
When
a
mixture of 2,4-dichlorobenzaldoxime and
water was stirred at room temperature (25 8C) for 2 h. After the
reaction was complete (TLC), insoluble hexamethylenetetramine
cyclopentanone oxime or 4-nitrobenzaldoxime and aceto-
phenone oxime or 4-chlorobenzaldoxime and 4-bromo-
benzophenone oxime in CCl
HMTAB at room temperature (25 8C) for a period of
, 3 and 2 h, respectively, the ketoximes cyclopentanone
was removed by ®ltration and washed with CCl
4
(2Â 10 ml);
the CCl layer was dried over anhdrous Na SO . Removal of the
4
2
4
4
was allowed to react with
solvent under reduced pressure gave the product in good yield and
in almost pure form.
4
oxime, acetophenone oxime and 4-bromobenzophenone
oxime underwent chemoselectively oxidative deoximation
giving cyclopentanone (80%), acetophenone (86%) and
bromobenzophenone (89%) whereas the aldoximes 2,4-
dichlorobenzaldoxime, 4-nitrobenzaldoxime and 4-chloro-
benzaldoxime were recovered unchanged.
Received, 23rd September 1997; Accepted, 14th November 1997
Paper E/7/06884K
References
1
Y. H. Kim, J. C. Jung and K. S. Kim, Chem. Ind., 1992, 31 and
references cited therein.
Table 2 shows the oxidative cleavage of tosylhydrazones
with HMTAB in CCl to give the corresponding carbonyl
4
2
S. R. Sandler and W. Karo, Organic Functional Group
Preparations, Academic Press, London, 1989, p. 430; T. W.
Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, Wiley, New York, 1991.
compounds in good yields. The aliphatic ketone tosylhydra-
zone shown in entry 1 underwent oxidative cleavage with
HMTAB to give the a-bromoketone due to subsequent
bromination of the regenerated ketone. The present pro-
cedure is general for the oxidative cleavage of aliphatic,
aromatic, heteroaromatic and cyclic tosylhydrazones and
no trace of acid was formed owing to over oxidation of
regenerated aldehyde. In contrast recently reported method-
ology, involving the use of 70% TBHP, is suitable only for
the deprotection of ketone tosylhydrazones and failed
for aliphatic and heteroaromatic tosylhydrazones. In this
connection, the present methodology is important and
noteworthy.
3
4
G. W. Kabalka, R. D. Pace and P. P. Wadgaonkar, Synth.
Commun., 1990, 20, 2453 and references cited therein.
R. E. Donaldson, J. C. Saddler, S. Byrn, A. T. Mckenzie and
P. L. Fuch, J. Org. Chem., 1983, 48, 2167 and references cited
therein.
5 J. C. Lee, K. H. Kwak, J. P. Hwang, Tetrahedron Lett., 1990,
3
2
1, 6677; B. Tamani, and N. Goudarizian, Eur. Polym. J., 1992,
8, 1035.
6
D. P. Curran, J. F. Brill and D. M. Rakiewicz, J. Org. Chem.,
984, 49, 1654; J. Drabowicz, Synthesis, 1990, 125; E. J. Corey,
P. B. Hopkines, S. Kim, S. Yoo, K. P. Nambiar and J. R. Falk,
1
J. Am. Chem. Soc., 1979, 101, 7131.
7 P. Laszlo and E. Polla, Synthesis, 1985, 439.
8
G. A. Olah, Q. Liao, C. S. Lee and G. K. Suryaprakash,
Synlett, 1993, 427.
R. Joseph, A. Sudalai and T. Ravindranthan, Tetrahedron Lett.,
In conclusion, we hope that the present deprotection
methodology of oximes and tosylhydrazones ®nds wide
application in organic systhesis because of the simplicity of
work-up and use of readily prepared oxidant (HMTAB)
under neutral and mild conditions.
9
1994, 35, 5493; P. Kumar, V. R. Hegde, B. Pandey and
T. Ravindranathan, J. Chem. Soc., Chem. Commun., 1993, 1553.
10 N. B. Barhate, A. S. Gajare, R. D. Wakharkar and A. Sudalai,
Tetrahedron Lett., 1997, 38, 635.
11 D. H. R. Barton, D. J. Lester and S. V. Ley, J. Chem. Soc.,
Perkin Trans. 1, 1980, 1212.
Experimental
Preparation of the Hexamethylenetetramine±Bromine Complex.Ð
A solution of bromine (20.0 g, 125 mmol) in CHCl (100 ml) was
3
12 I. Yavari and A. Shaabani, J. Chem. Res. (S), 1994, 274.
13 For a review of positive halogens, see A. Foucaud, Chem.
Halides, Pseudo-halides, Azides, 1983, 1, 441.
14 S. Kondo, M. Ohira, S. Kawasoe, H. Kunisada and Y. Yuki,
J. Org. Chem., 1993, 58, 5003.
15 F. Minisci, E. Vismara, F. Fontana, E. Platone and J. Faraci,
J. Chem. Soc., Perkin Trans. 2, 1989, 123.
16 L. K. Blair, S. Hobbs, N. Bagnoli, L. Husband and N. Badika,
J. Org. Chem., 1992, 57, 1600.
added dropwise with stirring to a solution of hexamethylene-
tetramine (8.5 g, 60 mmol) in chloroform (100 ml). A yellow solid
separated out as the bromine was taken up. The mixture was stirred
for an additional 30 min, then the yellow solid was collected by
vacuum ®ltration. Yield: 25.5 g (92%), mp = 170±175 8C (dec.);
�
1
ꢀ
1
1
max/cm (KBr) 1460, 1360, 1325, 1045, 840 and 782 (Found: C,
5.9; H, 2.7; N, 12.8. C 12Br requires C, 15.87; H, 2.63; N,
2.68%). The active bromine content of this complex is 1.5 mol Br
6
H
4 4
N
2
17 R. E. Banks, S. N. Mohialdin-Kha€af, G. S. Lal, I. Sharif and
R. G. Syvert, J. Chem. Soc., Chem. Commun., 1992, 595.
per mol of the complex, as determined by thiosulfate titrations.