Unusual reaction of chloramine-T with araldoximes

Article abstract of DOI:10.1021/jo020473j

Reaction of araldoximes with 4 equiv of chloramine-T in refluxing methanol produces N-(p-tolyl)-N-(p-tosyl)benzamides via addition of 2 equiv of chloramine-T to the intermediate nitrile oxide followed by extrusion of sulfur dioxide.

Full text of DOI:10.1021/jo020473j

Un u su a l Rea ction of Ch lor a m in e-T w ith
Ar a ld oxim es
V. Padmavathi,*,† K. Venugopal Reddy,†
A. Padmaja,† and P. Venugopalan‡
Department of Chemistry, Sri Venkateswara University,
Tirupathi 517502, India, and Department of Chemistry,
Punjab University, Chandigarh 160014, India
vkpuram2001@yahoo.com
Received J uly 16, 2002
methanol for 48 h followed by purification on a silica gel
column furnished two compounds, 4a and 5 (Scheme 1).
Abstr a ct: Reaction of araldoximes with 4 equiv of chlor-
amine-T in refluxing methanol produces N-(p-tolyl)-N-(p-
tosyl)benzamides via addition of 2 equiv of chloramine-T to
the intermediate nitrile oxide followed by extrusion of sulfur
dioxide.
SCHEME 1
Chloramine-T (1), a representative example of N-
halogeno-N-metallosulfonamides, is a versatile reagent
in organic synthesis.1,2 It is established that in solution
chloramine-T exhibits a series of equilibria. It reacts with
a wide variety of functional groups effecting an array of
transformations because of its ability to act as source of
different species, such as (a) chloronium ion; (b) hypo-
chlorite; (c) N-anions, which act both as bases and nu-
cleophiles; (d) tosylnitrene, etc.1 One of the most com-
monly exploited reactions of chloramine-T is oxidation,
as it is a very good oxidizing agent in both acidic and
basic media.2 Chloramine-T has been used for the in situ
oxidation of oximes and hydrazones of aldehydes to
generate the nitrile oxides and nitrile imines (eq 1),
respectively.3 Synthesis of a variety of isoxazolines and
pyrazolines have been developed via the 1,3-dipolar
cycloadditions of olefins with the in situ generated nitrile
oxides and nitrile imines (eq 2).4 In 1989, Hassner and
Rai5 reported an improved procedure via preformation
of a stable nitrile oxide from the corresponding oxime and
1 equiv of chloramine-T in ethanol and subsequent
reaction with olefins. As a continuation of our interest
in the generation of multi-heterocyclic systems via 1,3-
dipolar cycloaddition reactions of nitrile oxides and nitrile
imines to a variety of olefins,6 we have investigated the
reaction of araldoxime 2a and 1,5-diphenyl-1,4-penta-
dien-3-one (3) in the presence of an excess of chloramine-
T. However, in contrast to the expected isoxazoline, it
resulted in the formation of an unusual product,7 and
herein we describe the details of these investigations.
Reaction of p-chlorobenzaldoxime (2a ) with 2 equiv of
chloramine-T (1) in the presence of dienone 3 in refluxing
The polar compound 5 was readily identified as p-
toluenesulfonamide, the common end product in the
oxidation reactions with chloramine-T.
Spectral analysis of the less polar compound 4a readily
indicated the absence of incorporation of the dienone 3
in the product. To substantiate further, the reaction was
carried out in the absence of any olefin, which also
generated the same mixture of compounds 4a and 5. It
was found that presence of 4 equiv of chloramine-T
furnishes optimal yield of 4a . The IR spectrum of 4a
exhibited the presence of tosyl and amide groups. The
1H and 13C NMR spectra clearly showed the presence of
three 1,4-disubstituted benzene moieties. Presence of two
1
aromatic methyl groups (δ 2.45 and 2.32 ppm) in the H
NMR spectrum suggested the incorporation of two mol-
ecules of chloramine-T and one molecule of oxime in the
product 4a , which is further supported from its elemental
analysis. The presence of an amide group was further
supported by the presence of the carbonyl carbon reso-
nance at δ 168.6 ppm in the 13C NMR spectrum. Presence
of an upfield AB quartet at δ 7.07 and 6.97 ppm due to
one of the benzene rings suggested a deep-seated change.
Hence, the structure of the product 4a was solved by
X-ray analysis. Good single crystals of 4a were grown
(6) (a) Padmavathi, V.; Reddy, A. V. B.; Sumathi, R. P.; Padmaja,
A.; Reddy, D. B. Indian J . Chem. 1998, 37B, 1286. (b) Padmavathi,
V.; Sumathi, R. P.; Reddy, A. V. B.; Reddy, D. B. Heterocycl. Commun.
1998, 4, 163. (c) Padmavathi, V.; Sumathi, R. P.; Babu, N. C. J . Chem.
Res. 1999, 610. (d) Padmavathi, V.; Sumathi, R. P.; Balaiah, A.;
Padmaja, A.; Reddy, D. B. Phosphorus, Sulfur Silicon 2000, 160, 61.
(e) Padmavathi, V.; Sumathi, R. P.; Reddy, K. V.; Reddy, A. S.; Reddy,
D. B. Synth. Commun. 2000, 30, 4007. (f) Padmavathi, V.; Reddy, K.
V.; Padmaja, A.; Reddy, D. B. Synth. Commun. 2002, 32, 1227; (g)
Padmavathi, V.; Reddy, K. V.; Balaiah, A.; Reddy, T. V. R.; Reddy, D.
B. Heteroat. Chem. 2002, 13, 6.
† Sri Venkateswara University.
‡ Punjab University.
(1) Campbell, M. M.; J ohnson, G. Chem. Rev. 1978, 78, 65.
(2) Agarwal, M. C.; Upadhyay, S. K. J . Sci. Ind. Res. 1990, 49, 13.
(3) (a) Rai, K. M. L.; Hassner, A. Synth. Commun. 1997, 27, 467.
(b) Rai, K. M. L.; Hassner, A. Indian J . Chem. 1997, 36B, 242. (c) Rai,
K. M. L.; Hassner, A. Synth. Commun. 1989, 19, 2799.
(4) Peter A. W. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; Vol. 4, p 1111.
(5) Hassner, A.; Rai, K. M. L. Synthesis 1989, 57.
(7) To the best of our knowledge there is no report in the literature
on the formation of such an unusual product in the reaction of oximes
with chloramine-T.
10.1021/jo020473j CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/09/2003
J . Org. Chem. 2003, 68, 1567-1570
1567

SCHEME 2
SCHEME 3
F IGURE 1. X-ray structure of 4a .
TABLE 1.
a
b
Tol ) 4-methylphenyl; Ts ) 4-methylphenylsulfonyl. Eight
equivalents of 1 was employed. c Melting points are uncorrected.
oxime moieties of the dioxime 2f to produce the bisamide
4f. The reaction proceeded even with the pyridine carb-
aldoxime. Analogous to phenolic and anilino nitroso
compounds which do not react with chloramine-T,8
compounds containing a chloro substituent at the ortho
position of the oxime group (Scheme 2) failed to produce
the product 4 and instead generated the iminol ethers
6a ,b, indicating the intermediacy of a nitroso compound
in the reaction.
from methanol and subjected to X-ray diffraction analy-
sis, which unambiguously established the structure of the
product 4a as N-(4-tolyl)-N-(4-toluenesulfonyl)-4-chlo-
robenzamide, which was totally unexpected. Perspective
view of the X-ray structure of 4a is depicted in Figure 1.
To check the generality of the reaction, various aral-
doximes were treated with 4 equiv of chloramine-T in
refluxing methanol. The results are summarized in Table
1. The reaction proceeded more readily when electron-
withdrawing groups are present in the benzene ring. It
is worth noting that the reaction proceeded with both the
(8) Parrar, W. V.; Gulland, J . M. J . Chem. Soc. 1944, 368.
1568 J . Org. Chem., Vol. 68, No. 4, 2003

TABLE 2. Cr ysta l Da ta a n d Str u ctu r e Refin em en t for Am id e 4a
identification code
empirical formula
formula weight
sv1
C21H18ClNO3S
399.87
temperature
293(2) K
Mo KR, 0.71073 Å
monoclinic, P21/c
radiation used, wavelength
crystal system, space group
unit cell dimensions
a ) 8.311(1) Å
R ) 90°
â ) 92.25(1)°
γ ) 90°
b ) 10.723(1) Å
c ) 22.036(2) Å
volume
1962.3(3) Å3
Z, calculated density
absorption coefficient
F(000)
4, 1.354 Mg/m3
0.322 mm-1
832
crystal size
θ range for data collection
scan type
scan speed
scan range (ω)
background measurement
0.29 × 0.25 × 0.19 mm
1.85-24.50°
2θ-θ
variable, 2.0-60.0°/min in ω
0.86° plus KR separation
stationary crystal and stationary counter at the beginning
and end of scan, each for 25.0% of total scan time
0 e h e 9, -12 e k e 0, -25 e l e 25
3497
index ranges
reflections collected
independent reflections
refinement method
3253 [R(int) ) 0.0150]
full-matrix least-squares on F2
3253/0/245
data/restraints/parameters
goodness-of-fit on F2
1.024
weighting scheme
1/[σ2(Fo2) + (0.0447P)2 + 0.47P], P ) (max(Fo2,0) + 2*Fc2)/3
13.28:1
data-to-parameter ratio
final R indices, 2572 reflections [I > 2σ(I)]
R indices (all data)
extinction coefficient
largest diff. peak and hole
R1 ) 0.0360, wR2 ) 0.0917
R1 ) 0.0488, wR2 ) 0.0996
0.0060(7)
0.160 and -0.221 e‚Å-3
methanol (25 mL) at room temperature. The reaction mixture
was refluxed for 48 h, and the inorganic salts were filtered off.
The filtrate was concentrated, and the residue was extracted
with dichloromethane. The organic extract was washed with
water and brine and dried over anhydrous Na2SO4. Evaporation
of the solvent and purification of the residue by column chro-
matography (silica gel) using ethyl acetate-hexane (1:3) as
eluent furnished N-(4-tolyl)-N-(4-tosyl)-4-chlorobenzamide 4a
(0.072 g, 28%) and the tosyl amide 5 (0.270 g, 61%), mp.134-
136 °C (lit. 137-138 °C). Da ta for 4a : mp 186-187 °C; IR (neat)
νmax cm-1 1696, 1363, 1260, 1185, 1168, 1083; 1H NMR (300
MHz, CDCl3 + CCl4) δ 7.79 (2 H, d, J ) 8.4 Hz), 7.39 (2 H, d,
J ) 8.4 Hz), 7.29 (2 H, d, J ) 8.4 Hz), 7.14 (2 H, d, J ) 8.4 Hz),
7.07 (2 H, d, J ) 8.1 Hz), 6.99 (2 H, d, J ) 8.1 Hz), 2.45 (3 H, s),
2.32 (3 H, s); 13C NMR (75 MHz, CDCl3 + CCl4) δ 168.6 (C),
144.6 (C), 139.3 (C), 138.1 (C), 135.4 (C), 134.8 (C), 132.3 (C),
131.0 (2 C, CH), 130.1 (2 C, CH), 130.0 (2 C, CH), 129.7 (2 C,
CH), 129.2 (2 C, CH), 128.4 (2 C, CH), 21.8 (CH3), 21.3 (CH3).
Anal. Calcd for C21H18ClNO3S: C 63.07; H 4.53; N 3.50. Found:
C 62.95; H 4.52; N 3.22.
A tentative mechanism, via the nitrile oxide 7, for the
formation of the product 4 is depicted in Scheme 3. First,
chloramine-T oxidizes the oxime 2a to the nitrile oxide
7. Addition of chloramine-T to the nitrile oxide 7 followed
by elimination of chloride results in the formation of the
nitroso compound 8, which is stabilized when a chloro
substituent is present at ortho position and led to the
formation of the iminol ethers 6. It is well-established
that chloramine-T does not add to phenolic and anilino
nitroso compounds.8 In the absence of a stabilizing group
at the ortho position, addition of one more molecule of
chloramine-T to the nitroso group in 8 generates the
intermediate 9,8 which undergoes an intramolecular
Friedel-Crafts type reaction leading to the formation of
the intermediate 10. Addition of water to 10 leads to
chloro diazo intermediate 11 with the loss of sulfur
dioxide. Finally loss of nitrogen and chloride ion trans-
forms the intermediate 11 into 4. A tentative mechanism
for the formation of 5 is also shown in Scheme 3.
In conclusion, we have discovered an unusual reaction
of chloramine-T with oximes, which is unprecedented in
the literature. Reaction of an araldoxime with 4 equiv of
chloramine-T furnishes N-(4-tolyl)-N-(4-tosyl)benzamide
via addition of two molecules of chloramine-T to the
intermediate nitrile oxide with extrusion of one molecule
of sulfur dioxide. A probable mechanism based on a
nitroso intermediate is proposed. Formation of the amides
4 in the present studies points to the limitation of the
utility of chloramine-T as an oxidant for the generation
of nitrile oxides from aldoximes.
R ea ct ion of 2,4-Dich lor ob en za ld oxim e w it h Ch lor -
a m in e-T. Chloramine-T‚3H2O (0.845 g, 3.0 mmol) was added
to a solution of the oxime 2g (0.142 g, 0.75 mmol) in methanol
(25 mL) at room temperature. It was refluxed for 48 h, and the
inorganic salts were filtered off. The filtrate was concentrated,
and the residue was extracted with dichloromethane. The
organic extract was washed with water and brine and dried over
anhydrous Na2SO4. Evaporation of the solvent and purification
of the residue by column chromatography (silica gel) using ethyl
acetate-hexane (1:3) as eluent furnished the iminol ether 6a
(0.058 g, 26.5%) and the tosyl amide 5 (0.306 g, 51.2%). Da ta
for 6a : mp 138-140 °C; IR (neat) νmax cm-1 1620, 1582, 1323,
1160, 1092, 681; 1H NMR (300 MHz, CDCl3 + CCl4) δ 7.70 (2 H,
d, J ) 8.4 Hz), 7.40 (1 H, d, J ) 7.8 Hz), 7.39 (1H, s), 7.35 (1 H,
d, J ) 8.4 Hz), 7.24 (2 H, d, J ) 7.8 Hz), 3.99 (3 H, s), 2.43 (3 H,
s); 13C NMR (75 MHz, CDCl3 + CCl4) δ 167.8 (C), 143.4 (C), 138.3
(C), 137.3 (C), 132.2 (C), 130.7 (C), 130.2 (CH), 129.5 (CH), 129.3
(2 C, CH), 127.3 (2 C, CH), 126.9 (CH), 56.2 (CH3), 21.7 (CH3).
Exp er im en ta l Section
Gen er a l P r oced u r e. Rea ction of 4-Ch lor oben za ld oxim e
w ith Ch lor a m in e-T. Chloramine-T‚3H2O (0.726 g, 2.6 mmol)
was added to a solution of the oxime 2a (0.1 g, 0.640 mmol) in
Anal. Calcd for
C15H13Cl2NO3S: C 50.29; H 3.66; N 3.91.
Found: C 50.13; H 3.60; N 3.70.
J . Org. Chem, Vol. 68, No. 4, 2003 1569

X-r a y An a lysis of 4a . Good single crystals of 4a were grown
from methanol, and a single crystal with dimension 0.29 ×
0.25 × 0.19 mm was mounted along the largest dimension and
used for data collection. The intensity data were collected on a
single-crystal diffractometer equipped with molybdenum sealed
tube (λ ) 0.71073 Å) and highly oriented graphite monochro-
mator. The lattice parameters and standard deviations were
obtained by least-squares fit to 40 reflections (10.62° < 2θ <
30.36°). The data were collected by 2θ-θ scan mode with a
variable scan speed ranging from 2.0° to a maximum of 60.0°/
min. The data were corrected for Lorentz and polarization
factors. The structure was solved by direct methods using
SHELX-979 package and also refined using the same. A weight-
ing scheme of the form w ) 1/[σ2(Fo2) + (aP)2 + bP] with a )
0.0447 and b ) 0.47 was used. The refinement converged to a
final R value of 0.0360. Details of X-ray analysis are given in
Table 2.
Ack n ow led gm en t. We thank Professor D. Bhaskar
Reddy, Emeritus Professor of UGC, for his helpful
discussions and suggestions. K.V.R. thanks C.S.I.R.
New Delhi for the award of a senior research fellowship.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 4a -f and 6a ,b and X-ray crystal-
lographic data for compound 4a . This material is available free
of charge via the Internet at http://pubs.acs.org.
(9) Sheldrick, G. M. SHELX-97, Program for the solution and
refinement of crystal structures; University of Go¨ttingen: Go¨ttingen,
Germany, 1997.
J O020473J
1570 J . Org. Chem., Vol. 68, No. 4, 2003