Facile cleavage of N-arylsulfonyl bond of N-arylsulfonyl-imidazolidinone with magnesium in methanol

Article abstract of DOI:10.1002/jhet.5570410514

Cleavage of N-arylsulfonyl bond in N-arylsulfonylimidazolidinones is best carried out selectively with magnesium in methanol.

Full text of DOI:10.1002/jhet.5570410514

Sep-Oct 2004
737
Facile Cleavage of N-Arylsulfonyl Bond of N-Arylsulfonyl-
imidazolidinone with Magnesium in Methanol
Upender K Nadir* and R. Vijaya Krishna
Department of chemistry, Indian Institute of Technology Delhi, Hauz Khas,
New Delhi-110016, India. E-mail: ukn@chemistry.iitd.ac.in, FAX: +91-11-26581102
Received March 2, 2004
Cleavage of N-arylsulfonyl bond in N-arylsulfonylimidazolidinones is best carried out selectively with
magnesium in methanol.
J. Heterocyclic Chem., 41, 737 (2004).
Table 1
Introduction.
Desulfonylation of N-Arylsulfonyl Imidazolidinones with
Sulfonyl groups are often used as protecting groups for
nitrogen heteroaromatics like pyrroles, indoles, pyrazoles,
imidazoles, etc., they are also frequently employed to acti-
vate aziridines for reaction with nucleophiles [1]. In all
these cases, the N-sulfonyl group needs to be cleaved sub-
sequently. However it is not always easy to remove the
N-sulfonyl group. Even though a wide variety of synthetic
methods for the cleavage of the N-S bond are available [2],
the selection of the proper reagent depends on the nature of
other groups present in the product and their susceptibility
to the conditions chosen. In general harsh reaction condi-
tions [3] and long reaction times need to be avoided.
In this paper, we present our efforts to find a general yet
mild method for the selective desulfonylation of imidazo-
lidinones that leaves the five-membered ring intact.
R e c e n t l y, excellent results in the reduction of alkyl
sulfones have been achieved by using magnesium in
methanol as the cleaving agent [4]. However this method
has not been widely used, and only a few examples have
been briefly reported [5]. In any case no example pertain-
ing to imidazolidinones are known.
We have reported a regio- [6] and stereo-selective [7]
synthesis of imidazolidinones based on the reaction of N-
arylsulfonylaziridines with isocyanates catalyzed by
sodium and lithium iodides. In order to utilize these imida-
zolidinones to prepare enantiomerically pure diamines and
diamino-acids we required a mild method for cleavage of
the N-arylsulfonyl bond without affecting an ester or ben-
zyl group. Here we report development of a facile method
to do this.
Magnesium/Methanol
Entry
R
R
R
3
Mg
(eq) (h)
Time Temp
Yield [a]
(%)
1
2
1
2
3
4
5
6
7
CH
CH
CH
H
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
8
4
8
8
8
8
8
24
8
8
8
8
rt
42(50)
30(60)
78
80
78
3
3
3
reflux
reflux
reflux
reflux
reflux
reflux
Cl
CH
CH
CH Ph
Ph
8
6
81
65
3
3
2
COOMe
Values in parentheses are recovery yield of starting compound; [a] isolated
through column chromatography (silica gel, benzene/ethylacetate).
liquid NH3 [9] yielded similar results. With tetrabutylam-
monium fluoride [10] (TBAF), 1a was converted to 2a in
diminished yield (30%). All these methods gave a complex
mixture with the ester imidazolidinone 1e, from which no
pure product could be isolated. With SmI2 [11] no reaction
occurred and the starting imidazolidinone could be recov-
ered unchanged.
Table 2
Desulfonylation of N-Arylsulfonyl Imidazolidinones with
Various Reducing Agents like Sodium Naphthalenide,
Na/liquid NH TBAF, and SmI
3,
2
Entry
Reactant (3)
R
Conditions
Product Yield [a]
(4)
57
53
30
(5)
17
26
1
2
3
4
5
6
7
H
A
A
B
B
C
C
D
Results and Discussion.
COOMe
H
COOMe
H
COOMe
H
[b]
[b]
[b]
Deprotection of imidazolidinones 1 a - c could be
achieved using magnesium turnings (8 equiv.) in methanol
at the reflux temperatures for 8 hours. The desired imida-
zolidinone 2a was obtained in 78-81% yields. Under these
conditions, the benzyl and methoxycarbonyl groups were
unaffected as shown by conversion of 1d to 2b and 1e to
2c (Scheme 1 and Table 1).
Other reductive methods were less effective (Table 2).
Thus with sodium naphthalenide [8] 1a gave, besides the
product 2a, the ring opened product 3a (17 %). Sodium in
No reaction [c]
[a] Isolated through column chromatography(silica gel, benzene/EtOAc);
[b] non analyzed complex mixture of compounds; [c] starting material
was recovered. Conditions A: Na metal (5 mmole), Naphthalene (5.5
mmole), DME (5 ml), imidazolidinone (0.25 mmole) in DME (1 ml), -78
°C, 5 min; Conditions B: Na metal (10 eq), liq. NH , -78 °C, 45 min.
3
Conditions C: TBAF (1eq), THF, reflux, 1.5 h. Conditions D: SmI (2.5
eq), THF, rt.
2

738
U. K Nadir and R. V. Krishna
Vol. 41
Scheme 1
-1
125.6, 127.1, 127.6, 128.2, 138.9, 140.6, 159; ν
+
(KBr)/cm
max
1689 (C=O), 3259 (N-H); m/z 238(M , 100%), 181(44),
161(31), 104(28), 91(39).
A n a l. Calcd. for C H N O; C, 75.69; H, 5.92; N, 11.77.
15 14
2
Found: C, 75.64; H, 5.71; N, 11.68.
1-Benzyl-5-phenylimidazolidin-2-one (2b).
This compound has mp 132-134 °C;
(300MHz,CDCl ): δ 3.28 (t, 1H, J=8.4 Hz, -CH -), 3.55 (d, 1H,
1
H
NMR
3
H
2
J=14.89 Hz, -CH Ph) 3.7 (t, 1H, J=8.8 Hz, -CH -), 4.44 (t, 1H,
2
J=8.37 Hz, -CHPh-), 4.8 (s, 1H, -NH-), 4.91 (d, 1H, J=14.9 Hz, -
2
13
CH Ph), 7.11-7.39 (m, 10H, Ar); C NMR: δ 45.1, 51.15, 55.6,
2
123.6, 124.0, 125.8, 126.8, 127.3, 127.8, 128.4, 128.6, 129.2,
C
-1
(KBr)/cm 1678 (C=O), 3225
129.4, 134.8, 139.8, 158.3; ν
max
(N-H); m/z 253(M+2, 100%), 146, 132, 91.
A n a l. Calcd. for C H N O; C, 76.26; H, 6.40; N, 11.12.
Found: C, 76.14; H, 6.23; N, 11.03.
15 14
2
Conclusions.
Methyl 2-Oxo-1,5-diphenylimidazolidine-2-one (2c).
It has been found that among the various reduction meth-
ods viz. sodium naphthalenide, sodium in liquid NH3,
TBAF, SmI2and magnesium in methanol, the last one is the
most convenient for cleavage of N-arylsulfonyl bond in N-
arylsulfonyl imidazolidinones. Major advantages of the
method are: 1) the cleavage is effected without affecting the
benzyl or methoxycarbonyl group and 2) ring opening of
the imidazolidinone moiety does not take place.
1
This compound has mp 193-195 °C; H NMR (300MHz,
CDCl ): δ 3.25 (s, 3H, -OCH ), 4.76 (d, 1H, J=9.55 Hz, -
3
CHCOOCH ), 5.2 (s, 1H, -NH-), 5.57 (d, 1H, J=9.54 Hz, -CHPh-
H
3
3
), 6.96-7.46 (m, 10H, Ar); C NMR: δ 53.1, 61.4, 62.3, 119.3,
13
C
121.5, 123.6, 124.2, 125.7, 126.3, 127.5, 128.1, 129.7, 130.3,
-1
(KBr)/cm 1703 (C=O), 1754
136.5, 137.7, 150.8, 169.1; ν
max
(COOMe), 3218 (N-H); m/z 297(M+1, 100%), 237(36), 194(30),
181(10), 119(15), 91(29).
Anal. Calcd. for C
H N O; C, 68.98; H, 5.78; N, 9.46.
17 17 2
Found: C, 68.95; H, 5.63; N, 9.41.
EXPERIMENTAL
N-Phenyl-N'-(2-phenylethyl)urea (3a)
1
This compound has mp 144-146 °C; H NMR (300MHz,
CDCl ): δ 2.81 (t, 2H, J=6.8 Hz, -CH CH -), 3.49 (q, 2H,
Melting points were determined on micro melting-point appa-
ratus and are uncorrected. TLC on aluminum backed silica plates
60F visualisation was accomplished with UV light. IR spectra
3
J=6.75, 12.8 Hz, -CH CH - ), 4.9 (s, 1H, -NH-), 6.48 (s, 1H, -
H
2
2
254,
2
NH-), 7.0-7.4 (m, 10H, Ar); H NMR (300 MHz, CDCl , D O):
2
1
1
were recorded on Nicolet 5DX FTIR instrument. Both H and
13
C NMR (CDCl , internal standard TMS) spectra were recorded
3
2
δ
CH CH -), 7.0-7.4(m, 10H, Ar); C NMR: δ 34.4, 39.1, 116.1,
2.8 (t, 2H, J=6.83 Hz, -CH CH -), 3.49(t, 2H, J=6.85 Hz, -
2 2
3
H
1
13
on DPX-300 Brucker instrument (300 MHz, H). Chemical shifts
(δ and δ ) are quoted in parts per million (ppm). Low-resolu-
2
119.6, 124.3, 126.6, 126.8, 127.0, 137.8, 138.7, 153.8; ν
2
C
H
tion mass spectra (m/z) were recorded using a Hewlett Packard
C
max
(KBr)/cm 1646 (NHCONH), 3305 (NH), 3346 (NH); m/z
-1
+
Model-5989 spectrometer with only molecular ions (M ), and
+
241(M+1, 30%), 240(M , 29%), 149(10), 136(15), 120(8),
105(12), 91(20), 93(100%).
A n a l . Calcd. for C H N O; C, 75.06; H, 6.72; N,
1 5 1 6 2
11.67.Found: C, 74.92, H, 6.46; N, 11.53.
major peaks being reported with intensities quoted as percent-
ages of the base peak. Microanalyses were performed using
Perkin Elmer 240 CHN elemental analyzer.
Typical Procedure.
Acknowledgement.
A mixture of imidazolidinone 1a (0.50 g, 1.27 mmole), mag-
nesium (0.25 g, 10.2 mmole) and methanol (30 ml) was refluxed
for 8 hours. After the reaction was over, the reaction mixture was
cooled and an equal volume of ethyl acetate was added. The
whole was then filtered through a silica gel pad and the filtrate
concentrated in vacuo. The residue was purified by column chro-
matography (silica gel, 2:1 Benzene/ethyl acetate) to give the
desired product(s). All new starting and product compounds
R. Vijaya Krishna thanks CSIR, New Delhi for the award of
fellowship.
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C

Sep-Oct 2004
Facile Cleavage of N-Arylsulfonyl Bond of N-Arylsulfonylimidazolidinone
739
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