Synthesis of arylidenehydrazono- and glycopyranosylhydrazino- sulfonylbenzylidene-2,4-imidazolidinediones as potential antiviral and antitumoral agents

Article abstract of DOI:10.1016/S0008-6215(98)00024-X

A series of 5-[(Z)-(4-(2-(E)-arylidene)hydrazonosulfonylbenzylidene)]- 2,4-imidazolidinediones 6a h and 5-[(Z)-(4-(2-β-D- glycopyranosyl)hydrazinosulfonylbenzylidene)]-2,4-imidazolidinediones 10a j were synthesized via two different routes. The compounds did not display any antiviral and antitumoral activity.

Full text of DOI:10.1016/S0008-6215(98)00024-X

Carbohydrate Research 306 (1998) 567±573
Note
Synthesis of arylidenehydrazono- and
glycopyranosylhydrazino-sulfonylbenzylidene-
2,4-imidazolidinediones as potential antiviral
and antitumoral agents
Ahmed I. Khodair 1
Chemistry Department, Faculty of Education, Tanta University (Kafr El-Sheikh Branch),
Tanta, Egypt
Received 30 September 1997; accepted 9 January 1998
Abstract
A series of 5-[(Z)-(4-(2-(E)-arylidene)hydrazonosulfonylbenzylidene)]-2,4-imidazolidinediones
6a±h and 5-[(Z)-(4-(2-ꢀ-d-glycopyranosyl)hydrazinosulfonylbenzylidene)]-2,4-imidazolidinediones
10a±j were synthesized via two di€erent routes. The compounds did not display any antiviral and
antitumoral activity. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: 2,4-Imidazolidinediones; Hydrazones; Glycopyranosylhydrazines; Antiviral; Antitumor agents
There has been a considerable interest in the
synthesis and properties of derivatives of 2,4-imi-
dazolidinedione which are useful synthetic inter-
mediates and have also found applications as
therapeutics [1±4], and as fungicides and herbicides
[5] as well. Furthermore, several sulfonyl deriva-
tives of 2,4-imidazolidinedione have been shown to
possess antifungal activity [6±8] and inhibition
properties of aldose reductase from rat and bovine
lenses [9,10]. As a part of our program directed
towards new, simple and ecient procedures for
the synthesis of antiviral and antitumor agents [11±
16], the linking of 5-substituted-2,4-imidazolidine-
diones to an hydrophilic moiety such as a glycose
was considered.
Structures such as 10a±j were selected and their
synthesis planned by coupling of the two moieties
by an sulfonyl unit. In a ®rst approach, the pre-
paration of simpler analogs such as 6a±h was ®rst
studied in order to test two synthetic pathways and
the possible tautomeric equilibrium of such struc-
tures.
The present report describes the synthesis and
biological evaluation of a series of 5-[(Z)-(4-(2(E )
arylidene)hydrazonosulfonylbenzylidene)]-2,4-imi-
dazolidinediones 6a±h and 5-[(Z)-(4-(2-ꢀ-d-glyco-
pyranosyl)hydrazinosulfonylbenzylidene)]-2,4-imi-
dazolidinediones 10a±j.
1
Present address: Laboratoire de Chimie XII, Universite
de Poitiers et CNRS, 40 Avenue du Recteur Pineau, F-86022
Poitiers, France. Fax: (33) 0 5 494 53501; e-mail: ahmed.kho-
dair@mailexcite.com
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00024-X

568
A.I. Khodair/Carbohydrate Research 306 (1998) 567±573
1
1. Results and discussion
spectral data (IR, H NMR, 13C NMR and MS).
1
Typically, the H NMR spectrum of compound 6b
5-(Z)-Benzylidene-2,4-imidazolidinediones 1a,b
(Scheme 1) were prepared following the method of
Tan et al. [17] via the condensation of benzalde-
hyde with 2,4-imidazolidinedione and its 3-methyl
derivative in glacial acetic acid in the presence of
anhydrous sodium acetate. Compounds 1a,b were
treated with a large excess of chlorosulfonic acid at
room temperature to give 5-[(Z)-(4-(chlorosulfony-
lbenzylidene)]-2,4-imidazolidinedione 2a [8] and
5-[(Z)-(4-(chlorosulfonylbenzylidene)]-3-methyl-2,4-
imidazolidinedione 2b, respectively. 2-(E )-Aryli-
dene hydrazones 5a±d [18] were reacted with the
sulfonyl chlorides 2a,b to give 5-[(Z)-(4-(2-
(E )-arylidene)hydrazonosulfonylbenzylidene)]-2,4-
imidazolidinediones 6a±h. Compounds 6a±h were
independently synthesized through the condensa-
tion of aromatic aldehydes 4a±d with 5-[(Z)-(4-
hydrazinosulfonylbenzylidene)]-2,4-imidazolidine-
dione 3a [8] and its 3-methyl derivative 3b, which
in turn were prepared by the condensation of the
sulfonyl chlorides 2a,b with hydrazine hydrate in
dioxane. The structures of 6a±h were established
and con®rmed by their elemental analyses and
showed a singlet at ꢁ 6.56 ppm assigned to a vinyl
proton, indicating the presence of a Z-con®gura-
tion for the exocyclic double bond, in agreement
1
with the H NMR spectra of 5-(E )- and 5-(E )-
arylidene-2,4-imidazolidinediones whose vinyl pro-
tons respectively appear at ꢁ 6.10±6.35 and 6.40±
6.75 ppm [14±17]. The singlet at ꢁ 7.95 ppm was
assigned to the vinyl proton at the other exo-
cyclic double bond, indicating the presence of a
E-con®guration for this bond, in agreement with
the 1H NMR spectra and the conformational
analysis of 5-(Z)-arylidene-2-[(2-(E)-benzylidene)-
hydrazono]-4-imidazolidinediones whose vinyl
protons appear at 7.75±8.25 ppm [16,19] (Table 1).
The 13C NMR spectrum of compound 6b was
characterized by a signal at ꢁ 106.99 ppm assigned
to a vinyl carbon atom, supporting the Z-con®g-
uration of the exocyclic double bond, in agreement
with the 13C NMR spectra of 5-(E )- and 5-(Z )-ary-
lidene-2,4-imidazolidinediones whose vinyl carbon
atoms give signal respectively at ꢁ 105±112 ppm and
113±120 ppm [14±17]. The signal at 147.61 ppm was
assigned to the other vinyl carbon atom (Table 2).
Scheme 1.

A.I. Khodair/Carbohydrate Research 306 (1998) 567±573
569
Table 1
IR and H NMR data for 2±10
1
1
Compound
IR (KBr)(cm
)
1H NMR (Me2SO)/ꢁ
2a
2b
Ð
Ð
11.15 (s, 1 H, N-lH ), 8.10±7.60 (m, 4 H, Ar-H ), 6.46 (s, 1 H, =CH ), 2.95 (s, 3 H,
Me)
11.00 (s, l H, N-3H ), 10.25 (s, 1 H, N-lH ), 8 50 (s, l H, NHSO2), 7.80 (m, 4 H, Ar-
H ), 6.50 (s, 1 H, =CH ), 3.42 (s, 2 H, NH2)
11.40 (s, l H, N-lH ), 8.48 (s, 1 H, NHSO2), 7.80 (m, 4 H, Ar-H ), 6.57 (s, 1 H,
=CH ), 3.40 (s, 2 H, NH2), 2.96 (s, 3 H, Me)
11.60 (s, 1 H, N-3H ), 11.40 (s, l H, NHSO2), 10.75 (s, l H, N-lH ), 7.94 (s, 1 H,
N=CH ), 7.83±7.40 (m, 9 H, Ar-H ), 6.42 (s, 1 H, =CH )
11.50 (s, 2 H, NHSO2, N-3H ), 10.86 (s, l H, N-lH ), 7.99 (s, l H, N=CH ), 7.94±
7.07 (m, 8 H, Ar-H ), 6.52 (s, 1 H, =CH ), 3.86 (s, 3 H, O Me)
11.52 (s, 2 H, NHSO2, N-3H ), 10.84 (s, 1 H, N-lH ), 8.02 (s, 1 H, N=CH ), 7.90±
7.15 (m, 8 H, Ar-H ), 6.50 (s, 1 H, =CH ), 2.32 (s, 3 H, Ar-Me)
11.55 (s, 2 H, NHSO2, N-3H ), 10.85 (s, 1 H, N-lH ), 8.1 (s, 1 H, N=CH ), 7.90±
7.25 (m, 8 H, Ar-H ), 6.56 (s, 1 H, =CH )
11.62 (s, 2 H, NHSO2, N-3H ), 10.94 (s, 1 H, N-lH ), 7.95 (s, 1 H, N=CH ), 7.88±
7.37 (m, 9 H, Ar-H ), 6.53 (s, 1 H, =CH ), 2.93 (s, 3 H, N-3Me)
11.48 (s, l H, NHS02), 10.80 (s, l H, N-lH ), 7.98 (s, 1 H, N=CH ), 7.92±7.10 (m, 8
H, Ar-H ), 6.55 (s, 1 H, =CH ), 3.85 (s, 3 H, OMe), 2.90 (s, 3 H, N-3Me)
11.50 (s, 1 H, NHS02), 10.80 (s, 1 H, N-lH ), 8.05 (s, 1 H, N=CH ), 7.96±7.20 (m, 8
H, Ar-H ), 6.50 (s, 1 H, =CH ), 2.92 (s, 3 H, N-3Me), 2.34 (s, 3 H, Ar-Me)
11.50 (s, 1 H, NHS02), 10.86 (s, l H, N-lH ), 8.12 (s, l H, N=CH ), 7.9±7.25 (m, 8 H,
Ar-H ), 6.55 (s, 1 H, =CH ), 2.93 (s, 3 H, N-3 Me)
3450±3200 (NH ), 1780, 1725
(C=O), 1370, 1168(SO2)
Ð
3a
3b
6a
6b
6c
6d
6e
6f
3450±3200 (NH ), 1780, 1720
(C=O), 1372, 1165 (SO2)
3450±3200 NH, 1770, 1725
(C=O), 1370, 1160 (SO2)
3450±3200 (NH ), 1780, 1715
(C=O), 1378, 1172 (SO2)
3450±3200 NH, 1770, 1725
(C=O), 1374, 1170 (SO2)
3450±3200 NH, 1780, 1720
(C=O), 1370, 1160 (SO2)
3450±3200 (NH ), 1780, 1720
(C=O), 1375, 1168 (SO2)
3450±3200 (NH ), 1775, 1718
(C=O), 1373, 1165 (SO2)
3450±3200 (NH ), 1778, 1728
(C=O), 1370, 1166 (SO2)
3450±3200 (NH ), 1778, 1720
(C=O), 1370, 1168 (SO2)
3450±3200 (OH, NH ), 1780, 1720
(C=O), 1370, 1160 (SO2)
6g
6h
10a
11.41 (s, 1 H, N-3 H ), 10.78 (s, l H, N-lH ), 9.01 (s, 1 H, NHSO2), 8.47 (s, 1 H,
0
0
NH ), 8.47±7.80 (m, 4 H, Ar-H ), 6.45 (s, 1 H, =CH ), 5.52 (d, J1 , 2 =7.89 Hz, l H,
H-10), 4.98 ((m, 1 H, HO-20), 4.91 (d, J=4.30 Hz, 1 H, HO-30), 4.51 (d, J=4.05 Hz,
1 H, HO-40), 4.36 (d, J=4.11 Hz, 1 H, H O-60), 3.45±3.60 (m, 4 H, H-50, H-60, H-20),
3.02 (m, 1 H, H-30), 2.91 (m, 1 H, H-40)
10b
10c
10d
120e
10f
3450±3200 (OH, NH, 1776, 1723
(C=O), 1372, 1166 (SO2)
11.50 (s, l H, N-3H ), 10.87 (s, l H, N-lH ), 9.12 (s, l H, NHS02), 8.30 (s, 1 H, NH ),
0
0
0
8.23±7.89 (m, 4 H, Ar-H ), 6.55 (s, 1 H, =CH ), 5.46 (d, J1 , 2 =7.80 Hz, l H, H-1 ),
4.90 ((s, l H, HO-20), 4.60 (s, 1 H, H O-30), 4.40 (m, 1 H, HO-40), 4.21 (m, 1 H, H O-
60), 3.68±3.32 (m, 6 H, H-40, H-30, H-50, H-60, H-20)
3450±3200 (OH, NH ), 1780, 1728
(C=O), 1370, 1162 (SO2)
11.50 (s, l H, N-3H ), 10.84 (s, l H, N-lH ), 9.10 (s, 1 H, NHS02), 8.15±7.89 (m, 4 H,
0
0
0
A-H ), 8.30 (s, 1 H, NH ), 6.50 (s, 1 H, =CH ), 5.52 (d, J1 , 2 =7.68 Hz, l H, H-1 ),
4.90 ((s, l H, HO-20), 4.60 (s, 1 H, HO-30), 4.40 (m, 1 H, HO-40), 4.20 (m, 1 H, HO-
60), 3.70±3.30 (m 6 H H-40, H-30, H-50, H-60, H-20)
3450±3200 (OH, NH ), 1776, 1725
(C=O), 1370, 1164 (SO2)
11.41 (s, l H, N-3H ), 10.98 (s, l H, N-lH ), 9.04 (s, 1 H, NHS02), 8.46 (s, 1 H, NH ),
0
0
0
8.23±7.90 (m, 4 H, Ar-H ), 6.56 (s, 1 H, =CH ), 5.51 (d, J1 , 2 =7.75 Hz, l H, H-1 ),
4.89 (s, 1 H, HO-20), 4.53 (m, l H, HO-30), 4.32 (s, l H, HO-40), 3.72±2.98 (m, 5 H,
H-40, H-30, H-50, H-20)
3450±3200 (OH, NH ), 1778, 1722
(C=O), 1369, 1160 (SO2)
11.51 (s, l H, N-3H ), 10.88 (s, l H, N-lH ), 9.17 (s, 1 H, NHSO2), 8.46 (s, 1 H, NH ),
0
0
0
8.20±7.91 (m, 4 H, Ar-H ), 6.56 (s, 1 H, =CH ), 5.52 (d, J1 , 2 =8.05 Hz, l H, H-1 ),
5.11 (s, 1 H, HO-20), 4.32 (s, 1 H, HO-30), 3.72±3.26 (m, 6 H, H-40, H-30, H-50, H-20,
HO-40)
3450±3200 (OH, NH ), 1778, 1720
(C=O), 1370, 1162 (SO2)
10.99 (s, l H, N-lH ), 9.00 (s, 1 H, NHSO2), 7.84±7.76 (m, 5 H, Ar-H, NH ), 6.56 (s,
0
0
0
0
1 H, =CH ), 5.50 (d, J1 , 2 =8.16 Hz, 1 H, H-1 ), 4.95 (m, 1 H, HO-2 ), 4.88 (d,
J=4.33 Hz, 1 H, HO-30), 4.45 (dd, J=4.10, 7.90 Hz, 1 H, HO-40), 4.32 (d,
J=4.11 Hz, 1 H, HO-60), 3.63 (t, J=10.98 Hz, H-20), 3.46±3.37 (m, 3 H, H-50, H-60),
3.04 (m, 1 H, H-30), 2.97 (s, 3 H, N-3 Me), 2.93 (m, 1 H, H-40)
10g
10h
10i
10j
3450±3200 (OH, NH ), 1772, 1718
(C=O), 1370, 1165 (SO2)
10.87 (s, l H, N-lH ), 9.12 (s, 1 H, NHSO2), 7.89 (m, 5 H, Ar-H, NH ), 6.55 (s, 1 H,
0
0
0
0
=CH ), 5.50 (d, J1 , 2 =7.59 Hz, 1 H, H-l ), 4.98 (s, 1 H, HO-2 ), 4.62 (s, 1 H, HO-
30), 4.43 (m, 1 H, HO-40), 4.20 (m, 1 H, HO-60), 3.30±3.70 (m, 6 H, H-40, H-30, H-50,
H-60, H-20), 2.95 (s, 3H, N-3 Me)
3450±3200 (OH, NH ), 1780, 1720
(C=O), 1370, 1160 (SO2)
10.97 (s, l H, N-lH ), 8.99 (s, 1 H, NHSO2), 7.81 (m, 5 H, Ar-H, NH ), 6.57 (s, 1 H,
0
0
0
0
=CH ), 5.50 (d, J1 , 2 =7.86 Hz, 1 H, H-l ), 4.93 (s, 1 H, HO-2 ), 4.88 (s, 1 H, HO-
30), 4.45 (s, 1 H, HO-40), 4.31 (s, 1 H, HO-60), 3.63 (t, J=9.24 Hz, 1 H, H-20), 3.35±
3.46 (m, 3 H, H-50, H-60), 3.01±2.92 (m, 5 H, H-40, N-3 Me, H-30)
3450±200 (OH, NH ), 1775, 1720
(C=O), 1370, 1160 (SO2)
10.85 (s, l H, N-lH ), 9.01 (s, 1 H, NHSO2), 7.91 (m, 5 H, Ar-H, NH ), 6.60 (s, 1 H,
0
0
0
0
=CH ), 5.50 (d, J1 , 2 =7.89 Hz, 1 H, H-l ), 5.12 (s, 1 H, HO-2 ), 4.55 (s, 1 H, HO-
30), 4.32 (s, 1 H, HO-40). 2.98±3.70 (m, 5 H, H-40, H-30, H-50, H-20), 2.94 (s, 3 H, N-
3 Me)
3450±3200 (OH, NH ), 1780, 1720
(C=O), 1366, 1160 (SO2)
10.97 (s, l H, N-lH ), 9.03 (s, 1 H, NHSO2), 7.95 (m, 5 H, Ar-H, NH ), 6.50 (s, 1 H,
0
0
0
0
=CH ), 5.36 (d, J1 , 2 =8.17 Hz, 1 H, H-l ), 5.12 (s, 1 H, HO-2 ), 4.35 (s, 1 H, HO-
30), 3.26±3.70 (m, 6 H, H-40, H-30, H-50, H-2, HO-40), 2.96 (s, 3 H, N-3 Me)

570
A.I. Khodair/Carbohydrate Research 306 (1998) 567±573
The reaction of 2a,b with 2-(E )-polyhydroxyalk-
hydrazonosulfonylbenzylidene)]-2,4-imidazolidine-
diones 9a±j as intermediate. This intermediate then
cyclizes via intramolecular nucleophilic attack by
the oxygen atom at 50-position of the sugar moiety
to give 10a±j. Compounds 10a±j were also pre-
pared by the condensation of 3a,b with mono-
saccharides 8a±e under the same conditions. The
structures of 10a±j were established on the basis of
ylidene hydrazones 7a±e [19,20] (Scheme 2) was not
as straightforward as with 5a±d. Heating of 2a,b
with 7a±e in methanol for 2 h gave 5-[(Z)-(4-(2-ꢀ-d-
glycopyranosyl)hydrazinosulfonylbenzylidene)]-2,4-
imidazolidinediones 10a±j. The formation of 9
from 2 and 7 is assumed to proceed by a sequence
initiated by an exchange reaction between the
chlorosulfonyl group of 2 and the amino group
of 7 to give 5-[(Z)-(4-(2-polyhydroxyalkylidene)
1
their elemental analyses and spectral data (IR, H
NMR, 13C NMR and MS). Analytical data for 10a
Table 2
13C NMR data for some selected compounds listed in Table 1
Compound
13C NMR (Me2SO)/ꢁ
6e
164.26 (C-4), 155.60 (C-2), 147.61 (HC=N), 138.17, 137.71, 133.79, 130.40, 130.04, 129.20, 129.03, 127.68,
127.03, (C-Arom, C-5), 106.99 (=CH), 24.57 (N-3 Me)
10a
10b
10d
10f
165.62 (C), 155.98 (C-2), 138.70, 137.38, 130.40, 130.04, 129.76, 128.16, (C-Arom, C-5), 106.54 (=CH), 90.29 (C-
l0), 78.22 (C-30), 77.23 (C-50), 70.84 (C-20), 70.73 (C-40), 61.48 (C-60)
165.68 (C-4), 156.07 (C-2), 138.69, 137.40, 130.40, 130.09,129.86, 128.11 (C-Arom, C-5), 107.31 (=CH), 91.13
(C-l0), 76.78 (C-30), 73.97 (C-50), 68.64 (C-20), 68.23 (C-40), 61.06 (C-60)
165.69 (C-4), 156.10 (C-2), 138.33,137.40,129.72,128.28,127.73 (C-Arom, C-5), 106.62 (=CH), w 90.95 (C-10),
74.39 (C-30), 71.07 (C-50), 70.26 (C-20), 63.60 (C-40)
164.26 (C-4), 155.55 (C-2), 138.82,137.13,129.72,128.81,127.95 (C-Arom, C-5), 107.31 (=CH), 90.19 (C-10),
78.10 (C-30), 77.15 (C-50), 70.89 (C-20), 70.66 (C-40), 62.08 (C-60), 24.52 (N-3 Me)
10h
165.45 (C-4), 156.58 (C-2), 138.52, 138.16, 130.63, 129.49, 128.97 (C-Arom, C-5), 108.84 (=CH), 90.73 (C-10),
78.48 (C-30), 77.41 (C-50), 71.48 (C-20), 71.01 (C-40), 62.40 (C-60), 25.42 (N-3 Me)
Scheme 2.

A.I. Khodair/Carbohydrate Research 306 (1998) 567±573
571
revealed a molecular formula C16H20N4O9S (m/z
1
NMR spectra were measured on a Bruker Advance
DPX 300 MHz spectrometer for solns in
(CD3)2SO, using Me4Si as internal standard.
Chemical shifts are given in ꢁ and J values in Hz.
Mass spectra were recorded on a Finnigan MAT-
INCOS 500 spectrometer with ionization by elec-
tron impact (70 eV). Elemental analysis were
obtained from the Microanalytical Center at Cairo
University. 5-[(Z)-(4-Chlorosulfonylbenzylidene)]-
2,4-imidazolidinedione 2a and 5-[(Z)-(4-hydrazin-
osulfonylbenzylidene)]-2,4-imidazolidinedione 3a
were prepared according to the method of Cremlyn
et al. [8]. 2-(E)-Arylidene hydrazones 5a±d and
2-(E)-polyhydroxyalkylidene hydrazones 7a±e were
prepared according to published methods [18±20].
Biological evaluation.ÐCompounds 6a±h and
10a±j have been examined for antiviral and anti-
444). The H and 13C NMR spectra were used to
con®rm this structure for the product. Thus, the 1H
NMR spectrum of 10a showed a doublet at ꢁ 5.52
ppm which was assigned to the anomeric proton of
0
0
the glucose moiety with J1 ,2 coupling constant of
7.89 Hz in agreement with a diaxial orientation for
the corresponding protons, and then a ꢀ-con®g-
uration of the glucopyranosyl hydrazine 10a which
excludes the possibility of a glucose hydrazone 9a.
The singlet at ꢁ 6.45 ppm is due to the vinyl proton,
indicating the presence of a Z-con®guration for the
exocyclic double bond. The four NH groups
appeared as four singlets at ꢁ 8.47, 9.01, 10.78 and
11.41 ppm (exchangeable with deuterium oxide).
1
The H NMR spectrum of 10h (methanol-d4) was
characterized by the presence of a doublet at ꢁ 5.46
ppm due to the anomeric proton of the mannose
moiety with spin-spin coupling constant of 8.09 Hz
which corresponds to a diaxial orientation for H-10
and H-20 protons, in agreement with a ꢀ-con®g-
uration of the mannopyranosyl hydrazine 10h
which excludes the possibility of the mannose
hydrazone 9h. The singlet at ꢁ 6.59 ppm was
assigned to the vinyl proton, indicating the pre-
sence of a Z-con®guration for the exocyclic double
bond (Table 1). The 13C NMR spectrum of com-
pound 10b showed a signal at 90.20 ppm which
was assigned to C-10 in the ꢀ-con®guration. Five
signals appeared at ꢁ 78.14, 77.15, 70.89, 70.66 and
62.08 ppm corresponding respectively to C-30, C-50,
C-20, C-40 and C-60 of the galactose moiety, in
support of the exclusive ꢀ-con®guration of the
galactopyranosyl hydrazine 10b which excludes
the possibility of the galactose hydrazone 9b. In
the literature, the d-ribose E-thiosemicarbazone and
4-(ꢀ-d-ribopyranosyl)-thiosemicarbazide anomeric
protons are described respectively at ꢁ 146.79 and
87.10 ppm [21]. The signal at ꢁ 107.31 ppm is due
to the vinyl carbon atom, indicating the presence of
a Z-con®guration of the exocyclic double bond
(Table 2).
1
tumoral properties. Both, even at 100 ꢂg mL did
not inhibit HIV-1 [22]. No antiviral activity against
herpes and in¯uenza virus was found. No anti-
tumoral activity in the NCI in vitro disease-orien-
ted human cells screening panel assay was found
[23,24].
5-[(Z)-(4-Chlorosulfonylbenzylidene)]-3-methyl-
2,4-imidazolidinedione 2b. General procedure.Ð
5-(Z)-Benzylidene-3-methyl-2,4-imidazolidinedione
1b [17] (2.02 g, 0.01 mol) was added portionwise to
ꢀ
chlorosulfonic acid (10 mL) at 0 C with stirring.
The solution was stirred for 6 h at room tempera-
ture and poured into ice (50 g). The precipitate was
®ltered o€, washed with water, dried under reduced
pressure and crystallized from EtOH to give 2b
(Table 3).
5 - [(Z) - (4 - Hydrazinosulfonylbenzylidene)] - 3-
methyl-2,4-imidazolidinedione 3b. General pro-
cedure.ÐA mixture of the sulfonyl chloride 2b
(3.00 g, 0.01 mol) and hydrazine hydrate (1.00 g,
0.02 mol) in dioxane (50 mL) was initially stirred at
ꢀ
0 C and then left at room temperature for 4 h.
Addition of ice gave a precipitate which was ®l-
tered o€, washed with water, dried under reduced
pressure and crystallized from EtOH to a€ord 3b
(Table 3).
5-[(Z)-(4(2-(E)-Arylidene)hydrazonosulfonyl-
benzylidene)]-2,4-imidazolidinediones 6a±h. General
procedures.ÐMethod A: A mixture of 5-[(Z)-(4-
chlorosulfonylbenzylidene)]-2,4-imidazolidinediones
2a,b (0.05 mol) and 2-(E )-arylidene hydrazones
5a,b [18] (0.05 mol) in anhyd EtOH (30 mL) was
heated under re¯ux for 2 h. After cooling, the
separated solid was collected and recrystallized
from EtOH to give 6a±h (Table 3).
2. Experimental
General method.ÐMelting points are uncor-
rected. Precoated aluminum sheets of Silica Gel 60
F254 (E. Merck) were used for TLC. Detection was
e€ected by viewing under a short-wavelength UV
lamp. IR spectra were obtained (KBr disc) on a
Pye Unicam Spectra-1000 equipment. H and 13C
1

572
A.I. Khodair/Carbohydrate Research 306 (1998) 567±573
Table 3
Yields, melting points and analytical data for 2±10
Compound
mp (ꢀC)
Yield (%)
Mol formula
Found/Calcd (%)
H
M+ (m/z)
C
N
2a
2b
3a
3b
6a
6b
6c
6d
270
298
219
209
245
240
258
252
237
209
227
238
227
194
192
184
206
202
160
188
172
173
87
80
78
C10H7ClN2O4S (286)
C11H9ClN4O4S (300)
C10H10N4O4S (282)
C11H12N4O4S (296)
C17H14N4O4S (370)
C18H16N4O5S (400)
C18H16N4O4S (384)
C17H13CIN4O4S (404)
C18H16N4O4S (384)
C19H18N4O5S (414)
C19H18N4O5S (398)
C18H15ClN4O4S (418)
C16H20N4O9S (444)
C16H20N4O9S (444)
C16H20N4O9S (444)
C15H18N4O8S (414)
C15H18N4O8S (414)
C17H22N4O9S (458)
C17H22N4O9S (458)
C17H22N4O9S (458)
C16H20N4O8S (428)
C16H20N4O8S (428)
[Ref. 3]
43.65/43.92
[Ref. 3]
2.90/3.01
9.37/9.31
300
76
44.86/44.59
54.90/55.13
54.43/53.99
56.53/56.24
50.21/50.43
56.61/56.24
54.73/55.06
57.52/57.27
51.35/51.62
43.06/43.24
42.98/43.24
43.02/43.24
43.16/43.47
43.28/43.47
44.25/44.54
44.27/44.54
44.40/44.54
44.49/44.85
44.44/44.85
4.11/4.08
3.79/3.81
3.99/4.03
4.00/4.19
3.32/3.23
4.16/4.19
4.35/4.38
4.57/4.55
3.59/3.61
4.35/4.53
4.48/4.53
4.28/4.53
4.24/4.38
4.19/4.38
4.69/4.83
4.55/4.83
4.42/4.83
4.66/4.70
4.60/4.70
18.79/18.91
15.06/15.12
13.86/13.99
14.42/14.57
13.78/13.83
14.48/14.57
13.44/13.52
14.12/14.06
13.20/13.37
12.47/12.60
12.52/12.60
12.46/12.60
13.32/13.52
13.45/13.52
12.16/12.22
12.08/12.22
12.05/12.22
12.97/13.08
12.86/13.08
296
370
400
384
404
384
414
398
418
444
444
444
414
414
458
458
458
428
428
70a 83b
75a 87b
78a 85b
77 90
6e
6f
6g
71a 82b
72a 84b
70a 80b
79a 92b
69a 80b
72a 83b
74a 82b
74a 79b
68a 76b
76a 85b
78a 82b
70a 83b
72a 80b
63a 78b
6h
10a
10b
10c
10d
10e
10f
10g
10h
10i
10j
a
Method A.
Method B.
b
Method B:ÐA suspension of 5-[(Z)-(4-hydrazino-
sulfonylbenzylidene)]-2,4-imidazolidinediones 3a,b
(0.05 mole) in anhyd EtOH (30 mL) and the appro-
priate aldehyde 4a±d (0.05 mole) was heated under
re¯ux for 2 h. During the reaction period, the
hydrazine dissolved with the formation of hydra-
zone. It was ®ltered and recrystallized from EtoH
to give 6a±h in quantitative yield (Table 3).
was heated under re¯ux until the reaction was
judged complete by TLC (6 h, 95:5 CHCl3-MeOH).
Cooling to room temperature, resulted in a pre-
cipitate which was collected by ®ltration and
recrystallized from MeOH to give 10a±j in quanti-
tative yield (Table 3).
5-[(Z)-(4-(2-ꢀ-D-Glycopyranosyl)hydrazinosul-
fonylbenzylidene)]-2,4-imidazolidinediones 10a±j.
General procedures. Method A: A mixture of
5-[(Z)-(4-chlorosulfonylbenzylidene)]-2,4- imidazo-
lidinediones 2a,b (0.05 mol) and 2-(E)-poly-
hydroxyalkylidene hydrazones 7a±e [19,20]
(0.05 mole) in MeOH (50 mL) was heated under
re¯ux until the reaction was found complete by
TLC (4 h, 95:5 CHCl3±MeOH). Cooling to room
temperature resulted in a precipitate which was
collected by ®ltration and recrystallized from
MeOH to give 10a±j (Table 3).
Acknowledgements
The author expresses gratitude and thanks to
Professor Nils G. Johansson, Medicinal Chemistry,
Medivir AB, Huddinge, Sweden, for carrying out
the antiviral testing, Professor John P. Bader,
Antiviral Evaluation Branch and Professor V. L.
Narayanan, Drug Synthesis and Chemistry
Branch, National Cancer Institute, Bethesda, USA
for carrying out the antitumor screening.
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