5-anthracenylidene-and 5-(4-benzyloxy-3-methoxy)benzylidene-hydantoin, 2-thiohydantoin derivatives, synthesis, and s-alkylation

Article abstract of DOI:10.1080/10426507.2010.525977

5-Anthracenylidene-and 5-(4-benzyloxy-3-methoxy)benzylidene-hydantoin and 2-thiohydantoin derivatives 3a-g were prepared by condensation of anthracene-9-carboxaldehyde and 4-benzyloxy-3-methoxybenzylaldehyde with hydantoin and 2-thiohydantoin derivatives.

Full text of DOI:10.1080/10426507.2010.525977

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5-Anthracenylidene and 5-(4-
Benzyloxy-3-methoxy)benzylidene-
hydantoin and 2-Thiohydantoin
Derivatives, Synthesis, and S-Alkylation
Youssef L. Aly a , Ashraf A. El-Shehawy a , Adel M. Attia b & Mohmed
E. Sobh a
a Chemistry Department, Faculty of Science, Kafr El-Sheikh
University, Kafr El-Sheikh, Egypt
b Chemistry Department, College of Pharmacy, Taif University,
Kingdom of Saudi Arabia
Version of record first published: 04 Aug 2011.
To cite this article: Youssef L. Aly, Ashraf A. El-Shehawy, Adel M. Attia & Mohmed E. Sobh (2011):
5-Anthracenylidene and 5-(4-Benzyloxy-3-methoxy)benzylidene-hydantoin and 2-Thiohydantoin
Derivatives, Synthesis, and S-Alkylation, Phosphorus, Sulfur, and Silicon and the Related Elements,
186:7, 1572-1584
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Phosphorus, Sulfur, and Silicon, 186:1572–1584, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.525977
5-ANTHRACENYLIDENE AND 5-(4-BENZYLOXY-3-
METHOXY)BENZYLIDENE-HYDANTOIN AND
2-THIOHYDANTOIN DERIVATIVES, SYNTHESIS,
AND S-ALKYLATION
Youssef L. Aly,1 Ashraf A. El-Shehawy,1 Adel M. Attia,2
and Mohmed E. Sobh1
1Chemistry Department, Faculty of Science, Kafr El-Sheikh University,
Kafr El-Sheikh, Egypt
2Chemistry Department, College of Pharmacy, Taif University,
Kingdom of Saudi Arabia
GRAPHICAL ABSTRACT
R2
O
R1N
NH
SR3
R1= H, CH3, R2= 4-PhCH2-3-MeO-benzylidene and anthrcenylidene
R3= CH3, CH2COOEt, CH2COPh, CH2CH=CH2, CH2C(CH3)=CH2
Abstract 5-Anthracenylidene- and 5-(4-benzyloxy-3-methoxy)benzylidene-hydantoin and
2-thiohydantoin derivatives 3a-g were prepared by condensation of anthracene-9-
carboxaldehyde and 4-benzyloxy-3-methoxybenzylaldehyde with hydantoin and 2-
thiohydantoin derivatives. Compounds 3a, b, f undergo Mannich reaction with formaldehyde
and morpholine to give the corresponding Mannich products 4a–c. For the synthesis of
alkylmercaptohydantoin 5a–o, the potassium salt of compounds 3a, b, e, f were reacted
with an alkylhalide, either methyl iodide, phenacyl bromide, ethyl bromo acetate, allyl
bromide, or methallyl bromide, under stirring at room temperature to afford the alkylmer-
captohydantoins 5a–o. Acid hydrolysis of compounds 5a–c afforded the corresponding
arylidene-hydantoin derivatives 3c, d, g. 2-Methylmercapto-hydantoin derivatives 5a, c
were reacted with some secondary amines such as morpholine or piperidine to afford 5-(4-
benzyloxy-3-methoxy)benzylidene-2-morpholino- or piperidino glycocyamidine derivatives
7a, 5-anthracenylidene-2-morpholin-, or piperidino glycocyamidine derivatives 7b, c.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords 5-Arylidene-hydantoin; synthesis; S-alkyl derivatives; 2-thiohydantoin
Received 12 May 2010; accepted 19 September 2010.
Address correspondence to Youssef L. Aly, Chemistry Department, Faculty of Science, Kafr El-Sheikh
University, Elgysh Street, Kafr El-Sheikh, Egypt. E-mail: ylaly2002@hotmail.com
1572

2-THIOHYDANTOIN DERIVATIVES
1573
INTRODUCTION
Hydantoin and the 2-thiohydantoin ring system have proved to be an interesting class
of heterocyclic compounds.1,2
Many hydantoin- and 2-thiohydantoin-containing natural and synthetic products ex-
hibit diverse biological activities, such as antitumor,3,4 antiarrhytmic,5 and anticonvul-
sant properties.6,7 Aplysinopsins, isolated from marine organisms,3,8,9 are examples of
hydantoin-containing natural products exhibiting cytotoxicity toward cancer cells3 and the
ability to affect neurotransmitters.8 The nucleosides of several 5-arylidene-3-aryl-hydantoin
and 2-thiohydantoin show potent activity against herpes simplex virus (HSV),10 human im-
munodeficiency virus (HIV),11 and the leukemia subpanel.12
Hydantoin compounds containing hydroxyl groups in the side chain have been
identified as highly specific DNA intercalators. 3-[(S)-3,4-Dihydroxybutyl]-5-[(pyren-1-
yl)methylidene]imidazolidine-2,4-dione, upon insertion as a bulge, stabilizes a DNA triplex
at pH = 6.0 and 7.2 as well as a DNA/DNA parallel duplex at pH = 6.0.13
Those results are interesting and encouraged us to resume our interest in the
chemistry of hydantoin and 2-thiohydantoin derivatives.14–19 Herein we report the syn-
thesis of new 5-anthracenylidene- and 5-(4-benzyloxy-3-methoxy)benzylidene-hydantoin,
2-thiohydantoin derivatives, and some S-alkyl derivatives. These synthesized compounds
may be important for future development of conjugated DNA intercalators.
RESULTS AND DISCUSSION
Taking advantage of our previous experience on the synthesis of arylidine
hydantoin and 2-thiohydantoin derivatives,14–19 5-anthracenylidene- and 5-(4-benzyloxy-
3-methoxy)benzylidene-hydantoin, 2-thiohydantoin derivatives 3a–g were prepared
in 50–90% yield by reacting anthracene-9-carboxaldehyde (1) and 4-benzyloxy-3-
methoxybenzylaldehyde (2) with hydantoin and 2-thiohydantoin derivatives in ethanol in
1
the presence of a few drops of piperidine (Scheme 1). H-NMR spectrum of compounds
3a–g showed signals in the range of 7.0–8.6 ppm corresponding to the aromatic protons.
Moreover, 13C-NMR spectrum of 3a–g showed peaks in the range of 112.5–115.2
ppm corresponding to (CH C) of the aryliedene group and 165.7 ppm, 178.0 ppm
corresponding to C O and C S groups of the hydantoin and 2-thiohydantoin moieties,
respectively.
Reaction of 3a, b, f with formaldehyde and morpholine in ethanol at room
temperature afforded the Mannich base products 5-(4-benzyloxy-3-methoxy)benzylidene-
3-morpholinomethyl-2-thiohydantoin derivatives 4a, b in 71–75% yield and 5-
anthracenylidene-3-morpholinomethyl-2-thiohydantoin derivatives 4c in 63% yield
(Scheme 2).
Microanalytical and spectral data of compounds 4a–c are fully consistent with the
structure assigned (see Experimental section).
For the synthesis of alkylmercaptohydantoin 5a–o the potassium salt of compounds
3a, b, e, f were reacted with an alkylhalides, either methyl iodide, phenacyl bromide, ethyl
bromo acetate, allyl bromide, or methallyl bromide, under stirring at room temperature
to afford the alkylmercaptohydantoin 5a–o (Scheme 3). The yields were, in most cases,
moderate and typically in the range of 65–80%. No signal was observed for C S of the
thiohydantoin moiety at C2 in 13C-NMR at 178.0–179.0 ppm, and showed a signals in
the range of 167.0–170.5 ppm corresponding to (C N) indicated that the alkylation took

1574
Y. L. ALY ET AL.
CHO
O
R1N
NH
R2
O
1
X
R1N
NH
Piperidine
O
CHO
X
3a-g
R1, R2
R1 = H, R2 = 4-PhCH2O-3-MeO-benzylidene, X = S
R1 = CH3, R2 = 4-PhCH2O-3-MeO-benzylidene, X = S
CH3O
3a-g
2
a)
b)
c)
R1 = H,
R2 = 4-PhCH2O-3-MeO-benzylidene, X = O
d) R1 = CH3, R2 = 4-PhCH2O-3-MeO-benzylidene, X = O
R1 = H, R2 = Anthrcenylidene, X = S
e)
R1 = CH3, R2 = Anthrcenylidene, X = S
f)
R1 = H,
R2 = Anthrcenylidene, X = O
g)
Scheme 1
place on the sulfur atom at C2 of the hydantoin moiety to give S-alkylhydantoin derivatives
(Scheme 3).
Acid hydrolysis of compounds 5a–c afforded the corresponding arylidene-hydantoin
derivatives 3c, d, g through the elimination of MeSH (Scheme 4).
For the synthesis of glycocyamidine derivatives 7a–c, the 2-methylmercapto-
hydantoin derivatives 5a, c were reacted with some secondary amines such as mor-
pholine or piperidine 6 to afford 5-(4-benzyloxy-3-methoxy)benzylidene-2-morpholino-
glycocyamidine derivative 7a in a 65% yield and 5-anthracenylidene-2-morpholino or
-piperidino glycocyamidine derivatives 7b, c in 52–65% yield (Scheme 5). The 1H-NMR
spectrum of compounds 7a, b showed signals at 3.5 ppm (m, 4H, 2CH2N) and 3.7 ppm (m,
4H, 2CH2O) for the morpholine moiety; moreover, the 13C-NMR spectrum of compound
R2
R2
O
NCH2
O
Str. , RT
R1N
R1N
N
O
+ HCHO + HN
O
NH
S
S
4a-c
3a,b,f
4a-c R1 , R2
R1 = H, R2 = 4-PhCH2O-3-MeO-benzylidene
a)
b) R1 = CH3, R2 = 4-PhCH2O-3-MeO-benzylidene
R1 = CH3, R2 = Anthrcenylidene
c)
Scheme 2

2-THIOHYDANTOIN DERIVATIVES
1575
R2
O
R2
O
4
5
R3X
R1N
1
+
NH
3
N
1
R N
2
S
SR3
5a-o
3a,b,e,f
R3X = CH3I, BrCH2COOEt, BrCH2COPh, BrCH2CH=CH2, BrCH2CCH3=CH2
Comp. No.
R1
R2
R3
H
4-PhCH2O-3-MeO-benzylidene CH3
5a
5b
5c
5d
5e
5f
CH3 4-PhCH2O-3-MeO-benzylidene CH3
H
H
Anthracenylidene
CH3
4-PhCH2O-3-MeO-benzylidene CH2COOEt
CH3 4-PhCH2O-3-MeO-benzylidene CH2COOEt
H
Anthracenylidene
CH2COOEt
CH2COOEt
CH3 Anthracenylidene
5g
5h
5i
CH3 4-PhCH2O-3-MeO-benzylidene CH2COPh
Anthracenylidene CH2COPh
CH3 4-PhCH2O-3-MeO-benzylidene CH2 CH=CH2
H
5j
H
H
Anthracenylidene
CH2 CH=CH2
5k
5l
4-PhCH2O-3-MeO-benzylidene CH2C(CH3)=CH2
CH3 4-PhCH2O-3-MeO-benzylidene CH2C(CH3)=CH2
5m
5n
5o
H
Anthracenylidene
CH2C(CH3)=CH2
CH2C(CH3)=CH2
CH3 Anthracenylidene
Scheme 3
7c showed peaks in the range of 20.6–44.4 ppm corresponding to piperidine carbon atoms
(see Experimental section).
EXPERIMENTAL
General Consideration
The purity of the prepared compounds was confirmed by melting point and by thin-
layer chromatography (TLC). The structure of the prepared compounds was established

1576
Y. L. ALY ET AL.
R2
R2
O
O
HCl
R1N
R1N
NH
N
SCH3
O
5a-c
3c,d,g
R1 , R2
3c,d,g
c)
R1 = H, R2 = 4-PhCH2O-3-OCH3-benzylidene
R1 = CH3, R2 = 4-PhCH2O-3-OCH3-benzylidene
R1 = H, R2 = Anthrcenylidene
d)
g)
Scheme 4
by microelemental analysis (CHN) and spectral analysis, namely, infrared (IR) and 1H and
13C-NMR spectroscopy. All melting points are uncorrected and were performed by the
open capillary method using a three-sample melting point apparatus (Rum, model 4000).
Microanalysis was performed at the Microanalytical Center, Faculty of Science, Cairo
University.
IR spectra were recorded on a Perkin-Elmer 1420 spectrophotometer using a KBr
1
wafer technique. The H- and 13C-NMR spectra were recorded using a Bruker 400 spec-
trophotometer, 300 MHz for 1H-NMR and 75 MHz for 13C-NMR. CDCl3 and DMSO-d6
were used as solvents and tetramethylsilane (TMS) as internal standard, and the chemical
shifts are expressed as δ ppm.
All analytical samples were homogenous by TLC, which was performed on silica
gel 60 F sheet (0.2 mm) with C6H6/CHCl3 (2:5), v/v), benzene/ether (2:1, v/v), and ben-
zene/methanol (9:1, v/v) as the developing eluents. The spots were detected with UV model
UVGL-58. Selected 1H- and 13C-NMR spectra are shown in Figures S1–S6 (Supplemental
Materials, available online).
R2
R2
O
O
X
- CH3SH
R1N
+
N
R1N
N
NH
SCH3
N
X
5a,c
6
7a-c
7a-c
a)
R1, R2
R1 = H, R2 = 4-PhCH2O-3-OCH3-benzylidene, X = O
b) R1 = H, R2 = Anthrcenylidene, X = O
R1 = H, R2 = Anthrcenylidene, X = CH 2
c)
Scheme 5

2-THIOHYDANTOIN DERIVATIVES
1577
General Procedure for the Synthesis
5-(4-Benzyloxy-3-methoxy)benzylidene-2-thiohydantoin,
derivatives
3a, b, 5-(4-benzyloxy-3-methoxy)benzylidene hydantoin derivatives 3c, d,
5-anthracenylidene-2-thiohydantoin derivatives 3e, f, and 5-anthracenyl
idene hydantoin, derivatives 3g. A mixture of 4-benzyloxy-3-methoxy benzalde-
hyde 2 (2.42 g, 0.01 mol) and/or anthracene-9-carboxaldehyde 1 (2.06 g, 0.01 mol)
and hydantoin or 2-thiohydantoin derivatives (0.01 mol) in absolute ethanol (40 mL)
in the presence of a few drops of piperidine (3–5 drops) was heated under reflux
until the starting material was consumed (TLC). The solid obtained was filtered off
while hot, washed with ethanol, and recrystallized from acetic acid to give 5-(4-
benzyloxy-3-methoxy)benzylidene-2-thiohydantoin, derivatives 3a, b, 5-(4-benzyloxy-
3-methoxy)benzylidene hydantoin derivatives 3c, d, 5-anthracenylidene-2-thiohydantoin
derivatives 3e, f, and 5-anthracenylidene hydantoin, derivatives 3g.
5-(4-Benzyloxy-3-methoxy)benzylidene-2-thiohydantoin 3a. Yield 90%;
m.p. = 260–262 ◦C. IR (cm−1): 3284–3122 (N1H and N3H), 1725 (C O); δH (ppm) (300
MHz, DMSO-d6): 3.9 (s, 3H, OCH3), 5.2 (s, 2H, OCH2), 6.5 (s, 1H, CH = C), 7.1–7.4
(m, 8H, Har), 12.2 (br s, 2H, 2NH); δC (ppm) (75 MHz, DMSO-d6): 55.8 (OCH3), 69.7
(OCH2), 112.5 (CH C), 113.2 (C CH), 113.6, 124.1, 125.3, 125.2, 127.8, 127.9, 128.4,
136.7, 149.0, 149.1 (Car), 165.6 (C O), 178.6 (C S). Anal. Calcd. for C18H16N2O3S
(340): C, 63.51; H, 4.74; N, 8.23. Found: C, 63.22; H, 4.47; N, 7.98.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-2-thiohydantoin-3b.
Yield 85%; m.p. = 155–157 ◦C. IR (cm−1): 3124 (NH), 1725 (C O). δH (ppm) (300 MHz,
DMSO-d6): 3.4 (s, 3H, NCH3), 3.9 (s, 3H, OCH3), 5.2 (s, 2H, OCH2), 6.5 (s, 1H, CH =
C), 7.1–7.5 (m, 8H, Har), 12.2 (s, 1H, N3H); δC (ppm) (75 MHz, DMSO-d6): 35.8 (NCH3),
55.9 (OCH3), 69.7 (OCH2), 112.5 (CH C), 113.2 (C CH), 113.5, 124.1, 125.3, 125.9,
127.8, 127.9, 128.4, 136.7, 149.0, 149.1 (Car), 165.7 (C O), 178.7 (C S). Anal. Calcd.
for C19H18N2O3S (354): C, 64.39; H, 5.12; N, 7.9. Found; C, 64.01; H, 4.91; N, 7.54.
5-(4-Benzyloxy-3-methoxy) benzylidene hydantoin 3c. Yield 82%; m.p. =
300–302 ◦C. IR (cm−1): 3309–3154 (2NH), 1714 (C O). δH (ppm) (400 MHz, DMSO-d6):
3.8 (s, 3H, OCH3), 5.1 (s, 2H, OCH2), 6.7 (s, 1H, CH = C), 7.1–8.1 (m, 8H, Har), 12.2
ppm (2s, 2H, 2NH); δC (ppm) (100 MHz, DMSO-d6): 55.1 (OCH3), 69.7 (OCH2), 112.8
(CH C), 113.8 (C CH), 121.2, 125.7, 127.5, 127.8, 128.4, 134.2, 136.7, 137.50, 148.7,
149.2 (Car), 159.3 (C O at C2), 163.3 (C O at C4). Anal. Calcd. for C18H16N2O4 (324):
C, 66.66; H, 4.97; N, 8.64. Found; C, 66.21; H, 4.72; N, 8.32.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl hydantoin 3d. Yield
◦
80%; m.p. = 244–246 C. IR (cm−1): 3158 (NH), 1708 (C O); δH (ppm) (400 MHz,
DMSO-d6): 3.3 (s, 3H, NCH3), 3.9 (s, 3H, OCH3), 5.1 (s, 2H, OCH2), 6.7 (s, 1H, CH =
C), 7.1–7.93 (m, 8H, Har), 11.7 (s, 1H, N3H); δC (ppm) (100 MHz, DMSO-d6): 34.4
(NCH3), 55.3 (OCH3), 69.7 (OCH2), 112.8 (CH C), 114.2 (C CH), 125.9, 127.8, 127.8,
127.9, 128.4, 136.8, 137.2, 148.9, 149.4, 149.5 (Car), δ = 158.8, 166.7 (C O at C2 and
C O at C4 of the hydantoin moiety, respectively). Anal. Calcd. for C19H18N2O4 (338): C,
67.45; H, 5.36; N, 8.28. Found: C, 67.02; H, 5.12; N, 7.92.
5-Anthracenylidene-2-thiohydantoin 3e. Yield 85%; m.p. = 313–315 ◦C. IR
(cm−1): 3405–3122 (2NH), 1737 (C O). δH (ppm) (300 MHz, DMSO-d6): 7.3 (s, 1H, CH =
C), 7.5–8.6 (m, 9H, Har), 11.6, 12.4 (2s,1H, 2NH); δC (ppm) (75 MHz, DMSO-d6): 115.2
(CH C), 119.3 (C CH), 125.4, 125.4, 126.4, 127.8, 128.8, 129.3, 130.9, 133.4 (Car),

1578
Y. L. ALY ET AL.
164.5 (C O), 179.1 (C S). Anal. Calcd. for C18H12N2OS (304.3): C, 71.03; H, 3.97; N,
9.2. Found: C, 70.76; H, 3.61; N, 8.86.
5-Anthracenylidene-1-methyl-2-thiohydantoin 3f. Yield 80%; m.p. = above
◦
320 C. IR (cm−1): 3320 (NH), 1737 (C O); δH (ppm) (400 MHz, DMSO-d6): 3.4 (s,
3H, NCH3), 6.8 (s, 1H, CH = C), 7.5–8.6 (m, 9H, Har), 11.6 (s,1H, NH); δC (ppm) (100
MHz, DMSO-d6): 28.4 (NCH3), 113.8 (CH C), 115.4 (C CH), 125.4, 126.3, 127.8, 128.5,
128.8, 129.3, 130.9, 133.4 (Car), 164.5 (C O), 179.0 (C S). Anal. Calcd. for C19H14N2OS
(318): C, 71.67; H, 4.43; N, 8.8. Found; C, 71.28; H, 4.12; N, 8.46.
5-Anthracenylidene hydantoin 3g. Yield 55%; m.p. = 178–180 ◦C. IR (cm−1):
3299–3187 (2NH), 1735, 1731 (2C O); δH (ppm) (400 MHz, DMSO-d6): 7.2 (s, 1H, CH
= C), 7.5–8.6 (m, 9H, Har), 11.3, 11.7 (2s, 1H, 2NH); δC (ppm) (100 MHz, DMSO-d6):
115.4 (CH C), 117.9 (C CH), 125.3, 125.5, 126.2, 126.8, 127.5, 128.7, 130.9, 133.1
(Car), 154.9, 164.1 (2C O). Anal. Calcd. for C18H12N2O2 (288): C, 74.99; H, 4.2; N, 9.72.
Found: C, 74.65; H, 3.87; N, 9.43.
General Procedure for the Synthesis of
3-Morpholino-Methyl-2-Thiohydantoin Derivatives 4a–c
A mixture of 3a, b and/or 3f (0.01 mol), formaldehyde (1.0 mL, 40% solu-
tion), and morpholine (0.01 mol) in ethanol (30 mL) was stirred at room temperature
overnight until the starting material was consumed (TLC), the solid formed was
filtered off, washed with ethanol, and recrystallized from ethyl alcohol to give
5-(4-benzyloxy-3-methoxy)benzylidene-3-morpholinomethyl-2-thiohydantoin 4a, 5-(4-
benzyloxy-3-methoxy)benzylidene-1-methyl-3-morpholinometh-yl-2-thiohydantoin 4b,
and 5-anthracenylidene-1-methyl-3-morpholinomethyl-2-thiohydantoin 4c.
5-(4-Benzyloxy-3-methoxy)benzylidene-3-morpholinomethyl-2-thiohyd
◦
antoin 4a. Yield 75%; m.p. = 187–189 C. IR (cm−1): 3120 (NH), 1725 (C O); δH
(ppm) (400 MHz, DMSO-d6): 2.5 (m, 4H, 2CH2Nmorph), 3.3 (m, 4H, 2CH2Omorph), 3.9
(s, 3H, OCH3), 4.67 (s, 2H, NCH2N), 5.1 (s, 2H, OCH2), 6.5 (s, 1H, CH = C), 7.1–7.7
(m, 8H, Har), 12.0 (s, 1H, N1H); δC (ppm) (100 MHz, DMSO-d6): 43.6 (2CH2Nmorph),
51.3 (NCH2N), 55.9 (OCH3), 65.4 (2CH2Omorph), 69.9 (OCH2), 113.3 (CH C), 113.6
(C CH), 123.2, 124.2, 125.3, 125.9, 127.8, 127.9, 128.4, 136.8, 149.1, 149.2 (Car), 165.8
(C O), 178.6 (C S). Anal. Calcd. for C23H25N3O4S (439): C, 62.85; H, 5.73; N, 9.56.
Found: C, 62.54; H, 5.48; N, 9.31.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-3-morpholinomethyl-
◦
2-thiohydantoin 4b. Yield 71%; m.p. = 198–200 C. IR (cm−1): 1733 (C O), 1640
(C C); δH (ppm) (400 MHz, DMSO-d6): 2.6 (m, 4H, 2CH2Nmorph), 3.3 (s, 3H, NCH3),
3.5 (m, 4H, 2CH2Omorph), 3.9 (s, 3H, OCH3), 4.7 (s, 2H, NCH2N), 5.2 (s, 2H, OCH2), 6.6
(s, 1H, CH = C), 7.1–7.6 (m, 8H, Har); δC (ppm) (100 MHz, DMSO-d6): 28.2 (NCH3),
45.3 (2CH2Nmorph), 51.1 (NCH2N), 55.8 (OCH3), 66.0 (2CH2Omorph), 69.7 (OCH2), 113.2
(CH C), 113.7 (C CH), 124.1, 124.3, 125.2, 127.7, 128.4, 132.7, 133.7, 136.7, 149.0,
149.3 (Car), 165.1 (C O), 179.4 (C S). Anal. Calcd. for C24H27N3O4S (453): C, 63.56;
H, 6.00; N, 9.29. Found: C, 63.28; H, 5.72; N, 9.01.
5-Anthracenylidene-1-methyl-3-morpholinomethyl-2-thiohydantoin 4c.
◦
Yield 63%; m.p. = 285–286 C. IR (cm−1): 1737 (C O), 1640 (C C). δH (ppm) (300
MHz, DMSO-d6): 2.7 (m, 4H, 2CH2Nmorph), 3.4 (s, 3H, NCH3), 3.7 (m, 4H, 2CH2Omorph),
4.8 (s, 2H, NCH2N), 7.2 (s, 1H, CH = C), 7.4–8.0 (m, 9H, Har); δC (ppm) (75 MHz,

2-THIOHYDANTOIN DERIVATIVES
1579
DMSO-d6): 49.9 (NCH3), 51.5 (2CH2Nmorph), 62.9 (NCH2N), 65.4 (2CH2Omorph), 110.3
(CH C), 113.1 (C CH), 125.8, 126.8, 127.4, 128.9, 129.3, 129.8, 130.0, 130.8 (Car),
163.8 (C O), 179.2 (C S). Anal. Calcd. for C24H23N3O2S (417): C, 69.06; H, 5.51; N,
10.07. Found: C, 68.86; H, 5.34; N, 9.83.
General Procedure for the Synthesis of 2-Methylthio-Hydantoin
Derivatives 5a–c
Potassium hydroxide solution (0.01 mol, 0.56 g) in distilled water (10 mL) was added
to a suspended solution of compound 3a, b and/or 3e (0.01 mol) in ethanol (30 mL). The
reaction mixturewas stirred for 10min, andthenmethyl iodide (0.01mol) inethanol (10mL)
was added to the reaction mixture dropwise. The reaction mixture was kept under stirring
at room temperature until the starting material was consumed (TLC for 3 h); the resulting
precipitate was filtered off, washed with distilled water and ethyl alcohol, and recrystallized
from acetic acid to give 5-(4-benzyloxy-3-methoxy)benzylidene-2-methylthiohydantoin
5a, 5-(4-benzyloxy-3-meth-oxy)benzylidene-1-methyl-2-methylthiohydantoin 5b, and 5-
anthra-cenylidene-2-methylthiohydantoin 5c.
5-(4-Benzyloxy-3-methoxy)benzylidene-2-methylthiohydantoin
5a.
Yield 80%; m.p. = 242–244 C. IR (cm−1): 3150 (NH), 1708 (C O), 1635 (C N);
δH (ppm) (300 MHz, DMSO-d6): 2.7 (s, 3H, SCH3), 3.8 (s, 3H, OCH3), 5.2 (s, 2H,
OCH2), 6.7 (s, 1H, CH = C), 7.1–8.7 (s, 8H, Har), 11.7 (s, 1H, N1H); δC (ppm) (75 MHz,
DMSO-d6): 12.1 (SCH3), 55.1 (OCH3), 69.7 (OCH2), 112.8 (CH C), 113.8 (CH C),
121.2, 125.7, 127.5, 127.8, 127.9, 128.4, 136.7, 137.5, 148.7, 149.2 (Car), 163.2 (C O),
170.6 (C N). Anal. Calcd. for C19H18N2O3S (354): C, 64.39; H, 5.12; N, 7.9. Found: C,
64.05; H, 4.87; N, 7.62.
◦
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-2-methylthiohydantoin
5b. Yield 81%; 239–241 ◦C. IR (cm−1): 1708 (C O), 1590 (C N); δH (ppm) (400 MHz,
DMSO-d6): 2.7 (s, 3H, SCH3), 3.5 (s, 3H, NCH3), 4.0 (s, 3H, OCH3), 5.1 (s, 2H, OCH2),
6.7 (s, 1H, CH = C), 7.1–8.2 (m, 8H, Har); δC (ppm) (100 MHz, DMSO-d6): 24.0 (SCH3),
39.1 (NCH3), 55.1 (OCH3), 69.8 (OCH2), 113.9 (CH C), 114.6 (C CH), 121.4, 125.8,
127.3, 127.8, 128.3, 136.6, 137.4, 14.1, 148.7, 149.3 (Car), 162.2 (C O), 170.4 (C N).
Anal. Calcd. for C20H20N2O3S (368): C, 65.20; H, 5.47; N, 7.60. Found: C, 64.85; H,
5.12; N, 7.24.
5-Anthracenylidene-2-methylthiohydantoin 5c. Yield 75%; m.p.
=
287–289 C. IR (cm−1): 3156 (NH), 1712 (C O), 1640 (C N); δH (ppm) (400 MHz,
DMSO-d6): 2.3 (s, 3H, SCH3), 6.75 (s, 1H, CH = C), 7.5–8.6 (m, 9H, Har), 11.9 (s, 1H,
N1H). δC (ppm) (100 MHz, DMSO-d6): 12.0 (SCH3), 118.2 (CH C), 120.2 (C CH),
125.4, 125.8, 126.1, 127.9, 128.4, 129.2, 130.7, 136.2 (Car), 165.9 (C O), 169.7 (C N).
Anal. Calcd. for C19H14N2OS (318): C, 71.67; H, 4.43; N, 8.8. Found: C, 71.28; H, 4.17;
N, 8.48.
◦
General Procedure for the Synthesis of
2-Carboethoxymethylthiohydantoin, Derivatives 5d–g
A solution of potassium hydroxide (0.56 g, 0.01 mol) in distilled water (10 mL)
was added to a solution of 3a, b, and/or 3e, f in ethanol (30 mL). The mixture
was stirred for 10 min and then ethyl bromoacetate (0.01 mol) in ethanol (10 mL)
was added dropwise to the reaction mixture. The reaction mixture was stirred at
room temperature until the starting material was consumed (TLC) for 3 h; the

1580
Y. L. ALY ET AL.
resulting precipitate was filtered off, washed with distilled water and ethanol sev-
eral times to remove potassium bromide, and recrystallized from acetic acid to give
5-(4-benzyloxy-3-methoxy) benzylidene-2-carboethoxylmethylthiohydantoin 5d, 5-(4-
benzyloxy-3-methoxy)benzylidene-1-methyl-2-carboethoxylmethylthiohydantoin
5e,
5-anthracenylidene-2-carboethoxylmethyl-thiohydantoin 5f, and 5-anthracenylidene-1-
methyl-2-carboethoxylmethylthiohydantoin 5g.
5-(4-Benzyloxy-3-methoxy)benzylidene-2-carboethoxymethylthiohyda
◦
ntoin 5d. Yield 86%; m.p. = 187–189 C. IR (cm−1): 3141 (NH), 1750 (C O, ester),
1702 (C O hyd.); δH (ppm) (400 MHz, DMSO-d6): 1.1 (m, 3H, CH3CH2), 2.8 (s, 2H,
SCH2), 3.8 (s, 3H, OCH3), 4.2 (m, 2H, OCH2CH3), 5.2 (s, 2H, OCH2), 6.7 (s, 1H, CH =
C), 7.4–8.1 (m, 8H, Har), 11.8 (s, 1H, N1H). δC (ppm) (100 MHz, DMSO-d6): 13.9
(CH3CH2), 31.8 (SCH2CO), 55.3 (OCH3), 61.3 (OCH2CH3), 69.7 (OCH2Ph), 112.9
(CH C), 114.1 (C CH), 125.9, 127.8, 127.9, 127.9, 128.4, 136.7, 137.2, 148.9, 149.4,
149.5 (CAr), 164.2 (C O at C4), 167.9 (C N), 170.4 (C O of acetate group). Anal.
Calcd. for C22H22N2O5S (426): C, 61.96; H, 5.20; N, 6.57. Found: C, 61.65; H, 5.03; N,
6.28.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-2-carboethoxymethyl
thiohydantoin 5e. Yield 80%; m.p. = 237–239 ◦C. IR (cm−1): 1755 (C O, of acetate),
1705 (C O, hyd); δH (ppm) (400 MHz, DMSO-d6): 1.2 (m, 3H, CH3CH2), 3.4 (s, 2H,
SCH2), 3.9 (s, 3H, NCH3), 4.1 (m, 2H, OCH2CH3), 4.2 (s, 3H, OCH3), 5.2 (s, 2H,
OCH2), 6.7 (s, 1H, CH = C), 7.1–8.1 (m, 8H, Har). δC (ppm) (100 MHz, DMSO-d6): 13.9
(CH3CH2), 31.7 (SCH2), 38.1 (NCH3), 55.2 (OCH3), 61.3 (OCH2CH3), 69.7 (OCH2Ph),
112.9 (CH C), 114.1 (CH C), 125.8, 127.2, 127.7, 127.8, 128.3, 128.8, 136.7, 137.1,
148.8, 149.38 (10 Car), 161.6 (C O, hyd), 167.9 (C N), 170.4 (C O of acetate group).
Anal. Calcd. for C23H24N2O5S (440): C, 62.71; H, 5.49; N, 6.36. Found: C, 62.45; H,
5.27; N, 6.04.
5-Anthrac◦enylidene-2-carboethoxymethylthiohydantoin 5f. Yield 75%;
m.p. = 285–287 C. IR (cm−1): 3151 (NH), 1755 (C O acetate), 1720 (C O, hyd), δH
(ppm) (300 MHz, DMSO-d6): 1.1 (m, 3H, CH3CH2), 2.7 (s, 2H, SCH2), 3.5 (m, 2H,
OCH2CH3), 6.9 (s, 1H, CH = C), 7.5–8.6 (m, 9H, Har), 11.9 (s, 1H, N1H); δC (ppm) (75
MHz, DMSO-d6): 13.5 (CH3), 31.6 (SCH2), 60.8 (OCH2CH3), 117.7 (CH C), 119.1
(C CH), 125.4, 125.9, 127.8, 127.9, 128.4, 129.1, 130.7, 133.5 (Car), 161.4, (C O at C4 of
hydantoin), 167.3 (C N), 169.3 (C O, acetate carbonyl). Anal. Calcd. for C22H18N2O3S
(390): C, 67.69; H, 4.61; N, 7.18. Found: C, 67.46; H, 4.37; N, 7.14.
5-Anthracenylidene-1-methyl-2-carboethoxymethylthiohydantoin 5g.
◦
Yield 72%; m.p. = 180–182 C. IR (cm−1): 1745 (C O, ester), 1702 (C O, hyd); δH
(ppm) (400 MHz, DMSO-d6): 1.1 (m, 3H, CH3CH2), 3.0 (s, 2H, SCH2), 3.8 (s, 3H,
NCH3), 4.2 (m, 2H, OCH2CH3), 6.7 (s, 1H, CH = C), 7.6–8.6 (m, 9H, Har). δC (ppm) (100
MHz, DMSO-d6): 13.9 (CH3CH2), 31.7 (SCH2), 38.1 (NCH3), 61.3 (OCH2CH3), 112.8
(CH C), 113.7 (C CH), (125.3, 125.5, 126.2, 126.8, 127.5, 128.8, 130.9, 133.1 (Car),
161.9 (C O at C4 of hydantoin), 170.4 (C N) and 172.2 (C O of acetate group). Anal.
Calcd. for C23H20N2O3S (404): C, 68.30; H, 4.98; N, 6.93. Found: C, 68.06; H, 4.67; N,
6.68.
General Procedure for the Synthesis of 2-Benzoyl-Methylthiohydantoin
Derivatives 5h, i
A solution of 5-(4-benzyloxy-3-methoxy)benzylidne-2-thiohydantoin derivatives 3b
and/or 5-anthracenylidene-2-thiohydantoin derivatives 3e (0.01 mol), aqueous potassium

2-THIOHYDANTOIN DERIVATIVES
1581
hydroxide (0.56 g, 0.01 mol) in distilled water (10 mL), and phenacyl bromide (1.99 g,
0.01 mole) in ethanol (50 mL) was stirred at room temperature. The stirring was con-
tinued until the starting material was consumed (about 1–3 h). The precipitate ob-
tained was filtered off, washed with distilled water and ethanol several times to re-
move the formed potassium bromide salt, and recrystallized from acetic acid to give 5-
(4-benzyloxy-3-methoxy)benzylidene-1-methyl-2-benzoylmethylthiohydantoin 5h and 5-
anthracenylidene-2-benzoylmethylthiohydantoin 5i.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-2-benzoylmethylthioh
◦
ydantoin 5h. Yield 75%; m.p. = 240–242 C. IR (cm−1): 1710, 1690 (2C O), 1640
(C N); δH (ppm) (400 MHz, DMSO-d6): 2.9 (s, 2H, SCH2), 3.4 (s, 3H, NCH3), 3.9 (s,
3H, OCH3), 5.1 (s, 2H, OCH2), 6.8 (s, 1H, CH = C), 7.4–8.1 (m, 13H, Har). δC (ppm)
(100 MHz, DMSO-d6): 35.1 (SCH2), 38.1 (NCH3), 54.7 (OCH3), 69.6 (OCH2), 112.6
(CH C), 113.7 (C CH), 121.5, 125.6, 127.1, 127.6, 127.8, 128.2, 128.3, 128.8, 133.7,
135.3, 136.6, 137.2, 148.6, 149.1 (Car), 161.9 (C O at C4), 168.7 (C N), 192.1 (C O of
benzoyl moiety). Anal. Calcd. for C27H24N2O4S (458): C, 68.63; H, 5.12; N, 5.93. Found:
C, 68.38; H, 4.87; N, 5.72.
5-Anthracenylidene-2-benzoylmethylthiohydantoin
5i. Yield
74%;
m.p. = 205–207 C. IR (cm−1): 3158 (NH), 1720 (C O of hydantoin), 1660 (C O of
benzoyl), 1640 (C N). δH (ppm) (400 MHz, DMSO-d6): 3.6 (s, 2H, SCH2CO), 6.8 (s,
1H, CH = C), 7.3–8.6 (m, 14H, Har), 12.1 (s, 1H, N1H); δC (ppm) (100 MHz, DMSO-d6):
37.8 (SCH2 CO), 117.6 (CH C), 118.6 (C CH), 125.2, 125.9, 127.5, 127.8, 128.3, 129.2,
130.6, 133.1, 135.4, 137.1, 137.8, 142.2 (Car), 164.5 (C O of hydantoin at C4), 169.6
(C N), 192.4 (C O of benzoyl moiety). Anal. Calcd. for C26H18N2O2S (422): C, 73.91;
H, 4.29; N, 6.63. Found: C, 73.62; H, 4.01; N, 6.32.
◦
General Procedure for the Synthesis of 2-Allylthiohydantoin
Derivatives 5j, k
To a solution of each 3b and/or 3e (0.01 mol) in ethanol, potassium hydroxide (0.01
mol 0.56 g) in distilled water (10 mL) was added. The mixture was stirred at room tempera-
ture for 10 min, and then 0.01 mol of allyl bromide in ethanol (10 mL) was added dropwise.
The reaction mixture was kept under stirring at room temperature until the starting material
was consumed (TLC, 3 h). The resulting precipitate was filtered off, washed with water and
ethanol, and recrystallized from ethanol to give 5-(4-benzyloxy-3-methoxy)benzylidene-
1-methyl-2-allylthiohydantoin 5j and 5-anthracenylidene-2-allylthiohydantoin 5k.
5-(4-Benzyloxy-3-methoxy)benzylidene-1-methyl-2-allylthiohydantoin
5j. Yield 70%; m.p. = 202–204 ◦C. IR (cm−1): 1708 (C O), 1570 (C C); δH (ppm) (300
MHz, DMSO-d6): 2.8 (d, 2H, SCH2), 3.6 (s, 3H, NCH3), 3.8 (s, 3H, OCH3), 4.2–4.3 (d,
2H, CH2 = CH), 4.7–4.8 (m, 1H, CH = CH2), 5.1 (s, 2H, OCH2), 6.7 (s, 1H, CH = C),
7.1–8.3 (m, 8H, Har); δC (75 MHz, DMSO-d6): 14.7 (SCH2), 24.2 (NCH3), 55.0 (OCH3),
69.7 (OCH2), 112.8 (CH2 = CH), 113.5 (CH CH2), 121.1 (CH C), 122.3 (C CH),
125.8, 125.9, 127.5, 127.8, 127.8, 128.4, 136.7, 137.5, 148.7, 149.2 (Car), 162.6 (C O),
170.5 (C N). Anal. Calcd. for C22H22N2O3S (394): C, 66.98; H, 5.62; N, 7.10. Found: C,
66.62; H, 5.44; N, 6.83.
5-Anthracenylidene-2-allylthiohydantoin 5k. Yield 75%; m.p. = 271–
◦
273 C. IR (cm−1): 3135 (NH), 1714 (C O); δH (ppm) (300 MHz, DMSO-d6): 3.1 (d,
2H, SCH2), 4.5 (d, 2H, CH2 = CH), 5.1–5.2 (m, 1H, CH = CH2), 7.07 (s, 1H, CH
= C), 7.4–8.6 (m, 9H, Har), 11.7 (s, 1H, N1H); δC (ppm) (75 MHz, DMSO-d6): 27.5

1582
Y. L. ALY ET AL.
(SCH2), 114.1 (CH2 = CH), 114.6 (CH CH2), 120.2 (CH C), 122.2 (C CH), 125.3,
126.3, 127.9, 128.8, 130.9, 133.2, 136.6, 137.6 (Car), 165.7 (C O), 170.0 (C N). Anal.
Calcd. for C21H16N2OS (344): C, 73.23; H, 4.68; N, 8.13. Found: C, 72.89; H, 4.42; N,
7.86.
General Procedure for the Synthesis of 2-Methallylthiohydantoin
Derivatives 5l–o
To a well-stirred solution of 3a, b and/or 3e, f (0.01 mol) and potassium hydroxide
(0.56 g, 0.01 mol) in a mixture of water (20 mL) and ethanol (30 mL) was added
methallyl bromide (0.011 mol) in ethanol (10 mL) drop by drop. The solution was
stirred at room temperature for 3 h until the starting material was consumed (TLC).
The reaction mixture was triturated with water and the solid product obtained was
filtered off, washed with water and ethanol, and recrystallized from ethyl alcohol to give
5-(4-benzyloxy-3-methoxy)benzylidene-2-methallylthiohydantoin 5l, 5-(4-benzyloxy-
3-methoxy)benzylidene-1-methyl-2-methallylthiohydantoin 5m, 5-anthracenylidene-2-
methallylthiohydantoin 5n, and 5-anthracenylidene-1-methyl-2-methallylthiohydantoin
5o.
5-(4-Benzyloxy-3-me◦thoxy)benzylidene-2-methallylthiohydantoin
5l.
Yield 88%; m.p. = 209–211 C. IR (cm−1): 3145 (NH), 1712 (C O), 1592 (C C). δH
(ppm) (400 MHz, DMSO-d6): 1.8 (s, 3H, CH3), 3.0 (s, 2H, SCH2), 3.9 (s, 3H, OCH3), 4.5
(s, 2H, CH2 = C), 5.1 (s, 2H, OCH2), 6.7 (s, 1H, CH = C), 7.10–8.1 (m, 8H, Har), 11.7
(s, 1H, N1H). δC (ppm) (100 MHz, DMSO-d6): 21.1 (CH3C), 29.5 (SCH2), 55.2 (OCH3),
69.7 (OCH2), 112.0 (CH2 = C), 112.9 (C CH2), 113.9 (CH C), 114.8 (C CH at C5),
121.5, 125.8, 127.4, 127.9, 127.9, 128.4, 136.7, 140.2, 148.8, 149.4 (Car), 162.3 (C O at
C4 of hydantoin), 170.5 (C N). Anal. Calcd. for C22H22N2O3S (394): C, 66.98; H, 5.62;
N, 7.10. Found: C, 66.62; H, 5.38; N, 6.87.
5-(4-Benzyloxy-3-methoxy)ben◦zylidene-1-methyl-2-methallylthiohydan
toin 5m. Yield 75%; m.p. = 215–217 C. IR (cm−1): 1708 (C O), 1629 (C N). δH
(ppm) (400 MHz, DMSO-d6): 1.8 (s, 3H, CH3C), 3.3 (s, 2H, SCH2), 3.8 (s, 3H, NCH3),
4.0 (s, 3H, OCH3), 4.9–5.1 (s, 2H, CH2 = C), 5.2 (s, 2H, OCH2), 6.7 (s, 1H, CH = C),
7.1–8.2 (m, 8H, Har). δC (ppm) (100 MHz, DMSO-d6): 21.0 (CH3-C), 28.4 (SCH2), 36.7
(NCH3), 55.2 (OCH3), 69.7 (OCH2), 112.9 (CH2 = C), 113.9 (CH2 = C), 114.9 (CH C),
116.4 (CH C), 125.7, 127.4, 127.7, 127.8, 128.3, 136.6, 137.3, 140.1, 148.7, 149.3 (Car),
162.2 (C O), 170.4 (C N). Anal. Calcd. for C23H24N2O3S (408): C, 67.62; H, 5.92; N,
6.86. Found: C, 67.45; H, 5.68; N, 6.53.
5-Anthracenylidene-2-methallylthiohydantoin 5n. Yield 75%; m.p. =
◦
219–221 C. IR (cm−1): 3145 (NH), 1712 (C O), 1641 (C N); δH (ppm) (300 MHz,
DMSO-d6): 1.6 (s, 3H, CH3C), 3.5 (s, 2H, SCH2), 4.7 (s, 2H, CH2 = C), 7.0 (s, 1H, CH =
C), 7.5–8.6 (m, 9H, Har), 11.9 (s, 1H, N1H). δC (ppm) (75 MHz, DMSO-d6): 20.8 (CH3),
35.6 (SCH2), 114.2 (CH2 = C), 114.8 (C CH2), 117.1 (CH C), 118.5 (C CH), 125.4,
125.9, 126.1, 127.9, 128.5, 129.2, 133.6, 136.6 (Car), 164.9 (C O), 169.6 (C N). Anal.
Calcd. for C22H18N2OS (358): C, 73.72; H, 5.06; N, 7.81. Found: C, 73.48; H, 4.82; N,
7.56.
5-Anthracenylidene-1-methyl-2-methallylthiohydantoin 5o. Yield 69%;
m.p. = 250–252 ◦C. IR (cm−1): 1714 (NH), 1640 (C N); δH (ppm) (400 MHz, DMSO-d6):
1.8 (s, 3H, CH3C), 2.8 (s, 2H, SCH2), 3.6 (s, 3H, NCH3), 4.9–5.1 (s, 2H, CH2 = C), 6.7
(s, 1H, CH = C), δ = 7.4–8.1 (m, 9H, Har); δC (ppm) (100 MHz, DMSO-d6): 20.9 (CH3),

2-THIOHYDANTOIN DERIVATIVES
1583
31.5 (SCH2), 36.0 (NCH3), 113.9 (CH2 = C), 114.5 (C CH2), 121.3 (CH C), 122.1
(C CH), 125.4, 126.3, 127.8, 129.4, 130.9, 133.4, 137.2, 140.3 (Car), 162.2 (C O), 170.5
(C N). Anal. Calcd. for C23H20N2OS (358): C, 74.16; H, 5.41; N, 7.52. Found: C, 73.83;
H, 5.05; N, 7.26.
Action of Concentrated Hydrochloric Acid on
2-Methylmercapto-Hydantoin Derivatives, Synthesis of (3c, d, g)
A mixture of (5a-c) (1.0 g) in ethanol (30 mL) and concentrated hydrochloric acid (10
mL, 36.5%) was refluxed for 3 h until the starting material was consumed (TLC). During
the reaction the odor of methylthiol could easily be detected. The reaction mixture was con-
centrated to half its volume, cooled, filtered off, washed with water and ethyl alcohol several
times, and recrystallized from acetic acid to give 5-(4-benzyloxy-3-methoxy) benzylidene
hydantoin 3c, 5-(4-benzyloxy-3-methoxy)benzylidene hydantoin 3d, 5-anthracenylidene
hydantoin 3g; m.p. of the prepared compounds showed no depression when admixed with
authentic samples.
General Procedure for the Synthesis of 2-Morpholin-oglycocyamidine
Derivatives (7a,b)
A mixture of 5a and/or 5c (0.01 mol) and morpholine (5 mL) was heated under reflux
in an oil bath until the starting material was consumed (TLC, 4 h). During the reaction
the odor of methylthiol could easily be detected. The solid product obtained on hot was
cooled, triturated with water, filtered off, washed with distilled water and ethanol several
times, and recrystallized from acetic acid to give 5-(4-benzyloxy-3-methoxy)benzylidene-
2-morpholino-glycocyamidine 7a and 5-anthracenylidene-2-morpholinoglycocyamidine
7b.
5-(4-Benzyloxy-3-methoxy)benzylidene-2-morpholino-glycocyamidine
7a. Yield 65%; m.p. = 230–232 ◦C. IR (cm−1): 3120 (NH), 1697 (C O); δH (ppm) (400
MHz, DMSO-d6): 3.6 (m, 4H, 2CH2Nmorph), 3.7 (m, 4H, 2CH2Omorph), 3.8 (s, 3H, OCH3),
5.0 (s, 2H, OCH2), 6.6 (s, 1H, CH = C), 7.00–7.5 (m, 8H, Har), 11.3 (s, 1H, N1H); δC (100
MHz, DMSO-d6): 44.7 (2CH2Nmorph), 55.2 (OCH3), 65.5 (2CH2Omorph), 69.7 (OCH2Ph),
112.9 (CH C), 113.4 (C CH), 123.6, 125.9, 127.7, 127.8, 128.3, 129.1, 136.9, 139.2,
147.5, 148.6 (Car), 157.8 (C O), 171.8 (C N). Anal. Calcd. C22H23N3O4 (393): C, 67.16;
H, 5.89; N, 10.68. Found: C, 66.83; H, 5.61; N, 10.36.
5-Anthracenylidene-2-morpholinoglycocyamidine 7b. Yield 70%; m.p. =
above 350 ◦C. IR (cm−1): 3160 (NH), 1715 (C O); δH (ppm) (400 MHz, DMSO-d6): 3.4
(m, 4H, 2CH2Nmorph), 3.6 (m, 4H, 2CH2Omorph), 7.1 (s, 1H, CH = C), 7.5–8.6 (m, 9H, Har),
11.5 (s, 1H, N1H); δC (ppm) (100 MHz, DMSO-d6): 44.7 (2CH2Nmorph), 65.2 (2CH2Omorph),
112.3 (CH C), 114.0 (C CH), 125.4, 125.5, 126.0, 126.9, 128.6, 129.1, 130.9, 137.2 (Car),
166.8 (C O at C4 of hydantoin), 175.7 (C N). Anal. Calcd. for C22H19N3O2 (357): C,
73.93; H, 5.36; N, 11.76. Found: C, 73.61; H, 5.13; N, 11.54.
General Procedure for the Synthesis of 2-Piperidinoglycocyamidine
Derivatives 7c
A mixture of 5c (0.01 mol) and piperidine (5 mL) was heated under reflux temperature
in an oil bath until the starting material was consumed (TLC). During the reaction the odor

1584
Y. L. ALY ET AL.
of the evolved methylthiol could easily be detected. The reflux was continued until the odor
of CH3SH ceased (for 4 h). The reaction mixture was left to cool at room temperature.
The crystalline substances were separated, filtered off, washed with water and ethanol, and
crystallized from acetic acid to give 5-anthracenylidene-2-piperidinoglycocyamidine 7c.
5-Anthracenylidene-2-piperidinoglycocyamidine 7c. Yield 65%; m.p. =
above 330 ◦C. IR (cm−1): 3150 (NH), 1725 (C O), 1640 (C N), 1560 (C C); δH (ppm)
(400 MHz, DMSO-d6): 1.4–1.5 (m, 6H, 3CH2piper), 3.1–3.4 (m, 4H, 2CH2Npiper), 7.1 (s,
1H, CH = C), 7.5–8.6 (m, 9H, Har), 11.5 (s, 1H, N1H); δC (ppm) (100 MHz, DMSO-d6):
20.6–25.0 (3CH2piper), 44.4 (2CH2Npiper) 105.5 (CH C), 120.5 (C CH) 125.3, 125.7,
126.2, 127.5, 128.6, 128.7, 130.1, 130.9 (Car), 160.3(C O), 166.3 (C N). Anal. Calcd.
for C23H21N3O (355): C, 77.72; H, 5.96; N, 11.82. Found: C, 77.46; H, 5.68; N, 11.59.
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