Alkylation of thiohydantoins including synthesis, conformational and configurational studies of some acetylated s-pyranosides

Article abstract of DOI:10.1080/10426500490257131

5-Benzylidene-2-thiohydantoin (1) and 5,5-dimethyl-2,4-dithiohydantoin (6) undergo Mannich reaction with formaldehyde and morpholine to give the corresponding Mannich products 2 and 7, respectively. Subsequent reaction of the product 2 and 7 with phenacyl

Full text of DOI:10.1080/10426500490257131

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ALKYLATION OF THIOHYDANTOINS INCLUDING
SYNTHESIS, CONFORMATIONAL AND CONFIGURATIONAL
STUDIES OF SOME ACETYLATED S-PYRANOSIDES
Youssef L. Aly a , Ahmed A. El-Barbary b & Ashraf A. El-Shehawy a
a Chemistry Department, Faculty of Education, Tanta University, Tanta, Egypt
b Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
Version of record first published: 11 Aug 2010.
To cite this article: Youssef L. Aly , Ahmed A. El-Barbary & Ashraf A. El-Shehawy (2004): ALKYLATION OF THIOHYDANTOINS
INCLUDING SYNTHESIS, CONFORMATIONAL AND CONFIGURATIONAL STUDIES OF SOME ACETYLATED S-PYRANOSIDES, Phosphorus,
Sulfur, and Silicon and the Related Elements, 179:1, 185-202
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Phosphorus, Sulfur, and Silicon, 179:185–202, 2004
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ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490257131
ALKYLATION OF THIOHYDANTOINS INCLUDING
SYNTHESIS, CONFORMATIONAL AND
CONFIGURATIONAL STUDIES OF SOME
ACETYLATED S-PYRANOSIDES
Youssef L. Aly,a Ahmed A. El-Barbary,b
and Ashraf A. El-Shehawya
Chemistry Department, Faculty of Education, Tanta University,
Tanta, Egypta and Chemistry Department, Faculty of Science,
Tanta University, Tanta, Egyptb
(Received April 4, 2003; accepted July 26, 2003)
5-Benzylidene-2-thiohydantoin (1) and 5,5-dimethyl-2,4-dithiohydan-
toin (6) undergo Mannich reaction with formaldehyde and morpho-
line to give the corresponding Mannich products 2 and 7, respec-
tively. Subsequent reaction of the product 2 and 7 with phenacyl
bromide gives the corresponding 2-benzolmethylthiohydantoin Reac-
tionof 5-benzylidene-2-carbomethoxythiohydantoin (5b) with P2S5 af-
forded 4-benzylideneimidazo[2,1-b]-thiazole-2-thione-5-one (13) as the
sole product. Reaction of 2-thio and 2,4-dithiohydantoin derivatives
2 and 7 with (2,3,4,6-tetra-O-acetyl-α–D-gluco- or galgcto- pyranosyl)
bromide or (2,3,4-tri-O-acetyl-α-xylopyranosyl) bromide afforded the
corresponding S-gluco- galacto- or xylosides (14–19). Many attempts to
deacetylation of the resulting S-nucleosides and to get N-nucleosides
were tried.
Keywords: Ethylchloroacetate; morpholine; phenacyl bromide; S-
Pyranosides; thiohydantoins
Hydantoin derivatives have found use in medicine; they have mainly
been described as anticonvulsant agent.1 Authors reported that 2-
deoxyuridine with 5-methyl-2-thiohydantoin as the heterocycle in the
5-position showed cytotoxicity against MT-4 cell at 100 mM.2 Some
acylic nucleoside analogues have achieved considerable success as
antiviral agents3 because of their low toxicity for normal cells with
having an inhibitory activity against herpes simplex virus (HSV).
Thanks are due to Danish International Development Agency (DANIDA) for their
support.
Address correspondence to Y. L. Aly, Chemistry Department, Faculty of Education,
Kafr El-Sheikh, Tanta University, Tanta, Egypt. E-mail: ylaly2002@hotmail.com
185

186
Y. L. Aly et al.
Several 5-substituted pyrimidine nucleosides show potent activity
against the HSV.4 There should be an obvious interest in glycosy-
lated hydantoin derivatives because of their resemblance with nat-
ural nucleosides. Hydantoin nucleosides are not common described
in the literature.5–12 Recently pentofuranosyl-2-thiohydantoin13 and
pentofuranosyl-1-hydantoin derivatives14,15 have been reported. The
present article deals with the synthesis of some new pyranosides, con-
taining a hydantoin nucleus as an aglycone moiety.
RESULTS AND DISCUSSION
The synthesis of Mannich bases derived from 5-substituted-2-thio-
hydantoin was previously studied and the site of attack was re-
ported to be only at position three.16 Thus, when 5-benzylidene-2-thio-
hydantoim (1) was allowed to react with formaldehyde and morpholine
in ethanol at room temperature, 5-benzylidene-3-morpholinomethyl-
2-thiohydantoin (2) was obtained. The reaction of compound 2
with phenacyl bromide in aqueous sodium hydroxide and ethanol
at room temperature afforded the corresponding 5-benzylidene-3-
morpholinomethyl-2-benzoylmethylthiohydantoin (3). Microanalytical
and spectral data of compounds 2 and 3 were fully consistent with the
structures assigned (cf. Experimental).
The reaction of 1 with ethyl chloro- formate or acetate in differ-
ent alkaline medium was also investigated, but the starting materi-
als were recovered unchanged. Thus, we have tried the reaction of 4,
as potassium salt of 1, with ethyl chloro- formate or acetate by fu-
sion at 90–100◦C for 10 hours yielded the corresponding 5-benzylidene
-2-carboethoxythiohydantoin (5a) and 5-benzylidene-2-carboethoxy-
methylthiohydantoin (5b), respectively microanalytical and spectral
data of 5b were found to be completely identical with reported values.16
The structure of compound 5a is established by the correct analytical
and spectral data. Its IR spectrum of showed the absence of the stretch-
ing vibration frequency of C S at 1310 cm−1, and the appearance of a
strong stretching vibration frequency of C O (ester) at 1760 cm−1, and
1
C N at 1566 cm−1. H-NMR spectrum of 5a showed a triplet at 1.42–
1.53 ppm corresponding to 3H (CH3) and a quartet at 4.51–4.59 ppm
corresponding to 2H (CH2). Moreover, 13C-NMR spectrum of 5a showed
signals at 147.73 ppm (C O of hydantoin) and 194.38 ppm (C O, es-
ter), while signals at 65.17 and 13.95 ppm are corresponding to CH2
and CH3, respectively.
To the best of our knowledge, no work has been done on the reaction
of 2,4-dithiohydantoins with Mannich base. Thus, when, 5,5-dimethyl-

Alkylation of Thiohydantoins
187
2,4-dithiohydantoin (6) was treated with formaldehyde and morpholine,
it yields the corresponding 5,5-dimethyl-3-morpholinomethyl-2,4-
dithiohydantoin (7). Microanalytical and spectral data of compound 7
were fully consistent with the assigned structure (cf. Experimental).
On treatment of 7 with one equivalent of phenacyl bromide in
the presence aqueous sodium hydroxide, 5,5-dimethyl-3-morpholino-
methyl-2-benzoylmethylthio-4-thiohydantoin (8) was obtained. While,
one equivalent of compound (6) reacts with two equivalents of phenacyl
bromide under the same reaction conditions yielded 5,5-dimethyl-2,4-
dibenzoylmethylthiohydantoin (9). The structure of compounds 8 and 9
was proven by their spectral data. Their IR spectra exhibited a strong
carbonyl stretching frequency at 1690 cm−1, whereas they lack absorp-
tion in the region of 3300 cm−1, confirming the absence of NH group.
1H-NMR, 13C-NMR and M.S. spectroscopy were found in agreement
with the proposed structures (cf. Experimental).
It is well known that phosphorous pentasulphide is a good thion-
ating reagent for the transformation of hydantoin to the corre-
sponding thiohydantoin.17 In our work, we have found that 5-
benzylidene-2-carboethoxymethylthiohydantoin (5b) reacts with phos-
phorous pentasulphide in boiling anhydrous dioxane to furnish
4-benzylideneimidazo[2,1-b]-thiazole-2-thione-5-one (13) as the sole
product.
For the formation of compound 13, it is postulated that compound
5b was first thiated with phosphorous pentasulphide to give the thio-
noester 10 which either looses ethanol followed by ring closure to give
13 (path A) or rearranges18,19 to give the thionoester 11. Subsequent

188
Y. L. Aly et al.
thiation of 11 affords 12 that suffers expulsion of ethanethiol accompa-
nied by ring closure to yield the final product 13 (path B). The structure
of compound 13 was proven by microanalysis and spectral data, its IR
spectrum showed the absence of the stretching frequency of C O (es-
ter) at 1760 cm−1, and NH at 3300 cm−1, while a strong absorption at
1720 cm−1 corresponding to C O of hydantoin moiety still appears. Its
1H-NMR showed a signlet at 4.03 ppm (2H, S-CH2). Its 13C-NMR spec-
trum showed peaks at 140.69 (C N), 169.17 (C O of hydantoin moiety),
in addition to two peaks at 61.12 and 194.80 ppm, characteristic of CH2
and C S, respectively.
Treatment of 5-arylidene-3-substituted-2-thiohydantoins (2a–d) and
5,5-Dimethyl-3-morpholinomethyl-2,4-dithiohydantoin (7) with 2,3,4,
21,22
6-tetra-O-acetyl-α-D-glucopyranosyl- bromide
in acetone in the
presence of aqueous potassiuum hydroxide yielded the S-glucosides,

Alkylation of Thiohydantoins
189
5-arylidene-3-substituted-2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-thiogluco-
pyranosyl)hydantoins (14a–d) and 5,5-dimethyl-3-orpholinomethyl-
2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-thioglucopyranosyl)-4-thiohydantoin
(15), respectively, presumably through Walden inversion.20 The struc-
ture of compounds 14a–d and 15 is established by microanalytical and
spectral data.
In the IR spectra of 14a–d and 15, a strong absorption bands at 1760–
1755 cm−1 were observed due to the acetate carbonyl, in addition to the
absorption bands at 920–910 and 770–760 cm−1 region characterized for
asymmetrical and symmetrical vibration of the glucopyranoside ring.21
1H-NMR spectra of compounds 14 and 15 show two doublets of the
anomeric protons at δ = 6.06 and 6.64 ppm region with a large coupling
constant (J = 10.18 and 10.20 Hz), respectively corresponding to the di-
axial orientation of H-1ꢁ and H-2ꢁ protons indicating the presence of only
isomers in the 4C1 (D) conformation.22 13C-NMR spectra of compounds
14 and 15 are characterized by a signal at δ = 80.03–80.97 ppm re-
gion corresponding to C-1ꢁ atom of β-anomer.23 No signals are observed
for the C S at C-2 of the thiohydantoin indicating that the coupling
reaction took place at the sulfur atom giving the 2-S-glucosides.
Reaction of compounds 2a–f and 7 with 2,3,4,6-tetra-O-acetyl-α-D-
galactopyranosyl bromide21,22 yielded the corresponding 5-arylidene-
3-substituted-2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-thiogalactopyranosyl)-
hydantoins (16a–f) and 5,5-dimethyl-3-morpholinomethyl-2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-
tetra-O-acetyl-β-D-thiogalctopyranosyl)-4-thiohydantoin (17), respec-
tively, The Structure of 16a–f and 17 is established by microanalytical

190
Y. L. Aly et al.
and spectral data. IR spectra of 16a–f and 17 show strong absorption
band at 1760–1755 cm−1, due to the acetate carbonyl, in addition to the
absorption band at 915–910 and 770–760 cm−1 region characterized
for asymmetrical and symmetrical vibrations of the pyranoside ring of
D-galactose21, respectively.
1H-NMR spectra of compounds 16 and 17 show anomeric proton with
coupling constant (J1ꢁ, 2ꢁ) in the order of 10.30–10.34 Hz and that the
(J2ꢁ, 3ꢁ) is 10.12–10.16 Hz indicating that the H-1ꢁ, H-2ꢁ and H-3ꢁ protons
are all axially oriented. The splitting constants of (J3ꢁ, 4ꢁ) and (J4ꢁ, 5ꢁ)
are between 3.26–3.29 and 2.89–3.17 Hz showing their axial-equatorial
4
relationship. Thus, the C1 (D) conformation and the β-configuration
predominate over the other possible structures.22 Further support of the
structures was confirmed by the chemical shifts of the acetoxy groups.
A lower field acetoxy at 2.15 ppm assigned as the axial acetoxy groups
at C-4ꢁ and the other three remaining acetoxy groups were relatively at
higher fields δ = 1.63–2.09 ppm indicating their equatorial orientation.
The 4C1 (D) conformation and the β-configuration was also confirmed by
13C-NMR spectrum which showed a signal at δ = 80.56 ppm correspond-
ing to C-1ꢁ of β-anomer.23 No signals are observed for the C S at C-2 of
the thiohydantoin indicating the formation of the 2-thiogalactosides.
Reaction of compounds 2a–c,e and 7 with 2,3,4-tri-O-acetyl-α-D-
xylopyranosyl bromide28,29 was also investigated which afforded the
corresponding 5-arylidene-3-substituted-2-(2ꢁ,3ꢁ,4ꢁ-tri-O-acetyl-β-D-
thioxylopyranosyl)hydantoins (18a–d) and 5,5-dimethyl-3-morpholino-
methyl-2-(2ꢁ,3ꢁ,4ꢁ-tri-O-acetyl-β-D-thioxylopyranosyl)-4-thiohydantoin

Alkylation of Thiohydantoins
191
(19), respectively. The structure of compounds 18a–d and 19 is
established by microanalytical and spectral data.
IR spectra of compounds 18 and 19 show the absence of the stretching
vibration frequencies of NH within 3200–3150 cm−1, and appearance
of the strong bands at 1760–1755 cm−1 due to the acetate carbonyl. The
absorption bands at 920–910 and 770–760 cm−1 region are character-
ized for asymmetrical and symmetrical vibrations of the xylopyranoside
ring21, respectively.
1H-NMR spectra of compounds 18 and 19 were similar to that of the
previously synthesized S-glucosides 14–17. The anomeric protons were
found to be at lower field (δ = 6.05–6.08 ppm) than the other sugar ring
protons with coupling constants (J1ꢁ, 2ꢁ) in the order of 7.73–7.52 Hz
due to the diaxial orientation between H-1ꢁ and H-2ꢁ which indicates
the β-configuration and 4C1 (D) conformation.22 The acetoxy group sig-
nals of these compounds provided further verification of the favored 4C1
(D) confirmation and β-configuration, since these signals lie within the
range expected for equatorial secondary acetoxy groups. 13C-NMR spec-
tra of compounds 18 and 19 showed signals at the region of δ = 80.65–
81.26 ppm corresponding to C-1ꢁ of β-anomer.23 No signals are observed
for the C S at C-2 of the thiohydantoin indicating the formation of the
S-xylosides.
In all cases, the I3C-NMR spectra of compounds 14–19 showed no sig-
nals corresponding to C S of hydantoin moiety at C-2 indicating that
the coupling took place at sulfur atom to give the S-gluco-, galacto- and
xylo-sides. These results are in good agreement with earlier findings

192
Y. L. Aly et al.
reported by Wagner and Dietzsch24 and Abdel-Megeid et al.25 for sim-
ilar structures. We have tried to get N-nucleosides through the re-
action of 5-benzylidene-3-phenyl-2-(chloromercurithio)hydantoin (20),
prepared by the reaction of 2e with mercuric chloride,26 with (2,3,4,6-
tetra-O-acetyl-α-D-galactopyranosyl) bromide (ABGal.) in dry toluene
or xylene, in the presence of sodium hydroxide, but we obtained the
S-galactoside 16e as the sole prduct.
It is worth to mention that all attempts to get N-glucosides from
the reaction of sodium or potassium salt of some arylidene hydantoin
derivatives (21a,b) with (2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)
bromide (ABG) in different basic mediums (NaOH, EtONa, NaH, KOH,
K2CO3 or NaOMe/MeOH) at different temperatures (0◦C, room temper-
ature) were unsuccessful.
Moreover, we have tried the rearrangement of the S-galactosides
16a,e to the crrosonding N-Galactosides by their reaction with mer-
curic bromide in toluene or xylene, but cleavage for 16a,e took place
giving 2a,e may be due to the decomposition of the S-galactosides un-
der the reaction conditions.
16a,e + HgBr2 → 2a,e
Deacetylation of the S-glucoside 14d with different concentrations of
methanolic ammonia or sodium ethoxide at 0◦C or at room temperature
afforded a mixture of 2d and 22. Their m.p. and mixed m.p. with au-
thentic samples of 5-(4-chlorobenzylidene)-3-methyl-2-thiohydantoin27

Alkylation of Thiohydantoins
193
and 5-(4-chlorobenzylidene)-3-methylhydantoin27, respectively, gave no
depression. Nothing of the deprotected S-nucleosides could be detected
by thin layer chromatography and this result showed the unstability of
this type of nucleosides in alkaline medium.
EXPERIMENTAL
All melting points are uncorrected. Microanalyses were performed by
microanalytical center at Cairo University. IR were recorded on Perkin-
1
Elmer 1420 spectrophotometer using KBr Wafer Technique. The H-
NMR spectra were recorded using a Bruecker 250 MHz spectropho-
tometer using CDC13 and DMSO as solvents and TMS as internal
standard. Chemical shift values are expressed in δ ppm units. 13C-NMR
spectra were recorded on a Bruecker 250 MHz spectrophotometer. TMS
was used to determine the carbon chemical shifts and expressed in ppm.
All analytical samples were homogeneous by thin-layer chromatogra-
phy, which was performed on EM silica gel 60F sheet (0.2 mm) with
C6H6/CHC13 (2:5, V/V) and in ether/benzene (2:1, V/V) as the develop-
ing solvents. The spots were detected with U.V. Model UVGL-58.
Reaction of 1 or 6 with Formaldehyde and Morpholine:
General Procedure
A mixture of 5-benzylidene-2-thiohydantoin (1) or 5,5-dimethyl-2,4-
dithiohydantoin (6) (0.01 mole), formaldeyde (1.0 ml, 40% solution)
and morpholine (0.01 mole) in ethanol (30 ml) was stirred at room
temperature for three hours and left overnight at room temperature.
The solvent was evaporated to dryness under vacuum and the re-
sulting residual solid was crystallized from aqueous ethanol to give
the corresponding 5-benzylidene-3-morpholinomethyl-2-thiohydantoin
(2) and 5,5-dimethyl-3-morpholinomethyl-2,4-dithiohydantoin (7),
respectively.
For compound 2; m.p.: 148◦C, yield: 93%. Calc. for C15H17N3O2S: C,
59.41; H, 5.61; N, 13.86; S, 10.56; found: C, 59.40; H, 5.63; N, 13.85; S,

194
Y. L. Aly et al.
10.56. IR (cm−1): 3100 (NH), 2950 (CH aliphatic), 1720 (CO of hydan-
toin); 1640 (C C); 1315 (C S). 1H-NMR (CDC13): δ (ppm) = 2.71–2.75
(4H, t, 2C-CH2-N); 3.62–3.65 (4H, t, 2C-CH2-O); 4.83 (2H, s, N-CH2-
N); 6.74 (1H, s, Ph-CH C); 7.41–7.46 (5H, m, aromatic protons); 9.37
(1H, s, N-1H). 13C-NMR (CDCl3): δ (ppm) = 51.36 (2 CH2-N); 62.72 (N-
CH2-N); 66.73 (2CH2-O); 132.62 (C-5 of hydantoin); 164.76 and 179.57
(C O and C S); 113.42, 129.61, 126.13, 129.30 and 129.07 (aromatic
carbons).
For compound 7; m.p.: 133◦C, yield: 89%. Calc. for C10H17N3OS2: C,
46.33; H, 6.56; N, 16.22; S, 24.71; found: C, 46.40; H, 6.55; N, 16.20; S,
24.59. IR (cm−1): 3100 (NH), 2950 (CH aliphatic), 1310 (C S). 1H-NMR
(CDC13): δ (ppm) = 1.50 (6H, s, 2CH3); 1.64 (2H, s, 2N-CH2-N); 2.89
(4H, s, CH2-N-CH2); 3.70 (4H, s, CH2-O-CH2); 9.13 (1H, s, N-1H,). Ms,
m/z.:259 (M+, 16%, C10H17N3OS2+), 160 (16%, C5H8N2S2), 100 (100%,
C5H10O+ or C4H6NS+), 56 (9.5%, C3H6N+), 57 (2%; C3H7N).
Action of Potassium Ethoxide on Compound 1
5-Bnezylidene-2-thiohydantoin (1) (0.01 mole) was added to a solu-
tion of potassium ethoxide (0.39 gm of potassium, 0.01 mole, in 20 ml
absolute ethanol) in ice bath with vigorous stirring for 30 minutes.
The starting material was dissolved and the potassium salt was sepa-
rated. The solid product was filtered off, washed with ether to give 5-
benzylidene-2-potssiothiohydantoin (4); m.p.: 287◦C, yield: 55%. Calc.
for C10H7N2OSK: C, 49.50; H, 2.89; N, 11.55; S, 13.20; found: C, 49.33;
H, 2.71; N, 11.43; S, 13.06.
Reaction of 5-BenzyIidene-2-potassiothiohydantoin (4)
with Ethyl Chloroformate or-Acetate
A mixture of compound (4) (0.01 mole) and ethyl chloroformate or
chlroroacetate (5 ml) was heated under reflux in an oil bath at 90–
100◦C for 10 hours. The reaction mixture was filtered off while hot
and the filtrate was triturated with ethanol to give a solid which on
filtration and recrystallization from ethanol afforded the correspond-
ing 5-benzylidene-2-carboethoxythiohydantoin (5a) and 5-benzylidene-
2-carboethoxymethylthiohydantoin (5b), respectively.
For compound 5a; m.p.: 229◦C, yield: 65%. Calc. for C13H12N2O3S:
C, 56.52; H, 4.85; N, 10.14; S, 11.59; found: C, 56.60; H, 4.80; N, 9.90;
S, 11.81. IR (cm−1): 3110 (NH), 2950 (CH aliphatic), 1760 (C O, es-
1
ter) 1720 (C O of hydantoin), 1565 (C N). H-NMR (CDC13): δ (ppm)
= 1.42–153 (3H, t, CH3-C); 4.51-4.59 (2H, q, CH2-C); 7.07 (1H, s,
Ph-CH C); 7.40–8.07 (5H, m, aromatic protons); 10.56 (1H, s, N-1H).

Alkylation of Thiohydantoins
195
13C-NMR (CDC13): δ (ppm) = 147.73, 169.95 and 133.41 (C-2, C-4
and C-5 of hydantoin); 125.10, 132.40, 128.18, 131.59 and 130.30 (aro-
matic carbons); 194.38, 65.17 and 13.95 (carboethoxy carbons). M.p.
and mixed m.p. of 5b with an authentic sample of 5-benzylidene-2-
carboethoxymethylthiohydantoin gave no depression.16
Reaction of Compounds 2, 6 and 7 with Phenacyl
Bromide: General Procedure
A mixture of 2, 6 or 7 (0.01 mole) in aqueous potassium hydroxide
(0.56 gm, 0.01 mole, in 10 ml water), ethanol (30 ml), and phenacyl bro-
mide (2.2 gm, 0.011 mole) was stirred at room temperature for 1–2 hr.
The reaction mixture was triturated with water. The solid product
was filtered off and crystallized from ethanol to give 5-benzylidene-
3-morpholinomethyl-2-benzoylmethylthiohydantoin (3), 5,5-dimethyl-
3-morpholinomethyl-2-benzoylmethyIthio-4-thiohydantoin (8) and 5,5-
dimethyl-2,4-dibenzoylmethylthiohydantoin (9).
For compound 3; m.p.: 165◦C, yield: 92%. Calc. for C23H23N3O3S: C,
65.56; H, 5.46; N, 9.98; S, 7.60; found: C, 65.61; H, 5.47; N, 9.95; S,
7.51. IR (cm−1): 2950 (CH aliphatic), 1720 (C O of hydantoin), 1690
(C O of benzoyl), 1560 (C N), 700 (C S ). 1H-NMR (CDCl3): δ (ppm)
= 2.64 (4H, s, 2 C-CH2-O); 4.37 (2H, s, S-CH2-CO); 4.78 (2H, s, N-
CHrN); 6.89 (1H, s, Ph CH C); 7.06–8.11 (10H, m, aromatic protons).
13C-NMR (CDC13): δ (ppm) = 163.80, 169.90 and 137.59 (C-2, C-4 and
C-5 of hydantoin); 62.55, 50.63 and 66.46 (morpholinomethyl carbons);
38.42, 191.96, 133.82, 128.17, 131.58 and 129.54 (benzoylmethyl car-
bons); 124.41, 135.55, 133.68 and 128.73 (benzylidene carbons).
For compound 8; m.p.: 134◦C, yield: 90%. Calc. for C18H23N3O2S3:
C, 57.29; H, 6.10; N, 11.14; S, 16.98; found: C, 57.30; H, 6.23; N, 11.10;
S, 17.02. IR (Cm−1): 2980 (CH aliphatic), 1690 (C O of benzoyl), 1550
(C N), 700 (C-S-C).
For compound 9; m.p.: 110◦C, yield: 85%. Calc. for C21H20N2O2S2: C,
63.64; H, 5.05; N, 7.07; S, 16.16; found: C, 63.70; H, 5.21; N, 7.02; S,
15.96. IR (Cm−1): 3000 (CH aliphatic), 1690 (C O of benzoyl), 1550
(C N), 700 (C S C). 1H-NMR (CDC13): δ (ppm) = 1.36 (6H, s, 2
CH3); 4.68 (2H, s, S-CH2-CO at C-4); 4.78 (2H, s, S-CH2-CO at C-2);
7.46–8.05 (1 OH, m, aromatic protons). 13C-NMR (CDCI3): δ (ppm) =
192.38, 169.63 and 82.60 (C-2, C-4 and C-5 of hydantoin); 24.90 (2 CH3);
39.32, 202.51, 134.98, 128.47, 133.45 and 128.29 (benzoylmethyl car-
bons at C-2); 40.81, 193.47, 135.34, 128.64, 133.80 and 128.35 (benzoyl-
methyl carbons at C-4). Ms, m/z 396( M+, 3%, C21H20N2O2S2), 291 (3%,
C14H15N2OS2), 268 (5%, C12 H20N2OS2), 246 (5%, C13H14N2OS), 106
(7%, Ph-CHO), 105 (100%, Ph-CO+), 78 (4%; C6H6).

196
Y. L. Aly et al.
Reaction of Compound 5b with Phosphorous
Pentasulfide
A mixture of compound 5b (0.01 mole) and phosphorus pentasulfide
(0.012 mole) was refluxed in anhydrous dioxane (50 ml) with vigor-
ous stirring for one hr. To the reaction mixture, 2 gm of zinc dust
and 1 gm of activated charcoal was added and heating was contin-
ued 5 minutes more. The hot solution was filtered off, evaporated to
dryness and the residue was crystallized from ethanol to give the
corresponding 4-benzylideneimidazo[2,l-b]thiazole-2-thione-5-one (13);
m.p.: 165◦C, yield: 86%. Calc. for C12H8N2OS2: C, 55.20; H, 3.00; N,
10.70; S, 24.90; found: C, 55.38; H, 3.08; N, 10.77; S, 24.60. IR (cm−1):
3000 (CH aliphatic), 1720 (C O of hydantoin), 1565 (C N), 1320 (C S),
710 (C-S-C). 1H-NMR (CDCl3): δ (ppm) = 4.03 (2H, s, S-CH2); 5.77 (1H,
s, Ph-CH C); 7.36–7.46 (5H, m, aromatic protons). 13C-NMR(CDC13):
δ (ppm) = 140.69, 169.17 and 137.73 (C-2, C-4 and C-5 of hydan-
toin); 161.21 and 194.80 (CH2 and C S, respectively); 120.70, 130.18,
127.40, 128.97 and 128.44 (benzylidene carbons). Ms, m/z (260, M+,
18%, C12H8N2OS2), 220 (72%, C10H8N2S2), 219 (74%, C10H7N2S+), 160
2
(3%, C9H6NS+), 117 (13.5%, C8H7N), 116 (12%, C8H6N+).
Reaction of Compounds 2 and 1 with 2,3,4,6-Tetra-
O-acetyl-α-D-gluco- or Galactopyranosyl Bromide
and 2,3,4-Tri-O-acetyl-α-D-xylopyranosyl Bromide
General Procedure
To a solution of 2 and 7 (0.01 mole) in aqueous potassium hydrox-
ide (0.56 gm, 0.01 mole, in 6 ml distilled water), a solution of (2,3,4,6-
tetra-O-acetyl-α-D-gluco- or galacto -pyranosyl) bromide or (2,3,4-tri-
O-acetyl-α-D-xylopyranosyl) bromide (0.011 mole) in acetone (30 ml)
was added. The reaction mixture was stirred at room temperature un-
til the starting material was consumed (TLC). The solvent was evap-
orated under reduced pressure at 40◦C and the residue was washed
with distilled water to remove the formed potassium bromide. The re-
sulting solid was dried and crystallized from ethanol to give 14a–d, 15,
16a–f, 17, 18a–d and 19. The physical and analytical data are listed in
Tables I–III.
Action of Mercuric Chloride on
5-Benzylidene-3-phenyl-2-thiohydantoin 2e
A mixture of 2e (0.01 mole) and sodium hydroxide (0.4 gm, 0.01 mole)
in 50% aqueous ethanol (20 ml) was added slowly to a stirred solution

Alkylation of Thiohydantoins
197
TABLE I Experimental Data of Compounds 14–19
Analysis (Calcd./Found)
Compd.
No.
Time
(hr)
M.P.
(◦C)
Yield
(%)
Mol. Formula
(Mol. Wt.)
C
H
N
S
14a
14b
14c
14d
15
2
8
190
198
201
219
97
89
C29H35N3O11
(633.66)
C25H28N2O10
(548.60)
C26H3oN2O11
(578.59)
C25H27C1N2O10
(583.01)
S
54.97
55.10
54.74
54.81
53.87
53.97
51.50
51.39
48.89
48.60
54.97
55.10
54.74
54.90
53.97
53.90
51.50
51.80
59.01
58.50
58.12
58.12
48.89
48.60
55.61
55.80
55.46
55.40
54.54
54.70
60.22
59.93
48.74
48.90
5.53
5.60
5.11
5.21
5.19
5.28
4.63
4.70
5.94
5.80
5.53
5.60
5.11
5.20
5.19
5.20
4.63
4.38
4.92
5.00
5.00
5.05
5.94
5.80
5.52
5.70
5.04
4.90
5.14
5.00
4.83
4.70
5.99
6.10
6.63
6.70
5.11
4.88
4.84
4.88
4.80
4.81
7.13
7.10
6.63
6.70
5.11
5.00
4.84
4.80
4.80
4.50
4.59
4.40
4.37
4.40
7.13
7.10
7.48
7.50
5.88
5.70
5.53
5.60
5.20
5.30
8.12
8.30
5.05
4.90
5.84
5.80
5.53
5.52
4.59
4.39
10.86
10.53
5.05
4.90
5.84
5.97
5.53
5.48
5.49
5.30
5.24
5.11
5.00
4.80
10.86
10.63
5.70
5.50
6.72
6.50
6.32
6.11
5.94
5.80
12.38
12.20
91
S
S
6
93
4
87
S
1
85
C24H35N3O10S2
(589.67)
29H35N3O11
(633.67)
16a
16b
16c
16d
16e
16f
17
2
95
93
C
S
S
S
15
20
20
12
8
135
160
149
130
117
84
93.5
94.5
89
C
C
25H28N2O10
(548.60)
26H30N2O11
(578.59)
C25H27C1N2O10
(583.01)
S
84.5
91
C
30H3oN2O10
(610.63)
S
C
31H32N2O11
(640.50)
S
1.5
1
87
C
24H35N3O10S2
(589.67)
18a
18b
18e
18d
19
107
170
133
194
89
83
C26H31N3O9S
(561.61)
5
87
C
C
C
22H24N2O8S
(476.50)
23H26N2O9S
(506.52)
27H26N2O8S
(538.57)
4
85
2
86
1
87
C21H3,N3O8S2
(517.61)
of mercuric chloride (2.72 gm, 0.01 mole) in ethanol (30 ml) until
the starting material was consumed (TLC). The solid formed was fil-
tered off, washed with 25 ml distilled water and dried to give 5-
benzylidene-3-phenyl-2-(chIoromercurithio)hydantoin 20; m.p.: 291◦C,
yield: 95%. Calc. for C16H11N2OSHgCl: C, 37.24; H, 2.14; N, 5.43;
S, 6.21; CI, 6.89; found: C, 37.16; H, 2.11; N, 5.26; S, 6.05; Cl,
6.73.

198
Y. L. Aly et al.
TABLE II 1H-NMR and 13C-NMR Spectral Data of the Newly Prepared
S-Nucleosides
1H-NMR (δ ppm)
13C-NMR (δ ppm)
14a; 1.73 (3H, s, CH3-CO.at C-6ꢁ), 1.98 (3H,
s, CH3-CO at C-4ꢁ), 2.04 (6H, s,
14a; 80.36, 68.78, 72.96, 68.01, 75.25,
65.85 (C-1ꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ, C-5ꢁ
and C-ꢁ); 20.25, 20.34, 20.25,
20.13 (4CH3 of acetoxy groups at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 169.50,
169.81, 169.34,169.25 (4C O at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 161.98,
168.62, 137.61 (C-2, C-4 and
C-5); 124.20, 133.86, 128.70,
132.09, 30.70 (benzylidene
2CH3-CO at C-2ꢁ and C-3ꢁ), 2.47 (4H, s,
2C-CH2-N), 3.34 (2H, s, N-CH2-N), 3.55
(4H, s, 2C-CH2-O), 4.04–4.12 (2H, m,
H-6ꢁ and H-6ꢁꢁ at C-6ꢁ), 4.14–4.24 (1H at
C-4ꢁ, m), 5.02–5.09 (1H at C-2ꢁ, t),
5.33–5.40 (1H at C-3ꢁ, t), 5.63-5.67 (1H
at C-5ꢁ, t), 5.94–5.98 (1H at C-1ꢁ, d,
anomeric proton, J = 10.18 Hz), 6.99
(1H, s, Ph-CH C), 7.48–8.32 (5H, m,
aromatic).
carbons); 50.27, 61.66, 62.12
(4CH2, morpholinomethyl
carbons).
14b; 1.79 (3H, s, CH3-CO at C-6ꢁ), 2.50 (3H,
s, CH3-CO at C-4ꢁ), 2.07 (3H, s,
14b; 80.97, 68.97, 76.90, 68.97, 76.95,
61.71 (C-lꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ, C-5ꢁ
and C-6ꢁ); 20.24, 20.38, 20.41,
20.41 (4CH3 of acetoxy groups at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 170.38,
169.35, 169.86, 169.35 (4C O at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 161.24,
169.25, 137.84 (C-2, C-4 and C-5);
125.34, 134.05, 128.54, 131.86,
130.03, (benzylidene carbons);
26.49 (N-CH3).
14d; 80.03, 68.84, 72.68, 67.93, 75.22,
61.70 (C-1ꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ, C-5ꢁ
and C-6ꢁ); 20.04, 20.24, 20.04,
20.24 (4CH3 of acetoxy groups at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 169.36,
169.74, 169.36, 169.74 (4C O at
C-2ꢁ, C-3ꢁ, C-41 and C-6ꢁ); 162.41,
168.26, 138.16 (C-2, C-4 and C-5);
122.14, 134.49, 128.70, 133.58,
132.85 (benzylidene carbons);
26.41 (N-CH3).
16d; 80.56, 67.68, 70.62, 66.37, 74.86,
61.69 (C-1ꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ, C-5ꢁ
and C-6ꢁ); 20.23, 20.29, 20.18,
19.91 (4CH3 of acetoxy groups at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 169.63,
169.86, 169.58, 169.28 (4C O at
C-2ꢁ, C-3ꢁ, C-4ꢁ and C-6ꢁ); 162.58,
168.29, 138.13 (C-2, C-4 and C-5);
122.10, 134.40, 128.66, 133.59,
132.79 (benzylidene carbons);
26.37 (N-CH3).
CH3-CO at C-2ꢁ), 2.08 (3H, s, CH3-CO
at C-3ꢁ), 3.13 (3H, s, N3-CH3),
3.46–3.97 (2H, m, H-6ꢁ and H-6ꢁꢁ at
C-6ꢁ), 4.15–4.28 (1H at C-4ꢁ, m),
5.11–5.19 (1H at C-2ꢁ, t), 5.33–5.47 (2H
at C-3ꢁ and C-5ꢁ, m), 5.85–5.89 (1H at
C-1ꢁ, d, anomeric proton, J = 10.20 Hz),
7.02 (1H, s, Ph-CH C), 7.42–8.14 (5H,
m, aromatic).
15; 1.50 (6H, s, 2CH3 at C-5), 1.91 (3H, s,
CH3-CO at C-6ꢁ), 1.98 (3H, s, CH3-CO
at C-4ꢁ), 2.06 (3H, s, CH3-CO at C-2ꢁ),
2.12 (3H, s, CH3-CO at C-3ꢁ), 2.89 (2H,
s, N-CH2-N), 3.68 (4H, s, 2C-CH2-N),
3.89 (4H, s, 2C-CH2-O), 4.19–4.45 (2H,
m, H-6ꢁ and H-6ꢁꢁ at C-6ꢁ), 5.24–5.27
(1H at C-4ꢁ, m), 4.34–4.38 (1H at C-2ꢁ,
t), 6.33–6.34 (1H at C-3ꢁ, t), 4.46–4.47
(1H at C-5ꢁ, t), 6.63–6.64 (1H at C-1ꢁ, d,
anomeric proton, J = 10.17 Hz).
16d; 1.63 (3H, s, CH3-CO at C-6ꢁ), 1.98 (3H,
s, CH3-CO at C-4ꢁ), 2.09 (3H, s,
CH3-COatC-2ꢁ), 2.15 (3H, s,
CH3-COatC-3ꢁ), 3.07 (3H, s, N3-CH3),
4.01–4.08 (2H, m, H-6ꢁ and H-6ꢁꢁ at
C-6ꢁ), 4.56 (1H at C-4ꢁ, m), 5.21–5.28
(1H at C-2ꢁ, t), 5.43 (1H at C-3ꢁ, t),
5.59–5.62 (1H at C-5ꢁ, t), 6.04–6.08 (1H
at C-1ꢁ, d, anomeric proton, J =
10.34 Hz), 6.99 (1H, s, Ph-CH C),
7.51–7.54 (2H, d, aromatic), 8.31–8.34
(2H, d, aromatic).
(Continued on next page)

Alkylation of Thiohydantoins
199
TABLE II (Continued)
1H-NMR δ ppm
13C-NMR (δ ppm)
17; 1.18–1.30 (4H, t, 2C-CH2-N), 1.35–1.40 (4H,
t, 2C-CH2-0), 1.34 (6H, s, 2CH3 at C-5), 1.98
(3H, s, CH3-CO at C-6ꢁ), 1.99 (3H, s, CH3-CO
at C-4ꢁ), 2.00 (3H, s, CH3-CO at C-2ꢁ), 2.01
(3H, s, CH3-CO at C-3ꢁ), 3.32 (2H, s,
18a; 80.80, 65.84, 68.66, 67.62,
70.59 (C-1ꢁ C-2ꢁ, C-3ꢁ, C-4ꢁ
and C-5ꢁ); 20.30, 20.43,
20.30 (3CH3 of acetoxy
groups at C-2ꢁ, C-3ꢁ and
C-4ꢁ); 169.16, 169.16,
N-CH2-N), 4.36–4.43 (lH, m, at C-4ꢁ),
5.11–5.19 (1H at C-2ꢁ, t), 5.23–5.42 (IH at
C-3ꢁ, t), 5.74–5.78 (1H at C-5ꢁ, t), 6.30–6.38
(1H, d, anomeric proton, J = 10.34).
169.44 (SCO at C-2ꢁ, C-3ꢁ
and C-4ꢁ); 162.49, 168.73,
137.45 (C-2, C-4 and C-5);
124.04, 133.78, 128.69,
131.90, 130.06
18a; 2.06 (9H, s, 3CH3-CO at C-2ꢁ, C-3ꢁ and C-4ꢁ),
2.48 (2H, s, N-CH2-N), 3.22 (4H, s,
2C-CH2-N), 3.55 (4H, s, 2C-CH2-0), 3.79-3.82
(1H at C-2ꢁ, t), 4.15–4.26 (1H at C-4ꢁ, m),
4.95–4.97 (1H at C-3ꢁ, m), 5.21–5.27 (1H at
C-5ꢁ, t, J = 7.82, diequatorial orientation
between H-5ꢁe and H-4ꢁ), 5.40–5.49 (1H at
C-5ꢁ, t, J = 7.52, diaxial orientation between
H-5ꢁ. and H-4ꢁ), 6.06–6.09 (1H at C-1ꢁ, d,
anomeric proton, J = 7.52 Hz), 6.97 (1H, s,
Ph-CH C), 7.47–8.26 (5H, m, aromatic).
18c; 2.10 (9H, s, 3CH3-CO at C-2ꢁ, C-3ꢁ and C-4ꢁ),
3.12 (3H, s, N3-CH3). 3.86 (3H, s, Ar-OCH3),
3.60–3.67 (1H at C-4ꢁ, t), 5.01–5.18 (1H at
C-3ꢁ, m), 4.27–4.32 (IH at C-2ꢁ, m), 5.21–5.24
(IH at C-5ꢁ, t, J = 7.56 Hz. diequatorial
orientation between H-5ꢁe and H-4ꢁ),
(benzylidene carbons);
50.26, 62.03, 64.55 (4CH2,
morpholinomethyl
carbons).
18c; 81.26, 65.45, 68.88, 67.87,
70.87 (C-1ꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ
and C-5ꢁ); 20.55, 20.61,
20.54 (3CH3 of acetoxy
groups at C-2ꢁ, C-3ꢁ and
C-4ꢁ); 169.43, 169.55,
169.49 (3C O at C-2ꢁ, C-3ꢁ
and C-4ꢁ); 161.19. 169.30,
135.98 (C-2, C-4 and C-5);
141.14, 135.86, 125.86,
130.99, 129.94 (benzylidene
carbons); 26.48, 55.24
(N-CH3, Ar-OCH3).
5.29–5.35 (1H at C-5ꢁ, t, J = 7.56 Hz, diaxial
orientation between H-5ꢁ, and H-4d),
6.05–6.08 (1H at C-1ꢁ, d, anomeric proton, J = 18d; 80.65, 64.61, 68.59, 67.61,
7.73 Hz), 6.93 (1H, s, Ph CH C), 6.96–6.98
(2H, d, aromatic), 8.06–8.09 (2H, d, aromatic).
18d; 1.98 (3H, s, CH3-CO at C-4ꢁ), 2.05 (6H, s,
2CH3-CO at C-2ꢁ, C-3ꢁ), 3.77–3.84 (1H, t, at
C-2ꢁ), 4.12–4.15 (1H at C-4ꢁ, m), 4.95 (1H at
C-3ꢁ, m), 5.18–5.24 (IH at C-5ꢁ, t, J = 7.20 Hz,
diequatorial orientation between H-5ꢁe and
H-4ꢁ), 5.42–5.48 (1H at C-5ꢁ, t, J = 7.15 Hz,
diaxial orientation between H-5ꢁꢁ, and H-4ꢁ),
6.13–6.16 (1H at C-1ꢁ, d, anomeric proton, J
= 7.51 Hz), 7.07 (1H, s, Ph CH C),
70.73 (C-lꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ
and C-5ꢁ); 20.24, 20.26,
20.42 (3CH3 of acetoxy
groups at C-2ꢁ, C-3ꢁ and
C-4ꢁ); 169.08, 169.43,
169.16 (3C 0 at C-2ꢁ, C-3ꢁ
and C-4ꢁ); 161.30, 167.67,
137.24 (C-2, C-4 and C-5);
124.39, 133.81, 127.62,
131.96, 128.75 (benzylidene
carbons); 124.39, 130.89,
128.56 (N-C6H5)
7.42–8.33 (5H, m, aromatic).
Reaction of Compound 20 with 2,3,4,6-Tetra-O-acetyl-
α-D-galactopyranosyl Bromide
A suspension of 20 (4.39 gm, 0.01 mole) in xylene (150 ml) was dis-
tilled until 50 ml of the distillate was collected, cooled and added

200
Y. L. Aly et al.
TABLE III Mass Spectral Data of the Newly Prepared S-Nucleosides
Comp. no.
Mass spectral data
14b
M+ 548 (0.5%, C25H28N2O10S), m/z 332 (4%, C14H20O9), 331 (18%,
C14H19O+), 218 (41%, C11H10N2OS), 169 (33%, C8H9O+), 145 (5%,
9
4
C9H7NO), 144 (6%, C9H6NO+), 127 (9%, C6H7O+3 ), 117 (29%,
C8H7N), 116 (7%, C8H6N+), 109 (17%, C6H502+), 81 (5%, C5H5O+5 ),
73 (3%, CH3NCS), 43 (100%, CH3CO).
14c
15
M+ 578 (2%, C26H30N2O11S), m/z 332 (2%, C14H20O9), 331 (10%,
C14H19O+), 248 (7%, CI2H12N2O2S), 247(1.5%, C12H11N2O2S+), 174
9
(4%, C10H8NO+), 169 (38%, C8H9O+), 147 (4%, C9H9NO), 132 (3%,
2
C8H6NO+), 127 (9%, C6H7O3+), 1094(33%, C6H5O2), 73 (1%,
CH3NCS+), 43 (100%, CH3CO).
M+ 589 (1.5%, C24H35N3O10 S2), m/z 331 (1%, C14H19O+), 169 (7%,
9
C8H9O+), 160 (20%, C5H8N2S+), 159 (7%, C5H7N202S+), 145 (3%,
2
C4H5N42S+), 127 (4%, C6H7O+2), 109 (8%, C6H5O+), 101 (6%,
3
C5H11NO2), 100 (62%, C5H10NO+), 86 (13%, C3H42NS+), 43 (100%,
CH3CO).
16a
16c
16e
18b
18c
M+ 534 (0.9%, C24H26N2O10S), m/z 332 (2%, C14H20O9), 331 (9%,
C14H19O+), 204 (7%, C10H8N2OS), 169 (10%, C8H9O+), 145 (3%,
9
4
C9H7NO), 127 (5%, C6H70+), 117 (7%, C9H7N), 109(8.5%, C6H5O+),
101 (5.5%, C5H11NO), 100 3(84%, C5H10NO), 81 (3.5%, C5H5O+), 59
2
(2.5%, HCNS), 43 (100%, CH3CO).
M+ 578 (6%, C26H3oN2O11S), m/z 332 (4%, C14H2009), 331 (26%,
C14H19O+), 248 (23%, C12H12N2O2S), 247 (2%, C12H11N2O2S+), 174
9
(4%, C10 H8NO+), 169 (4%, C8H9O+), 147 (9%, C9H9NO), 146 (4%,
2
4
C9H8NO+), 132 (5%, C8H6NO+), 127 (9%, C6H7O+3 ), 109 (19%,
C6H5O+2 ), 81 (5%, C5H5O+), 73 (2%, CH3NCS), 43 (100%, CH3CO).
M+ 610 (0.6%, C3oH3oN2O1oS), m/z 332 (3.5%, C14H20O9), 331 (12%,
C14H19O+), 280 (12%, C16H12N2O2S), 279 (6.5%, C16H11N2O2S+),
169 (22%9; C8H9O4+), 145 (2%, C9H7NO), 144 (2%, C9H6NO+), 127
(7%, C6H70+3 ), 117 (19%, C8H7N), 116 (7%, C8H6N+), 109 (17%,
C6H5O+2 ), 81 (5%, C5H5O+), 43 (100%, CH3CO).
M+ 476 (0.2%, C22H24N2O8S), m/z 259 (3%, C11H15O+), 218 (13%,
7
C
11H10N2OS), 199 (2%, C9H11O+), 157 (5%, C7H, O+), 144 (2.5%,
C9H6NO+), 139 (10%, C7H7O3+),3117 (7%, C8H7N), 116 (5%,
C8H6N+), 97 (18%, C5H5O2+); 73 (2%, CH3NCS), 69 (4.5%, C4H5O+),
43 (100%, CH3CO).
4
M+ 506 (2%, C23H26N2O9S), m/z 259 (4.5%, C11H15O+), 248 (10%,
7
C12H12N2O2S), 199 (4%, C9H11O+), 174 (3.5%, C10H8N0+), 157
5
2
(12%, C7H9O+4 ), 147 (7.5%, C9H9NO), 146 (4%, C8H8NO+), 139
(16%, C7H7O3), 132 (5.5%, C8H6NO+), 97 (27%, C5H5O2+), 73 (4%,
C2H3NS), 69 (5%, C4H5O+), 43 (100%, CH3CO).
to a powdered (2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl) bromide
(4.52 gm, 0.011 mole). The mixture was heated under reflux (mois-
ture excluded) for two hours and filtered off. The residue was washed
with hot xylene and evaporated under vaccum and cooled. The resid-
ual solid product was extracted with chloroform (200 ml). Thevsolvent

Alkylation of Thiohydantoins
201
was evaporated to dryness and the solid residue was crystallized from
ethanol to give 5-benzylidene-3-phenyl-2-(2ꢁ,3’,4ꢁ,6ꢁ-tetra-O-acetyl-β-
D-thiogalactopyranosyl)hydantoin; mp.: 130◦C, yield 86%. The product
showed no depression of m.p. and m.m.p. when admixed with 16e.
Attempted Deprotection of 5-(4-Chlorobenzylidene)-
3-methyl-2-(2ꢀ ,3ꢀ ,4ꢀ ,6ꢀ -tetra-O-acetyl-β-D-
thioglucopyranosyl)hydantoin (14d)
a) By Using NH3/MeOH
To a suspension of the S-glucoside 14d (0.01 mole) in absolute
methanol (25 ml), a saturated solution of ammonia in absolute methanol
(25 ml) was added. The reaction mixture was stirred at room temper-
ature for 24 hrs until the starting material was consumed (TLC). The
reaction mixture was evaporated to dryness under vacuum and the re-
sulting solid was crystallized from methanol to give 0.79 gm (35% of
the yield; m.p.: 202–204◦C). Its mixed m.p. with an authentic sample
of 5-(4-chlorobenzylidene)-3-methyl-2-thiohydantoin (2d)27 gave no de-
pression. The filtrate was evaporated to dryness to give a solid product
(1.47 gm, 65% of th. Yield); m.p. 261◦C. Its mixed m.p. with an authen-
tic sample of 5-(4-chlorobenzylidene)-3-methylhydantoin (22) gave no
depression.27
b) By Using NaOEt/EtOH or NaOMe/MeOH
A suspension of equimolecular amounts of 14d and sodium ethox-
ide in ethanol (25 ml) was stirred at room temperature for 30 min. The
reaction mixture was evaporated to dryness. The residual solid was dis-
solved in water (10 ml) and acidified with HC1. After standing at room
temperature for some hours, a solid precipitated which was collected by
filtration, washed with water, dried and crystallized to give 2d (44% of
th. yield) and 22 (56% of th. yield). Their m.p. and mixed m.p. gave no
depression.27
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c
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