Reactions of 5-arylidene-2-thiohydantoins with halogenated compounds and anthranilic acid

Article abstract of DOI:10.1080/104265090968677

5-arylidene-2-thiohydantoins 1a-c react with ethyl α-chloroacetate 2 and monochloroacetone to give the respective 2-imidazolinones 3a-c and 2-acetonylmercaptohydantoins 9a-c. Compounds 3a-c react with benzenediazonium chloride to afford hydrazones 5a-c. T

Full text of DOI:10.1080/104265090968677

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Reactions of 5-Arylidene-2-
thiohydantoins with
Halogenated Compounds and
Anthranilic Acid
Asmaa A. Magd El-Din a , Salwa A. Elsharabasy b &
Aisha Y. Hassan b
a National Products Department, National Research
Centre, Dokki, Cairo, Egypt
b Faculty of Science, Al-Azhar University, Cairo,
Egypt
Version of record first published: 01 Feb 2007.
To cite this article: Asmaa A. Magd El-Din , Salwa A. Elsharabasy & Aisha Y. Hassan
(2006): Reactions of 5-Arylidene-2-thiohydantoins with Halogenated Compounds and
Anthranilic Acid, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:1,
53-67
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Phosphorus, Sulfur, and Silicon, 181:53–67, 2006
Copyright © Taylor & Francis LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090968677
Reactions of 5-Arylidene-2-thiohydantoins with
Halogenated Compounds and Anthranilic Acid
Asmaa A. Magd El-Din
National Products Department, National Research Centre, Dokki,
Cairo, Egypt
Salwa A. Elsharabasy
Aisha Y. Hassan
Faculty of Science, Al-Azhar University, Cairo, Egypt
5-arylidene-2-thiohydantoins 1a–c react with ethyl α-chloroacetate 2 and mono-
chloroacetone to give the respective 2-imidazolinones 3a–c and 2-acetonylmercap-
tohydantoins 9a–c.
Compounds 3a–c react with benzenediazonium chloride to afford hydrazones 5a–c.
The reaction of 1a–c with ethylene bromide and with α,α-dichloroacetone gives the
respective alkyl mercapto-derivatives 13a–c and 14a–c. The reaction of polyphos-
phoric acid with 3a–c, 9a–c, 13a–c and 14a–c yields the respective thiazolones
7a–c , imidazothioles 10a–c, imidazo-thiazoles 15a–c and imidazothiazines 16a–
c. The mercapto-hydantoins 17a–d react with anthranilic acid to give quinazolin-
3,5-diones 19a,b and/or 21a,b. Structural elucidation for the new products are
based on compatible elementary and spectroscopic evidences.
Keywords 5-Arylidene-2-thiohydantoins; anthranilic acid; dihlogenated compounds;
mono-; polyphosphoric acid
INTRODUCTION
The considerable biological and medicinal activities of thiazoles and im-
idazoquinazolines have stimulated recent interest in the synthesis of
derivatives of these condensed heterocyclic ring systems.1−6 As a part
of our program directed towards the development of new simple proce-
dures for the synthesis of fused azoles,7−12 the reactions of 5-arylidene-
2-thiohydantoins 1a–c with monohalogenated and dihalogenated com-
pounds, in addition to the reaction of products with anthranilic acid
and polyphosphoric acid, were investigated.
Received November 20, 2004; in final form March 20, 2005.
Address correspondence to Asmaa A. Magd El-Din, National Products Department,
National Research Center, Dokki, Cairo, Egypt. E-mail: asmaaaly 2003@yahoo.com
53

54
A. A. Magd El-Din et al.
RESULTS AND DISCUSSION
It has been found that compounds 1a–c reacted with ethyl α-chloro-
acetoacetate 2 in ethanol in the presence of sodium ethoxide at room
temperature to yield products corresponding to the addition of one
molecule of each of 1a–c to one molecule of 2 followed by the loss of one
molecule of HCl. The reaction products could be formulated as ethyl α-
(4-arylidene-2-imidazolin-5-one-2-yl-thio)acetoacetates 3a–c based on
elemental analyses and spectral data. The IR spectra of 3a–c showed
the presence of absorption bands for one NH group and three carbonyl
1
groups. H-NMR spectrum of 3c was found in good agreement with
the assigned structure only (cf., Scheme 1 and Expecrimental section).
SCHEME 1

Reactions of 5-Arylidene-2-thiohydantoins
55
Furthermore, treatment of 3a with ethanol-hydrochloric acid mixture
resulted in the formation of 5-benzylidene hydantoin (4).13
Compounds 3a–c coupled with benzenediazonium chloride in ethanol
in the presence of sodium acetate in a Japp-Klingemann reaction to give
ethyl 1-(4-arylidene-2-imidazolin-5-one-2-yl-thio)glyoxalate 1-phenyl-
hydrazones 5a–c. The structures of 5a–c were supported by elemen-
tal analysis and spectral data (cf., Experimental section). Moreover,
compounds 5a–c also were synthesized by an alternative route via the
reaction of 1a–c with ethyl 1-chloroglyoxalate 1-phenylhydrazone (6)
(from benzene diazonium chloride and ethyl α-chloroacetoacetate, cf.,
Scheme 1).
When compounds 3a–c were heated with polyphosphoric acid,
2-acetyl-6-arylidene-imidazo[2, 1-b] thiazol-3,5-diones 7a–c, and not
their isomeric forms compounds 8a–c, were obtained (cf., Scheme 2).
The structure of 7a–c was considered more probable to represent
SCHEME 2

56
A. A. Magd El-Din et al.
the cyclization products on the basis that the hydrogen atom at-
tached to the nitrogen atom at position-3 ( CO NH) in 5-substituted-2-
alkylmercaptohydantoins,14,15 which is the only active site. Compounds
7a–c gave the correct elemental analysis and spectral data.
Similarly, 5-arylidene-2-thiohydantoins 1a–c reacted with mono-
chloroacetone under the same experimental conditions to yield 2-
acetonylmercaptohydantoin derivatives 9a–c. Compounds 9a–c gave
the correct elemental analysis and spectral data. In addition, 9a was
hydrolysed with ethanol-concentrated hydrochloric acid mixture to give
5-benzylidene hydantoin (4).13
Compounds 9a–c were converted into imidazo[2,1-b]thiazole deriva-
tives 10a–c, via elimination of water in each case, by heating with
polyphosphoric acid (cf., Scheme 2). Products 10a–c gave the correct
elemental analyses and spectral data (cf., Experimental section).
Compounds 9a–c reacted with benzaldehyde in ethanolic sodium
ethoxide solution to give cinnamoylmethylmercapto derivatives 11a–
c (cf., Scheme 2). The IR spectra of 11a–c showed the presence of one
1
NH group, two C O groups, and C N. In addition, the H-NMR spec-
trum of 11a in DMSO- d6 revealed signals for one exchangeable NH,
CH2, COCH, and two ylidinic CH together with aromatic protons (cf.,
Experimental section). On the other hand, 9a–c coupled with benzene-
diazonium chloride to afford the azo derivatives 12a–c, which gave the
correct elemental analyses and spectral data (cf., Experimental section).
The work also was extended to study the behaviour of 5-arylidene-
2-thiohydantoins 1a–c towards dihalogenated compounds. Thus, when
a mixture of equimolar amounts of each of 1a–c and ethylene bromide
and/or α,α-dichloroacetone in ethanol containing an equimolar amount
of sodium ethoxide was stirred at room temperature, the alkylmercapto
derivatives 13a–c and 14a–c were obtained, respectively, based on el-
emental analysis and spectral data. Moreover, when 13a and/or (14a)
were treated with ethanol-concentrated hydrochloric acid mixture, 5-
benzylidene hydantoin (4)13 was obtained in each case. Compounds
13a–c and 14a–c were cyclized via the elimination of HBr and HCl,
respectively, by heating with polyphosphoric acid to give imidazo[2,1-
b]thiazole derivatives 15a–c and imidazo[2,1-b]thiazine derivatives
16a–c respectively (cf., Scheme 3).
Work is extended further to investigate the behavior of 5-ylidene-
2-methylmercapto hydantoin derivatives 17a,b towards the action of
anthranilic acid for the synthesis of some new imidazo[2,1-b] quinazo-
lines containing 2-furyl and 2-thianyl moieties required for biological
activity studies. Thus, it was found that compounds 17a,b reacted with
anthranilic acid to afford products corresponding to the addition of one
molecule of each of 17a,b to one molecule of anthranilic acid with the

Reactions of 5-Arylidene-2-thiohydantoins
57
SCHEME 3
elimination of one molecule of methane thiol and one molecule of wa-
ter. The reaction products were formulated as 2-ylidene imidazo[2,1-b]-
quinazoline-3,5-diones 19a,b or their isomeric forms 20a,b (cf., Scheme
4). The structure of 19a,b was considered more probable to represent
the cyclization products based on the report that the hydrogen atom
attached to N-3 is the only active site on 5-arylidene-2-alkylmercapto-
hydantoins,14,15 and hence it facilitates the loss of water, which is nec-
essary for the cyclization step. This fact was supported from previ-
ous results from this laboratory for other 5-arylidene-2-thiohydantoin
derivatives.17 On the other hand, 17c,d reacted with anthranilic acid to
give 1-phenyl-3-ylidene-imidazo[2,1-b] quinazoline-2, 5-diones 21a,b.
The formation of 19a,b and 21a,b is assumed to proceed via the con-
densation of the amino group of anthranilic acid with the methylmer-
capto derivatives 17a–d and with the elimination of methane thiol
to give nonisolable intermediates 18a–d, respectively, which cyclize
readily with the loss of water under the applied reaction conditions
to give the final isolable products 19a,b and 21a,b, respectivey (cf.,
Scheme 4).

58
A. A. Magd El-Din et al.
SCHEME 4
EXPERIMENTAL
All melting point are uncorrected. The IR spectra were recorded on
a Perkin-Elmer 1430 spectrophotometer in KBr discs. The 1H-NMR
spectra were recorded on a varian EM 390-90 MHz spectrometer using
deuterated DMSO-d as a solvent and TMS as an internal standard.
6

Reactions of 5-Arylidene-2-thiohydantoins
59
Chemical shifts are exposed as δ ppm units. Microanalytical data were
obtained by the Microanalytical Centre at the Faculty of Sciences, Cairo
University.
Reactions of 5-Arylidene-2-thiohydantoins 1a–c with Ethyl
α-Chloro-acetoacetate 2
A solution of each of 1a–c (0.01 mole) in ethanol (50 mL) contain-
ing sodium ethoxide (prepared from 0.25 g, 0.011g atom sodium) was
treated with ethyl α-chloroacetoacetate 2 (0.01 mole). The reaction mix-
ture was stirred for 3 h and left overnight at room temperature. The
solid obtained was filtered off, washed with water, and then crystal-
lized from ethanol to give yellow crystals of ethyl α-(4-arylidene-2-
imidazolin-5-one-2-yl-thio)acetoacetate 3a–c.
3a, m.p. 178◦C, yield 72%, elemental analysis for C16H16N2O4S,
Calcd. C, 57.83; H, 4.82; N, 8.43; S, 9.64; found: C, 57.62; H, 5.14; N,
8.20; S, 9.51; IR (cm−1: 3360 (NH), 1735, 1720, 1690 (3 C O) and 1640
(C N).
3b, m.p. 195-6◦C, yield 73%, elemental analysis for C17H18N2O5S,
Calcd. C, 56.35; H, 4.97; N, 7.73; S, 8.84; found: C, 56.11; H, 5.23; N,
7.90; S, 8.62; IR (cm−1): 3380 (NH), 1735, 1725, 1700 (3 C O) and 1640
(C N).
3c, m.p. 210◦C, yield 78%, elemental analysis for C16H15N2O4SCl,
Calcd. C, 52.39; H, 4.09; N, 7.64; S, 8.73; Cl, 9.69; found: C, 52.60; H, 4.31;
N, 7.52; S, 8.94; Cl, 9.41; IR (cm−1: 3390 (NH), 1730, 720, 1700 (3 C O)
and 1645 (C N); and 1H-NMR (δ ppm): 1.9 (t, 3H, CH2 CH3), 2.8 (s, 3H,
COCH3), 4.1 (q, 2H, CH2CH3), 4.5 (s, 1H, S-CH), 6.4 (s, 1H, Ar-CH ),
7.2–7.5 (m, 4H, Ar-H) and 9.1 (s, 1H, NH, exchangeable with D2O).
Action of Conc. Hydrochloric Acid on 3a
A mixture of 3a (1 g), ethanol (20 mL), and concentrated hydrochlo-
ric acid (8 mL) was refluxed for 2 h. A solid product was obtained. On
cooling, the solid was filtered off and crystallized from ethanol to give
5-benzylidene hydantoin (4), [m.p. 220◦ C, yield 65%], showing no de-
pression in its melting point when admixed with an authentic sample.13
Preparation of Ethyl 1-[4-Arylidene-2-imidazolin-5-one-
2-yl-thio]-glyoxalate 1-Phenylhydrazones 5a–c
Method (A): From 3a–c with Diazonium Salts
Compounds 3a–c (0.01 mole) were suspended in 50 mL of ethanol
containing 3 g of sodium acetate. The mixture was cooled in an ice bath,

60
A. A. Magd El-Din et al.
treated with an equimolar amount with benzenediazonium chloride,
and left for 1 h and then poured onto cold water. The precipitate formed
was collected, dried, and crystallized from ethanol as reddish-brown
crystals of 5a–c.
Method (B): From 1a–c with Ethyl 1-Chloroglyoxalate
1-Phenyl-hydrazone 6
A solution of 5-benzylidene-2-thiohydantoins 1a–c (0.01 mole) in
ethanol (50 mL) containing sodium ethoxide (0.011 mole) was treated
with ethyl 1-chloroglyoxalate 1-phenylhydrazone (6) (from benzene-
diazonium chloride, and ethyl α-chloroacetoacetate). The reaction mix-
ture was stirred at room temperature for 3 h and left overnight at room
temperature. The solid that was obtained was filtered off and washed
with water and then crystallized from ethanol to give 5a–c (showing
no depression in melting points when admixed with samples 5a–c, pre-
pared as described above).
5a, m.p. 230◦C, yield 60%, elemental analysis for C20H18N4O3S,
Calcd. C, 60.91; H, 4.57; N, 14.21; S, 8.12; found: C, 60.67; H, 4.25; N,
14.57; S, 8.00; IR (cm−1: 3380, 3260 (2NH), 1730, 1715 (2 C O) and 1640
(C N)1 H-NMR (δ ppm): 1.7 (t, 3H, CH2 CH3), 4.1 (q, 2H, CH2CH3),
6.2 (s, 1H, Ar-CH ), 7.2–7.5 (m, 10H, Ar-H) and 9.8, 11.3 (2s, 2H, 2 NH,
exchangeable with D2O).
5b, m.p. 260◦C, yield 62%, elemental analysis for C21H20N4O4S,
Calcd. C, 59.43; H, 4.72; N, 13.21; S, 7.55; found: C, 59.23; H, 4.51;
N, 13.05; S, 7.81; IR (cm−1: 3400, 3310 (2NH), 1735, 1720 (2 C O) and
1635 (C N).
5c, m.p. 294–295◦C, yield 70%, elemental analysis for C20H17N4O3
SCl, Calcd. C, 56.01; H, 3.97; N, 13.06; S, 7.47; Cl, 8.28; found: C, 56.20;
H, 4.21; N, 12.84; S, 7.70; Cl, 8.52; IR (cm−1: 3390, 3280 (2NH), 1735,
1720 (2 C O) and 1640 (C N).
Preparation of 2-Acetyl-6-arylidene imidazo[2,1-b]-
thiazol-3,5-diones 7a–c
A mixture of each of 3a–c (1 g) and polyphosphoric acid (prepared
from 4 g of phosphorus pentoxide and 4 mL of 85% phosphoric acid)
was heated on the water bath for 1 h and then in an oil bath (125–
130◦C) for 30 min. After cooling, the reaction mixture was poured onto
ice-cold water and neutralized with potassium carbonate solution. The
solid thus obtained was crystallized from ethanol to give deep yellow
crystals identified as 7a–c.
7a, m.p. 235◦ C, yield 72%, elemental analysis for C14H10N2O3S,
Calcd. C, 58.74; H, 3.49; N, 9.69; S, 11.19; Found: C, 58.56; H, 3.70;

Reactions of 5-Arylidene-2-thiohydantoins
61
N, 9.61; S, 11.50; IR (cm−1: 1690, 1710, 1720 (3 C O) and 1635 (C N)
1
and H-NMR (δ ppm): 2.8 (s, 3H, CH3), 4.4 (s, 1H, SC H), 6.3 (s, 1H,
Ar-CH ) and 7.2–7.5 (m, 5H, Ar-H).
7b, m.p. 250◦C, yield 70%, elemental analysis for C15H12N2O4S,
Calcd. C, 56.96; H, 3.79; N, 8.86; S, 10.13; Found: C, 56.71; H, 3.64;
N, 8.56; S, 9.95; IR (cm−1): 1700, 1715, 1720 (3 C O) and 1640 (C N).
7c, m.p. 280◦C, yield 75%, elemental analysis for C14H9N2O3SCl,
Calcd. C, 52.42; H, 2.81; N, 8.74; S, 9.98; Cl, 11.07; found: C, 52.24; H,
3.10; N, 8.53; S, 10.20; Cl, 11.32; IR (cm−1: 1695, 1720, 1725 (3 C O)
and 1645 (C N).
Reaction of 1a–c with Monochloroacetone
A solution of each of 1a–c (0.01 mole) in ethanol (50 mL) containing
sodium ethoxide (prepared from 0.25 g, 0.011 g atom sodium) were
treated with monochloroacetone (0.01 mole). The reaction mixture was
stirred for 2 h and was worked up as in of the preparations of 3a–c. The
reaction products were crystallized from ethanol to give yellow crystals
of 2-acetonylmercaptohydantoin derivatives 9a–c.
9a, m.p. 170◦ C, yield 82%, elemental analysis for C13H12N2O2S,
Calcd. C, 60.00; H, 4.62; N, 10.77; S, 12.31; Found: C, 60.21; H, 4.50; N,
10.93; S, 12.50; IR (cm−1: 3370 (NH), 2950 (saturated CH), 1720, 19695
(2 C O) and 1640 (C N) and 1 H-NMR (δ ppm): 2.6 (t, 3H, CH3), 4.1 (s,
2H, S- CH2), 6.5 (s, 1H, Ar-CH ), 7.2–7.4 (m, 5H, Ar-H) and 8.3 (s, 1H,
NH, exchangeable with D2O).
9b, m.p. 185◦C, yield 78%, elemental analysis for C14H14N2O3S,
Calcd. C, 57.93; H, 4.83; N, 9.66; S, 11.03; Found: C, 57.75; H, 4.63; N,
9.46; S, 11.30; IR (cm−1: 3380 (NH), 2960 (saturated CH), 1720, 19695
(2 C O) and 1645 (C N).
9c, m.p. 205–206◦C, yield 85%, elemental analysis for C13H11N2-
O2SCl, Calcd. C, 52.97; H, 3.74; N, 9.51; S, 10.87; Cl, 12.05; Found:
C, 53.10; H, 3.82; N, 9.35; S, 10.66; Cl, 12.22; IR (cm−1: 3340 (NH), 2970
(saturated CH), 1725, 1700 (2 C O) and 1640 (C N).
Action of Conc. Hydrochloric Acid on 9a
A mixture of 9a (1 g), ethanol (20 mL), and conc. hydrochloric acid (8 mL)
was refluxed for 2 h. The solid product obtained on cooling was filtered
off and crystallized from ethanol to give 5-benzylidene-hydantoin (4)
(m.p. 220◦C), yield 65% (showing no depression in melting point when
admixed with authentic sample).13

62
A. A. Magd El-Din et al.
Preparation of 6-Arylidene-3-methyl-imidazo[2,1-b]thiazol-5-
one Derivatives 10a–c
A mixture of each of 9a–c (1 g) and polyphosphoric acid (prepared from
4 g of phosphorus pentoxide and 4 mL of 85% phosphoric acid) was
heated on the water bath for 1 h and then in an oil bath (125–130◦C)
for 30 min. The reaction mixture was worked up as in the preparations
of 7a–c. The solid obtained was crystallized from ethanol to give deep
yellow crystals identified as 10a–c.
10a, m.p. 150◦C, yield 65%, elemental analysis for C13H10N2OS,
Calcd. C, 64.46; H, 4.13; N, 11.57; S, 13.22; found: C, 64.25; H, 4.40; N,
11.42; S, 13.50; IR (cm−1: 2960 (saturated CH), 1720 (C O) and 1635
1
(C N) and H-NMR (δ ppm): 2.3 (t, 3H, CH3), 6.3, 6.7 (2s, 2H, 2CH )
and 7.2–7.5 (m, 5H, Ar-H).
10b, m.p. 165◦C, yield 72%, elemental analysis for C14H12N2O2S,
Calcd. C, 61.76; H, 4.41; N, 10.29; S, 11.76; Found: C, 61.53; H, 4.70; N,
10.62; S, 12.00; IR (cm−1: 2970 (saturated CH), 1725 (C O) and 1640
(C N).
10c, m.p. 175◦C, yield 75%, elemental analysis for C13H9N2OSCl,
Calcd. C, 56.42; H, 3.25; N, 10.13; S, 11.57; Cl, 12.84; found: C, 56.70;
H, 3.12; N, 9.96; S, 11.73; Cl, 12.50; IR (cm−1): 2980 (saturated CH),
1720 (C O) and 1645 (C N).
Action of Benzaldehyde on 9a–c
A solution of each of 9a–c (0.01 mole) in ethanol (50 mL) contain-
ing sodium ethoxide (prepared from 0.25 g, 0.011 g atom sodium) was
treated with benzaldehyde (1.1 mole). The reaction mixture was stirred
for 3 h and left overnight at room temperature. The solid obtained
was filtered off, washed with water, and then crystallized from acetic
acid to give brown crystals of cinnamoyl methylmercapto derivatives
11a–c.
11a, m.p. 280–281◦C, yield 70%, elemental analysis for C20H16N2-
O2S, Calcd. C, 68.97; H, 4.59; N, 8.05; S, 9.19; found: C, 68.66; H, 4.80;
N, 8.31; S, 9.50; IR (cm−1: 3360 (NH), 1715, 1690 (2 C O) and 1640
(C N) and 1 H-NMR (δ ppm): 4.8 (s, 2H, CH2), 6.4 (s, 1H, Ar-CH ), 6.6,
6.8 (2d, 2H, COCH CHPh), 7.2–7.6 (m, 10H, Ar-H) and 9.1 (s, 1H, NH,
exchangeable with D2O).
11b, m.p. > 300◦C, yield 72%, elemental analysis for C21H18N2O3S,
Calcd. C, 66.66; H, 4.76; N, 7.41; S, 8.47; found: C, 66.46; H, 4.58; N,
7.70; S, .23; IR (cm−1: 3380 (NH), 1720, 1685 (2 C O) and 1635 (C N).
11c, m.p. > 300◦C, yield 78%, elemental analysis for C20 H15N2O2-
SCl, Calcd. 62.74; H, 3.92; N, 7.32; S, 8.36; Cl, 9.28; Found: C, 62.53;

Reactions of 5-Arylidene-2-thiohydantoins
63
H, 4.11; N, 7.50; S, 8.13; Cl, 9.65; IR (cm−1): 3410 (NH), 1725, 1690 (2
C O) and 1645 (C N).
Action of Benzenediazonium Chloride on 9a–c
A cold solution of benzenediazonium chloride (0.01 mole) (prepared from
the equivalent amount of the aniline, HCl and NaNO2) gradually was
added to a cold solution of 9a–c (0.01 mole) dissolved in pyridine (25
mL) for 30 min at 0–5◦C. The reaction mixture was stirred in the ice
box for 2 h. The solid product that was formed was collected by filtra-
tion, washed with water, and then crystallized from ethanol to give red
crystals of 12a–c.
12a, m.p. 280◦C, yield 60%, elemental analysis for C19H16N4O2S,
Calcd. C, 62.64; H, 4.39; N, 15.38; S, 8.79; found: C, 62.23; H, 4.15; N,
15.50; S, 8.46; IR (cm−1: 3370 (NH), 1720, 1680 (2 C O) and 1635 (C N)
1
and H-NMR (δ ppm): 2.7 (s, 3H, COC H3), 5.1 (s, 1H, CH), 6.3 (s, 1H,
Ar-CH ), 7.2–7.6 (m, 10H, Ar-H) and 9.5 (s, 1H, NH, exchangeable with
D 2O).
12b, m.p. 230◦C, yield 68%, elemental analysis for C20H18N4O3S,
Calcd. C, 60.91; H, 4.57; N, 14.21; S, 8.12; found: C, 61.20; H, 4.35; N,
14.00; S, 8.40; IR (cm−1: 3380 (NH), 1725, 1690 (2 C O) and 1640 (C N).
12c, m.p. 298◦C, yield 71%, elemental analysis for C19H15N4O2SCl,
Calcd. C, 57.21; H, 3.76; N, 14.05; S, 8.03; Cl, 8.91; found: C, 57.50; H,
3.46; N, 14.03; S, 7.79; Cl, 9.20; IR (cm−1: 3390 (NH), 1725, 1695 (2
C O) and 1640 (C N).
Reaction of 1a–c with Ethylenebromide and/or
α,α‘-Dichloroacetone
A solution of each of 1a–c (0.01 mole) in ethanol (50 mL) contain-
ing sodium ethoxide (prepared from 0.25 g, 0.011 g atom sodium)
was treated with each of ethylene bromide and/or α,α‘-dichloroacetone
(0.01 mole). The reaction mixture was stirred for 5 h and worked up
as was the preparations of 3a–c. The reaction products were crys-
tallized from ethanol to give yellow crystals of alkylmercapto deriva-
tives 13a–c and/or brown crystals of alkylmercapto derivatives 14a–c
(cf. Table I).
Action of Conc. Hydrochloric Acid on Each of 13a and 14a:
Preparation of 2-Alkyl Mercaptohydantoin Derivatives 13a–c
and 14a–c
A solution of 13a and/or 14a (1 g), ethanol (20 mL) and conc.
hydrochloric acid (8 mL) was refluxed for 2 h. The solid product

64

Reactions of 5-Arylidene-2-thiohydantoins
65
obtained on cooling was filtered off and crystallized from ethanol to
give 5-benzylidenehydantoin (4) [m.p. 220◦C (yield 65%)] showing no
depression in melting point when admixed with an authentic sample.13
Action of Polyphosphoric Acid on 13a–c and 14a–c:
Preparation of Imidazo[2,1-b]thiazole Derivatives 15a–c and
Imidazo-[2,1-b]thiazine Derivatives 16a–c
A mixture of each of 13a–c and/or 14a–c (1 g) and polyphosphoric acid
(prepared from 4 g of phosphorus pentoxide and 4 mL of 85% phos-
phoric acid) was heated on the water bath for 1 h and then in an oil
bath (125–130◦C) for 30 min. The reaction mixture was worked up as
was the preparations of 7a–c. The solid obtained was crystallized from
ethanol to give deep yellow crystals identified as imidazo[2,1-b]thiazole
derivatives 15a–c and/or deep brown crystals of imidazo[2,1- b]thiazine
derivatives 16a–c (cf. Table II).
Preparation of 2-Ylidene Imidazo[2,1-b]quinazoline-3,5-diones
19a,b
A mixture of 0.01 mole of each of 5-ylidene-2-methylmercapto-
hydantoins 17a,b16 (0.01 mole) and anthranilic acid (0.01 mole) was
heated in ethanol (50 mL). During the reaction, the odor of the evolved
methanethiol easily could be detected. The heating was continued until
the odor of CH3SH ceased (for 5 h). The reaction mixture was left to
cool at room temperature. The crystalline substances were separated
and crystallized from acetic acid as brown crystals of 19a,b.
19a, m.p. 220◦C, yield 70%, elemental analysis for C15H9N3O3, Calcd.
C, 64.52; H, 3.23; N, 15.05; found: C, 64.60; H, 3.52; N, 15.21; IR (cm−1):
3330 (NH), 1725, 1690 (2 C O) and 1645 (C N).
19b, m.p. 280–281◦C, yield 72%, elemental analysis for C15H9N3O2S,
Calcd. C, 61.02; H, 3.05; N, 14.24; S, 10.85; found: C, 61.31; H, 3.20; N,
14.22; S, 11.00; IR (cm−1: 3305 (NH), 1720, 1685 (2 C O) and 1640
(C N) and 1H-NMR (δ ppm): 6.2 (s, 1H, Ar-CH ), 6.6–6.9 (m, 3H, thio-
phene H-3, H-4 and H-5), 7.2–7.5 (m, 4H, Ar-H) and 11.1 (s, 1H, NH,
exchangeable with D2O).
Preparation of 1-Phenyl-3-ylideneimidazo[2,1-b]quinazoline-
2,5-diones 21a,b
A mixture of 0.01 mole of each of 5-ylidene-2-methylmercapto-
hydantoins 17c,d (0.01 mole) and anthranilic acid (0.01 mole) was
heated in ethanol (50 mL). During the reaction, the odor of the evolved

66

Reactions of 5-Arylidene-2-thiohydantoins
67
methanethio easily could be detected. The reaction was worked up
as previously described, and the solid obtained was crystallized from
ethanol as brown crystals of 21a,b.
21a, m.p. 296◦C, yield 70%, elemental analysis for C21 H13N3O3,
Calcd. C, 70.98; H, 3.66; N, 11.83; Found: C, 70.76; H, 3.54; N, 14.00; IR
(cm−1): 1720, 1685 (2 C O) and 1640 (C N) and 1H-NMR (δ ppm): 6.1
(s, 1H, CH ), 6.7–7.0 (m, 3H, thiophene H-3, H-4, and H-5) and 7.2–7.6
(m, 9H, Ar-H).
21b, m.p. 292◦C, yield 72%, elemental analysis for C21H13N3O2S,
Calcd. C, 67.92; H, 3.50; N, 11.32; S, 8.63; found: C, 68.10; H, 3.37; N,
11.14; S, 8.52; IR (cm−1: 1715, 1690 (2 C O) and 1635 (C N).
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