Solvent-free, mild, facile, and rapid one-pot three-component synthesis of some novel imidazo[2,1-b]naphtho[1,2-e][1,3] thiazin-10-ones using p-TSA

Article abstract of DOI:10.1080/17415993.2014.885031

Novel [2,1-b]naphtho[1,2-e][1,3]thiazin-10-ones were synthesized in 63-89% yield via a three-component reaction of an aromatic aldehyde, β-naphthol, and thiohydantoin in the presence of 10 mol% p-toluene sulfonic acid under solvent-free conditions. This is the first protocol to be reported for the synthesis of the title compounds. The significant features of the present protocol are simplicity, high yields, eco-friendliness, and convenient purification that does not require chromatography.

Full text of DOI:10.1080/17415993.2014.885031

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Solvent-free, mild, facile, and rapid
one-pot three-component synthesis of
some novel imidazo[2,1-b]naphtho[1,2-
e][1,3] thiazin-10-ones using p-TSA
Mohammad M. Ghanbaria, Marzieh Jamalia & Gyula Battab
a Young Researchers and Elite Club, Marvdasht Branch, Islamic
Azad University, Marvdasht, Iran
b Department of Organic Chemistry, University of Debrecen,
Debrecen, Hungary
Published online: 11 Feb 2014.
To cite this article: Mohammad M. Ghanbari, Marzieh Jamali & Gyula Batta , Journal of Sulfur
Chemistry (2014): Solvent-free, mild, facile, and rapid one-pot three-component synthesis of some
novel imidazo[2,1-b]naphtho[1,2-e][1,3] thiazin-10-ones using p-TSA, Journal of Sulfur Chemistry,
DOI: 10.1080/17415993.2014.885031
To link to this article: http://dx.doi.org/10.1080/17415993.2014.885031
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Journal of Sulfur Chemistry, 2014
http://dx.doi.org/10.1080/17415993.2014.885031
Solvent-free, mild, facile, and rapid one-pot three-component
synthesis of some novel imidazo[2,1-b]naphtho[1,2-e][1,3]
thiazin-10-ones using p-TSA
Mohammad M. Ghanbaria∗, Marzieh Jamalia and Gyula Battab
aYoung Researchers and Elite Club, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran;
bDepartment of Organic Chemistry, University of Debrecen, Debrecen, Hungary
(Received 3 December 2013; accepted 15 January 2014)
Novel [2,1-b]naphtho[1,2-e][1,3]thiazin-10-ones were synthesized in 63–89% yield via a three-component
reaction of an aromatic aldehyde, β-naphthol, and thiohydantoin in the presence of 10 mol% p-toluene
sulfonic acid under solvent-free conditions. This is the first protocol to be reported for the synthesis of the
title compounds.The significant features of the present protocol are simplicity, high yields, eco-friendliness,
and convenient purification that does not require chromatography.
O
Ph
O
Ar
Ph
O
H
HO
Ph
N
S
PTSA
120oC
Ar
Ph
NH
S
+
N
+
HN
Keywords: thiohydantoins; aldehyde; β-naphthol; one-pot reaction; solvent-free
1. Introduction
Natural and synthetic heterocycles have recently attracted much attention in the fields of agro-
chemical and medicinal chemistry due to their wide range of biological activities and therapeutic
applications.[1–3] Hydantoin and 2-thiohydantoin derivatives are important nitrogen containing
heterocycles, which play key roles in the production of amino acids,[4] valuable intermediates
for the synthesis of pharmaceuticals and biologically active compounds, such as antibiotics,
anti-diabetics, anti-cancer drugs, pesticides, antiarrhythmics, anticonvulsant agents, and other
biologically activities.[5–7] As part of our study on heterocyclic and carbocyclic systems,[8–13]
we report the synthesis of 9,9-diphenyl-12-aryl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one, using a green synthetic method (Table 1). This new one-pot synthesis involves the
reaction of thiohydantoins 1, aromatic aldehyde 2 and β-naphthol in the presence of a catalytic
amount of p-toluene sulfonic acid (TSA) under thermal solvent-free conditions (Scheme 1).
∗Corresponding author. Email: m.mehdi.ghanbari@gmail.com
© 2014 Taylor & Francis

2
M.M. Ghanbari et al.
Table 1. Synthesis of 9,9-diphenyl-12-aryl-9H-imidazo[2,1-b]
naphtho[1,2-e][1,3]thiazin-10(12H)-one derivatives in the presence
of p-TSA under solvent-free conditions.
Entry
Ar
Products
Yield (%)
M.p. (◦C)
1
2
3
4
5
6
7
8
4-MeC6H4
4-ClC6H4
3a
3b
3c
3d
3e
3f
72
79
87
63
84
89
83
69
203
208
328
343
187
Red oil
213–215
190–192
4-NO2C6H4
4-MeOC6H4
4-OHC6H4
2,4-DiOHC6H3
4-FC6H4
3g
3h
5-Br-2-OHC6H3
O
Ph
O
Ar
Ph
O
HO
Ph
N
S
PTSA
120oC
Ar
Ph
NH
S
+
N
+
H
HN
1
2
3
Scheme 1. Synthesis of imidazo [2,1-b]naphtho[1,2-e][1,3]thiazin-10-ones.
2. Results and discussion
In a typical reaction, benzaldehyde (1.0 mmol) was reacted with β-naphthol (1.0 mmol) and
thiohydantoin (1.0 mmol) in the presence of a catalytic amount of p-TSA under thermal solvent-
free conditions to obtain 9,9-diphenyl-12-aryl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one in good yield. Salient features of this method are mild reaction conditions,
eco-friendliness, ease of isolation of product, and an excellent reusability of the catalyst.
Although we have not yet established experimental proof for the mechanism of the forma-
tion of compounds 3, a possible rationalization for the formation of the products is proposed in
Scheme 2. It is sensible to assume that the initial event is the formation of intermediates 4 from
the arylaldehyde and thiohyantoin. Subsequently, intermediate 4 is attacked by β-naphthol to
produce complex 6. Finally, an elimination of water from 6 affords product 3.
O
Ph
Ph
O
Ph
HN
Ar
HO
Ph
N
-H2O
-H2O
3
1 + 2
+
HN
N
Ar
S
HO
S
OH
4
6
Scheme 2. Proposed mechanism.
The 1H NMR spectrum of 3a exhibited two sharp singlets readily recognized as arising from
a methyl group (δ = 2.12 ppm), a CH group (δ = 6.78 ppm), and a multiplet for the aromatic
(δ = 7.14–7.98 ppm) protons. The 1H and 13C NMR spectra of 3b–g are similar to those of 3a
except for the aryl moieties, which exhibited characteristic signals with appropriate chemical
shifts. The structural assignments of compounds 3a–g made on the basis of their NMR spectra
were supported by their IR spectra.

Journal of Sulfur Chemistry
3
3. Conclusions
The reaction between thiohydantoins, β-naphthol, and aromatic aldehydes provides a simple
one-pot synthesis of imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-10-ones of potential synthetic and
pharmaceutical interest. The present procedure has the advantage that the reaction is performed
under neutral conditions, and the starting material can be used without any modification. This
reaction is simple, gives high yields, is eco-friendly, and does not require chromatographic
purification.
4. Experimental
Aldehyde and β-naphthol were obtained from Fluka and were used without further purification.
5,5-Diarylthiohydantoins were prepared by known methods.[14,15] Melting points (uncorrected)
were measured on an Electrothermal 9100 apparatus. Elemental analyses for C, H, N, and S were
performedusingaHeraeusCHN-S-Rapidanalyzer.Theexperimentaldatawereingoodagreement
with the calculated values. 1H and 13C NMR spectra (DMSO-d6) were measured with a Bruker
DRX-360 Avance spectrometer. IR spectra were recorded on a Shimadzu IR-460 spectrometer.
4.1. General procedure for the preparation of 9,9-diphenyl-12-aryl-9H-imidazo[2,1-b]
naphtho[1,2-e][1,3]thiazin-10(12H)-one 3
A mixture of the aldehyde (1 mmol), thiohydantoin (1 mmol), β-naphthol (1 mmol) and catalytic
amountof p-TSA(0.1 mmol)wasstirredat120◦Cfor3 h. Completionofthereactionwasindicated
by TLC. The reaction was cooled to room temperature, then ethylacetate (5 mL) was added and
the mixture stirred for 5 min. The solid obtained was removed by filtration and recrystallized from
ethanol.
4.1.1. 9,9-diphenyl-12-(p-tolyl)-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-10(12H)-one
(3a)
Red powder; m.p.: 200–203◦C;+yield: 3.6 g (72%). IR (KBr) (νmax/cm−1):1702 (C O), 1671
=
=
(C N). MS (EI) m/z 496.16 (M , > 2). Anal. Calcd (%) for C33H24N2OS (496.62): C, 79.81; H,
4.87; N, 5.64; S, 6.46. Found: C, 79.79; H, 4.86; N, 5.65; S, 6.45. 1H-NMR (360 MHz, DMSO-
d6): δ = 2.12 (3 H, s, Me), 6.78 (1 H, s, CH), 7.14–7.98 (20 H, m, Ar). 13C NMR (90 MHz,
DMSO-d6): δ = 21.3(CH3), 35.7 (CH), 73.0 (C), 123.8, 125.0, 125.9, 126.3, 126.6, 127.5, 128.2,
128.5, 128.8, 129.1, 129.4, 129.7, 129.9, 130.1, 130.3, 130.7, 131.9, 132.6, 134.9, 138.2, 142.2,
=
146.0, 166.2 (C O), 186.1 [NC(S)N].
4.1.2. 12-(4-chlorophenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3b)
Yellowpowder;m.p.:208◦C;yield:4.1 g(79%). IR(KBr)(νmax/cm−1):1723(C O), 1657(C N),
=
=
722 (C–Cl). Anal. Calcd (%) for C32H21ClN2OS (517.04): C, 75.34; H, 4.09; N, 5.42; S, 6.20.
1
Found: C, 75.32; H, 4.08; N, 5.43; S, 6.21. H-NMR (360 MHz, DMSO-d6): δ = 6.98 (1 H, s,
CH), 7.14–7.68 (20 H, m, Ar). 13C NMR (90 MHz, DMSO-d6): δ = 37.5 (CH), 73.2 (C), 124.1,
125.0, 125.9, 126.0, 126.8, 127.0, 128.1, 128.4, 128.7, 128.9, 129.2, 129.3, 129.6, 129.9, 130.2,
=
130.5, 130.6, 130.9, 131.7, 132.6, 134.9, 142.2, 146.2, 184.2 (C O), 192.7 [NC(S)N].

4
M.M. Ghanbari et al.
4.1.3. 12-(4-nitrophenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3c)
Yellow powder; m.p.: 328◦C; yield: 4.6 g (87%). IR (KBr) (νmax/cm−1): 1743 (C O), 1660
=
+
=
(C N), 1495, 1332 (NO2). MS (EI) m/z 527.13 (M , > 2). Anal. Calcd (%) for C32H21N3O3S
(527.59): C, 72.85; H, 4.01; N, 7.96; S, 6.08. Found: C, 72.87; H, 4.02; N, 7.95; S, 6.10. 1H-NMR
(360 MHz, DMSO-d6): δ = 6.96 (1 H, s, CH), 7.49–8.73 (20 H, m, Ar). 13C NMR (90 MHz,
DMSO-d6): δ = 35.7 (CH), 73.0 (C), 122.6, 124.2, 125.2, 125.6, 126.1, 126.4, 126.9, 127.7,
128.2, 128.5, 128.6, 128.9, 129.2, 129.5, 129.8, 130.1, 131.1, 132.3, 132.6, 134.8, 142.1, 142.4,
=
146.3, 149.1, 153.1, 173.7 (C O), 190.9 [NC(S)N].
4.1.4. 12-(4-methoxyphenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3d)
Red powder; m.p.: 343◦ C; yield: 3.2 g (63%). IR (KBr) (νmax/cm−1): 1698 (C O), 1654 (C N).
Anal. Calcd (%) for C33H24N2O2S (512.62): C, 77.32; H, 4.72; N, 5.46; S, 6.26. Found: C, 77.30;
H, 4.73; N, 5.45; S, 6.26. 1H-NMR (360 MHz, DMSO-d6): δ = 3.33 (3 H, s, OMe), 6.98 (1 H, s,
CH), 7.13–7.52(20 H, m, Ar).
=
=
4.1.5. 12-(4-hydroxyphenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3e)
Red powder; m.p.: 187◦C; yield: 4.2 g (84%). IR (KBr) (νmax/cm−1): 3440 (OH), 1712 (C O),
=
=
1649 (C N). Anal. Calcd (%) for C32H22N2O2S (498.59): C, 77.09; H, 4.45; N, 5.62; S, 6.43.
1
Found: C, 77.10; H, 4.45; N, 5.61; S, 6.42. H-NMR (360 MHz, DMSO-d6): δ = 6.55 (1 H, s,
CH), 6.97–7.95 (20 H, m, Ar), 8.65 (1 H, br s, OH). 13C NMR (90 MHz, DMSO-d6): δ = 36.2
(CH), 73.5 (C), 117.1, 123.8, 125.0, 125.9, 126.2, 126.7, 127.5, 128.1, 128.3, 128.6, 128.7, 129.1,
129.5, 129.7, 129.8, 130.6, 130.8, 132.5, 134.9, 138.2, 142.1, 156.0, 159.8, 176.6 (C=O), 193.3
[NC(S)N].
4.1.6. 12-(2,4-dihydroxyphenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3f)
Red oil; yield: 4.6 g (89%). IR (KBr) (νmax/cm−1): 3427 (OH), 1731 (C O), 1678 (C N). Anal.
Calcd (%) for C32H22N2O3S (514.59): C, 74.69; H, 4.31; N, 5.44; S, 6.23. Found: C, 74.70; H,
4.32; N, 5.45; S, 6.21. 1H-NMR (360 MHz, DMSO-d6): δ = 6.42 (1 H, br s, OH), 6.80 (1 H, s,
CH), 7.14–7.68 (19 H, m, Ar), 7.85 (1 H, br s, OH). 13C NMR (90 MHz, DMSO-d6): δ = 36.0
(CH), 73.2 (C), 106.0, 110.6, 113.1, 123.8, 125.0, 125.9, 126.4, 126.8, 127.5, 128.2, 128.3, 128.7,
128.9, 129.1, 129.6, 130.0, 130.5, 131.2, 131.8, 132.4, 135.0, 138.2, 142.1, 156.1, 156.9, 170.6
=
=
=
(C O), 184.8 [NC(S)N].
4.1.7. 12-(4-fluorophenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho[1,2-e][1,3]thiazin-
10(12H)-one (3g)
Orange powder; m.p.: 213-215◦C; yield: 4.1 g (83%). IR (KBr) (νmax/cm−1): 1709 (C O), 1648
(C N), 1198 (C F). Anal. Calcd (%) for C32H21FN2OS (500.59): C, 76.78; H, 4.23; N, 5.60; S,
6.41. Found: C, 76.80; H, 4.22; N, 5.59; S, 6.41. 1H-NMR (360 MHz, DMSO-d6): δ = 6.82 (1 H,
s, CH), 7.12–8.04 (20 H, m, Ar).

Journal of Sulfur Chemistry
5
4.1.8. 12-(5-bromo-2-hydroxyphenyl)-9,9-diphenyl-9H-imidazo[2,1-b]naphtho
[1,2-e][1,3]thiazin-10(12H)-one (3h)
Red powder; m.p.: 190–192◦C; yield: 3.98 g (69%). IR (KBr) (νmax/cm−1): 1698 (C O), 1665
=
=
(C N), 652 (C Br). Anal. Calcd (%) for C32H21BrN2O2S (577.49): C, 66.55; H, 3.67; N, 4.85;
S, 5.55. Found: C, 66.54; H, 3.66; N, 4.87; S, 6.56. 1H-NMR (360 MHz, DMSO-d6): δ = 6.51
(1 H, s, OH), 6.84 (1 H, s, CH), 7.14–8.23 (19 H, m, Ar).
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