Montmorillonite K10: an effective catalyst for synthesis of 2-aminothiazoles

Article abstract of DOI:10.1007/s11164-016-2587-7

An efficient one-pot synthesis of 2-aminothiazoles from methylcarbonyl and thiourea has been developed using montmorillonite-K10 as a catalyst at 80?°C in DMSO medium. A plausible mechanism is proposed in which α-iodomethylcarbonyls are formed via methylcarbonyls as raw material using iodine as iodination reagent.

Full text of DOI:10.1007/s11164-016-2587-7

Res Chem Intermed
DOI 10.1007/s11164-016-2587-7
Montmorillonite K10: an effective catalyst for synthesis
of 2-aminothiazoles
Javad Safari1 Masoud Sadeghi1
•
Received: 11 April 2016 / Accepted: 19 May 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract An efficient one-pot synthesis of 2-aminothiazoles from methylcarbonyl
and thiourea has been developed using montmorillonite-K10 as a catalyst at 80 °C
in DMSO medium. A plausible mechanism is proposed in which a-iodomethyl-
carbonyls are formed via methylcarbonyls as raw material using iodine as iodination
reagent.
Keywords Montmorillonite-K10 Á 2-Aminothiazole Á Thiourea Á Methylcarbonyls Á
Iodine
Introduction
Thiazole (or 1,3-thiazole) is one of the members of the azole families [1]. Thiazole
and its derivatives are one of the main components in a variety of natural
compounds [2]. Meanwhile, 2-aminothiazole derivatives as a subgroup of thiazole
family are important because of their medical applications as anti-HIV, antidiabetic,
antibacterial, antifungal, anti-oxidant, antitubercular, anti-inflammatory, anticancer,
antihypertensive, and neuroprotective [3–8]. Also, there is an appropriate attention
to this class of compounds in synthetic organic and medicinal chemistry. There are
various ways to synthesize this category of compounds (Fig. 1) [9–18]. Each of the
methods listed in Fig. 1 has positive and negative features; however, it seems that
the use of methyl carbonyl and thiourea as precursors is the most convenient
method.
In 2012, Wu and his colleagues proposed their method for the synthesis of
2-aminthiazole via a direct way using a CuO/I2 system and acetophenone and
thiourea as raw materials [19]. Although the scope of raw materials for aromatic
&
Javad Safari
Safari@kashanu.ac.ir; Safari_jav@yahoo.com
1
Department of Organic Chemistry, University of Kashan, P.O. Box 87317-51167, Kashan, Iran
123

J. Safari, M. Sadeghi
Fig. 1 Common methods for the synthesis of 2-aminothiazole
ketones has been well examined, but there is no reported information about aliphatic
ketones as a substrate.
In recent years, different protocols have been introduced for the synthesis of
2-aminothiazole using methylcarbonyls and thiourea as substrates. Some of these
methods include the following: NaICl2, [20] O2/KI/[Bmim]OTf, [21] and CBr4/
Et3N, [22] and Fe3O4@SiO2.TiO2/NBS [23]. Despite the advantages of the previous
methods, there is still a need to improve the synthesis of 2-aminothiazoles using
new strategies and catalysts, due to the significant importance of the class of
compounds in synthetic chemistry and pharmaceuticals.
Montmorillonite K10 (MMT-K10) is a layered aluminasilicate clay which has
many applications in synthetic organic reactions [24–29]. The featured properties of
montmorillonite are as follows: low cost, ease of handling, non-corrosiveness,
suitable surface area (250 m2/g), and reusability.
In continuation of previous workscarried out in our laboratory and in others, here
we reveal MMT-K10 as an inexpensive, green and efficient catalyst in combination
with iodine in the role of a reagent as a successful and efficient system for the
synthesis of 2-aminothiazoles.
Experimental
General
All chemicals were purchased from Merck. Melting points were determined using
an Electrothermal 9100 apparatus and are uncorrected. FT-IR spectra were recorded
1
as KBr pellets on a Shimadzu FT IR-8400S spectrometer. HNMR (400 MHz) and
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Montmorillonite K10: an effective catalyst for synthesis…
13CNMR spectra were obtained using a Bruker DRX-400 AVANCE spectrometer.
Analytical thin-layer chromatography (TLC) was accomplished on 0.2-mm
precoated plates of silica gel 60 F-254 (Merck) or neutral alumina oxide gel 60F
254 (Merck). Morphological characteristics of the nanostructures were character-
ized using a scanning electron microscope (SEM; EVO LS 10; Carl Zeiss,
Germany) operating at an accelerating voltage of 20 kV under high vacuum.
Procedure for preparation of MMT-Mn1
A sample of 1 gMMT-K10 clay was stirredwith1 M metal nitrate (Al, Cuand Zn) solution
for 3 days, filtered, and then washed with plenty of water to remove excess aluminium
nitrate. The product was dried at 90 °C under vacuum tray drying for overnight [30].
Procedure for preparation of MMT-WCl6
To a solution of montmorillonite K10 clay (2.7 g) in 50 mL of 2-propanol, 0.081 g of
WCl6 in 10 mL 2-propanol was added. The reaction mixture was stirred at room
temperature for 4 h. Then, the propanol was removed under reduced pressure and the
catalyst was dried in an oven at 110 °C for 3 h. The MMT-WCl6 was obtained as a fine
powder. The amount of tungsten loading was determined to be about 0.61 wt% [31].
Procedure for preparation of 2-aminothiazole by MMT-K10
A mixture of methylcarbonyl (0.5 mmol), thiourea (0.5 mmol), iodine (0.5 mmol),
DMSO (2 mL) and 20 mg MMT-K10 was stirred at 80 °C. After completion of the
reaction (monitored by TLC, petroleum:ethyl acetate, 4:1), the catalyst was
separated by filtration, and then the solvent was removed under reduced pressure.
The crude product was dissolved in hot water, extracted with ether (3 9 30 mL),
and adjusted to pH = 9–10 by ammonia to give the solid products. Finally, the
resulting precipitate was recrystallyzed by EtOH.
Thiazole-2-amine Pale yellow powder, m.p. = 89–90, Yield: 98 mg (98 %), IR
(KBr): 3410, 3289, 3084, 1629, 1521, 1491, 698 (cm-1), 1H NMR (400 MHz, DMSO-
d6): d = 6.52 (d, J = 3.7 Hz, 1H), 6.75 (s, 2H, NH2, D2O exchangeable), 6.90 (d,
J = 3.7 Hz, 1H), 13C NMR (100 MHz, DMSO-d6): d = 168.3, 138.1, 106.0., HRMS
(ESI): m/z [M ? H]? calcd for C3H4N2S: 101.0173; found: 101.0178.
4-Phenylthiazol-2-amine Yellow crystal, m.p. = 151–153, Yield: 163 mg (93 %),
1
IR (KBr): 3424, 3256, 2856, 1623, 1519, 1336, 728 (cm-1), H NMR (400 MHz,
DMSO-d6): d = 6.92 (s, 1H, thiazole), 7.22 (s, 2H, NH2, D2O exchangeable), 7.32
(t, J = 7.9 Hz, 1H, Ar–H), 7.69 (t, J = 7.9 Hz, 2H, Ar–H), 7.71 (m, J = 7.05 Hz, 2H,
Ar–H), 13C NMR (100 MHz, DMSO-d6): d = 167.5, 151.1, 134.6, 128.6, 127.7, 126.0,
102.7, HRMS (ESI): m/z [M ? H]? calcd for C9H9N2S: 177.0418; found: 177.0477.
4-(4-Nitrophenyl)thiazol-2-amine Yellow crystal, m.p. = 285–286, Yield:
1
212 mg (96 %), IR (KBr): 3400, 3115, 1626, 1596, 1507, 1331, 722 (cm-1), H
NMR (400 MHz, DMSO-d6): d = 7.45 (s, 1H, thiazole), 8.00 (d, J = 8.6 Hz, 2H,
123

J. Safari, M. Sadeghi
Ar–H), 8.28 (d, J = 8.6 Hz, 2H, Ar–H), 13C NMR (100 MHz, DMSO-d6):
d = 168.5, 147.8, 145.9, 140.8, 126.2, 124.0, 106.5, HRMS (ESI): m/z [M ? H]?
calcd for C9H7ClN2S: 221.03; found 221.23.
4-(4-Chlorophenyl)thiazol-2-amine White crystal, m.p. = 160–162, Yield: 186 mg
(89 %), IR (KBr): 3426, 2924, 1628, 1570, 1495, 744 (cm-1), 1H NMR (400 MHz,
DMSO-d6): d = 7.24 (s, 1H, thiazole, D2O exchangeable), 7.55 (d, J = 8.4 Hz, 2H,
Ar–H), 7.73 (d, J = 8.4 Hz, 2H, Ar–H), 8.43 (s, 2H, NH2, D2O exchangeable), 13
C
NMR (100 MHz, DMSO-d6): d = 169.2, 149.3, 134.4, 132.1, 129.0 (2C), 127.8 (2C),
102.7, HRMS (ESI): m/z [M ? H]? calcd for C9H7ClN2S: 211.0097; found 211.0092.
4-(3-Methylphenyl)thiazol-2-amine Yellow powder, m.p. = 88–91, Yield:
1
167 mg (88 %), IR (KBr): 3425, 2919, 1605, 1521, 1468, 714 (cm-1), H NMR
(400 MHz, DMSO-d6): d = 2.48 (s, 3H, CH3), 6.95 (s, 1H, thiazole), 7.02 (s, 2H,
NH2), 7.05 (d, J = 7.8 Hz, 1H, Ar–H), 7.22 (t, 1H, J = 7.9 Hz, Ar–H), 7. 56 (d,
J = 7.9 Hz, 1H, Ar–H), 7. 60 (s, 1H, Ar–H), 13C NMR (100 MHz, DMSO-d6):
d = 21.6, 122, 123.4, 129, 130.4, 133, 137.7, 138.9, 169, HRMS (ESI): m/
z [M ? H]? calcd for C10H10N2S: 190.269; found: 191.0
4-(2-Hydroxyphenyl)thiazol-2-amine Yellow powder, m.p. = 138–139, Yield:
1
163 mg (85 %), IR (KBr): 3246, 2064, 1635, 1569, 1461, 743 (cm-1), H NMR
(400 MHz, DMSO-d6): d = 6.88 (t, 1H, J = 7.6 Hz, 1H, ArH), 6.89 (d,
J = 8.24 Hz, 1H, ArH), 7.16 (s, 1H, thiazole, D2O exchangeable), 7.24 (t,
J = 8.24 Hz, 1H, ArH), 7.52 (d, J = 7.6 Hz, 1H, ArH), 8.70 (s, 1H, OH, D2O
exchangeable), 13C NMR (100 MHz, DMSO-d6): d = 168.3, 155.5, 147.2, 128.9,
126.3, 118.9, 118.3, 116.9, 100.5, HRMS (ESI): m/z [M ? H]? calcd for
C9H8N2OS: 193.0, found 193.1
4-(4-Hydroxyphenyl)thiazol-2-amine Yellow powder, m.p. = 198–200, Yield:
1
174 mg (91 %), IR (KBr): 3447, 2921, 1610, 1504, 1435, 834 (cm-1), H NMR
(400 MHz, DMSO-d6): d = 6.69 (d, J = 8.5 Hz, 2H, Ar–H), 6.70 (s, 1H, thiazole),
6.95 (d, 2H, NH2), 7.58 (d, J = 8.5 Hz, 2H, Ar–H), 9.50 (s, OH), 13C NMR
(100 MHz, DMSO-d6): d = 168.3, 156.9, 149.9, 127.1, 126.3, 115.4, 98.8, HRMS
(ESI): m/z [M ? H]? calcd for C9H9N2OS: 193.0430; found: 193.0427.
4-Methyl-5(ethoxycarbonyl)thiazol-2-amine White powder, m.p. = 177–179,
1
Yield: 182 mg (98 %), IR (KBr): 3374, 3085, 1674, 1515, 1373, 756 (cm-1), H
NMR (400 MHz, DMSO-d6): d = 1.21 (t, J = 7.1, 3H, CH3), 2.48 (s, 3H, CH3),
4.12 (q, 2H, CH2), 7.71 (S, 2H, NH2), 13C NMR (100 MHz, DMSO-d6): d = 14.71,
17.45, 60.32, 107.90, 159.69, 162.47, 170.71, HRMS (ESI): m/z [M ? H]? calcd
for C7H10N2O2S: 186.05; found: 186.23.
4-Methyl-5(methoxycarbonyl)thiazol-2-amine White powder, m.p. = 225–226,
Yield: 170 mg (99 %), IR (KBr): 3374, 3085, 1682, 1644, 1504, 1320, 758
(cm-1), 1H NMR (400 MHz, DMSO-d6): d = 2.57 (s, 3H, CH3), 3.85 (s, 3H, CH3),
6.12 (S, 2H, NH2), 13C NMR (100 MHz, DMSO-d6): d = 15.4, 51.5, 116, 155.5,
166.5, 169.1, HRMS (ESI): m/z [M ? H]? calcd for C6H8N2O2S: 172.03; found:
172.20.
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Montmorillonite K10: an effective catalyst for synthesis…
4-Methyl-5(allyloxycarbonyl)thiazol-2-amine White powder, m.p. = 148–149,
1
Yield: 194 mg (98 %), IR (KBr): 3375, 3083, 1672, 1514, 1374, 754 (cm-1), H
NMR (400 MHz, DMSO-d6): d = 2.38 (s, 3H, CH3), 4.15 (d, J = 5.4 Hz, 2H,
CH2), 5.26 (d, 1H, CH), 7.30 (d, 1H, CH), 5.92 (m, 1H, CH), 7.52 (s, 2H, NH2), 13
C
NMR (100 MHz, DMSO-d6): d = 16.4, 67, 116.11, 118.2, 132.1, 155.5, 166.5,
169.1, HRMS (ESI): m/z [M ? H]? calcd for C6H8N2O2S: 198.5 found: 198.24.
Results and discussion
The reaction conditions were optimized for the synthesis of 2-aminothiazole using
acetophenone and thiourea as model substrates and the obtained results are given in
Table 1.
Table 1 Optimization of the reaction conditions
Entry
Catalyst (mg)
Solvent
Temperature (°C)
Yield (%)
1
–
EtOH
80
80
80
80
80
80
80
80
80
80
80
80
90
70
80
80
80
80
65
66
67
55
50
50
60
90
50
35
40
35
85
80
85
96
94
92
2
Bentonite (10)
MMT-K10 (10)
MMT-Al3? (10) [30]
MMT-Cu2? (10) [30]
MMT-Zn2?(10) [30]
MMT-WCl6 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (10)
MMT-K10 (5)
MMT-K10 (20)
MMT-K10 (30)
MMT-K10 (40)
EtOH
3
EtOH
4
EtOH
5
EtOH
6
EtOH
7
EtOH
8
DMSO
CH3CN
EtOAc
THF
9
10
11
12
13
14
15
16
17
18
CH3OH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Reaction condition: acetophenone (1 eq), thiourea (1 eq), iodine (1 eq), catalyst, and solvent stirred at
80 °C for 2 h
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J. Safari, M. Sadeghi
Table 2 MMT-K10 catalyzed synthesis of 2-aminothiazoles
Entry
1
ketone
Product
Yield (%)
98
2
96
3
4
92
98
5
6
7
91
90
94
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Montmorillonite K10: an effective catalyst for synthesis…
Table 2 continued
Entry
ketone
Product
Yield (%)
8
99
9
99
99
10
Reaction condition: acetophenone (0.5 mmol), thiourea (0.5 mmol), iodine (0.5 mmol), MMT-K10
(20 mg), and DMSO (2 mL) stirred at 80 °C for 2 h
In the absence of the catalyst, 65 % of product was obtained at 80 °C in EtOH
medium (Table 1, entry 1).
We screened various clays and modified clays as the catalyst, such as bentonite
MMT-Al3?, MMT-Cu2?, MMT-Zn2?, and MMT-WCl6, to obtain the best catalyst
for the synthesis of 2-aminothiazole. The best results were obtained for MMT-K10
[30]. The various solvents were examined and in the meantime dimethyl sulfoxide
(DMSO) showed the best performance. Further, the temperature and the catalysis
loading were evaluated at 80 °C and 20 mg, respectively, anf the optimized amount
of the catalyst was chosen.
To develop the scope of the results, various methylcarbonyls as substrate were
screened including methyl ketones, ketones, aldehydes, b-ketoesters, and
diketone (Table 2).
The results showed that there are greater yields for more acidic substrates than
for less acidic substrates. Ethyl acetoacetate, methyl acetoacetate, and allyl
acetoacetate were almost entirely converted to the product (99 %). Acetaldehyde
showed a very good yield (98 %) and the acetophenone derivatives displayed an
acceptable performance ([90 %). Notably, 2-hydroxyacetophenone has the lowest
performance because of steric hindrance and the electron donating of hydroxyl
group (–OH).
Based on our previous understanding about the nature of the reaction mechanism
and the structure of the catalyst, it is assumed that a-halo carbonyl species plays a
key role in the reaction mechanism. [23]. Montmorillonite-K10 can act as a solid
acid catalyst due to the existence of both Bronsted and Lewis acid sites. In the
suggested mechanism, montmorillonite-K10 clay polarizes the carbonyl group of
acetophenone and produces a-iodoacetophenone (I) (Scheme 1). Subsequently, a
nucleophilic attack occurs in the a-position of the carbonyl group by
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J. Safari, M. Sadeghi
Scheme 1 Proposed mechanism for the synthesis of 2-aminothiazoles using MMT-K10
carbamimidothioic acid species (III). Finally, clay-promoted dehydrogenation gives
2-aminothiazoles (Scheme 1).
Conclusions
In summary, we have demonstrated a green and efficient protocol for the synthesis
of 2-aminothiazoles using montmorillonite-K10 as the catalyst. We have used
methylcarbonyl compounds and thiourea as raw materials. This method is
convenient, highly efficient and avoids the use of expensive reagents, and catalysts.
Acknowledgment We gratefully acknowledge the financial support from the Research Council of the
University of Kashan for supporting this work by Grant No. 256722/III.
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