Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2018.06.057

We have investigated ultrasound-assisted synthesis of guanidine derivatives using 1H-Pyrazole-1-carboxamidine (PyzCA) and S-substituted isothiouronium sulfate (MeITU). The guanylations of several amines are promoted by ultrasound sonication under solvent-free conditions, and proceed under mild conditions. It is of particular interest that the guanylations do not require bases in most cases.

Full text of DOI:10.1016/j.tet.2018.06.057

Tetrahedron xxx (2018) 1e4
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ultrasound-assisted synthesis of substituted guanidines using
1H-pyrazole-1-carboxamidine and S-methylisothiouronium sulfate
under solvent-free conditions
Mitsue Fujita*, Yoshio Furusho
Department of Chemistry, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
We have investigated ultrasound-assisted synthesis of guanidine derivatives using 1H-Pyrazole-1-
carboxamidine (PyzCA) and S-substituted isothiouronium sulfate (MeITU). The guanylations of several
amines are promoted by ultrasound sonication under solvent-free conditions, and proceed under mild
conditions. It is of particular interest that the guanylations do not require bases in most cases.
© 2018 Elsevier Ltd. All rights reserved.
Received 8 May 2018
Received in revised form
21 June 2018
Accepted 23 June 2018
Available online xxx
Keywords:
Guanidine
Solvent-free
Ultrasound
1H-pyrazole-1-carboxamidine
hydrochloride
S-methylisothiouronium sulfate
1. Introduction
such as low yields and harsh conditions.
Sonochemical methods have recently proved a powerful tech-
Guanidine functionality is often found in a number of biologi-
cally and pharmaceutically relevant compounds, playing important
roles in functions of those molecules [1e5]. A wide range of bio-
logical activities are attributed to the high basicity and ability to
form strong hydrogen bonds under physiological conditions,
including antibacterial, antifungal, antiviral, anti-inflammatory,
and anti-tumor activities [4,5]. Furthermore, various guanidines
have been employed as key building blocks for supramolecules,
synthetic receptors, sensors as well as catalysts [6e12].
The demand for guanidine derivatives have thus been growing
to date. Accordingly, various new synthetic methods have been
developed for obtaining this class of compounds [13,14]. Among
them, guanylation of amines is the most popular way to guanidine
derivatives, since the starting materials are often readily available
and relatively inexpensive [15e30]. Several kinds of guanylation
reagents have been developed to date, including isothiouronium
salts, carbodiimides, cyanamides, 1H-pyrazole-1-carboxamidine,
etc. Nevertheless, these methods sometimes confront problems
nique for facilitating various chemical reactions [31e37]. Ultrasonic
energy can cause the formation and adiabatic collapse of transient
cavitation bubbles of gaseous substances [38]. Owing to this cavi-
tation effect, solubility, diffusivity, penetration, and mass trans-
portation and turbulent flow of chemical species are enhanced in
certain reactions. Consequently, ultrasound in organic synthesis
often shortens reaction times and reduces the formation of unde-
sired side products, thereby enhancing product yield and selectivity
and requiring in milder conditions than conventional methods. In
addition, the ultrasound-assisted synthesis is applicable to solvent-
free or low-solvent conditions [39e44]. Therefore, it is often called
a green method with its high efficiency, economic performance,
low energy demand, and low instrumental requirement. Moreover,
it reduces significantly the process time as compared to conven-
tional heating methods.
1H-Pyrazole-1-carboxamidine (PyzCA) is quite often employed
to guanylate amines for the purpose of synthesizing bioactive
compounds sometimes with complicated chemical structures,
since the guanylation proceeds with high yield and selectivity
[23e30]. However, it requires, in general, solvent and base. On the
other hand, guanylation of amines with S-substituted
* Corresponding author.
E-mail address: mitue@belle.shiga-med.ac.jp (M. Fujita).
https://doi.org/10.1016/j.tet.2018.06.057
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: M. Fujita, Y. Furusho, Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-
carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions, Tetrahedron (2018), https://doi.org/10.1016/
j.tet.2018.06.057

2
M. Fujita, Y. Furusho / Tetrahedron xxx (2018) 1e4
isothiouronium salt (MeITU) is one of the most often used method
to obtain substituted guanidines [15e22]. It is generally carried out
using polar solvents such as water and alcohols with an excess of
base under reflux conditions for a long period of time. Thus, both
methods with above guanylating reagents have much room for
improvement, especially in light of green process.
In the present work, we have explored the application of ul-
trasound to guanylation of amines with PyzCA or MeITU. We have
found that the guanylation proceeds under solvent-free conditions
when ultrasound was applied. In addition, the guanylation does not
require base in most cases.
Octanamine, a primary amine with a secondary alkyl group, gave
a similar result to that for cyclohexylamine, i.e., ultrasound irradi-
ation accelerated the guanylation when compared to that with
magnetic stirring (entries 7e8). Piperidine, a cyclic secondary
amine, was guanylated with a little acceleration by ultrasound
(entry 9). Guanylation of dibutylamine, a secondary amine with
two alkyl chains, proceeded slower than that of piperidine (entry
10). This is probably because that the steric hindrance of secondary
amine with two alkyl chains is larger than that with a cyclic sec-
ondary amine structure, as is often observed in organic reactions.
Aniline was hardly guanylated, arising from the low nucleophilicity
of the aromatic amino group (entry 11). Application of ultrasound
resulted in lowering the yield, although the reason is not clear at
present. Unexpectedly, guanylation of 4-methoxyaniline (p-anisi-
dine) was much accelerated by ultrasound (entries 12e14). Thus,
no distinct frequency dependence was observed for the accelera-
tion of the guanylation reactions, although it is proposed that ul-
trasound with frequency lower than 100 kHz mainly induces
mechanical effects [45], while that with frequency higher than
100 kHz chiefly bring about chemical effects [46].
It is of great importance to compare our results with conven-
tional methods using PyzCA in solution. For example, it was re-
ported that N-cyclohexylguanidinium chloride was obtained in 84%
yield by stirring a solution of cyclohexylamine, PyzCA, and diiso-
propylethylamine in DMF at ambient temperature for a few hours
[23], while we demonstrated here that the yield was increased up
to 97% by ultrasound application on a mixture of cyclohexylamine
and PyzCA for few hours, as described above (entry 3). Thus, the
ultrasound method gave higher yields than the conventional
methods in most cases (cyclohexylamine [23,29], 2-ethanolamine
[23], 1-octanamine [30], piperidine [23], 4-methoxyaniline [23]),
except for aniline [23]. Another interesting point is that the ultra-
sound method does not require base for activating the reaction, in
contrast to the conventional methods which often require organic
2. Results and discussion
We first chose guanylation of cyclohexylamine using PyrCA to
see how it works to apply ultrasound to the mixture (Table 1, en-
tries 1e3). The reaction was almost completed (97% yield) within
1.5 h at 25 ꢀC under ultrasound irradiation with a high frequency of
480 kHz, while the yield reached only 63% with magnetic stirring
instead of ultrasound irradiation. The guanylation was thus accel-
erated by ultrasound irradiation. The high frequency ultrasound
promoted the reaction to a certain extent than the low frequency
ultrasound, although the effect does not seem clear. We then
investigated the guanylation of various amines using PyzCA, as
shown in Table 1. Guanylations of primary amines with a primary
alkyl group completed within 0.17 h (10 min) with magnetic stir-
ring, so that the effect of ultrasound could not be confirmed (entries
4 and 5). 1-octadecanamine (stearylamine) is a primary amine with
a long alkyl chain. Nevertheless, its guanylation was much slower
than that of 1-octanamine (entry 6). This is probably because 1-
octadecanamine exists in solid state (m.p. 50e52 ꢀC). It is well-
known that ultrasound irradiation on heterogeneous, solid-liquid
mixture often accelerates organic reactions, while application of
ultrasound on solid-solid mixture does not work out well [37]. 2-
Table 1
Guanylation of various amines using 1H-pyrazole-1-carboxamidine hydrochloride (PyzCA) at 25 ꢀC.a
Amineb
Time (h)
USLF
Yield (%)c
USHF
Stirringf
d
Entry
e
1
2
3
4
5
6
7
8
Cyclohexylamine (ꢁ18)
0.5
1.0
1.5
0.17
0.17
3
0.5
1
0.5
3
49
92
82
88
97(93)
98
98(99)
48
72
89
89
17
63
99
99
40
2-Ethanolamine (10)
95
95
24
78
89
95
14
4
1-Octanamine (ꢁ5 to ꢁ1)
1-Octadecanamine (50e52) (Stearylamine)
2-Octanamineg
65
83
21
24
9
Piperidine (ꢁ7)
10
11
12
13
14
Dibutylamine (ꢁ62)
Aniline (ꢁ6)
2
1.5
2
7
68
4-Methoxyaniline (56e59)
(p-anisidine)
81
86
3
91
50
a
Amine (1.0 mmol); PyzCA (1.05 mmol).
b
c
d
e
f
Melting point (ꢀC) of the amine is in the parenthesis.
Estimated by GC based on the formation of 1H-pyrazole. Isolated yield is in the parenthesis.
Ultrasound with a low frequency of 36.6 kHz was applied.
Ultrasound with a high frequency of 480 kHz was applied.
Reaction mixture was magnetically stirred.
g
Oil at room temperature.
Please cite this article in press as: M. Fujita, Y. Furusho, Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-
carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions, Tetrahedron (2018), https://doi.org/10.1016/
j.tet.2018.06.057

M. Fujita, Y. Furusho / Tetrahedron xxx (2018) 1e4
3
Table 3
bases, although the reason is not clear at present.
Effect of base on guanylation using PyzCA at 25 ꢀC.a
We next examined effect of temperature on the guanylations of
aniline and dibutylamine, which did not proceed very much at
25 ꢀC (Table 2). Aniline gave improved yields at an elevated tem-
perature of 40 ꢀC, where ultrasound acceleration was observed
(entries 1e3). Similarly, guanylation of dibutylamine reached 94%
yield 2 h after low frequency ultrasound irradiation at 50 ꢀC, while
it remained 71% without ultrasound (entries 4e6). It should be
noted here that aniline was guanylated in 48% yield by the con-
ventional method (in refluxing nitrobenzene for 5 h) [23], unlike
the ultrasound method which achieved 84% yield just by elevating
the reaction temperature up to 40 ꢀC.
We also examined the effect of base on the guanylation
employing aniline and dibutylamine (Table 3). 50 mol% of Na2CO3
was added to the mixture of aniline and PyzCA, to which ultrasound
was irradiated for 1 h. The guanylated aniline was obtained in 81%
and 72% yields with low frequency and high frequency irradiations,
respectively, and ultrasound acceleration was thus observed (entry
2). Addition of diisopropylethylamine (DIEA) also enhanced the
yield, and ultrasound acceleration was observed (entry 4). How-
ever, the reaction in the presence of 50 mol% of K2CO3 resulted in
low yields (entry 3). In contrast to aniline, guanylation of dibutyl-
amine did not show ultrasound acceleration either in the presence
or in the absence of Na2CO3 (entries 5 and 6).
c
Entry
Amine
Base
Time (h)
USLF
Yield (%)b
USHF
Stirringe
d
1
2
3
4
5
6
Aniline
none
Na2CO3
2
1
1
1
3
2
4
81
7
21
53
33
48
21
10
f
72
25
72
17
g
K2CO3
DIEAh
none
69
14
17
Dibutylamine
c
Na2CO3
a
Amine (1.0 mmol); PyzCA (1.05 mmol).
b
c
Estimated by GC based on the formation of 1H-pyrazole.
Ultrasound with a low frequency of 36.6 kHz was applied.
Ultrasound with a high frequency of 480 kHz was applied.
Reaction mixture was magnetically stirred.
Na2CO3 (0.5 mmol).
d
e
f
g
h
K2CO3 (0.5 mmol).
DIEA (0.05 mL ¼ 0.3 mmol).
PyzCA or MeITU is promoted by ultrasound sonication and pro-
ceeds under solvent-free conditions. It is of particular interest that
the guanylation does not require bases in most cases. This facile and
efficient method represents an alternative to the conventional
methods using solvent and base with heating. We believe that this
method will find use in the development of guanidine-based ma-
terials, and studies toward this end are ongoing in our group.
Finally, we investigated the guanylation using S-methyl-
isothiouronium sulfate (MeITU) by employing a couple of amines
(Table 4). Guanylation of 1-octanamine at 25 ꢀC with MeIU showed
ultrasound acceleration, although the yields remained low (entries
1 and 2). Elevating the temperature to 40 ꢀC, the yields increased
very much, especially when the high-frequency ultrasound was
applied (entries 3 and 4). The results are really remarkable when
considering that, in conventional methods, the guanylation using
MeITU is generally carried out in an alcoholic solvent for more than
10 h to complete the reaction. For example, it was reported that
heating a solution of 1-octanamine and MeITU in EtOH at 100 ꢀC for
18 h gave N-octylguanidinium sulfate in 35% yield [16]. Similarly,
cyclohexylamine exhibited ultrasound acceleration, and the yield
rose to 88% when the low-frequency ultrasound was irradiated
(entries 5 and 6). Guanylation of piperidine, a secondary amine, was
also accelerated by ultrasound (entries 7 and 8). However, the yield
remained low under the conditions, and was less than that of the
conventional method (68% yield, in refluxing water for 2 h) [20].
Thus, the guanylation using MeITU was accelerated by ultrasound
irradiation, although the reaction rates were not as high as that of
guanylation using PyzCA.
4. Experimental section
4.1. General procedures
All chemicals are commercially available and used as received.
Bath type sonochemical reactors having a 36.6 kHz or 480 kHz
frequency (Honda electrics, Japan) were used. The bath tempera-
ture was maintained by circulating thermo-controlled water
[45e47] and the water level inside the bath was kept constant.
Power of ultrasound introduced into
a reaction vessel was
measured by calorimetrically and was adjusted to 5 W unless
otherwise noted. Yields were determined by GC or 1H NMR (JEOL
ECZ-400S). The GC analysis was performed on a Shimadzu GC-2014
with a flame ionization detector and a capillary column Restek
Rtx®-1 (30 m ꢂ 0.25 mm ꢂ 0.25
mm). The column temperature was
first held at 80 ꢀC for 2 min, and then elevated to 230 ꢀC with an
increasing rate of 5 ꢀC/min. The temperatures of the injector and
the detector were kept constant at 230 ꢀC and 250 ꢀC, respectively.
4.2. General procedure of ultrasound-assisted guanylation of
amines with 1H-pyrazole-1-carboxamidine hydrochloride
3. Conclusions
In a cylindrical reaction flask with a flat bottom, the amine
(1.0 mmol) and 1H-pyrazole-1-carboxamidine hydrochloride
(1.05 mmol) were placed. The mixture was subjected to ultrasound
in a 36.6 or 480 kHz thermo-controlled ultrasonic bath. Control
experiments without ultrasound irradiation were carried out with
magnetic stirring of ca. 840 rpm. After the reaction, the mixture was
dissolved in ethanol (1/1 (v/v), 5 mL). The resultant ethanolic so-
lution was subjected to GC analysis to estimate the yield of the
guanidine.
In summary, we have found that guanylation of amine with
Table 2
Effect of temperature on guanylation using PyzCA.a
Entry Amine
Temp. (ꢀC) Time (h) USLF
Yield (%)b Stirringe
USHF
c
d
1
2
3
4
5
6
Aniline
25
40
40
2
1
2
3
3
2
4
7
21
77
84
14
58
94
69
77
17
72
49
21
Dibutylamine 25
4.3. General procedure of ultrasound-assisted guanylation of
amines with S-methylisothiouronium sulfate
40
50
71
a
b
c
Amine (1.0 mmol); PyzCA (1.05 mmol).
In a cylindrical reaction flask with a flat bottom, the amine
(1.0 mmol) and 1H-pyrazole-1-carboxamidine hydrochloride
(1.0 mmol) were placed. The mixture was subjected to ultrasound
in a 36.6 or 480 kHz thermo-controlled ultrasonic bath. Control
Estimated by GC based on the formation of 1H-pyrazole.
Ultrasound with a low frequency of 36.6 kHz was applied.
Ultrasound with a high frequency of 480 kHz was applied.
Reaction mixture was magnetically stirred.
d
e
Please cite this article in press as: M. Fujita, Y. Furusho, Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-
carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions, Tetrahedron (2018), https://doi.org/10.1016/
j.tet.2018.06.057

4
M. Fujita, Y. Furusho / Tetrahedron xxx (2018) 1e4
Table 4
Guanylation of various amines using S-methylisothiouronium sulfate (MeITU).a
d
e
Entry
Amineb
Temp. (ꢀC)
25
Time (h)
USLF
Yield (%)c USHF
Stirringf
1
2
3
4
5
6
7
8
1-Octanamine (ꢁ5 to ꢁ1)
1
2
1
2
1
2
1
2
20
25
39
63
45
88
20
34
12
26
80
87
42
71
23
17
9
17
43
40
40
40
Cyclohexylamine (ꢁ18)
Piperidine (ꢁ7)
16
8
a
Amine (1.0 mmol); MeITU (1.0 mmol).
b
c
d
e
f
Melting point (ꢀC) of the amine is in the parenthesis.
Estimated by 1H NMR.
Ultrasound with a low frequency of 36.6 kHz was applied.
Ultrasound with a high frequency of 480 kHz was applied.
Reaction mixture was magnetically stirred.
347e351.
[21] N. Aoyagi, Y. Furusho, T. Endo, Synlett 25 (2014) 983e986.
[22] S. Goswami, A. Hazra, S. Jana, Bull. Chem. Soc. Jpn. 82 (2009) 1175e1181.
[23] M.S. Bernatowicz, Y. Wu, G.R. Matsueda, J. Org. Chem. 57 (1992) 2497e2502.
[24] L. Mi, A.D. White, Q. Shao, P. Setlow, Y. Li, S. Jiang, Chem. Sci. 5 (2014)
3320e3324.
experiments without ultrasound irradiation were carried out with
magnetic stirring of ca. 400 rpm. After the reaction, the mixture
was dissolved in a mixed solvent of ethanol and water (1/1 (v/v),
5 mL). After the resultant solution was evaporated to dryness, the
mixture was subjected to 1H NMR analysis using DMSO‑d6 as
deuterated solvent to determine the yield of the guanidine.
ꢀ
ꢀ
[25] I. Heredero-Bermejo, J. Sanchez-Nieves, J. Soliveri, R. Gomez, F.J. de la Mata,
~
ꢀ
J.L. Copa-Patino, Perez-Serrano, J. Int. J. Pharm. 509 (2016) 1e7.
[26] J. Fu, C. Yu, L. Li, S.Q. Yao, J. Am. Chem. Soc. 137 (2015) 12153e12160.
[27] J. Sen, A. Chaudhuri, J. Med. Chem. 48 (2005) 812e820.
[28] A.S. Tikhomirov, A.E. Shchekotikhin, Y.-H. Lee, Y.-A. Chen, C.-A. Yeh,
V.V. Tatarskiy, L.G. Dezhenkova, V.A. Glazunova, J. Balzarini, A.A. Shtil,
M.N. Preobrazhenskaya, P.J. Chueh, J. Med. Chem. 58 (2015) 9522e9534.
[29] S. Dijols, J.-L. Boucher, M. Lepoivre, D. Lefevre-Groboillot, M. Moreau,
Y. Frapart, E. Rekka, A.L. Meade, D.J. Stuehr, D. Mansuy, Biochemistry 41
(2002) 9286e9292.
Acknowledgment
This work was supported by Iwatani Naoji Foundation and
Tokyo Ohka Foundation.
References
[30] T.A. Bakka, O.R. Gautun, Synth. Commun. 47 (2017) 169e172.
[31] T.J. Mason, Chem. Soc. Rev. 26 (1997) 443e451.
[32] G. Cravotto, P. Cintas, Chem. Soc. Rev. 35 (2006) 180e196.
[33] R.B.N. Baig, R.S. Varma, Chem. Soc. Rev. 41 (2012) 1559e1584.
[34] P. Saurabh, K. Balbir, P. Anupama, K. Harish, Current Org. Chem. 17 (2013)
1790e1828.
[35] D.H. Bremner, Ultrason. Sonochem. 1 (1994) S119eS124.
[36] M. Pattarawarapan, S. Jaita, S. Wangngae, W. Phakhodee, Tetrahedron Lett. 57
(2016) 1354e1358.
[37] T. Kimura, in: P.-K. Choi, N. Enomoto, H. Harada, K. Okitsu, K. Yasui (Eds.), In
Sonochemistry and the Acoustic Bubble, Elsevier, Amsterdam, 2015,
pp. 171e186.
[38] Y. Son, M. Lim, J. Khim, M. Ashokkumar, Ultrason. Sonochem. 19 (2012)
16e21.
[39] C. Cui, C. Zhu, X.-J. Du, Z.-P. Wang, Z.-M. Li, W.-G. Zhao, Green Chem. 14 (2012)
3157e3163.
[40] K.M. Al-Zaydi, R.M. Borik, R.A. Mekheimer, M.H. Elnagdi, Ultrason. Sonochem.
17 (2010) 909e915.
[41] J.-Y. He, H.-X. Xin, H. Yan, X.-Q. Song, R.-G. Zhong, Ultrason. Sonochem. 18
(2011) 466e469.
[42] G. Imanzadeh, F. Kazemi, M. Zamanloo, Y. Mansoori, Ultrason. Sonochem. 20
(2013) 722e728.
[43] J.-Y. He, H.-Z. Jia, Q.-G. Yao, S.-J. Liu, H.-K. Yue, H.-W. Yu, R.-S. Hu, Ultrason.
Sonochem. 22 (2015) 144e148.
[44] P.D. Tomke, V.K. Rathod, Ultrason. Sonochem. 27 (2015) 241e246.
[45] K.V.B. Tran, T. Kimura, T. Kondo, S. Koda, Ultrason. Sonochem. 21 (2014)
716e721.
[46] S. Koda, T. Kimura, T. Kondo, H. Mitome, Ultrason. Sonochem. 10 (2003)
149e156.
[47] T. Kimura, T. Sakamoto, J.-M. Leveque, H. Sohmiya, M. Fujita, S. Ikeda, T. Ando,
Ultrason. Sonochem. 3 (1996) S157eS161.
[1] D. Castagnolo, S. Schenone, M. Botta, Chem. Rev. 111 (2011) 5247e5300.
[2] R.G.S. Berlinck, A.C.B. Burtoloso, A.E. Trindade-Silva, S. Romminger,
R.P. Morais, K. Bandeira, C.M. Mizuno, Nat. Prod. Rep. 27 (2010) 1871e1907.
[3] R.G.S. Berlinck, S. Romminger, Nat. Prod. Rep. 33 (2016) 456e490.
[4] S. Tahir, A. Badshah, R.A. Hussain, Bioorg. Chem. 59 (2015) 39e79.
[5] F. Saczewski, Ł. Balewski, Expert Opin. Ther. Pat. 19 (2009) 1417e1448.
[6] D. Leow, C.-H. Tan, Chem. Asian J. 4 (2009) 488e507.
[7] T. Ishikawa, Chem. Pharm. Bull. 58 (2010) 1555e1564.
[8] Y. Sohtome, K. Nagasawa, Chem. Commun. (J. Chem. Soc. Sect. D) 48 (2012)
7777e7789.
[9] P. Selig, Synthesis 45 (2013) 703e718.
[10] C. Najera, J.M. Sansano, E. Gomez-Bengoa, Pure Appl. Chem. 88 (2016)
562e578.
[11] K. Hosoya, M. Odagi, K. Nagasawa, Tetrahedron Lett. 59 (2018) 687e696.
[12] T. Misaki, N.-R. Choi, A. Morita, T. Sugimura, Tetrahedron Lett. 56 (2015)
5063e5066.
[13] A.R. Katritzky, B.V. Rogovoy, ARKIVOC (2005) 49e87.
[14] C. Alonso-Moreno, A. Antinolo, F. Carrillo-Hermosilla, A. Otero, Chem. Soc.
Rev. 43 (2014) 3406e3425.
ꢀ
[15] M. Villarroya, L. Gandía, M.G. Lopez, A.G. García, S. Cueto, J.-L. García-Navio,
J. Alvarez-Builla, Bioorg. Med. Chem. 4 (1996) 1177e1183.
[16] C. Dardonville, I. Rozas, L.F. Callado, J.J. Meana, Bioorg. Med. Chem. 10 (2002)
1525e1533.
[17] A. Kraus, P. Ghorai, T. Birnkammer, D. Schnell, S. Elz, R. Seifert, S. Dove,
G. Bernhardt, A. Buschauer, ChemMedChem 4 (2009) 232e240.
[18] G.D. Coxon, B.L. Furman, A.L. Harvey, J. McTavish, M.H. Mooney, M. Arastoo,
A.R. Kennedy, J.M. Tettey, R.D. Waigh, J. Med. Chem. 52 (2009) 3457e3463.
[19] A. Porcheddu, G. Giacomelli, A. Chighine, S. Masala, Org. Lett.
6 (2004)
4925e4927.
[20] D. Guo, Y. Liu, T. Li, N. Wang, X. Zhai, C. Hu, P. Gong, Sci. China Chem. 55 (2012)
Please cite this article in press as: M. Fujita, Y. Furusho, Ultrasound-assisted synthesis of substituted guanidines using 1H-pyrazole-1-
carboxamidine and S-methylisothiouronium sulfate under solvent-free conditions, Tetrahedron (2018), https://doi.org/10.1016/
j.tet.2018.06.057