A Base-Free Multicomponent Domino Approach: One-Pot Synthesis of 2-Iminothiazolines via Oxy-Iodination of Arylacetylenes

Article abstract of DOI:10.1055/s-0035-1560502

A simple and an efficient multicomponent domino protocol is developed for the synthesis of 2-iminothiazolines starting from simple and readily available arylacetylenes, amines, and phenyl isothiocyanates under base-free conditions. The present method invo

Full text of DOI:10.1055/s-0035-1560502

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, 399–403
letter
399
G. S. Kumar et al.
Letter
Synlett
A Base-Free Multicomponent Domino Approach: One-Pot Synthe-
sis of 2-Iminothiazolines via Oxy-Iodination of Arylacetylenes
G. Santosh Kumar
R1
N
multicomponent
metal-free
A. Sanjeeva Kumar
H. M. Meshram*
S
NH4I, H2O2
R-NH2
Ar
Ar
I
AcOH, r.t., 6 h
R1NCS
N
base-free
R
70 °C, 1 h
Medicinal Chemistry and Pharmacology Division,
CSIR-Indian Institute of Chemical Technology, Uppal Road,
Tarnaka, Hyderabad, Telangana 500007, India
hmmeshram@yahoo.com
Ar
rapid synthesis
65–82%
broad substrate scope
Received: 27.05.2015
Accepted after revision: 03.09.2015
Published online: 20.11.2015
F
NH
O
S
O
N
DOI: 10.1055/s-0035-1560502; Art ID: st-2015-b0397-l
S
NH
N
F
N
O
Abstract A simple and an efficient multicomponent domino protocol
is developed for the synthesis of 2-iminothiazolines starting from sim-
ple and readily available arylacetylenes, amines, and phenyl isothiocya-
nates under base-free conditions. The present method involves oxy-
iodination of the arylacetylenes with ammonium iodide and hydrogen
peroxide, followed by cyclization processes. A number of diversely func-
tionalized 2-iminothiazolines are synthesized in good to excellent
yields.
KHG22394
CO2H
PFT-α
HN
O
HN
S
O
H2N
N
N
Me
Me
PS-028
Key words arylacetylenes, amines, isothiocyanates, multicomponent
reactions, base-free, metal-free conditions
Figure 1 Representative examples of biologically active 2-iminothiazo-
The thiazole moiety is a core constituent in various
pharmaceuticals as well as agrochemicals such as acari-
cides, insecticides and plant growth regulators.1 Many nat-
urally occurring 2-iminothiazolines exhibit important bio-
logical activities, such as muscarinomimetic,2a anti-HIV,2b
fungicidal,2c analgesic,2d antibacterial,2e antifungal,2f mela-
nin-reducing (skin-whitening agent)2g platelet GPIIb/IIIa re-
ceptor antagonism,2h anti-inflammatory, analgesic and ki-
nase (CDK1, CDK5 and GSK3) inhibition.2i Some representa-
tive examples of biologically active compounds containing a
2-iminothiazoline moiety are shown in Figure 1.
As a result of this prevalence and the prominence of
2-iminothiazolines derivatives, numerous methods have
been developed for their synthesis. The most convenient
method to obtain the 2-iminothiazoline core is via the reac-
tion between thiourea derivatives and α-halo carbonyl
compounds.3 However, the use of highly toxic and lachry-
matory phenacyl bromides makes this method less pre-
ferred in the present era of green chemistry.
line derivatives
On the other hand, Murru et al.4 reported one-pot reac-
tions to furnish 2-iminothiazolines. Although, various syn-
thetic procedures have been described toward the synthesis
of 2-iminothiazolines, there have been no reports on meth-
ods involving the oxy-iodination of alkynes for the effective
synthesis of 2-iminothiazolines.
Concerning environmental problems and pollution, the
development of new synthetic methods that are less haz-
ardous to human health is highly desirable. This can be
achieved through the correct choice of starting materials,
atom-economic methodologies with a minimum number of
chemical steps, and the appropriate use of greener re-
agents. Hydrogen peroxide has emerged as a green oxidant
and its by-product is water.5 Multicomponent reactions
(MCRs) play important roles in pharmaceutical chemistry.
Atom economy, simplicity, and time-saving are important
features of multicomponent reactions.6 On the other hand,
domino reactions lead to the construction of complex mol-
ecules from simple starting materials in a single synthetic
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 399–403

400
G. S. Kumar et al.
Letter
Synlett
operation, with efficient bond-forming processes and high
atom economy (Scheme 1).7 This approach has distinct ad-
vantageous features such as decreased amounts of solvents,
reagents, catalysts, and adsorbents, and a reduction in the
number of purification processes. In continuation of our re-
search toward expanding the scope of 2-iminothiazoline
derivatives and multicomponent reactions,8 we herein doc-
ument a one-pot, multicomponent domino (MCD) ap-
proach for the synthesis of 2-iminothiazoline derivatives
from simple and readily available arylacetylenes, amines,
and phenyl isothiocyanates using ammonium iodide and
hydrogen peroxide in acetic acid (Scheme 2). To the best of
our knowledge, this is the first report on the oxy-iodination
of arylacetylenes using these reagents.
ble 1, entries 11–13). To further optimize the conditions,
the reaction was studied in different organic solvents such
as acetonitrile, methanol and dichloromethane. We found
that acetic acid was the most suitable solvent affording
maximum conversion into the product 4a (Table 1, entries
14–16). It was assumed that acetic acid forms an intermedi-
ate acetate–iodonium species (see Scheme 5), which facili-
tates the easy generation of an iodonium ion.
Table 1 Optimization of the Reaction Conditions for the Synthesis of
2-Iminothiazoline Derivativesa
Ph
N
PhNH2
S
2a
conditions
+
Ph
N
PhNCS
Ph
Ph
4a
1a
3a
R1
R2
A
C
B
D
+
+
P
Entry
Catalyst
Oxidant (mmol)
Solvent
Yield (%)b
1
2
NH4I
I2
H2O2 (1.1)
H2O2 (1.1)
H2O2 (1.1)
H2O2 (1.1)
H2O2 (1.1)
H2O2 (2.2)
H2O2 (2.2)
H2O2 (2.2)
H2O2 (2.2)
H2O2 (2.2)
TBHP (2.2)
DTBP (2.2)
MCPBA (2.2)
H2O2 (2.2)
H2O2 (2.2)
H2O2 (2.2)
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
MeCN
47
13
35
38
20
90
75
80
70
NR
20
NR
NR
10
15
5
Scheme 1 The present multicomponent-convergent domino strategy
R2
3
NaI
S
R1-NH2
N
NH4I, H2O2
4
KI
Ar
I
Ar
R2NCS
N
R1
5
n-Bu4NI
NH4I
NaI
AcOH, r.t., 6 h
Ar
70 °C, 1 h
6
Scheme 2 Synthesis of 2-iminothiazoline derivatives via a multicom-
ponent domino strategy
7
8
KI
9
n-Bu4NI
–
Our initial studies were directed toward examining the
plausibility of our protocol and optimization of the reaction
conditions. Thus, we investigated different reaction condi-
tions using phenylacetylene (1a), aniline (2a), and phenyl
isothiocyanate (3a) as model substrates in the presence of
different iodine sources including ammonium iodide, io-
dine (I2), sodium iodide, potassium iodide and tetrabu-
tylammonium iodide, and hydrogen peroxide (1.1 mmol) in
acetic acid at room temperature (Table 1). It was observed
that the reactions proceeded using ammonium iodide (Ta-
ble 1, entries 1–5). Increasing the amount of hydrogen per-
oxide (from 1.1 mmol to 2.2 mmol) gave the desired prod-
uct 4a in 90% yield (Table 1, entry 6). The structure of the
product was confirmed by means of IR, 1H NMR and
13C NMR spectroscopy and mass spectrometry. When sodi-
um iodide, potassium iodide or tetrabutylammonium io-
dide was used as the iodine source (instead of ammonium
iodide) in the presence of hydrogen peroxide (2.2 mmol),
the reactions proceeded to afford the desired product 4a in
yields of up to 80% (Table 1, entries 7–9). However, the reac-
tion failed in the absence of an iodine source (Table 1, entry
10), which indicated that the use of an iodine source in
combination with an excess of a co-oxidant was essential
for this reaction to proceed successfully. Next, we studied
other oxidants including tert-butyl hydroperoxide (TBHP),
di-tert-butyl peroxide (DTBP) and m-chloroperoxybenzoic
acid, but these proved to be ineffective for this reaction (Ta-
10
11
12
13
14
15
16
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
MeOH
CH2Cl2
a Reaction conditions: phenylacetylene (1a) (1 mmol), iodine source (2
mmol), 30% H2O2 (2.2 mmol), solvent, 6 h, r.t., then aniline (2a) (1 mmol),
phenyl isothiocyanate (3a) (1 mmol), 1 h, 70 °C.
b Yield of isolated product. NR = no reaction.
Having developed optimized conditions for the synthe-
sis of 4a, we next applied these conditions to a range of dif-
ferent amines, arylacetylenes and isothiocyanates for the
synthesis of 2-iminothiazoline derivatives. The experimen-
tal results are summarized in Scheme 3. Amines such as
phenyl, benzylic, aliphatic and cyclic were converted
smoothly into the desired products in moderate to excellent
yields (4a,e,k,o,w). Regarding the arylacetylenes, the exper-
imental results revealed that electron-donating arylacety-
lenes gave similar yields of the desired products
(4d,f,g,l,m,p,v,x) compared to electron-withdrawing aryl-
acetylenes (4b,c,h–j,n,q–u,y). This implied that the elec-
tronic nature of the arylacetylenes had little influence on
the reaction efficiency. It is worth mentioning that benzyl
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 399–403

401
G. S. Kumar et al.
Letter
Synlett
(3b) and benzoyl isothiocyanates (3c) underwent the domi-
no reaction with arylacetylenes 1 and benzylamine (2b)
under the same reaction conditions to furnish the corre-
sponding products in high yields (4z and 4aa).
In order to address the necessity for acetic acid in this
multicomponent domino strategy, we carried out a few
control experiments. The reaction of phenylacetylene (1a)
with ammonium iodide and hydrogen peroxide was con-
ducted both with and without acetic acid (Scheme 4). In the
former reaction, the corresponding (iodoethynyl)benzene
was obtained in 96% yield at room temperature, but in the
latter reaction, the formation of (iodoethynyl)benzene was
not observed. These results indicate that the presence of
acetic acid is necessary for the success of the iodoalkyne
synthesis. Moreover, to determine whether the iodoalkyne
is an intermediate during the synthesis of 2-iminothiazo-
lines 4, the reaction of (iodoethynyl)benzene with aniline
(2a) and phenyl isothiocyanate (3a) was next examined,
both at room temperature and under heating conditions.
Consequently, the expected product 4a was obtained in 82%
yield on heating at 70 °C, but the reaction at room tempera-
ture gave product 4a in a low 10% yield. These results indi-
cate that the iodoalkyne is one of the intermediates during
the synthesis of 2-iminothiazolines, and proves that acetic
acid is necessary for both stages.
R2
R1 NH2
2
3
NH4I, H2O2
S
N
Ar
I
Ar
AcOH, r.t.
6 h
R2NCS
N
R1
1
70 °C, 1 h
Ar
4
Ph
Ph
Ph
Ph
S
S
S
N
N
S
N
N
N
N
N
N
Ph
Ph
Ph
Ph
Ph
Cl
F
4c 75%
Ph
4d 77%
4a 80%
4b 72%
Ph
S
N
Ph
S
Ph
S
S
N
N
N
N
N
N
N
Ph
Ph
Ph
Ph
Ph
OMe
Br
4h 75%
4e 82%
4g 78%
4f 77%
Ph
Ph
S
Ph
S
Ph
S
NH4I, H2O2
S
N
Ph
I
N
N
Ph
Ph
N
AcOH, r.t., 6 h
96%
1a
1a
N
N
N
N
Ph
Ph
Ph
NH4I, H2O2
r.t., 6 h
Ph
Ph
Ph
I
0%
Cl
NO2
4j 73%
4i 73%
4k 77%
Ph
4l 74%
Ph
Ph
S
N
Ph
Ph
S
PhNH2 (2a)
S
N
S
Ph
I
N
S
N
(3a)
PhNCS
N
N
AcOH, 70 °C, 1 h
N
N
N
Ph
N
Ph
Ph
Ph
Ph
82%
NO2
OMe
Ph
4n 70%
4p 67%
4m 75%
4o 70%
Ph
PhNH2 (2a)
S
N
Ph
Ph
N
Ph
S
Ph
I
PhNCS (3a)
AcOH, 12 h, r.t.
S
N
S
N
S
N
N
Ph
Ph
N
N
N
N
Et
Et
10%
Scheme 4 Control experiments
Cl
NO2
Br
F
4t 68%
4r 65%
4q 65%
4s 67%
Ph
N
Ph
Ph
N
Ph
S
N
A putative mechanism for this ammonium iodide/hy-
drogen peroxide catalyzed multicomponent domino reac-
tion of arylacetylenes 1 with amines 2 and isothiocyanates
3 is proposed based on previous reports,9 and is illustrated
in Scheme 5. Initially, hydrogen peroxide oxidizes the io-
dide (I–) (NH4I) into an iodonium species (I+) (HOI), which
further reacts with the arylacetylene in the presence of ace-
tic acid to give the iodoalkyne product A. Next, the carbon
adjacent to iodine in A is attacked by the sulfur of thiourea
derivative B (generated in situ from amine 2 and isothiocy-
anate 3) to furnish the intermediate C. Finally, alkyne C un-
dergoes intramolecular cyclization to afford the 5-aryl-2-
iminothiazoline 4 as the final product. The previously re-
ported X-ray crystal structures4 of 2-iminothiazolines es-
tablished that they adopt syn (Z) stereochemistry due to the
steric hindrance between the R2 and N–R1 groups.
S
S
N
S
N
N
N
N
Et
Et
Ph
Br
S
4w 69%
4u 69%
4v 70%
4x 66%
Ph
N
Ph
Ph
S
N
S
N
N
N
N
Bu
Ph
Ph
Cl
OMe
4y 73%
4z 70%
4aa 71%
Scheme 3 Scope of the amines, arylacetylenes and isothiocyanates.
Reaction conditions: arylacetylene 1 (1 mmol), NH4I (2 mmol), 30% H2O2
(2.2 mmol), AcOH, 6 h, r.t., then amine 2 (1 mmol), isothiocyanate 3 (1
mmol), 1 h, 70 °C. Yields are those of isolated products.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 399–403

402
G. S. Kumar et al.
Letter
Synlett
NH4I + H2O2
NH4OH + HOI
H2O + MeCOO I
HOI + MeCOOH
H
N
H
N
R1
R2
R2
R2
S
B
S
N
S
N
MeCOO I
MeCOOH
I
Ar
Ar
NH
R1
N
R1
Ar
R1-NH2
2
Ar
A
4
C
+
R2NCS
3
1
Scheme 5 A plausible mechanistic pathway for the formation of 5-aryl-2-iminothiazolines
We believe that the present method, which proceeds via
the oxy-iodination of arylacetylenes and avoids the use of
highly toxic and lachrymatory phenacyl bromides, might
serve as an alternative procedure for the synthesis of 2-imi-
nothiazolines.10 Moreover, the present method provides a
route to access 2-iminothiazolines which have not been
prepared earlier (Scheme 3, 4b,i,m,o–r,s–v,w,x,y,z,aa).
In conclusion, we have established a highly improved
procedure for the regioselective synthesis of 5-aryl-2-imi-
nothiazolines as single isomeric products, which is based
on a multicomponent domino strategy using an ammoni-
um iodide/hydrogen peroxide system. The present protocol
involves four different reactions in a single pot: iodination,
two nucleophilic additions, and a nucleophilic substitution.
The base- and metal-free conditions, high efficiency and
improved regioselectivity over other conventional methods
should make the present protocol practical for the prepara-
tion of functionalized 5-aryl-2-iminothiazoline deriva-
tives.11 We believe that the present method might find fu-
ture applications in organic synthesis and pharmaceutical
chemistry.
Kranz, L.; Luthardt, H.; Roethling, T.; Kaestner, A. DD 258168,
1988; Chem. Abstr. 1989, 111, 2681g.
(2) (a) Ivanov, Y. Y.; Tkachenko, S. E.; Proshin, A. N.; Bachurin, S. O.
Biomed. Khim. 2003, 49, 92. (b) Manaka, A.; Sato, M.; Aoki, M.;
Tanaka, M.; Ikeda, T.; Toda, Y.; Yamane, Y.; Nakaike, S. Bioorg.
Med. Chem. 2001, 11, 1031. (c) Aamer, S.; Sabah, Z.; Maryam, J.;
Bushra, M. Turk. J. Chem. 2008, 32, 585. (d) Misra, V. S.; Saxena,
A. J. Indian Chem. Soc. 1970, 47, 23. (e) Hassan, H. Y.; El-Kousi, N.
A.; Farghaly, Z. S. Chem. Pharm. Bull. 1998, 46, 863. (f) Bae, S.;
Hahn, H. G.; Nam, K. D.; Mah, H. J. Comb. Chem. 2005, 7, 7.
(g) Kim, D. S.; Jeong, Y. M.; Park, I. K.; Hahn, H. G.; Lee, H. K.;
Kwon, S. B.; Jeong, J. H.; Yang, S. J.; Sohn, U. D.; Park, K. C. Biol.
Pharm. Bull. 2007, 30, 180. (h) Manaka, A.; Sato, M.; Aoki, M.;
Tanaka, M.; Ikeda, T.; Toda, Y.; Yamang, Y.; Nakaike, S. Bioorg.
Med. Chem. Lett. 2001, 11, 1031. (i) Sondhi, S. M.; Singh, N.;
Lahoti, A. M.; Bajaj, K.; Kumar, A.; Lozach, O.; Meijer, L. Bioorg.
Med. Chem. 2005, 13, 4291.
(3) (a) Hantzsch, A.; Weber, J. H. Chem. Ber. 1887, 20, 3118.
(b) Traumann, V. Liebigs Ann. Chem. 1888, 31. (c) Svetlik, J. J. Org.
Chem. 1990, 55, 4740. (d) D’hooghe, M.; Waterinckx, A.; De
Kimpe, N. J. Org. Chem. 2005, 70, 227. (e) Sanemitsu, Y.;
Kawamura, S.; Satoh, J.; Katayama, T.; Hashimoto, S. J. Pestic. Sci.
2006, 31, 305. (f) De Kimpe, N.; Boelens, M.; Declercq, J. P. Tetra-
hedron 1993, 49, 3411. (g) De Kimpe, N.; De Cock, W.; Keppens,
M.; De Smaele, D.; Meszaros, A. J. Heterocycl. Chem. 1996, 33,
1179. (h) Ingle, S. T.; Kapley, S. M.; Chande, M. S. Proc. Indian
Acad. Sci., Chem. Sci. 1980, 89, 295. (i) Wang, X.; Wang, F.; Quan,
Z.; Zhang, Z.; Wang, M. Synth. Commun. 2006, 36, 2453. (j) Xia,
M.; Lu, Y.-D. Synth. Commun. 2006, 36, 1637. (k) Manaka, A.;
Ishii, T.; Takahashi, K.; Sato, M. Tetrahedron Lett. 2005, 46, 419.
(l) Heravi, M. M.; Moghimi, S. Tetrahedron Lett. 2012, 53, 392.
(4) Murru, S.; Singh, C. B.; Kavala, V.; Patel, B. K. Tetrahedron 2008,
64, 1931.
Acknowledgment
G.S.K. and A.S.K. thank the CSIR for the award of fellowships. We are
grateful to Dr. Ahmed Kamal, Director IICT, for his support and en-
couragement. The authors also thank the CSIR, New Delhi for finan-
cial support as part of the XII Five Year Plan program under the title
ORIGIN (CSC-0108).
(5) (a) Backvall, J. E. Modern Oxidation Methods, 2nd ed.; Wiley-
VCH: Weinheim, 2011. (b) Lane, B. S.; Burgess, K. Chem. Rev.
2003, 103, 2457. (c) Sanderson, W. R. Pure Appl. Chem. 2000, 72,
1289.
Supporting Information
Supporting information for this article is available online at
(6) For reviews on multicomponent reactions, see: (a) Zhu, J. P.;
Bienaymé, H. Multicomponent Reactions; Wiley-VCH: Wein-
heim, 2005. (b) Ramón, D. J.; Yus, M. Angew. Chem. Int. Ed. 2005,
44, 1602. (c) Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J. Org.
Chem. 2004, 4957. (d) Muravyova, E. A.; Shishkina, S. V.;
Musatov, V. I.; Knyazeva, I. V.; Shishkin, O. V.; Desenko, S. M.;
Chebanov, V. A. Synthesis 2009, 1375. (e) Maggi, R.; Ballini, R.;
Sartori, G.; Sartorio, R. Tetrahedron Lett. 2004, 45, 2297.
(f) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3169.
(g) Khodaei, M. M.; Khosropour, A. R.; Moghanian, H. Synlett
http://dx.doi.org/10.1055/s-0035-1560502.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
(1) (a) Nagasaki, F.; Yamada, T.; Takahashi, E.; Kitagawa, Y.; Hatano,
R. JP 63250371, 1988; Chem. Abstr. 1989, 110, 192810
(b) Hoelzel, H.; Creuzburg, D.; Stohr, P.; Dehne, H.; Teller, J.;
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 399–403

403
G. S. Kumar et al.
Letter
Synlett
2006, 916. (h) Huang, S.; Pan, Y.; Zhu, Y.; Wu, A. Org. Lett. 2005,
7, 3797. (i) Kumar, R.; Raghuvanshi, K.; Verma, R. K.; Singh, M. S.
Tetrahedron Lett. 2010, 51, 5933. (j) Prajapati, D.; Gohain, D.
Beilstein J. Org. Chem. 2006, 2, 11.
completion of the reaction, the mixture was filtered, and the fil-
trate treated with aq Na2S2O3 solution and then extracted with
EtOAc. The combined organic layer was dried over Na2SO4 and
evaporated under reduced pressure. Purification by column
chromatography (hexane–EtOAc, 9.5:0.5) furnished the corre-
sponding thiazol-2-imine 4. All the obtained products were
characterized from their IR, 1H NMR, 13C NMR, MS and HRMS
spectral data.
(7) For reviews on domino reactions, see: (a) Tietze, L. F.; Brasche,
G.; Gericke, K. Domino Reactions in Organic Synthesis; Wiley-
VCH: Weinheim, 2006. (b) Tietze, L. F. Chem. Rev. 1996, 96, 115.
(c) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A. Chem. Commun.
2003, 551.
(8) (a) Kumar, G. S.; Ragini, S. P.; Meshram, H. M. Tetrahedron Lett.
2013, 54, 5974. (b) Chandrasekhara Rao, L.; Meshram, H. M.;
Satish Kumar, N.; Nageswara Rao, N.; Jagadhheesh Babu, N. Tet-
rahedron Lett. 2014, 55, 1127. (c) Meshram, H. M.; Babu, B. M.;
Kumar, G. S.; Thakur, P. B.; Bangade, V. M. Tetrahedron Lett.
2013, 54, 2296.
(Z)-N-[4-(4-Fluorophenyl)-3-phenylthiazol-2(3H)-
ylidene]aniline (4b)
Yield: 249.20 mg (72%); pale yellow solid; mp 172–174 °C. IR
(KBr): 703, 752, 1099, 1267, 1402, 1589, 1621 cm–1 1H NMR
.
(300 MHz, CDCl3): δ = 5.92 (s, 1 H), 6.88 (t, J = 8.54 Hz, 2 H),
6.99–7.10 (m, 5 H), 7.22–7.27 (m, 3 H), 7.28–7.35 (m, 4 H). 13C
NMR (75 MHz, CDCl3): δ = 97.1, 115.2 (d, 2JC–F = 21.7 Hz), 121.5,
4
(9) Narender, N.; Reddy, K. S. K.; Krishna Mohan, K. V. V.; Kulkarni,
S. J. Tetrahedron Lett. 2007, 48, 6124.
123.2, 127.6, 127.7 (d, JC–F = 2.7 Hz), 128.8, 128.9, 129.3, 129.9
3
1
(d, JC–F = 8.1 Hz), 137.7, 138.8, 151.7, 159.9, 162.4 (d, JC–F
=
(10) Thiazol-2-imines 4; General Procedure
248.8 Hz). MS (ESI): m/z = 347 [M + H]+. HRMS (ESI): m/z [M +
H]+calcd for C21H16N2FS: 347.1012; found: 347.1004.
(11) For a review on 2-iminothiazolidines (i.e., compounds related to
2-iminothiazolines), see: D’hooghe, M.; De Kimpe, N. Tetrahe-
dron 2006, 62, 513.
A 30% aq solution of H2O2 (2.2 mmol) was added dropwise to a
vigorously stirred solution of NH4I (2.2 mmol) and arylacety-
lene 1 (1 mmol) in AcOH (3 mL), and the resulting mixture was
allowed to stir at r.t. After 6 h, amine 2 and isothiocyanate 3
were added and the mixture was stirred at 70 °C for 1 h. After
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 399–403