Chemoselective synthesis of biheterocyclic skeletons tetrahydro-1H-pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives via multicomponent self-sorting domino strategy

Article abstract of DOI:10.1016/j.tet.2015.06.104

Abstract A highly efficient chemoselective synthesis of multifunctionalized tetrahydro-1H-pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives has been established from arylglyoxal monohydrates, nitriles, and thioureas. A series of control experiments suggested that this reaction proceeded through the convergent integration of two self-sorting domino sequences. This synthetic strategy is promising for diversity-oriented synthesis of alkaloid analogues.

Full text of DOI:10.1016/j.tet.2015.06.104

Accepted Manuscript
Chemoselective synthesis of biheterocyclic skeletons tetrahydro-1H-
pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives via
multicomponent self-sorting domino strategy
Qun Cai, Feng-Cheng Jia, Deng-Kui Li, Cheng Xu, Ke-Rong Ding, An-Xin Wu
PII:
S0040-4020(15)01001-7
10.1016/j.tet.2015.06.104
TET 26940
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 May 2015
Revised Date: 25 June 2015
Accepted Date: 29 June 2015
Please cite this article as: Cai Q, Jia F-C, Li D-K, Xu C, Ding K-R, Wu A-X, Chemoselective synthesis
of biheterocyclic skeletons tetrahydro-1H-pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole
derivatives via multicomponent self-sorting domino strategy, Tetrahedron (2015), doi: 10.1016/
j.tet.2015.06.104.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Chemoselective synthesis of biheterocyclic
skeletons tetrahydro-1H-pyrrolo[1,2-
c]imidazole and tetrahydropyrrolo[1,2-
c]thiazole derivatives via multicomponent
self-sorting domino strategy
Leave this area blank for abstract info.
a
a
a
a
a
a,b,
Qun Cai , Feng-Cheng Jia , Deng-Kui Li , Cheng Xu , Ke-Rong Ding , and An-Xin Wu *.
a
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China
Normal University, Wuhan 430079, P. R. China.
b
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Chemoselective synthesis of biheterocyclic skeletons tetrahydro-1H-pyrrolo[1,2-
c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives via multicomponent self-
sorting domino strategy
a
a
a
a
a
Qun Cai , Feng-Cheng Jia , Deng-Kui Li , Cheng Xu , Ke-Rong Ding , and An-Xin
Wu *
a,b,
a
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A highly efficient chemoselective synthesis of multifunctionalized tetrahydro-1H-pyrrolo[1,2-
c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives has been established from
arylglyoxal monohydrates, nitriles, and thioureas. A series of control experiments suggested that
this reaction proceeded through the convergent integration of two self-sorting domino
sequences. This synthetic strategy is promising for diversity-oriented synthesis of alkaloid
analogues.
Available online
Keywords:
chemoselective synthesis
tetrahydro-1H-pyrrolo[1,2-c]imidazole
tetrahydropyrrolo[1,2-c]thiazole
multicomponent self-sorting domino
alkaloid analogue
1
. Introduction
In recent years, multicomponent domino reactions (MDRs)
synthesis, which proceeded through the construction of
pyrrolidine ring from limited substrates imidazolidine-2,4-dione
or 2-thioxoimidazolidin-4-one (Scheme 2a). Functionalized
6
have been broadly utilized for the construction of diverse and
complex molecules through the sequential combination of three
or more simple substrates in a single synthetic operation. In most
cases, the reported MDRs proceeded along a linear synthetic
route (Scheme 1a). Based on our interest in novel domino
reactions, we have successfully developed a self-sorting domino
reaction, which allowed a single substrate to be simultaneously
involved in multiple different domino sequences and generated
suitable intermediates to converge on the product in a one-pot
pyrrolothiazoles are the central skeletons for numerous alkaloids
and endowed with a wide range of biological activities such as
1
7
8
9
10
hepatoprotective, antibiotic, antidiabetic, anticonvulsant, and
11
antileukemic actions. The synthetic analogues of pyrrolo[1,2-
c]thiazoles also have significance in drug discovery and
agrochemical applications . However, reports on their synthesis
2
12
13
12,14
are scarce.
The main and universal synthetic method focused
on the construction of pyrrolidine ring via 1,3-dipolar
cycloaddition of azomethine ylides generated in situ from the
3
process (Scheme 1b). In this work, a novel synthetic strategy, the
reaction of thiazolidine-4-carboxylic acid and dicarbonyl
combination of MDRs and self-sorting domino reactions is
discussed. In this multicomponent self-sorting domino reaction
strategy, it was envisioned that the single substrate A could be
divided into two parts to react with substrates B and C,
respectively, in two independent branching synthetic routes; and
the corresponding intermediates A-B and A-C could finally react
with each other to converge on the target molecule (Scheme 1c).
Tetrahydro-1H-pyrrolo[1,2-c]imidazole derivatives have
12c-12e,14
compounds to dipolarophiles
(Scheme 2b). In this work,
based on the aforementioned multicomponent self-sorting
domino reaction strategy, we reported a novel method for
chemoselective synthesis of multifunctionalized tetrahydro-1H-
pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole
derivatives from simple and readily available substrates, which
went through the simultaneous construction of pyrrolidine and
imidazolidine or thiazolidine rings (Scheme 2c).
4
5
broad applications in medicinal and agrochemical chemistry.
However, up to now, rare examples have been reported for their
—
——
*
Corresponding author. Tel./fax: +86 027 6786 7773; e-mail: chwuax@mail.ccnu.edu.cn (A. X. Wu)

2
Tetrahedron
ACCEPTED MA
1
NUSC
M
EtOH
R
eOIP
H
T
65
80
80
80
80
80
100
66
130
110
110
60
40
40
40
20
30
30
60
60
40
30
60
60
40
20
30
30
30
30
26
38
85
78
15
0
0
0
0
12
17
0
0
0
0
0
50
54
60
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
trace
trace
12
trace
trace
trace
0
10
14
11
48
66
80
68
trace
trace
trace
i-PrOH
t-BuOH
glycol
CH CN
1,4-dioxane
THF
3
DMF
DMSO
0
1
2
3
4
5
6
7
8
Scheme 1. Domino reaction strategies.
Ac O
2
HOAc
HOAc
HOAc
HOAc
EtOH
EtOH
EtOH
80
100
120
r.t.
40
1
a
60
Reaction was performed with 1a (2.0 mmol), 2a (1.2 mmol), 3a (1.0
mmol), solvent (3 mL).
b
Isolated yields.
With the optimized conditions in hand, the generality and
scope of tetrahydro-1H-pyrrolo[1,2-c]imidazoles 4 synthesis with
HOAc as the solvent was investigated. To our delight, the
reaction demonstrated wide tolerence for diverse substituents of
arylglyoxals, nitriles, and thioureas, as shown in Table 2.
Arylglyoxals bearing electron-neutral (e.g., 4-H, 4-Me), electron-
rich (e.g., 4-OMe, 3,4-OCH O), electron-deficient (e.g., 3-NO ),
Scheme 2. Protocols for the synthesis of pyrrolo[1,2-c]imidazole
and pyrrolo[1,2-c]thiazoles.
2
2
and halogenated (e.g., 4-F, 2-Cl, 4-Cl, 3,4-Cl , 3-Br, 4-Br)
2
substituents were converted to the corresponding products in
moderate to excellent yields (47−88%; 4aa−4ka). In addition, 2-
naphthyl and heteroaryl substituents (e.g., 2-thienyl) gave the
moderate yields (49−52%; 4la−4ma). Notably, methyl 2-
cyanoacetate and ethyl 2-cyanoacetate could also afford the
products 4na and 4oa in 50% and 52% yields, respectively.
Furthermore, a variety of thioureas with different substituents,
such as methyl, n-butyl, phenyl, benzyl, and phenethyl groups,
were also explored. Gratifyingly, both N-alkyl and N-aryl
thioureas were well tolerated under the reaction conditions and
afforded the expected products in satisfactory yields (53−80%;
4ab−4af). The structures of 4ab and 4ad were also
unambiguously confirmed by X-ray diffraction analysis (See
Supplementary Information (SI)).
2
. Results and Discussion
Our study commenced by optimizing the reaction conditions
in order to achieve the chemoselectivity towards skeleton 4 or 5
respectively, using phenylglyoxal monohydrate 1a, malononitrile
2
4
obtained in 38% yield (Table 1, Entry 1). Subsequently, a series
of other alcohols (ethanol, isopropanol, t-butanol, and glycol)
were screened as the solvent (Table 1, Entries 2-5). Much to our
satisfaction, EtOH was found most effective to produce 5aa with
a and thiourea 3a as model substrates. To our delight, product
aa was provided in 26% yield in refluxing methanol, with 5aa
trace amount of 4aa. Other solvents, such as CH CN, 1,4-dioxane
and THF nearly gave no reaction (Table 1, Entries 6-8), and
DMF, DMSO and Ac O gave the poor conversion (Table 1,
3
2
Entries 9-11). To our surprise, when the reaction proceeded in
HOAc at 60 °C, 4aa was obtained in 48% isolated yield without
After the successful synthesis of tetrahydro-1H-pyrrolo[1,2-
c]imidazoles 4, our attention turned to the reaction scope of
tetrahydropyrrolo[1,2-c]thiazoles 5, using EtOH to replace HOAc
as the solvent (Table 3). Much to our satisfaction, a set of diverse
substituted arylglyoxals with groups such as methyl, methoxy,
chloro and bromo groups were found compatible under the
optimal reaction conditions with good yields (78−89%; 5ba−5fa).
Meanwhile, heterocycle (e.g., 2-thiophenyl) and steric hindrance
(e.g., 1-naphthyl and 2-naphthyl) arylglyoxals were also tolerated
in this reaction to afford the desired products 5ga-5ia in 50-75%
yields. Additionally, N-alkyl and N-aryl thioureas were also
examined, which reacted smoothly with 1a and 2a to obtain the
desired products (46−75%; 5ab−5ad). The structure of 5aa was
unambiguously confirmed by X-ray diffraction analysis (See SI).
5
aa produced (Table 1, Entry 12). Then, a range of different
temperatures were examined to improve the yields, and 100 °C
was found to give the best yield of compound 4aa (Table 1,
Entries 13-15). In addition, variations to the temperature
gradient in EtOH were also tested, but better yields of 5aa were
not achieved (Table 1, Entries 16-18 vs Entry 2). Based on the
experiments described above, the optimal reaction conditions
were determined as follows: the reaction in HOAc at 100 °C
yielded compound 4aa as a sole product, while in EtOH at 80 °C
gave compound 5aa as the major product.
Table 1. Optimization of the reaction conditions for the selective
a
synthesis of 4aa and 5aa.
Table 2. Scope of arylglyoxals, nitriles and thioureas for
a
tetrahydro-1H-pyrrolo[1,2-c]imidazoles 4
b
Temp
°C)
Time
(min)
yield (%)
Entry
Solvent
(
4aa
5aa

3
ACCEPTED MANUSCRIPT
Scheme 3. Control experiments to prove the mechanism
To gain some insight into the mechanism of the tetrahydro-1H-
pyrrolo[1,2-c]imidazoles synthesis, series of control
4
a
experiments were performed as shown in Scheme 3. (E)-Ethyl 2-
cyano-4-oxo-4-phenylbut-2-enoate A was firstly synthesized
15
according to a known method, and subsequently reacted with
phenylglyoxal monohydrate 1a and thiourea 3a under the
standard conditions to afford the corresponding product 4oa in
7
6% yield (Scheme 3a). The prefabricated 5-phenyl-2-
thioxoimidazolidin-4-one B was subjected to the reaction with 1a
and ethyl 2-cyanoacetate 2o under the standard conditions to
furnish the product 4oa in 70% yield (Scheme 3b). Moreover,
treatment with A and B under the standard conditions directly
generated the highest yield of the target product 4oa (Scheme 3c).
These results clearly confirmed that A and B were the key
intermediates in this transformation.
a
Reaction was performed with 1 (2.0 mmol), 2 (1.2 mmol), 3 (1.0 mmol) in
HOAc (3 mL) at 100 °C for 20-60 min.
Table 3. Scope of arylglyoxals and thioureas for
a
tetrahydropyrrolo[1,2-c]thiazoles 5
Scheme 4. Possible mechanism for forming tetrahydro-1H-
pyrrolo[1,2-c]imidazoles 4
Scheme 5. Possible mechanism for forming tetrahydropyrrolo
[
1,2-c]thiazoles 5
16
Based on the above results and previous literature, a feasible
mechanism for the formation of tetrahydro-1H-pyrrolo[1,2-
c]imidazoles 4 was presented in Scheme 4. Initially, intermediate
A was formed by means of a Knoevenagel condensation between
phenylglyoxal monohydrate 1a and malononitrile 2a.
Simultaneously, thiohydantoin intermediate B was formed via
a
Reaction was performed with 1 (2.0 mmol), 2a (1.2 mmol), 3 (1.0 mmol) in
16b-16c
condensation of 1a and thiourea 3a.
Then, the Michael
EtOH (3 mL) at 80 °C for 20-60 min.
addition of intermediate B to intermediate A gave intermediate C,
16e
which subsequently underwent intramolecular cyclization to
form intermediate D. Finally, D tautomerized to the product 4aa.
A possible and similar mechanism was also proposed for the
synthesis of tetrahydropyrrolo[1,2-c]thiazole derivatives 5 in
16,17
accordance with the relative literature,
The phenylglyoxal monohydrate 1a reacted with malononitrile
a and thiourea 3a, respectively, to afford intermediate A and 2-
as shown in Scheme 5.
2

4
Tetrahedron
aminothiazol-5(4H)-one B’, which further r
A
ea
C
cte
C
d
E
w
P
it
T
h
E
ea
D
ch MAch
N
ro
U
ma
S
to
C
gr
R
ap
I
hy on silica gel (eluent: petroleum ether/EtOAc) to
P
T
other to form intermediate C’. Subsequently, C’ underwent
afford the product 4aa as a yellow solid.
intramolecular cyclization and tautomerization to yield product
4
.2.2 General procedure for synthesis of 5 (5aa as an
5
aa. These reaction mechanisms were consistent with the
example)
designed multicomponent self-sorting domino reactions strategy.
A mixture of phenylglyoxal monohydrate 1a (2.0 mmol),
It can be postulated that the chemoselectivity towards
skeletons 4 and 5 depends on the relative acidity of the solvents.
We thought the S-lone pair electron on the sulfur atom of the
thiourea 3a would combine with the acid proton to form 3a’ and
the affinity of sulfur atom would be reduced with HOAc as the
solvent, so we proposed the condensation product of 1a and 3a
would be B (Scheme 4). This orientation led to the product 4aa.
Acid solvent favored skeleton 4, while neutral solvent led to
skeleton 5 as the major product because the protonation ability of
sulfur atom of the thiourea in neutral solvent (EtOH) was worse
than that in acid solvent (HOAc).
malononitrile 2a (1.2 mmol), thiourea 3a (1.0 mmol) in EtOH (3
mL) was stirred at 80 °C for 40 min till almost completed
conversion of the substrates by TLC analysis, then extracted with
EtOAc three times (3×50 mL). The extract was dried over
anhydrous Na SO and concentrated in vacuo. The crude product
2
4
was purified by column chromatography on silica gel (eluent:
petroleum ether/EtOAc) to afford the product 5aa as a yellow
solid.
4.3. Characterization data
4
.3.1
5-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-
3
. Conclusion
tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4aa)
1
Yield 80%; yellow solid. mp >300 °C. H NMR (DMSO-d , 400
In conclusion, a convenient and efficient multicomponent self-
sorting domino reaction has been established for the
chemoselective synthesis of tetrahydro-1H-pyrrolo[1,2-
6
MHz): δ (ppm) 12.87 (s, 1H), 8.15 (d, J = 8.0 Hz, 2H), 8.00 (s,
2
3
1
1
3
1
H), 7.74 (t, J = 7.0 Hz, 1H), 7.66-7.56 (m, 4H), 7.55-7.42 (m,
13
H), 5.08 (s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm)
6
c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives
through solvent-switching. Initial studies of the mechanism
suggest that this reaction proceeded through the convergent
integration of two self-sorting domino sequences. This practical
synthetic strategy also demonstrated potential for the
construction of complex heterocyclic compounds. Further studies
of the application of this multicomponent self-sorting domino
reaction are currently underway in our laboratory and will be
reported in due course.
96.0, 181.0, 172.9, 154.7, 136.1, 134.7, 133.9, 129.5, 129.3,
29.1, 128.9, 125.0, 117.1, 76.4, 59.7, 55.1. IR (KBr): 3438,
300, 3141, 2923, 2361, 2195, 1770, 1669, 1634, 1583, 1465,
–1
448, 1239, 1163, 1105, 738, 694, 544 cm . HRMS (ESI): m/z
+
[
M+H] calcd for C H N O S: 375.0910; found: 375.0908.
20 15 4 2
4
.3.2 5-amino-7-(4-methylbenzoyl)-1-oxo-3-thioxo-7a-(p-tolyl)-
2
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
(4ba)
4
4
. Experimental
1
Yield 72%; yellow solid. mp 103-104 °C. H NMR (DMSO-d ,
4
6
00 MHz): δ (ppm) 12.81 (s, 1H), 8.02 (d, J = 7.6 Hz, 2H), 7.95
s, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.31
d, J = 7.6 Hz, 2H), 4.97 (s, 1H), 2.40 (s, 3H), 2.33 (s, 3H).
.1. General
(
(
1
3
All substrates and reagents were commercially available and
C
used without further purification. TLC analysis was performed
using pre-coated glass plates. Column chromatography was
performed using silica gel (200–300 mesh). IR spectra were
recorded on a Perkin-Elmer PE-983 infrared spectrometer as KBr
NMR (DMSO-d , 100 MHz): δ (ppm) 195.6, 181.0, 173.0, 154.7,
6
1
7
2
45.4, 138.9, 133.2, 131.6, 129.6, 129.5, 129.1, 124.8, 117.1,
6.3, 59.9, 55.0, 21.3, 20.6. IR (KBr): 3403, 2957, 2924, 2853,
189, 1765, 1670, 1644, 1460, 1361, 1251, 1021, 851, 816, 599
–1 1
–1
+
pellets with absorption in cm . H spectra were recorded in
CDCl or DMSO-d on 400/600 MHz NMR spectrometers and
cm . HRMS (ESI): m/z [M+H] calcd for C H N O S:
22
19
4
2
3
6
403.1223; found: 403.1231.
resonances (δ) are given in parts per million relative to
tetramethylsilane. Data are reported as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet),
4
.3.3 5-amino-7-(4-methoxybenzoyl)-7a-(4-methoxyphenyl)-1-
oxo-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
carbonitrile (4ca)
Yield 65%; yellow solid. mp 128-129 °C. H NMR (DMSO-d ,
400 MHz): δ (ppm) 12.77 (s, 1H), 8.11 (d, J = 8.8 Hz, 2H), 7.92
(s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.08 (t, J = 8.8 Hz, 4H), 4.94 (s,
13
coupling constants (Hz) and integration. C spectra were
recorded in CDCl3 or DMSO-d6 on 100/150 MHz NMR
spectrometers and resonances (δ) are given in ppm. HRMS were
obtained on a Bruker Apex-Ultra 7.0T FTMS equipped with an
electrospray source (ESI or APCI). The X-ray crystal structure
determination of 4ab, 4ad and 5aa were obtained on a Bruker
SMART APEX CCD system. Melting points were determined
using XT-4 apparatus and not corrected.
1
6
13
1H), 3.88 (s, 3H), 3.79 (s, 3H). C NMR (DMSO-d , 100 MHz):
6
δ (ppm) 194.6, 181.6, 164.4, 160.0, 132.1, 127.9, 126.9, 126.4,
117.3, 114.5, 114.3, 76.2, 60.1, 55.8, 55.4, 55.0. IR (KBr): 3408,
2959, 2925, 2853, 2187, 1764, 1644, 1598, 1257, 1024, 803, 541
cm . HRMS (ESI): m/z [M+H] calcd for C H N O S:
4
–1
+
22
19
4
4
4
4
.2. General procedure for synthesis of 4 and 5
35.1122; found: 435.1124.
.2.1 General procedure for synthesis of 4 (4aa as an
example)
4.3.4
5-amino-7a-(benzo[d][1,3]dioxol-5-yl)-7-
(
benzo[d][1,3]dioxole-5-carbonyl)-1-oxo-3-thioxo-2,3,7,7a-
A mixture of phenylglyoxal monohydrate 1a (2.0 mmol),
tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4da)
Yield 55%; white solid. mp >300 °C. H NMR (DMSO-d , 400
MHz): δ (ppm) 12.77 (s, 1H), 7.92 (s, 1H), 7.80 (d, J = 8.0 Hz,
1
6
Hz, 2H), 4.95 (s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm)
1
1
malononitrile 2a (1.2 mmol), thiourea 3a (1.0 mmol) in HOAc (3
mL) was stirred at 100 °C for 20 min till almost completed
conversion of the substrates by TLC analysis, then extracted with
EtOAc three times (3×50 mL). The extract was washed with 10%
1
6
H), 7.59 (s, 1H), 7.14-7.07 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H),
.95 (d, J = 8.4 Hz, 1H), 6.19 (d, J = 4.0 Hz, 2H), 6.09 (d, J = 7.2
NaHCO3 solution (w/w), dried over anhydrous Na SO4 and
13
2
6
concentrated in vacuo. The crude product was purified by column
94.2, 181.0, 173.1, 154.5, 152.9, 148.2, 148.2, 148.0, 129.6,
28.6, 126.9, 118.3, 117.3, 108.5, 108.3, 106.1, 102.5, 101.8,

5
7
1
6.3, 60.1, 54.9. IR (KBr): 3408, 3131, 2194, 1766, 1664, 1644,
132.2, 132.0, 131.8, 131.3, 131.2, 129.4, 127.7, 125.5, 117.0,
ACCEPTED MANUSCRIPT
–1
442, 1250, 1110, 1039, 820, 538 cm . HRMS (ESI): m/z
75.3, 58.7, 55.1. IR (KBr): 3385, 3325, 3191, 2188, 1766, 1652,
1581, 1463, 1359, 1243, 1031, 703, 574 cm . HRMS (ESI): m/z
+
–1
[
M+H] calcd for C H N O S: 463.0707; found: 463.0703.
22
15
4
6
+
[
M+H] calcd for C H Cl N O S: 510.9351; found: 510.9350.
20
11
4
4
2
4
.3.5 5-amino-7-(3-nitrobenzoyl)-7a-(3-nitrophenyl)-1-oxo-3-
4
3
.3.10 5-amino-7-(3-bromobenzoyl)-7a-(3-bromophenyl)-1-oxo-
-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
carbonitrile (4ea)
Yield 47%; yellow solid. mp >300 °C. H NMR (DMSO-d , 400
MHz): δ (ppm) 13.12 (s, 1H), 8.85 (s, 1H), 8.57 (t, J = 8.4 Hz,
1
carbonitrile (4ja)
Yield 85%; white solid. mp 284-285 °C. H NMR (DMSO-d ,
6
1
6
6
00 MHz): δ (ppm) 12.95 (s, 1H), 8.32 (s, 1H), 8.12 (d, J = 7.8
Hz, 1H), 8.07 (s, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.76 (s, 1H), 7.72
d, J = 7.8 Hz, 1H), 7.62-7.53 (m, 2H), 7.50 (t, J = 7.8 Hz, 1H),
2
H), 8.44 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.20 (s, 2H), 8.05 (d,
13
J = 8.0 Hz, 1H), 7.94-7.83 (m, 2H), 5.38 (s, 1H). C NMR
DMSO-d , 100 MHz): δ (ppm) 193.7, 181.2, 172.2, 154.7, 148.2,
(
(
13
6
5
1
.20 (s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm) 194.3,
6
1
1
2
48.1, 137.8, 135.8, 134.9, 131.9, 131.9, 130.8, 128.9, 124.4,
24.1, 120.4, 117.0, 75.5, 58.3, 55.5. IR (KBr): 3457, 3318, 3172,
80.9, 172.3, 154.6, 138.3, 137.3, 135.7, 132.3, 132.2, 131.1,
–1
131.0, 128.5, 128.0, 124.2, 122.4, 122.3, 117.0, 75.6, 59.0, 55.0.
IR (KBr): 3396, 3143, 2200, 1751, 1651, 1585, 1472, 1441, 1368,
1
194, 1741, 1686, 1529, 1489, 1346, 1184, 728, 678 cm .
+
HRMS (APCI): m/z [M+H] calcd for C H N O S: 465.0612;
found: 465.0614.
–1
+
20
13
6
6
242, 1158, 680, 630 cm . HRMS (APCI): m/z [M+H] calcd
for C H Br N O S: 530.9121; found: 530.9118.
20
13
2
4
2
4
.3.6 5-amino-7-(4-fluorobenzoyl)-7a-(4-fluorophenyl)-1-oxo-3-
4
3
.3.11 5-amino-7-(4-bromobenzoyl)-7a-(4-bromophenyl)-1-oxo-
-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
carbonitrile (4fa)
Yield 88%; yellow solid. mp >300 °C. H NMR (DMSO-d , 600
MHz): δ (ppm) 12.89 (s, 1H), 8.28-8.18 (m, 2H), 8.00 (s, 2H),
7
2
1
1
5
1
1
carbonitrile (4ka)
Yield 85%; yellow solid. mp >300 °C. H NMR (DMSO-d , 600
MHz): δ (ppm) 13.00 (s, 1H), 8.13 (d, J = 7.8 Hz, 2H), 8.10 (s,
1H), 7.87 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.58 (d, J
6
1
6
.65-7.56 (m, 2H), 7.43 (t, J = 9.0 Hz, 2H), 7.38 (t, J = 9.0 Hz,
13
H), 5.08 (s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm)
13
6
=
7.8 Hz, 2H), 5.14 (s, 1H); C NMR (DMSO-d , 100 MHz): δ
6
94.5, 181.1, 172.9, 167.3, 164.8, 163.9, 161.4, 154.7, 132.9,
32.8, 132.1, 130.7, 127.5, 127.4, 117.1, 116.2, 116.0, 75.9, 59.4,
5.1. IR (KBr): 3382, 3305, 3254, 3195, 2195, 1765, 1647, 1592,
(
1
ppm) 195.0, 181.1, 172.5, 154.7, 135.4, 132.9, 132.1, 131.6,
29.3, 127.4, 123.0, 117.1, 75.9, 59.2, 55.0. IR (KBr): 3427,
2962, 2924, 2360, 2191, 1767, 1647, 1584, 1262, 1097, 1024,
–1
458, 1361, 1237, 1157, 1091, 838, 699, 543cm . HRMS (ESI):
–1
+
+
802, 683 cm . HRMS (ESI): m/z [M+H] calcd for
C H Br N O S: 530.9121; found: 530.9117.
m/z [M+H] calcd for C H F N O S: 411.0722; found:
4
20
13
2
4
2
20
13
2
4
2
11.0726.
4
.3.12 7-(2-naphthoyl)-5-amino-7a-(naphthalen-2-yl)-1-oxo-3-
4
.3.7 5-amino-7-(2-chlorobenzoyl)-7a-(2-chlorophenyl)-1-oxo-3-
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
carbonitrile (4la)
Yield 52%; yellow solid. mp >300 °C. H NMR (DMSO-d
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
carbonitrile (4ga)
Yield 57%; yellow solid. mp >300 °C. H NMR (DMSO-d , 600
MHz): δ (ppm) 12.94 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.02 (s,
2
=
1
1
6
, 600
6
MHz): δ (ppm) 12.99 (s, 1H), 9.05 (s, 1H), 8.16-8.13 (m, 2H),
.12 (s, 1H), 8.09 (s, 3H), 8.04 (d, J = 7.2 Hz, 2H), 8.02-7.95 (m,
2H), 7.79 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.65 (t, J =
8
H), 7.66 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.58 (d, J
13
8.4 Hz, 2H), 5.09 (s, 1H). C NMR (DMSO-d , 100 MHz): δ
13
6
7
.8 Hz, 1H), 7.63-7.58 (m, 2H), 5.43 (s, 1H). C NMR (DMSO-
d6, 100 MHz): δ (ppm) 195.8, 181.3, 173.1, 154.9, 135.7, 133.6,
33.1, 132.5, 132.2, 131.2, 130.0, 129.6, 129.1, 128.8, 128.4,
(ppm) 194.7, 181.0, 172.5, 154.6, 139.8, 138.6, 135.3, 134.9,
1
5
1
34.2, 132.7, 132.6, 131.4, 129.4, 129.1, 127.1, 117.0, 75.8, 59.2,
5.0. IR (KBr): 3320, 3132, 2182, 1760, 1672, 1646, 1588, 1371,
1
–1
127.9, 127.7, 127.3, 127.1, 124.2, 123.9, 123.5, 122.9 117.4, 76.6,
59.9, 56.1, 55.3. IR (KBr): 3405, 3189, 2197, 1744, 1647, 1468,
1
260, 1094, 1011, 859, 762, 538 cm . HRMS (APCI): m/z
+
[
M+H] calcd for C H Cl N O S: 443.0131; found: 443.0128.
–1
+
20
13
2
4
2
363, 1245, 737, 701, 538 cm . HRMS (ESI): m/z [M+H] calcd
for C H N O S: 475.1223; found: 475.1228.
28
19
4
2
4
.3.8 5-amino-7-(4-chlorobenzoyl)-7a-(4-chlorophenyl)-1-oxo-3-
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-
4
.3.13 5-amino-1-oxo-7a-(thiophen-2-yl)-7-(thiophene-2-
carbonitrile (4ha)
Yield 82%; yellow solid. mp >300 °C. H NMR (DMSO-d , 400
1
carbonyl)-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-
c]imidazole-6-carbonitrile (4ma)
Yield 49%; yellow solid. mp 173-174 °C. H NMR (DMSO-d ,
400 MHz): δ (ppm) 12.98 (s, 1H), 8.32 (d, J = 4.0 Hz, 1H), 8.22
6
MHz): δ (ppm) 12.92 (s, 1H), 8.15 (d, J = 8.8 Hz, 2H), 8.00 (s,
1
6
2
H), 7.66 (d, J = 8.4 Hz, 2H), 7.64-7.57 (m, 4H), 5.09 (s, 1H).
1
3
C NMR (DMSO-d , 100 MHz): δ (ppm) 194.7, 181.1, 172.6,
6
(
(
(
d, J = 4.8 Hz, 1H), 7.95 (s, 2H), 7.67 (d, J = 5.2 Hz, 1H), 7.39
d, J = 3.6 Hz, 1H), 7.37-7.32 (m, 1H), 7.18-7.12 (m, 1H), 4.99
s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm) 189.2, 181.2,
1
7
2
8
54.7, 139.9, 134.9, 134.3, 132.6, 131.5, 129.1, 127.1, 117.1,
5.8, 59.2, 55.1. IR (KBr): 3380, 3305, 3252, 3192, 2968, 2361,
195, 1764, 1645, 1586, 1490, 1458, 1362, 1250, 1092, 1009,
13
6
–1
+
172.1, 154.7, 141.1, 138.9, 138.4, 137.1, 129.5, 127.9, 127.3,
1
1
HRMS (APCI): m/z [M+H] calcd for C H N O S : 387.0039;
found: 387.0038.
53, 696, 547 cm . HRMS (ESI): m/z [M+H] calcd for
26.1, 117.2, 75.1, 60.3, 55.6. IR (KBr): 3369, 2922, 2195, 1763,
C H Cl N O S: 443.0131; found: 443.0138.
–1
20
13
2
4
2
643, 1465, 1439, 1408, 1357, 1250, 1025, 734, 712, 531 cm .
+
16
11
4
2 3
4
1
6
.3.9 5-amino-7-(3,4-dichlorobenzoyl)-7a-(3,4-dichlorophenyl)-
-oxo-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-
-carbonitrile (4ia)
1
4.3.14 methyl 5-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carboxylate
4na)
Yield 50%; yellow solid. mp >300 °C. H NMR (DMSO-d
MHz): δ (ppm) 12.87 (s, 1H), 8.13 (d, J = 7.6 Hz, 2H), 7.73 (t, J
Yield 60%; yellow solid. mp 274-275 °C. H NMR (DMSO-d ,
6
2
(
6
00 MHz): δ (ppm) 13.08 (s, 1H), 8.46 (s, 1H), 8.13 (d, J = 8.4
Hz, 3H), 7.94 (d, J = 8.4 Hz, 1H), 7.91-7.88 (m, 2H), 7.58 (d, J =
1
13
, 400
6
8
.4 Hz, 1H), 5.28 (s, 1H). C NMR (DMSO-d , 100 MHz): δ
6
(ppm) 193.5, 181.1, 172.2, 154.6, 137.8, 136.6, 134.0, 132.5,

6
Tetrahedron
1
=
7.6 Hz, 1H), 7.68 (s, 1H), 7.63-7.54 (m, 5H), 7.53-7.46 (m,
Yield 80%; yellow solid. mp 240-241 °C. H NMR (CDCl , 600
ACCEPTED MANUSCRIPT
3
13
3
H), 4.94 (s, 1H), 3.33 (s, 3H). C NMR (DMSO-d , 100 MHz):
MHz): δ (ppm) 7.96 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H),
6
δ (ppm) 200.7, 181.8, 173.3, 165.1, 153.6, 136.9, 135.8, 134.3,
29.3, 129.2, 128.8, 127.6, 124.7, 82.8, 77.3, 54.4, 50.1. IR
KBr): 3413, 3296, 3109, 1761, 1679, 1606, 1523, 1443, 1380,
7.57-7.48 (m, 4H), 7.48-7.42 (m, 3H), 7.33 (d, J = 7.2 Hz, 2H),
7.28 (t, J = 7.2 Hz, 2H), 7.26-7.23 (m, 1H), 6.46 (s, 2H), 5.15-
1
(
13
4.95 (m, 2H), 4.76 (s, 1H). C NMR (CDCl , 100 MHz): δ (ppm)
3
–1
+
1
312, 1109, 962, 720, 695 cm . HRMS (ESI): m/z [M+H] calcd
194.6, 180.4, 171.6, 155.5, 135.8, 134.8, 134.4, 133.8, 129.6,
129.3, 129.2, 128.9, 128.4, 128.1, 127.7, 124.8, 116.7, 75.2, 61.6,
for C H N O S: 408.1013; found: 408.1014.
21
18
3
4
5
7.3, 45.1. IR (KBr): 3356, 3241, 3181, 2194, 1754, 1675, 1650,
–1
4
.3.15 ethyl 5-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-
1588, 1396, 1251, 940, 697, 527 cm . HRMS (APCI): m/z
[M+H] calcd for C H N O S: 465.1380; found: 465.1381
+
2
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carboxylate
27
21
4
2
(
4oa)
1
Yield 52%; yellow solid. mp 135-136 °C. H NMR (DMSO-d ,
4.3.20 5-amino-7-benzoyl-1-oxo-2-phenethyl-7a-phenyl-3-thioxo-
2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
(4af)
6
4
00 MHz): δ (ppm) 12.86 (s, 1H), 8.12 (d, J = 7.6 Hz, 2H), 7.72
(t, J = 7.2 Hz, 1H), 7.63 (s, 2H), 7.60-7.55 (m, 4H), 7.51 (t, J =
7
0
2
1
2
.6 Hz, 2H), 7.47-7.43 (m, 1H), 4.94 (s, 1H), 3.84-3.68 (m, 2H),
1
13
Yield 75%; yellow solid. mp 246-247 °C. H NMR (CDCl
3
, 600
.76 (t, J = 6.8 Hz, 3H). C NMR (DMSO-d , 100 MHz): δ (ppm)
6
MHz): δ (ppm) 7.97 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H),
.57-7.48 (m, 4H), 7.47-7.38 (m, 3H), 7.24-7.05 (m, 5H), 6.52 (s,
H), 4.70 (s, 1H), 4.05 (t, J = 7.8 Hz, 2H), 3.11-2.98 (m, 2H).
01.0, 181.9, 173.3, 164.9, 153.9, 136.9, 136.0, 134.1, 129.3,
29.1, 128.7, 124.6, 82.9, 77.3, 58.6, 54.2. IR (KBr): 3380, 3276,
975, 1744, 1664, 1530, 1312, 1258, 1203, 1103, 773, 690, 530
7
2
13
C
–1
+
NMR (CDCl
3
, 100 MHz): δ (ppm) 194.9, 180.9, 171.4, 155.7,
cm . HRMS (ESI): m/z [M+H] calcd for C H N O S:
4
22
20
3
4
1
1
3
7
37.4, 135.8, 134.8, 133.9, 129.5, 129.3, 129.2, 129.0, 128.8,
28.4, 126.5, 124.8, 75.1, 61.8, 57.6, 43.0, 32.6. IR (KBr): 3392,
279, 3061, 2190, 1729, 1671, 1638, 1586, 1446, 1372, 1249,
22.1169; found: 422.1171.
4
2
.3.16 5-amino-7-benzoyl-2-methyl-1-oxo-7a-phenyl-3-thioxo-
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
–1
+
05, 574 cm . HRMS (APCI): m/z [M+H] calcd for
C H N O S: 479.1536; found: 479.1536.
28
23
4
2
(4ab)
1
Yield 54%; yellow solid. mp 244-245 °C. H NMR (DMSO-d ,
4
J = 7.2 Hz, 1H), 7.63-7.56 (m, 4H), 7.55-7.48 (m, 3H), 5.19 (s,
1
1
1
3
6
4
.3.21
5-amino-7-benzoyl-3-imino-1-oxo-7a-phenyl-1,3,7,7a-
tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile (5aa)
00 MHz): δ (ppm) 8.14 (d, J = 8.0 Hz, 2H), 8.10 (s, 1H), 7.75 (t,
13
H), 3.21 (s, 3H). C NMR (DMSO-d , 100 MHz): δ (ppm)
Yield 85%; yellow solid. mp 190-192 °C. 1H NMR (DMSO-d6,
600 MHz): δ (ppm) 10.10 (s, 1H), 8.15 (d, J = 7.8 Hz, 2H), 8.01
(s, 1H), 7.74 (t, J = 7.2 Hz, 1H), 7.65 (d, J = 7.2 Hz, 2H), 7.59 (t,
J = 7.8 Hz, 2H), 7.55 (t, J = 7.8 Hz, 2H), 7.53-7.49 (m, 1H), 5.08
(s, 1H). C NMR (DMSO-d , 150 MHz): δ (ppm) 196.2, 195.4,
6
95.9, 181.0, 171.8, 154.8, 135.7, 134.8, 133.7, 129.7, 129.5,
29.1, 129.0, 125.3, 117.1, 75.2, 59.4, 55.9, 28.2. IR (KBr): 3361,
–1
188, 2194, 1753, 1648, 1579, 1392, 1305, 1041, 701, 574 cm .
+
13
HRMS (ESI): m/z [M+H] calcd for C H N O S: 389.1067;
found: 389.1070.
21
17
4
2
6
155.8, 155.7, 151.6, 136.8, 134.7, 134.1, 129.7, 129.6, 129.3,
1
29.0, 125.3, 118.0, 82.6, 56.1. IR (KBr): 3325, 3168, 2188,
–1
4
2
.3.17 5-amino-7-benzoyl-2-butyl-1-oxo-7a-phenyl-3-thioxo-
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
1748, 1667, 1645, 1447, 1347, 1104, 915, 704 cm . HRMS
(ESI): m/z [M+H] calcd for C H N O S: 375.09102; found:
375.09054.
+
20
15
4
2
(4ac)
1
Yield 53%; white solid. mp 227-228 °C. H NMR (CDCl , 400
3
MHz): δ (ppm) 7.97 (d, J = 7.2 Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H),
4.3.22 5-amino-3-imino-7-(4-methylbenzoyl)-1-oxo-7a-(p-tolyl)-
1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ba)
7
3
.56-7.48 (m, 4H), 7.47-7.42 (m, 3H), 6.62 (s, 2H), 4.71 (s, 1H),
.86-3.75 (m, 2H), 1.78-1.68 (m, 2H), 1.40-1.30 (m, 2H), 0.93 (t,
1
13
Yield 89%; white solid. mp 188-190 °C. H NMR (DMSO-d ,
6
J = 7.6 Hz, 3H). C NMR (CDCl , 100 MHz): δ (ppm) 194.8,
3
6
00 MHz): δ (ppm) 10.05 (s, 1H), 8.02 (d, J = 7.8 Hz, 2H), 7.97
1
1
3
1
81.1, 171.6, 155.7, 135.9, 134.7, 133.9, 129.5, 129.3, 129.2,
29.0, 124.7, 75.0, 61.7, 57.4, 41.9, 28.7, 19.9, 13.6. IR (KBr):
376, 3306, 3244, 3188, 2956, 2196, 1757, 1675, 1652, 1589,
(
(
s, 1H), 7.51 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.8 Hz, 2H), 7.34
1
3
d, J = 7.8 Hz, 2H), 4.98 (s, 1H), 2.41 (s, 3H), 2.34 (s, 3H).
C
–1
+
NMR (DMSO-d , 150 MHz): δ (ppm) 195.8, 195.5, 155.8, 155.7,
6
389, 1055, 696, 572 cm . HRMS (APCI): m/z [M+H] calcd
1
1
1
51.8, 145.4, 139.3, 134.0, 131.7, 129.8, 129.6, 129.6, 125.1,
18.0, 82.5, 56.1, 21.4, 20.7. IR (KBr): 3318, 3176, 2186, 1747,
for C H N O S: 431.1536; found: 431.1540.
24
23
4
2
–1
644, 1570, 1447, 1350, 1109, 915, 753 cm . HRMS (ESI): m/z
4
.3.18 5-amino-7-benzoyl-1-oxo-2,7a-diphenyl-3-thioxo-
+
[
M+H] calcd for C H N O S: 403.12232; found: 403.12155.
22 19 4 2
2
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
(
4ad)
1
4.3.23
5-amino-3-imino-7-(4-methoxybenzoyl)-7a-(4-
Yield 70%; white solid. mp >300 °C. H NMR (DMSO-d , 400
MHz): δ (ppm) 8.22 (d, J = 8.0 Hz, 2H), 8.17 (s, 2H), 7.77 (t, J =
6
methoxyphenyl)-1-oxo-1,3,7,7a-tetrahydropyrrolo[1,2-
c]thiazole-6-carbonitrile (5ca)
7
7
5
1
1
.2 Hz, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.6 Hz, 2H),
.60-7.55 (m, 4H), 7.54-7.50 (m, 2H), 7.36 (d, J = 7.6 Hz, 2H),
.31 (s, 1H). C NMR (DMSO-d , 100 MHz): δ (ppm) 196.2,
80.6, 171.3, 154.8, 135.5, 134.8, 133.7, 132.7, 129.7, 129.6,
29.5, 129.4, 129.2, 128.92, 128.3, 125.3, 117.0, 75.6, 59.7, 56.1.
1
Yield 78%; yellow solid. mp 176-178 °C. H NMR (DMSO-d ,
600 MHz): δ (ppm) 10.01 (s, 1H), 8.10 (d, J = 8.4 Hz, 2H), 7.92
6
13
6
(s, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.12-7.06 (m, 4H), 4.94 (s, 1H),
13
3
.88 (s, 3H), 3.80 (s, 3H). C NMR (DMSO-d , 150 MHz): δ
6
IR (KBr): 3336, 3241, 3181, 2190, 1770, 1649, 1582, 1447, 1374,
1
C H N O S: 451.1223; found: 451.1224.
(
1
ppm) 195.5, 194.9, 164.2, 160.2, 155.8, 151.7, 132.0, 128.5,
27.0, 126.5, 118.1, 114.6, 114.2, 82.3, 56.5, 55.9, 55.7, 55.4. IR
(KBr): 3415, 3308, 2187, 1748, 1641, 1599, 1510, 1443, 1343,
–1
+
286, 703, 563cm . HRMS (APCI): m/z [M+H] calcd for
26
19
4
2
–1
+
1
255, 1105, 915, 836 cm . HRMS (ESI): m/z [M+H] calcd for
4
2
.3.19 5-amino-7-benzoyl-2-benzyl-1-oxo-7a-phenyl-3-thioxo-
,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile
C H N O S: 435.11215; found: 435.11139.
22
19
4
4
(4ae)

7
4
.3.24
5-amino-3-imino-7-(3-methoxybenzoyl)-7a-(3-
131.4, 130.6, 130.2, 129.6, 128.9, 128.8, 128.5, 126.9, 126.8,
ACCEPTED MANUSCRIPT
methoxyphenyl)-1-oxo-1,3,7,7a-tetrahydropyrrolo[1,2-
c]thiazole-6-carbonitrile (5da)
126.3, 125.6, 125.0, 123.6, 117.6, 83.8, 79.2(CCHCl3), 56.8, 56.8.
IR (KBr): 3452, 3258, 2188, 1739, 1637, 1568, 1440, 1350, 1270,
1120, 911, 876, 737 cm . HRMS (ESI): m/z [M+H] calcd for
C H N O S: 475.12232; found: 475.12191.
–1
+
1
Yield 85%; yellow solid. mp 131-133 °C. H NMR (DMSO-d ,
6
6
28
19
4
2
00 MHz): δ (ppm) 10.06 (s, 1H), 8.00 (s, 2H), 7.75 (d, J = 5.4
Hz, 1H), 7.62 (s, 1H), 7.53-7.42 (m, 2H), 7.33-7.27 (m, 1H),
4
.3.29 7-(2-naphthoyl)-5-amino-3-imino-7a-(naphthalen-2-yl)-1-
oxo-1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile
5ia)
7
3
1
1
5
1
.22-7.12 (m, 2H), 7.09 (d, J = 8.4 Hz, 1H), 5.10 (s, 1H), 3.85 (s,
13
H), 3.81 (s, 3H). C NMR (DMSO-d , 150 MHz): δ (ppm)
6
(
95.5, 195.1, 159.7, 159.5, 155.7, 151.4, 138.3, 135.3, 130.3,
30.0, 122.2, 121.2, 118.1, 117.1, 114.7, 113.5, 111.6, 82.5, 56.1,
6.1, 55.5, 55.3. IR (KBr): 3391, 3274, 3077, 2833, 2186, 1752,
1
Yield 75%; yellow solid. mp 210-212 °C. H NMR (DMSO-d ,
600 MHz): δ (ppm) 10.19 (s, 1H), 9.03 (s, 1H), 8.22 (s, 1H),
8.17-8.05 (m, 7H), 8.05-8.00 (m, 2H), 7.82 (d, J = 9.0 Hz, 1H),
7.72 (t, J = 7.8 Hz, 1H), 7.68-7.59 (m, 3H), 5.43 (s, 1H).
6
–1
644, 1487, 1447, 1346, 1264, 1116, 928, 741, 549 cm . HRMS
+
13
(
ESI): m/z [M+H] calcd for C H N O S: 435.11215; found:
C
22
19
4
4
4
35.11161.
NMR (DMSO-d , 150 MHz): δ (ppm) 196.0, 195.4, 156.0, 151.6,
6
1
35.6, 134.2, 133.2, 132.5, 132.1, 131.3, 130.0, 129.5, 129.2,
4
.3.25
5-amino-7-(4-chlorobenzoyl)-7a-(4-chlorophenyl)-3-
128.7, 128.5, 127.8, 127.6, 127.4, 127.2, 127.1, 124.5, 123.9,
122.8, 118.0, 82.8, 56.4, 56.2. IR (KBr): 3380, 3279, 2176, 1741,
imino-1-oxo-1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-
carbonitrile (5ea)
–1
1637, 1449, 1353, 1105, 917, 751 cm . HRMS (ESI): m/z
+
1
[M+H] calcd for C28H N O S: 475.12232; found: 475.12188.
19 4 2
Yield 80%; yellow solid. mp 179-180 °C. H NMR (DMSO-d ,
6
6
00 MHz): δ (ppm) 10.14 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.01
13
4.3.30
5-amino-7-benzoyl-3-(methylimino)-1-oxo-7a-phenyl-
(s, 2H), 7.76-7.53 (m, 6H), 5.09 (s, 1H). C NMR (DMSO-d6,
1
,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ab)
1
1
50 MHz): δ (ppm) 195.1, 194.8, 155.7, 151.2, 139.8, 135.6,
34.5, 132.7, 131.5, 129.2, 129.1, 127.2, 117.8, 82.0, 55.9, 55.6.
1
Yield 46%; yellow solid. mp 192-194 °C. H NMR (CDCl , 600
3
IR (KBr): 3335, 3174, 2189, 1739, 1648, 1445, 1347, 1095, 978,
MHz): δ (ppm) 7.99 (d, J = 7.8 Hz, 2H), 7.65 (t, J = 7.8 Hz, 1H),
7.58 (d, J = 6.0 Hz, 2H), 7.52 (t, J = 7.8 Hz, 2H), 7.48-7.42 (m,
–1
+
9
4
17 cm . HRMS (ESI): m/z [M+H] calcd for C H C N O S:
20 13 l2 4 2
13
43.01308; found: 443.01286.
.3.26 5-amino-7-(4-bromobenzoyl)-7a-(4-bromophenyl)-3-
3H), 6.59 (s, 2H), 4.70 (s, 1H), 3.22 (s, 3H). C NMR (CDCl3,
50 MHz): δ (ppm) 195.8, 193.4, 156.7, 148.7, 136.8, 134.6,
1
4
134.2, 129.6, 129.3, 129.2, 129.0, 125.0, 117.8, 81.9, 58.3, 57.6,
41.0. IR (KBr): 3359, 2975, 2895, 1925, 1661, 1446, 1381, 1089,
imino-1-oxo-1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-
carbonitrile (5fa)
–1
+
1049, 881, 665 cm . HRMS (ESI): m/z [M+H] calcd for
1
C
21
H
17
N
4
O
2
S: 389.1067; found: 389.1073.
Yield 82%; yellow solid. mp 188-189 °C. H NMR (DMSO-d ,
6
6
00 MHz): δ (ppm) 10.14 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H), 8.01
4
.3.31
5-amino-7-benzoyl-3-(butylimino)-1-oxo-7a-phenyl-
(s, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H), 7.57 (d,
13
1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ac)
J = 8.4 Hz, 2H), 5.08 (s, 1H). C NMR (DMSO-d , 150 MHz): δ
6
1
(ppm) 195.0, 155.7, 151.1, 136.0, 133.0, 132.1, 132.0, 131.5,
Yield 75%; red solid. mp 170-172 °C. H NMR (CDCl , 400
3
1
2
29.1, 127.5, 123.1, 117.8, 82.0, 55.8, 55.6. IR (KBr): 3382,
975, 2896, 1923, 1757, 1654, 1452, 1382, 1088, 1049, 881, 667
MHz): δ (ppm) 7.98 (d, J = 8.0 Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H),
7.58-7.55 (m, 2H), 7.51 (t, J = 8.0 Hz, 2H), 7.46-7.34 (m, 3H),
6.78 (s, 2H), 4.68 (s, 1H), 3.42-3.20 (m, 2H), 1.72-1.57 (m, 2H),
–1
+
cm . HRMS (ESI): m/z [M+H] calcd for C H Br N O S:
5
20
13
2
4
2
13
30.91205; found: 530.91138.
1.47-1.32 (m, 2H), 0.95 (t, J = 7.2 Hz, 3H). C NMR (CDCl3,
00 MHz): δ (ppm) 195.7, 193.7, 156.8, 146.8, 136.9, 134.5,
1
4
2
.3.27 5-amino-3-imino-1-oxo-7a-(thiophen-2-yl)-7-(thiophene-
-carbonyl)-1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-
134.3, 129.5, 129.2, 129.1, 128.9, 124.9, 118.0, 81.5, 58.2, 57.0,
54.7, 32.7, 20.4, 13.8. IR (KBr): 3324, 3223, 2959, 2188, 1742,
–1
carbonitrile (5ga)
1655, 1448, 1215, 1035, 916, 811, 702 cm . HRMS (ESI): m/z
+
1
[M+H] calcd for C24
H
23
N
4
O
2
S: 431.15362; found: 431.15439.
Yield 50%; gray solid. mp 179-181 °C. H NMR (DMSO-d , 600
6
MHz): δ (ppm) 10.15 (s, 1H), 8.31 (d, J = 2.4 Hz, 1H), 8.22 (d, J
4
1
.3.32
5-amino-7-benzoyl-1-oxo-7a-phenyl-3-(phenylimino)-
=
4.8 Hz, 1H), 7.93 (s, 1H), 7.68 (d, J = 4.8 Hz, 1H), 7.43 (d, J =
,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ad)
3
4
1
1
1
.0 Hz, 1H), 7.35 (t, J = 4.2 Hz, 1H), 7.18 (t, J = 4.2 Hz, 1H),
13
1
.99 (s, 1H). C NMR (DMSO-d , 150 MHz): δ (ppm) 194.7,
Yield 66%; yellow solid. mp 228-230 °C. H NMR (CDCl , 600
MHz): δ (ppm) 8.01 (d, J = 7.2 Hz, 2H), 7.69-7.63 (m, 3H), 7.57-
7.46 (m, 5H), 7.37 (t, J = 7.8 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H),
7.06 (d, J = 7.8 Hz, 2H), 6.62 (s, 2H), 4.74 (s, 1H). C NMR
(CDCl , 150 MHz): δ (ppm) 195.7, 193.3, 156.1, 149.4, 147.4,
6
3
89.8, 155.8, 151.1, 141.2, 141.1, 138.1, 136.8, 129.4, 128.4,
27.5, 126.3, 117.9, 81.1, 57.0, 56.8. IR (KBr): 3328, 3166, 2187,
–1
13
746, 1645, 1452, 1413, 1351, 1099, 851, 719 cm . HRMS
+
(ESI): m/z [M+H] calcd for C H N O S : 387.00386; found:
16
11
4
2
3
3
3
87.00335.
136.5, 134.7, 134.2, 129.8, 129.5, 129.2, 129.1, 125.7, 124.9,
1
21.3, 82.1, 59.2, 58.1. IR (KBr): 3394, 3238, 2924, 2189, 1770,
–1
4
.3.28 7-(1-naphthoyl)-5-amino-3-imino-7a-(naphthalen-1-yl)-1-
1664, 1443, 1344, 1138, 1025, 927, 759, 701 cm . HRMS (ESI):
m/z [M+H] calcd for C H N O S: 451.12232; found:
+
oxo-1,3,7,7a-tetrahydropyrrolo[1,2-c]thiazole-6-carbonitrile
5ha)
26
19
4
2
(
451.12252.
1
Yield 62%; yellow solid. mp 196-197 °C. H NMR (DMSO-d ,
6
Acknowledgments
6
8
00 MHz): δ (ppm) 10.25 (s, 1H), 8.71 (d, J = 8.4 Hz, 1H), 8.44-
.40 (m, 1H), 8.33 (s, HCHCl3), 8.31 (d, J = 8.4 Hz, 1H), 8.26 (d, J
We are grateful to the National Natural Science Foundation of
China (Grant Nos. 21272085 and 21472056) for financial support.
We would also like to thank Dr. Chuanqi Zhou, Hebei University, for
analytical support.
=
7.2 Hz, 1H), 8.19 (s, 2H), 8.15-8.08 (m, 3H), 7.88-7.83 (m, 1H),
7
1
1
.78-7.73 (m, 1H), 7.72-7.65 (m, 3H), 7.65-7.59 (m, 2H), 5.45 (s,
H). C NMR (DMSO-d , 150 MHz): δ (ppm) 198.0, 193.8,
55.4, 151.7, 134.9, 134.9, 134.8, 134.8, 133.7, 132.0, 131.8,
13
6

8
Tetrahedron
Supplementary data
Wong, K. K. Bioorg. Med. Chem. Lett. 2004, 14, 4539. (b) Santos, K.;
ACCEPTED MANUSCRIPT
Laranjo, M.; Abrantes, A. M.; Brito, A. F.; Gonçalves, C.; Ribeiro, A. B.
S.; Botelho, M. F.; Soares, M. I. L.; Oliveira, A. S. R.; Pinho e Melo, T.
M. V. D. Eur. J. Med. Chem. 2014, 79, 273. (c) Prasanna, P.;
Balamurugan, K.; Perumal, S.; Yogeeswari, P.; Sriram, D. Eur. J. Med.
Chem. 2010, 45, 5653. (d) Karthikeyan, S. V.; Bala, B. D.; Raja, V. P. A.;
Perumal, S.; Yogeeswari, P.; Sriram, D. Bioorg. Med. Chem. Lett. 2010,
Supplementary data related to this article can be found online at
doi:
2
0, 350. (e) Maheswari, S. U.; Balamurugan, K.; Perumal, S.;
References and notes
Yogeeswari, P.; Sriram, D. Bioorg. Med. Chem. Lett. 2010, 20, 7278.
3. W. Franke, F. Blume, F. Arndt and R. Rees, Eur. Pat. Appl. 1989, EP
298405 A2 19890111.
1
1
2
3
.
.
.
For representative reviews and references, see: (a) Barry, B. T.; Dennis,
G. H. Chem. Rev. 2009, 109, 4439. (b) Dömling, A. Chem. Rev. 2006,
14. (a) Yang, J.-M.; Hu, Y.; Li, Q.; Yu, F.; Cao, J.; Fang, D.; Huang, Z.-B.;
Shi, D.-Q. ACS Comb. Sci. 2014, 16, 139. (b) Maheswari, S. U.; Perumal,
S. Tetrahedron Lett. 2013, 54, 7044. (c) Chandraprakash, K.; Sankaran,
M.; Uvarani, C.; Shankar, R.; Ata, A.; Dallemer, F.; Mohan, P. S.
Tetrahedron Lett. 2013, 54, 3896. (d) Revathy, K.; Lalitha, A. RSC Adv.,
2014, 4, 279.
1
06, 17. (c) Ganem, B. Acc. Chem. Res. 2009, 42, 463. (d) Ivanov, A. S.
Chem. Soc. Rev. 2008, 37, 789. (e) de Meijere, A.; von Zezschwitz, P.;
Bräse, S. Acc. Chem. Res. 2005, 38, 413. (f) Ramón, D. J.; Yus, M.
Angew. Chem. Int. Ed. 2005, 44, 1602. (g) Liéby-Muller, F.;
Constantieux, T.; Rodriguez, J. J. Am. Chem. Soc. 2005, 127, 17176. (h)
Zhu, J.; Bienaymé, H. Multicomponent Reactions; Wiley-VCH:
Weinheim, 2005. (i) Wipf, P.; Stephenson, C. R. J.; Okumura, K. J. Am.
Chem. Soc. 2003, 125, 14694. (j) Tietze, L. F.; Brasche, G.; Gericke, K.
Domino Reactions in Organic Synthesis; Wiley-VCH: Weinheim, 2006.
15. Murai, M.; Yoshida, S.; Miki, K.; Ohe, K. Chem. Commun., 2010, 46,
3366.
16. (a) Koley, S.; Chowdhury, S.; Chanda, T.; Ramulu, B. J.; Samai, S.;
Motisa, L.; Singh, M. S. Tetrahedron 2015, 71, 301. (b) Eftekhari-Sis, B.;
Zirak, M.; Akbari, A. Chem. Rev. 2013, 113, 2958. (c) Muccioli, G. G.;
Wouters, J.; Charlier, C.; Scriba, G. K. E.; Pizza, T.; Di Pace, P.; De
Martino, P.; Poppitz, W.; Poupaert, J. H.; Lambert, D. M. J. Med. Chem.
2006, 49, 872. (d) Feng, X.; Wang, Q.; Lin, W.; Dou, G.-L.; Huang, Z.-
B.; Shi, D.-Q. Org. Lett. 2013, 15, 2542. (e) Karamthulla, S.; Pal, S.;
Khan, Md. N.; Choudhury, L. H. RSC Adv, 2013, 3, 15576.
17. (a) McKay, W. R.; Proctor, G. R. J. Chem. Soc., Perkin Trans. 1, 1981,
2443. (b) Attanasi, O. A.; De Crescentini, L.; Favi, G.; Filippone, P.;
Giorgi, G.; Mantellini, F.; Perrulli, F. R.; Spinelli, D. Tetrahedron 2008,
64, 3837.
(k) Gawande, M. B.; Bonifácio, V. D. B.; Luque, R.; Branco, P. S.;
Varma, R. S. Chem. Soc. Rev., 2013, 42, 5522.
For representative references, see: (a) Simon, C.; Peyronel, J. F.;
Rodriguez, J. Org. Lett. 2001, 3, 2145. (b) Li, W.-B.; Zhang, J.-L. Chem.
Commun. 2010, 46, 8839. (c) Hong, D.; Zhu, Y.-X.; Li, Y.; Lin, X.-F.;
Lu, P.; Wang, Y.-G. Org. Lett. 2011, 13, 4668. (d) Wang, X.; Xu, X.-P.;
Wang, S.-Y.; Zhou, W.-Q.; Ji, S.-J. Org. Lett. 2013, 15, 4246. (e) Jiang,
B.; Yi, M.-S.; Shi, F.; Tu, S.-J.; Pindi, S.; McDowell, P.; Li, G.-G. Chem.
Commun. 2012, 48, 808. (f) Li, T.-J.; Yin, H.-M.; Yao, C.-S.; Wang, X.-
S.; Jiang, B.; Tu, S.-J.; Li, G.-G. Chem. Commun. 2012, 48, 11966. (g)
Jiang, B.; Ye, Q.; Fan, W.; Wang, S.-L.; Tu, S.-J.; Li, G.-G. Chem.
Commun. 2014, 50, 6108. (h) Hu, J.-D.; Cao, C.-P.; Lin, W.; Hu, M.-H.;
Huang, Z.-B.; Shi, D.-Q. J. Org. Chem. 2014, 79, 7935. (i) Feng, X.;
Wang, J.-J.; Xun, Z.; Zhang, J.-J.; Huang, Z.-B.; Shi, D.-Q. Chem.
Commun. 2015, 51, 1528.
(a) Yin, G.-D.; Zhou, B.-H.; Meng, X.-G.; Wu, A.-X.; Pan, Y.-J. Org.
Lett. 2006, 8, 2245. (b) Yin, G.-D.; Wang, Z.-H.; Chen, A.-H.; Gao, M.;
Wu, A.-X.; Pan, Y.-J. J. Org. Chem. 2008, 73, 3377. (c) Gao, M.; Yin,
G.-D.; Wang, Z.-H.; Wu, Y.-D.; Guo, C.; Pan, Y.-J.; Wu, A.-X.
Tetrahedron 2009, 65, 6047. (d) Xue, W.-J.; Zheng, K.-L.; Li, H.-Z.;
Gao, F.-F.; Wu, A.-X. Tetrahedron Lett. 2014, 55, 4212. (e) Yang, Y.;
Gao, M.; Zhang, D.-X.; Wu, L.-M.; Shu, W.-M.; Wu, A.-X. Tetrahedron
2
012, 68, 7338. (f) Yang, Y.; Gao, M.; Wu, L.-M.; Deng, C.; Zhang, D.-
X.; Gao, Y.; Zhu, Y.-P.; Wu, A.-X. Tetrahedron 2011, 67, 5142.
(a) Marco, I.; Valhondo, M.; Martın-Fontecha, M.; Vázquez-Villa, H.;
Del Rıo, J.; Planas, A.; Sagredo, O.; Ramos, J. A.; Torrecillas, I. R.;
Pardo, L.; Frechilla, D.; Benhamú, B.; López-Rodrıguez, M. L. J. Med.
Chem. 2011, 54, 7986. (b) Valhondo, M.; Marco, I.; Martín-Fontecha,
M.; Vázquez-Villa, H.; Ramos, J. A.; Berkels, R.; Lauterbach, T.;
Benhamú, B.; López-Rodríguez, M. L. J. Med. Chem. 2013, 56, 7851.
(a) Mappes, C. J.; Pommer, E. H.; Rentzea, C.; Zeeh, B. U.S. Patent
4
5
.
.
́
́
́
1
980, 4, 198 423. (b) Cseke, C.; Gerwick, B. C.; Crouse, G. D.;
Murdoch, M. G.; Green, S. B.; Heim, D. R. Pestic. Biochem. Physiol.
996, 55, 210.
1
6
7
8
9
.
.
.
.
(a) Rajarathinam, B.; Vasuki, G. Org. Lett. 2012, 14, 5204. (b) Daboun,
H. A. F.; Abdou, S. E.; Hussein, M. M.; Elnagdi, M. H. Synthesis 1982,
6
, 502.
Hasegawa, M.; Nakayama, A.; Yokohama, S.; Hosokami, T.;
Kurebayashi, Y.; Ikeda, T.; Shimoto, Y.; Ide, S.; Honda, Y.; Suzuki,
N. Chem. Pharm. Bull. 1995
(a) Baldwin, J. E.; Freeman, R. T.; Lowe, C.; Schofield, C. J.; Lee, E.
Tetrahedron 1989 45, 4537. (b) Baldwin, J. E.; Lowe, C.; Schofield,
C. J.; Lee, E. Tetrahedron Lett. 1986 27, 3461
(a) Aicher, T. D.; Knorr, D. C.; Smith, H. C. Tetrahedron Lett. 1998
, 8579. (b) Aicher, T. D.; Balkan, B.; Bell, P. A.; Brand, L. J.;
, 43, 1125.
,
,
.
,
3
9
Cheon, S. H.; Deems, R. O.; Fell, J. B.; Fillers, W. S.; Fraser, J. D.;
Gao, J.; Knorr, D. C.; Kahle, G. G.; Leone, C. L.; Nadelsen, J.;
Simpson, R.; Smith, H. C. J. Med. Chem. 1998, 41, 4556.
1
0. (a) Trapani, G.; Franco, M.; Latrofa, A.; Genchi, G.; Brigiani, M.;
Mazzoccoli, M.; Persichella, M.; Serra, M.; Biggio, G.; Liso, G. Eur.
J. Med. Chem. 1994
Carotti, A.; Cellamare, S.; Serra, M.; Ghiani, C. A.; Tuligi, G.; Biggio,
G.; Liso, G. J. Pharm. Pharmacol. 1996 48, 834
, 29, 197. (b) Trapani, G.; Franco, M.; Latrofa, A.;
,
.
1
1
1. Soares, M. I. L.; Brito, A. F.; Laranjo, M.; Abrantes,A. M. M.; Botelho,
F.; Paixão, J. A.; Matos Beja, A.; Ramos Silva, M.; Pinho e Melo, T. M.
V. D. Eur. J. Med. Chem. 2010, 45, 4676.
2. (a) Shankaran, K.; Donnelly, K. L.; Shah, S. K.; Guthikonda, R. N.;
MacCoss, M.; Humes, J. L.; Pacholok, S. G.; Grant, S. K.; Kelly, T. M.;

ACCEPTED MANUSCRIPT
Supporting Information Available
Chemoselective synthesis of biheterocyclic skeletons
tetrahydro-1H-pyrrolo[1,2-c]imidazole and tetrahydropyrrolo[1,2-c]thiazole derivatives
via multicomponent self-sorting domino strategy
a
a
a
a
a
a,b
Qun Cai , Feng-Cheng Jia , Deng-Kui Li , Cheng Xu , Ke-Rong Ding ,and An-Xin Wu*
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China
b
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: chwuax@mail.ccnu.edu.cn (A. X. Wu)
Table of Contents
page
1
2
. General.………………………………………………........…...................................S2
. General procedure for synthesis of 4, 5, A and B………………….…………......S2
3
4
5
. Spectral data of compounds 4, 5, A and B………….……….………….…….S3-S14
. Molecular structures and crystallographic data of compounds 4ab, 4ad and 5aa……..S15
. H NMR and C NMR spectra of compounds 4, 5, A and B………………S16-S49
1
13
-S1-

ACCEPTED MANUSCRIPT
1. General
All substrates and reagents were commercially available and used without further
purification. TLC analysis was performed using pre-coated glass plates. Column
chromatography was performed using silica gel (200-300 mesh). IR spectra were recorded
–1
on a Perkin-Elmer PE-983 infrared spectrometer as KBr pellets with absorption in cm .
1H spectra were recorded in CDCl
or DMSO-d on 400/600 MHz NMR spectrometers and
3
6
resonances (δ) are given in parts per million relative to tetramethylsilane. Data are
reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m =
13
multiplet), coupling constants (Hz) and integration. C spectra were recorded in CDCl
3
or
DMSO-d on 100/150 MHz NMR spectrometers and resonances (δ) are given in ppm.
6
HRMS were obtained on a Bruker Apex-Ultra 7.0T FTMS equipped with an electrospray
source (ESI or APCI). The X-ray crystal structure determination of 4ab, 4ad and 5aa were
obtained on a Bruker SMART APEX CCD system. Melting points were determined using
XT-4 apparatus and not corrected.
2. General procedure for synthesis of 4, 5, A and B
2
.1 General procedure for synthesis of 4 (4aa as an example)
A mixture of phenylglyoxal monohydrate 1a (2.0 mmol), malononitrile 2a (1.2 mmol),
thiourea 3a (1.0 mmol) in HOAc (3 mL) was stirred at 100 °C for 20 min till almost
completed conversion of the substrates by TLC analysis, then extracted with EtOAc three
times (3 × 50 mL). The extract was washed with 10% NaHCO
3
solution (w/w), dried over
anhydrous Na SO and concentrated in vacuo. The crude product was purified by column
2
4
chromatography on silica gel (eluent: petroleum ether/EtOAc) to afford the product 4aa as
a yellow solid.
2
.2 General procedure for synthesis of 5 (5aa as an example)
A mixture of phenylglyoxal monohydrate 1a (2.0 mmol), malononitrile 2a (1.2 mmol),
thiourea 3a (1.0 mmol) in EtOH (3 mL) was stirred at 80 °C for 40 min till almost
completed conversion of the substrates by TLC analysis, then extracted with EtOAc three
times (3 × 50 mL). The extract was dried over anhydrous Na
2
SO and concentrated in
4
vacuo. The crude product was purified by column chromatography on silica gel (eluent:
petroleum ether/EtOAc) to afford the product 5aa as a yellow solid.
2
.3 General procedure for synthesis of A1
A solution of phenylglyoxal monohydrate 1a (1.38 g, 10 mmol) and MS4A (2.0 g) in
MeCN (20 mL) was added ethyl cyanoacetate 2o (10 mmol), and the mixture was stirred
overnight at 80 °C . The resulting mixture was filtered through short silica gel pad, and
concentrated in vacuo. The crude product was purified by column chromatography on
silica gel to afford corresponding compound Ethyl 2-cyano-4-oxo-4-phenylbut-2-enoate A
as yellow solids.
-S2-

ACCEPTED MANUSCRIPT
2
.4 General procedure for synthesis of B
A mixture of phenylglyoxal monohydrate 1a (1.0 mmol) and thiourea 3a (1.0 mmol) in
HOAc (3 mL) was stirred at 100 °C for 20 min till almost completed conversion of the
substrates by TLC analysis, then extracted with EtOAc three times (3 × 20 mL). The
extract was washed with 10% NaHCO
3
solution (w/w), dried over anhydrous Na
2
SO and
4
concentrated in vacuo. The crude product was purified by column chromatography on
silica gel (eluent: petroleum ether/EtOAc) to afford the product B as a white solid.
3. Spectral data of compounds 4, 5, A and B.
(
E)-ethyl 2-cyano-4-oxo-4-phenylbut-2-enoate (A)
1
1
Yield 87%; yellow solid. mp 64-65 °C (ref. 64 °C ). H NMR (CDCl
3
, 400 MHz): 8.44 (s, 1H),
8
.04-7.94 (m, 2H), 7.72-7.67 (m, 1H), 7.56 (t, J = 7.6 Hz, 2H), 4.44 (q, J = 7.2 Hz, 2H), 1.43
+
(t, J = 7.2 Hz, 3H). HRMS (ESI): m/z [M+Na] calcd for C13
H
11NNaO : 252.0631; found:
3
252.0634.
5
-phenyl-2-thioxoimidazolidin-4-one (B)
1
Yield 83%; white solid. mp 188-189 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 11.87 (s,
1
H), 10.50 (s, 1H), 7.45-7.41 (m, 2H), 7.40-7.36 (m, 1H), 7.27 (d, J = 7.2 Hz, 2H), 5.40 (s,
13
1H). C NMR (DMSO-d , 150 MHz): δ (ppm) 183.0, 174.9, 134.6, 129.0, 128.6, 126.8, 64.0.
6
–1
IR (KBr): 3459, 3333, 3159, 2898, 1741, 1536, 1496, 1406, 1263, 1163, 723, 697 cm .
HRMS (ESI): m/z [M+Na] calcd for C
+
9
H
8
N NaOS: 215.02495; found: 215.02486.
2
5
-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]
imidazole-6-carbonitrile (4aa)
Yield 80%; yellow solid. mp >300 °C . H NMR (DMSO-d
.15 (d, J = 8.0 Hz, 2H), 8.00 (s, 2H), 7.74 (t, J = 7.0 Hz, 1H), 7.66-7.56 (m, 4H), 7.55-7.42
1
6
, 400 MHz): δ (ppm) 12.87 (s, 1H),
8
13
(
m, 3H), 5.08 (s, 1H). C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 196.0, 181.0, 172.9, 154.7,
36.1, 134.7, 133.9, 129.5, 129.3, 129.1, 128.9, 125.0, 117.1, 76.4, 59.7, 55.1. IR (KBr): 3438,
300, 3141, 2923, 2361, 2195, 1770, 1669, 1634, 1583, 1465, 1448, 1239, 1163, 1105, 738,
1
3
6
–1
+
94, 544 cm . HRMS (ESI): m/z [M+H] calcd for C20
H
15
N
4
2
O S: 375.0910; found: 375.0908.
-S3-

ACCEPTED MANUSCRIPT
5
-amino-7-(4-methylbenzoyl)-1-oxo-3-thioxo-7a-(p-tolyl)-2,3,7,7a-tetrahydro-1H-p
yrrolo[1,2-c]imidazole-6-carbonitrile (4ba)
1
Yield 72%; yellow solid. mp 103-104 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 12.81 (s,
1
H), 8.02 (d, J = 7.6 Hz, 2H), 7.95 (s, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H),
13
7.31 (d, J = 7.6 Hz, 2H), 4.97 (s, 1H), 2.40 (s, 3H), 2.33 (s, 3H). C NMR (DMSO-d , 100
6
MHz): δ (ppm) 195.6, 181.0, 173.0, 154.7, 145.4, 138.9, 133.2, 131.6, 129.6, 129.5, 129.1,
1
24.8, 117.1, 76.3, 59.9, 55.0, 21.3, 20.6. IR (KBr): 3403, 2957, 2924, 2853, 2189, 1765,
–1
+
1670, 1644, 1460, 1361, 1251, 1021, 851, 816, 599 cm . HRMS (ESI): m/z [M+H] calcd for
S: 403.1223; found: 403.1231.
C
22
H
19 4
N O
2
5
-amino-7-(4-methoxybenzoyl)-7a-(4-methoxyphenyl)-1-oxo-3-thioxo-2,3,7,7a-tetr
ahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ca)
1
Yield 65%; yellow solid. mp 128-129 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 12.77 (s,
1
4
1
H), 8.11 (d, J = 8.8 Hz, 2H), 7.92 (s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.08 (t, J = 8.8 Hz, 4H),
13
6
.94 (s, 1H), 3.88 (s, 3H), 3.79 (s, 3H). C NMR (DMSO-d , 100 MHz): δ (ppm) 194.6, 181.6,
64.4, 160.0, 132.1, 127.9, 126.9, 126.4, 117.3, 114.5, 114.3, 76.2, 60.1, 55.8, 55.4, 55.0. IR
–1
(
(
KBr): 3408, 2959, 2925, 2853, 2187, 1764, 1644, 1598, 1257, 1024, 803, 541 cm . HRMS
ESI): m/z [M+H] calcd for C22
+
H
19
N
4
O S: 435.1122; found: 435.1124.
4
5
-amino-7a-(benzo[d][1,3]dioxol-5-yl)-7-(benzo[d][1,3]dioxole-5-carbonyl)-1-oxo-3-
thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4da)
1
Yield 55%; white solid. mp >300 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 12.77 (s, 1H),
7
.92 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.59 (s, 1H), 7.14-7.07 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H),
13
6
.95 (d, J = 8.4 Hz, 1H), 6.19 (d, J = 4.0 Hz, 2H), 6.09 (d, J = 7.2 Hz, 2H), 4.95 (s, 1H). C
, 100 MHz): δ (ppm) 194.2, 181.0, 173.1, 154.5, 152.9, 148.2, 148.2, 148.0,
29.6, 128.6, 126.9, 118.3, 117.3, 108.5, 108.3, 106.1, 102.5, 101.8, 76.3, 60.1, 54.9. IR
NMR (DMSO-d
6
1
-S4-

ACCEPTED MANUSCRIPT
–1
(
(
KBr): 3408, 3131, 2194, 1766, 1664, 1644, 1442, 1250, 1110, 1039, 820, 538 cm . HRMS
+
ESI): m/z [M+H] calcd for C22
H
15
N
4
O S: 463.0707; found: 463.0703.
6
5
1
-amino-7-(3-nitrobenzoyl)-7a-(3-nitrophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahydro-
H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ea)
1
Yield 47%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 13.12 (s, 1H),
8
.85 (s, 1H), 8.57 (t, J = 8.4 Hz, 2H), 8.44 (s, 1H), 8.38 (d, J = 8.4 Hz, 1H), 8.20 (s, 2H), 8.05
13
(
d, J = 8.0 Hz, 1H), 7.94-7.83 (m, 2H), 5.38 (s, 1H). C NMR (DMSO-d
6
, 100 MHz): δ (ppm)
93.7, 181.2, 172.2, 154.7, 148.2, 148.1, 137.8, 135.8, 134.9, 131.9, 131.9, 130.8, 128.9,
24.4, 124.1, 120.4, 117.0, 75.5, 58.3, 55.5. IR (KBr): 3457, 3318, 3172, 2194, 1741, 1686,
1
1
1
4
–1
+
529, 1489, 1346, 1184, 728, 678 cm . HRMS (APCI): m/z [M+H] calcd for C20
H
13
N
6
6
O S:
65.0612; found: 465.0614.
5
-amino-7-(4-fluorobenzoyl)-7a-(4-fluorophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahydr
o-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4fa)
1
Yield 88%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 12.89 (s, 1H),
8
.28-8.18 (m, 2H), 8.00 (s, 2H), 7.65-7.56 (m, 2H), 7.43 (t, J = 9.0 Hz, 2H), 7.38 (t, J = 9.0
13
Hz, 2H), 5.08 (s, 1H). C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 194.5, 181.1, 172.9, 167.3,
64.8, 163.9, 161.4, 154.7, 132.9, 132.8, 132.1, 130.7, 127.5, 127.4, 117.1, 116.2, 116.0, 75.9,
9.4, 55.1. IR (KBr): 3382, 3305, 3254, 3195, 2195, 1765, 1647, 1592, 1458, 1361, 1237,
157, 1091, 838, 699, 543cm . HRMS (ESI): m/z [M+H] calcd for C20
11.0722; found: 411.0726.
1
5
1
4
–1
+
H
13
F
N
2 4
2
O S:
5
-amino-7-(2-chlorobenzoyl)-7a-(2-chlorophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahyd
ro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ga)
1
Yield 57%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 12.94 (s, 1H),
8
(
1
.15 (d, J = 8.4 Hz, 2H), 8.02 (s, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 9.0 Hz, 2H), 7.58
d, J = 8.4 Hz, 2H), 5.09 (s, 1H). 13C NMR (DMSO-d
, 100 MHz): δ (ppm) 194.7, 181.0,
72.5, 154.6, 139.8, 138.6, 135.3, 134.9, 134.2, 132.7, 132.6, 131.4, 129.4, 129.1, 127.1,
6
-S5-

ACCEPTED MANUSCRIPT
1
1
4
17.0, 75.8, 59.2, 55.0. IR (KBr): 3320, 3132, 2182, 1760, 1672, 1646, 1588, 1371, 1260,
–
1
+
094, 1011, 859, 762, 538 cm . HRMS (APCI): m/z [M+H] calcd for C20
H
13Cl
N
2 4
2
O S:
43.0131; found: 443.0128.
5
-amino-7-(4-chlorobenzoyl)-7a-(4-chlorophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahyd
ro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ha)
1
Yield 82%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 12.92 (s, 1H),
8.15 (d, J = 8.8 Hz, 2H), 8.00 (s, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.64-7.57 (m, 4H), 5.09 (s, 1H).
13C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 194.7, 181.1, 172.6, 154.7, 139.9, 134.9, 134.3,
1
32.6, 131.5, 129.1, 127.1, 117.1, 75.8, 59.2, 55.1. IR (KBr): 3380, 3305, 3252, 3192, 2968,
–1
2361, 2195, 1764, 1645, 1586, 1490, 1458, 1362, 1250, 1092, 1009, 853, 696, 547 cm .
+
HRMS (ESI): m/z [M+H] calcd for C20
H
13Cl
N
2 4
2
O S: 443.0131; found: 443.0138.
5
-amino-7-(3,4-dichlorobenzoyl)-7a-(3,4-dichlorophenyl)-1-oxo-3-thioxo-2,3,7,7a-t
etrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ia)
1
Yield 60%; yellow solid. mp 274-275 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 13.08 (s,
1
H), 8.46 (s, 1H), 8.13 (d, J = 8.4 Hz, 3H), 7.94 (d, J = 8.4 Hz, 1H), 7.91-7.88 (m, 2H), 7.58
(
d, J = 8.4 Hz, 1H), 5.28 (s, 1H). 13C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 193.5, 181.1,
1
1
1
5
72.2, 154.6, 137.8, 136.6, 134.0, 132.5, 132.2, 132.0, 131.8, 131.3, 131.2, 129.4, 127.7,
25.5, 117.0, 75.3, 58.7, 55.1. IR (KBr): 3385, 3325, 3191, 2188, 1766, 1652, 1581, 1463,
–1
+
359, 1243, 1031, 703, 574 cm . HRMS (ESI): m/z [M+H] calcd for C20
H
11Cl
N
4 4
2
O S:
10.9351; found: 510.9350.
5
-amino-7-(3-bromobenzoyl)-7a-(3-bromophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahyd
ro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ja)
1
Yield 85%; white solid. mp 284-285 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 12.95 (s,
1
H), 8.32 (s, 1H), 8.12 (d, J = 7.8 Hz, 1H), 8.07 (s, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.76 (s, 1H),
13
7.72 (d, J = 7.8 Hz, 1H), 7.62-7.53 (m, 2H), 7.50 (t, J = 7.8 Hz, 1H), 5.20 (s, 1H). C NMR
-S6-

ACCEPTED MANUSCRIPT
(
6
DMSO-d , 100 MHz): δ (ppm) 194.3, 180.9, 172.3, 154.6, 138.3, 137.3, 135.7, 132.3, 132.2,
1
31.1, 131.0, 128.5, 128.0, 124.2, 122.4, 122.3, 117.0, 75.6, 59.0, 55.0. IR (KBr): 3396, 3143,
–1
2200, 1751, 1651, 1585, 1472, 1441, 1368, 1242, 1158, 680, 630 cm . HRMS (APCI): m/z
+
[M+H] calcd for C20
H
13Br
2
N
4
O S: 530.9121; found: 530.9118.
2
5
-amino-7-(4-bromobenzoyl)-7a-(4-bromophenyl)-1-oxo-3-thioxo-2,3,7,7a-tetrahyd
ro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ka)
1
Yield 85%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 13.00 (s, 1H),
8
(
1
.13 (d, J = 7.8 Hz, 2H), 8.10 (s, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.58
d, J = 7.8 Hz, 2H), 5.14 (s, 1H); 13C NMR (DMSO-d
, 100 MHz): δ (ppm) 195.0, 181.1,
72.5, 154.7, 135.4, 132.9, 132.1, 131.6, 129.3, 127.4, 123.0, 117.1, 75.9, 59.2, 55.0. IR
6
–1
(KBr): 3427, 2962, 2924, 2360, 2191, 1767, 1647, 1584, 1262, 1097, 1024, 802, 683 cm .
+
HRMS (ESI): m/z [M+H] calcd for C20
H
13Br
2
N
4
O S: 530.9121; found: 530.9117.
2
7
1
-(2-naphthoyl)-5-amino-7a-(naphthalen-2-yl)-1-oxo-3-thioxo-2,3,7,7a-tetrahydro-
H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4la)
1
Yield 52%; yellow solid. mp >300 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 12.99 (s, 1H),
9.05 (s, 1H), 8.16-8.13 (m, 2H), 8.12 (s, 1H), 8.09 (s, 3H), 8.04 (d, J = 7.2 Hz, 2H), 8.02-7.95
(
(
1
1
2
m, 2H), 7.79 (d, J = 9.0 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.65 (t, J = 7.8 Hz, 1H), 7.63-7.58
13
m, 2H), 5.43 (s, 1H). C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 195.8, 181.3, 173.1, 154.9,
35.7, 133.6, 133.1, 132.5, 132.2, 131.2, 130.0, 129.6, 129.1, 128.8, 128.4, 127.9, 127.7,
27.3, 127.1, 124.2, 123.9, 123.5, 122.9 117.4, 76.6, 59.9, 56.1, 55.3. IR (KBr): 3405, 3189,
–1
+
197, 1744, 1647, 1468, 1363, 1245, 737, 701, 538 cm . HRMS (ESI): m/z [M+H] calcd for
S: 475.1223; found: 475.1228.
C
28
H
19 4
N O
2
5
-amino-1-oxo-7a-(thiophen-2-yl)-7-(thiophene-2-carbonyl)-3-thioxo-2,3,7,7a-tetra
hydro-1H-pyrrolo[1,2-c]imidazole-6-carbonitrile (4ma)
1
Yield 49%; yellow solid. mp 173-174 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 12.98 (s,
1H), 8.32 (d, J = 4.0 Hz, 1H), 8.22 (d, J = 4.8 Hz, 1H), 7.95 (s, 2H), 7.67 (d, J = 5.2 Hz, 1H),
-S7-

ACCEPTED MANUSCRIPT
7
.39 (d, J = 3.6 Hz, 1H), 7.37-7.32 (m, 1H), 7.18-7.12 (m, 1H), 4.99 (s, 1H). 13C NMR
(
6
DMSO-d , 100 MHz): δ (ppm) 189.2, 181.2, 172.1, 154.7, 141.1, 138.9, 138.4, 137.1, 129.5,
1
1
C
27.9, 127.3, 126.1, 117.2, 75.1, 60.3, 55.6. IR (KBr): 3369, 2922, 2195, 1763, 1643, 1465,
–1
+
439, 1408, 1357, 1250, 1025, 734, 712, 531 cm . HRMS (APCI): m/z [M+H] calcd for
: 387.0039; found: 387.0038.
16
H
11 4
N O
2
S
3
methyl
-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]
imidazole-6-carboxylate (4na)
Yield 50%; yellow solid. mp >300 °C . H NMR (DMSO-d
.13 (d, J = 7.6 Hz, 2H), 7.73 (t, J = 7.6 Hz, 1H), 7.68 (s, 1H), 7.63-7.54 (m, 5H), 7.53-7.46
5
1
6
, 400 MHz): δ (ppm) 12.87 (s, 1H),
8
13
(
m, 3H), 4.94 (s, 1H), 3.33 (s, 3H). C NMR (DMSO-d
6
, 100 MHz): δ (ppm) 200.7, 181.8,
73.3, 165.1, 153.6, 136.9, 135.8, 134.3, 129.3, 129.2, 128.8, 127.6, 124.7, 82.8, 77.3, 54.4,
0.1. IR (KBr): 3413, 3296, 3109, 1761, 1679, 1606, 1523, 1443, 1380, 1312, 1109, 962, 720,
1
5
6
–
1
+
95 cm . HRMS (ESI): m/z [M+H] calcd for C21
H
18
N
3
4
O S: 408.1013; found: 408.1014.
ethyl
-amino-7-benzoyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]
imidazole-6-carboxylate (4oa)
Yield 52%; yellow solid. mp 135-136 °C . H NMR (DMSO-d
H), 8.12 (d, J = 7.6 Hz, 2H), 7.72 (t, J = 7.2 Hz, 1H), 7.63 (s, 2H), 7.60-7.55 (m, 4H), 7.51 (t,
J = 7.6 Hz, 2H), 7.47-7.43 (m, 1H), 4.94 (s, 1H), 3.84-3.68 (m, 2H), 0.76 (t, J = 6.8 Hz, 3H).
13C NMR (DMSO-d
, 100 MHz): δ (ppm) 201.0, 181.9, 173.3, 164.9, 153.9, 136.9, 136.0,
34.1, 129.3, 129.1, 128.7, 124.6, 82.9, 77.3, 58.6, 54.2. IR (KBr): 3380, 3276, 2975, 1744,
5
1
6
, 400 MHz): δ (ppm) 12.86 (s,
1
6
1
1
C
–1
+
664, 1530, 1312, 1258, 1203, 1103, 773, 690, 530 cm . HRMS (ESI): m/z [M+H] calcd for
S: 422.1169; found: 422.1171.
22
H
20 3
N O
4
5
-amino-7-benzoyl-2-methyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyr
rolo[1,2-c]imidazole-6-carbonitrile (4ab)
-S8-

ACCEPTED MANUSCRIPT
1
Yield 54%; yellow solid. mp 244-245 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 8.14 (d, J =
8
(
.0 Hz, 2H), 8.10 (s, 1H), 7.75 (t, J = 7.2 Hz, 1H), 7.63-7.56 (m, 4H), 7.55-7.48 (m, 3H), 5.19
s, 1H), 3.21 (s, 3H). 13C NMR (DMSO-d
, 100 MHz): δ (ppm) 195.9, 181.0, 171.8, 154.8,
35.7, 134.8, 133.7, 129.7, 129.5, 129.1, 129.0, 125.3, 117.1, 75.2, 59.4, 55.9, 28.2. IR (KBr):
6
1
3
–1
361, 3188, 2194, 1753, 1648, 1579, 1392, 1305, 1041, 701, 574 cm . HRMS (ESI): m/z
+
[M+H] calcd for C21
H
17
N
4
O S: 389.1067; found: 389.1070.
2
5
-amino-7-benzoyl-2-butyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrro
lo[1,2-c]imidazole-6-carbonitrile (4ac)
1
Yield 53%; white solid. mp 227-228 °C . H NMR (CDCl
3
, 400 MHz): δ (ppm) 7.97 (d, J = 7.2
Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.56-7.48 (m, 4H), 7.47-7.42 (m, 3H), 6.62 (s, 2H), 4.71 (s,
1
3
1
H), 3.86-3.75 (m, 2H), 1.78-1.68 (m, 2H), 1.40-1.30 (m, 2H), 0.93 (t, J = 7.6 Hz, 3H). C
NMR (CDCl , 100 MHz): δ (ppm) 194.8, 181.1, 171.6, 155.7, 135.9, 134.7, 133.9, 129.5,
29.3, 129.2, 129.0, 124.7, 75.0, 61.7, 57.4, 41.9, 28.7, 19.9, 13.6. IR (KBr): 3376, 3306,
3
1
3
–1
244, 3188, 2956, 2196, 1757, 1675, 1652, 1589, 1389, 1055, 696, 572 cm . HRMS (APCI):
+
m/z [M+H] calcd for C24
H
23
N
4
O S: 431.1536; found: 431.1540.
2
5
2
-amino-7-benzoyl-1-oxo-2,7a-diphenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,
-c]imidazole-6-carbonitrile (4ad)
1
Yield 70%; white solid. mp >300 °C . H NMR (DMSO-d
6
, 400 MHz): δ (ppm) 8.22 (d, J = 8.0
Hz, 2H), 8.17 (s, 2H), 7.77 (t, J = 7.2 Hz, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.6 Hz,
1
3
2
(
1
3
H), 7.60-7.55 (m, 4H), 7.54-7.50 (m, 2H), 7.36 (d, J = 7.6 Hz, 2H), 5.31 (s, 1H). C NMR
DMSO-d , 100 MHz): δ (ppm) 196.2, 180.6, 171.3, 154.8, 135.5, 134.8, 133.7, 132.7, 129.7,
29.6, 129.5, 129.4, 129.2, 128.92, 128.3, 125.3, 117.0, 75.6, 59.7, 56.1. IR (KBr): 3336,
6
–1
241, 3181, 2190, 1770, 1649, 1582, 1447, 1374, 1286, 703, 563cm . HRMS (APCI): m/z
+
[M+H] calcd for C26
H
19
N
4
O S: 451.1223; found: 451.1224.
2
5
-amino-7-benzoyl-2-benzyl-1-oxo-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-pyrr
olo[1,2-c]imidazole-6-carbonitrile (4ae)
-S9-

ACCEPTED MANUSCRIPT
1
Yield 80%; yellow solid. mp 240-241 °C . H NMR (CDCl
3
, 600 MHz): δ (ppm) 7.96 (d, J =
7.8 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H), 7.57-7.48 (m, 4H), 7.48-7.42 (m, 3H), 7.33 (d, J = 7.2
Hz, 2H), 7.28 (t, J = 7.2 Hz, 2H), 7.26-7.23 (m, 1H), 6.46 (s, 2H), 5.15-4.95 (m, 2H), 4.76 (s,
13
1
H). C NMR (CDCl
3
, 100 MHz): δ (ppm) 194.6, 180.4, 171.6, 155.5, 135.8, 134.8, 134.4,
1
33.8, 129.6, 129.3, 129.2, 128.9, 128.4, 128.1, 127.7, 124.8, 116.7, 75.2, 61.6, 57.3, 45.1. IR
–1
(
KBr): 3356, 3241, 3181, 2194, 1754, 1675, 1650, 1588, 1396, 1251, 940, 697, 527 cm .
+
HRMS (APCI): m/z [M+H] calcd for C27
H
21
N
4
O S: 465.1380; found: 465.1381.
2
5
-amino-7-benzoyl-1-oxo-2-phenethyl-7a-phenyl-3-thioxo-2,3,7,7a-tetrahydro-1H-
pyrrolo[1,2-c]imidazole-6-carbonitrile (4af)
1
Yield 75%; yellow solid. mp 246-247 °C . H NMR (CDCl
3
, 600 MHz): δ (ppm) 7.97 (d, J =
7
.8 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.57-7.48 (m, 4H), 7.47-7.38 (m, 3H), 7.24-7.05 (m, 5H),
13
6.52 (s, 2H), 4.70 (s, 1H), 4.05 (t, J = 7.8 Hz, 2H), 3.11-2.98 (m, 2H). C NMR (CDCl , 100
3
MHz): δ (ppm) 194.9, 180.9, 171.4, 155.7, 137.4, 135.8, 134.8, 133.9, 129.5, 129.3, 129.2,
1
29.0, 128.8, 128.4, 126.5, 124.8, 75.1, 61.8, 57.6, 43.0, 32.6. IR (KBr): 3392, 3279, 3061,
–1
+
2190, 1729, 1671, 1638, 1586, 1446, 1372, 1249, 705, 574 cm . HRMS (APCI): m/z [M+H]
S: 479.1536; found: 479.1536.
calcd for C28
H
23
4
N O
2
5
-amino-7-benzoyl-3-imino-1-oxo-7a-phenyl-1,3,7,7a-tetrahydropyrrolo[1,2-c]thia
zole-6-carbonitrile (5aa)
6
Yield 85%; yellow solid. mp 190-192 °C . 1H NMR (DMSO-d , 600 MHz): δ (ppm) 10.10 (s,
1
H), 8.15 (d, J = 7.8 Hz, 2H), 8.01 (s, 1H), 7.74 (t, J = 7.2 Hz, 1H), 7.65 (d, J = 7.2 Hz, 2H),
13
7
.59 (t, J = 7.8 Hz, 2H), 7.55 (t, J = 7.8 Hz, 2H), 7.53-7.49 (m, 1H), 5.08 (s, 1H). C NMR
, 150 MHz): δ (ppm) 196.2, 195.4, 155.8, 155.7, 151.6, 136.8, 134.7, 134.1, 129.7,
29.6, 129.3, 129.0, 125.3, 118.0, 82.6, 56.1. IR (KBr): 3325, 3168, 2188, 1748, 1667, 1645,
(
DMSO-d
6
1
1
3
–1
+
447, 1347, 1104, 915, 704 cm . HRMS (ESI): m/z [M+H] calcd for C20
H
15
N
4
2
O S:
75.09102; found: 375.09054.
5
-amino-3-imino-7-(4-methylbenzoyl)-1-oxo-7a-(p-tolyl)-1,3,7,7a-tetrahydropyrrol
o[1,2-c]thiazole-6-carbonitrile (5ba)
-S10-

ACCEPTED MANUSCRIPT
1
Yield 89%; white solid. mp 188-190 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.05 (s,
1
H), 8.02 (d, J = 7.8 Hz, 2H), 7.97 (s, 1H), 7.51 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.8 Hz, 2H),
13
7.34 (d, J = 7.8 Hz, 2H), 4.98 (s, 1H), 2.41 (s, 3H), 2.34 (s, 3H). C NMR (DMSO-d , 150
6
MHz): δ (ppm) 195.8, 195.5, 155.8, 155.7, 151.8, 145.4, 139.3, 134.0, 131.7, 129.8, 129.6,
1
1
4
29.6, 125.1, 118.0, 82.5, 56.1, 21.4, 20.7. IR (KBr): 3318, 3176, 2186, 1747, 1644, 1570,
–1
+
447, 1350, 1109, 915, 753 cm . HRMS (ESI): m/z [M+H] calcd for C22
H
19
N
4
2
O S:
03.12232; found: 403.12155.
5
-amino-3-imino-7-(4-methoxybenzoyl)-7a-(4-methoxyphenyl)-1-oxo-1,3,7,7a-tetra
hydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ca)
1
Yield 78%; yellow solid. mp 176-178 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.01 (s,
1
1
1
5
H), 8.10 (d, J = 8.4 Hz, 2H), 7.92 (s, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.12-7.06 (m, 4H), 4.94 (s,
13
H), 3.88 (s, 3H), 3.80 (s, 3H). C NMR (DMSO-d , 150 MHz): δ (ppm) 195.5, 194.9, 164.2,
6
60.2, 155.8, 151.7, 132.0, 128.5, 127.0, 126.5, 118.1, 114.6, 114.2, 82.3, 56.5, 55.9, 55.7,
5.4. IR (KBr): 3415, 3308, 2187, 1748, 1641, 1599, 1510, 1443, 1343, 1255, 1105, 915, 836
–
1
+
cm . HRMS (ESI): m/z [M+H] calcd for C22
H
19
N
4
O S: 435.11215; found: 435.11139.
4
5
-amino-3-imino-7-(3-methoxybenzoyl)-7a-(3-methoxyphenyl)-1-oxo-1,3,7,7a-tetra
hydropyrrolo[1,2-c]thiazole-6-carbonitrile (5da)
1
Yield 85%; yellow solid. mp 131-133 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.06 (s,
1
H), 8.00 (s, 2H), 7.75 (d, J = 5.4 Hz, 1H), 7.62 (s, 1H), 7.53-7.42 (m, 2H), 7.33-7.27 (m, 1H),
13
7
.22-7.12 (m, 2H), 7.09 (d, J = 8.4 Hz, 1H), 5.10 (s, 1H), 3.85 (s, 3H), 3.81 (s, 3H). C NMR
, 150 MHz): δ (ppm) 195.5, 195.1, 159.7, 159.5, 155.7, 151.4, 138.3, 135.3, 130.3,
30.0, 122.2, 121.2, 118.1, 117.1, 114.7, 113.5, 111.6, 82.5, 56.1, 56.1, 55.5, 55.3. IR (KBr):
(
DMSO-d
6
1
3
–1
391, 3274, 3077, 2833, 2186, 1752, 1644, 1487, 1447, 1346, 1264, 1116, 928, 741, 549 cm .
+
HRMS (ESI): m/z [M+H] calcd for C22
H
19
N
4
O S: 435.11215; found: 435.11161.
4
-S11-

ACCEPTED MANUSCRIPT
5
-amino-7-(4-chlorobenzoyl)-7a-(4-chlorophenyl)-3-imino-1-oxo-1,3,7,7a-tetrahydr
opyrrolo[1,2-c]thiazole-6-carbonitrile (5ea)
1
Yield 80%; yellow solid. mp 179-180 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.14 (s,
1
H), 8.15 (d, J = 8.4 Hz, 2H), 8.01 (s, 2H), 7.76-7.53 (m, 6H), 5.09 (s, 1H). 13C NMR
(
6
DMSO-d , 150 MHz): δ (ppm) 195.1, 194.8, 155.7, 151.2, 139.8, 135.6, 134.5, 132.7, 131.5,
1
1
29.2, 129.1, 127.2, 117.8, 82.0, 55.9, 55.6. IR (KBr): 3335, 3174, 2189, 1739, 1648, 1445,
–1
+
347, 1095, 978, 917 cm . HRMS (ESI): m/z [M+H] calcd for C20
H
13
C
l2
N
4
2
O S: 443.01308;
found: 443.01286.
5
-amino-7-(4-bromobenzoyl)-7a-(4-bromophenyl)-3-imino-1-oxo-1,3,7,7a-tetrahyd
ropyrrolo[1,2-c]thiazole-6-carbonitrile (5fa)
1
Yield 82%; yellow solid. mp 188-189 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.14 (s,
1
7
1
H), 8.07 (d, J = 8.4 Hz, 2H), 8.01 (s, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 9.0 Hz, 2H),
13
6
.57 (d, J = 8.4 Hz, 2H), 5.08 (s, 1H). C NMR (DMSO-d , 150 MHz): δ (ppm) 195.0, 155.7,
51.1, 136.0, 133.0, 132.1, 132.0, 131.5, 129.1, 127.5, 123.1, 117.8, 82.0, 55.8, 55.6. IR
–1
(KBr): 3382, 2975, 2896, 1923, 1757, 1654, 1452, 1382, 1088, 1049, 881, 667 cm . HRMS
+
(ESI): m/z [M+H] calcd for C20
H
13Br
2
N
4
O S: 530.91205; found: 530.91138.
2
5
-amino-3-imino-1-oxo-7a-(thiophen-2-yl)-7-(thiophene-2-carbonyl)-1,3,7,7a-tetra
hydropyrrolo[1,2-c]thiazole-6-carbonitrile (5ga)
1
Yield 50%; gray solid. mp 179-181 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.15 (s, 1H),
8
.31 (d, J = 2.4 Hz, 1H), 8.22 (d, J = 4.8 Hz, 1H), 7.93 (s, 1H), 7.68 (d, J = 4.8 Hz, 1H), 7.43
13
(
(
1
1
3
d, J = 3.0 Hz, 1H), 7.35 (t, J = 4.2 Hz, 1H), 7.18 (t, J = 4.2 Hz, 1H), 4.99 (s, 1H). C NMR
DMSO-d , 150 MHz): δ (ppm) 194.7, 189.8, 155.8, 151.1, 141.2, 141.1, 138.1, 136.8, 129.4,
28.4, 127.5, 126.3, 117.9, 81.1, 57.0, 56.8. IR (KBr): 3328, 3166, 2187, 1746, 1645, 1452,
6
–1
+
413, 1351, 1099, 851, 719 cm . HRMS (ESI): m/z [M+H] calcd for C16
87.00386; found: 387.00335.
H
11
4
N O
2 3
S :
7
-(1-naphthoyl)-5-amino-3-imino-7a-(naphthalen-1-yl)-1-oxo-1,3,7,7a-tetrahydrop
yrrolo[1,2-c]thiazole-6-carbonitrile (5ha)
-S12-

ACCEPTED MANUSCRIPT
1
Yield 62%; yellow solid. mp 196-197 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.25 (s,
1
8
1
H), 8.71 (d, J = 8.4 Hz, 1H), 8.44-8.40 (m, 1H), 8.33 (s, HCHCl3), 8.31 (d, J = 8.4 Hz, 1H),
.26 (d, J = 7.2 Hz, 1H), 8.19 (s, 2H), 8.15-8.08 (m, 3H), 7.88-7.83 (m, 1H), 7.78-7.73 (m,
13
H), 7.72-7.65 (m, 3H), 7.65-7.59 (m, 2H), 5.45 (s, 1H). C NMR (DMSO-d , 150 MHz): δ
6
(ppm) 198.0, 193.8, 155.4, 151.7, 134.9, 134.9, 134.8, 134.8, 133.7, 132.0, 131.8, 131.4,
1
7
1
30.6, 130.2, 129.6, 128.9, 128.8, 128.5, 126.9, 126.8, 126.3, 125.6, 125.0, 123.6, 117.6, 83.8,
9.2(CCHCl3), 56.8, 56.8. IR (KBr): 3452, 3258, 2188, 1739, 1637, 1568, 1440, 1350, 1270,
–1
+
120, 911, 876, 737 cm . HRMS (ESI): m/z [M+H] calcd for C28
H
19
N
4
O S: 475.12232;
2
found: 475.12191.
7
-(2-naphthoyl)-5-amino-3-imino-7a-(naphthalen-2-yl)-1-oxo-1,3,7,7a-tetrahydrop
yrrolo[1,2-c]thiazole-6-carbonitrile (5ia)
1
Yield 75%; yellow solid. mp 210-212 °C . H NMR (DMSO-d
6
, 600 MHz): δ (ppm) 10.19 (s,
1
H), 9.03 (s, 1H), 8.22 (s, 1H), 8.17-8.05 (m, 7H), 8.05-8.00 (m, 2H), 7.82 (d, J = 9.0 Hz, 1H),
13
7.72 (t, J = 7.8 Hz, 1H), 7.68-7.59 (m, 3H), 5.43 (s, 1H). C NMR (DMSO-d , 150 MHz): δ
6
(ppm) 196.0, 195.4, 156.0, 151.6, 135.6, 134.2, 133.2, 132.5, 132.1, 131.3, 130.0, 129.5,
1
29.2, 128.7, 128.5, 127.8, 127.6, 127.4, 127.2, 127.1, 124.5, 123.9, 122.8, 118.0, 82.8, 56.4,
–1
56.2. IR (KBr): 3380, 3279, 2176, 1741, 1637, 1449, 1353, 1105, 917, 751 cm . HRMS (ESI):
+
m/z [M+H] calcd for C28
H
19
N
4
O S: 475.12232; found: 475.12188.
2
5
,
-amino-7-benzoyl-3-(methylimino)-1-oxo-7a-phenyl-1,3,7,7a-tetrahydropyrrolo[1
2-c]thiazole-6-carbonitrile (5ab)
Yield 46%; yellow solid. mp 192-194 °C . H NMR (CDCl
1
3
, 600 MHz): δ (ppm) 7.99 (d, J =
7
7
.8 Hz, 2H), 7.65 (t, J = 7.8 Hz, 1H), 7.58 (d, J = 6.0 Hz, 2H), 7.52 (t, J = 7.8 Hz, 2H),
13
.48-7.42 (m, 3H), 6.59 (s, 2H), 4.70 (s, 1H), 3.22 (s, 3H). C NMR (CDCl , 150 MHz): δ
3
(ppm) 195.8, 193.4, 156.7, 148.7, 136.8, 134.6, 134.2, 129.6, 129.3, 129.2, 129.0, 125.0,
1
1
3
17.8, 81.9, 58.3, 57.6, 41.0. IR (KBr): 3359, 2975, 2895, 1925, 1661, 1446, 1381, 1089,
–
1
+
049, 881, 665 cm . HRMS (ESI): m/z [M+H] calcd for C21
H
17
N
4
O S: 389.1067; found:
2
89.1073.
-S13-

ACCEPTED MANUSCRIPT
5
-amino-7-benzoyl-3-(butylimino)-1-oxo-7a-phenyl-1,3,7,7a-tetrahydropyrrolo[1,2
-
c]thiazole-6-carbonitrile (5ac)
Yield 75%; red solid. mp 170-172 °C . H NMR (CDCl
Hz, 2H), 7.63 (t, J = 7.6 Hz, 1H), 7.58-7.55 (m, 2H), 7.51 (t, J = 8.0 Hz, 2H), 7.46-7.34 (m,
H), 6.78 (s, 2H), 4.68 (s, 1H), 3.42-3.20 (m, 2H), 1.72-1.57 (m, 2H), 1.47-1.32 (m, 2H), 0.95
1
3
, 400 MHz): δ (ppm) 7.98 (d, J = 8.0
3
13
(t, J = 7.2 Hz, 3H). C NMR (CDCl
3
, 100 MHz): δ (ppm) 195.7, 193.7, 156.8, 146.8, 136.9,
1
34.5, 134.3, 129.5, 129.2, 129.1, 128.9, 124.9, 118.0, 81.5, 58.2, 57.0, 54.7, 32.7, 20.4, 13.8.
–1
IR (KBr): 3324, 3223, 2959, 2188, 1742, 1655, 1448, 1215, 1035, 916, 811, 702 cm . HRMS
+
(ESI): m/z [M+H] calcd for C24
H
23 4
N O
2
S: 431.15362; found: 431.15439.
5
-amino-7-benzoyl-1-oxo-7a-phenyl-3-(phenylimino)-1,3,7,7a-tetrahydropyrrolo[1
,
2-c]thiazole-6-carbonitrile (5ad)
1
Yield 66%; yellow solid. mp 228-230 °C . H NMR (CDCl
3
, 600 MHz): δ (ppm) 8.01 (d, J =
7
.2 Hz, 2H), 7.69-7.63 (m, 3H), 7.57-7.46 (m, 5H), 7.37 (t, J = 7.8 Hz, 2H), 7.20 (t, J = 7.2
13
Hz, 1H), 7.06 (d, J = 7.8 Hz, 2H), 6.62 (s, 2H), 4.74 (s, 1H). C NMR (CDCl
3
, 150 MHz): δ
(ppm) 195.7, 193.3, 156.1, 149.4, 147.4, 136.5, 134.7, 134.2, 129.8, 129.5, 129.2, 129.1,
1
1
4
25.7, 124.9, 121.3, 82.1, 59.2, 58.1. IR (KBr): 3394, 3238, 2924, 2189, 1770, 1664, 1443,
–1
+
344, 1138, 1025, 927, 759, 701 cm . HRMS (ESI): m/z [M+H] calcd for C26
H
19
N
4
2
O S:
51.12232; found: 451.12252.
Reference:
1) Murai, M.; Yoshida, S.; Miki, K.; Ohe, K. Chem. Commun., 2010, 46, 3366.
(
4
. Molecular structure and crystallographic data of compounds 4ab, 4ac and 5aa
Figure S1 X-ray crystal structure of compounds 4ab
Crystal Data for Compound 4ab: C21 S, MW = 388.44, triclinic, a = 8.2937(17) Å, b =
0.301(2) Å, c = 11.634(2) Å, α= 104.611(3)°, β= 90.670(3)°, γ= 99.561(3)°, V = 947.0(3)
H
16 4
N O
2
1
-S14-

ACCEPTED MANUSCRIPT
3
-1
Å , T = 298(2) K , space group P-1, Z = 2, m(Mo–Ka) = 0.196 mm , 6761 reflections collected, 3862
unique [R(int) = 0.0234] which were used in all calculations. The final wR2 (F2) was 0.1360. CCDC
1010799 contains the supplementary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre.
Figure S2 X-ray crystal structure of compounds 4ad
Crystal Data for Compound 4ad: C26
H
18
N
4
O S, MW = 450.50, monoclinic, a = 8.703(5) Å, b =
2
3
17.389(11) Å, c = 15.391(9) Å, α= 90°, β= 104.495(9)°, γ= 90°, V = 2255(2) Å , T = 298(2)
-
1
K , space group P2(1)/n, Z = 4, m(Mo–Ka) = 0.175 mm , 15624 reflections collected, 4652 unique
R(int) = 0.0253] which were used in all calculations. The final wR2 (F2) was 0.1241. CCDC 1010798
[
contains the supplementary crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
Figure S3 X-ray crystal structure of compounds 5aa
Crystal Data for Compound 5aa: C20
H
14 4
N O
2
S, MW = 374.41, triclinic, a = 9.2655(15) Å, b =
9
.9525(16) Å, c = 12.714(2) Å, α= 111.089(2)°, β= 95.131(3)°, γ= 106.325(3)°, V = 1025.7(3)
3
-1
Å , T = 298(2) K , space group P-1, Z = 2, m(Mo–Ka) = 0.178 mm , 3992 reflections collected, 3992
unique [R(int) = 0.0000] which were used in all calculations. The final wR2 (F2) was 0.1441. CCDC
1010796 contains the supplementary crystallographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre.
1
13
5
. H NMR and C NMR spectra of compounds 4, 5, A and B.
-S15-

ACCEPTED MANUSCRIPT
-S16-

ACCEPTED MANUSCRIPT
-S17-

ACCEPTED MANUSCRIPT
-S18-

ACCEPTED MANUSCRIPT
-S19-

ACCEPTED MANUSCRIPT
-S20-