One-pot chemo/regio/stereoselective generation of a library of functionalized spiro-oxindoles/pyrrolizines/pyrrolidines from α-aroylidineketene dithioacetals

Article abstract of DOI:10.1039/c5ra05123a

An efficient chemo/regio/stereoselective synthesis of novel and functionalized spiro-oxindole/pyrrolizine/pyrrolidine scaffolds has been achieved. The in situ generated azomethine ylide from isatin & l-proline/phenyl alanine underwent 1,3-dipolar cycloadd

Full text of DOI:10.1039/c5ra05123a

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One-pot chemo/regio/stereoselective generation
of a library of functionalized spiro-oxindoles/
pyrrolizines/pyrrolidines from a-aroylidineketene
dithioacetals†
Cite this: RSC Adv., 2015, 5, 33705
Pandi Dhanalakshmi, Seenivasagaperumal Sriram Babu,
Solaimalai Thimmarayaperumal and Sivakumar Shanmugam*
An efficient chemo/regio/stereoselective synthesis of novel and functionalized spiro-oxindole/pyrrolizine/
pyrrolidine scaffolds has been achieved. The in situ generated azomethine ylide from isatin & L-proline/
phenyl alanine underwent 1,3-dipolar cycloaddition with a-aroylidineketene dithioacetals under simple
reaction conditions affording spiro-oxindole derivatives. This protocol exhibits an interesting double
bond selectivity of a-aroylidineketene dithioacetals. Furthermore, utilizing this spiro-oxindoles scaffold,
biologically important benzimidazole and pyrimidine based poly heterocycles were also synthesized.
Received 23rd March 2015
Accepted 31st March 2015
DOI: 10.1039/c5ra05123a
www.rsc.org/advances
6
-pyrrolylpyrimidine by 1,3-dipolar cycloaddition of a-aroylidi-
neketene dithioacetals, (p-tolylsulfonyl)methyl isocyanide
multicomponent
Introduction
Assembly of polycyclic frameworks is a fascinating topic of (TosMIC) and guanidine nitrate via
a
1
22
interest to many researchers in modern organic chemistry. The reaction.
framework present in the spiro-oxindole core is part of a large
Multicomponent reactions (MCRs) are eco-friendly reac-
number of bioactive, naturally occurring alkaloids and medic- tions wherein three or more components react to yield complex
23
2
–4
inally relevant compounds.
For example, the naturally molecules with high atom economy by incorporating all the
5
6
occurring (ꢀ)-horsline, spirotryptostatin A & B, (+)-elaco- starting materials. MCRs are cost and time effective and afford
7
8
mine, alstonisine and MI-129 (ref. 9) comprise spiro-oxindole the desired products in good yield under simple and mild
24
skeleton (Fig. 1). These compounds were reported to show reaction conditions in synthetic organic chemistry and drug
antitubercular and discovery programs. These synthetic methods provide quick
anti-infective properties. At the same time, the highly access to offer more powerful platform to assemble libraries of
substituted pyrrolidine system is constituted as core skeleton of structurally complex molecules.
many natural products.
The 1,3-dipolar cycloaddition is one of the most prominent emerged as versatile intermediates in organic synthesis to
1
0,11
12
25
antibacterial, antitumor, antibiotic,
13
26
1
4
Over the decades, a-aroylidineketene dithioacetals 3 have
15
protocol to construct spiro-oxindoles starting from simple synthesize substituted and fused aromatic heterocyclic frame-
substrates. This is exemplied by the increased number of works.
16
22,27
In the present work, we report the multicomponent
publications depicting the synthesis of novel spiro heterocycles reaction involving a 1,3-dipolar cycloaddition of 3, isatin and
via 1,3-dipolar cycloaddition with different dipolarophiles in
17–19
recent time.
In particular, the multicomponent 1,3-dipolar
cycloaddition of azomethine ylides generated in situ from the
decarboxylative condensation of 1,2-dicarbonyl compounds and
a-amino acids to exocyclic olenic dipolarophiles have attracted
20
a great deal of attention.
In addition, cycloaddition on various dipolarophiles such as
21
di and tribenzylidine acetone has been extensively studied.
Recently, we have reported a chemo/regioselective synthesis of
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University,
Madurai – 625 021, Tamil Nadu, India. E-mail: shivazzen@mkuniversity.org
†
Electronic supplementary information (ESI) available. CCDC 988416–988419
and 1040486. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c5ra05123a
Fig. 1 Biologically important spiro-oxindoles/pyrrolidine scaffold.
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0
a-amino acid to afford spiro-oxindole derivatives. To the best of Table 2 One-pot multicomponent synthesis of 2 -(3,3-bis(methyl-
0
0
0
0
0
0
0
0
thio)acryloyl)-1 -(aryl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -
our knowledge, this is the rst report on the synthesis of spiro-
oxindole derivatives from a-aroyilidineketene dithioacetals 3.
a
pyrrolizin]-2-one 4
Results and discussion
22
Following our reported procedure variety of a-aroylidineketene
dithioacetals were synthesized by condensing 4,4-
3
bis(methylthio)but-3-en-2-one with various aryl/heteroaryl alde-
hydes under basic conditions in excellent yields. For the
preliminary investigation, the cycloaddition of isatin 1a, L-proline
ꢁ
2
a and 3l was performed in acetonitrile (ACN) at 70 C for 90 min
(
Table 1, entry 1). This condition results only one product which
b
0
0
Entry
Ar 3
Product
Yield (%)
was characterised as 2 -(3,3-bis(methylthio)acryloyl)-1 -(4-bro-
0
0
0
0
0
0
0
mophenyl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrro-
lizin]-2-one 4l which reveals that the in situ generated azome-
thine ylide undergoes a 1,3-dipolar cycloaddition only on the
double bond B of 3 rather than A. The more polar nature of
push–pull alkene (A) of 3, prevents the double cycloaddition
even though isatin and L-proline were taken as excess.
This selective cycloaddition is signicant to build a library of
poly heterocycles for biological screening. An efficient way to
generate 4l was encouraged us to further optimize the reaction
conditions by varying the reaction temperature and solvent
1
2
3
4
5
6
7
8
9
C
6
H
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
91
94
92
95
96
92
90
96
93
98
94
99
88
90
91
90
86
88
90
93
92
2-CH –C H
4-CH
4-CH(CH
4-OEt–C
2-OMe–C
3-OMe–C
4-OMe–C H4
6
2-F–C
4-F–C
2-Br–C
4-Br–C
4-CN–C
2,4-Cl –C
2,4-F –C
3,4-OMe–C
2-OMe,5-Br–C H3
2-Cl,5-NO
3-Br,4-F–C
5-Br–C
5-Br–C
3
6
4ꢀ
4ꢀ
3
–C
6
H
)
3
2
–C
6
H
4
6
H
4
6
H
H
4
4
6
6
H
H
4
1
1
1
1
1
1
1
0
1
2
3
4
5
6
6
4
6
H
4
6
H
4
(
Table 1).
6
H
4
2
6
H
3
2
6 3
H
6
H
3
Table 1 Optimization of the reaction conditions for three component
synthesis of 4l
a
17
6
18
19
20
21
2 6 3
–C H
6
H
3
4s
4t
4u
4
H
H
2
S
N
5
3
a
Reaction conditions: 1a (1 mol), 2a (1 mol), 3a–u (1 mol), methanol
ꢁ
b
(10 vol), reux at 60 C for 1 h. Isolated yield aer recrystallization
from ethanol–DCM mixture.
Solvent plays a crucial role in the effective formation of 4l in
high yield. Compound 4l was isolated in 89% yield, when isatin
1
a and L-proline 2a was heated with dipolarophile 3l for 90 min at
ꢁ
90 C in ethanol (Table 1, entry 2). Almost quantitative yield 99%
e
ꢁ
b
Entry
Solvent
Temp. ( C)
Time (min)
Yield (%) was obtained when the cycloaddition was performed in methanol
Table 1 entry 3), while other alcoholic solvents such as ethanol,
(
1
2
3
4
5
6
7
8
9
ACN
70
90
65
rt
65
80
80
69
90
100
40
65
100
90
90
60
120
90
90
90
89
99
65
65
70
50
50
78
92
96
88
85
isopropyl alcohol (IPA) gave only moderate yields (Table 1
entries 1 & 7). Notably, cycloaddition using methanol at room
temperature suppressed the product yield (Table 1, entry 4).
Meanwhile, diluting the reaction could dramatically reduce
the yield of 4l (Table 1, entries 5 & 6). Aprotic solvents like THF
(Table 1, entry 8) and 1,4-dioxane (Table 1, entry 9) provided
reduced yields, while solvent like DMF (Table 1, entry 10) gave 4l
in 92% yield. Quite impressively, the corresponding product 4l
was obtained in 96% yield in dichloromethane (Table 1, entry
EtOH
MeOH
MeOH
c
c
MeOH/H
2
O
2
EtOH/H O
d
IPA
THF
4
c
c
c
c
c
c
90
60
60
90
60
60
1,4-Dioxan
DMF
1
1
1
1
0
1
2
3
DCM
Benzene
Toluene
11). The product yield was drastically reduced, when the reac-
tion was conducted in nonpolar solvents such as benzene and
a
a-Aroylidineketene dithioacetals 3l (1 mol), isatin 1a (1 mol) and toluene (Table 1, entries 12 & 13).
b
L-proline 2a (1 mol), solvent (10 vol), temp., time. Isolated yields.
c
e
d
Polar solvents afforded 4l as a solid aer the initial work up
without need of additional purication. The 1,3-dipolar
Yields aer column chromatography. Reaction time in hour.
Reactions performed at the boiling points of the respective solvents.
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a
Table 3 Scope of the isatin
Fig. 4 X-Ray crystal structures of 4kb.
Scheme 1 Reaction of 1a, 2a and 3l in gram scale.
a
All the reactions were carried out with 1b–d (1 mol), 2a (1 mol) and 3
1 mol) in 5 mL of MeOH and yields were isolated aer recrystallization
(
from ethanol–DCM mixture.
Scheme 2 Plausible mechanism for 4.
and functional group tolerance of this new transformation
under optimized condition, in order to nd out the generality of
the reaction (Table 2). A broad range of dipoles and dipolar-
ophiles provided an access to diverse array of functionalized
spiroindoline-pyrrolizine intermediates in excellent yield.
Varying the substituents of dipolarophile, the reaction was
compatible with all halogenated derivatives such as 4i, 4j, 4k, 4l,
4n, 4o and 4s in excellent yield (Table 2). Interestingly, dipo-
Fig. 2 X-Ray crystal structures of 4l.
larophiles containing heterocyclic moieties such as 4t & 4u also
provided the desired spiro scaffold without any difficulties
cycloaddition of 3l (1 mol), isatin 1a (1 mol), and L-proline 2a (Table 2, entries 20 & 21).
ꢁ
(
1 mol) in methanol at 65 C for 60 min via MCR was found to be
We explored the possibility of generating azomethine ylide
the best optimized reaction condition to afford 4l in excellent from substituted isatin and L-proline. Derivatives of isatins 1b–d
yield (Table 1, entry 3). We then examined the substrate scope such as 5-methoxy, 5-nitro and 6-bromo were reacted with
Scheme 3 Three component synthesis of 5b using primary amino
Fig. 3 X-Ray crystal structures of 4db.
acid.
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Table 4 Synthesis of functionalized spiro-pyrrolidine derivatives 5 via
a
sequential addition
Scheme 4 Utility of 4h towards the synthesis of spiro-benzimidazole
8a (method A). Reaction conditions: (i) 4h (1 mol), 7 (1 mol), AcOH/
water, reflux, 1 h.
(Scheme 1). It is worth mentioned that this could be highly
important in the synthetic application.
As shown in Scheme 2, we postulated the plausible mecha-
nism for the regio and stereoselective formation of spiro-
oxindoles. Initially, the reaction proceeds via condensation of
1
and 2 to furnish intermediate imine I followed by loss of CO
2
to generate azomethine ylide II. Finally, electron rich carbon of
azomethine ylide II undergoes 1,3-dipolar cycloaddition selec-
tively with b-carbon of double bond B of 3 to afford spiro-
cycloadducts 4 with four stereogenic center.
To elaborate the scope of this present protocol, L-proline was
replaced with primary amino acid such as L-phenyl alanine 2b
(Scheme 3). The cycloaddition of 3b, 1a and L-phenylalanine 2b
were performed under the optimized reaction conditions to
furnish 60% yield of expected product 5b along with 2-((1Z,4E)-
a
Reaction conditions: (i) 1 (1 mol), 2b (1 mol), methanol (10 vol), RT,
5 min. (ii) 3 (1 mol) reux at 60 C for 1 h. Yields aer column
5-(4-methoxyphenyl)-1-(methylthio)-3-oxopenta-1,4-dienylamino)-
ꢁ
1
2-phenylacetic acid 6 in 20% yield (Scheme 3, conrmed by
chromatography.
LC-MS).
To avoid the formation of S,N-acetal 6, the sequential addi-
L-proline with various dipolarophiles underwent multicompo- tion was performed by mixing phenylalanine 2b, isatin 1a
nent cycloaddition to afford spiro-oxindoles 4 in excellent yields together for 15 min, once the formation of azomethine ylide was
(Table 3). In all the cases, the product was isolated without the conrmed the compound 3b was added to the mixture to reux
need of any additional purication (Table 3). The products 4 for 1 h. The sequential cycloaddition was successful to afford 5b
1
13
were well characterized by H, C, and mass spectral data.
in 80% yield. Using this technique several novel spiro-
In order to determine the stereoselectivity, the structure of 4l pyrrolidine 5 were synthesized in good yield (Table 4). The
Fig. 2), 4db (Fig. 3) and 4kb (Fig. 4) was conrmed by single structure of 5g was conrmed on the basis of single crystal X-ray
crystal X-ray analysis. This cycloaddition is stereoselective analysis (Fig. 5).
(
28
28
affording only one diastereomer of 4 exclusively, even though
Recently, aryl substituted ketene dithioacetals 3 has been
four stereocenters are present in these cycloadducts.
reported to aid the synthesis of molecules which demonstrates
29
The present protocol was examined with 3l by performed on antileishmanial activity. With the ready accessibility of spiro
a larger scale to give 4l in excellent yield which reects the based diverse ketene dithioacetal scaffold established, next, the
generality and ease of performing on milligram scale synthetic potential of 4 has been illustrated through the
Scheme 5 Synthesis of 8a via MCR (method B). Reaction conditions:
(
i) 3h (1 mol), 1a (1 mol), 2a (1 mol), and 7 (1 mol), AcOH (cat.)/H
2
O,
Fig. 5 X-Ray crystal structures of 5g.
reflux, 1 h.
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a
Table 6 Synthesis of spiro-pyrimidines 10a–d
Scheme 6 Synthesis of spiro benzimidazole 8a via 2-styryl benz-
imidazole 9.
synthesis of new compounds with additional heterocycles such
as benzimidazole and pyrimidine.
a
Reaction conditions: (i) 4 (1 mol), guanidine nitrate (1.5 mol), NaH
ꢁ
(1.5 mol), MeOH or EtOH, 65–70 C, 10 h. Isolated yield aer column
Poly heterocylces 8a was achieved from the cyclo- chromatography.
30
condensation reaction of the 4h with OPD 7 in AcOH
cat.)/H O media (Scheme 4). Inspired by the successful results,
(
2
active poly heterocycles 8a–c were synthesised from corre-
sponding substituted reagent 4 (Table 5). However, biologically
important benzimidazole with spiro-oxindole skeleton is rare
combinations in organic synthesis.
The curiosity towards the synthesis of poly heterocycles
which contains biologically active pyrimidine moiety 10 was
intensied by exploring our reported procedure. However,
compound 4 was allowed to react with guanidine nitrate in the
presence of NaH base under reux condition for 10 h to afford
few spiro compounds 4 was investigated with OPD 7 under
acidic condition. To optimize the best reaction condition, three
different methods were executed to obtain 8. In method A,
compound 4h and 7 was allowed to undergo cyclocondensation
ꢁ
in dilute acid condition at 100 C for 1 h to afford 8 in 78% yield.
Water being a greened solvent was the preferred choice though
similar results were observed with methanol and ethanol
22
(
Scheme 4, method A).
1
The cyclocondensation product 8a was conrmed by H &
1
0a–d in good yields (Table 6).
The current work depicts the potential of a-aroylidineketene
1
3
C NMR spectroscopy. Next, the cycloaddition was proceeding
via MCR by involving 3h, 1a, 2a and OPD 7 in the presence of
catalytic amount of AcOH in water at reux for 1 h to afford 8a in
dithioacetal as key synthetic intermediates. The methodology
described in this paper provides environmentally attractive
synthetic approach with very high yields and atom efficiency.
Moreover, this synthetic protocol provided a practical access to
various biologically important N-based poly heterocycles with
minimum number of synthetic steps.
30% yield (Scheme 5 method B).
We have acquired a new method to synthesize 8a even
though MCR reaction gives 30% yield, as it involves additional
purications steps. Alternatively, in step-I, styryl benzimidazole
9
was synthesized in 87% yield by condensing 3h and 7 under
AcOH/H O media. In the step-II, styryl benzimidazole 9 was
2
reacted with azomethine ylide (adduct of 1a and 2a) to give 8a in Conclusions
very poor yield (10%, Scheme 6).
In summary, we have demonstrated the straight forward chemo/
Among three different methods, method A (cyclization
reaction of 4h with OPD 7) was the best on the basis of yields
and isolation procedure. Following method A, biologically
regio/stereoselective synthesis of spiro-oxindole/pyrrolidine/
derivatives in excellent yields with four chiral centers. The
current method discloses many advantages such as high atom
economy, ready accessibility of the starting materials, simple
reaction conditions under greener medium. This protocol
involves in broad substrate scope, excellent functional group
tolerance and leaves active site for further synthetic trans-
formation. Furthermore, the utility of cycloadduct was demon-
strated through the synthesis of N-based poly heterocycles such
as benzimidazole/pyrimidine moieties with spiro platform.
Table 5 Synthesis of poly heterocycles 8 containing benzimidazole
a
moiety
Experimental section
General remarks
Melting points were determined in open capillary tubes and
were uncorrected. IR spectra were taken on a Jasco FT-IR
ꢀ
1
a
instrument in KBr pellets and reported in cm . Mass spectra
were performed with Agilent mass spectrometer and recorded
Reaction conditions: (i) 4h (1 mol), 7 (1 mol), AcOH/water, reux, 1 h,
yields given aer column chromatography.
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in positive & negative mode with an ESI source. The H and
Paper
1
13
C
(d, J ¼ 7.6 Hz, 1H), 6.91 (t, J ¼ 7.2 Hz, 1H), 7.11–7.17 (m, 3H), 7.27
1
3
NMR spectra of the new compounds were measured at 300 and (t, J ¼ 8 Hz, 3H), 10.45 (s, 1H); C NMR (100 MHz, DMSO-d ) d :
6
C
400 MHz in DMSO-d6 with TMS as the internal standard. 14.5, 16.7, 19.0, 21.0, 27.5, 30.5, 47.6, 51.2, 56.5, 67.9, 72.9, 73.4,
Chemical shis are expressed in ppm, coupling constant 110.0, 112.1, 121.5, 126.1, 127.2, 128.0, 129.4, 129.5, 136.0, 138.1,
ꢀ
1
(
J values) are given in Hertz (Hz) and spin multiplicities are 142.5, 163.3, 180.2, 189.0; IR (ATR KBr cell, cm ) 730, 1148,
indicated by the following symbols: s (singlet), d (doublet), 1430, 1500, 1616, 1726, 2800, 3298; LC-MS calcd m/z: 464 found
+
28 2 2 2
t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), td 465 [(M + 1)] . Anal. calcd for C26H N O S : C, 67.21; H, 6.07; N,
(
triplet of doublets). Elemental analyses were carried out with 6.03: found; C, 67.18; H, 6.05; N, 6.00.
0
0
0
0
0
Perkin Elmer 2400 Series II analyzer. Silica gel-G plates (Merck)
were used for TLC analysis with a mixture of petroleum ether 6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4d. Off
2 -(3,3-Bis(methylthio)acryloyl)-1 -(4-isopropylphenyl)-1 ,2 ,5 ,
0
0
0
0
ꢁ
ꢁ
1
(60–80 C) and ethyl acetate as eluent. All chemicals were white solid; isolated yield 0.32 (95%); M. Pt. 134–136 C; H NMR
purchased and used without further purication.
(400 MHz, DMSO-d ) d : 1.17 (s, 3H), 1.19 (s, 3H), 1.62–1.68 (m,
6 H
2
1
3
H), 1.76–1.81 (m, 2H), 2.14 (s, 3H), 2.32 (s, 3H), 2.33–2.38 (m,
H), 2.40–2.44 (m, 1H), 2.80–2.87 (m, 1H), 3.43–3.47 (m, 1H),
.63–3.76 (m, 2H), 3.98 (d, J ¼ 11.6 Hz, 1H), 5.61 (s, 1H), 6.77 (d,
General procedure for the synthesis of 4
A mixture of isatin 1 (1 mol), L-proline 2 (1 mol) and 1,1- J ¼ 7.6 Hz, 1H), 6.91 (t, J ¼ 7.6 Hz, 1H), 7.13–7.20 (m, 3H), 7.24 (t,
1
3
bis(methylthio)-5-arylpenta-1,4-dien-3-one 3 (1 mol) was heated J ¼ 7.2 Hz, 1H), 7.31 (d, J ¼ 8 Hz, 2H), 10.46 (s, 1H); C NMR (100
ꢁ
to reux in methanol (3 ml) at 65 C for indicated time (Table 2). MHz, DMSO-d
) d : 14.5, 16.6, 19.0, 24.4, 27.5, 30.5, 47.6, 51.2,
6 C
Aer completion of the reaction (TLC), the mixture was cooled 56.5, 67.9, 72.9, 73.5, 110.0, 112.1, 121.5, 126.2, 127.2, 128.1,
to room temperature and poured in to ice cold water. Then the 129.4, 138.5, 142.6, 147.0, 163.3, 180.2, 189.0; IR (ATR KBr cell,
ꢀ
1
resulting solid was ltered and recrystallized from ethanol– cm ) 750, 1136, 1483, 1616, 1728, 2980, 3217; LC-MS calcd m/z:
+
DCM to give analytically pure product 4.
492 found 493 [(M + 1)] . Anal. calcd for C28
32 2 2 2
H N O S : C, 68.26;
0
0
0
0
0
0
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -phenyl-1 ,2 ,5 ,6 ,7 ,7a -hexa- H, 6.55; N, 5.69; found: C, 68.22; H, 6.51; N, 5.65.
0
0 0 0 0 0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(4-ethoxyphenyl)-1 ,2 ,5 ,6 ,
hydrospiro[indoline-3,3 -pyrrolizin]-2-one 4a. Off white solid;
ꢁ
1
0
0
0
isolated yield 0.328 g (91%); M. Pt. 160–162 C; H NMR (400 7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4e. Off
ꢁ
1
MHz, DMSO-d
6
) d
H
: 1.65–1.69 (m, 2H), 1.78–1.83 (m, 2H), 2.15 white solid; isolated yield 0.309 g (96%); M. Pt. 166–168 C; H
) d
(
3
6
s, 3H), 2.23 (s, 3H), 2.33–2.37 (m, 1H), 2.40–2.49 (m, 1H), 3.68– NMR (400 MHz, DMSO-d
6
H
: 1.30 (t, J ¼ 6.8 Hz, 1H), 1.62–1.68
.77 (m, 2H), 4.00 (d, J ¼ 11.9 Hz, 1H), 6.77 (d, J ¼ 7.6 Hz, 1H), (m, 2H), 1.75–1.82 (m, 2H), 2.15 (s, 3H), 2.24 (s, 3H), 2.31–2.36
.92 (td, J ¼ 0.4 Hz, 7.6 Hz, 1H), 7.14–7.26 (m, 3H), 7.33 (t, J ¼ 7.6 (m, 1H), 2.38–2.44 (m, 1H), 3.61–3.72 (m, 2H), 3.92 (d, J ¼ 11.6
1
3
Hz, 2H), 7.39 (d, J ¼ 6.8 Hz, 2H), 10.46 (s, 1H); C NMR (100 Hz, 1H), 3.99 (q, J ¼ 6.8 Hz, 2H), 5.62 (s, 1H), 6.76 (d, J ¼ 7.6 Hz,
MHz, DMSO-d ) d : 15.5, 16.6, 27.4, 30.5, 47.6, 51.5, 67.9, 72.9, 2H), 6.85–6.95 (m, 3H), 7.16 (d, J ¼ 7.6 Hz, 1H), 7.24 (d, J ¼ 7.6
6
C
1
3
7
1
1
4
3.5, 110.0, 112.1, 121.5, 126.1, 127.0, 127.2, 128.2, 129.0, 129.5, Hz, 1H), 7.28 (d, J ¼ 8.4 Hz, 2H), 10.44 (s, 1H); C NMR (100
ꢀ1
41.2, 142.6, 163.4, 180.1, 189.0; IR (ATR KBr, cm ) 702, 748, MHz, DMSO-d
6 C
) d : 14.5, 15.2, 16.7, 27.4, 30.5, 47.6, 50.7, 63.4,
134, 1489, 1502, 1616, 1708, 2850, 3082, 3188; LC-MS calcd m/z: 68.0, 72.9, 73.4, 110.0, 112.2, 114.9, 121.5, 126.2, 127.2, 129.1,
+
50 found 451 [(M + 1)] . Anal. calcd for C25
H
26
N
2
O
2
S
2
: C, 66.63; 129.4, 132.8, 142.5, 157.7, 163.2, 180.2, 189.9.; IR (ATR KBr cell,
ꢀ
1
H, 5.82; N, 6.22; found: C, 66.60; H, 5.77; N, 6.20.
cm ) 713, 1192, 1571, 1640, 1716, 2870, 3280; LC-MS calcd m/z:
0
0
0
0
0
0
0
0
+
2
-(3,3-Bis(methylthio)acryloyl)-1 -o-tolyl-1 ,2 ,5 ,6 ,7 ,7a -hexa- 494 found 495 [(M + 1)] . Anal. calcd for C27
H
30
N
2
O
3
S
2
: C, 65.56;
0
hydrospiro[indoline-3,3 -pyrrolizin]-2-one 4b. Off white solid; H, 6.11; N, 5.66; found: C, 65.53; H, 6.08; N, 5.64.
ꢁ
1
0
0
0
0
0
0
isolated yield 0.33 g (94%); M. Pt. 158–160 C; H NMR (400
MHz, DMSO-d ) d : 1.59–1.68 (m, 2H), 1.77–1.83 (m, 2H), 2.14 7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4f. Off
s, 3H), 2.22 (s, 3H), 2.35–2.48 (m, 2H), 2.49 (s, 3H), 3.74–3.78 white solid; isolated yield 0.315 g (92%); M. Pt. 138–140 C; H
) d : 1.64–1.70 (m, 2H), 1.76–1.81 (m,
.77–6.79 (m, 1H), 6.92–6.96 (m, 1H), 6.98–7.09 (m, 1H), 7.14– 3H), 2.14 (s, 3H), 2.22 (s, 3H), 2.31–2.40 (m, 2H), 3.64–3.69 (m,
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2-methoxyphenyl)-1 ,2 ,5 ,6 ,
0
0
0
6
H
ꢁ
1
(
(
6
7
m, 1H), 3.92–3.94 (m, 1H), 3.96 (d, J ¼ 9.24 Hz, 1H), 5.52 (s, 1H), NMR (400 MHz, DMSO-d
6
H
1
3
.25 (m, 4H), 7.38 (d, J ¼ 7.32 Hz, 1H), 10.50 (s, 1H); C NMR 1H), 3.82 (s, 3H), 4.03–4.08 (m, 1H), 4.24 (d, J ¼ 12.4 Hz, 1H),
) d
: 14.8, 17.2, 19.0, 19.8, 20.3, 27.6, 30.7, 5.66 (s, 1H), 6.77 (d, J ¼ 7.6 Hz, 1H), 6.94 (q, J ¼ 7.2 Hz, 2H), 6.99
6.3, 69.7, 73.5, 110.1, 111.8, 121.7, 126.1, 126.4, 126.5, 126.6, (d, J ¼ 8 Hz, 1H), 7.14–7.21 (m, 3H), 7.32 (d, J ¼ 6.4 Hz, 1H),
(100 MHz, DMSO-d
6
C
4
1
1
1
1
3
6 C
26.7, 126.8, 127.0, 129.4, 129.5, 130.6, 131.2, 137.1, 137.6, 10.44 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.6,
ꢀ
1
39.6, 142.5, 163.3, 180.1, 188.9; IR (ATR KBr cell, cm ) 726, 31.1, 45.3, 47.3, 56.1, 66.0, 72.1, 73.4, 110.1, 111.7, 111.8, 121.1,
030, 1480, 1587, 1602, 1740, 2984, 3178; LC-MS calcd m/z: 464 121.5, 126.4, 126.8, 128.0, 128.6, 129.4, 142.7, 158.0, 163.3,
+
ꢀ1
found 465 [(M + 1)] . Anal. calcd for C26
H
28
N
2
O
2
S
2
: C, 67.21; H, 180.0, 189.3; IR (ATR KBr cell, cm ) 748, 1024, 1240, 1492,
6
.07; N, 6.03; found: C, 67.15; H, 6.03; N, 6.01.
1618, 1716, 2872, 2960, 3134; LC-MS calcd m/z: 480 found 481
0
0
0
0
0
0
0
0
+
2
-(3,3-Bis(methylthio)acryloyl)-1 -p-tolyl-1 ,2 ,5 ,6 ,7 ,7a -hexa- [(M + 1)] . Anal. calcd for C26
H
28
N
2
O
3
S
: C, 64.97; H, 5.87; N,
2
0
hydrospiro[indoline-3,3 -pyrrolizin]-2-one 4c. Off white solid; 5.83; found: C, 64.92; H, 5.83; N, 5.80.
ꢁ
1
0 0 0 0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(3-methoxyphenyl)-1 ,2 ,5 ,
isolated yield 0.323 g (92%); M. Pt. 158–160 C; H NMR (400
MHz, DMSO-d ) d : 1.62–1.70 (m, 2H), 1.75–1.82 (m, 2H), 2.15 (s, 6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4g. Off
0
0
0
0
6
H
ꢁ
1
3
1
H), 2.25 (s, 3H), 2.31 (s, 3H), 2.32–2.38 (m, 1H), 2.40–2.44 (m, white solid; isolated yield 0.309 g (90%); M. Pt. 146–148 C; H
H), 3.63–3.74 (m, 2H), 3.96 (d, J ¼ 11.6 Hz, 1H), 5.62 (s, 1H), 6.77 NMR (400 MHz, DMSO-d ) d : 1.65–1.69 (m, 2H), 1.77–1.82 (m,
6
H
33710 | RSC Adv., 2015, 5, 33705–33719
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0 0 0 0 0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2-bromophenyl)-1 ,2 ,5 ,6 ,
3
1
6
H), 2.15 (s, 3H), 2.23 (s, 3H), 2.32–2.34 (m, 1H), 2.40–2.48 (m,
H), 3.65–3.95 (m, 5H), 3.97 (d, J ¼ 11.5 Hz, 1H), 5.63 (s, 1H), 7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4k. Off
0
0
0
ꢁ
1
.75–6.79 (m, 2H), 6.91 (td, J ¼ 0.76 Hz, 7.56 Hz, 1H), 6.95–6.97 white solid; isolated yield 0.303 g (94%); M. Pt. 154–156 C; H
(
(
m, 2H), 7.17 (td, J ¼ 0.96 Hz, 8 Hz, 1H), 7.21–7.26 (m, 2H), 10.48 NMR (400 MHz, DMSO-d ) d : 1.64–1.78 (m, 4H), 2.14 (s, 3H),
6
H
13
s, 1H); C NMR (100 MHz, DMSO-d
6
) d
0.4, 47.6, 51.5, 55.4, 56.5, 67.7, 72.8, 73.5, 110.0, 112.1, 112.2, Hz, 1H), 4.28 (t, J ¼ 11.6 Hz, 1H), 5.56 (s, 1H), 6.78 (d, J ¼ 7.2 Hz,
14.2, 120.2, 121.5, 126.1, 127.2, 129.5, 130.0, 142.6, 142.9, 1H), 6.94 (t, J ¼ 7.2 Hz, 1H), 7.12–7.19 (m, 3H), 7.37 (d, J ¼ 7.6
59.8, 163.4, 180.1, 189.0; IR (ATR KBr cell, cm ) 715, 781, Hz, 1H), 7.51 (d, J ¼ 8 Hz, 1H), 7.61 (d, J ¼ 8 Hz, 1H), 10.49 (s,
C
: 14.5, 16.7, 19.0, 27.4, 2.22 (s, 3H), 2.33–2.48 (m, 2H), 3.65–3.70 (m, 1H), 4.11 (d, J ¼ 12
3
1
1
1
ꢀ
1
1
3
051, 1268, 1379, 1480, 1649, 1729, 2873, 1046, 3189; LC-MS 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.3, 30.1,
6 C
+
calcd m/z: 480 found 481 [(M
+ 1)] . Anal. calcd for 47.5, 49.4, 67.9, 73.3, 73.5, 110.3, 111.6, 121.7, 125.5, 126.0,
C H N O S : C, 64.97; H, 5.87; N, 5.83; found: C, 64.93; H, 128.6, 128.7, 128.8, 129.7, 133.2, 140.0, 142.7, 163.8, 179.8,
2
6
28 2 3 2
ꢀ
1
5
.80; N, 5.78.
188.5; IR (ATR KBr cell, cm ) 713, 1197, 1425, 1602, 1716, 2918,
0
0
0
0
0
+
2
0
-(3,3-Bis(methylthio)acryloyl)-1 -(4-methoxyphenyl)-1 ,2 ,5 , 3200; LC-MS calcd m/z: 529 found 530 [(M + 1)] . Anal. calcd for
,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4h. Off C H BrN O S : C, 56.71; H, 4.76; N, 5.29; found: C, 56.68; H,
0
0
0
6
2
5
25
2 2 2
ꢁ
1
white solid; isolated yield 0.329 g (96%); M. Pt. 154–156 C; H 4.70; N, 5.24.
NMR (400 MHz, DMSO-d
2
1
1
0
0
0
0
0
0
6
) d
H
: 1.66–1.68 (m, 2H), 1.75–1.81 (m,
2 -(3,3-Bis(methylthio)acryloyl)-1 -(4-bromophenyl)-1 ,2 ,5 ,
0
0
0
0
H), 2.15 (s, 3H), 2.24 (s, 3H), 2.30–2.34 (m, 1H), 2.35–2.41 (m, 6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4l. Off
ꢁ
1
H), 3.60–3.72 (m, 5H), 3.91 (d, J ¼ 11.56 Hz, 1H, 3H), 5.61 (s, white solid; isolated yield 0.319 g (99%); M. Pt. 158–160 C; H
H), 6.76 (d, J ¼ 7.64 Hz, 1H), 6.87–6.92 (m, 3H), 7.16 (dd, J ¼ NMR (400 MHz, DMSO-d ) d : 1.64–1.70 (m, 4H), 1.78–1.82 (m,
6
H
.68 Hz, 7.64 Hz, 1H), 7.24 (d, J ¼ 7.36 Hz, 1H), 7.30 (d, J ¼ 7.36 2H), 2.15 (s, 3H), 2.25 (s, 3H), 2.31–2.36 (m, 1H), 2.39–2.45 (m,
1
3
Hz, 1H), 10.50 (s, 1H); C NMR (100 MHz, DMSO-d
6
) d
6.7, 27.4, 30.5, 47.6, 50.7, 55.5, 68.0, 72.9, 73.4, 110.0, 112.1, Hz, 1H), 6.91 (td, J ¼ 0.8 Hz, 7.6 Hz, 1H), 7.17 (td, J ¼ 1.2 Hz, 7.6
14.4, 121.5, 126.1, 127.2, 129.1, 129.4, 132.9, 142.5, 158.4, Hz, 1H), 7.24 (d, J ¼ 7.6 Hz, 1H), 7.36 (d, J ¼ 8.4 Hz, 2H), 7.51 (d,
C
: 14.5, 1H), 3.70 (m, 2H), 3.95–3.98 (m, 1H), 5.60 (s, 1H), 6.77 (d, J ¼ 7.6
1
1
1
1
4
5
ꢀ
1
13
63.2, 180.1, 189.0; IR (ATR KBr cell, cm ) 750, 1041, 1234, J ¼ 8.4 Hz, 2H), 10.49 (s, 1H); C NMR (100 MHz, DMSO-d ) d :
6
C
479, 1604, 1728, 2892, 3064, 3199; LC-MS calcd m/z: 480 found 14.1, 16.3, 27.0, 29.9, 47.2, 50.4, 67.4, 72.2, 73.0, 109.6, 111.6,
+
81 [(M + 1)] . Anal. calcd for C H N O S : C, 64.97; H, 5.87; N, 119.6, 121.1, 125.5, 126.8, 129.1, 130.1, 131.4, 140.3, 142.1,
2
6
28 2 3 2
ꢀ
1
.83; found: C, 64.93; H, 5.83; N, 5.79.
163.2, 179.6, 188.3; IR (ATR KBr cell, cm ) 749, 1128, 1428,
-(3,3-Bis(methylthio)acryloyl)-1 -(2-uorophenyl)-1 ,2 ,5 ,6 , 1614, 1720, 2829, 3153; LC-MS calcd m/z: 529 found 530 [(M +
0
0
0
0
0
0
2
0
0
0
+
7
,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4i. Off 1)] . Anal. calcd for C H BrN O S : C, 56.71; H, 4.76; N, 5.29;
25 25 2 2 2
ꢁ
1
white solid; isolated yield 0.325 g (93%); M. Pt. 160–162 C; H found: C, 56.65; H, 4.73; N, 5.26.
0
0
0
0
0
0
0
NMR (400 MHz, DMSO-d
2
1
6
) d
H
: 1.65–1.68 (m, 2H), 1.79–1.84 (m,
4-(2 -(3,3-Bis(methylthio)acryloyl)-2-oxo-1 ,2 ,5 ,6 ,7 ,7a -hexa-
0
0
H), 2.15 (s, 3H), 2.26 (s, 3H), 2.32–2.48 (m, 2H), 3.73–3.78 (m, hydrospiro[indoline-3,3 -pyrrolizine]-1 -yl)benzonitrile 4m. Off
ꢁ
1
H), 3.90–3.95 (m, 1H), 4.17 (d, J ¼ 12 Hz, 1H), 5.61 (s, 1H), 6.78 white solid; isolated yield 0.304 g (88%); M. Pt. 168 C; H NMR
(
(
d, J ¼ 7.5 Hz, 1H), 6.94 (dd, J ¼ 0.8 Hz, 7.2 Hz, 1H), 7.14–7.19 (400 MHz, DMSO-d ) d : 1.68–1.80 (m, 4H), 2.15 (s, 3H), 2.24 (s,
6
H
13
m, 4H), 7.23–7.29 (m, 5H), 7.47–7.51 (m, 1H), 10.56 (s, 1H);
C
3H), 2.32–2.36 (m, 1H), 3.75–3.84 (m, 2H), 4.02 (d, J ¼ 11.6 Hz,
NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.5, 30.7, 45.0, 47.4, 1H), 5.58 (s, 1H), 6.77 (d, J ¼ 7.2 Hz, 1H), 6.91 (t, J ¼ 7.6 Hz, 1H),
6
C
6
1
1
1
1
6.6, 71.7, 73.3, 110.1, 111.6, 115.8, 116.0, 121.6, 125.1, 125.9, 7.17 (d, J ¼ 7.6 Hz, 1H), 7.25 (d, J ¼ 7.6 Hz, 1H), 7.61 (d, J ¼ 8 Hz,
13
27.0, 127.6, 128.7, 128.8, 129.6, 129.7, 142.5, 159.9, 162.4, 2H), 7.78 (d, J ¼ 8 Hz, 1H), 10.50 (s, 1H); C NMR (100 MHz,
63.7, 179.9, 188.5; IR (ATR KBr cell, cm ) 729, 1390, 1488, DMSO-d ) d : 14.2, 16.3, 27.0, 29.8, 47.3, 51.0, 67.3, 72.1, 73.0,
ꢀ
1
6
C
640, 1720, 2850, 3184; LC-MS calcd m/z: 468 found 469 [(M + 109.4, 109.7, 111.4, 119.0, 121.2, 125.4, 126.9, 129.0, 129.3,
+
ꢀ1
)] . Anal. calcd for C25
H
25FN
2
O
2
S
2
: C, 64.08; H, 5.38; N, 5.98; 132.5, 142.1, 146.9, 163.5, 179.6, 188.1; IR (ATR KBr cell, cm
)
found: C, 64.04; H, 5.33; N, 5.93.
709, 1018, 1322, 1490, 1608, 1704, 2230, 2860, 3110; LC-MS
0
0
0
0
0
0
+
2
-(3,3-Bis(methylthio)acryloyl)-1 -(4-uorophenyl)-1 ,2 ,5 ,6 , calcd m/z: 475 found 476 [(M
+ 1)] . Anal. calcd for
0
0
0
7
,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4j. Off C H N O S : C, 65.66; H, 5.30; N, 8.83; found: C, 65.61; H,
26 25 3 2 2
ꢁ
1
white solid; isolated yield 0.342 g (98%); M. Pt. 146–148 C; H 5.27; N, 8.78.
0
0
0
0
0
NMR (400 MHz, DMSO-d
6
) d
H
: 1.64–1.70 (m, 2H), 1.78–1.82 (m,
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2,4-dichlorophenyl)-1 ,2 ,5 ,
0
0
0
0
2
1
H), 2.15 (s, 3H), 2.24 (s, 3H), 2.31–2.36 (m, 1H), 2.38–2.43 (m, 6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4n. Off
ꢁ
1
H), 3.71–3.73 (m, 2H), 3.94–3.96 (m, 1H), 5.60 (s, 1H), 6.77 (d, J white solid; isolated yield 0.293 g (90%); M. Pt. 126–128 C; H
7.6 Hz, 1H), 6.91 (td, J ¼ 0.68 Hz, 7.52 Hz, 1H), 7.12–7.18 (m, NMR (400 MHz, DMSO-d ) d : 1.66–1.71 (m, 2H), 1.77–1.84 (m,
¼
6
H
1
3
3
H), 7.24 (d, J ¼ 7.4 Hz, 1H), 7.41–7.44 (m, 2H), 10.56 (s, 1H);
C
2H), 2.16 (s, 3H), 2.25 (s, 3H), 2.34–2.45 (m, 2H), 3.65–3.71 (m,
NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.4, 30.3, 47.6, 50.6, 1H), 4.13 (d, J ¼ 11.8 Hz, 1H), 4.20–4.25 (m, 1H), 5.57 (s, 1H),
6
C
6
1
1
3
8.0, 72.7, 73.4, 110.0, 112.0, 115.5, 115.8, 121.5, 126.0, 127.2, 6.79 (d, J ¼ 7.6 Hz, 1H), 6.92–6.96 (m, 1H), 7.12–7.23 (m, 2H),
29.5, 129.9, 130.0, 137.3, 142.5, 160.2, 162.6, 163.5, 180.1, 7.41 (dd, J ¼ 2.16 Hz, 8.44 Hz, 1H), 7.57–7.65 (m, 1H), 7.69–7.71
ꢀ
1
13
88.8; IR (ATR KBr cell, cm ) 721, 1197, 1440, 1620, 1728, 2890, (m, 1H), 10.50 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5,
6
C
+
188; LC-MS calcd m/z: 468 found 469 [(M + 1)] . Anal. calcd for 16.6, 27.3, 30.3, 46.6, 47.4, 67.6, 72.8, 73.2, 110.2, 111.6, 114.2,
: C, 64.08; H, 5.38; N, 5.98; found: C, 64.03; H, 121.8, 125.8, 126.7, 128.3, 129.3, 129.9, 130.1, 131.8, 132.1,
25 2 2 2
C H25FN O S
5.36; N, 5.95.
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1
33.9, 135.0, 137.6, 142.6, 164.0, 166.3, 179.8, 182.6, 188.3; IR 1H), 8.08 (dd, J ¼ 2.4 Hz, 8.8 Hz, 1H), 8.40 (d, J ¼ 2.4 Hz, 1H),
ꢀ
1
1
3
(ATR KBr cell, cm ) 758, 860, 1498, 1616, 1723, 2878, 2930, 10.63 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.1,
6 C
+
3101; LC-MS calcd m/z: 519 found 520 [(M + 1)] . Anal. calcd for 30.0, 47.3, 47.6, 67.8, 72.7, 73.3, 110.2, 111.9, 121.8, 123.3, 123.8,
C H ClN O S : C, 57.80; H, 4.66; N, 5.39; found: C, 57.78; H, 125.7, 126.9, 129.8, 131.4, 140.7, 141.0, 142.6, 147.3, 163.9, 179.8,
2
5
24
2 2 2
ꢀ
1
4
.63; N, 5.35.
188.4; IR (ATR KBr cell, cm ) 740, 1120, 1498, 1520, 1640, 1733,
0
0 0 0 0
-(3,3-Bis(methylthio)acryloyl)-1 -(2,4-diuorophenyl)-1 ,2 ,5 , 2198, 2940, 3184; LC-MS calcd m/z: 530 found 431 [(M + 1)] . Anal.
+
2
0
0
0
0
6
,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4o. Off calcd for C25
H24ClN O S
3 4 2
: C, 56.65; H, 4.56; N, 7.93; found: C,
ꢁ
1
white solid; isolated yield 0.309 g (91%); M. Pt. 140–142 C; H 56.61; H, 4.53; N, 7.88.
NMR (400 MHz, DMSO-d
0
0
) d
6 H
: 1.59–1.70 (m, 2H), 1.79–1.85 (m,
2 -(3,3-Bis(methylthio)acryloyl)-1 -(3-bromo-4-uorophenyl)-
0
0
0
0
0
0
0
2
1
(
H), 2.16 (s, 3H), 2.27 (s, 3H), 2.32–2.45 (m, 2H), 3.74–3.78 (m, 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
H), 3.77–3.92 (m, 1H), 4.14 (d, J ¼ 12 Hz, 1H), 5.60 (s, 1H), 6.78 4s. Off white solid; isolated yield 0.284 g (90%); M. Pt. 116–118
ꢁ
C; H NMR (400 MHz, DMSO-d ) d : 1.65–1.68 (m, 2H), 1.76–
6 H
1
dd, J ¼ 4.4 Hz, 7.6 Hz, 1H), 6.93 (t, J ¼ 7.2 Hz, 1H), 7.07 (td, J ¼ 2
Hz, 8.4 Hz, 1H), 7.15–7.22 (m, 3H), 7.57 (q, J ¼ 8.4 Hz, 1H), 10.53 1.81 (m, 2H), 2.15 (s, 3H), 2.24 (s, 3H), 2.33–2.35 (m, 1H), 2.38–
1
3
(
s, 1H); C NMR (100 MHz, DMSO-d
6
) d
C
: 14.5, 16.6, 19.0, 27.4, 2.45 (m, 1H), 3.72–3.76 (m, 2H), 3.91–3.94 (m, 1H), 5.59 (s, 1H),
3
1
1
8
0.6, 44.6, 47.5, 56.5, 66.5, 71.4, 73.3, 104.1, 104.4, 104.6, 110.1, 6.76 (d, J ¼ 7.6 Hz, 1H), 6.89 (t, J ¼ 7.6 Hz, 1H), 7.16 (t, J ¼ 7.6 Hz,
12.0, 121.7, 123.9, 124.0, 125.8, 127.0, 129.6, 130.8, 130.9, 142.5, 1H), 7.24 (d, J ¼ 7.6 Hz, 1H), 7.32 (t, J ¼ 8.8 Hz, 1H), 7.42–7.45
ꢀ
1
13
59.8, 160.2, 163.8, 179.9, 188.5; IR (ATR KBr cell, cm ) 748, (m, 1H), 7.73–7.75 (m, 1H), 10.46 (s, 1H); C NMR (100 MHz,
46, 1132, 1425, 1502, 1616, 1708, 2870, 3080, 3190; LC-MS calcd DMSO-d ) d : 14.5, 16.6, 27.3, 30.0, 47.7, 50.3, 67.8, 72.5, 73.4,
6
C
+
m/z: 486 found 487 [(M + 1)] . Anal. calcd for C H F N O S : C, 108.2, 110.0, 112.1, 117.1, 121.5, 125.9, 127.2, 129.2, 129.3,
2
5
24
2
2
2
2
6
1.71; H, 4.97; N, 5.76; found: C, 61.71; H, 4.95; N, 5.70.
129.6, 133.3, 139.6, 142.5, 156.3, 158.7, 163.6, 180.0, 188.7; IR
0
0
0
0
ꢀ1
2
-(3,3-Bis(methylthio)acryloyl)-1 -(3,4-dimethoxyphenyl)-1 ,2 , (ATR KBr cell, cm ) 750, 1047, 1136, 1246, 1475, 1490, 1618,
0
0
0
0
0
+
5
,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
4p. 1716, 2882, 3253; LC-MS calcd m/z: 547 found 548 [(M + 1)] .
ꢁ
1
Off white solid; isolated yield 0.296 g (90%); M. Pt. 148 C; H Anal. calcd for C25
H
24BrFN
2
O
2
S
2
: C, 54.84; H, 4.42; N, 5.12;
NMR (400 MHz, DMSO-d
6
) d
H
: 1.65–1.69 (m, 2H), 1.76–1.81 (m, found: C, 54.80; H, 4.39; N, 5.09.
0
0
2
1
6
1
H), 2.14 (s, 3H), 2.22 (s, 3H), 2.31–2.40 (m, 2H), 3.59–3.67 (m,
2 -(3,3-Bis(methylthio)acryloyl)-1 -(5-bromothiophen-2-yl)-
0
0
0
0
0
0
0
H), 3.70 (s, 3H), 3.78 (s, 3H), 3.91 (d, J ¼ 12 Hz, 1H), 5.64 (s, 1H), 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
.75 (d, J ¼ 7.6 Hz, 1H), 6.87–6.92 (m, 3H), 7.15 (d, J ¼ 7.6 Hz, 4t. Off white solid; isolated yield 0.297 g (93%); M. Pt. 128–130
1
3
ꢁ
1
H), 7.25 (d, J ¼ 7.6 Hz, 1H), 10.39 (s, 1H); C NMR (100 MHz,
C; H NMR (400 MHz, DMSO-d ) d : 1.66–1.75 (m, 2H), 1.78–
6 H
DMSO-d
7
1
6
) d
2.8, 73.5, 110.0, 112.1, 112.3, 112.5, 119.9, 121.4, 126.2, 127.2, 2.44 (m, 2H), 3.76–3.82 (m, 2H), 3.91–3.94 (m, 1H), 5.61 (s, 1H),
29.4, 133.5, 142.6, 148.0, 149.2, 163.2, 180.1, 189.2; IR (ATR KBr 6.76 (d, J ¼ 7.6 Hz, 1H), 6.85–6.91 (m, 2H), 7.05 (d, J ¼ 3.72 Hz,
C
: 14.5, 16.7, 27.4, 30.4, 47.6, 51.2, 56.0, 56.4, 67.8, 1.82 (m, 1H), 1.88–1.93 (m, 1H), 2.19 (s, 3H), 2.28 (s, 3H), 2.32–
ꢀ1
13
cell, cm ) 720, 1081, 1420, 1606, 1750, 2158, 2300, 2950, 3112; 1H), 7.13–7.19 (m, 2H), 10.48 (s, 1H); C NMR (100 MHz,
+
LC-MS calcd m/z: 510 found 511 [(M + 1)] . Anal. calcd for DMSO-d
6 C
) d : 14.6, 16.7, 27.3, 30.3, 46.8, 47.6, 68.7, 72.1, 73.5,
C H N O S : C, 63.50; H, 5.92; N, 5.49; found: C, 63.46; H, 109.3, 110.1, 111.7, 121.5, 125.5, 126.0, 127.3, 129.6, 130.5,
2
7
30 2 4 2
ꢀ
1
5
.89; N, 5.46.
142.4, 146.4, 164.8, 176.8; IR (ATR KBr cell, cm ) 723, 983,
0
0
-(3,3-Bis(methylthio)acryloyl)-1 -(5-bromo-2-methoxyphenyl)- 1421, 1614, 1720, 2900, 3148; LC-MS calcd m/z: 535 found 536
2
0
0
0
0
0
0
0
+
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4q. [(M + 1)] . Anal. calcd for C23
H
23BrN
2
O
2
S
3
: C, 51.58; H, 4.33; N,
ꢁ
1
Off white solid; isolated yield 0.268 g (86%); M. Pt. 178 C; H 5.23; found: C, 51.53; H, 4.30; N, 5.16.
NMR (400 MHz, DMSO-d
.25 (s, 4H), 3.80–3.84 (m, 2H), 3.84 (s, 3H), 3.96–4.02 (m, 1H), 5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
0
0
0
0
) d
6 H
: 1.64–1.76 (m, 4H), 2.14 (s, 4H),
2 -(3,3-Bis(methylthio)acryloyl)-1 -(5-bromopyridin-3-yl)-1 ,2 ,
0
0
0
0
0
2
4
4u.
ꢁ
1
.22 (d, J ¼ 12 Hz, 1H), 5.64 (s, 1H), 6.76 (d, J ¼ 7.2 Hz, 1H), 6.91 (t, Off white solid; isolated yield 0.296 g (92%); M. Pt. 156–158 C; H
J ¼ 7.6 Hz, 1H), 6.97 (d, J ¼ 8.8 Hz, 1H), 7.14–7.18 (m, 2H), 7.36 (d, NMR (400 MHz, DMSO-d ) d : 1.66–1.72 (m, 2H), 1.78–1.84 (m,
6
H
1
3
J ¼ 8.4 Hz, 1H), 7.50 (s, 1H), 10.44 (s, 1H); C NMR (75 MHz, 2H), 2.16 (s, 3H), 2.25 (s, 3H), 2.33–2.38 (m, 1H), 2.41–2.49 (m,
DMSO-d ) d : 13.5, 15.1, 25.8, 29.0, 44.4, 55.5, 64.6, 70.2, 71.8, 1H), 3.75–3.82 (m, 2H), 4.01–4.06 (m, 1H), 5.61 (s, 1H), 6.78 (d, J ¼
6
C
1
1
1
09.0, 111.1, 111.6, 113.2, 120.4, 125.8, 128.4, 129.5, 130.0, 130.6, 7.56 Hz, 1H), 6.92 (dd, J ¼ 0.72 Hz, 7.52 Hz, 1H), 7.18 (dd, J ¼ 1
ꢀ1
41.6, 156.4, 162.2, 178.9, 188.2; IR (ATR KBr cell, cm ) 760, 890, Hz, 7.68 Hz, 1H), 7.26 (t, J ¼ 7.44 Hz, 1H), 8.11 (t, J ¼ 2.4 Hz, 1H),
1
3
101, 1435, 1607, 1744, 2188, 2998, 3014; LC-MS calcd m/z: 559 8.56 (d, J ¼ 2.2 Hz, 1H), 8.62 (d, J ¼ 1.8 Hz, 1H), 10.50 (s, 1H);
C
+
found 560 [(M + 1)] . Anal. calcd for C26
H
28
N
2
O
S
3 2
: C, 55.81; H, NMR (100 MHz, DMSO-d
67.4, 72.1, 73.4, 110.1, 112.0, 120.8, 121.6, 125.8, 129.7, 138.1,
-(3,3-Bis(methylthio)acryloyl)-1 -(2-chloro-5-nitrophenyl)- 139.2, 142.5, 148.6, 149.0, 163.7, 179.8, 188.6; IR (ATR KBr cell,
6 C
) d : 14.5, 16.6, 27.2, 29.8, 47.7, 48.5,
4
.86; N, 5.01; found: C, 55.76; H, 4.83; N, 4.99.
0
0
2
0
0
0
0
0
0
0
ꢀ1
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4r. cm ) 712, 1066, 1188, 1386, 1421, 1612, 1713, 2945, 3259; LC-MS
ꢁ
1
+
Off white solid; isolated yield 0.283 g (88%); M. Pt. 152–154 C; H calcd m/z: 530 found 531 [(M + 1)] . Anal. calcd for C H BrN -
2
4
24
3
NMR (400 MHz, DMSO-d
6
) d
H
: 1.65–1.71 (m, 2H), 1.81–1.85 (m,
O
2 2
S : C, 54.34; H, 4.56; N, 7.92; found: C, 54.29; H, 4.51; N, 7.90.
0 0 0 0 0 0
2 -(3,3-Bis(methylthio)acryloyl)-5-methoxy-1 -o-tolyl-1 ,2 ,5 ,6 ,
1
1
1
7
H), 2.17 (s, 3H), 2.23 (s, 3H), 2.38–2.43 (m, 1H), 2.49–2.53 (m,
0
0
0
H), 3.81–3.86 (m, 1H), 4.19 (d, J ¼ 11.6 Hz, 1H), 4.33–4.40 (m, 7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4ba. Off
ꢁ
1
H), 5.58 (s, 1H), 6.81 (d, J ¼ 7.6 Hz, 1H), 6.95 (t, J ¼ 7.6 Hz, 1H), white solid; isolated yield 0.360 g (96%); M. Pt. 200–202 C; H
.14 (d, J ¼ 7.2 Hz, 1H), 7.21 (t, J ¼ 7.6 Hz, 1H), 7.78 (d, J ¼ 8.8 Hz, NMR (400 MHz, DMSO-d ) d : 1.71–1.82 (m, 2H), 1.83–1.87 (m,
6
H
33712 | RSC Adv., 2015, 5, 33705–33719
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Paper
RSC Advances
ꢁ
1
2
3
¼
H), 2.18 (s, 3H), 2.22 (s, 3H), 2.37–2.42 (m, 1H), 2.55 (s, 3H),
C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.61–1.81 (m, 4H), 2.15 (s,
.71 (s, 3H), 3.76–3.81 (m, 1H), 3.94 (t, J ¼ 9.6 Hz, 1H), 4.04 (d, J 3H), 2.23 (s, 3H), 2.35–2.48 (m, 1H), 3.77 (m, 3H), 3.89 (t, J ¼ 10
11.2 Hz, 1H), 5.54 (s, 1H), 6.70–6.72 (m, 2H), 6.78 (dd, J ¼ 2.4 Hz, 1H), 4.13 (d, J ¼ 12 Hz, 1H), 5.59 (s, 1H), 6.67–6.76 (m, 3H),
1
3
Hz, 8.4 Hz, 1H), 7.09 (t, J ¼ 7.2 Hz, 1H), 7.15–7.21 (m, 2H), 7.40 7.12–7.25 (m, 3H), 7.51 (t, J ¼ 6.8 Hz, 1H), 10.31 (s, 1H); C NMR
1
3
(
d, J ¼ 8 Hz, 1H), 10.38 (s, 1H); C NMR (100 MHz, DMSO-d
6
)
(75 MHz, DMSO-d
: 14.5, 16.5, 20.2, 27.5, 30.6, 46.3, 47.4, 55.8, 69.7, 73.5, 73.8, 65.6, 70.6, 72.8, 109.4, 110.9, 112.8, 113.5, 114.9, 115.2, 124.2,
10.3, 112.2, 113.8, 114.3, 126.4, 126.6, 126.8, 127.5, 130.6, 126.4, 126.7, 127.9, 128.8, 135.0, 153.7, 155.7, 158.1, 162.7,
6 C
) d : 13.6, 15.4, 26.5, 29.6, 43.9, 46.5, 55.0,
d
1
1
C
ꢀ
1
35.9, 137.0, 139.6, 154.6, 163.3, 180.0, 189.1; IR (ATR KBr cell, 178.9, 187.7; IR (ATR KBr cell, cm ) 732, 1450, 1730, 2918,
cm ) 731, 1197, 1489, 1728, 2684, 3416; LC-MS calcd m/z: 494 3024, 3450; LC-MS calcd m/z: 498 found 499 [(M + 1)] . Anal.
found 495 [(M + 1)] . Anal. calcd for C H N O S : C, 65.56; H, calcd for C H FN O S : C, 62.63; H, 5.46; N, 5.62; found: C,
ꢀ
1
+
+
2
7
30
2
3
2
26 27
2 3 2
6
.11; N, 5.66; found: C, 65.51; H, 6.08; N, 5.64.
62.60; H, 5.41; N, 5.58.
0
0
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -(4-isopropylphenyl)-5-
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2-bromophenyl)-5-methoxy-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
methoxy-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
2
1
-one 4da. Off white solid; isolated yield 0.325 g (91%); M. Pt. 4ka. Off white solid; isolated yield 0.313 g (92%); M. Pt. 212–214
ꢁ
1
ꢁ
1
34–136 C; H NMR (400 MHz, DMSO-d
) d
6 H
: 1.18 (d, J ¼ 6.8
C; H NMR (400 MHz, DMSO-d ) d : 1.65–1.68 (m, 2H), 1.78–
6 H
Hz, 6H), 1.66–1.67 (m, 2H), 1.76–1.82 (m, 2H), 2.36 (s, 1H), 2.43– 1.84 (m, 2H), 2.18 (s, 3H), 2.24 (s, 3H), 2.34–2.37 (m, 1H), 2.43–
2
1
2
.45 (m, 1H), 2.80–2.87 (m, 1H), 3.59–3.76 (m, 5H), 3.95 (d, J ¼ 2.48 (m, 1H), 3.60–3.65 (m, 1H), 3.69–3.73 (m, 4H), 3.91 (d, J ¼
2 Hz, 1H), 5.61 (s, 1H), 6.68 (d, J ¼ 8.4 Hz, 1H), 6.74–6.78 (m, 12 Hz, 1H), 5.64 (s, 1H), 6.69 (d, J ¼ 8.4 Hz, 1H), 6.75–6.81 (m,
H), 7.18 (d, J ¼ 8 Hz, 2H), 7.31 (d, J ¼ 7.6 Hz, 2H), 10.26 (s, 1H); 2H), 6.89 (d, J ¼ 2.8 Hz, 2H), 7.30 (d, J ¼ 8.8 Hz, 2H), 10.29 (s,
1
3
13
C NMR (75 MHz, DMSO-d ) d : 13.5, 23.3, 26.3, 29.3, 32.4, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.6, 27.3, 30.0,
6
C
6
C
4
1
6.5, 50.0, 55.0, 66.9, 71.7, 72.6, 109.1, 112.9, 113.6, 125.8, 127.0, 47.4, 49.3, 55.8, 67.9, 73.4, 73.7, 110.5, 111.9, 113.9, 114.0, 125.5,
35.0, 135.2, 137.4, 145.9, 153.6, 178.9, 188.1; IR (ATR KBr cell, 127.3, 128.7, 128.8, 133.2, 136.0, 140.0, 154.6, 163.7, 179.6,
ꢀ
1
ꢀ1
cm ) 750, 1136, 1480, 1720, 2980, 3500; LC-MS calcd m/z: 522 188.6; IR (ATR KBr cell, cm ) 742, 1199, 1489, 1693, 1726, 2860,
found 523 [(M + 1)] . Anal. calcd for C29
+
+
34 2 3 2
H N O S : C, 66.63; H, 3263; LC-MS calcd m/z: 559 found 560 [(M + 1)] . Anal. calcd for
6
.56; N, 5.36; found: C, 66.58; H, 6.53; N, 5.30.
C
26
H
27BrN
2
O
3
S
2
: C, 55.81; H, 4.86; N, 5.01; found: C, 55.78; H,
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -(4-ethoxyphenyl)-5-methoxy- 4.81; N, 4.98.
0
0
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4ea.
2 -(3,3-Bis(methylthio)acryloyl)-1 -(4-bromophenyl)-5-methoxy-
ꢁ
1
0
0
0
0
0
0
0
Off white solid; isolated yield 0.32 g (92%); M. Pt. 150 C; H NMR 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
400 MHz, DMSO-d ) d
H), 1.76–1.86 (m, 2H), 2.18 (s, 3H), 2.20 (s, 3H), 2.33–2.37 (m,
(
6
H
: 1.32 (t, J ¼ 6.8 Hz, 1H), 1.66–1.70 (m, 4la. Off white solid; isolated yield 0.319 g (94%); M. Pt. 186–188
ꢁ
1
2
1
1
C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.64–1.69 (m, 2H), 1.77–
H), 2.43–2.47 (m, 1H), 3.60–3.65 (m, 1H), 3.71 (s, 4H), 3.91 (d, J ¼ 1.84 (m, 2H), 2.17 (s, 3H), 2.23 (s, 3H), 2.32–2.51 (m, 2H), 3.67–
1.6 Hz, 1H), 4.00 (q, J ¼ 6.8 Hz, 1H), 5.63 (s, 1H), 6.69 (d, J ¼ 8.4 3.71 (m, 5H), 3.92 (d, J ¼ 11.5 Hz, 1H), 5.60 (s, 1H), 6.68 (d, J ¼
Hz, 1H), 6.75–6.77 (m, 1H), 6.80–6.81 (m, 1H), 6.87 (d, J ¼ 8.8 Hz, 8.36 Hz, 1H), 6.74–6.76 (m, 1H), 6.80 (d, J ¼ 2.44 Hz, 1H), 7.37
1
3
2
H), 7.30 (d, J ¼ 8.4 Hz, 2H), 10.29 (s, 1H); C NMR (100 MHz, (dd, J ¼ 1.76 Hz, 6.88 Hz, 2H), 7.49–7.51 (m, 2H), 10.31 (s, 1H);
13
DMSO-d ) d : 14.5, 15.2, 16.7, 27.4, 30.3, 47.6, 50.7, 56.0, 63.4,
C NMR (100 MHz, DMSO-d ) d : 14.6, 16.6, 27.3, 30.1, 47.6,
6 C
6
C
6
1
8.0, 72.8, 73.7, 79.6, 110.1, 112.4, 113.8, 114.7, 114.9, 127.5, 50.7, 56.0, 56.5, 67.8, 72.5, 73.6, 110.2, 112.3, 114.0, 120.0, 127.3,
29.1, 132.8, 136.0, 154.6, 157.7, 163.1, 180.0, 189.2; IR (ATR KBr 130.5, 131.8, 136.0, 140.7, 154.7, 163.4, 179.9, 188.9; IR (ATR KBr
ꢀ1
ꢀ1
cell, cm ) 780, 1190, 1429, 1700, 2888, 3200, 3540; LC-MS calcd cell, cm ) 745, 1145, 1428, 1690, 1718, 2875, 2928, 3198, 3435;
m/z: 524 found 525 [(M + 1)] . Anal. calcd for C28
+
+
H
32
N
2
O
4
S
2
: C, LC-MS calcd m/z: 559 found 560 [(M + 1)] . Anal. calcd for C26
27BrN : C, 55.81; H, 4.86; N, 5.01; found: C, 55.75; H, 4.80;
-(3,3-Bis(methylthio)acryloyl)-5-methoxy-1 -(3-methoxy- N, 4.95.
-
64.09; H, 6.15; N, 5.34; found: C, 64.07; H, 6.11; N, 5.29.
H
2 3 2
O S
0
0
2
0
0
0
0
0
0
0
0
0
phenyl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-
2 -(3,3-Bis(methylthio)acryloyl)-1 -(3-bromo-4-uorophenyl)-
0 0 0 0 0 0 0
2
1
2
3
-one 4ga. Off white solid; isolated yield 0.346 g (95%); M. Pt. 5-methoxy-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrro-
96 C; H NMR (400 MHz, DMSO-d ) d : 1.06–1.85 (m, 4H), lizin]-2-one 4sa. Off white solid; isolated yield 0.299 g (90%); M.
ꢁ
1
6
H
ꢁ
1
.18 (s, 3H), 2.24 (s, 3H), 3.67–3.70 (m, 4H), 3.73–3.76 (m, 4H), Pt. 120–122 C; H NMR (400 MHz, DMSO-d
.95–3.96 (m, 1H), 5.66 (s, 1H), 6.69 (d, J ¼ 8.4 Hz, 1H), 6.75–6.83 4H), 2.19 (s, 3H), 2.26 (s, 3H), 2.37–2.51 (m, 2H), 3.71–3.75 (m,
6 H
) d : 1.68–1.84 (m,
(
m, 3H), 6.97–6.99 (m, 2H), 7.25 (t, J ¼ 8 Hz, 1H), 10.31 (s, 1H); 5H), 3.92–3.95 (m, 1H), 5.63 (s, 1H), 6.70 (d, J ¼ 8.08 Hz, 1H),
1
3
C NMR (100 MHz, DMSO-d
6
) d
C
: 14.5, 16.7, 27.3, 30.3, 47.6, 6.77 (d, J ¼ 8.28 Hz, 1H), 6.84 (s, 1H), 7.34 (d, J ¼ 8.48 Hz, 1H),
13
5
1
1
1.4, 55.4, 56.0, 56.5, 67.8, 72.7, 73.7, 110.2, 112.2, 112.4, 113.8, 7.46 (s, 1H), 7.80 (d, J ¼ 6.36 Hz, 1H), 10.34 (s, 1H); C NMR
14.3, 114.8, 120.2, 127.5, 130.0, 136.0, 142.9, 154.7, 159.8, (100 MHz, DMSO-d ) d : 14.6, 16.7, 27.2, 29.9, 47.7, 50.1, 67.8,
6
C
ꢀ
1
63.3, 180.0, 189.2; IR (ATR KBr cell, cm ) 738, 1303, 1489, 72.6, 73.7, 79.7, 108.2, 110.2, 112.3, 114.0, 114.7, 117.3, 127.3,
+
1712, 3431; LC-MS calcd m/z: 510 found 511 [(M + 1)] . Anal. 129.2, 133.4, 139.6, 139.6, 154.3, 156.3, 158.7, 163.5, 179.8,
ꢀ
1
30 2 4 2
calcd for C27H N O S : C, 63.50; H, 5.92; N, 5.49; found: C, 188.9; IR (ATR KBr cell, cm ) 755, 1480, 1720, 2918, 3270, 3578;
6
+
3.44; H, 5.88; N, 5.43.
LC-MS calcd m/z: 577 found 578 [(M + 1)] . Anal. calcd for C26
-
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -(2-uorophenyl)-5-methoxy-
H
26BrN : C, 54.07; H, 4.54; N, 4.85; found: C, 54.03; H, 4.51;
2 3 2
O S
0
0
0
0
0
0
0
1
4
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one N, 4.79.
ia. Off white solid; isolated yield 0.346 g (93%); M. Pt. 206–208
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0
0
-(3,3-Bis(methylthio)acryloyl)-1 -(5-bromothiophen-2-yl)-5- 110.3, 112.0, 122.3, 126.9, 127.0, 127.2, 128.2, 137.8, 142.1,
2
0
0
0
0
0
0
0
ꢀ1
methoxy-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 149.2, 164.9, 180.6, 189.0; IR (ATR KBr cell, cm ) 748, 1368,
2
1
1
3
6
-one 4ta. Off white solid; isolated yield 0.334 g (99%); M. Pt. 1445, 1630, 1700, 2970, 3320; LC-MS calcd m/z: 537 found 538
54 C; H NMR (400 MHz, DMSO-d ) d
6 H
: 1.68–1.77 (m, 2H), [(M + 1)] . Anal. calcd for C28H N O S : C, 62.54; H, 5.81; N,
31 3 4 2
.81–1.93 (m, 2H), 2.18 (s, 3H), 2.25 (s, 3H), 2.32–2.47 (m, 2H), 7.81; found: C, 62.48; H, 5.78; N, 7.80.
ꢁ
1
+
0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(4-ethoxyphenyl)-5-nitro-
.44 (s, 3H), 3.74–3.87 (m, 2H), 3.93–3.98 (m, 1H), 5.64 (s, 1H),
.67–6.70 (m, 1H), 6.75–6.77 (m, 2H), 6.87–6.93 (m, 1H), 7.07 (d, 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
0
0
0
0
0
0
0
1
3
J ¼ 3.6 Hz, 1H), 10.34 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 4eb. Off white solid; isolated yield 0.341 g (93%); M. Pt. 190–192
6
C
ꢁ
1
1
1
1
1
5
4.6, 16.7, 27.3, 30.1, 46.7, 47.6, 56.1, 68.6, 72.1, 73.7, 109.3,
10.3, 112.0, 114.1, 114.7, 126.1, 126.9, 130.5, 135.9, 146.5, 1.68–1.76 (m, 2H), 1.78–1.88 (m, 2H), 2.14 (s, 3H), 2.24 (s, 3H),
C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.31 (t, J ¼ 6.8 Hz, 3H),
ꢀ
1
54.7, 164.1, 179.6, 188.4; IR (ATR KBr cell, cm ) 748, 1078, 2.38–2.43 (m, 1H), 2.49–2.54 (m, 1H), 3.65–3.71 (m, 1H), 3.76–
343, 1470, 1628, 1709, 2918, 3440; LC-MS calcd m/z: 565 found 3.81 (m, 1H), 3.94–4.01 (m, 3H), 5.68 (s, 1H), 6.88 (d, J ¼ 8.8 Hz,
+
66 [(M + 1)] . Anal. calcd for C24
H
25BrN
2
O
3
S
3
: C, 50.97; H, 4.46; 2H), 6.98 (d, J ¼ 8.4 Hz, 1H), 7.33 (d, J ¼ 8.8 Hz, 2H), 7.99 (d, J ¼
13
N, 4.95; found: C, 50.91; H, 4.43; N, 4.90.
2 Hz, 1H), 8.17 (dd, J ¼ 2 Hz, 8.4 Hz, 1H), 11.20 (s, 1H); C NMR
-(3,3-Bis(methylthio)acryloyl)-1 -(5-bromopyridin-3-yl)-5- (100 MHz, DMSO-d ) d : 14.5, 15.2, 16.7, 27.4, 30.0, 47.8, 50.7,
methoxy-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 63.4, 68.4, 72.9, 73.0, 110.3, 112.1, 115.0, 122.4, 126.9, 127.2,
0
0
2
6
C
0
0
0
0
0
0
0
2
2
2
1
-one 4ua. Off white solid; isolated yield 0.312 g (92%); M. Pt. 129.2, 132.1, 142.1, 149.2, 157.8, 164.8, 180.6, 189.1; IR (ATR KBr
ꢁ
1
ꢀ1
08–210 C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.67–1.81 (m, cell, cm ) 746, 910, 1049, 1332, 1483, 1739, 2972, 3354; LC-MS
+
H), 1.83–1.87 (m, 2H), 2.18 (s, 3H), 2.24 (s, 3H), 2.35–2.39 (m, calcd m/z: 538 found 539 [(M
+
1)] . Anal. calcd for
H), 2.45–2.51 (m, 1H), 3.69 (s, 3H), 3.73–3.79 (m, 2H), 4.02 (d, J
11.3 Hz, 1H), 5.62 (s, 1H), 6.69 (d, J ¼ 8.4 Hz, 1H), 6.75–6.78 5.39; N, 7.72.
C
27
H
29
N
3
O
5
S
2
: C, 60.09; H, 5.42; N, 7.79; found: C, 60.05; H,
¼
0
0
(
2
(
m, 1H), 6.83 (d, J ¼ 2.4 Hz, 1H), 8.13 (t, J ¼ 2 Hz, 1H), 8.55 (d, J ¼
2 -(3,3-Bis(methylthio)acryloyl)-1 -(3-methoxyphenyl)-5-nitro-
1
3
0
0
0
0
0
0
0
.2 Hz, 1H), 8.63 (d, J ¼ 1.76 Hz, 1H), 10.36 (s, 1H); C NMR 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
ꢁ
100 MHz, DMSO-d ) d : 14.6, 16.6, 27.2, 29.7, 47.7, 48.4, 56.1, 4gb. Off white solid; isolated yield 0.33 g (88%); M. Pt. 162 C;
6
C
1
6
1
7.4, 72.1, 73.6, 110.2, 112.3, 114.1, 120.7, 127.1, 135.9, 138.2,
39.2, 148.6, 148.9, 154.8, 163.9, 179.7, 188.7; IR (ATR KBr cell, (m, 2H), 2.14 (s, 3H), 2.24 (s, 3H), 2.40–2.50 (m, 1H), 2.55 (s, 1H),
6 H
H NMR (400 MHz, DMSO-d ) d : 1.69–1.77 (m, 2H), 1.79–1.86
ꢀ
1
cm ) 704, 823, 1016, 1203, 1489, 1645, 1716, 2868, 3024, 3417, 3.71–3.85 (m, 5H), 4.01 (t, J ¼ 12 Hz, 1H), 5.70 (s, 1H), 6.80 (d, J ¼
+
3
514; LC-MS calcd m/z: 560 found 561 [(M + 1)] . Anal. calcd for 8 Hz, 2H), 6.97–7.01 (m, 3H), 7.26 (t, J ¼ 7.6 Hz, 1H), 8.01 (s, 1H),
1
3
C
25
H26BrN
3
O
3
S
2
: C, 53.57; H, 5.68; N, 7.50; found: C, 53.52; H, 8.17 (dd, J ¼ 1.2 Hz, 8.8 Hz, 1H), 11.21 (s, 1H). C NMR (100
5
.64; N, 7.48.
MHz, DMSO-d ) d : 14.6, 16.7, 27.3, 30.0, 47.8, 51.4, 55.5, 68.1,
6
C
0
0
0
0
0
0
0
2
-(3,3-Bis(methylthio)acryloyl)-5-nitro-1 -o-tolyl-1 ,2 ,5 ,6 ,7 , 72.9, 73.1, 110.3, 112.1, 112.5, 114.2, 120.2, 122.4, 127.0, 130.1,
a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4bb. Off white 142.1, 142.2, 149.3, 159.9, 165.0, 180.6, 189.1; IR (ATR KBr cell,
solid; isolated yield 0.347 g (90%); M. Pt. 200–204 C; H NMR cm ) 720, 840, 1130, 1480, 1740, 2800, 3260; LC-MS calcd m/z:
0
0
7
ꢁ
1
ꢀ1
+
(
400 MHz, DMSO-d
6
) d
: 1.64–1.79 (m, 2H), 1.82–1.91 (m, 2H), 525 found 526 [(M + 1)] . Anal. calcd for C26H N O S : C, 59.41;
H
27 3 5 2
2
4
(
.14 (s, 3H), 2.21 (s, 3H), 2.49–2.59 (m, 4H), 3.85–3.90 (m, 1H), H, 5.18; N, 7.99; C, 59.38; H, 5.11; N, 7.94.
0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2-uorophenyl)-5-nitro-
.00 (t, J ¼ 9.2 Hz, 1H), 4.09 (d, J ¼ 11.2 Hz, 1H), 5.56 (s, 1H), 7.00
0
0
0
0
0
0
0
d, J ¼ 8.4 Hz, 1H), 7.01–7.11 (m, 1H), 7.16–7.23 (m, 2H), 7.45 (d, J 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
7.2 Hz, 1H), 7.92 (d, J ¼ 7.2 Hz, 1H), 8.19 (dd, J ¼ 2 Hz, 8.4 Hz, 4ib. Off white solid; isolated yield 0.352 g (92%); M. Pt. 206–208
¼
1
3
ꢁ
1
1
2
1
1
1
1
H), 11.28 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.6,
C; H NMR (400 MHz, DMSO-d ) d : 1.84–1.90 (m, 4H), 2.14 (s,
6 H
6
C
0.1, 27.4, 30.3, 46.5, 47.6, 69.9, 73.0, 73.5, 110.3, 112.0, 122.3, 3H), 2.26 (s, 3H), 2.42–2.45 (m, 1H), 2.49–2.52 (m, 1H), 3.85–3.89
26.7, 126.8, 126.9, 127.0, 127.2, 130.7, 137.0, 138.8, 142.1, 149.2, (m, 1H), 3.93–3.98 (m, 1H), 4.21 (d, J ¼ 11.68 Hz, 1H), 5.66 (s, 1H),
ꢀ
1
64.9, 180.5, 189.0; IR (ATR KBr cell, cm ) 749, 1140, 1480, 6.99 (d, J ¼ 8.64 Hz, 1H), 7.00–7.21 (m, 2H), 7.26–7.31 (m, 1H),
600, 1728, 2970, 3300; LC-MS calcd m/z: 508 found 509 [(M + 7.58, (q, J ¼ 7.8 Hz, 1H), 7.94 (d, J ¼ 2.24 Hz, 1H), 8.18 (dd, J ¼ 2.28
+
13
27 3 4 2
)] . Anal. calcd for C26H N O S
6 C
: C, 61.27; H, 5.34; N, 8.25; Hz, 8.64 Hz, 1H), 11.30, (s, 1H); C NMR (100 MHz, DMSO-d ) d :
found; C, 61.23; H, 5.29; N, 8.20.
14.6, 16.6, 27.4, 30.3, 45.2, 47.7, 56.5, 68.8, 71.6, 73.0, 110.4, 111.6,
0
0
-(3,3-Bis(methylthio)acryloyl)-1 -(4-isopropylphenyl)-5-nitro- 116.2, 122.2, 125.2, 126.7, 126.9, 127.1, 129.0, 127.1, 129.0, 129.9,
2
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 1421, 149.2, 159.9, 162.4, 165.3, 180.4, 188.5; IR (ATR KBr cell,
ꢀ
1
4
db. Off white solid; isolated yield 0.335 g (91%); M. Pt. 196–198 cm ) 710, 1170, 1300, 1490, 1748, 2800, 3400; LC-MS calcd m/z:
ꢁ
1
+
C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.18 (d, J ¼ 6.88 Hz, 6H), 513 found 514 [(M + 1)] . Anal. calcd for C25
3 4 2
H24FN O S : C, 58.46;
1
2
3
1
¼
.70–1.73 (m, 2H), 1.81–1.87 (m, 2H), 2.14 (s, 3H), 2.21 (s, 3H), H, 4.71; N, 8.18; found: C, 58.42; H, 4.66; N, 8.15.
0 0
2 -(3,3-Bis(methylthio)acryloyl)-1 -(2-bromophenyl)-5-nitro-
.39–2.43 (m, 1H), 2.47–2.52 (m, 2H), 2.80–2.87 (m, 1H), 3.67–
0
0
0
0
0
0
0
.73 (m, 1H), 3.78–3.83 (m, 1H), 4.00 (d, J ¼ 11.8 Hz, 1H), 5.66 (s, 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
H), 6.98 (d, J ¼ 8.64 Hz, 1H), 7.20 (d, J ¼ 8.16 Hz, 2H), 7.35 (d, J 4kb. Off white solid; isolated yield 0.311 g (89%); M. Pt. 226–228
ꢁ
1
8.16 Hz, 2H), 7.99 (d, J ¼ 2.28 Hz, 1H), 8.17 (dd, J ¼ 2.32 Hz,
6 H
C; H NMR (400 MHz, DMSO-d ) d : 1.83–1.88 (m, 4H), 2.15 (s,
1
3
8
.64 Hz, 1H), 11.28 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 3H), 2.21 (s, 3H), 2.44–2.55 (m, 1H), 3.67–3.82 (m, 1H), 4.17 (d, J
6 C
1
4.5, 16.7, 24.3, 24.4, 27.4, 30.1, 33.5, 47.8, 51.2, 68.3, 72.9, 73.1, ¼ 11.6 Hz, 1H), 4.29–4.35 (m, 1H), 5.62 (s, 1H), 7.01 (d, J ¼ 8.68
Hz, 1H), 7.19 (td, J ¼ 1.56 Hz, 8 Hz, 1H), 7.42 (td, J ¼ 1.04 Hz,
33714 | RSC Adv., 2015, 5, 33705–33719
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.56 Hz, 1H), 7.61–7.66 (m, 2H), 7.97 (d, J ¼ 2.28 Hz, 1H), 8.20 1H), 3.82–3.89 (m, 2H), 4.12 (d, J ¼ 11.2 Hz, 1H), 6.99 (d, J ¼ 8.64
13
(
d, J ¼ 2.24 Hz, 8.6 Hz, 1H), 11.35 (s, 1H); C NMR (100 MHz, Hz, 1H), 8.01 (d, J ¼ 2.24 Hz, 1H), 8.16–8.19 (m, 2H), 8.57 (d, J ¼
13
DMSO-d ) d : 14.6, 16.7, 27.2, 29.8, 47.7, 49.5, 55.4, 68.1, 73.0, 2.2 Hz, 1H), 8.67 (d, J ¼ 1.8 Hz, 1H), 11.30 (s, 1H); C NMR (100
6
C
7
1
3.5, 110.5, 111.6, 122.0, 125.4, 127.0, 127.1, 128.9, 129.0, 129.1, MHz, DMSO-d ) d : 14.6, 16.7, 27.1, 29.3, 48.0, 48.4, 67.5, 72.3,
6 C
33.3, 139.3, 142.0, 149.3, 165.4, 180.1, 188.5; IR (ATR KBr cell, 73.0, 110.3, 112.2, 120.8, 122.5, 126.7, 127.1, 133.3, 138.5, 142.3,
ꢀ
1
ꢀ1
cm ) 752, 1130, 1494, 1710, 2879, 3387; LC-MS calcd m/z: 574 148.5, 149.1, 165.0, 180.3, 188.6; IR (ATR KBr cell, cm ) 724,
found 575 [(M + 1)] . Anal. calcd for C25
H, 4.21; N, 7.31; found: C, 52.22; H, 4.16; N, 7.29.
+
3 4 2
H24BrN O S : C, 52.26; 906, 1480, 1708, 2800, 3058, 3423; LC-MS calcd m/z: 575 found
+
4 4 2
576 [(M + 1)] . Anal. calcd for C24H23BrN O S : C, 50.09; H, 4.03;
0
0
2
0
-(3,3-Bis(methylthio)acryloyl)-1 -(4-bromophenyl)-5-nitro- N, 9.74; found: C, 50.02; H, 4.00; N, 9.70.
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
0
0
0
0
0
0
0 0 0 0 0 0
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -o-tolyl-1 ,2 ,5 ,6 ,
0 0 0
1
4
lb. Off white solid; isolated yield 0.325 g (93%); M. Pt. 196–198 7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 4bc. Off
ꢁ
1
ꢁ
1
C; H NMR (400 MHz, DMSO-d ) d : 1.73–1.78 (m, 2H), 1.80– white solid; isolated yield 0.366 g (89%); M. Pt. 160–162 C; H
6
H
1
2
6 H
.78 (m, 2H), 2.14 (s, 3H), 2.25 (s, 3H), 2.39–2.44 (m, 1H), 2.48– NMR (400 MHz, DMSO-d ) d : 1.64–1.77 (m, 2H), 1.79–1.85 (m,
.55 (m, 1H), 3.73–3.81 (m, 2H), 3.99 (d, J ¼ 11.28 Hz, 1H), 5.66 2H), 2.19 (s, 3H), 2.25 (s, 3H), 2.39–2.51 (m, 2H), 2.54 (s, 3H),
(
(
s, 1H), 6.98 (d, J ¼ 8.68 Hz, 1H), 7.42 (d, J ¼ 8.48 Hz, 2H), 7.52 3.73–3.78 (m, 1H), 3.93 (t, J ¼ 9.52 Hz, 1H), 4.07 (d, J ¼ 11.62 Hz,
d, J ¼ 8.44 Hz, 2H), 8.00 (d, J ¼ 2.28 Hz, 1H), 8.17 (dd, J ¼ 2.24 1H), 5.55 (s, 1H), 6.94 (s, 1H), 7.07–7.10 (m, 1H), 7.14–7.21 (m,
1
3
13
Hz, 8.6 Hz, 1H), 11.27 (s, 1H); C NMR (100 MHz, DMSO-d
) d
6 C
:
4H), 7.38 (d, J ¼ 7.72 Hz, 1H), 10.67 (s, 1H); C NMR (100 MHz,
1
1
1
1
1
4.6, 16.7, 27.3, 29.8, 47.8, 50.8, 68.1, 72.6, 73.0, 110.3, 111.9, DMSO-d ) d : 14.5, 16.5, 20.4, 27.7, 30.8, 46.4, 47.4, 69.6, 73.3,
6 C
20.3, 122.5, 126.9, 127.0, 130.6, 131.9, 140.0, 142.2, 149.2, 73.7, 111.8, 112.9, 122.2, 124.4, 125.5, 126.5, 126.8, 130.7, 137.1,
ꢀ
1
ꢀ1
65.1, 180.5, 188.8; IR (ATR KBr cell, cm ) 760, 1400, 1498, 139.3, 144.3, 163.9, 180.0, 188.8; IR (ATR KBr cell, cm ) 727,
760, 2800, 3117, 3289; LC-MS calcd m/z: 574 found 575 [(M + 1134, 1325, 1494, 1602, 1710, 2854, 3159, 3320; LC-MS calcd m/z:
+
+
)] . Anal. calcd for C25
H24BrN
3
O
4
S
2
: C, 52.26; H, 4.21; N, 7.31; 541 found 542 [(M + 1)] . Anal. calcd for C26
2 2 2
H27BrN O S : C,
found: C, 52.20; H, 4.18; N, 7.29.
57.45; H, 5.01; N, 5.15; found: C, 57.40; H, 4.97; N, 5.13.
0
0
0 0
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(4-isopropylphenyl)-
2
-(3,3-Bis(methylthio)acryloyl)-1 -(3-bromo-4-uorophenyl)-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
5
2
2
4
1
8
-nitro-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
-one 4sb. Off white solid; isolated yield 0.307 g (90%); M. Pt. 4dc. Off white solid; isolated yield 0.344 g (88%); M. Pt. 170–172
10–212 C; H NMR (400 MHz, DMSO-d ) d : 1.66–1.85 (m,
H), 2.14 (s, 3H), 2.24 (s, 3H), 2.42–2.48 (m, 1H), 2.51–2.53 (m, 1.62–1.71 (m, 2H), 1.78–1.80 (m, 2H), 2.19 (s, 3H), 2.23 (s, 3H),
H), 3.80 (d, J ¼ 7.2 Hz, 2H), 3.97 (s, 1H), 5.67 (s, 1H), 6.97 (d, J ¼ 2.36–2.37 (m, 2H), 2.81–2.88 (m, 1H), 3.62–3.73 (m, 2H), 3.99 (d, J
.4 Hz, 1H), 7.33 (t, J ¼ 8.8 Hz, 1H) 7.47–7.50 (m, 1H), 7.82–7.84 ¼ 12 Hz, 1H), 5.63 (s, 1H), 6.93 (s, 1H), 7.11 (d, J ¼ 7.6 Hz, 1H),
ꢁ
1
ꢁ
1
C; H NMR (400 MHz, DMSO-d ) d : 1.18 (d, J ¼ 6.8 Hz, 6H),
6
H
6
H
13
(
m, 1H), 8.00 (s, 1H), 8.16 (dd, J ¼ 1.6 Hz, 8.8 Hz, 1H), 11.20 (s, 7.19–7.24 (m, 3H), 7.31 (d, J ¼ 8 Hz, 2H), 10.62 (s, 1H); C NMR
13
1
4
1
1
1
1
6 C 6 C
H); C NMR (100 MHz, DMSO-d ) d : 14.6, 16.7, 27.1, 29.5, (100 MHz, DMSO-d ) d : 14.5, 16.7, 20.4, 27.5, 30.5, 33.5, 47.6,
7.9, 50.1, 68.1, 72.7, 73.0, 108.3, 108.5, 110.3, 112.1, 117.4, 51.1, 67.8, 73.1, 73.3, 112.0, 112.8, 122.1, 124.1, 125.7, 127.0, 128.1,
22.5, 127.0, 129.4, 133.4, 138.9, 142.2, 149.2, 156.4, 158.8, 129.0, 138.0, 144.3, 147.1, 164.0, 180.0, 188.9; IR (ATR KBr cell,
ꢀ
1
ꢀ1
65.1, 180.5, 188.8; IR (ATR KBr cell, cm ) 740, 1280, 1640, cm ) 734, 812, 1165, 1329, 1446, 1620, 1732, 3219, 3384; LC-MS
+
718, 2300, 3088, 3421; LC-MS calcd m/z: 592 found 593 [(M + calcd m/z: 569 found 570 [(M + 1)] . Anal. calcd for C H BrN -
2
8
31
2
+
)] . Anal. calcd for C25
H23BrFN
3
O
4
S
2
: C, 50.68; H, 3.91; N, 7.09;
O
2 2
S : C, 58.84; H, 5.47; N, 4.90; found: C, 58.80; H, 5.41; N, 4.88.
0 0
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(4-ethoxyphenyl)-
found: C, 50.62; H, 3.88; N, 7.07.
0
0
0
0
0
0
0
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -(5-bromothiophen-2-yl)-5- 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
0
0
0
0
0
0
0
nitro-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 4ec. Off white solid; isolated yield 0.355 g (91%); M. Pt. 200–202
ꢁ
1
2
1
2
3
-one 4tb. Off white solid; isolated yield 0.319 g (92%); M. Pt.
96–198 C; H NMR (400 MHz, DMSO-d ) d : 1.83–1.96 (m, 4H), 1.63–1.70 (m, 2H), 1.72–1.80 (m, 2H), 2.18 (s, 3H), 2.26 (s, 3H),
.17 (s, 3H), 2.29 (s, 3H), 2.37–2.42 (m, 1H), 2.49–2.54 (m, 1H), 2.36–2.39 (m, 2H), 3.60–3.72 (m, 2H), 3.93 (d, J ¼ 11.8 Hz, 1H),
.81–3.88 (m, 2H), 4.02–4.07 (m, 1H), 5.70 (s, 1H), 6.92 (d, J ¼ 3.6 4.00 (q, J ¼ 6.92 Hz, 2H), 5.65 (s, 1H), 6.88 (d, J ¼ 8.56 Hz, 2H),
C; H NMR (400 MHz, DMSO-d
6
) d
H
: 1.32 (t, J ¼ 6.88 Hz, 3H),
ꢁ
1
6
H
Hz, 1H), 6.97 (d, J ¼ 8.4 Hz, 1H), 7.07 (d, J ¼ 4 Hz, 1H), 7.97 (d, J ¼ 6.92 (s, 1H), 7.11 (dd, J ¼ 1.48 Hz, 7.92 Hz, 1H), 7.23 (d, J ¼ 8.04
1
3
13
2
(
.4 Hz, 1H), 8.17 (dd, J ¼ 2 Hz, 8.4 Hz, 1H), 11.24 (s, 1H); C NMR Hz, 1H), 7.29 (d, J ¼ 8.56 Hz, 2H), 10.59 (s, 1H); C NMR (100
100 MHz, DMSO-d ) d : 14.6, 16.8, 27.2, 29.7, 46.8, 47.9, 68.8, MHz, DMSO-d ) d : 14.5, 15.2, 16.7, 27.5, 30.4, 47.6, 50.6, 63.4,
2.2, 73.0, 109.6, 110.4, 111.8, 122.6, 126.4, 126.5, 127.1, 130.7, 67.9, 73.0, 73.2, 112.1, 112.8, 114.9, 122.1, 124.1, 125.6, 129.0,
6
C
6
C
7
1
6
ꢀ
1
ꢀ1
42.2, 145.7, 149.1, 165.7, 180.3, 188.3; IR (ATR KBr cell, cm
)
132.5, 144.3, 157.8, 163.9, 180.0, 189.0; IR (ATR KBr cell, cm )
94, 732, 1093, 1336, 1481, 1624, 1716, 2854, 3227, 3042; LC-MS 779, 1103, 1498, 1711, 2253, 3299; LC-MS calcd m/z: 573 found
+
+
calcd m/z: 580 found 581 [(M + 1)] . Anal. calcd for C H BrN - 574 [(M + 1)] . Anal. calcd for C H BrN O S : C, 56.54; H, 5.10;
2
3
22
3
27 29
2 3 2
O S : C, 47.58; H, 3.82; N, 7.24; found: C, 47.51; H, 3.80; N, 7.19. N, 4.88; found: C, 56.50; H, 5.08; N, 4.83.
4
3
0
0
0
0
2
-(3,3-Bis(methylthio)acryloyl)-1 -(5-bromopyridin-3-yl)-5-
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(3-methoxyphenyl)-
0
0
0
0
0
0
0
0
0
0
0
0
0
0
nitro-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- 1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
-one 4ub. Off white solid; isolated yield 0.328 g (94%); M. Pt. 4gc. Off white solid; isolated yield 0.367 g (92%); M. Pt. 150 C;
16–218 C; H NMR (400 MHz, DMSO-d
H), 2.15 (s, 3H), 2.25 (s, 3H), 2.40–2.49 (m, 1H), 2.50–2.59 (m, (m, 2H), 2.19 (s, 3H), 2.24 (s, 3H), 2.35–2.36 (m, 2H), 3.64–3.75
ꢁ
2
2
4
ꢁ
1
1
6
) d
H
: 1.70–1.91 (m,
6 H
H NMR (400 MHz, DMSO-d ) d : 1.66–1.70 (m, 2H), 1.76–1.82
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(
6
m, 5H), 3.98 (d, J ¼ 11.6 Hz, 1H), 5.65 (s, 1H), 6.78–6.80 (m, 1H), 2H), 3.69–3.76 (m, 2H), 3.95 (d, J ¼ 11.6 Hz, 1H), 5.63 (s, 3H),
.91–6.97 (m, 3H), 7.09–7.11 (m, 1H), 7.22–7.25 (m, 2H), 10.60 6.91 (d, J ¼ 1.76 Hz, 1H), 7.09 (dd, J ¼ 1.76 Hz, 7.96 Hz, 1H), 7.23
1
3
(
s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.5, 16.7, 27.5, 30.4, (t, J ¼ 7.89 Hz, 1H), 7.33 (t, J ¼ 8.68 Hz, 1H), 7.42–7.46 (m, 1H),
6
C
13
4
1
1
1
1
7.6, 51.4, 55.4, 67.6, 72.9, 73.3, 110.0, 112.0, 112.3, 112.8, 114.2, 7.76 (dd, J ¼ 2.08 Hz, 6.8 Hz, 1H), 10.70 (s, 1H). C NMR (100
20.1, 122.2, 124.1, 125.6, 129.0, 130.1, 142.6, 144.3, 159.8, MHz, DMSO-d ) d : 14.6, 16.6, 27.3, 29.9, 47.6, 50.1, 67.6, 72.6,
64.0, 179.9, 188.9; IR (ATR KBr cell, cm ) 734, 1360, 1684, 73.2, 112.0, 112.9, 117.1, 117.3, 122.3, 124.1, 125.3, 129.0, 133.3,
6
C
ꢀ
1
ꢀ
1
704, 3060, 3168, 3320; LC-MS calcd m/z: 559 found 560 [(M + 144.3, 164.1, 179.8, 185.6; IR (ATR KBr cell, cm ) 748, 1128,
+
2 3 2
)] . Anal. calcd for C26H27BrN O S : C, 55.81; H, 4.86; N, 5.01; 1348, 1494, 1608, 1710, 3328; LC-MS calcd m/z: 626 found 627
+
found: C, 55.75; H, 4.83; N, 4.94.
[(M + 1)] . Anal. calcd for C25
H
23Br
2
FN
2
O
2
S
2
: C, 47.94; H, 3.70;
0
0
0
2
0
-(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(2-uorophenyl)- N, 4.47: found: C, 47.90; H, 3.68; N, 4.43.
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
ic. Off white solid; isolated yield 0.363 g (89%); M. Pt. 134 C; phen-2-yl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrro-
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(5-bromothio-
ꢁ
0
0
0
0
0
0
0
4
1
6 H
H NMR (400 MHz, DMSO-d ) d : 1.60–1.71 (m, 2H), 1.78–1.83 lizin]-2-one 4tc. Off white solid; isolated yield 0.345 g (94%); M.
ꢁ
1
(m, 2H), 2.18 (s, 3H), 2.27 (s, 3H), 2.32–2.38 (m, 2H), 3.72–3.77 Pt. 130–132 C; H NMR (400 MHz, DMSO-d
6 H
) d : 1.67–1.78 (m,
(
m, 1H), 3.85–3.90 (m, 1H), 4.17 (d, J ¼ 12 Hz, 1H), 5.62 (s, 1H), 2H), 1.79–1.95 (m, 1H), 2.24 (s, 3H), 2.32 (s, 3H), 2.35–2.46 (m,
6
7
1
1
1
.91 (s, 1H), 7.11–7.19 (m, 4H), 7.24–7.29 (m, 1H), 7.50 (d, J ¼ 2H), 3.78–3.83 (m, 2H), 3.91–3.97 (m, 1H), 5.66 (s, 1H), 6.87 (d, J
13
.48 Hz, 1H), 10.75 (s, 1H); C NMR (100 MHz, DMSO-d
6
) d
C
:
¼ 3.64 Hz, 1H), 6.92 (s, 1H), 7.06–7.10 (m, 2H), 7.19 (d, J ¼ 8 Hz,
13
4.5, 16.6, 27.6, 30.7, 45.1, 47.4, 66.4, 71.7, 73.2, 111.5, 112.9, 1H), 10.65 (s, 1H); C NMR (100 MHz, DMSO-d ) d : 14.6, 16.7,
6
C
16.1, 122.2, 124.3, 125.2, 125.3, 127.2, 127.3, 128.8, 128.9, 27.4, 30.2, 46.7, 47.6, 68.5, 72.2, 73.3, 109.4, 111.7, 112.9, 122.4,
29.8, 144.3, 159.9, 162.4, 164.3, 179.8, 188.4; IR (ATR KBr cell, 124.2, 124.9, 126.1, 129.2, 130.6, 144.2, 146.1, 164.8, 179.6,
ꢀ
1
ꢀ1
cm ) 760, 1128, 1444, 1620, 1700, 1780, 2980, 3420; LC-MS 188.1; IR (ATR KBr cell, cm ) 761, 1384, 1606, 1700, 2456, 3071,
calcd m/z: 547 found 548 [(M + 1)] . Anal. calcd for C25
+
+
H
24
-
3309; LC-MS calcd m/z: 614 found 615 [(M + 1)] . Anal. calcd for
BrFN
2
O
2
S
2
: C, 54.84; H, 4.42; N, 5.12; C, 54.81; H, 4.38; N, 5.08.
C
23
H
22Br
2
N
2
O
2
S
3
: C, 44.96; H, 3.61; N, 4.56; found: C, 44.93; H,
0
0
2
-(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(2-bromophenyl)- 3.56; N, 4.52.
0
0
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
2 -(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(5-bromopyridin-
0 0 0 0 0 0 0
4
kc. Off white solid; isolated yield 0.333 g (90%); M. Pt. 204–206 3-yl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-
ꢁ
1
C; H NMR (400 MHz, DMSO-d ) d : 1.66–1.83 (m, 4H), 2.19 (s, one 4uc. Off white solid; isolated yield 0.34 g (92%); M. Pt. 194–
6
H
ꢁ
H), 2.24 (s, 3H), 2.36–2.39 (m, 2H), 3.65–3.70 (m, 1H), 4.13 (d, J 196 C; H NMR (400 MHz, DMSO-d ) d : 1.79–1.80 (m, 2H),
6 H
1
3
¼
11.9 Hz, 2H), 4.19–4.25 (m, 1H), 5.58 (s, 1H), 6.93 (d, J ¼ 1.8 1.81–1.84 (m, 2H), 2.21 (s, 3H), 2.29 (s, 3H), 2.38–2.45 (m, 2H),
Hz, 1H), 7.07 (d, J ¼ 8.04 Hz, 1H), 7.14–7.18 (m, 2H), 7.39 (td, J ¼ 3.74–3.79 (m, 2H), 4.08 (d, J ¼ 11.36 Hz, 1H), 5.65 (s, 1H), 6.94 (s,
1
.08 Hz, 1.6 Hz, 1H), 7.53 (dd, J ¼ 1.44 Hz, 7.92 Hz, 1H), 7.63 1H), 7.12 (dd, J ¼ 1.36 Hz, 7.88 Hz, 1H), 7.25 (d, J ¼ 8 Hz, 1H),
1
3
1
3
(
dd, J ¼ 1.2 Hz, 8 Hz, 1H), 10.65 (s, 1H); C NMR (100 MHz, 8.12 (s, 1H), 8.58 (s, 1H), 8.64 (s, 1H), 10.69 (s, 1H); C NMR
DMSO-d ) d : 14.5, 16.6, 27.4, 30.1, 47.5, 49.4, 67.8, 73.1, 73.5, (100 MHz, DMSO-d ) d : 14.6, 16.7, 27.4, 29.8, 47.7, 48.4, 67.2,
11.5, 113.0, 122.3, 124.4, 125.4, 128.3, 128.7, 128.8, 128.9, 72.2, 73.2, 112.0, 112.9, 120.8, 122.4, 125.2, 129.0, 138.1, 138.9,
6
C
6
C
1
1
7
6
4
ꢀ
1
ꢀ1
33.3, 139.7, 144.4, 164.4, 179.6, 188.4; IR (ATR KBr cell, cm
32, 1491, 1614, 1722, 2829, 1241, 3284, 3425; LC-MS calcd m/z: 709, 1480, 1722, 2827, 3248, 3423; LC-MS calcd m/z: 609 found
08 found 609 [(M + 1)] . Anal. calcd for C25
9.35; H, 3.98; N, 4.60; C, 49.30; H, 3.96; N, 4.54.
)
144.3, 148.6, 149.1, 164.1, 179.7, 188.4; IR (ATR KBr cell, cm )
+
+
2 2 2 2 2 3 2 2
H24Br N O S : C, 610 [(M + 1)] . Anal. calcd for C24H23Br N O S : C, 47.30; H,
3.80; N, 6.90; found: C, 47.28; H, 3.76; N, 6.85.
0
0
-(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(4-bromophenyl)-
2
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
General procedure for the synthesis of 5
4
lc. Off white solid; isolated yield 0.344 g (93%); M. Pt. 190–192
ꢁ
1
C; H NMR (400 MHz, DMSO-d ) d : 1.65–1.71 (m, 2H), 1.74– A mixture of isatin 1 (1 mol), L-phenylalanine 2 (1 mol) was taken
6
H
1
3
1
7
.84 (m, 2H), 2.19 (s, 3H), 2.26 (s, 3H), 2.35–2.36 (m, 2H), 3.65– in methanol and heated for 15 min. This led to the formation of
.72 (m, 1H), 3.92–3.98 (m, 1H), 5.61 (s, 1H), 6.90 (d, J ¼ 1.8 Hz, azomethine ylide which was treated with 1,1-bis(methylthio)-5-
H), 7.10 (dd, J ¼ 1.8 Hz, 7.96 Hz, 1H), 7.23 (d, J ¼ 8.04 Hz, 1H), arylpenta-1,4-dien-3-one 3 and continued heating for further
.35 (d, J ¼ 8.48 Hz, 2H), 7.51 (d, J ¼ 1.6 Hz, 2H), 10.65 (s, 1H); indicated time in Table 2. Aer completion of the reaction
1
3
6 C
C NMR (100 MHz, DMSO-d ) d : 14.5, 16.7, 27.5, 30.2, 47.6, checked by TLC, the mixture was concentrated in vacuo. Column
5
1
0.7, 67.6, 72.7, 73.2, 111.8, 112.9, 120.1, 122.2, 124.1, 125.3, chromatography of the residue gave the pure product 5.
0
0
0
29.0, 130.5, 131.8, 140.4, 144.3, 164.2, 179.8, 188.6; IR (ATR KBr
5 -Benzyl-3 -(3,3-bis(methylthio)acryloyl)-6-bromo-4 -phenyl-
ꢀ1
0
cell, cm ) 760, 1126, 1348, 1490, 1708, 2878, 3380; LC-MS calcd spiro[indoline-3,2 -pyrrolidin]-2-one 5a. Pale yellow solid; iso-
m/z: 608 found 609 [(M + 1)] . Anal. calcd for C H Br N O S : lated yield 0.398 g (86%); M. Pt. 130 C; H NMR (400 MHz,
+
ꢁ
1
2
5
24
2 2 2 2
C, 49.35; H, 3.98; N, 4.60; found: C, 49.30; H, 3.94; N, 4.58.
6 H
DMSO-d ) d : 2.13–2.22 (m, 6H), 2.68–2.73 (m, 2H), 3.58–3.67
0
0
-(3,3-Bis(methylthio)acryloyl)-6-bromo-1 -(3-bromo-4-uo- (m, 3H), 3.92 (s, 1H), 5.48 (s, 1H), 6.86–6.92 (m, 2H), 6.99–7.07
2
0
0
0
0
0
0
0
13
rophenyl)-1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]- (m, 3H), 7.11–7.39 (m, 9H), 10.60 (s, 1H); C NMR (75 MHz,
2
1
2
-one 4sc. Off white solid; isolated yield 0.328 g (91%); M. Pt. DMSO-d ) d : 14.4, 14.6, 16.5, 22.2, 52.5, 66.2, 67.6, 69.0, 112.1,
6 C
ꢁ
1
50–152 C; H NMR (400 MHz, DMSO-d
6 H
) d : 1.68–1.72 (m, 113.1, 121.7, 126.3, 127.1, 127.7, 128.5, 128.8, 129.0, 129.5,
ꢀ
1
H), 1.76–1.81 (m, 2H), 2.19 (s, 3H), 2.27 (s, 3H), 2.32–2.38 (m, 139.6, 140.8, 143.8, 162.9, 189.5; IR (ATR KBr cell, cm ) 740,
33716 | RSC Adv., 2015, 5, 33705–33719
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1
5
520, 1600, 1726, 2967, 3140, 3240; LC-MS calcd m/z: 579 found 1490, 1640, 1748, 3220, 3380; LC-MS calcd m/z: 579 found 580
+
+
80 [(M + 1)] . Anal. calcd for C H BrN O S : C, 60.10; H, 4.70; [(M + 1)] . Anal. calcd for C H BrN O S : C, 60.10; H, 4.70; N,
2
9
27
2
2
2
29 27
2 2 2
N, 4.83; found: C, 60.05; H, 4.67; N, 4.76.
4.83; found: C, 60.05; H, 4.67; N, 4.80.
0
0
0
0
0
0
5
-Benzyl-3 -(3,3-bis(methylthio)acryloyl)-4 -o-tolylspiro[indo-
5 -Benzyl-3 -(3,3-bis(methylthio)acryloyl)-4 -(furan-2-yl)spiro-
0
0
line-3,2 -pyrrolidin]-2-one 5b. Pale yellow solid; isolated yield [indoline-3,2 -pyrrolidin]-2-one 5v. Pale yellow solid; isolated
.311 g (80%); M. Pt. 122 C; H NMR (400 MHz, DMSO-d
.11 (s, 3H), 2.19 (s, 3H), 2.54 (s, 3H), 2.58–2.64 (m, 1H), 2.70–
ꢁ
1
ꢁ
1
0
2
2
3
0
1
1
1
1
7
+
6
) d
H
:
yield 0.318 g (78%); M. Pt. 118 C; H NMR (400 MHz, DMSO-d
6
)
d
H
: 2.19 (s, 3H), 2.21 (s, 3H), 2.74–2.79 (m, 1H), 2.89–2.97 (m,
.76 (m, 2H), 3.08–3.10 (m, 1H), 3.69 (d, J ¼ 10 Hz, 1H), 3.88– 2H), 3.65–3.82 (m, 1H), 5.49 (s, 1H), 6.25–6.26 (m, 1H), 6.38–6.39
.96 (m, 2H), 5.36 (s, 1H), 6.74 (d, J ¼ 7.6 Hz, 1H), 6.85 (td, J ¼ (m, 1H), 6.70 (d, J ¼ 7.6 Hz, 1H), 6.78 (d, J ¼ 4 Hz, 2H), 7.07–7.27
1
3
.8 Hz, 7.6 Hz, 1H), 7.06–7.24 (m, 10H), 7.49 (d, J ¼ 7.6 Hz, 1H), (m, 6H), 7.58 (s, 1H), 10.43 (s, 1H); C NMR (75 MHz, DMSO-d )
6
1
3
0.47 (s, 1H); C NMR (75 MHz, DMSO-d ) d : 14.5, 14.8, 16.4, dC: 14.6, 16.5, 45.7, 63.7, 64.3, 69.0, 106.8, 109.2, 110.9, 112.7,
6
C
9.8, 20.3, 48.5, 68.1, 69.0, 69.5, 109.2, 113.2, 121.8, 125.9, 126.2, 121.8, 122.0, 125.7, 126.4, 128.5, 129.1, 129.6, 129.8, 139.4,
26.5, 126.7, 127.1, 128.4, 129.1, 129.2, 130.5, 137.4, 137.6, 142.0, 154.3, 162.7, 181.7, 189.2; IR (ATR KBr cell, cm ) 704,
39.8, 140.3, 142.1, 162.0, 182.3, 190.2; IR (ATR KBr cell, cm
48, 1619, 1750, 2948, 3300; LC-MS calcd m/z: 514 found 515 [(M found 491 [(M + 1)] . Anal. calcd for C27
ꢀ
1
ꢀ
1
)
1081, 1280, 1490, 1649, 1720, 2916, 3100; LC-MS calcd m/z: 490
+
H
26
N
2
O
3
S
2
: C, 66.10; H,
+
30 2 2 2
1)] . Anal. calcd for C30H N O S : C, 70.01; H, 5.87; N, 5.44; 5.34; N, 5.71; found: C, 66.04; H, 5.30; N, 5.68.
0
0
0
found: C, 69.07; H, 5.80; N, 5.41.
5 -Benzyl-3 -(3,3-bis(methylthio)acryloyl)-5-methoxy-4 -(naph-
0
0
0
0
5
-Benzyl-3 -(3,3-bis(methylthio)acryloyl)-4 -(4-isopropylphenyl)- thalen-1-yl)spiro[indoline-3,2 -pyrrolidin]-2-one 5w. Pale yellow
0
ꢁ
1
spiro[indoline-3,2 -pyrrolidin]-2-one 5d. Pale yellow solid; iso- solid; isolated yield 0.313 g (81%); M. Pt. 118 C; H NMR (400
lated yield 0.315 g (85%); M. Pt. 172 C; H NMR (400 MHz, MHz, DMSO-d ) d : 2.07 (s, 3H), 2.17 (s, 3H), 2.77–2.82 (m, 1H),
ꢁ
1
6
H
DMSO-d
6 H
) d : 1.09–1.21 (m, 6H), 2.11–2.22 (m, 6H), 2.63–2.74 3.12 (s, 1H), 3.68–3.74 (m, 4H), 3.83–3.88 (m, 1H), 4.06 (s, 1H),
(
m, 2H), 2.83–2.94 (m, 2H), 3.51–3.56 (m, 1H), 3.62 (d, J ¼ 10.8 5.42 (s, 1H), 6.68–6.79 (m, 4H), 7.01–7.17 (m, 6H), 7.48–8.21 (m,
1
3
Hz, 1H), 3.87–3.88 (m, 1H), 5.40 (s, 1H), 6.71 (d, J ¼ 7.6 Hz, 1H), 6H), 10.32 (s, 1H); C NMR (75 MHz, DMSO-d
6
C
) d : 13.0, 15.1,
6
9
.82 (t, J ¼ 7.2 Hz, 1H), 6.89 (d, J ¼ 7.6 Hz, 1H), 7.08–7.22 (m, 54.9, 66.4, 67.7, 69.4, 105.2, 109.6, 110.9, 112.0, 124.8, 125.0,
1
3
H), 7.31 (d, J ¼ 8 Hz, 2H), 10.44 (s, 1H); C NMR (75 MHz, 125.2, 126.1, 127.0, 127.9, 128.1148.8, 154.2, 157.6, 163.0, 180.2,
ꢀ
1
DMSO-d ) d : 14.5, 16.4, 24.3, 24.4, 33.5, 52.4, 66.0, 69.3, 109.2, 188.3; IR (ATR KBr cell, cm ) 738, 1136, 1430, 1646, 1749, 2860,
6
C
+
1
1
1
1
13.1, 121.8, 125.8, 126.3, 127.0, 128.4, 128.6, 129.6, 142.1, 3320; LC-MS calcd m/z: 580 found 581 [(M + 1)] . Anal. calcd for
ꢀ
1
47.0, 142.1, 147.0, 189.3; IR (ATR KBr cell, cm ) 780, 1168, C H N O S : C, 70.32; H, 5.55; N, 4.82; found: C, 70.28; H,
3
4
32 2 3 2
600, 1720, 2897, 3300; LC-MS calcd m/z: 542 found 543 [(M + 5.50; N, 4.80.
+
0
0
0
0
0
0
)] . Anal. calcd for C32
H
34
N
2
O
2
S
2
: C, 70.81; H, 6.31; N, 5.16;
2 -(1H-Benzo[d]imidazol-2-yl)-1 -(4-methoxyphenyl)-1 ,2 ,5 ,6 ,
0 0 0
7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 8a. Off
found: C, 70.79; H, 6.27; N, 5.13.
0
0
0
ꢁ
1
5
-Benzyl-3 -(3,3-bis(methylthio)acryloyl)-6-bromo-4 -(3-
white solid; isolated yield 0.073 g (78%); M. Pt. 138 C; H NMR
) d : 1.81–1.96 (m, 2H), 2.42–2.45 (m, 1H),
0
methoxyphenyl)spiro[indoline-3,2 -pyrrolidin]-2-one 5g. Pale (400 MHz, DMSO-d
yellow solid; isolated yield 0.377 g (87%); M. Pt. 196 C; H NMR 2.70–2.75 (m, 1H), 3.67 (s, 3H), 3.89–3.95 (m, 1H), 4.01–4.09 (m,
6
H
ꢁ
1
(
1
400 MHz, DMSO-d ) d : 2.19 (s, 3H), 2.22 (s, 3H), 2.59–2.68 (m, 1H), 4.38 (d, J ¼ 12.4 Hz, 1H), 6.59 (d, J ¼ 7.6 Hz, 1H), 6.77 (td, J
6
H
H), 2.75 (dd, J ¼ 3.2 Hz, 14 Hz, 1H), 3.54 (t, J ¼ 10.4 Hz, 1H), 3.63 ¼ 0.8 Hz, 7.6 Hz, 1H), 6.85 (d, J ¼ 8.8 Hz, 2H), 6.95–7.01 (m, 3H),
(
6
d, J ¼ 10.8 Hz, 1H), 3.76 (s, 3H), 3.86–3.87 (m, 1H), 5.49 (s, 1H), 7.15–7.17 (m, 1H), 7.29 (d, J ¼ 7.2 Hz, 1H), 7.36–7.39 (m, 3H),
1
3
.80–6.87 (m, 3H), 6.93 (s, 1H), 6.97 (d, J ¼ 7.6 Hz, 1H), 7.01 (dd, J 10.29 (s, 1H), 11.84 (s, 1H); C NMR (75 MHz, DMSO-d
6 C
) d :
¼
1.6 Hz, 7.6 Hz, 1H), 7.09–7.16 (m, 3H), 7.21–7.30 (m, 3H), 10.59 27.3, 30.4, 48.0, 53.0, 55.4, 57.3, 72.4, 74.4, 109.9, 111.2, 114.5,
1
3
(
s, 1H). C NMR (75 MHz, DMSO-d
6 C
) d : 14.6, 16.5, 52.6, 55.4, 118.7, 120.9, 121.2, 121.9, 126.2, 127.3, 129.0, 129.3, 132.3,
6
1
1
7
6
6.1, 67.6, 69.1, 112.0, 112.1, 113.1, 114.9, 120.8, 121.6, 124.4, 134.3, 142.6, 143.2, 151.5, 158.5, 169.0, 179.8; IR (ATR KBr cell,
ꢀ
1
26.3, 127.6, 128.4, 128.8, 129.5, 129.8, 130.0, 130.3, 130.4, 139.8, cm ) 831, 1125, 1428, 1404, 1625, 2981, 3481; LC-MS calcd m/z:
ꢀ
1
+
42.6, 143.8, 159.8, 162.7, 182.0, 189.6; IR (ATR KBr cell, cm
)
450 found 451 [(M + 1)] . Anal. calcd for C H N O : C, 74.65;
28 26 4 2
65, 1299, 1610, 1740, 2696, 3280; LC-MS calcd m/z: 609 found H, 5.82; N, 12.44; found: C, 74.59; H, 5.78; N, 12.40.
+
0 0
2 -(1H-Benzo[d]imidazol-2-yl)-6-bromo-1 -(3-methoxyphenyl)-
10 [(M + 1)] . Anal. calcd for C30
H
29BrN
2
O
3
S
2
: C, 59.11; H, 4.80;
0 0 0 0 0 0 0
N, 4.60; found: C, 59.05; H, 4.73; N, 4.57.
1 ,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
0
0
0
ꢁ
1
5
-Benzyl-3 -(3,3-bis(methylthio)acryloyl)-4 -(4-bromophenyl)- 8b. Off white solid; isolated yield 0.076 g (80%); M. Pt. 144 C; H
0
spiro[indoline-3,2 -pyrrolidin]-2-one 5l. Pale yellow solid; iso- NMR (400 MHz, DMSO-d
6 H
) d : 1.74–1.81 (m, 2H), 1.92–1.96 (m,
ꢁ
1
lated yield 0.299 g (85%); M. Pt. 118 C; H NMR (400 MHz, 2H), 2.20–2.26 (m, 1H), 2.68–2.71 (m, 1H), 3.48–3.55 (m, 1H),
DMSO-d ) d : 2.14 (s, 3H), 2.18 (s, 3H), 2.70 (d, J ¼ 6 Hz, 2H), 3.69 (m, 1H), 3.94–3.97 (m, 1H), 4.11 (t, J ¼ 9.6 Hz, 1H), 4.43 (d, J
6
H
3
.54–3.62 (m, 2H), 3.85–3.88 (m, 1H), 5.39 (s, 1H), 6.72 (d, J ¼ 7.6 ¼ 12 Hz, 1H), 6.73–6.76 (m, 1H), 6.92–7.03 (m, 5H), 7.18–7.29 (m,
13
Hz, 1H), 6.81 (td, J ¼ 3.2 Hz, 6.8 Hz, 1H), 6.91 (d, J ¼ 8 Hz, 1H), 3H), 7.39–7.42 (m, 1H), 10.48 (s, 1H), 11.94 (s, 1H); C NMR (75
7
1
6
1
1
.09–7.23 (m, 6H), 7.34 (J ¼ 8.4 Hz, 2H), 7.53 (d, J ¼ 8.4 Hz, 2H), MHz, DMSO-d
6
) d
: 14.6, 16.4, 52.3, 111.3, 112.3, 112.8, 114.2, 120.1, 121.4, 122.0, 122.1, 123.6, 125.5,
6.1, 67.8, 69.3, 109.3, 113.0, 120.0, 121.8, 125.8, 126.3, 128.4, 130.1, 134.3, 142.0, 143.2, 144.4, 151.3, 159.8, 179.6; IR (ATR KBr
C
: 27.3, 30.3, 48.0, 53.8, 55.4, 56.9, 72.2, 74.2,
1
3
6 C
0.46 (s, 1H); C NMR (75 MHz, DMSO-d ) d
ꢀ
1
29.1, 129.6, 130.4, 130.6, 131.0, 131.8, 139.6, 140.7, 142.0, cell, cm ) 752, 1134, 1332, 1625, 2883, 3441; LC-MS calcd m/z:
ꢀ
1
62.4, 182.0, 189.5: IR (ATR KBr cell, cm ) 720, 1019, 1336,
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 33705–33719 | 33717

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RSC Advances
Paper
+
5
28 found 529 [(M + 1)] . Anal. calcd for C28
4 2
H25BrN O : C, 63.52;
C
25
H24FN
5
O
2
: C, 67.40; H, 5.43; N, 15.72; found: C, 67.33; H,
H, 4.76; N, 10.58; found: C, 63.48; H, 4.73; N, 10.53.
5.40; N, 15.68.
0
0
0
0
0
0
0
0
0
0
0
0
2
-(1H-Benzo[d]imidazol-2-yl)-1 -p-tolyl-1 ,2 ,5 ,6 ,7 ,7a -hexa-
2 -(2-Amino-6-ethoxypyrimidin-4-yl)-1 -(4-uorophenyl)-1 ,2 ,
0
0
0
0
0
0
hydrospiro[indoline-3,3 -pyrrolizin]-2-one 8c. Off white solid; 5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 10d.
ꢁ
1
ꢁ
1
isolated yield 0.082 g (88%); M. Pt. 148 C; H NMR (400 MHz, Off white solid; isolated yield 0.076 g (78%); M. Pt. 116 C; H
DMSO-d ) d : 1.72–1.80 (m, 2H), 1.92–1.97 (m, 2H), 2.20 (s, 3H), NMR (400 MHz, DMSO-d ) d
.25–2.27 (m, 1H), 2.41–2.45 (m, 1H), 2.72–2.74 (m, 1H), 3.92– (m, 2H), 1.80–1.91 (m, 2H), 2.35–2.40 (m, 1H), 2.46–2.52 (m,
.95 (m, 1H), 4.06–4.11 (m, 1H), 4.42 (d, J ¼ 12.4 Hz, 1H), 6.60 (d, 1H), 3.72–3.80 (m, 1H), 3.86–3.91 (m, 1H), 3.96–4.04 (m, 1H),
6
H
6
H
: 1.15 (t, J ¼ 6.8 Hz, 3H), 1.67–1.75
2
3
J ¼ 7.2 Hz, 1H), 6.77 (t, J ¼ 7.6 Hz, 1H), 6.95–7.01 (m, 3H), 7.08 5.59 (s, 1H), 6.10 (s, 1H), 6.67 (d, J ¼ 7.6 Hz, 1H), 6.87 (td, J ¼ 0.8
(
d, J ¼ 8 Hz, 2H), 7.12–7.17 (m, 1H), 7.27–7.35 (m, 4H), 10.30 (s, Hz, 7.6 Hz, 1H), 7.06–7.15 (m, 3H), 7.38 (d, J ¼ 7.2 Hz, 1H), 7.43–
1
3
1
3
1
3
1
H), 11.85 (s, 1H); C NMR (75 MHz, DMSO-d ) d : 21.0, 27.3, 7.46 (m, 2H), 10.13 (s, 1H); C NMR (75 MHz, DMSO-d ) d :
6
C
6
C
0.4, 48.0, 53.4, 57.2, 72.4, 74.4, 109.9, 120.9, 121.9, 126.2, 127.4, 14.7, 27.7, 30.6, 47.6, 51.2, 61.2, 62.7, 73.1, 74.8, 95.1, 109.8,
29.3, 129.6, 136.3, 137.5, 142.6, 151.5, 179.8; IR (ATR KBr cell, 115.6, 115.8, 120.7, 126.1, 127.6, 129.0, 129.8, 129.9, 137.1,
ꢀ
1
cm ) 752, 1134, 1332, 1625, 2883, 3441; LC-MS calcd m/z: 434 142.8, 159.8, 162.8, 163.0, 166.8, 169.7, 179.9; IR (ATR KBr cell,
+
ꢀ1
found 435 [(M + 1)] . Anal. calcd for C28
H
26
N
4
O: C, 77.39; H, cm ) 856, 1180, 1700, 2490, 3390; LC-MS calcd m/z: 459 found
+
6
.03; N, 12.89; found: C, 77.33; H, 6.00; N, 12.85.
460 [(M + 1)] . Anal. calcd for C26
H
26FN
5
O
2
: C, 67.96; H, 5.70; N,
0
0
2
-(2-Amino-6-methoxypyrimidin-4-yl)-1 -(4-methoxyphenyl)- 15.24; found: C, 67.93; H, 5.65; N, 15.18.
0
0
0
0
0
0
0
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
ꢁ
1
0a. Off white solid; isolated yield 0.081 g (85%); M. Pt. 118 C;
1
Acknowledgements
H NMR (400 MHz, DMSO-d ) d : 1.43–1.74 (m, 2H), 1.80–1.92
6
H
(
(
1
7
m, 2H), 2.33–2.53 (m, 2H), 3.55 (s, 3H), 3.68–3.81 (m, 5H), 4.00
d, J ¼ 12 Hz, 1H), 5.59 (s, 1H), 6.12 (s, 1H), 6.66 (d, J ¼ 7.6 Hz,
SS thank DST and UGC-MRP, New Delhi, for nancial assistance.
We thank DST-IRHPA for funding towards higher resolution NMR
spectrometer. PD thanks the UGC, New Delhi for the fellowship
under UGC-BSR Meritorious. We thank Dr P. Thilagar, Department
of IPC, IISc Bangalore for analyzing the single crystal X-ray data.
H), 6.86 (d, J ¼ 8.4 Hz, 3H), 7.08 (td, J ¼ 0.8 Hz, 7.6 Hz, 1H),
13
.31 (d, J ¼ 8.8 Hz, 2H), 7.38 (d, J ¼ 7.6 Hz, 1H), 10.10 (s, 1H);
) d : 27.8, 30.7, 47.6, 51.4, 53.0, 55.4,
2.7, 73.1, 74.9, 95.1, 109.8, 114.4, 120.7, 126.2, 127.5, 129.0,
32.6, 142.8, 158.4, 162.8, 167.1, 170.0, 180.0; IR (ATR KBr cell,
C
NMR (75 MHz, DMSO-d
6
1
6
C
ꢀ
1
cm ) 1140, 1750, 2380, 3328; LC-MS calcd m/z: 457 found 458
Notes and references
+
[(M + 1)] . Anal. calcd for C26
H
27
N
5
O
3
: C, 68.25; H, 5.95; N,
1
5.31; found: C, 68.21; H, 5.90; N, 15.29.
1 (a) A. D. Melhado, W. E. Brenzovitch, A. D. Lackner and
F. D. A. Toste, J. Am. Chem. Soc., 2010, 132, 8885–8887; (b)
G. L. Adams, P. J. Carroll and A. B. Smith, J. Am. Chem.
Soc., 2013, 135, 519–528; (c) S. A. Snyder, S. P. Breazzano,
A. G. Ross, Y. Lin and A. L. Zografos, J. Am. Chem. Soc.,
2009, 131, 1753–1765; (d) R. A. Yoder and J. N. Johnston,
Chem. Rev., 2005, 105, 4730–4756; (e) J. K. Sutherland, in
Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon
Press, Elmsford, NY, 1991, vol. 1, pp. 341–377.
2 For recent reviews: (a) M. A. Borad, M. N. Bhoi, N. P. Prajapati
and H. D. Patel, Synth. Commun., 2014, 44, 897–922; (b)
N. Lashgari and G. M. Ziarani, ARKIVOC, 2012, 277–320; (c)
M. M. M. Santos, Tetrahedron, 2014, 70, 9735–9757.
3 (a) S. T. Hilton, T. C. T. Ho, G. Pljevaljcic and K. Jones, Org.
Lett., 2000, 2, 2639–2641; (b) F. Yu, R. Huang, H. Ni, J. Fan,
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0
0
2
-(2-Amino-6-ethoxypyrimidin-4-yl)-1 -(4-methoxyphenyl)-
0
0
0
0
0
0
0
1
1
,2 ,5 ,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one
ꢁ
0b. Off white solid; isolated yield 0.078 g (80%); M. Pt. 108 C;
1
H NMR (400 MHz, DMSO-d ) d : 1.09–1.28 (m, 3H), 1.69–1.98
6
H
(m, 4H), 2.19–2.36 (m, 2H), 3.66–3.79 (m, 6H), 3.97–4.00 (m,
2H), 5.98 (s, 1H), 6.00 (s, 1H), 6.70–6.86 (m, 4H), 7.03–7.07 (m,
1
3
1
d
9
1
3
H), 7.29–7.34 (m, 3H), 10.05 (s, 1H); C NMR (75 MHz, DMSO-
) d : 14.7, 27.7, 30.6, 47.6, 51.2, 55.4, 61.2, 62.4, 73.2, 74.9,
5.1, 109.8, 114.4, 120.6, 127.6, 129.0, 132.7, 143.0, 158.4, 162.8,
6
C
ꢀ
1
67.1, 170.0, 180.9; IR (ATR KBr cell, cm ) 1125, 1748, 2520,
152, 3420; LC-MS calcd m/z: 471 found 472 [(M + 1)] . Anal.
+
calcd for C H N O : C, 68.77; H, 6.20; N, 14.85; found: C,
6
2
7
27 5 3
8.73; H, 6.15; N, 14.83.
0
0
0
0
2
0
-(2-Amino-6-methoxypyrimidin-4yl)-1 -(4-uorophenyl)-1 ,2 ,
0
0
0
0
5
,6 ,7 ,7a -hexahydrospiro[indoline-3,3 -pyrrolizin]-2-one 10c.
ꢁ
1
Off white solid; isolated yield 0.076 g (80%); M. Pt. 128 C; H
NMR (400 MHz, DMSO-d ) d : 1.70–1.73 (m, 2H), 1.83–1.89 (m,
H), 2.36–2.40 (m, 1H), 2.48–2.53 (m, 1H), 3.56 (s, 3H), 3.74–3.78
6
H
2
(
m, 1H), 3.85–3.91 (m, 1H), 4.01 (d, J ¼ 12.4 Hz, 1H), 5.60 (s, 1H),
5 (a) A. Jossang, P. Jossang, H. A. Hadi, T. Sevenet and B. Bodo,
J. Org. Chem., 1991, 56, 6527–6530; (b) U. K. Syam Kumar,
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2407–2412.
8 R. C. Eldereld and R. E. Gilman, Phytochemistry, 1972, 11,
6
1
2
4
1
1
.15 (s, 2H), 6.67 (d, J ¼ 7.6 Hz, 1H), 6.87 (td, J ¼ 1.2 Hz, 7.6 Hz,
H), 7.06–7.15 (m, 3H), 7.38 (d, J ¼ 7.6 Hz, 1H), 7.42–7.46 (m,
1
3
H), 10.14 (s, 1H); C NMR (75 MHz, DMSO-d ) d : 27.7, 30.6,
6
C
7.6, 51.3, 53.0, 62.8, 73.0, 74.8, 95.0, 109.8, 115.6, 115.8, 120.7,
26.1, 127.6, 129.1, 129.8, 129.9, 137.0, 142.8, 162.8, 166.8,
ꢀ1
70.1, 179.9; IR (ATR KBr cell, cm ) 1176, 1740, 2360, 3340; LC-
+
MS calcd m/z: 445 found 446 [(M + 1)] . Anal. calcd for
339–343.
33718 | RSC Adv., 2015, 5, 33705–33719
This journal is © The Royal Society of Chemistry 2015

View Article Online
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1
1
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