Copper-Catalyzed Domino Addition, Hydroamination, and Cyclization: A Multicomponent Approach to Spiro Oxazolidinone Derivatives

Article abstract of DOI:10.1021/acs.joc.8b02461

A copper-catalyzed one-pot multicomponent protocol has been developed for construction of spiro heterocycles. The domino approach leads to the synthesis of spiro oxazolidinones starting from ketones, arylacetylenes, and isocyanates via catalytic addition,

Full text of DOI:10.1021/acs.joc.8b02461

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Article
Copper-catalyzed Domino Addition, Hydroamination and Cyclization:
A Multicomponent Approach to Spiro Oxazolidinone Derivatives
Gal Reddy Potuganti, Divakar Reddy Indukuri, Jagadeesh Babu Nanubolu, and Manjula Alla
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 22 Nov 2018
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Copper-catalyzed Domino Addition, Hydroamination and
Cyclization: A Multicomponent Approach to Spiro
Oxazolidinone Derivatives
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†‡
†‡
Gal Reddy Potuganti,
Alla.*†‡
Divakar Reddy Indukuri,
Jagadeesh Babu Nanubolu‖ Manjula
†Flouro-Agrochemicals Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007,
India.
‖Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500
007, India.
‡Academy of Scientific and Innovative Research, CSIR- Indian Institute of Chemical Technology, Tarnaka,
Hyderabad, 500007, India.
Email: manjula@iict.res.in
Abstract
Copper-catalysed one-pot multicomponent protocol has been developed for construction of
spiro heterocycles. The domino approach, leads to synthesis of spiro oxazolidinones starting
from ketones, arylacetylenes, and isocyanates via catalytic addition, hydroamination and
cyclization involving consecutive C-C, C-O, and C-N bond formations.
INTRODUCTION
Metal catalysed domino transformations allow construction of complex molecules
from readily available starting materials.1 Additionally, these metal mediated domino
transformations involving intramolecular hydroamination as a key step, leading to formation
of multiple C-C and C-N bonds, have become reliable and valuable tool for assembling
structurally diverse N-heterocycles.2 A classic metal catalysed three component approach
involving assembly of alkyne, carbonyl, and amine has been much adopted for construction
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of many N-heterocycles such as oxazolidinones. Oxazolidinones and their derivatives have
been widely used not only as chiral synthons or chiral auxiliaries 3 but also pharmaceuticals 4
and agrochemicals 5 due a diverse range of biological activities.6
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The feasibility of C-C bond formation, through C-H activation of terminal alkynes to
carbonyl compound has been a much investigated protocol for construction of propargyl
alcohols. These compounds are versatile building blocks for natural products and also
oxazolidinones.7 Direct nucleophilic addition of alkyne to ketones is rather difficult due to its
lower reactivity compared with aldehydes and imines.8 In recent years, metal mediated C-H
activation direct alkynylation has been explored for synthesis of propargyl alcohol of
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carbonyls supported by various catalysts such as copper,
zinc-mediated, 10 silver, NHC-
12
13
silver complexes,11 copper/guanidine,
literature.
and Rh-Phosphine
etc., has been reported in
On the other hand catalytic hydroamination i.e., nucleophilic addition of N-H across
C-C multiple bonds followed by cyclization has been an important tool in synthesis of many
spiro oxazolidinone. Bäckvall et al reported palladium catalyzed intramolecular
hydroamination of propargylic carbamates (Scheme 1a).14 Later on, Liu and co-workers
reported ruthenium complex catalyzed domino addition/exo cycloisomerization of
propargylic alcohols and tosyl isocyanates (Scheme 1b).15 Looper and co-workers reported
rhodium catalyzed hydroamination of propargyl guanidines.16 Silver catalyzed activation of
internal propargylic alcohols in supercritical carbon dioxide has been reported by Zhao’s et al
(Scheme 1c).17 While numerous synthetic approaches to access spiro oxazolidinones have
been investigated many of them involve harsh reaction conditions, and use of expensive
catalysts.
As a part of our group’s continuous efforts towards development of copper-catalyzed
reaction protocols, 18 one of the major objectives was to uncover a synthetic procedure that
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allows multiple carbon-carbon and/or carbon-heteroatom bond formations. Prior reports on
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such transformations by Sun,19 Yamada,20 and Nair served as inspiration behind the
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proposed one-pot multicomponent copper-mediated protocol (Scheme 1d). Herein, we report
copper-catalysed synthesis of spiro oxazolidinone framework as a viable alternative to the
existing expensive catalyst based (Ag, Pd, Ru, Au) methods.
Scheme 1: Previous and Present Approaches:
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Previous work:
This work: (d) Synthesis of Spiro oxazololidinones from readily available starting materials.
Results and Discussion
An assessment study on suitability of the proposed method has been performed using
N-methyl isatin (1a), phenylacetylene (2a), and phenyl isocyanate (3a) as model substrates.
The desired product (Z)-4'-benzylidene-1-methyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-
2,2'-dione (4a) was obtained in 43 % yield using copper iodide (CuI) as the catalyst,
triethylamine (Et3N) as the base, and toluene as the solvent. The reaction proceeds at room
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temperature during 12 h under nitrogen atmosphere (Table 1, Entry 1). The optimum reaction
parameters
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Table 1: Synthesis of spiro oxazolidione-oxindole employing various reaction parameters.a
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Entry
1
Catalyst
CuI
Base
Et3N
solvent
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
DMF
Yield (%)b
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2
CuI
tBuOK
DIPEA
DBU
K2CO3
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
DBU
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3
CuI
36
4
CuI
86
5
CuI
NRc
59
6
CuI
7
CuI
52
8
CuI
CH3CN
DCM
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9
CuI
25
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CuI
EtOH
NR
Trace
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CuI
-
CuCl
CuBr
CuOAc
Cu(OAc)2
Cu(OTf)2
-
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
67
48
Trace
Trace
NR
aReaction Conditions: Reaction was carried out with 1a (0.621 mmol, 1equiv), CuI (10 mol %), 2a (0.745
mmol, 1.2 equiv), DBU (0.31 mmol, 0.5 equiv) and 3a (0.745 mmol, 1.2 equiv) in anhydrous toluene (3 mL) at
room temperature for 12 h under N2 atmosphere; bisolated yields were reported. cNo Reaction.
were evaluated systematically and results summarized in Table 1. Firstly, a series of bases,
such as Et3N, potassium tert-butoxide, DIPEA DBU and K2CO3 were tested (Entries 1- 5).
Among them DBU has been found to be the most effective base for this reaction (Entry 4).
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It has been observed that reaction proceeds most smoothly in toluene compared to
other solvents (DMSO, DMF, CH3CN, and DCM, Entries 6 -9). The reaction didn’t proceed
at all with EtOH as a solvent (Entry 10). A non polar solvent which helps in the formation of
the copper acetylide, and subsequent formation of the propargyl alcohol on reacting with the
electrophilic carbonyl carbon, serves as a better solvent for this reaction. In a polar protic
solvent such as ethanol, the formation of the copper acetylide is not possible. Therefore, the
reaction doesn’t progress. The reaction did not proceed at all in absence of the solvent (Entry
11).
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A comparison of catalyst efficiency has been examined at this stage, employing
various copper salts such as CuCl, CuBr, CuOAc, Cu(OAc)2 and Cu(OTf)2 (Entries 12 - 16).
Among them, CuI has been found to be the most suitable catalyst. As expected, reaction did
not proceed in the absence of catalyst (Entry 17).
The successfully optimized reaction conditions were adopted for screening various
substrates to evaluate the scope of this reaction. To begin with a range of different isocyanates
were tested (Scheme 2). Phenyl isocyanates with neutral or electron donating substituents (4-
H, 4-Me, 4-OMe) resulted in excellent yields of corresponding products (4a-4c, 75-86%).
Halogen containing phenyl isocyantates also led to formation of desired spiro oxazolidione
products in good to excellent yields (4d-4f, 65-88%). The structure of the product 4e was
confirmed by X-ray analysis (Figure-1 & S1).21 Reaction with phenyl isocyanate having
electron withdrawing substituent resulted in lower yield of corresponding product (4g, 47
%). Aliphatic isocyanates afforded the expected product with slightly lower yields compared
to phenyl isocyanates (4h-4i, 65-70%).
The substrate scope was investigated with respect to various N-methyl isatins and
phenyl acetylenes as well (Scheme 2). In general, benzene ring substitutions on N-methyl
isatin, as exemplified by 5-bromo, 5-methyl, 5-methoxy groups, gave moderate yields (4j-4l,
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66-71%). Substitutions on phenylacetylene such as 3-methyl and 3-methoxy resulted in
marginally decreased reaction yields (4m-4n, 71-73%). Halogen substituted phenylacetylene
gave moderate yield (4o, 64 %,). The reaction was unsuccessful with alkyl acetylenes under
the established reaction conditions. Isatin with an unprotected N-H group didn’t react.
Scheme 2: Scope of spiro oxazolidinone-oxindoles.a,b
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aReaction Conditions: Reaction was carried out with 1 (0.621 mmol, 1equiv), CuI (10 mol %), 2 (0.745 mmol,
1.2 equiv), DBU (0.31 mmol, 0.5 equiv) and 3 (0.745 mmol, 1.2 equiv) in anhydrous toluene (3 mL) at room
temperature for 12 h under N2 atmosphere; bisolated yields were reported
Further, the scope of this protocol was extended to other carbonyl compounds.
Cyclohexanone reacts by the established protocol to give moderate yield the product of 6a
compared with N-methyl isatin product of 4a. Once again it was noticed that the reaction
efficiency depends on electronic properties of phenyl isocyanates. As earlier phenyl
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isocyanates with neutral and electron donating (4-H, 4-Me, 4-OMe) groups attached to
phenyl ring gave better yields (Scheme 3, 6a-6c, 61-65%), while substrates with electron
withdrawing group attached phenyl isocyanate gave lower yields (6d, 42%). Gratifyingly,
halo substituted phenyl isocyanates were also successfully converted to the expected products
(6e-6g, 57-60%). The structure of the product 6f was confirmed using single-crystal X-ray
diffraction (Figure-1 & S2).21 In addition, aliphatic isocyanate also followed trend and gave
product in moderate yields (Scheme 3, 6h, 62 %).
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Scheme 3: Scope of cyclohexane containing spiro-oxazolidinones.a, b
aReaction Conditions: Reaction was carried out with 5 (0.621 mmol, 1equiv), CuI (10 mol %), 2 (0.745 mmol,
1.2 equiv), DBU (0.31 mmol, 0.5 equiv) and 3 (0.745 mmol, 1.2 equiv) in anhydrous toluene (3 mL) at room
temperature for 12 h under N2 atmosphere; bisolated yields were reported.
Carbonyls such as 9-fluorenone and acenaphthoquinone (Scheme 4) were successfully
utilized for this protocol. However, the yields were moderate (8a & 10a, 62 & 65 %). The
reaction was unsuccessful with acyclic ketones such as 3-pentanone, isobutyl methyl ketone
and t-butyl methyl ketone under the established reaction conditions.
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Scheme 4: Scope of Different Carbonyls. a, b
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aReaction Conditions: Reaction was carried out with 7 or 9 (0.621 mmol, 1 equiv), CuI (10 mol %), 2 (0.745
mmol, 1.2 equiv), DBU (0.31 mmol, 0.5 equiv) and 3 (0.745 mmol, 1.2 equiv) in anhydrous toluene (3 mL) at
room temperature for 12 h under N2 atmosphere; bisolated yields were reported.
Figure-1: Crystal structure of 4e and 6f.
4e
6f
Once, the scope of the protocol was established, our attention was focused on the
possible mechanism of the reaction. A series of control experiments were conducted to obtain
insights on the reaction pathway (Scheme 5). Firstly, the reaction was performed in a
stepwise manner and reaction intermediates isolated and characterized. N-Methyl isatin on
nucleophilic addition of copper acetylide of phenylacetylene yields the corresponding
propargyl alcohol in 89% yield (Scheme 5 i). The reaction is rapid and proceeds exclusively
under nitrogen atmosphere. The propargyl alcohol intermediate (11) reacts with phenyl
isocyanate in the presence of DBU leading to formation of propargyl carbamate in 86 % yield
(12, Scheme 5 ii). Compound 12 could be isolated in absence of catalyst. While in the
presence of base and copper salts compound 4a was formed exclusively and no carbamate
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could be isolated. The hydroamination reaction does proceed even in non-anhydrous
conditions without alteration of product yield. Both propargylation and hydroamination steps
did not proceed in the absence of catalyst (Scheme 5 i & iii). However, carbamate does form
even in the absence of catalyst. It was also observed that when the one-pot protocol was
carried out in aerobic conditions no product formation was observed (Scheme 5 iv), which
indirectly indicates reaction proceeds via propargyl alcohol intermediate (11).
Scheme 5: Control Experiments.
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The following reaction mechanism is proposed based on our experimental
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observations and previous literature reports
(Scheme 6). Initially, copper (I) iodide
coordinates with the phenylacetylene activating the terminal C-H bond. The abstraction of the
terminal proton easily by DBU leads to the formation of copper acetylide nucleophile (A),
and DBU.HI. Copper acetylide then attacks the electrophilic carbonyl carbon afford the
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addition product (C).9-13, 22a DBU.HI helps in removal of the copper from addition product to
give propargyl alcohol (D). The hydroxyl of propargylic alcohol participated in the
nucleophilic addition to the isocyanate carbon followed by intramolecular exo cyclization of
carbmate intermediate (E). Carbamate undergoes intramolecular hydroamination across the
internal C-C multiple bond, activated by copper (I) salts, resulting formation of
corresponding oxazolidinone product (4a, 88 % Scheme 5 iii). the hydroaminaton yields
desired oxazolidinone (4a). Role of copper is multifaceted in the reaction protocol. It is
involved in elecrophilic activation of triple bond for generation of acetylide and carbonyl
group as well as subsequent assistance in hydroamination.
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Scheme 6: Proposed Mechanism.
Conclusions
To summarize a convenient one-pot MCR approach for construction of spiro
heterocycles has be demonstrated successfully via a copper-catalyzed domino reaction. The
protocol involving simple starting materials such carbonyl compounds, arylacetylene, and
isocyanates proceeds through catalytic addition, hydroamination, and cyclization involving,
formation of three bonds, a C-C, a C-N, and a C-O. Once the optimized conditions were
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established this domino protocol has been successfully applied to a range of isocyanates,
substituted phenylacetylenes, substituted N-methyl isatins and other carbonyls compounds,
demonstrating its broad scope. This synthetic method with good functional group tolerance
coupled with simple substrates and reagents is a valuable tool for construction of important
sprio heterocyclic frameworks.
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EXPERIMENTAL SECTION
General Information: Commercially available reagents were used without further
purification unless otherwise specified. All the reactions were performed under an
atmosphere of nitrogen in oven-dried glassware with magnetic stirring. All reactions were
monitored by TLC analyses were performed on glass plates coated with silica gel 60 F254.
Plates were visualized using UV light (254 nm) and/or iodine. Organic solutions were dried
(Na2SO4) and concentrated under reduced pressure in a Büchi rotary evaporator. Column
chromatography was performed on silica gel (60×120 mesh) on a glass column. Melting points
1
(mp) were determined in capillary tubes and are uncorrected. H NMR spectra were recorded
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at 300, 400 and 500 MHz (using TMS, as a reference), and C NMR were recorded at 75,
100, 125 MHz (using the CDCl3 triplet centred at δ 77.0 Hz as reference) in CDCl3 and
CDCl3+DMSO as solvent at ambient temperature. Data are reported as follows: chemical
shift, integration, multiplicity (s = singlet, d = doublet, dd = doublet of doublet, br = broad, t
= triplet, q = quartet, m = multiplet). Chemical shifts were reported as (δ) in parts per million
(ppm) and Coupling constants J values are given in Hz Mass (ESI) data were recorded on
quadruple mass spectrometry. HRMS data were obtained by the ESI ionization sources. IR
spectra were recorded on a FTIR spectrometer as KBr pellets or neat.
All chemicals were purchased from Sigma-Aldrich, Spectrochem, and avra chemicals Pvt.
Ltd. India and used as received. The Spiro Oxazolidione-oxindole and other derivatives
preparation and procedures experiments are given below.
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Experimental procedure for the Preparation of (Z)-4'-benzylidene-1-methyl-3'-
phenylspiro[indoline-3,5'-oxazolidine]-2,2'-dione (4a).
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To a stirred mixture of 1-methyl-1H-indole-2, 3-dione 1a (0.621 mmol, 1equiv), CuI (10 mol
%), and phenylacetylene 2a (0.745 mmol, 1.2equiv) in anhyd toluene (3 mL), DBU (0.31
mmol, 0.5 equiv) was added at 25 °C under a N2 atmosphere. After 15 min added phenyl
isocyanate 3a (0.745 mmol, 1.2 equiv). Stirring was continued at 25 °C temperature until the
starting material was completely consumed (TLC monitoring). After completion, the mixture
was quenched with sat.aq NH4Cl (5 mL) and extracted with EtOAc (2 × 25 mL). The
combined organic layers were dried (anhyd Na2SO4) and evaporated under reduced pressure
to dryness. The crude product thus obtained was purified by column chromatography (60–
120 mesh, and EtOAc : hexane, 5:95) to afford pure 4a as a white solid; yield: 205mg (86%);
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0
m.p 216-218 C.
Experimental procedure for the Preparation of (Z)-4-benzylidene-3-phenyl-1-oxa-3-
azaspiro[4.5]decan-2-one (6a). To a stirred mixture of Cyclohexanone 5a (0.621 mmol,
1equiv), CuI (10 mol %), and phenylacetylene 2a (0.745 mmol, 1.2equiv) in anhyd toluene (3
mL), DBU (0.31 mmol, 0.5 equiv) was added at 25 °C under a N2 atmosphere. After 15 min
added phenyl isocyanate 3a (0.745 mmol, 1.2 equiv).Stirring was continued at this
temperature until the starting material was completely consumed (TLC monitoring). After
completion, the mixture was quenched with sat.aq NH4Cl (5 mL) and extracted with EtOAc
(2 × 25 mL). The combined organic layers were dried (anhyd Na2SO4) and evaporated under
reduced pressure to dryness. The crude product thus obtained was purified by column
chromatography (activated silica gel, 60–120 mesh, and EtOAc : hexane, 3:97) to afford pure
6a as a white solid; yield: 130mg (65%); 160-162 0C.
Experimental procedure for the Preparation of ((Z)-4'-benzylidene-3'-(p-tolyl)spiro[fluorene-
9,5'-oxazolidin]-2'-one (8a) OR (Z)-4'-benzylidene-3'-(p-tolyl)-2H-spiro[acenaphthylene-
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1,5'-oxazolidine]-2,2'-dione (10a). To
a
stirred mixture of 9-fluorenone
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acenapthoquinone 9 (0.621 mmol, 1equiv), CuI (10 mol %), and phenylacetylene 2a (0.745
mmol, 1.2equiv) in anhyd toluene (3 mL), DBU (0.31 mmol, 0.5 equiv) was added at 25 °C
under a N2 atmosphere. After 15 min added phenyl isocyanate 3a (0.745 mmol, 1.2
equiv).Stirring was continued at this temperature until the starting material was completely
consumed (TLC monitoring). After completion, the mixture was quenched with sat.aq NH4Cl
(5 mL) and extracted with EtOAc (2 × 25 mL). The combined organic layers were dried
(anhyd Na2SO4) and evaporated under reduced pressure to dryness. The crude product thus
obtained was purified by column chromatography (activated silica gel, 60–120 mesh, and
EtOAc : hexane, 3:97)
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(Z)-4'-Benzylidene-1-methyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-dione (4a)
4a as white solid (205mg, 86% yield); m.p 216-218 OC; eluent, hexane/ethyl acetate 95:5; 1H
NMR (300 MHz, CDCl3+DMSO-d6) δ 7.53 (t, J = 7.0 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.12
(m, 5H), 7.03 (d, J = 7.9 Hz, 1H), 6.92 – 6.79 (m, 3H), 6.63 (d, J = 7.2 Hz, 2H), 5.31 (s, 1H),
3.32 (s, 3H); 13C NMR (75 MHz, CDCl3+DMSO-d6) δ 171.0, 154.6, 144.6, 134.0, 131.6,
127.8, 127.7, 126.7, 126.5, 125.8, 125.3, 125.0, 123.5, 108.8, 103.6, 26.2; IR (KBr): 1777,
1723, 1611, 1213, 1106, 1020, 758, 698 cm-1; HRMS (ESI) m/z: calcd for C24H19O3N2
(M+H) 383.1392; found 383.1400.
(Z)-4'-Benzylidene-1-methyl-3'-(p-tolyl)spiro[indoline-3,5'-oxazolidine]-2,2'-dione (4b).
O
4b as a white solid (185mg, 75% yield); m.p 210-212 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.53 (m 2H), 7.22 (t, J = 7.4 Hz, 1H), 7.02 (m,
3H), 6.90 (m, 3H), 6.83 (t, J = 7.2 Hz, 2H), 6.63 (d, J = 7.2 Hz, 2H), 5.27 (s, 1H), 3.32 (s,
3H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 171.1, 154.8, 144.5, 136.7,
134.2, 131.6, 131.4, 128.3, 127.8, 126.4, 125.6, 125.3, 124.9, 124.0, 123.5, 108.7, 103.2,
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26.2, 20.4; IR (KBr): 1781, 1723, 1611, 1211, 1106, 1020, 753, 704 cm-1; HRMS (ESI) m/z:
calcd for C25H21O3N2 (M+H) 397.1547; found 397.1552.
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(Z)-4'-Benzylidene-3'-(4-methoxyphenyl)-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4c).
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4c as a white solid (208mg, 81% yield); m.p 160-162 OC; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.55 (t, J = 7.2 Hz, 2H), 7.37 (d, J = 9.0 Hz, 1H),
7.25 (t, J = 7.3 Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H), 6.97 – 6.89 (m, 1H), 6.88 – 6.82 (m, 2H),
6.66 (d, J = 3.6 Hz, 2H), 6.64 (d, J = 5.9 Hz, 2H), 5.29 (s, 1H), 3.73 (s, 3H), 3.34 (s, 3H); 13C
NMR (100 MHz, CDCl3+DMSO-d6) δ 171.0, 158.0, 144.5, 134.4, 131.6, 127.8, 126.8, 126.4,
125.6, 125.9, 123.9, 123.4, 120.0, 113.4, 113.0, 108.7, 102.9, 54.9, 26.2; IR (KBr): 1781,
1722, 1608, 1222, 1102, 1019, 753, 704 cm-1; HRMS (ESI) m/z: calcd for C25H21O4N2
(M+H) 413.1496; found 413.1497.
(Z)-4'-Benzylidene-3'-(4-fluorophenyl)-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4d).
O
4d as a white solid (163mg, 65% yield); m.p 240-242 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.54 (t, J = 7.4 Hz, 2H), 7.24 (t, J = 7.5 Hz, 1H),
7.14 (d, J = 4.8 Hz, 1H), 7.11 (d, J = 4.8 Hz, 1H), 7.06 (d, J = 7.9 Hz, 1H), 6.92 (m, 3H), 6.81
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(t, J = 8.6 Hz, 2H), 6.66 (d, J = 7.2 Hz, 2H), 5.33 (s, 1H), 3.32 (s, 3H); C NMR (75 MHz,
CDCl3+DMSO-d6) δ 170.9, 154.4, 144.5, 134.1, 131.6, 131.3, 130.0, 127.7, 126.9, 126.8,
126.5, 125.9, 125.2, 123.5, 123.4, 114.7, 114.4, 108.7, 103.4, 26.1; C-F Coupling constants:
(126.8 JC-F, 8.6 Hz, 114.5 JC-F 23.0); IR (KBr): 1783, 1723, 1610, 1513, 1251, 1104, 1022,
753, 702 cm-1; HRMS (ESI) m/z: calcd for C24H18O3N2F (M+H) 401.1296; found 401.1313.
(Z)-4'-Benzylidene-3'-(4-chlorophenyl)-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-dione
(4e).
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4e as a white solid (228mg, 88% yield); m.p 220-222 OC; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.59 – 7.48 (m, 2H), 7.25 (d, J = 5.2 Hz, 1H), 7.22
(d, J = 7.1 Hz, 1H), 7.10 (m, 3H), 7.04 (d, J = 8.0 Hz, 1H), 6.99 – 6.87 (m, 3H), 6.66 (d, J =
7.3 Hz, 2H), 5.34 (s, 1H), 3.32 (s, 3H); 13C NMR (75 MHz, CDCl3+DMSO-d6) δ 171.0,
154.4, 144.6, 133.8, 132.6, 132.1, 131.8, 131.4, 128.1, 127.8, 126.7, 126.3, 126.1, 125.4,
123.6, 119.3, 108.9, 104.0, 26.3; IR (KBr): 1784, 1722, 1610, 1493, 1209, 1091, 1018, 753,
704 cm-1; HRMS (ESI) m/z: calcd for C24H18O3N2Cl (M+H) 417.1001; found 417.1019.
(Z)-4'-Benzylidene-3'-(3,4-dichlorophenyl)-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4f).
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4f as a white solid (208mg, 74% yield); m.p 208-210 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.59 – 7.52 (m, 2H), 7.27 – 7.20 (m, 2H), 7.19 (d,
J = 5.8 Hz, 1H), 7.06 (m, 2H), 7.01 (d, J = 9.3 Hz, 1H), 6.98 – 6.91 (m, 2H), 6.70 (d, J = 6.9
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Hz, 2H), 5.41 (s, 1H), 3.32 (s, 3H); C NMR (75 MHz, CDCl3+DMSO-d6) δ 170.7, 153.9,
144.5, 133.5, 133.1, 131.8, 131.3, 131.2, 130.2, 129.1, 127.6, 126.9, 126.7, 126.3, 125.4,
124.3, 123.5, 123.1, 108.8, 104.4, 26.2; IR (KBr): 1788, 1721, 1610, 1472, 1206, 1102, 1022,
753, 702 cm-1; HRMS (ESI) m/z: calcd for C24H17O3N2Cl2 (M+H) 451.0611; found
451.0619.
(Z)-4'-Benzylidene-1-methyl-3'-(4-nitrophenyl)spiro[indoline-3,5'-oxazolidine]-2,2'-dione
(4g).
O
4g as yellow solid (125mg, 47% yield); m.p 222-224 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.95 (d, J = 9.1 Hz, 2H), 7.60 – 7.53 (m, 2H), 7.35
(d, J = 9.0 Hz, 2H), 7.25 (t, J = 7.5 Hz, 1H), 7.06 (d, J = 8.0 Hz, 1H), 6.97 – 6.86 (m, 3H),
6.71 (d, J = 6.6 Hz, 2H), 5.49 (s, 1H), 3.33 (s, 3H); 13C NMR (75 MHz, CDCl3+DMSO-d6) δ
170.4, 153.4, 144.6, 144.4, 139.3, 132.7, 131.8, 131.1, 127.4, 126.7, 126.4, 125.3, 124.6,
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123.4, 122.7, 122.5, 108.8, 105.5, 26.0; IR (KBr): 1782, 1734, 1610,1524, 1231, 1112, 1015,
754, 700 cm-1; HRMS (ESI) m/z: calcd for C24H18O5N3 (M+H) 428.1241; found 428.1258.
(Z)-4'-Benzylidene-3'-hexyl-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-dione (4h).
O
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4h as a white solid (158mg, 65% yield); m.p 160-162 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.48 – 7.42 (m, 1H), 7.37 (dd, J = 7.5, 0.8 Hz, 1H), 7.30 –
7.27 (m, 1H), 7.26 – 7.22 (m, 2H), 7.19 – 7.14 (m, 1H), 7.12 (dd, J = 6.7, 0.8 Hz, 2H), 6.91
(d, J = 7.9 Hz, 1H), 5.19 (s, 1H), 3.58 – 3.45 (m, 1H), 3.43 – 3.32 (m, 1H), 3.25 (s, 3H), 1.31
– 1.17 (m, 2H), 1.16 – 1.07 (m, 2H), 1.04 – 0.94 (m, 2H), 0.88 (ddd, J = 12.5, 9.7, 6.1 Hz,
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2H), 0.78 (t, J = 7.3 Hz, 3H); C NMR (100 MHz, CDCl3 ) δ 171.7, 156.5, 145.0, 135.7,
133.7, 132.0, 131.8, 130.5, 129.3, 129.0, 128.2, 127.9, 127.2, 125.6, 125.5, 124.7, 123.9,
123.7, 108.9, 101.7, 43.8, 40.7, 31.1, 26.8, 25.6, 22.4, 13.9; IR (KBr): 1780, 1723, 1612,
1468, 1354, 1077, 1016, 753, 705 cm-1; HRMS (ESI) m/z: calcd for C24H27O3N2 (M+H)
391.2016; found 391.2024.
(Z)-4'-Benzylidene-3'-isopropyl-1-methylspiro[indoline-3,5'-oxazolidine]-2,2'-dione (4i).
O
4i as a white solid (150mg, 70% yield); m.p 190-192 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.43 (td, J = 7.8, 1.2 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.29 (t,
J = 7.3 Hz, 2H), 7.22 (dd, J = 8.7, 6.0 Hz, 1H), 7.16 (m, 3H), 6.90 (d, J = 7.9 Hz, 1H), 5.09
(s, 1H), 3.76 (m, 1H), 3.25 (s, 3H), 1.40 (dd, J = 9.8, 6.8 Hz, 6H); 13C NMR (100 MHz,
CDCl3+DMSO) δ 171.3, 155.1, 144.4, 136.2, 133.4, 131.4, 128.1, 127.7, 126.8, 125.0, 124.9,
123.5, 108.7, 101.6, 47.9, 26.2, 18.4; IR (KBr): 1774, 1727, 1611, 1467, 1296, 1102, 1018,
762, 704 cm-1; HRMS (ESI) m/z: calcd for C21H21O3N2 (M+H) 349.1547; found 349.1562.
(Z)-4'-Benzylidene-5-bromo-1-methyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-dione
(4j).
O
4j as a white solid (188mg, 66% yield); m.p 206-208 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.79 (s, 1H), 7.67 (dd, J = 8.4, 2.0 Hz, 1H), 7.12
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(br, 5H), 7.05 (d, J = 8.4 Hz, 1H), 6.93 – 6.79 (m, 3H), 6.66 (d, J = 7.1 Hz, 2H), 5.33 (s, 1H),
3.31 (s, 3H); 13C NMR (75 MHz, CDCl3+MSO-d6) δ 169.8, 153.5, 151.7, 143.1, 138.4,
133.8, 133.2, 132.8, 130.6, 127.6, 127.5, 127.0, 126.1, 125.8, 125.2, 125.0, 124.3, 120.7,
117.2, 114.8, 110.1, 102.9, 25.7; IR (KBr): 1779, 1743, 1610, 1493, 1221, 1110, 1022, 755,
694 cm-1; HRMS (ESI) m/z: calcd for C24H18O3N2Br (M+H) 461.0495; found 461.0510.
(Z)-4'-Benzylidene-1,5-dimethyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-dione (4k).
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4k as a white solid (168mg, 68% yield); m.p 208-210 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.34 (s, 1H), 7.31 (d, J = 8.1 Hz, 1H), 7.17 – 7.07
(m, 5H), 6.91 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 13.3, 5.9 Hz, 3H), 6.64 (d, J = 7.1 Hz, 2H),
5.31 (s, 1H), 3.29 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3+DMSO-d6) δ 170.9,
154.5, 142.0, 133.9, 133.8, 133.1, 131.8, 131.4, 127.6, 127.5, 126.51, 126.3, 125.7, 125.6,
124.9, 123.6, 108.5, 103.4, 26.1, 20.3; IR (KBr): 1780, 1738, 1625, 1499, 1219, 1111, 1022,
757,694 cm-1; HRMS (ESI) m/z: calcd for C25H21O3N2 (M+H) 397.1547; found 397.1569.
(Z)-4'-Benzylidene-5-methoxy-1-methyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4l).
4l as a white solid (164 mg, 71 % yield); m.p 228-230 OC; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.12 (m, 6H), 7.05 (dd, J = 8.6, 2.4 Hz, 1H), 6.97
(d, J = 8.5 Hz, 1H), 6.92 – 6.79 (m, 3H), 6.64 (d, J = 7.2 Hz, 2H), 5.31 (s, 1H), 3.83 (s, 3H),
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3.30 (s, 3H); C NMR (125 MHz, CDCl3+DMSO-d6) δ 170.0, 155.4, 153.7, 136.9, 133.3,
130.8, 127.0, 126.9, 125.9, 125.7, 125.0, 124.3, 124.0, 115.5, 111.3, 108.9, 102.6, 54.6, 25.5;
IR (KBr): 1781, 1722, 1608, 1220, 1102, 1019, 753, 704 cm-1; HRMS (ESI) m/z: calcd for
C25H21O4N2 (M+H) 413.1496; found 413.1503.
(Z)-1-Methyl-4'-(3-methylbenzylidene)-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-dione
(4m).
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4m as a white solid (175mg, 71% yield); m.p 208-210 OC; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.53 (dd, J = 5.5, 3.8 Hz, 1H), 7.22 (t, J = 7.6 Hz,
1H), 7.19 – 7.07 (m, 5H), 7.03 (d, J = 8.0 Hz, 1H), 6.78 (t, J = 7.5 Hz, 1H), 6.70 (d, J = 7.5
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Hz, 1H), 6.49 (d, J = 7.4 Hz, 1H), 6.40 (s, 1H), 5.27 (s, 1H), 3.32 (s, 3H), 1.96 (s, 3H); C
NMR (75 MHz, CDCl3+DMSO-d6) δ 171.2, 154.8, 144.7, 136.1, 134.3, 133.9, 131.7, 131.5,
129.1, 127.9, 126.8, 126.7, 126.6, 125.4, 125.1, 124.8, 124.1, 123.6, 108.8, 103.9, 26.3, 20.4;
IR (KBr): 1778,1725, 1610,1485, 1217, 1101, 1021, 754, 696 cm-1; HRMS (ESI) m/z: calcd
for C25H20O3N2Na (M+Na) 419.1366; found 419.1380.
(Z)-4'-(3-Methoxybenzylidene)-1-methyl-3'-phenylspiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4n).
O
4n as a white solid (188mg, 73% yield); m.p 168-170 C; eluent, hexane/ethyl acetate
95:5;1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.53 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.6 Hz,
1H), 7.13 (m, 5H), 7.05 (d, J = 7.9 Hz, 1H), 6.78 (t, J = 7.9 Hz, 1H), 6.45 (dd, J = 8.2, 1.9
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Hz, 1H), 6.27 (d, J = 7.6 Hz, 1H), 6.15 (s, 1H), 5.29 (s, 1H), 3.52 (s, 3H), 3.32 (s, 3H); C
NMR (75 MHz, CDCl3+DMSO-d6) δ 170.9, 157.8, 154.5, 144.5, 134.1, 134.0, 132.9, 131.6,
127.7, 127.5, 126.6, 125.3, 124.8, 123.7, 123.5, 120.4, 112.8, 112.3, 108.8, 103.5, 54.3, 26.2;
IR (KBr): 1782, 1727, 1609, 1470, 1215,1104,1021, 749, 694 cm-1; HRMS (ESI) m/z: calcd
for C25H21O4N2 (M+H) 413.1496; found 413.1513.
(Z)-4'-(4-Fluorobenzylidene)-1-methyl-3'-(p-tolyl)spiro[indoline-3,5'-oxazolidine]-2,2'-
dione (4o).
O
4o as a white solid (165mg, 64% yield); m.p 260-262 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (300 MHz, CDCl3+DMSO-d6) δ 7.52 (dd, J = 6.8, 4.1 Hz, 2H), 7.22 (t, J = 7.6 Hz,
1H), 7.13 (t, J = 4.8 Hz,, 4H), 7.04 (d, J = 8.1 Hz, 1H), 6.64 (d, J = 7.9 Hz, 2H), 6.51 (d, J =
8.0 Hz, 2H), 5.26 (s, H), 3.32 (s, 3H), 2.12 (s, 3H); 13C NMR (75 MHz, CDCl3+DMSO-d6) δ
171.0, 152.7, 144.5, 136.4, 135.5, 134.0, 133.2, 131.6, 130.7, 128.6, 127.7, 127.6, 127.1,
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1610, 1472, 1211, 1106, 1020, 753, 704 cm-1; HRMS (ESI) m/z: calcd for C25H20O3N2F
(M+H) 415.1453; found 415.1453.
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(Z)-4-Benzylidene-3-phenyl-1-oxa-3-azaspiro[4.5]decan-2-one (6a).
O
6a as a white solid (130mg, 65% yield); m.p 160-162 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.07 – 7.01 (m, 3H), 7.00 – 6.96 (m, 2H), 6.91 – 6.82 (m, 3H),
6.65 (dd, J = 7.2, 1.0 Hz, 2H), 5.59 (s, 1H), 2.15 (d, J = 13.0 Hz, 2H), 1.90 – 1.71 (m, 7H),
1.36 (m, 1H).13C NMR (100 MHz, CDCl3) δ 155.6, 142.4, 135.0, 133.4, 128.3, 128.2, 127.0,
126.8, 125.9, 125.6, 99.9, 84.8, 37.2, 24.7, 21.8. IR (KBr):1761, 1666, 1404, 1274, 1212,
1110, 757, 702 cm-1; HRMS (ESI) m/z: calcd for C21H22O2N (M+H) 320.1645; found
320.1652.
(Z)-4-Benzylidene-3-(p-tolyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6b).
O
6b as a white solid (127mg, 61% yield); m.p 144-146 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 6.91 – 6.81 (m, 7H), 6.65 (dd, J = 7.2, 1.0 Hz, 2H), 5.55 (s,
13
1H), 2.18 (s, 3H), 2.14 (d, J = 13.3 Hz, 2H), 1.89 – 1.69 (m, 7H), 1.42 – 1.26 (m, 1H); C
NMR (100 MHz, CDCl3) δ 155.7, 142.7, 136.8, 133.5, 132.4, 128.7, 128.4, 126.9, 125.7,
125.5, 99.6, 84.6, 37.2, 24.7, 21.8, 20.9; IR (KBr): 1761, 1666, 1404, 1273, 1213, 1111, 758,
702 cm-1; HRMS (ESI) m/z: calcd for C22H24O2N (M+H) 334.1802; found 334.1805.
(Z)-4-Benzylidene-3-(4-methoxyphenyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6c).
O
6c as a white solid (136mg, 62% yield); m.p 142-143 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 6.93 – 6.83 (m, 5H), 6.66 (dd, J = 7.2, 1.0 Hz, 2H), 6.59 –
6.52 (m, 2H), 5.56 (s, 1H), 3.68 (s, 3H), 2.13 (d, J = 12.4 Hz, 2H), 1.91 – 1.68 (m, 7H), 1.45
– 1.25 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 158.3, 155.8, 142.9, 133.4, 128.5, 127.9,
127.2, 127.0, 125.6, 113.5, 99.5, 84.6, 55.5, 37.3, 24.7, 21.8; IR (KBr):1756, 1661, 1513,
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1408, 1274, 1215, 1111, 760, 700 cm-1; HRMS (ESI) m/z: calcd for C22H24O3N (M+H)
350.1751; found 350.1755.
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(Z)-4-Benzylidene-3-(4-nitrophenyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6d).
O
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6d as a yellow solid (95mg, 42% yield); m.p 166-168 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 1.9 Hz, 2H), 7.19 – 7.14 (m, 2H), 6.96 – 6.86 (m,
3H), 6.68 (dd, J = 7.0, 1.2 Hz, 2H), 5.76 (s, 1H), 2.15 (d, J = 11.4 Hz, 2H), 1.90 – 1.74 (m,
7H), 1.45 – 1.31 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 154.4, 145.2, 141.2, 140.5, 133.0,
128.1, 127.4, 126.6, 125.7, 123.3, 101.8, 85.4, 37.0, 24.6, 21.7; IR (KBr):1757,1665, 1523,
1495, 1270, 1230, 1113, 1074, 757, 695 cm-1; HRMS (ESI) m/z: calcd for C21H21O4N2
(M+H) 365.1496; found 365.1513.
(Z)-4-Benzylidene-3-(4-fluorophenyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6e).
O
6e as a white solid (122mg, 58% yield); m.p 158-160 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 6.98 – 6.87 (m, 5H), 6.75 – 6.68 (m, 2H), 6.68 – 6.63 (m, 2H),
5.61 (s, 1H), 2.14 (d, J = 12.3 Hz, 2H), 1.89 – 1.69 (m, 7H), 1.41 – 1.30 (m, 1H).13C NMR
(125 MHz, CDCl3) δ 162.1,160.1, 155.5, 142.5, 133.2, 131.0, 128.4, 127.8, 127.6, 127.1,
125.9, 115.1, 114.9, 99.9, 84.9, 37.2, 24.7, 21.8; C-F Coupling constants: (161.1, JC-F 247.2
Hz, 127.7 JC-F, 8.7 Hz, 115.1 JC-F 23.1) ; IR (neat):1752,1664, 1602, 1506, 1271, 1217, 1113,
1090, 758, 707 cm-1; HRMS (ESI) m/z: calcd for C21H21O2NF (M+H) 338.1551; found
338.1554.
(Z)-4-Benzylidene-3-(4-chlorophenyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6f).
O
6f as a white solid (132mg, 60% yield); m.p 160-162 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.01 – 6.96 (m, 2H), 6.96 – 6.88 (m, 5H), 6.66 (d, J = 7.5 Hz,
13
2H), 5.62 (s, 1H), 2.13 (d, J = 12.2 Hz, 2H), 1.91 – 1.70 (m, 7H), 1.36 (m, 1H); C NMR
(100 MHz, CDCl3) δ 155.2, 142.2, 133.5, 133.2, 132.5, 128.4, 128.2, 127.2, 127.1, 126.0,
100.2, 84.9, 37.2, 24.7, 21.7; IR (neat):1753,1664, 1602, 1506, 1447, 1272, 1218, 1113,
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1090, 758, 695 cm-1; HRMS (ESI) m/z: calcd for C21H21O2NCl (M+H) 354.1255; found
354.1271.
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(Z)-4-Benzylidene-3-(3,4-dichlorophenyl)-1-oxa-3-azaspiro[4.5]decan-2-one (6g).
O
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6g as a white solid (140mg, 57% yield); m.p 178-180 C; eluent, hexane/ethyl acetate 97:3;
1H NMR (400 MHz, CDCl3) δ 7.10 (d, J = 8.6 Hz, 1H), 7.01 (d, J = 2.4 Hz, 1H), 6.99 – 6.92
(m, 3H), 6.89 (dd, J = 8.6, 2.4 Hz, 1H), 6.69 (d, J = 6.7 Hz, 2H), 5.67 (s, 1H), 2.13 (d, J =
11.9 Hz, 2H), 1.89 – 1.70 (m, 7H), 1.41 – 1.30 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
154.8, 142.0., 134.2, 133.1, 132.0, 130.7, 129.6, 128.3, 128.0, 127.4, 126.4, 125.2, 100.7,
85.1, 37.2, 24.6, 21.7; IR (KBr):1770,1674, 1473, 1400, 1271, 1221, 1110, 1027, 753, 698
cm-1; HRMS (ESI) m/z: calcd for C21H20O2NCl2 (M+H) 388.0866; found 388.0876.
(Z)-4-Benzylidene-3-hexyl-1-oxa-3-azaspiro[4.5]decan-2-one (6h)
1
6h as a color less oil (126mg, 62% yield); eluent, hexane/ethyl acetate 97:3; H NMR (400
MHz, CDCl3) δ 7.44 (m, 2H), 7.28 (m, 3H), 4.71 (s, 1H), 3.15 (dd, J = 12.9, 6.4 Hz, 2H),
2.28 – 2.17 (m, 2H), 2.05 – 1.84 (m, 2H), 1.74 – 1.60 (m, 5H), 1.55 – 144 (m, 2H), 1.28 (s,
6H), 0.87 (t, J = 5.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.7, 131.8, 128.0, 122.9,
89.8, 85.7, 75.3, 40.7, 37.5, 31.4, 29.9, 26.4, 25.2, 22.75, 22.5, 13.9; IR (neat); 1700, 1508,
1491, 1444, 1268, 1237, 1454, 1068, 754, 690 cm-1; HRMS (ESI) m/z: calcd for C21H30NO2
(M+H) 328.2271; found 328.2283.
(Z)-4'-Benzylidene-3'-(p-tolyl)spiro[fluorene-9,5'-oxazolidin]-2'-one (8a)
O
8a as a white solid (160mg, 62% yield); m.p 172-174 C; eluent, hexane/ethyl acetate 95:5
1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.6 Hz, 2H), 7.55 (d, J = 7.5 Hz, 2H), 7.48 (t, J =
7.5 Hz, 2H), 7.35 (t, J = 7.5 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.89
– 6.83 (m, 1H), 6.80 (t, J = 7.3 Hz, 2H), 6.58 (d, J = 7.0 Hz, 2H), 5.24 (s, 1H), 2.24 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 156.2, 144.2, 140.6, 137.4, 137.0, 132.9, 132.5, 130.6, 129.0,
128.8, 128.4, 126.9, 125.9, 125.1, 124.5, 120.5, 103.1, 89.8, 21.0; IR (neat); 1776, 1673,
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1512, 1450, 1283, 1221, 1107, 1006, 753, 737 cm-1; HRMS (ESI) m/z: calcd for C29H22NO2
(M+H) 416.1645; found 416.1646.
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(Z)-4'-Benzylidene-3'-(p-tolyl)-2H-spiro[acenaphthylene-1,5'-oxazolidine]-2,2'-dione (10a)
10a as a white solid (168mg, 65% yield); m.p 184-186 OC; eluent, hexane/ethyl acetate 95:5;
1H NMR (400 MHz, CDCl3) δ 7.81 (t, J = 8.1 Hz, 2H), 7.71 – 7.62 (m, 4H), 7.52 (d, J = 8.3
Hz, 2H), 7.42 (d, J = 7.1 Hz, 1H), 7.40 – 7.37 (m, 3H), 7.28 (d, J = 8.2 Hz, 2H), 7.10 (d, J =
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7.0 Hz, 1H), 6.01 (s, 1H), 2.42 (s, 3H).; C NMR (125 MHz, CDCl3) δ 161.7, 155.2, 138.5,
137.8, 137.5, 136.4, 132.4, 132.0, 130.3, 129.9, 129.0, 128.7, 128.5, 128.2, 126.5, 126.1,
125.9, 125.8, 120.4, 107.8, 99.8, 96.7, 77.3, 77.0, 76.8, 21.2; IR (neat); 1764, 1635, 1514,
1493, 1273, 1218, 1085, 1017, 770, 726 cm-1; HRMS (ESI) m/z: calcd for C28H20NO3 (M+H)
418.1438; found 418.1444
3-Hydroxy-1-methyl-3-(phenylethynyl)indolin-2-one (11)
O
11 as a very light yellow solid (146mg, 89% yield); m.p 164-166 C; eluent, hexane/ethyl
1
acetate 80:20; H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 1H), 7.42 (dd, J = 8.2, 1.5
Hz, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.33 – 7.27 (m, 1H), 7.28 – 7.22 (m, 2H), 7.15 (t, J = 7.6
Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 4.03 (s, 1H), 3.22 (s, 3H).; 13C NMR (100 MHz, CDCl3) δ
174.0, 143.0, 132.0, 130.4, 128.9, 128.1, 124.7, 123.7, 121.6, 108.8, 86.2, 85.5, 69.51, 26.6;
IR (neat); 3346, 2222, 1709, 1614, 1470, 1371, 1200, 1091, 993, 753, 692 cm-1; HRMS (ESI)
m/z: calcd for C17H13NO2Na (M+Na) 286.0838; found 286.0839.
1-methyl-2-oxo-3-(phenylethynyl)indolin-3-yl phenylcarbamate (12)
O
12 as a white solid (129mg, 88% yield); m.p 162-164 C; eluent, hexane/ethyl acetate 95:5;
1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.4 Hz, 1H), 7.38 (d, J = 6.7 Hz, 2H), 7.31 (t, J =
8.4 Hz, 1H), 7.25 – 7.14 (m, 7H), 7.05 (t, J = 7.6 Hz, 1H), 6.96 (m, 1H), 6.87 (s, 1H), 6.82 (d,
J = 7.9 Hz, 1H), 3.25 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.9, 150.3, 143.5, 138.3,
136.8, 132.2, 130.7, 129.3, 129.2, 129.0, 128.2, 127.1, 124.1, 123.97, 123.7, 123.5, 121.2,
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120.6, 118.9, 108.9, 87.7, 82.2, 27.01; IR (KBr); 3286, 2230, 1723, 1640, 1605, 1365, 1222,
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1078, 1015, 752, 690 cm-1; HRMS (ESI) m/z: calcd for C24H19N2O3 (M+H) 383.1395; found
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ASSOCIATED CONTENT
Supporting Information
Copies of 1H, 13C NMR spectra and Crystal data for the new compounds 4e and 6f including
CIF files. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding author
*E-mail: manjula@iict.res.in
ACKNOWLEDMENT
We would like to thanks Director, CSIR-IICT and AcSIR for facilities. PGR thanks CSIR and
IDR thanks DST, New Delhi for fellowship. Manuscript communication number:
IICT/Pubs./2018/254.
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