Base-promoted expedient access to spiroisatins: Synthesis and antitubercular evaluation of 1 h -1,2,3-triazole-tethered spiroisatin-ferrocene and isatin-ferrocene conjugates

Article abstract of DOI:10.1021/om4009229

The use of sodium hydride provides a convenient access to the synthesis of C-5-functionalized spiroisatins with the absence of the typical drawbacks associated with conventional protocols. The synthesized precursors, viz. N-alkylazido spiroisatins and their unprotected counterparts, were explored in Cu-mediated azide-alkyne cycloaddition reactions to probe the antitubercular structure-activity relationships (SAR) within the isatin-ferrocene-triazole conjugate family. The antitubercular evaluation studies of the synthesized conjugates revealed an improvement in the minimal inhibitory concentration (MIC) with the introduction of ferrocene nucleus, as evidenced by spiroisatin-ferrocene and isatin-ferrocene hybrids.

Full text of DOI:10.1021/om4009229

Article
pubs.acs.org/Organometallics
Base-Promoted Expedient Access to Spiroisatins: Synthesis and
Antitubercular Evaluation of 1H‑1,2,3-Triazole-Tethered Spiroisatin−
Ferrocene and Isatin−Ferrocene Conjugates
Kewal Kumar,† Christophe Biot,‡,§ Severine Carrere-Kremer,∥ Laurent Kremer,∥,⊥ Yann Guerardel,‡,§
́
̀
́
Pascal Roussel,# and Vipan Kumar*,†
†Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, Punjab, India
‡Unite
de Glycobiologie Structurale et Fonctionnelle, Universite Lille 1, F-59650 Villeneuve d’Ascq, France
§CNRS, UMR 8576, F-59650 Villeneuve d’Ascq, France
∥Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, UMR 5235 CNRS, Universite
Place Eugene Bataillon, 34095 Montpellier Cedex 05, France
⊥DIMNP, INSERM, Place Eugen
e Bataillon, 34095 Montpellier Cedex 05, France
#UMR CNRS 8181, United
e Catalyse et de Chimie du Solide (UCCS), ENSCL, University Lille Nord de France, F-59000 Lille,
́
́
́
Montpellier 2I,
̀
̀
́
France
S
* Supporting Information
ABSTRACT: The use of sodium hydride provides a
convenient access to the synthesis of C-5-functionalized
spiroisatins with the absence of the typical drawbacks
associated with conventional protocols. The synthesized
precursors, viz. N-alkylazido spiroisatins and their unprotected
counterparts, were explored in Cu-mediated azide−alkyne
cycloaddition reactions to probe the antitubercular structure−
activity relationships (SAR) within the isatin−ferrocene−
triazole conjugate family. The antitubercular evaluation studies
of the synthesized conjugates revealed an improvement in the
minimal inhibitory concentration (MIC) with the introduction
of ferrocene nucleus, as evidenced by spiroisatin−ferrocene
and isatin−ferrocene hybrids.
further complicates the selection of an appropriate treatment
plan as a result of (a) drug−drug interactions which lead to
subtherapeutic concentrations of antiretrovirals, (b) reduction
of compliance due to the increased pill burden, and (c)
increasing safety concerns due to overlapping toxic side effects.6
The United States Food and Drug Administration (FDA)
recently approved TMC207 (bedaquiline),7 the first anti-TB
drug in over five decades, for the treatment of MDR-TB and
XDR-TB in adults. Unfortunately, like other known second-line
antitubercular drugs, it is associated with serious side effects.7
Pertaining to the drug-resistant patterns, the synthesis of novel
antimycobacterial scaffolds that work on characteristic targets
with diverse mechanisms of action, with good potency, and
INTRODUCTION
■
Tuberculosis (TB) is a highly infectious disease caused by
Mycobacterium tuberculosis (M. tuberculosis).1 It is currently the
second leading cause of death, claiming 1.4 million lives
worldwide in 2011.2 Over 95% of TB deaths occur in low- and
middle-income countries, affecting mostly children and women
aged between 15 and 44 years.3 The chemotherapeutic options
for the treatment of first-line TB have not changed for almost
five decades, with the most recent drug, rifampin, being
introduced in the early 1960s.4 Moreover, factors such as
inconsistent treatment, patient noncompliance, and the lack of
available drugs especially in economically deprived countries
have also contributed to the failure in achieving its cure.5 The
emergence of multidrug-resistant strains of tuberculosis (MDR-
TB and XDR-TB) have increased the problems associated with
TB treatment. The frequent coinfection of TB in HIV patients
Received: September 16, 2013
© XXXX American Chemical Society
A
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with little or no toxicity as well as the lack of cross resistance
with existing drugs remains pivotal.
potential.33,34 Further, isatin−ferrocene and isatin−ferrocenyl
chalcones have been prepared and assayed for their
antimycobacterial efficacy.35 The anti-TB profiles revealed a
marked improvement in the activity of isatins with the
introduction of a ferrocene nucleus, with effects more
pronounced at longer chain lengths: propyl chain tethered
conjugates are more active than those with ethyl chains. In
continuation, the present paper is a logical extension of the
above protocol and involves the synthesis of isatin−ferrocene
conjugates tethered via longer alkyl chain lengths (n = 4−8)
along with their anti-TB potential. It was envisioned that the
introduction of a longer nonhydrolyzable alkane spacer would
enhance the lipophilicity, which is considered important for
antitubercular efficacy because of its contribution toward
increasing membrane permeability.36 A convenient protocol
was also developed for the preparation of spiroisatins with
subsequent utilization in the synthesis of spiroisatin−ferrocene
conjugates so as to ascertain the role of keto−carbonyl in the
inhibition assays.
Over the past few years, syntheses of organometallic
analogues of biologically active compounds have emerged as
an important strategy with potential advantages. These
advantages include the preparation of stable metal complexes
with predictable structures, the ability to tune ligand affinities
according to their electron transfer properties, substitution
rates, and reduction potentials, and efficient biological
targeting.8 Among the incredible number and variety of roles
that metals play in contemporary medicine, the introduction of
a ferrocenyl (Fc) moiety into a drug molecule has now been
recognized as a useful approach for the development of more
effective therapeutic applications: viz., ferrocenyl analogues of
the commercial antiestrogen tamoxifen and antiandrogen
nilutamide exhibited higher cytotoxicity on breast and prostate
cancer cells with respect to the reference drugs, respectively.9
The most symbolic example of the contribution of an Fc
nucleus to enhance the activity of an organic molecule is that of
ferroquine (FQ), a chloroquine (CQ) isostere with an Fc-based
side chain that is highly active against CQ-resistant strains of
malaria parasite and have the potential to express new
organometallic-specific modes of action.10 Using drug reposi-
tioning, FQ was also proven to be a new anti-hepatitis C virus
molecule that could be used in combination with other direct-
acting antivirals.11
Isatin is a privileged scaffold that is found as an endogenous
molecule in humans, and its analogues display a diverse array of
biological and pharmacological activities, which include anti-
HIV,12 antiviral,13 antitumor,14−16 antifungal,17,18 antiangio-
genic,19 anticonvulsant,20 anti-Parkinson’s disease therapeutic,21
and effective SARS coronavirus 3CL protease inhibitor.22 The
most enthralling application of isatins in organic synthesis is
indisputably because of the highly reactive C-3 carbonyl group,
which upon nucleophilic addition or spiroannulation trans-
forms it into 2-oxoindole compounds.23 2-Oxoindoles have
generated tremendous interest among synthetic organic and
medicinal chemists not only because of their biological
activities24−30 but also because of their occurrence in natural
products such as spirotryprostatins, horsfiline, gelsemine,
gelseverine, rhynchophylline, elacomine, etc. Although a
number of methods have been reported for the synthesis of
spiroisatins, these methods are invariably associated with a
number of drawbacks, including stringent reaction conditions,
longer reaction times, moderate yields, and the use of toxic
solvents such as benzene.31
RESULT AND DISCUSSION
■
The methodology involved an initial treatment of C-5-
substituted isatin with sodium hydride, resulting in the
formation of an intensely purple anionic solution that was
subsequently reacted with 2-bromoethanol. The reaction
mixture was then heated to 60 °C until the completion of
the reaction as evidenced by TLC. Then, the usual workup via
quenching with water, extraction with ethyl acetate, and
subsequent concentration under reduced pressure resulted in
the isolation of the corresponding C-5-substituted spiroisatins
in quantitative yields (Scheme 1).
Scheme 1. Synthesis of C-5-Substituted Spiroisatins 2
1H-1,2,3-Triazoles constitute an exhilarating class of
compounds which has also attracted the attention of both
synthetic and medicinal chemists due to their synthetic
accessibility via azide−alkyne cycloaddition reactions as well
as their great biological potential.32 The molecular framework is
highly stable under basic and acid hydrolysis and reductive and
oxidative conditions, indicative of a high aromatic stabilization.
The favorable properties of 1H-1,2,3-triazoles, including high
dipole moment, capability of hydrogen bonding, and rigidity
and stability under in vivo conditions are favorable factors in
the binding of biomolecular targets.
Recent revelations from our group have shown the
introduction of a ferrocene nucleus in the β-lactam family of
therapeutics linked through the 1H-1,2,3-triazole ring with an
extension toward the synthesis of mono and bis 1H-1,2,3-
triazole-tethered β-lactam−ferrocene and β-lactam−ferrocenyl-
chalcone hybrids and the evaluation of their antitubercular
Mechanistically, the reaction involved the initial generation
of an anion by the treatment of isatin with sodium hydride
followed by its nucleophilic attack on 2-bromoethanol to yield
the corresponding 1-(2-hydroxyethyl)-1H-indole-2,3-dione 4.37
This species upon intramolecular cyclization via a facile
nucleophilic addition of free −OH to the keto−carbonyl of
isatin resulted in the formation of an intermediate, viz. C-5-
substituted 8-hydroxy-9-oxa-1-azatricyclo[6.3.1.02,7]dodeca-
2,4,6-trien-12-one 5 with subsequent ring opening to yield
the desired spiroisatins 2, as shown in Scheme 2.
The structure assigned to the product 2 was unambiguously
confirmed using X-ray crystallographic studies, and the ORTEP
diagram of compound 2b is depicted in Figure 1.
The synthesized spiroisatins 2 were sufficiently pure and
were utilized as such for further synthetic endeavors: i.e., an
initial alkylation with dibromoalkanes with subsequent treat-
ment with sodium azide in dry DMF at 60 °C. The N-
B
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Scheme 2. Plausible Mechanism for the Formation of Spiroisatins 2
alkylazido precursors 8 thus formed were subjected to Cu-
promoted azide−alkyne cycloaddition reactions with ethynyl-
ferrocene (9) to yield the desired spiroisatin−ferrocene
conjugates 10 (Scheme 3). The structures of these conjugates
were assigned on the basis of analytical data and spectral
evidence. Compound 10i, for example, exhibited the molecular
ion peak [M]+ at m/z 498.1350 along with the characteristic
peaks in the 1H and 13C NMR spectra. The 1H NMR spectrum
exhibited a singlet at δ 4.06 corresponding to 5H (ferrocene
ring protons) along with the presence of two multiplets at δ
1.69−1.73 (2H) and 1.96−2.04 (2H) and two triplets at δ 3.69
(2H) and 4.41 (2H) corresponding to the butyl chain. The
presence of a characteristic signal at 173.5 ppm corresponding
to the spiroisatin ring carbonyl along with the requisite number
of carbons in its 13C NMR spectrum further corroborated the
structure assigned to spiroisatin−ferrocene hybrids.
The synthesized conjugates 10 were then subjected to
deprotection via refluxing in an HCl−methanol mixture.38
However, the reaction resulted in the decomposition of the
starting material without the isolation of the desired isatin−
Figure 1. ORTEP diagram of spiroisatin 2b.
Scheme 3. Cu-Promoted Synthesis of 1H-1,2,3-Triazole-Tethered Spiroisatin−Ferrocene Conjugates 10
C
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Scheme 4. Synthesis of 1H-1,2,3-Triazole-Tethered Isatin−Ferrocene Conjugates 12
Table 1. In Vitro Antimycobacterial Activity of Compounds 8a−x, 10a−x, 11a−p, and 12a−p against M. tuberculosis mc26230
compd
MIC (μM)
compd
MIC (μM)
compd
MIC (μM)
compd
MIC (μM)
8a
8b
8c
8d
8e
8f
>385
>360
>340
ND
10a
10b
10c
10d
10e
10f
>213
>205
>198
ND
11a
11b
11c
11d
11e
11f
>410
12a
12b
12c
12d
12e
12f
>220
>212
>195
>214
>215
>206
>199
>208
>209
>200
>194
>201
>202
>195
>189
>196
>382
164−328
>388
>365
>343
>325
ND
>207
>199
>193
ND
>387
>368
8g
8h
8i
10g
10h
10i
11g
11h
11i
171−242
184−368
>368
12g
12h
12i
>347
>327
>311
ND
>201
>194
>188
ND
8j
10j
11j
172−344
163−326
174−348
175−350
164−328
158−312
167−334
12j
8k
8l
10k
10l
11k
11l
12k
12l
8m
166−332
>313
>298
ND
10m
10n
10o
10p
10q
10r
10s
10t
>195
>187
>183
ND
11m
11n
11o
11p
12m
12n
12o
12p
8n
8o
8p
8q
158−316
>299
>286
ND
>190
>184
>179
ND
8r
8s
8t
8u
>303
144−287
137−274
ND
10u
10v
10w
10x
>185
>179
>174
ND
8v
8w
8x
cephalexin
ethionamide
isoniazid
rifampicin
72−144
90.36
2.92
0.12
ND= Not Determined.
ferrocene conjugates. Thus, in order to compare the
antitubercular profiles of the spiroisatin−ferrocene conjugates
with those of the deprotected isatin−ferrocene conjugates, a
series of corresponding hybrids 12 were prepared following our
recently reported protocol35 involving Cu-promoted azide−
alkyne cycloaddition reaction of N-alkylazido isatins 1139 and
ethynylferrocene, as shown in Scheme 4. The structures of the
hybrids were again confirmed using spectral data and analytical
evidence, which are provided in detail in the Experimental
Section; therefore, only the salient features are discussed here.
The compound 12a, for instance, showed a molecular ion peak
[M + H]+ at m/z 455.1181 along with the appearance of
characteristic singlets at δ 4.05 (5H), 4.30 (2H), and 4.71 (2H)
due to the ferrocene ring protons. The two multiplets at δ
1.73−1.80 and 2.01−2.05 and two triplets at δ 3.78 and 4.45
correspond to the protons of the butyl chain together with the
presence of a singlet at δ 7.47 (1H) as a result of a triazole ring
proton in the 1H NMR spectrum. The presence of the requisite
number of carbons along with the characteristic absorptions at
δ 158.3 and 183.1 in the 13C NMR spectrum further
corroborate the assigned structure.
The synthesized spiroisatin−ferrocene (10a−x) and isatin−
ferrocene (12a−p) molecular conjugates and their correspond-
ing precursors (8a−x, 11a−p) were evaluated for their
antitubercular potential, and the results were compared with
those for standard drugs: viz., cephalexin, ethionamide,
D
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102.3, 111.4, 113.2, 118.2, 126.0, 137.7, 157.7, 175.9; HRMS calcd for
C10H8FNO3 [M]+ m/z 209.0488, found 209.0483. Anal. Calcd: C,
57.42; H, 3.85; N, 6.70. Found: C, 57.51; H, 3.80; N, 6.58.
rifampicin, and isoniazid (Table 1). As is evident from Table 1,
although the synthesized conjugates and their precursors are
not as active as the standard drugs used, the introduction of the
ferrocene nucleus results in substantial enhancement in the
activity profiles of both N-alkylazido spiroisatins and N-
alkylazido isatins. Further, the activity profiles are shown to
be independent of the nature of the substituent at the C-5
position of the isatin, the length of the alkyl chain, and the
presence of either a keto−carbonyl or ketal unit at the C-3
position of the isatin ring.
In conclusion, the present paper describes a base-promoted
straightforward access to C-5-functionalized spiroisatins with-
out involving typical drawbacks of the conventional routes such
as long reaction times, moderate yields, and the use of toxic
solvents such as benzene. The synthesized precursors, viz. N-
alkylazido spiroisatins and N-alkylazido isatins, were explored
using Cu-promoted click chemistry approaches with ethnylfer-
rocene, yielding the corresponding 1H-1,2,3-triazole-tethered
spiroisatin−-ferrocene and isatin−ferrocene conjugates. The
synthesized hybrids were assayed for their antitubercular
potential, displaying enhancement in activity profiles with the
introduction of a ferrocene nucleus in comparison to their
organic precursors.
5′-Chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-one (2c): yield
1
97%; light brown solid; mp 134−135 °C; H NMR (CDCl3, 300
MHz) δ 4.30−4.38 (m, 2H, −OCH2), 4.52−4.65 (m, 2H, −OCH2),
6.73−6.81 (m, 1H, −ArH), 7.04−7.09 (m, 1H, −ArH), 7.29−7.33 (m,
2H, −ArH), 8.31 (s, 1H, −NH, exchangeable with D2O); 13C NMR
(CDCl3, 75 MHz) δ 65.4, 101.9, 110.1, 113.1, 122.3, 124.6, 131.5,
141.2, 173.5; HRMS calcd for C10H8ClNO3 [M]+ m/z 225.0193,
found 225.0186. Anal. Calcd: C, 53.23; H, 3.57; N, 6.21. Found: C,
53.16; H, 3.51; N, 6.32.
5′-Methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-one (2d): yield
1
93%; light yellow solid; mp 152−153 °C; H NMR (CDCl3, 300
MHz) δ 2.24 (s, 3H, −CH3), 4.25−4.34 (m, 2H, −OCH2), 4.56−4.67
(m, 2H, −OCH2), 6.60 (d, J = 8.4 Hz, 1H, −ArH), 7.27−7.38 (m, 2H,
−ArH), 8.34 (s, 1H, −NH, exchangeable with D2O); 13C NMR
(CDCl3, 75 MHz) δ 21.4, 65.1, 102.2, 110.3, 117.5, 121.6, 124.7,
131.5, 141.5, 174.8; HRMS calcd for C11H11NO3 [M]+ m/z 205.0739,
found 205.0732. Anal. Calcd: C, 64.38; H, 5.40; N, 6.83. Found: C,
64.49; H, 5.47; N, 6.71.
X-ray crystallographic data for 2b: molecular formula
C10H8FNO3, formula weight 209.17, crystal system monoclinic,
space group P21/n, a = 11.4436(6) Å, b = 5.2965(3) Å, c =
15.8782(9) Å, β = 97.601(3)°, V = 953.94(9) Å3, T = 293 K, Z = 4, Dc
= 1.456 g cm−3, 14778 reflections measured, 1976 independent
reflections, 1110 observed reflections (I > 3.0σ(I)), R1_obs = 0.0486,
goodness of fit = 1.12. Crystallographic data (excluding structure
factors) for spiroisatin 2b have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication number
CCDC 953368.
General Procedure for the Synthesis of N-Alkylazidospir-
oisatins 8a−x. To a solution of 2 (1 mmol) in dry DMF (10 mL)
was added K2CO3 (1.5 mmol), and the resulting suspension was
stirred at room temperature for 10 min. A solution of the
corresponding dibromoalkane (1.2 mmol) in dry DMF (5 mL) was
added dropwise to the above reaction mixture with subsequent heating
at 60 °C for 5 h. The progress of the reaction was monitored via TLC,
and on completion the reaction mixture was concentrated under
vacuum, washed with brine, and extracted with EtOAc (2 × 25 mL).
The combined organic layers were dried over anhydrous sodium
sulfate and concentrated under reduced pressure to result in the
isolation of the crude product 7 (73−81%), which was purified by
column chromatography (60−120 mesh) using EtOAc/hexane (10/
90) as eluent. To a stirred solution of 7 (1 mmol) in dry DMF (5 mL)
was added NaN3 (2 mmol) at room temperature, and the reaction
mixture was stirred at 60 °C for 1 h. On completion, the reaction
mixture was concentrated under reduced pressure and extracted with
EtOAc (2 × 25 mL). The combined organic layers were concentrated
under vacuum, resulting in the isolation of the crude product 8 (88−
95%), which was sufficiently pure for the next step.
EXPERIMENTAL SECTION
■
General Information. Melting points were determined with open
capillaries using a Veego Precision Digital Melting Point apparatus
(MP-D) and are uncorrected. 1H NMR spectra were recorded in
deuteriochloroform (deuterated chloroform) with JEOL 300 (300
MHz) spectrometers using TMS as an internal standard. Chemical
shift values are expressed as parts per million downfield from TMS,
and J values are in hertz. Splitting patterns are indicated as follows: s,
singlet; d, doublet; t, triplet; m, multiplet; dd, doublet of doublets;
ddd, doublet of doublets of doublets; br, broad peak. 13C NMR spectra
were recorded on JEOL 300 (75 MHz) spectrometers in
deuteriochloroform using TMS as internal standard. Elemental
analyses were performed with a Heraus CHN-O-Rapid Elemental
Analyzer. Mass spectra were recorded on a Bruker high-resolution
mass spectrometer (micrOTOF-QII). Column chromatography was
performed using silica gel (60−120 mesh).
General Procedure for the Synthesis of Spiroisatins 2a−d.
To a stirred suspension of NaH (1 mmol) in dry DMF (5 mL) was
added dropwise a solution of isatin 1 (1 mmol) in dry DMF (10 mL)
at 0 °C. The solution was stirred for 10 min, followed by the addition
of 2-bromoethanol (1.1 mmol). The reaction mixture was stirred for
15 min at room temperature with subsequent heating at 70 °C for 60
min. The progress of the reaction was monitored using TLC. On
completion, the reaction mixture was concentrated under reduced
pressure, washed with brine solution, extracted with EtOAc (2 × 25
mL), and dried over anhydrous sodium sulfate. The combined organic
layers were evaporated under reduced pressure, resulting in the
isolation of crude products (91−97%) which were recrystallized using
an 8/2 chloroform/hexane mixture.
Spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (2a): yield 95%; light
yellow solid; mp 129−130 °C; 1H NMR (CDCl3, 300 MHz) δ 4.29−
4.34 (m, 2H, −OCH2), 4.54−4.57 (m, 2H, −OCH2), 6.79−6.83 (m,
1H, −ArH), 7.03−7.07 (m, 1H, −ArH), 7.27−7.35 (m, 2H, −ArH),
8.24 (s, 1H, −NH, exchangeable with D2O); 13C NMR (CDCl3, 75
MHz) δ 65.8, 102.3, 110.7, 123.3, 124.3, 125.1, 131.6, 141.8, 175.6;
HRMS calcd for C10H9NO3 [M]+ m/z 191.0582, found 191.0577.
Anal. Calcd: C, 62.82; H, 4.74; N, 7.33. Found: C, 62.69; H, 4.71; N,
7.43.
1′-(2-Azidoethyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8a):
1
yield 90%; colorless oil; H NMR (CDCl3, 300 MHz) δ 3.51−3.55
(m, 2H, H1), 3.72−3.78 (m, 2H, H2), 4.26−4.37 (m, 2H, −OCH2),
4.51−4.64 (m, 2H, −OCH2), 6.77 (d, J = 8.1 Hz, 1H, −ArH), 7.03−
709 (m, 1H, −ArH), 7.29−7.36 (m, 2H, −ArH); 13C NMR (CDCl3,
75 MHz) δ 39.8, 48.4, 65.5, 102.7, 110.5, 123.1, 124.6, 125.5, 131.3,
141.6, 175.1; HRMS calcd for C12H12N4O3 [M]+ m/z 260.0909, found
260.0901. Anal. Calcd: C, 55.38; H, 4.65; N, 21.53. Found: C, 55.27;
H, 4.58; N, 21.67.
1′-(2-Azidoethyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8b): yield 88%; colorless oil; H NMR (CDCl3, 300 MHz) δ
3.54−3.59 (m, 2H, H1), 3.74−3.79 (m, 2H, H2), 4.29−4.34 (m, 2H,
−OCH2), 4.54−4.59 (m, 2H, −OCH2), 6.81−6.85 (m, 1H, −ArH),
7.04−7.12 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 39.4, 48.9,
65.9, 101.6, 109.6, 112.9, 117.8, 125.5, 139.6, 157.9, 173.4; HRMS
calcd for C12H11FN4O3 [M]+ m/z 278.0815, found 278.0807. Anal.
Calcd: C, 51.80; H, 3.98; N, 20.14. Found: C, 51.94; H, 3.93; N, 19.98.
1′-(2-Azidoethyl)-5′-chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
5′-Fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-one (2b): yield
91%; light brown solid; mp 157−158 °C; 1H NMR (CDCl3, 300
MHz) δ 4.27−4.38 (m, 2H, −OCH2), 4.50−4.58 (m, 2H, −OCH2),
6.76−6.80 (m, 1H, −ArH), 6.99−7.09 (m, 2H, −ArH), 8.35 (s, 1H,
−NH, exchangeable with D2O); 13C NMR (CDCl3, 75 MHz) δ 65.9,
1
one (8c): yield 89%; colorless oil; H NMR (CDCl3, 300 MHz) δ
E
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Article
3.52−3.61 (m, 2H, H1), 3.70−3.77 (m, 2H, H2), 4.25−4.33 (m, 2H,
−OCH2), 4.51−4.58 (m, 2H, −OCH2), 6.74−6.80 (m, 1H, −ArH),
7.03−7.11 (m, 1H, −ArH), 7.27−7.30 (m, 1H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 39.1, 48.4, 65.6, 102.0, 110.4, 113.7, 123.3, 124.6,
137.3, 141.3, 173.2; HRMS calcd for C12H11ClN4O3 [M]+ m/z
294.0520, found 294.0508. Anal. Calcd: C, 48.91; H, 3.76; N, 19.01.
Found: C, 48.73; H, 3.81; N, 18.87.
1′-(2-Azidoethyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-
one (8d): yield 93%; colorless oil; 1H NMR (CDCl3, 300 MHz) δ 2.24
(s, 3H, −CH3), 3.50−3.58 (m, 2H, H1), 3.71−3.78 (m, 2H, H2),
4.23−4.30 (m, 2H, −OCH2), 4.54−4.59 (m, 2H, −OCH2), 6.59 (d, J
= 8.1 Hz, 1H, −ArH), 7.29−7.37 (m, 2H, −ArH); 13C NMR (CDCl3,
75 MHz) δ 21.3, 38.9, 48.6, 65.5, 102.3, 110.4, 117.7, 121.6, 124.2,
131.7, 141.7, 175.2; HRMS calcd for C13H14N4O3 [M]+ m/z 274.1066,
found 274.1075. Anal. Calcd: C, 56.93; H, 5.14; N, 20.43. Found: C,
57.12; H, 5.05; N, 20.26.
C14H15FN4O3 [M]+ m/z 306.1128, found 306.1126. Anal. Calcd: C,
54.90; H, 4.94; N, 18.29. Found: C, 54.81; H, 4.83; N, 18.45.
1′-(4-Azidobutyl)-5′-chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8k): yield 92%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.74−1.84 (m, 4H, H2 + H3), 3.35 (t, J = 6.0 Hz, 2H, H1), 3.62 (t, J =
6.6 Hz, 2H, H4), 4.24−4.31 (m, 2H, −OCH2), 4.48−4.50 (m, 2H,
−OCH2), 6.71−6.78 (m, 1H, −ArH), 7.02−7.08 (m, 1H, −ArH),
7.27−7.36 (m, 1H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.2, 29.0,
36.5, 48.6, 65.6, 102.1, 110.6, 113.5, 123.7, 124.2, 137.4, 141.5, 173.9;
HRMS calcd for C14H15ClN4O3 [M]+ m/z 322.1033, found 322.1037.
Anal. Calcd: C, 52.10; H, 4.68; N, 17.36. Found: C, 52.22; H, 4.79; N,
17.17.
1′-(4-Azidobutyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8l): yield 89%; H NMR (CDCl3, 300 MHz) δ 1.79−1.88 (m,
4H, H2 + H3), 2.23 (s, 3H, −CH3), 3.30 (t, J = 6.3 Hz, 2H, H1), 3.66
(t, J = 6.3 Hz, 2H, H4), 4.25−4.29 (m, 2H, −OCH2), 4.48−4.55 (m,
2H, −OCH2), 6.62 (d, J = 7.8 Hz, 1H, −ArH), 7.29−7.34 (m, 2H,
−ArH); 13C NMR (CDCl3, 75 MHz) δ 21.4, 26.6, 29.3, 36.8, 48.2,
65.5, 102.1, 107.5, 117.9, 121.7, 124.4, 131.8, 141.2, 175.3; HRMS
calcd for C15H18N4O3 [M]+ m/z 302.1379, found 302.1372. Anal.
Calcd: C, 59.59; H, 6.00; N, 18.53. Found: C, 59.45; H, 5.86; N, 18.72.
1′-(5-Azidopentyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8m):
yield 91%; colorless oil; 1H NMR (CDCl3, 300 MHz) δ 1.30−1.36 (m,
2H, H3), 1.46−1.59 (m, 4H, H2 + H4), 3.13 (t, J = 6.3 Hz, 2H, H1),
3.58 (t, J = 6.6 Hz, 2H, H5), 4.19−4.27 (m, 2H, −OCH2), 4.47−4.54
(m, 2H, −OCH2), 6.73−6.81 (m, 1H, −ArH), 7.06−7.12 (m, 1H,
−ArH), 7.29−7.38 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ
24.4, 26.6, 27.8, 39.6, 51.2, 66.0, 102.4, 110.4, 123.3, 124.1, 125.4,
131.6, 147.3, 175.4; HRMS calcd for C15H18N4O3 [M]+ m/z 302.1379,
found 302.1367. Anal. Calcd: C, 59.59; H, 6.00; N, 18.53. Found: C,
59.74; H, 6.19; N, 18.36.
1′-(3-Azidopropyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8e):
1
yield 95%; colorless oil; H NMR (CDCl3, 300 MHz) δ 1.89 (t, J =
6.0 Hz, 2H, H2), 3.35 (t, J = 5.7 Hz, 2H, H1), 3.67 (t, J = 6.3 Hz, 2H,
H3), 4.25−4.31 (m, 2H, −OCH2), 4.48−4.53 (m, 2H, −OCH2),
6.79−6.86 (m, 1H, −ArH), 7.02−7.08 (m, 1H, −ArH), 7.29−7.38 (m,
2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.8, 36.2, 46.5, 65.6,
102.4, 110.6, 123.0, 124.1, 125.8, 131.2, 141.7, 175.4; HRMS calcd for
C13H14N4O3 [M]+ m/z 274.1066, found 274.1071. Anal. Calcd: C,
56.93; H, 5.14; N, 20.43. Found: C, 56.82; H, 5.09; N, 20.56.
1′-(3-Azidopropyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
one (8f): yield 91%; colorless oil; 1H NMR (CDCl3, 300 MHz) δ 1.83
(t, J = 5.7 Hz, 2H, H2), 3.38 (t, J = 6.0 Hz, 2H, H1), 3.71 (t, J = 6.0 Hz,
2H, H3), 4.24−4.32 (m, 2H, −OCH2), 4.49−4.54 (m, 2H, −OCH2),
6.84−6.89 (m, 1H, −ArH), 7.03−7.14 (m, 2H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 26.4, 37.2, 47.2, 65.5, 101.5, 109.3, 112.8, 117.6,
125.4, 139.4, 157.6, 173.2; Calcd for C13H13FN4O3 [M]+ m/z
292.0972, found 292.0964. Anal. Calcd: C, 53.42; H, 4.48; N, 19.17.
Found: C, 53.34; H, 4.40; N, 19.29.
1′-(5-Azidopentyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8n): yield 90%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.32−1.35 (m, 2H, H3), 1.36−1.62 (m, 4H, H2 + H4), 3.18 (t, J = 6.6
Hz, 2H, H1), 3.53 (t, J = 6.9 Hz, 2H, H5), 4.21−4.25 (m, 2H,
−OCH2), 4.49−4.51 (m, 2H, −OCH2), 6.67−6.68 (m, 1H, −ArH),
6.99−7.05 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 24.1, 26.8,
27.9, 39.7, 51.4, 66.2, 101.9, 109.7, 113.1, 117.9, 126.1, 140.0, 158.0,
173.3; HRMS calcd for C15H17FN4O3 [M]+ m/z 320.1285, found
320.1282. Anal. Calcd: C, 56.24; H, 5.33; N, 17.49. Found: C, 56.35;
H, 5.22; N, 17.29.
1′-(3-Azidopropyl)-5′-chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
one (8g): yield 95%; colorless oil; 1H NMR (CDCl3, 300 MHz) δ 1.91
(t, J = 6.3 Hz, 2H, H2), 3.33 (t, J = 6.3 Hz, 2H, H1), 3.73 (t, J = 6.6 Hz,
2H, H3), 4.27−4.35 (m, 2H, −OCH2), 4.53−4.61 (m, 2H, −OCH2),
6.76−6.82 (m, 1H, −ArH), 7.05−7.12 (m, 1H, −ArH), 7.33−7.35 (m,
1H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.3, 37.5, 47.8, 65.3,
102.4, 110.5, 113.6, 123.5, 124.3, 137.1, 141.2, 173.6; HRMS calcd for
C13H13ClN4O3 [M]+ m/z 308.0676, found 308.0665. Anal. Calcd: C,
50.58; H, 4.21; N, 18.15. Found: C, 50.72; H, 4.33; N, 18.01.
1′-(3-Azidopropyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-
1′-(5-Azidopentyl)-5′-chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8o): yield 89%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.29−1.36 (m, 2H, H3), 1.39−1.57 (m, 4H, H2 + H4), 3.20 (t, J = 6.0
Hz, 2H, H1), 3.58 (t, J = 6.0 Hz, 2H, H5), 4.26−4.31 (m, 2H,
−OCH2), 4.46−4.54 (m, 2H, −OCH2), 6.70−6.79 (m, 1H, −ArH),
7.06−7.11 (m, 1H, −ArH), 7.28−7.33 (m, 1H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 24.3, 26.7, 27.7, 39.4, 51.1, 65.9, 102.0, 110.5,
113.4, 123.8, 124.3, 137.5, 141.1, 173.8; HRMS calcd for
C15H17ClN4O3 [M]+ m/z 336.0989, found 336.0981. Anal. Calcd: C,
53.50; H, 5.09; N, 16.64. Found: C, 53.37; H, 4.96; N, 16.83.
1′-(5-Azidopentyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
2′-one (8h): yield 92%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.85 (t, J = 6.0 Hz, 2H, H2), 2.21 (s, 3H, −CH3), 3.36 (t, J = 6.6 Hz,
2H, H1), 3.69 (t, J = 6.3 Hz, 2H, H3), 4.24−4.33 (m, 2H, −OCH2),
4.52−4.58 (m, 2H, −OCH2), 6.61 (d, J = 7.8 Hz, 1H, −ArH), 7.32−
7.38 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 21.2, 26.7, 38.6,
48.3, 65.4, 102.2, 110.7, 117.6, 121.9, 124.3, 131.9, 141.5, 175.0;
HRMS calcd for C14H16N4O3 [M]+ m/z 288.1222, found 288.1213.
Anal. Calcd: C, 58.32; H, 5.59; N, 19.43. Found: C, 58.49; H, 5.68; N,
19.25.
1
one (8p): yield 88%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.29−1.38 (m, 2H, H3), 1.41−1.55 (m, 4H, H2 + H4), 2.20, (s, 3H,
−CH3), 3.17 (t, J = 6.3 Hz, 2H, H1), 3.54 (t, J = 6.6 Hz, 2H, H5),
4.29−4.37 (m, 2H, −OCH2), 4.44−4.55 (m, 2H, −OCH2), 6.60 (d, J
= 8.1 Hz, 1H, −ArH), 7.28−7.35 (m, 2H, −ArH); 13C NMR (CDCl3,
75 MHz) δ 21.7, 24.0, 26.6, 27.5, 39.7, 51.4, 65.8, 102.0, 110.4, 117.8,
121.6, 124.5, 131.6, 141.1, 175.1; HRMS calcd for C16H20N4O3 [M]+
m/z 316.1535, found 316.1539. Anal. Calcd: C, 60.75; H, 6.37; N,
17.71. Found: C, 60.90; H, 6.42; N, 17.56.
1′-(4-Azidobutyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8i):
1
yield 88%; colorless oil; H NMR (CDCl3, 300 MHz) δ 1.72−1.84
(m, 4H, H2 + H3), 3.34 (t, J = 6.0 Hz, 2H, H1), 3.66 (t, J = 6.6 Hz, 2H,
H4), 4.24−4.33 (m, 2H, −OCH2), 4.44−4.53 (m, 2H, −OCH2),
6.79−6.85 (m, 1H, −ArH), 7.04−7.11 (m, 1H, −ArH), 7.30−7.36 (m,
2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.3, 29.0, 37.1, 48.3, 65.2,
102.7, 110.5, 123.3, 124.0, 125.7, 131.1, 147.4, 175.5; HRMS calcd for
C14H16N4O3 [M]+ m/z 288.1222, found 288.1215. Anal. Calcd: C,
58.32; H, 5.59; N, 19.43. Found: C, 58.15; H, 5.46; N, 19.62.
1′-(4-Azidobutyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1′-(6-Azidohexyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8q):
1
yield 92%; colorless oil; H NMR (CDCl3, 300 MHz) δ 1.40−1.45
1
one (8j): yield 94%; colorless oil; H NMR (CDCl3, 300 MHz) δ
(m, 4H, H3 + H4), 1.55−1.67 (m, 2H, H2), 1.71−1.77 (m, 2H, H5),
3.25 (t, J = 6.6 Hz, 2H, H1), 3.70 (t, J = 6.3 Hz, 2H, H6), 4.20−4.27
(m, 2H, −OCH2), 4.44−4.49 (m, 2H, −OCH2), 6.68−6.73 (m, 1H,
−ArH), 7.03−7.13 (m, 1H, −ArH), 7.27−7.37 (m, 2H, −ArH); 13C
NMR (CDCl3, 75 MHz) δ 26.0, 26.4, 27.1, 28.4, 40.3, 51.4, 65.8,
102.1, 110.7, 123.1, 124.3, 125.6, 131.5, 147.6, 175.2; Calcd for
1.79−1.88 (m, 4H, H2 + H3), 3.31 (t, J = 6.3 Hz, 2H, H1), 3.63 (t, J =
6.9 Hz, 2H, H4), 4.22−4.27 (m, 2H, −OCH2), 4.48−4.52 (m, 2H,
−OCH2), 6.70−6.74 (m, 1H, −ArH), 6.98−7.07 (m, 2H, −ArH); 13
C
NMR (CDCl3, 75 MHz) δ 26.5, 29.2, 36.9, 48.5, 65.8, 101.5, 109.2,
112.8, 117.6, 125.6, 139.5, 157.6, 173.1; HRMS calcd for
F
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
C16H20N4O3 [M]+ m/z 316.1535, found 316.1541. Anal. Calcd: C,
60.75; H, 6.37; N, 17.71. Found: C, 60.91; H, 6.46; N, 17.53.
1′-(6-Azidohexyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
(m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 21.5, 26.1, 26.2, 26.4,
28.1, 28.5, 29.1, 40.0, 50.9, 65.8, 102.7, 110.8, 117.7, 121.2, 124.2,
131.6, 141.3, 175.8; HRMS calcd for C19H26N4O3 [M]+ m/z 358.2005,
found 358.2000. Anal. Calcd: C, 63.67; H, 7.31; N, 15.63. Found: C,
63.72; H, 7.28; N, 15.68.
General Procedure for the Synthesis of Spiroisatin−
Ferrocene-Based Hybrids 10a−x. To a well-stirred solution of
N-alkylazido spiroisatins 8 and ethynylferrocene 9 in a 9/1 ethanol/
water mixture were added copper sulfate (0.05 mmol) and sodium
ascorbate (0.13 mmol). The reaction mixture was stirred at room
temperature for 7−10 h. After completion of the reaction, as indicated
by TLC, water (20 mL) was added and the reaction mixture was
extracted with dichloromethane (2 × 30 mL). The combined organic
layers were dried over anhydrous sodium sulfate and concentrated
under reduced pressure, resulting in the crude product 10, which was
purified via column chromatography using a 60/40 EtOAc/hexane
mixture.
1
one (8r): yield 91%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.37−1.46 (m, 4H, H3 + H4), 1.51−1.65 (m, 2H, H2), 1.72−1.79 (m,
2H, H5), 3.21 (t, J = 6.0 Hz, 2H, H1), 3.66 (t, J = 6.6 Hz, 2H, H6),
4.22−4.28 (m, 2H, −OCH2), 4.48−4.53 (m, 2H, −OCH2), 6.83−6.89
(m, 1H, −ArH), 7.02−7.11 (m, 2H, −ArH); 13C NMR (CDCl3, 75
MHz) δ 26.5, 26.8, 27.3, 28.2, 40.2, 51.3, 66.0, 101.8, 109.6, 112.5,
117.4, 125.6, 139.8, 157.7, 173.6; HRMS calcd for C16H19FN4O3 [M]+
m/z 334.1441, found 344.1449. Anal. Calcd: C, 57.48; H, 5.73; N,
16.76. Found: C, 57.34; H, 5.87; N, 16.90.
1′-(2-Azidoethyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8s):
1
yield 93%; colorless oil; H NMR (CDCl3, 300 MHz) δ 1.34−1.46
(m, 4H, H3 + H4), 1.49−1.57 (m, 2H, H2), 1.74−1.81 (m, 2H, H5),
3.24 (t, J = 5.7 Hz, 2H, H1), 3.70 (t, J = 6.0 Hz, 2H, H6), 4.18−4.24
(m, 2H, −OCH2), 4.44−4.51 (m, 2H, −OCH2), 6.70−6.78 (m, 1H,
−ArH), 7.03−7.10 (m, 1H, −ArH), 7.29−7.36 (m, 1H, −ArH); 13C
NMR (CDCl3, 75 MHz) δ 26.1, 26.5, 27.2, 28.4, 40.5, 51.1, 65.9,
102.1, 110.8, 113.3, 123.6, 124.5, 137.2, 141.4, 173.7; HRMS calcd for
C16H19ClN4O3 [M]+ m/z 350.1146, found 350.1142. Anal. Calcd: C,
54.78; H, 5.46; N, 15.97. Found: C, 54.61; H, 5.36; N, 15.85.
1′-(6-Azidohexyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)ethyl)spiro[[1,3]-
dioxolane-2,3′-indolin]-2′-one (10a): yield 78%; dark brown oil;
NMR (CDCl3, 300 MHz) δ 3.93 (s, 5H, H6), 4.15−4.17 (m, 2H, H1),
4.25 (s, 2H, −OCH2), 4.34 (s, 2H, H5), 4.58−4.61 (m, 4H, −OCH2 +
H4), 4.65−4.68 (m, 2H, H2), 6.59−6.61 (m, 1H, −ArH), 7.01−7.05
(m, 1H, −ArH), 7.28−7.36 (m, 3H, H3+2ArH); 13C NMR (CDCl3, 75
MHz) δ 40.3, 47.4, 65.9, 66.6, 68.6, 69.5, 74.6, 101.9, 108.3, 120.1,
123.6, 123.8, 125.1, 131.9, 143.1, 173.8; HRMS calcd for
C24H22FeN4O3 [M]+ m/z 470.1036, found 440.1034. Anal. Calcd:
C, 61.28; H, 4.68; N, 11.91. Found: C, 61.25; H, 4.71; N, 11.85.
5′-Fluoro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)ethyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10b): yield 87%; dark brown
1
one (8t): yield 89%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.34−1.41 (m, 4H, H3 + H4), 1.53−1.58 (m, 2H, H2), 1.71−1.77 (m,
2H, H5), 2.24 (s, 3H, −CH3), 3.19 (t, J = 6.3 Hz, 2H, H1), 3.68 (t, J =
6.0 Hz, 2H, H6), 4.21−4.26 (m, 2H, −OCH2), 4.45−4.52 (m, 2H,
−OCH2), 6.63 (d, J = 7.8 Hz, 1H, −ArH), 7.29−7.37 (m, 2H, −ArH);
13C NMR (CDCl3, 75 MHz) δ 21.5, 26.3, 26.4, 27.0, 28.3, 40.3, 51.0,
65.6, 102.4, 107.7, 117.5, 121.5, 124.4, 131.7, 141.4, 175.6; HRMS
calcd for C17H22N4O3 [M]+ m/z 330.1692, found 330.1699. Anal.
Calcd: C, 61.80; H, 6.71; N, 16.96. Found: C, 61.86; H, 6.79; N, 16.86.
1′-(8-Azidooctyl)spiro[[1,3]dioxolane-2,3′-indolin]-2′-one (8u):
1
oil; H NMR (CDCl3, 300 MHz) δ 3.90 (s, 5H, H6), 4.14−4.19 (m,
2H, H1), 4.23 (s, 2H, −OCH2), 4.37 (s, 2H, H5), 4.54−4.59 (m, 4H,
−OCH2 + H4), 4.62−4.69 (m, 2H, H2), 6.80−6.87 (m, 1H, −ArH),
7.01−7.10 (m, 2H, −ArH), 7.49 (s, 1H, H3); 13C NMR (CDCl3, 75
MHz) δ 40.4, 47.2, 65.5, 66.2, 68.4, 69.6, 74.3, 101.4, 109.8, 112.6,
117.7, 125.4, 131.1, 134.8, 139.2, 157.6, 173.7; HRMS calcd for
C24H21FFeN4O3 [M]+ m/z 488.0141, found 488.0135. Anal. Calcd: C,
59.02; H, 4.30; N, 11.48. Found: C, 58.91; H, 4.23; N, 11.55.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)ethyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10c): yield 79%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 3.86 (s, 5H, H6), 4.11−4.18 (m, 2H,
1
yield 93%; colorless oil; H NMR (CDCl3, 300 MHz) δ 1.34−1.49
(m, 8H, H3 + H4 + H5 + H6), 1.52−1.57 (m, 2H, H2), 1.68−1.79 (m,
2H, H7), 3.27 (t, J = 6.0 Hz, 2H, H1), 3.63 (t, J = 5.7 Hz, 2H, H8),
4.25−4.33 (m, 2H, −OCH2), 4.44−4.56 (m, 2H, −OCH2), 6.69−6.77
(m, 1H, −ArH), 7.04−7.10 (m, 1H, −ArH), 7.27−7.38 (m, 2H,
−ArH); 13C NMR (CDCl3, 75 MHz) δ 26.1, 26.4, 26.7, 28.4, 28.5,
29.4, 40.3, 50.5, 65.8, 102.2, 110.6, 123.4, 124.1, 125.8, 131.4, 147.3,
175.1; HRMS calcd for C18H24N4O3 [M]+ m/z 344.1848, found
344.1841. Anal. Calcd: C, 62.77; H, 7.02; N, 16.77. Found: C, 62.71;
H, 7.06; N, 16.68.
H1), 4.20 (s, 2H, −OCH2), 4.38 (s, 2H, H5), 4.51−4.58 (m, 4H,
−OCH2 + H4), 4.65−4.70 (m, 2H, H2), 6.89−6.96 (m, 1H, −ArH),
7.28−7.35 (m, 2H, −ArH), 7.60 (s, 1H, H3); 13C NMR (CDCl3, 75
MHz) δ 40.1, 47.0, 65.4, 66.6, 68.7, 69.4, 74.4, 102.4, 110.6, 113.5,
123.5, 124.7,130.7, 134.6, 137.3, 141.5, 173.7; Calcd for
C24H21ClFeN4O3 [M]+ m/z 504.0383, found 504.0377. Anal. Calcd:
C, 57.14; H, 4.17; N, 11.11. Found: C, 57.06; H, 4.07; N, 11.19.
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)ethyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10d): yield 75%; dark brown
1′-(8-Azidooctyl)-5′-fluorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8v): yield 94%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.31−1.44 (m, 8H, H3 + H4 + H5 + H6), 1.48−1.57 (m, 2H, H2),
1.65−1.72 (m, 2H, H7), 3.22 (t, J = 6.6 Hz, 2H, H1), 3.61 (t, J = 6.3
Hz, 2H, H8), 4.22−4.31 (m, 2H, −OCH2), 4.45−4.53 (m, 2H,
−OCH2), 6.83−6.89 (m, 1H, −ArH), 7.07−7.10 (m, 2H, −ArH); 13
C
1
oil; H NMR (CDCl3, 300 MHz) δ 2.20 (s, 3H, −CH3), 3.86 (s, 5H,
NMR (CDCl3, 75 MHz) δ 26.2, 26.3, 26.8, 28.1, 28.3, 29.5, 40.4, 50.7,
65.4, 101.7, 109.6, 112.9, 117.5, 125.2, 139.1, 157.6, 173.3; HRMS
calcd for C18H23FN4O3 [M]+ m/z 362.1754, found 362.1759. Anal.
Calcd: C, 59.66; H, 6.40; N, 15.46. Found: C, 59.73; H, 6.48; N, 15.55.
1′-(8-Azidooctyl)-5′-chlorospiro[[1,3]dioxolane-2,3′-indolin]-2′-
H6), 4.14−4.19 (m, 2H, H1), 4.24 (s, 2H, −OCH2), 4.39 (s, 2H, H5),
4.50−4.56 (m, 4H, −OCH2 + H4), 4.61−4.67 (m, 2H, H2), 6.55 (d, J
= 7.5 Hz, 1H, −ArH), 7.28−7.36 (m, 2H, −ArH); 7.58 (s, 1H, H3);
13C NMR (CDCl3, 75 MHz) δ 21.4, 40.5, 47.6, 65.7, 66.9, 68.4, 69.5,
74.6, 102.1, 110.6, 117.9, 121.2, 124.0, 130.2, 131.6, 134.5, 141.4,
175.6; HRMS calcd for C25H24FeN4O3 [M + H]+ m/z 485.0919,
found 485.0915. Anal. Calcd: C, 61.98; H, 4.96; N, 11.57. Found: C,
61.90; H, 5.04; N, 11.64.
1
one (8w): yield 88%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.34−1.42 (m, 8H, H3 + H4 + H5 + H6), 1.43−1.55 (m, 2H, H2),
1.64−1.73 (m, 2H, H7), 3.23 (t, J = 5.7 Hz, 2H, H1), 3.59 (t, J = 6.6
Hz, 2H, H8), 4.26−4.34 (m, 2H, −OCH2), 4.41−4.50 (m, 2H,
−OCH2), 6.71−6.79 (m, 1H, −ArH), 7.06−7.11 (m, 1H, −ArH),
7.28−7.38 (m, 1H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.4, 26.5,
26.9, 28.0, 28.2, 29.6, 40.5, 50.6, 65.7, 102.5, 110.3, 113.6, 123.3, 124.2,
137.0, 141.7, 173.4; HRMS calcd for C18H23ClN4O3 [M]+ m/z
378.1459, found 378.1450. Anal. Calcd: C, 57.07; H, 6.12; N, 14.79.
Found: C, 57.13; H, 6.17; N, 14.69.
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)propyl)spiro[[1,3]-
1
dioxolane-2,3′-indolin]-2′ one (10e): yield 81%; dark brown oil; H
NMR (CDCl3, 300 MHz) δ 2.26 (s, 2H, H2), 3.64 (s, 2H, H1), 4.01 (s,
5H, H7), 4.22−4.31 (m, 6H, −OCH2 + H3 + H6), 4.52 (s, 2H, H5),
4.66 (s, 2H, −OCH2), 6.72−6.74 (m, 1H, −ArH), 7.03−7.06 (m, 1H,
−ArH), 7.30−7.33 (m, 2H, −ArH), 7.60 (s, 1H, H4); 13C NMR
(CDCl3, 75 MHz) δ 27.9, 36.7, 47.4, 65.8, 66.6, 68.6, 69.6, 75.2, 101.9,
108.7, 119.9, 123.6, 124.0, 125.0, 131.8, 143.2, 173.7; HRMS calcd for
C25H24FeN4O3 [M]+ m/z 484.1192, found 484.1189. Anal. Calcd: C,
61.98; H, 4.96; N, 11.57. Found: C, 61.85; H, 4.88; N, 11.62.
5′-Fluoro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)propyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10f): yield 79%; dark brown oil;
1′-(8-Azidooctyl)-5′-methylspiro[[1,3]dioxolane-2,3′-indolin]-2′-
1
one (8x): yield 89%; colorless oil; H NMR (CDCl3, 300 MHz) δ
1.31−1.42 (m, 8H, H3 + H4 + H5 + H6), 1.45−1.57 (m, 2H, H2),
1.61−1.74 (m, 2H, H7), 2.21 (s, 3H, −CH3), 3.21 (t, J = 6.9 Hz, 2H,
H1), 3.63 (t, J = 6.3 Hz, 2H, H8), 4.24−4.31 (m, 2H, −OCH2), 4.40−
4.48 (m, 2H, −OCH2), 6.66 (d, J = 8.4 Hz, 1H, −ArH), 7.30−7.39
G
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1H NMR (CDCl3, 300 MHz) δ 2.29 (s, 2H, H2), 3.66 (s, 2H, H1),
(CDCl3, 75 MHz) δ 21.5, 23.0, 27.2, 38.1, 49.5, 65.9, 66.4, 68.3, 69.5,
75.8, 102.2, 110.5, 117.9, 121.2, 124.4, 130.5, 131.7, 134.8, 141.4,
175.7; HRMS calcd for C27H28FeN4O3 [M + H]+ m/z 513.0925,
found 513.0917. Anal. Calcd: C, 63.28; H, 5.47; N, 10.94. Found: C,
63.23; H, 5.40; N, 11.02.
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)pentyl)spiro[[1,3]-
dioxolane-2,3′-indolin]-2′-one (10m): yield 82%; dark brown oil; 1H
NMR (CDCl3, 300 MHz) δ 1.31−1.39 (m, 2H, H3), 1.44−1.52 (m,
4H, H2 + H4), 3.17 (t, J = 6.0 Hz, 2H, H1), 4.06 (s, 5H, H9), 4.26−
4.32 (m, 4H, H5 + H8), 4.44−4.51 (m, 2H, −OCH2), 4.56 (s, 2H, H7),
4.69−4.76 (m, 2H, −OCH2), 6.73−6.78 (d, J = 7.8 Hz, 1H, −ArH),
7.02−7.09 (m, 1H, −ArH), 7.34−7.41 (m, 2H, −ArH), 7.47 (s, 1H,
H6); 13C NMR (CDCl3, 75 MHz) δ 24.6, 26.4, 27.5, 39.3, 51.0, 65.4,
66.3, 68.8, 69.7, 75.7, 102.5, 108.3, 118.4, 123.6, 123.7, 124.8, 131.9,
143.2, 173.8; HRMS calcd for C27H28FeN4O3 [M]+ m/z 512.1076,
found 512.1074. Anal. Calcd: C, 63.28; H, 5.47; N, 10.94. Found: C,
63.24; H, 5.41; N, 11.07.
4.04 (s, 5H, H7), 4.20−4.27 (m, 6H, −OCH2 + H3 + H6), 4.54 (s, 2H,
H5), 4.63 (s, 2H, −OCH2), 6.83−6.89 (m, 1H, −ArH), 7.03−7.11 (m,
2H, −ArH), 7.44 (s, 1H, H4); 13C NMR (CDCl3, 75 MHz) δ 27.7,
36.8, 47.5, 65.5, 66.4, 68.7, 69.8, 75.0, 101.1, 109.5, 112.8, 117.8, 125.6,
130.4, 134.5, 139.0, 157.2, 173.3; HRMS calcd for C25H23FFeN4O3
[M]+ m/z 502.1068, found 502.1060. Anal. Calcd: C, 59.76; H, 4.58;
N, 11.16. Found: C, 59.85; H, 4.65; N, 11.09.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)propyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10g): yield 80%; dark brown
oil;1H NMR (CDCl3, 300 MHz) δ 2.26 (s, 2H, H2), 3.61 (s, 2H, H1),
4.07 (s, 5H, H7), 4.23−4.29 (m, 6H, −OCH2 + H3 + H6), 4.53 (s, 2H,
H5), 4.60 (s, 2H, −OCH2), 6.88−6.97 (m, 1H, −ArH), 7.29−7.38 (m,
2H, −ArH), 7.63 (s, 1H, H4); 13C NMR (CDCl3, 75 MHz) δ 27.3,
36.5, 47.2, 65.3, 66.5, 68.9, 69.5, 75.7, 102.6, 110.4, 113.8, 123.9, 124.6,
130.2, 134.9, 137.3, 141.4, 173.3; HRMS calcd for C25H23ClFeN4O3
[M]+ m/z 518.1058, found 518.1056. Anal. Calcd: C, 57.92; H, 4.44;
N, 10.81. Found: C, 58.02; H, 4.49; N, 10.71.
5′-Fluoro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pentyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10n): yield 77%; dark brown
oil; 1H NMR (CDCl3, 300 MHz) δ 1.34−1.42 (m, 2H, H3), 1.46−1.57
(m, 4H, H2 + H4), 3.15 (t, J = 6.9 Hz, 2H, H1), 4.01 (s, 5H, H9),
4.22−4.30 (m, 4H, H5 + H8), 4.46−4.52 (m, 2H, −OCH2), 4.58 (s,
2H, H7), 4.71−4.74 (m, 2H, −OCH2), 6.80−6.90 (m, 1H, −ArH),
7.03−7.12 (m, 2H, −ArH), 7.48 (s, 1H, H6); 13C NMR (CDCl3, 75
MHz) δ 24.1, 26.3, 27.6, 39.2, 51.2, 65.3, 66.7, 68.5, 69.3, 75.4, 101.1,
109.5, 112.4, 117.9, 125.5, 130.5, 134.2, 139.5, 157.1, 173.2; HRMS
calcd for C27H27FFeN4O3 [M]+ m/z 530.1092, found 530.1088. Anal.
Calcd: C, 61.13; H, 5.09; N, 10.56. Found: C, 61.21; H, 5.17; N, 10.45.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pentyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10o): yield 84%; dark brown
oil; 1H NMR (CDCl3, 300 MHz) δ 1.33−1.45 (m, 2H, H3), 1.48−1.56
(m, 4H, H2 + H4), 3.13 (t, J = 6.3 Hz, 2H, H1), 4.03 (s, 5H, H9),
4.21−4.31 (m, 4H, H5 + H8), 4.41−4.47 (m, 2H, −OCH2), 4.56 (s,
2H, H7), 4.67−4.71 (m, 2H, −OCH2), 6.83−6.95 (m, 1H, −ArH),
7.30−7.37 (m, 2H, −ArH), 7.60 (s, 1H, H6); 13C NMR (CDCl3, 75
MHz) δ 24.4, 26.2, 27.4, 39.5, 51.0, 65.2, 66.4, 68.6, 69.8, 75.3, 102.4,
110.9, 113.8, 123.6, 124.3, 130.5, 134.5,137.7, 141.5, 173.3; HRMS
calcd for C27H27ClFeN4O3 [M]+ m/z 546.0519, found 546.0511. Anal.
Calcd: C, 59.34; H, 4.95; N, 10.26. Found: C, 59.23; H, 4.87; N, 10.20.
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)pentyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10p): yield 76%; dark brown
oil; 1H NMR (CDCl3, 300 MHz) δ 1.30−1.42 (m, 2H, H3), 1.44−1.52
(m, 4H, H2 + H4), 2.22 (s, 3H, −CH3), 3.20 (t, J = 6.3 Hz, 2H, H1),
4.02 (s, 5H, H9), 4.18−4.27 (m, 4H, H5 + H8), 4.42−4.47 (m, 2H,
−OCH2), 4.59 (s, 2H, H7), 4.63−4.70 (m, 2H, −OCH2), 6.53 (d, J =
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)propyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10h): yield 87%; dark brown
1
oil; H NMR (CDCl3, 300 MHz) δ 2.23 (s, 3H, −CH3), 2.29 (s, 2H,
H2), 3.68 (s, 2H, H1), 4.10 (s, 5H, H7), 4.24−4.31 (m, 6H, −OCH2 +
H3 + H6), 4.50 (s, 2H, H5), 4.64 (s, 2H, −OCH2), 6.51 (d, J = 7.8 Hz,
1H, −ArH), 7.29−7.39 (m, 2H, −ArH); 7.62 (s, 1H, H4); 13C NMR
(CDCl3, 75 MHz) δ 21.3, 27.2, 36.6, 47.7, 65.9, 66.3, 68.5, 69.8, 75.5,
102.0, 110.9, 117.6, 121.1, 124.5, 130, 131.8, 134.8, 141.1, 175.3;
HRMS calcd for C26H26FeN4O3 [M]+ m/z 498.1136, found 498.1141.
Anal. Calcd: C, 62.65; H, 5.22; N, 11.24. Found: C, 62.76; H, 5.31; N,
11.29.
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)butyl)spiro[[1,3]-
1
dioxolane-2,3′-indolin]-2′-one (10i): yield 87%; dark brown oil; H
NMR (CDCl3, 300 MHz) δ 1.69−1.73 (m, 2H, H2), 1.96−2.04 (m,
2H, H3), 3.69 (t, J = 6.3 Hz, 2H, H1), 4.06 (s, 5H, H8), 4.30−4.33 (m,
4H, −OCH2 + H7), 4.41 (t, J = 6.6 Hz, 2H, H4), 4.53−4.64 (m, 2H,
−OCH2), 4.71 (s, 2H, H6), 6.76−6.79 (d, J = 7.5 Hz, 1H, −ArH),
7.05−7.10 (m, 1H, −ArH), 7.32−7.41 (m, 2H, −ArH), 7.43 (s, 1H,
H5); 13C NMR (CDCl3, 75 MHz) δ 23.9, 27.2, 38.5, 49.2, 65.8, 66.5,
68.5, 69.4, 75.3, 102.0, 108.8, 118.8, 123.3, 123.9, 124.9, 131.7, 143.4,
173.5; HRMS calcd for C26H26FeN4O3 [M]+ m/z 498.1343, found
498.1350. Anal. Calcd: C, 62.65; H, 5.22; N, 11.24. Found: C, 62.57;
H, 5.18; N, 11.21.
5′-fFluoro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)butyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10j): yield 86%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.66−1.76 (m, 2H, H2), 1.95−2.01
(m, 2H, H3), 3.66 (t, J = 6.6 Hz, 2H, H1), 4.03 (s, 5H, H8), 4.28−4.34
(m, 4H, −OCH2 + H7), 4.44 (t, J = 6.0 Hz, 2H, H4), 4.54−4.63 (m,
2H, −OCH2), 4.69 (s, 2H, H6), 6.81−6.89 (m, 1H, −ArH), 7.04−7.10
(m, 2H, −ArH), 7.46 (s, 1H, H5); 13C NMR (CDCl3, 75 MHz) δ 23.5,
27.0, 38.4, 49.5, 65.4, 66.7, 68.6, 69.2, 75.6, 101.4, 109.4, 112.5, 117.7,
125.4, 130.2, 134.3, 139.1, 157.4, 173.6; HRMS calcd for
C26H25FFeN4O3 [M]+ m/z 516.1373, found 516.1379. Anal. Calcd:
C, 60.47; H, 4.84; N, 10.85. Found: C, 60.52; H, 4.89; N, 10.76.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)butyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10k): yield 77%; dark brown
oil;1H NMR (CDCl3, 300 MHz) δ 1.63−1.75 (m, 2H, H2), 1.98−2.04
(m, 2H, H3), 3.69 (t, J = 6.3 Hz, 2H, H1), 4.01 (s, 5H, H8), 4.29−4.37
(m, 4H, −OCH2 + H7), 4.42 (t, J = 6.3 Hz, 2H, H4), 4.55−4.61 (m,
2H, −OCH2), 4.68 (s, 2H, H6),6.84−6.92 (m, 1H, −ArH), 7.31−7.39
(m, 2H, −ArH), 7.64 (s, 1H, H5); 13C NMR (CDCl3, 75 MHz) δ 23.1,
27.3, 38.3, 49.6, 65.7, 66.8, 68.4, 69.1, 75.4, 102.5, 110.6, 113.5, 123.3,
124.9, 130.3, 134.8, 137.2, 141.7, 173.8; HRMS calcd for
C26H25ClFeN4O3 [M]+ m/z 532.1372, found 532.1368. Anal. Calcd:
C, 58.65; H, 4.69; N, 10.53. Found: C, 58.76; H, 4.77; N, 10.45.
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)butyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10l): yield 83%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.64−1.69 (m, 2H, H2), 1.88−1.95
8.7 Hz, 1H, −ArH), 7.31−7.37 (m, 2H, −ArH); 7.65 (s, 1H, H6); 13
C
NMR (CDCl3, 75 MHz) δ 21.4, 24.1, 26.0, 27.6, 39.9, 51.1, 65.3, 66.6,
68.8, 69.9, 75.1, 102.4, 110.6, 117.7, 121.3, 124.6, 130.4, 131.4, 134.2,
141.7, 175.5; HRMS calcd for C28H30FeN4O3 [M]+ m/z 526.1080,
found 526.1077. Anal. Calcd: C, 63.88; H, 5.70; N, 10.65. Found: C,
63.81; H, 5.82; N, 10.74.
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)hexyl)spiro[[1,3]-
dioxolane-2,3′-indolin]-2′-one (10q): yield 87%; Brown Solid; 1H
NMR (CDCl3, 300 MHz) δ 1.38−1.48 (m, 4H, H3 + H4), 1.51−1.68
(m, 2H, H2), 1.75−1.83 (m, 2H, H5), 3.21 (t, J = 6.3 Hz, 2H, H1), 4.03
(s, 5H, H10), 4.21−4.29 (m, 4H, H6 + H9), 4.41−4.46 (m, 2H,
−OCH2), 4.51 (s, 2H, H8), 4.64−4.69 (m, 2H, −OCH2), 6.74−6.81
(d, J = 8.4 Hz,, 1H, −ArH), 7.04−7.11 (m, 1H, −ArH), 7.31−7.42 (m,
2H, −ArH), 7.45 (s, 1H, H7); 13C NMR (CDCl3, 75 MHz) δ 26.2,
26.3, 27.4, 28.1, 40.0, 51.1, 65.3, 66.7, 68.4, 69.8, 75.4, 102.4, 108.5,
118.5, 123.7, 123.9, 124.6, 131.8, 143.6, 173.5; HRMS calcd for
C28H30FeN4O3 [M]+ m/z 526.1184, found 526.1188. Anal. Calcd: C,
63.88; H, 5.70; N, 10.65. Found: C, 63.82; H, 5.74; N, 10.79.
5′-Fluoro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)hexyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10r): yield 87%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.33−1.41 (m, 4H, H3 + H4), 1.52−
(m, 2H, H3), 2.21 (s, 3H, −CH3), 3.66 (t, J = 6.9 Hz, 2H, H1), 4.04 (s,
5H, H8), 4.20−4.29 (m, 4H, −OCH2 + H7), 4.46 (t, J = 6.0 Hz, 2H,
H4), 4.52−4.59 (m, 2H, −OCH2), 4.66 (s, 2H, H6),6.55 (d, J = 8.4 Hz,
1H, −ArH), 7.27−7.38 (m, 2H, −ArH), 7.60 (s, 1H, H5); 13C NMR
1.63 (m, 2H, H2), 1.73−1.80 (m, 2H, H5), 3.20 (t, J = 6.0 Hz, 2H, H1),
4.05 (s, 5H, H10), 4.22−4.28 (m, 4H, H6 + H9), 4.39−4.45 (m, 2H,
−OCH2), 4.56 (s, 2H, H8), 4.65−4.69 (m, 2H, −OCH2), 6.77−6.86
(m, 1H, −ArH), 7.07−7.14 (m, 2H, −ArH), 7.42 (s, 1H, H7); 13C
H
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
NMR (CDCl3, 75 MHz) δ 26.3, 26.5, 27.2, 28.0, 40.4, 51.5, 65.2, 66.4,
68.6, 69.7, 75.5, 101.2, 109.6, 112.6, 117.8, 125.4, 130.2, 134.7, 139.6,
157.2, 173.4; HRMS calcd for C28H29FFeN4O3 [M + H]+ m/z
545.1170, found 545.1175. Anal. Calcd: C, 61.76; H, 5.33; N, 10.29.
Found: C, 61.56; H, 5.21; N, 10.42.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)hexyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10s): yield 84%; dark brown oil;
NMR (CDCl3, 300 MHz) δ 1.37−1.48 (m, 4H, H3 + H4), 1.51−1.66
(m, 2H, H2), 1.71−1.83 (m, 2H, H5), 3.18 (t, J = 6.3 Hz, 2H, H1), 4.03
(s, 5H, H10), 4.22−4.29 (m, 4H, H6 + H9), 4.43−4.49 (m, 2H,
−OCH2), 4.58 (s, 2H, H8), 4.63−4.70 (m, 2H, −OCH2), 6.82−6.91
(m, 1H, −ArH), 7.33−7.38 (m, 2H, −ArH), 7.63 (s, 1H, H7); 13C
NMR (CDCl3, 75 MHz) δ 26.4, 26.6, 27.4, 28.2, 40.5, 51.7, 65.1, 66.6,
68.7, 69.9, 75.4, 102.5, 110.8, 113.6, 123.7, 124.5, 130.7, 134.2, 137.6,
141.6, 173.4; HRMS calcd for C28H29ClFeN4O3 [M]+ m/z 560.1284,
found 560.1288. Anal. Calcd: C, 60.00; H, 5.18; N, 10.00. Found: C,
59.92; H, 5.17; N, 10.11.
−CH3), 3.23 (t, J = 5.4 Hz, 2H, H1), 4.04 (s, 5H, H12), 4.19−4.28 (m,
4H, H8 + H11), 4.43−4.47 (m, 2H, −OCH2), 4.59 (s, 2H, H10), 4.62−
4.69 (m, 2H, −OCH2), 6.59 (d, J = 8.4 Hz, 1H, −ArH), 7.33−7.38
(m, 2H, −ArH), 7.61 (s, 1H, H9); 13C NMR (CDCl3, 75 MHz) δ 21.6,
26.1, 26.2, 26.7, 28.8, 28.9, 29.5, 40.8, 50.7, 65.1, 66.4, 68.4, 69.1, 75.5,
102.4, 110.5, 117.6, 121.4, 124.3, 130.1, 131.6, 134.9, 141.4, 175.6;
HRMS calcd for C31H36FeN4O3 [M]+ m/z 568.0418, found 568.0413.
Anal. Calcd: C, 65.49; H, 6.34; N, 9.86. Found: C, 65.38; H, 6.45; N,
9.93.
1-(4-Azidobutyl)-1H-indole-2,3-dione (11a): yield 83%; red oil; 1H
NMR (CDCl3, 300 MHz) δ 1.75−1.85 (m, 4H, H2 + H3), 3.36 (t, J =
5.7 Hz, 2H, H1), 3.61 (t, J = 6.3 Hz, 2H, H4), 6.77−6.82 (m, 1H,
−ArH), 7.02−7.10 (m, 1H, −ArH), 7.27−7.35 (m, 2H, −ArH); 13C
NMR (CDCl3, 75 MHz) δ 26.6, 29.3, 37.0, 48.7, 118.6, 123.4, 128.5,
130.7, 131.5, 138.3, 158.6, 183.5; HRMS calcd for C12H12N4O2 [M]+
m/z 244.0960, found 244.0954. Anal. Calcd: C, 59.01; H, 4.95; N,
22.94. Found: C, 58.96; H, 4.88; N, 23.03.
1-(4-Azidobutyl)-5-fluoro-1H-indole-2,3-dione (11b): yield 82%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.71−1.83 (m, 4H, H2 + H3),
3.33 (t, J = 6.6 Hz, 2H, H1), 3.59 (t, J = 6.9 Hz, 2H, H4), 6.78−6.85
(m, 1H, −ArH), 7.29−7.34 (m, 2H, −ArH); 13C NMR (CDCl3, 75
MHz) δ 26.6, 29.7, 36.8, 48.3, 111.5, 118.5, 125.7, 129.7, 137.4, 149.6,
158.6, 182.8; HRMS calcd for C12H11FN4O2 [M]+ m/z 262.0899,
found 262.0892. Anal. Calcd: C, 54.96; H, 4.23; N, 21.36. Found: C,
55.03; H, 4.28; N, 21.42.
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)hexyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10t): yield 89%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.33−1.44 (m, 4H, H3 + H4), 1.52−
1.63 (m, 2H, H2), 1.74−1.80 (m, 2H, H5), 2.21 (s, 3H, −CH3), 3.20
(t, J = 6.9 Hz, 2H, H1), 4.00 (s, 5H, H10), 4.21−4.26 (m, 4H, H6 +
H9), 4.47−4.51 (m, 2H, −OCH2), 4.54 (s, 2H, H8), 4.66−4.72 (m,
2H, −OCH2), 6.57 (d, J = 8.1 Hz, 1H, −ArH), 7.30−7.39 (m, 2H,
−ArH), 7.64 (s, 1H, H7); 13C NMR (CDCl3, 75 MHz) δ 21.5, 26.2,
26.4, 27.5, 28.1, 40.3, 51.8, 65.0, 66.8, 68.3, 69.8, 75.3, 102.5, 110.3,
117.5, 121.4, 124.8, 130.7, 131.3, 134.8, 141.8, 175.2; HRMS calcd for
C29H32FeN4O3 [M]+ m/z 540.1510, found 540.1516. Anal. Calcd: C,
64.44; H, 5.93; N, 10.37. Found: C, 64.54; H, 5.99; N, 10.25.
1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)octyl)spiro[[1,3]-
1-(4-Azidobutyl)-5-chloro-1H-indole-2,3-dione (11c): yield 85%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.74−1.84 (m, 4H, H2 + H3),
3.34 (t, J = 5.7 Hz, 2H, H1), 3.67 (t, J = 6.0 Hz, 2H, H4), 6.76−6.79
(m, 1H, −ArH), 7.06−7.13 (m, 1H, −ArH), 7.32−7.38 (m, 1H,
−ArH), 13C NMR (CDCl3, 75 MHz) δ 26.4, 29.2, 36.4, 48.8, 110.6,
117.5, 121.7, 124.9, 146.3, 149.3, 158.3, 182.2; HRMS calcd for
C12H11ClN4O2 [M]+ m/z 278.0570, found 278.0573. Anal. Calcd: C,
51.72; H, 3.98; N, 21.10. Found: C, 51.69; H, 4.02; N, 21.18.
1-(4-Azidobutyl)-5-methyl-1H-indole-2,3-dione (11d): yield 83%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.77−1.84 (m, 4H, H2 + H3),
2.22 (s, 3H, −CH3), 3.36 (t, J = 6.0 Hz, 2H, H1), 3.62 (t, J = 6.0 Hz,
2H, H4), 6.67 (d, J = 8.1 Hz, 1H, −ArH), 7.27−7.37 (m, 2H, −ArH);
13C NMR (CDCl3, 75 MHz) δ 21.3, 26.7, 29.0, 36.5, 48.6, 111.5,
121.8, 124.8, 138.5, 146.4, 149.6, 158.6, 182.3; HRMS calcd for
C13H14N4O2 [M]+ m/z 258.1116, found 258.1113. Anal. Calcd: C,
60.45; H, 5.46; N, 21.69. Found: C, 60.37; H, 5.52; N, 21.63.
1-(4-Azidopentyl)-1H-indole-2,3-dione (11e): yield 81%; red oil;
1H NMR (CDCl3, 300 MHz) δ 1.28−1.33 (m, 2H, H3), 1.34−1.55
(m, 4H, H2 + H4), 3.21 (t, J = 6.0 Hz, 2H, H1), 3.54 (t, J = 6.3 Hz, 2H,
H5), 6.77−6.84 (m, 1H, −ArH), 7.01−7.09 (m, 1H, −ArH), 7.29−
7.35 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 24.1, 26.2, 27.4,
39.8, 51.3, 118.8, 123.3, 128.3, 130.1, 131.4, 138.4, 158.7, 183.1;
HRMS calcd for C13H14N4O2 [M]+ m/z 258.1116, found 258.1111.
Anal. Calcd: C, 60.45; H, 5.46; N, 21.69. Found: C, 60.52; H, 5.50; N,
21.60.
1-(4-Azidopentyl)-5-fluoro-1H-indole-2,3-dione (11f): yield 88%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.35−1.39 (m, 2H, H3), 1.42−
1.61 (m, 4H, H2 + H4), 3.16 (t, J = 6.0 Hz, 2H, H1), 3.57 (t, J = 6.6 Hz,
2H, H5), 6.73−6.81 (m, 1H, −ArH), 7.30−7.37 (m, 2H, −ArH); 13C
NMR (CDCl3, 75 MHz) δ 24.3, 26.6, 27.8, 39.9, 51.2, 111.8, 118.1,
125.5, 129.6, 137.8, 149.5, 158.5, 182.6; HRMS calcd for
C13H13FN4O2 [M]+ m/z 276.1022, found 276.1019. Anal. Calcd: C,
56.52; H, 4.74; N, 20.28. Found: C, 56.56; H, 4.72; N, 20.31.
1-(4-Azidopentyl)-5-chloro-1H-indole-2,3-dione (11g): yield 90%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.25−1.33 (m, 2H, H3), 1.38−
1.59 (m, 4H, H2 + H4), 3.26 (t, J = 6.3 Hz, 2H, H1), 3.55 (t, J = 6.3 Hz,
2H, H5), 6.75−6.82 (m, 1H, −ArH), 7.09−7.14 (m, 1H, −ArH),
7.30−7.37 (m, 1H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 24.1, 26.3,
27.6, 39.7, 51.4, 110.9, 117.2, 121.5, 124.8, 146.1, 149.0, 158.6, 182.8;
HRMS calcd for C13H13ClN4O2 [M]+ m/z 292.0727, found 292.0721.
Anal. Calcd: C, 53.34; H, 4.48; N, 19.14. Found: C, 53.26; H, 4.50; N,
19.09.
1
dioxolane-2,3′-indolin]-2′-one (10u): yield 94%; dark brown oil; H
NMR (CDCl3, 300 MHz) δ 1.31−1.45 (m, 8H, H3 + H4 + H5 + H6),
1.49−1.59 (m, 2H, H2), 1.67−1.76 (s, 2H, H7), 3.25 (t, J = 5.7 Hz, 2H,
H1), 4.01 (s, 5H, H12), 4.19−4.28 (m, 4H, H8 + H11), 4.45−4.51 (m,
2H, −OCH2), 4.54 (s, 2H, H10), 4.60−4.64 (m, 2H, −OCH2), 6.76−
6.82 (d, J = 8.1 Hz, 1H, −ArH), 7.01−7.09 (m, 1H, −ArH), 7.29−7.39
(m, 2H, −ArH), 7.46 (s, 1H, H9); 13C NMR (CDCl3, 75 MHz) δ 26.2,
26.5, 26.6, 28.7, 28.8, 29.3, 40.1, 50.7, 65.1, 66.1, 68.5, 69.4, 75.5,
102.1, 108.6, 118.2, 123.5, 123.9, 124.7, 131.6, 143.0, 173.4; HRMS
calcd for C30H34FeN4O3 [M + H]+ m/z 555.1273, found 555.1271.
Anal. Calcd: C, 64.98; H, 6.14; N, 10.11. Found: C, 65.07; H, 6.20; N,
10.03.
5′-Fluoro-1′-(2-(4-Ferrocenyl-1H-1,2,3-triazol-1-yl)octyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10v): yield 89%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.27−1.39 (m, 8H, H3 + H4 + H5 +
H6), 1.44−1.55 (m, 2H, H2), 1.66−1.77 (s, 2H, H7), 3.21 (t, J = 5.4
Hz, 2H, H1), 4.05 (s, 5H, H12), 4.18−4.25 (m, 4H, H8 + H11), 4.43−
4.48 (m, 2H, −OCH2), 4.55 (s, 2H, H10), 4.59−4.66 (m, 2H,
−OCH2), 6.75−6.85 (m, 1H, −ArH), 7.05−7.11 (m, 2H, −ArH), 7.46
(s, 1H, H9); 13C NMR (CDCl3, 75 MHz) δ 26.0, 26.4, 26.5, 28.6, 28.9,
29.0, 40.2, 50.5, 65.5, 66.6, 68.3, 69.6, 75.6, 101.4, 109.7, 112.5, 117.7,
125.7, 130.0, 134.6, 139.3, 157.5, 173.8; HRMS calcd for
C30H33FFeN4O3 [M]+ m/z 572.1291, found 572.1287. Anal. Calcd:
C, 62.94; H, 5.77; N, 9.79. Found: C, 63.04; H, 5.84; N, 9.68.
5′-Chloro-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)octyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10w): yield 90%; dark brown
oil; 1H NMR (CDCl3, 300 MHz) δ 1.24−1.38 (m, 8H, H3 + H4 + H5
+ H6), 1.41−1.55 (m, 2H, H2), 1.63−1.76 (s, 2H, H7), 3.27 (t, J = 5.7
Hz, 2H, H1), 4.02 (s, 5H, H12), 4.20−4.29 (m, 4H, H8 + H11), 4.45−
4.53 (m, 2H, −OCH2), 4.58 (s, 2H, H10), 4.61−4.65 (m, 2H,
−OCH2), 6.84−6.93 (m, 1H, −ArH), 7.30−7.39 (m, 2H, −ArH), 7.65
(s, 1H, H9); 13C NMR (CDCl3, 75 MHz) δ 26.2, 26.3, 26.6, 28.7, 28.8,
29.1, 40.4, 50.8, 65.2, 66.2, 68.7, 69.3, 75.8, 102.1, 110.3, 113.9, 123.3,
124.9, 130.6, 1341, 137.4, 141.8, 173.6; HRMS calcd for
C30H33ClFeN4O3 [M]+ m/z 588.0280, found 588.0278. Anal. Calcd:
C, 61.22; H, 5.61; N, 9.52. Found: C, 61.14; H, 5.55; N, 9.48.
5′-Methyl-1′-(2-(4-ferrocenyl-1H-1,2,3-triazol-1-yl)octyl)spiro-
[[1,3]dioxolane-2,3′-indolin]-2′-one (10x): yield 80%; dark brown oil;
1H NMR (CDCl3, 300 MHz) δ 1.21−1.35 (m, 8H, H3 + H4 + H5 +
1-(4-Azidopentyl)-5-methyl-1H-indole-2,3-dione (11h): yield 81%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.28−1.35 (m, 2H, H3), 1.45−
1.53 (m, 4H, H2 + H4), 2.24, (s, 3H, −CH3), 3.19 (t, J = 6.9 Hz, 2H,
H6), 1.43−1.58 (m, 2H, H2), 1.62−1.74 (s, 2H, H7), 2.24 (s, 3H,
I
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
H1), 3.58 (t, J = 6.0 Hz, 2H, H5), 6.64 (d, J = 8.4 Hz, 1H, −ArH),
7.29−7.38 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 21.6, 24.4,
26.5, 27.2, 39.5, 51.3, 111.3, 121.7, 124.9, 138.2, 146.3, 149.2, 158.3,
182.5; HRMS calcd for C14H16N4O2 [M]+ m/z 272.1273, found
272.1267. Anal. Calcd: C, 61.75; H, 5.92; N, 20.58. Found: C, 61.81;
H, 5.99; N, 20.50.
1-(4-Azidooctyl)-5-methyl-1H-indole-2,3-dione (11p): yield 91%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.32−1.42 (m, 8H, H3 + H4 +
H5 + H6), 1.44−1.56 (m, 2H, H2), 1.63−1.77 (m, 2H, H7), 2.20 (s,
3H, −CH3), 3.25 (t, J = 6.3 Hz, 2H, H1), 3.66 (t, J = 6.6 Hz, 2H, H8),
6.67 (d, J = 8.1 Hz, 1H, −ArH), 7.31−7.38 (m, 2H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 21.3, 26.5, 26.7, 26.9, 28.2, 28.7, 29.5, 40.3, 50.8,
111.5, 121.7, 124.8, 138.4, 146.7, 149.2, 158.3, 182.7; HRMS calcd for
C17H22N4O2 [M]+ m/z 314.1742, found 314.1738. Anal. Calcd: C,
64.95; H, 7.05; N, 17.82. Found: C, 64.91; H, 7.08; N, 17.77.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)butyl]-1H-indole-2,3-dione
1
1-(4-Azidohexyl)-1H-indole-2,3-dione (11i): yield 88%; red oil; H
NMR (CDCl3, 300 MHz) δ 1.43−1.48 (m, 4H, H3 + H4), 1.52−1.65
(m, 2H, H2), 1.69−1.75 (m, 2H, H5), 3.23 (t, J = 6.0 Hz, 2H, H1), 3.74
(t, J = 6.6 Hz, 2H, H6), 6.71−6.78 (m, 1H, −ArH), 7.06−7.15 (m, 1H,
−ArH), 7.29−7.36 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ
26.2, 26.3, 27.5, 28.1, 40.6, 51.5, 118.7, 123.1, 128.1, 130.4, 131.7,
138.2, 158.5, 183.3; HRMS calcd for C14H16N4O2 [M]+ m/z 272.1273,
found 272.1269. Anal. Calcd: C, 61.75; H, 5.92; N, 20.58. Found: C,
61.81; H, 5.89; N, 20.64.
1
(12a): yield 88%; dark brown oil; H NMR (CDCl3, 300 MHz) δ
1.73−1.80 (m, 2H, H2), 2.01−2.05 (m, 2H, H3), 3.78 (t, J = 6.9 Hz,
2H, H1), 4.05 (s, 5H, H8), 4.30 (s, 2H, H7), 4.45 (t, J = 6.9 Hz, 2H,
H4), 4.71 (s, 2H, H6), 6.87−6.89 (m, 1H, −ArH), 7.08−7.14 (m, 1H,
−ArH), 7.47 (s, 1H, H5), 7.56−7.61 (m, 2H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 23.9, 27.3, 39.1, 49.1, 66.6, 68.7, 69.5, 75.3, 110.0,
117.4, 118.8, 123.4, 124.9, 131.7, 138.5, 150.4, 158.3, 183.1; HRMS
calcd for C24H22FeN4O2 [M + H]+ m/z 455.1165, found 455.1181.
Anal. Calcd: C, 63.44; H, 4.85; N, 12.33. Found: C, 63.54; H, 4.92; N,
12.25.
1-(4-Azidohexyl)-5-fluoro-1H-indole-2,3-dione (11j): yield 92%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.43−1.59 (m, 4H, H3 + H4),
1.60−1.62 (m, 2H, H2), 1.70−1.74 (m, 2H, H5), 3.27 (t, J = 6.3 Hz,
2H, H1), 3.73 (t, J = 6.3 Hz, 2H, H6), 6.86−6.90 (m, 1H, −ArH),
7.29−7.32 (m, 1H, −ArH), 7.55−7.57 (m, 1H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 26.2, 26.3, 27.0, 28.6, 40.1, 51.2, 111.1, 118.4,
125.3, 129.5, 137.6, 149.1, 157.6, 182.5; HRMS calcd for
C14H15FN4O2 [M]+ m/z 290.1179, found 290.1187. Anal. Calcd: C,
57.92; H, 5.21; N, 19.30. Found: C, 57.97; H, 5.15; N, 19.24.
1-(4-Azidohexyl)-5-chloro-1H-indole-2,3-dione (11k): yield 82%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.34−1.46 (m, 4H, H3 + H4),
1.51−1.60 (m, 2H, H2), 1.71−1.83 (m, 2H, H5), 3.27 (t, J = 5.7 Hz,
2H, H1), 3.66 (t, J = 6.3 Hz, 2H, H6), 6.69−6.75 (m, 1H, −ArH),
7.03−7.12 (m, 1H, −ArH), 7.28−7.38 (m, 1H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 26.2, 26.6, 27.6, 28.5, 40.2, 51.0, 110.5, 117.3,
121.7, 124.5, 146.3, 149.3, 158.1, 182.5; HRMS calcd for
C14H15ClN4O2 [M]+ m/z 306.0854, found 306.0848. Anal. Calcd: C,
54.82; H, 4.93; N, 18.26. Found: C, 54.79; H, 4.88; N, 18.31.
1-(4-Azidohexyl)-5-methyl-1H-indole-2,3-dione (11l): yield 87%;
red oil; 1H NMR (CDCl3, 300 MHz):δ 1.43−1.48 (m, 4H, H3 + H4),
1.53−1.59 (m, 2H, H2), 1.75−1.79 (m, 2H, H5), 2.22 (s, 3H, −CH3),
3.27 (t, J = 6.0 Hz, 2H, H1), 3.69 (t, J = 6.3 Hz, 2H, H6), 6.66 (d, J =
8.1 Hz, 1H, −ArH), 7.30−7.39 (m, 2H, −ArH); 13C NMR (CDCl3, 75
MHz) δ 21.5, 26.6, 26.8, 27.3, 28.6, 40.8, 51.4, 111.7, 121.4, 124.5,
138.5, 146.4, 149.0, 158.6, 182.8; HRMS calcd for C15H18N4O2 [M]+
m/z 286.1429, found 286.1422. Anal. Calcd: C, 62.92; H, 6.34; N,
19.57. Found: C, 62.87; H, 6.31; N, 19.55.
1-(4-Azidooctyl)-1H-indole-2,3-dione (11m): yield 91%; red oil;
1H NMR (CDCl3, 300 MHz) δ 1.33−1.46 (m, 8H, H3 + H4 + H5 +
H6), 1.51−1.56 (m, 2H, H2), 1.65−1.78 (m, 2H, H7), 3.24 (t, J = 6.6
Hz, 2H, H1), 3.66 (t, J = 5.7 Hz, 2H, H8), 6.73−6.79 (m, 1H, −ArH),
7.02−7.07 (m, 1H, −ArH), 7.30−7.38 (m, 2H, −ArH); 13C NMR
(CDCl3, 75 MHz) δ 26.0, 26.3, 26.6, 28.7, 28.9, 29.1, 40.2, 50.8, 118.8,
123.0, 128.2, 130.6, 131.8, 138.3, 158.7, 183.7; HRMS calcd for
C16H20N4O2 [M]+ m/z 300.1586, found 300.1592. Anal. Calcd: C,
63.98; H, 6.71; N, 18.65. Found: C, 64.02; H, 6.67; N, 18.59.
1-(4-Azidooctyl)-5-fluoro-1H-indole-2,3-dione (11n): yield 88%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.27−1.40 (m, 8H, H3 + H4 +
H5 + H6), 1.42−1.53 (m, 2H, H2), 1.63−1.70 (m, 2H, H7), 3.21 (t, J =
6.9 Hz, 2H, H1), 3.66 (t, J = 6.6 Hz, 2H, H8), 6.85−6.89 (m, 1H,
−ArH), 7.29−7.33 (m, 2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ
26.0, 26.4, 26.9, 28.3, 28.7, 29.1, 40.7, 50.8, 111.1, 118.2, 125.6, 129.4,
137.2, 149.8, 157.6, 182.6; HRMS calcd for C16H19FN4O2 [M]+ m/z
318.1525, found 318.1523. Anal. Calcd: C, 60.37; H, 6.02; N, 17.60.
Found: C, 60.43; H, 5.99; N, 17.62.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)butyl]-5-fluoro-1H-indole-
1
2,3-dione (12b): yield 81%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.70−185 (m, 2H, H2), 2.04−2.10 (m, 2H, H3), 3.69 (t, J =
6.6 Hz, 2H, H1), 4.01 (s, 5H, H8), 4.48 (s, 2H, H7), 4.60 (t, J = 6.6 Hz,
2H, H4), 4.74 (s, 2H, H6), 6.79−6.85 (m, 1H, −ArH), 7.29−7.33 (m,
2H, −ArH), 7.48 (s, 1H, H5); 13C NMR (CDCl3, 75 MHz) δ 24.3,
29.5, 36.6, 39.4, 65.7, 68.2, 69.5, 72.2, 111.5, 112.7, 124.1, 125.8, 132.7,
136.4, 146.5, 157.3, 159.7, 182.8; HRMS calcd for C24H21FFeN4O2
[M]+ m/z 472.0710, found 472.0716. Anal. Calcd: C, 61.02; H, 4.45;
N, 11.86. Found: C, 60.90; H, 4.32; N, 11.98.
5-Chloro-1-[2-(4-ferrocenyl-[1,2,3]triazol-1-yl)butyl]-1H-indole-
1
2,3-dione (12c): yield 81%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.73−1.85 (m, 4H, H2 + H3), 3.31 (t, J = 6.3 Hz, 2H, H1),
3.64 (t, J = 5.7 Hz, 2H, H4), 4.01 (s, 5H, H8), 4.60 (s, 2H, H7), 4.77 (s,
2H, H6), 6.91−6.96 (m, 1H, −ArH), 7.29−7.37 (m, 2H, −ArH), 7.60
(s, 1H, H5); 13C NMR (CDCl3, 75 MHz) δ 24.5, 26.6, 36.3, 39.7, 66.4,
68.4, 69.7, 75.3, 110.4, 117.5, 121.8, 124.9, 132.8, 138.9, 146.3, 149.1,
158.6, 182.5; HRMS calcd for C24H21ClFeN4O2 [M]+ m/z 488.1248,
found 488.1253. Anal. Calcd: C, 59.02; H, 4.30; N, 11.48. Found: C,
58.92; H, 4.18; N, 11.56.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)butyl]-5-methyl-1H-indole-
1
2,3-dione (12d): yield 75%; dark brown oil; H NMR (CDCl3, 300
MHz) δ1.73−183 (m, 2H, H2), 2.00−2.08 (m, 2H, H3), 2.21 (s, 3H,
−CH3), 3.64 (t, J = 6.0 Hz, 2H, H1), 4.07 (s, 5H, H8), 4.45 (s, 2H,
H7), 4.61 (t, J = 6.0 Hz, 2H, H4), 4.70 (s, 2H, H6), 6.60 (d, J = 8.4 Hz,
1H, −ArH), 7.30−7.37 (m, 2H, −ArH), 7.41 (s, 1H, H5);13C NMR
(CDCl3, 75 MHz) δ 21.6, 24.4, 26.7, 36.3, 39.5, 66.6, 68.3, 69.2, 75.5,
110.7, 117.8, 121.8, 124.9, 132.8, 138.7, 146.4, 149.5, 158.7, 182.2;
HRMS calcd for C25H24FeN4O2 [M]+ m/z 468.0624, found 468.0616.
Anal. Calcd: C, 64.10; H, 5.13; N, 11.97. Found: C, 63.97; H, 5.06; N,
11.95.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)pentyl]-1H-indole-2,3-dione
1
(12e): yield 79%; dark brown oil; H NMR (CDCl3, 300 MHz) δ
1.25−1.33 (m, 2H, H3), 1.73−1.77 (m, 2H, H2), 2.01−2.09 (m, 2H,
H4), 3.77 (t, J = 6.3 Hz, 2H, H1), 4.06 (s, 5H, H9), 4.30 (s, 2H, H8),
4.45 (t, J = 6.3 Hz, 2H, H5), 4.71 (s, 2H, H7), 6.86−6.89 (m, 1H,
−ArH), 7.08−7.13 (m, 1H, −ArH), 7.47 (s, 1H, H6), 7.56−7.60 (m,
2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 24.5, 26.1, 27.7, 39.4, 51.8,
66.8, 68.6, 69.8, 75.5, 110.4, 117.3, 118.7, 123.5, 124.6, 131.9, 138.2,
150.1, 158.0, 183.3; HRMS calcd for C25H24FeN4O2 [M]+ m/z
468.1639, found 468.1631. Anal. Calcd: C, 64.10; H, 5.13; N, 11.97.
Found: C, 64.23; H, 5.24; N, 11.86.
1-(4-Azidooctyl)-5-chloro-1H-indole-2,3-dione (11o): yield 93%;
red oil; 1H NMR (CDCl3, 300 MHz) δ 1.31−1.44 (m, 8H, H3 + H4 +
H5 + H6), 1.47−1.54 (m, 2H, H2), 1.66−1.72 (m, 2H, H7), 3.24 (t, J =
6.9 Hz, 2H, H1), 3.62 (t, J = 6.6 Hz, 2H, H8), 6.67−6.74 (m, 1H,
−ArH), 7.05−7.12 (m, 1H, −ArH), 7.27−7.34 (m, 1H, −ArH); 13C
NMR (CDCl3, 75 MHz) δ 26.1, 26.4, 26.6, 28.3, 28.5, 29.7, 40.2, 50.7,
110.7, 117.8, 121.3, 124.8, 146.2, 149.5, 158.4, 182.3; HRMS calcd for
C16H19ClN4O2 [M]+ m/z 334.1196, found 334.1188. Anal. Calcd: C,
57.40; H, 5.72; N, 16.73. Found: C, 57.47; H, 5.66; N, 16.69.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)pentyl]-5-fluoro-1H-indole-
1
2,3-dione (12f): yield 85%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.28−1.35 (m, 2H, H3), 1.71−1.79 (m, 2H, H2), 2.01−2.11
(m, 2H, H4), 3.70 (t, J = 5.7 Hz, 2H, H1), 4.03 (s, 5H, H9), 4.27 (s,
2H, H8), 4.46 (t, J = 5.7 Hz, 2H, H5), 4.67 (s, 2H, H7), 6.74−6.83 (m,
1H, −ArH), 7.32−7.39 (m, 2H, −ArH), 7.50 (s, 1H, H6); 13C NMR
(CDCl3, 75 MHz) δ 24.2, 26.6, 27.8, 39.1, 51.5, 66.6, 68.9, 69.7, 75.3,
111.3, 112.8, 124.0, 125.5, 132.9, 136.2, 146.6, 157.1, 159.6, 182.4;
J
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
HRMS calcd for C25H23FFeN4O2 [M]+ m/z 486.1482, found
486.1475. Anal. Calcd: C, 61.73; H, 4.73; N, 11.52. Found: C,
61.86; H, 4.85; N, 11.42.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)octyl]-1H-indole-2,3-dione
1
(12m): yield 75%; dark brown oil; H NMR (CDCl3, 300 MHz) δ
1.27−1.39 (m, 8H, H3 + H4 + H5 + H6), 1.67 (s, 2H, H2), 1.95 (s, 2H,
H7), 3.63 (t, J = 6.0 Hz, 2H, H1), 4.01 (s, 5H, H12), 4.31 (s, 2H, H11),
4.38 (t, J = 6.0 Hz, 2H, H8), 4.69 (s, 2H, H10), 6.80−6.87 (m, 1H,
−ArH), 7.06−7.14 (m, 1H, −ArH), 7.45 (s, 1H, H9), 7.53−7.61 (m,
2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.2, 26.6, 28.8, 28.9, 29.5,
30.3, 40.7, 50.0, 66.5, 68.7, 69.1, 75.4, 110.1, 117.3, 118.5, 123.6, 124.5,
131.7, 138.6, 149.4, 158.3, 182.7; HRMS calcd for C28H30FeN4O2
[M]+ m/z 510.1483, found 510.1478. Anal. Calcd: C, 65.88; H, 5.88;
N, 10.98. Found: C, 65.74; H, 5.73; N, 11.11.
5-Chloro-1-[2-(4-ferrocenyl-[1,2,3]triazol-1-yl)pentyl]-1H-indole-
1
2,3-dione (12g): yield 83%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.25−1.34 (m, 2H, H3), 1.73−1.81 (m, 2H, H2), 2.04−2.10
(m, 2H, H4), 3.70 (t, J = 6.3 Hz, 2H, H1), 4.04 (s, 5H, H9), 4.27 (s,
2H, H8), 4.49 (t, J = 6.3 Hz, 2H, H5), 4.69 (s, 2H, H7), 6.93−6.99 (m,
1H, −ArH), 7.30−7.39 (m, 2H, −ArH), 7.64 (s, 1H, H6); 13C NMR
(CDCl3, 75 MHz) δ 24.4, 26.6, 27.3, 39.2, 51.4,, 66.3, 68.6, 69.2, 75.1,
110.1, 117.8, 121.4, 124.7, 135.6, 138.7, 146.1, 149.4, 158.3, 182.4;
HRMS calcd for C25H23ClFeN4O2 [M]+ m/z 502.1261, found
502.1268. Anal. Calcd: C, 59.76; H, 4.58; N, 11.16. Found: C,
59.85; H, 4.67; N, 11.04.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)octyl]-5-fluoro-1H-indole-
1
2,3-dione (12n): yield 88%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.26−1.33 (m, 8H, H3 + H4 + H5 + H6), 1.66 (s, 2H, H2),
1.91 (s, 2H, H7), 3.68 (t, J = 6.9 Hz, 2H, H1), 4.06 (s, 5H, H12), 4.28
(s, 2H, H11), 4.33 (t, J = 6.9 Hz, 2H, H8), 4.72 (s, 2H, H10), 6.81−6.86
(m, 1H, −ArH), 7.27−7.29 (m, 2H, −ArH), 7.46 (s, 1H, H9); 13C
NMR (CDCl3, 75 MHz) δ 26.5, 27.0, 28.6, 28.8, 29.6, 30.0, 40.1, 50.1,
65.6, 68.6, 69.5, 75.4, 111.2, 112.2, 124.4, 124.7, 135.5, 136.8, 146.9,
157.8, 159.5, 182.9; HRMS calcd for C28H29FFeN4O2 [M]+ m/z
528.1594, found 528.1587. Anal. Calcd: C, 63.64; H, 5.49; N, 10.61.
Found: C, 63.59; H, 5.43; N, 10.75
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)pentyl]-5-methyl-1H-indole-
1
2,3-dione (12h): yield 78%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.21−1.34 (m, 2H, H3), 1.76−1.88 (m, 2H, H2), 2.01−2.09
(m, 2H, H4), 2.23 (s, 2H, −CH3), 3.68 (t, J = 5.4 Hz, 2H, H1), 4.02 (s,
5H, H9), 4.27 (s, 2H, H8), 4.45 (t, J = 5.4 Hz, 2H, H5), 4.71 (s, 2H,
H7), 6.55 (d, J = 8.1 Hz, 1H, −ArH), 7.29−7.39 (m, 2H, −ArH), 7.48
(s, 1H, H6); 13C NMR (CDCl3, 75 MHz) δ 21.2, 24.4, 26.8, 27.4, 39.1,
51.8, 66.1, 68.3, 69.6, 75.2, 110.5, 117.4, 121.3, 124.7, 132.5, 138.6,
146.7, 149.4, 158.5, 182.6; HRMS calcd for C26H26FeN4O2 [M]+ m/z
482.0736, found 482.0742. Anal. Calcd: C, 64.73; H, 5.39; N, 11.62.
Found: C, 64.63; H, 5.31; N, 11.51.
5-Chloro-1-[2-(4-ferrocenyl-[1,2,3]triazol-1-yl)octyl]-1H-indole-
1
2,3-dione (12o): yield 89%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.23−1.38 (m, 8H, H3 + H4 + H5 + H6), 1.64 (s, 2H, H2),
1.89 (s, 2H, H7), 3.69 (t, J = 6.6 Hz, 2H, H1), 4.07 (s, 5H, H12), 4.27
(s, 2H, H11), 4.35 (t, J = 6.6 Hz, 2H, H8), 4.70 (s, 2H, H10), 6.88−6.95
(m, 1H, −ArH), 7.31−7.37 (m, 2H, −ArH), 7.62 (s, 1H, H9); 13C
NMR (CDCl3, 75 MHz) δ 26.5, 27.8, 28.2, 28.7, 29.4, 30.3, 40.1, 50.7,
66.2, 68.5, 69.7, 75.2, 110.2, 117.6, 121.7, 124.8, 135.3, 138.1, 145.6,
149.6, 158.9, 182.8; HRMS calcd for C28H29ClFeN4O2 [M]+ m/z
544.1047, found 544.1041. Anal. Calcd: C, 61.76; H, 5.33; N, 10.29.
Found: C, 61.65; H, 5.24; N, 10.40.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)hexyl]-1H-indole-2,3-dione
1
(12i): yield 82%; dark brown oil; H NMR (CDCl3, 300 MHz) δ
1.29−1.38 (m, 4H, H3 + H4), 1.63−1.68 (m, 2H, H2), 1.88−1.94 (m,
2H, H5), 3.76 (t, J = 6.6 Hz, 2H, H1), 4.04 (s, 5H, H10), 4.29 (s, 2H,
H9), 4.39 (t, J = 6.3 Hz, 2H, H6), 4.73 (s, 2H, H8), 6.84−6.88 (m, 1H,
−ArH), 7.03−7.11 (m, 1H, −ArH), 7.49 (s, 1H, H7), 7.54−7.59 (m,
2H, −ArH); 13C NMR (CDCl3, 75 MHz) δ 26.1, 26.2, 27.5, 28.7, 40.5,
51.2, 66.3, 68.2, 69.7, 75.2, 110.0, 117.6, 118.9, 123.3, 124.4, 131.8,
138.5, 149.7, 158.4, 182.2; HRMS calcd for C26H26FeN4O2 [M]+ m/z
482.0581, found 482.0577. Anal. Calcd: C, 64.73; H, 5.39; N, 11.62.
Found: C, 64.66; H, 5.30; N, 11.73.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)octyl]-5-methyl-1H-indole-
1
2,3-dione (12p): yield 75%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.25−1.37 (m, 8H, H3 + H4 + H5 + H6), 1.61 (s, 2H, H2),
1.93 (s, 2H, H7), 2.24 (s, 3H, −CH3), 3.70 (t, J = 6.0 Hz, 2H, H1),
4.08 (s, 5H, H12), 4.21 (s, 2H, H11), 4.33 (t, J = 6.0 Hz, 2H, H8), 4.68
(s, 2H, H10), 6.55 (d, J = 7.5 Hz, 1H, −ArH), 7.30−7.39 (m, 2H,
−ArH), 7.46 (s, 1H, H9); 13C NMR (CDCl3, 75 MHz) δ 21.3, 26.3,
27.8, 28.4, 28.9, 29.5, 36.6, 40.8, 50.9, 66.0, 68.4, 69.5, 75.2, 110.6,
117.8, 121.1, 124.6, 132.8, 138.3, 146.4, 149.9, 158.7, 182.6; HRMS
calcd for C29H32FeN4O2 [M + H]+ m/z 525.0495, found 525.0488.
Anal. Calcd: C, 66.41; H, 6.11; N, 10.69. Found: C, 66.34; H, 6.02; N,
10.73.
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)hexyl]-5-fluoro-1H-indole-
1
2,3-dione (12j): yield 80%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.25−1.36 (m, 4H, H3 + H4), 1.60−1.69 (m, 2H, H2), 1.94−
2.03 (m, 2H, H5), 3.67 (t, J = 5.7 Hz, 2H, H1), 4.01 (s, 5H, H10), 4.34
(s, 2H, H9), 4.41 (t, J = 5.7 Hz, 2H, H6), 4.70 (s, 2H, H8), 6.76−6.81
(m, 1H, −ArH), 7.30−7.38 (m, 2H, −ArH), 7.41 (s, 1H, H7); 13C
NMR (CDCl3, 75 MHz) δ 26.0, 26.3, 27.2, 28.5, 40.4, 51.3, 66.0, 68.1,
69.5, 75.4, 111.1, 112.5, 124.4, 125.8, 132.6, 136.4, 146.8, 157.3, 159.4,
182.5; HRMS calcd for C26H25FFeN4O2 [M + H]+ m/z 501.0483,
found 501.0479. Anal. Calcd: C, 62.40; H, 5.00; N, 11.20. Found: C,
62.49; H, 5.11; N, 11.12.
Bacterial Strains and Growth Conditions. M. tuberculosis
mc27000, an unmarked version40 of mc26230, was grown at 37 °C
in Sauton’s medium supplemented with 109 μM of pantothenic acid.
Drug Susceptibility Testing. The susceptibility of M. tuberculosis
mc27000 to the various compounds was determined as reported
previously.41 In brief, Middlebrook 7H10 solid medium containing
oleic-albumin-dextrose-catalase enrichment (OADC) and 109 μM of
pantothenic acid was supplemented with increasing concentrations of
the chemical analogues. Serial 10-fold dilutions of each actively
growing culture were plated and incubated at 37 °C for 2−3 weeks.
The MIC was defined as the minimum concentration required to
inhibit 99% of the growth. All of the compounds were dissolved in
DMSO to carry out the inhibition assay.
5-Chloro-1-[2-(4-ferrocenyl-[1,2,3]triazol-1-yl)hexyl]-1H-indole-
1
2,3-dione (12k): yield 76%; dark brown oil; H NMR (CDCl3, 300
MHz) δ 1.31−1.38 (m, 4H, H3 + H4), 1.62−1.69 (m, 2H, H2), 1.90−
1.98 (m, 2H, H5), 3.69 (t, J = 6.9 Hz, 2H, H1), 4.05 (s, 5H, H10), 4.33
(s, 2H, H9), 4.41 (t, J = 6.9 Hz, 2H, H6), 4.72 (s, 2H, H8), 6.84−6.92
(m, 1H, −ArH), 7.29−7.38 (m, 2H, −ArH), 7.62 (s, 1H, H7); 13C
NMR (CDCl3, 75 MHz) δ 26.3, 26.8, 27.3, 28.5, 40.2, 51.4, 66.5, 68.9,
69.8, 75.1, 110.5, 117.3, 121.2, 124.4, 135.8, 138.2, 146.0, 149.3, 158.4,
182.5; HRMS calcd for C26H25ClFeN4O2 [M]+ m/z 516.0530, found
516.0522. Anal. Calcd: C, 60.47; H, 4.84; N, 10.85. Found: C, 60.57;
H, 4.90; N, 10.76.
ASSOCIATED CONTENT
1-[2-(4-Ferrocenyl-[1,2,3]triazol-1-yl)hexyl]-5-methyl-1H-indole-
■
1
2,3-dione (12l): yield 83%; dark brown oil; H NMR (CDCl3, 300
S
* Supporting Information
MHz) δ 1.33−1.39 (m, 4H, H3 + H4), 1.61−1.73 (m, 2H, H2), 1.90−
1.97 (m, 2H, H5), 2.20 (s, 3H, −CH3), 3.69 (t, J = 6.3 Hz, 2H, H1),
4.07 (s, 5H, H10), 4.30 (s, 2H, H9), 4.31 (t, J = 6.3 Hz, 2H, H6), 4.69
(s, 2H, H8), 6.56 (d, J = 8.7 Hz, 1H, −ArH), 7.32−7.38 (m, 2H,
−ArH), 7.48 (s, 1H, H7);13C NMR (CDCl3, 75 MHz) δ 21.1, 26.2,
26.7, 27.6, 28.5, 40.4, 51.7, 66.3, 68.1, 69.8, 75.5, 110.1, 117.7, 121.5,
124.9, 132.2, 138.7, 146.8, 149.6, 158.4, 182.3; HRMS calcd for
C27H28FeN4O2 [M]+ m/z 496.1483, found 496.1474. Anal. Calcd: C,
65.32; H, 5.65; N, 11.29. Found: C, 65.40; H, 5.72; N, 11.51.
1
Figures giving H and 13C NMR spectra for the representative
compounds 2a,b, 8b,j,n, 10a,e,i, 11j, and 12a,n and a CIF file
giving crystallographic data for 2b. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail for V.K.: vipan_org@yahoo.com.
■
K
dx.doi.org/10.1021/om4009229 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Chang, H.; Ruggeri, B. A.; Mallamo, J. P. Bioorg. Med. Chem. Lett.
2006, 16, 2158.
(15) Cane, A.; Tournaire, M. C.; Barritault, D.; Crumeyrolle-Arias,
Notes
The authors declare no competing financial interest.
M. Biochem. Biophys. Res. Commun. 2000, 276, 379.
ACKNOWLEDGMENTS
■
(16) Silveira, V. Ch.; Luz, J. S.; Oliveira, C. C.; Graziani, I.; Ciriolo,
M. R.; Costa-Ferreira, A. M. J. Inorg. Biochem. 2008, 102, 1090.
(17) Raj, A. A.; Raghunathan, R.; Sridevikumaria, M. R.; Raman, N.
Bioorg. Med. Chem. 2003, 11, 407.
(18) Rodriguez-Arguelles, M. C.; Mosquera-Vazaquez, S.; Touron-
Touceda, P.; Sanmartin-Matalobos, J.; Garcia-Deibe, A. M.; Belicchi-
Ferraris, M.; Pelosi, G.; Pelizzi, C.; Zani, F. J. Inorg. Biochem. 2007,
101, 138.
(19) Maskell, L.; Blanche, E. A.; Colucci, M. A.; Whatmore, J. L.;
Moody, Ch. J. Bioorg. Med. Chem. Lett. 2007, 17, 1575.
(20) Verma, M.; Pandyea, S. N.; Singh, K. N.; Stables, J. P. Acta
Pharm. 2004, 54, 49.
Financial assistance from Department of Science and
Technology, New Delhi, India, under Innovation in Science
Pursuit for Inspired Research (INSPIRE) Fellowship (K.K.) is
gratefully acknowledged. We thank Prof. W. R. Jacobs for the
generous gift of M. tuberculosis mc27000, which has been
approved for use in Biosafety Level 2 containment by the
Institutional Biosafety Committees of the Albert Einstein
College of Medicine and the University Montpellier 2. The
Fonds Europee
CNRS, Region Nord Pas-de-Calais, and Minister
l’Education Nationale de l’Enseignement Superieur et de la
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n de Dev
́
eloppement Reg
́
ional (FEDER),
́
̀
e de
́
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Neurochem. Int. 2005, 47, 216.
Recherche are acknowledged for funding of X-ray diffrac-
tometers.
(22) Chen, L. R.; Wang, Y. C.; Lin, Y. W.; Chou, S. Y.; Chen, S. F.;
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(23) Singh, G. S.; Desta, Z. Y. Chem. Rev. 2012, 112, 6104.
(24) Fensome, A.; Adams, W. R.; Adams, A. L.; Berrodin, T. J.;
Cohen, J.; Huselton, C.; Illenberger, A.; Karen, J. C.; Hudak, V. A.;
Marella, M. A.; Melenski, E. G.; McComas, C. C.; Mugford, C. A.;
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ABBREVIATIONS
■
TB, tuberculosis; MDR, multidrug resistant; XDR, extensively
drug resistant; MIC, minimal inhibitory concentration; FQ,
ferroquine; CQ, chloroquine
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